View source for Head and neck cancer

{{Short description|Cancer arises in the head or neck region}}
{{cs1 config|name-list-style=vanc}}
{{Infobox medical condition
| name = Head and neck cancer
| synonym = head and neck squamous cell carcinoma
| image = Diagram showing the parts of the pharynx CRUK 334.svg
| caption = Parts of the head and neck that can be affected by cancer
| field = [[Oncology]], [[oral and maxillofacial surgery]]
| risks = [[Alcohol (drug)|Alcohol]], [[tobacco]], [[Betel nut chewing|betel quid]], [[Human papillomavirus infection|human papillomavirus]], [[radiation exposure]], certain workplace exposures, [[Epstein–Barr virus]]<ref name="NCI" /><ref name=WCR2014 />
| diagnosis = [[Tissue biopsy]]<ref name="NCI" />
| differential = 
| prevention = Not using tobacco or alcohol<ref name=WCR2014 />
| treatment = Surgery, [[radiation therapy]], [[chemotherapy]], [[targeted therapy]]<ref name="NCI" />
| frequency = 5.5 million (affected during 2015)<!-- prevalence --><ref name=GBD2015Pre>{{cite journal | vauthors = Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, etal | collaboration = GBD 2015 Disease and Injury Incidence and Prevalence Collaborators | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 }}</ref>
| deaths = 379,000 (2015)<ref name=GBD2015De>{{cite journal | vauthors = Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A | collaboration = GBD 2015 Mortality and Causes of Death Collaborators | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 }}</ref>
}}
'''Head and neck cancer''' is a general term encompassing multiple [[cancer]]s that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips ([[oral cancer]]), voice box ([[Laryngeal cancer|laryngeal]]), throat ([[Nasopharyngeal carcinoma|nasopharyngeal]], [[Oropharyngeal cancer|oropharyngeal]],<ref name="NCI" /> [[Hypopharyngeal cancer|hypopharyngeal]]), [[Salivary gland tumour|salivary glands]], [[Paranasal sinus and nasal cavity cancer|nose and sinuses]].<ref name="Aupérin 178–186">{{cite journal | vauthors = Aupérin A | title = Epidemiology of head and neck cancers: an update | journal = Current Opinion in Oncology | volume = 32 | issue = 3 | pages = 178–186 | date = May 2020 | pmid = 32209823 | doi = 10.1097/CCO.0000000000000629 | s2cid = 214644380 }}</ref>

Head and neck cancer can present a wide range of symptoms depending on where the cancer developed. These can include an [[Mouth ulcer|ulcer in the mouth]] that does not heal, [[Hoarse voice|changes in the voice]], [[Dysphagia|difficulty swallowing]], [[Leukoplakia|red or white patches in the mouth]], and a [[Neck mass|neck lump]].<ref name=":11" /><ref name=":15">{{Cite journal |last1=Bradley |first1=Paula T. |last2=Lee |first2=Ying Ki |last3=Albutt |first3=Abigail |last4=Hardman |first4=John |last5=Kellar |first5=Ian |last6=Odo |first6=Chinasa |last7=Randell |first7=Rebecca |last8=Rousseau |first8=Nikki |last9=Tikka |first9=Theofano |last10=Patterson |first10=Joanne M. |last11=Paleri |first11=Vinidh |date=2024-06-17 |title=Nomenclature of the symptoms of head and neck cancer: a systematic scoping review |journal=Frontiers in Oncology |volume=14 |article-number=1404860 |doi=10.3389/fonc.2024.1404860 |doi-access=free |issn=2234-943X |pmc=11216301 |pmid=38952557}}</ref> <!-- Cause and diagnosis -->

The majority of head and neck cancer is caused by the use of [[Alcohol (drug)|alcohol]] or [[tobacco]] (including [[smokeless tobacco]]). An increasing number of cases are caused by the [[Human papillomavirus infection|human papillomavirus]] (HPV).<ref name="NCIfact">{{cite web |date=29 March 2017 |title=Head and Neck Cancers |url=https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet |access-date=7 February 2021 |publisher=[[National Cancer Institute|NCI]]}}</ref><ref name="WCR2014" /> Other risk factors include the [[Epstein–Barr virus]], chewing [[Betel nut chewing|betel quid]] (paan), [[radiation exposure]], poor nutrition and workplace exposure to certain toxic substances.<ref name="NCIfact" /> About 90% are pathologically classified as [[Squamous-cell carcinoma|squamous cell cancers]].<ref name=Vug2015>{{cite journal | vauthors = Vigneswaran N, Williams MD | title = Epidemiologic trends in head and neck cancer and aids in diagnosis | journal = Oral and Maxillofacial Surgery Clinics of North America | volume = 26 | issue = 2 | pages = 123–141 | date = May 2014 | pmid = 24794262 | pmc = 4040236 | doi = 10.1016/j.coms.2014.01.001 }}</ref><ref name=WCR2014>{{cite book|title=World Cancer Report 2014|date=2014|publisher=World Health Organization|isbn=978-92-832-0429-9|pages=Chapter 5.8}}</ref> The diagnosis is confirmed by a [[Biopsy|tissue biopsy]].<ref name="NCIfact" /> The degree of surrounding tissue invasion and distant spread may be determined by [[medical imaging]] and [[blood test]]s.<ref name="NCIfact" />

<!-- Prevention and treatment -->
Not using tobacco or alcohol can reduce the risk of head and neck cancer.<ref name=WCR2014 /> Regular dental examinations may help to identify signs before the cancer develops.<ref name="NCI" /> The [[HPV vaccine]] helps to prevent [[HPV-positive oropharyngeal cancer|HPV-related oropharyngeal cancer]].<ref name=":13" /> Treatment may include a combination of surgery, [[radiation therapy]], [[chemotherapy]], and [[targeted therapy]].<ref name="NCIfact" /> In the early stage head and neck cancers are often curable but 50% of people see their doctor when they already have an advanced disease.<ref name=":14" />

<!-- Epidemiology -->Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide, with 890,000 new cases documented and 450,000 people dying from the disease.<ref name=":3">{{cite journal |vauthors=Chow LQ |date=January 2020 |title=Head and Neck Cancer |journal=The New England Journal of Medicine |volume=382 |issue=1 |pages=60–72 |doi=10.1056/nejmra1715715 |pmid=31893516 |s2cid=209482428}}</ref> The usual age at diagnosis is between 55 and 65 years old.<ref name="SEER2016" /> The average [[Five-year survival rate|5-year survival]] following diagnosis in the [[Developed country|developed world]] is 42–64%.<ref name="SEER2016">{{cite web|title=SEER Stat Fact Sheets: Oral Cavity and Pharynx Cancer|url=http://seer.cancer.gov/statfacts/html/oralcav.html|website=SEER|access-date=29 September 2016|date=April 2016|url-status=live|archive-url=https://web.archive.org/web/20161115143038/http://seer.cancer.gov/statfacts/html/oralcav.html|archive-date=15 November 2016}}</ref><ref>{{cite book| vauthors = Beyzadeoglu M, Ozyigit G, Selek U |title=Radiation Therapy for Head and Neck Cancers: A Case-Based Review|date=2014|publisher=Springer|isbn=978-3-319-10413-3|page=18|url=https://books.google.com/books?id=zcGPBQAAQBAJ&pg=PA18|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910182726/https://books.google.com/books?id=zcGPBQAAQBAJ&pg=PA18|archive-date=2017-09-10}}</ref>{{TOC limit}}

==Signs and symptoms==
Head and neck cancers can cause a broad range of symptoms, many of which occur together. These can be categorised local (head and neck cancer-specific), general and [[Gastrointestinal tract|gastrointestinal]] symptoms. Local symptoms include changes in taste and voice, inflammation of the mouth or throat ([[mucositis]]), dry mouth ([[xerostomia]]), and difficulty swallowing ([[dysphagia]]). General symptoms include difficulty sleeping, tiredness, depression, nerve damage ([[peripheral neuropathy]]). Gastrointestinal symptoms are typically nausea and vomiting.<ref name=":11">{{Cite journal |last1=Mathew |first1=Asha |last2=Tirkey |first2=Amit Jiwan |last3=Li |first3=Hongjin |last4=Steffen |first4=Alana |last5=Lockwood |first5=Mark B. |last6=Patil |first6=Crystal L. |last7=Doorenbos |first7=Ardith Z. |date=2 October 2021 |title=Symptom Clusters in Head and Neck Cancer: A Systematic Review and Conceptual Model |journal=Seminars in Oncology Nursing |language=en |volume=37 |issue=5 |article-number=151215 |doi=10.1016/j.soncn.2021.151215|pmid=34483015 |pmc=8492544 }}</ref>

Symptoms predominantly include a sore on the face or oral cavity that does not heal, trouble swallowing, or a change in voice. In those with advanced disease, there may be unusual bleeding, facial pain, numbness or swelling, and visible lumps on the outside of the neck or oral cavity.<ref>{{cite journal | vauthors = McIlwain WR, Sood AJ, Nguyen SA, Day TA | title = Initial symptoms in patients with HPV-positive and HPV-negative oropharyngeal cancer | journal = JAMA Otolaryngology–Head & Neck Surgery | volume = 140 | issue = 5 | pages = 441–447 | date = May 2014 | pmid = 24652023 | doi = 10.1001/jamaoto.2014.141 | doi-access = free }}</ref> Head and neck cancer often begins with benign signs and symptoms of the disease, like an enlarged [[lymph node]] on the outside of the neck, a [[Hoarse voice|hoarse-sounding voice]], or a progressive worsening cough or sore throat. In the case of head and neck cancer, these symptoms will be notably persistent and become chronic. There may be a lump or a sore in the throat or neck that does not heal or go away. There may be difficulty or pain in swallowing. Speaking may become difficult. There may also be a persistent [[Ear pain|earache]].<ref>{{Cite book|title=Head and neck cancer: emerging perspectives|date=2003|publisher=Academic Press| vauthors = Ensley JF |isbn=978-0-08-053384-1|location=Amsterdam|oclc=180905431}}</ref>

Other symptoms can include: a lump in the lip, mouth, or gums; ulcers or mouth sores that do not heal; bleeding from the mouth or numbness; bad breath; discolored patches that persist in the mouth; a sore tongue; and slurring of speech if the cancer is affecting the tongue. There may also be congested sinuses, weight loss, and some numbness or paralysis of [[facial muscles]].{{citation needed|date=September 2024}}

===Mouth===
{{Main|Oral cancer}}
[[File:Oral cancer (1) squamous cell carcinoma histopathology.jpg|thumb|Squamous cell carcinoma of the mouth]]

Oral cancer affects the areas of the mouth, including the inner lip, [[tongue]], [[floor of the mouth]], [[gums]], and [[hard palate]]. Cancers of the mouth are strongly associated with [[tobacco]] use, especially the use of [[chewing tobacco]] or [[dipping tobacco]], as well as heavy [[alcohol (drug)|alcohol]] use. Cancers of this region, particularly the tongue, are more frequently treated with [[surgery]] than other head and neck cancers. Lip and oral cavity cancers are the most commonly encountered types of head and neck cancer.<ref name="Aupérin 178–186"/>

Surgeries for oral cancers include:{{citation needed|date=September 2024}}
* Maxillectomy (can be done with or without [[orbital exenteration]])
* Mandibulectomy (removal of the lower jaw or part of it)
* [[Glossectomy]] (tongue removal; can be total, hemi, or partial)
* Radical [[neck dissection]]
* Combinational (e.g., glossectomy and [[laryngectomy]] done together).

The defect is typically covered or improved by using another part of the body and/or skin grafts and/or wearing a [[prosthesis]].{{citation needed|date=September 2024}}

===Nose===
{{Main|Paranasal sinus and nasal cavity cancer|Sinonasal undifferentiated carcinoma}}

[[Paranasal sinus and nasal cavity cancer]] affects the [[nasal cavity]] and the [[paranasal sinuses]]. Most of these cancers are [[Squamous-cell carcinoma|squamous cell carcinomas]].<ref name="NCI19">{{cite web |title=Paranasal Sinus and Nasal Cavity Cancer Treatment (Adult) (PDQ®)–Patient Version |url=https://www.cancer.gov/types/head-and-neck/patient/adult/paranasal-sinus-treatment-pdq |publisher=National Cancer Institute |access-date=4 December 2019 |language=en |date=8 November 2019}}</ref>

===Nasopharynx===
{{main|Nasopharynx cancer}}

Nasopharyngeal cancer arises in the [[nasopharynx]], the region in which the [[nasal cavity|nasal cavities]] and the [[Eustachian tube]]s connect with the upper part of the throat. While some nasopharyngeal cancers are biologically similar to the common head and neck cancers, "poorly differentiated" nasopharyngeal carcinoma is [[lymphoepithelioma]], which is distinct in its [[epidemiology]], biology, clinical behavior, and treatment and is treated as a separate disease by many experts.{{citation needed|date=September 2024}}

===Throat===
{{Main|Oropharyngeal cancer|HPV-positive oropharyngeal cancer}}

Most [[oropharyngeal cancer]]s begin in the [[oropharynx]] (throat), the middle part of the throat that includes the [[soft palate]], the base of the [[tongue]], and the [[tonsil]]s.<ref name="NCI">{{cite web |title=Oropharyngeal Cancer Treatment (Adult) (PDQ®)–Patient Version |url=https://www.cancer.gov/types/head-and-neck/patient/adult/oropharyngeal-treatment-pdq |publisher=National Cancer Institute |access-date=28 November 2019 |language=en |date=22 November 2019}}</ref> Cancers of the tonsils are more strongly associated with [[human papillomavirus]] infection than are cancers of other regions of the head and neck. [[HPV-positive oropharyngeal cancer]] generally has a better outcome than HPV-negative disease, with a 54% better survival rate,<ref>{{cite journal | vauthors = O'Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA | title = Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis | journal = Oral Oncology | volume = 48 | issue = 12 | pages = 1191–1201 | date = December 2012 | pmid = 22841677 | doi = 10.1016/j.oraloncology.2012.06.019 | url = https://www.researchgate.net/publication/237088860 | url-status = live | archive-url = https://web.archive.org/web/20170910182726/https://www.researchgate.net/profile/Liam_Murray/publication/237088860_Human_papillomavirus_related_head_and_neck_cancer_survival_A_systematic_review_and_meta-analysis/links/53d645490cf2a7fbb2ea985f.pdf | archive-date = 2017-09-10 }}</ref> but this advantage for HPV-associated cancer applies only to oropharyngeal cancers.<ref>{{cite journal | vauthors = Ragin CC, Taioli E | title = Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis | journal = International Journal of Cancer | volume = 121 | issue = 8 | pages = 1813–1820 | date = October 2007 | pmid = 17546592 | doi = 10.1002/ijc.22851 | doi-access = free }}</ref>

People with oropharyngeal carcinomas are at high risk of developing a second primary head and neck cancer.<ref>{{cite journal | vauthors = Krishnatreya M, Rahman T, Kataki AC, Das A, Das AK, Lahkar K | title = Synchronous primary cancers of the head and neck region and upper aero digestive tract: defining high-risk patients | journal = Indian Journal of Cancer | volume = 50 | issue = 4 | pages = 322–326 | date = 2013 | pmid = 24369209 | doi = 10.4103/0019-509x.123610 | doi-access = free }}</ref>

===Hypopharynx===
{{Main|Hypopharyngeal cancer}}

The [[hypopharynx]] includes the pyriform sinuses, the posterior pharyngeal wall, and the postcricoid area. Tumors of the hypopharynx frequently have an advanced stage at diagnosis and have the most adverse prognoses of pharyngeal tumors. They tend to [[metastasis|metastasize]] early due to the extensive lymphatic network around the [[larynx]].{{citation needed|date=September 2024}}

===Larynx===
{{Main|Laryngeal cancer}}

Laryngeal cancer begins in the [[larynx]], or "voice box", and is the second most common type of head and neck cancer encountered.<ref name="Aupérin 178–186"/> Cancer may occur on the [[vocal folds]] themselves ("glottic" cancer) or on tissues above and below the true cords ("supraglottic" and "subglottic" cancers, respectively). Laryngeal cancer is strongly associated with [[tobacco smoking]].{{citation needed|date=September 2024}}

Surgery can include laser excision of small vocal cord lesions, partial laryngectomy (removal of part of the larynx), or total laryngectomy (removal of the whole larynx). If the whole larynx has been removed, the person is left with a permanent tracheostomy. Voice rehabilitation in such patients can be achieved in three important ways: esophageal speech, tracheoesophageal puncture, or electrolarynx. One would likely require intensive teaching, speech therapy, and/or an electronic device.{{citation needed|date=September 2024}}

===Trachea and salivary glands===
[[Tracheal tumor|Cancer of the trachea]] is a rare cancer usually classified as a [[lung cancer]].<ref>{{cite web |title=Throat cancer {{!}} Head and neck cancers |publisher=Cancer Research UK |url=https://www.cancerresearchuk.org/about-cancer/head-neck-cancer/throat |access-date=28 November 2019}}</ref>

Most [[Salivary gland tumour|tumors of the salivary glands]] differ from the common head and neck cancers in cause, [[histopathology]], clinical presentation, and therapy. Other uncommon tumors arising in the head and neck include [[teratoma]]s, [[adenocarcinomas]], [[adenoid cystic carcinoma]]s, and [[mucoepidermoid carcinoma]]s.<ref name="ridge">{{cite book |title=Cancer management: a multidisciplinary approach. |vauthors=Ridge JA, Glisson BS, Lango MN, Feigenberg S, Horwitz EM |date=2008 |isbn=978-1-891483-62-2 |veditors=Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ |edition=11th |pages=39–86 |chapter=Head and neck tumors. |publisher=Cmp United Business Media |chapter-url=http://thymic.org/uploads/reference_sub/04headneck.pdf}}</ref> Rarer still are [[melanomas]] and [[lymphomas]] of the upper aerodigestive tract.{{citation needed|date=September 2024}}

==Causes==
===Alcohol and tobacco===
{{Main|Tobacco smoking|Alcohol and cancer}}

[[Alcohol (drug)|Alcohol]] and [[tobacco]] use are major risk factors for head and neck cancer.  72% of head and neck cancer cases are caused by using both alcohol and tobacco.<ref name=":6">{{Cite journal |last1=Gormley |first1=Mark |last2=Creaney |first2=Grant |last3=Schache |first3=Andrew |last4=Ingarfield |first4=Kate |last5=Conway |first5=David I. |date=2022-11-11 |title=Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors |journal=British Dental Journal |language=en |volume=233 |issue=9 |pages=780–786 |doi=10.1038/s41415-022-5166-x |pmid=36369568 |pmc=9652141 |issn=0007-0610}}</ref> This rises to 89% when looking specifically at laryngeal cancer.<ref>{{Cite journal |last1=Hashibe |first1=Mia |last2=Brennan |first2=Paul |last3=Chuang |first3=Shu-chun |last4=Boccia |first4=Stefania |last5=Castellsague |first5=Xavier |last6=Chen |first6=Chu |last7=Curado |first7=Maria Paula |last8=Dal Maso |first8=Luigino |last9=Daudt |first9=Alexander W. |last10=Fabianova |first10=Eleonora |last11=Fernandez |first11=Leticia |last12=Wünsch-Filho |first12=Victor |last13=Franceschi |first13=Silvia |last14=Hayes |first14=Richard B. |last15=Herrero |first15=Rolando |date=2009-02-01 |title=Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium |journal=Cancer Epidemiology, Biomarkers & Prevention |language=en |volume=18 |issue=2 |pages=541–550 |doi=10.1158/1055-9965.EPI-08-0347 |issn=1055-9965 |pmc=3051410 |pmid=19190158}}</ref>

There is thought to be a dose-dependent relationship between alcohol use and development of head and neck cancer where higher rates of alcohol consumption contribute to an increased risk of developing head and neck cancer.<ref>{{Cite journal |last1=Tramacere |first1=Irene |last2=Negri |first2=Eva |last3=Bagnardi |first3=Vincenzo |last4=Garavello |first4=Werner |last5=Rota |first5=Matteo |last6=Scotti |first6=Lorenza |last7=Islami |first7=Farhad |last8=Corrao |first8=Giovanni |last9=Boffetta |first9=Paolo |last10=La Vecchia |first10=Carlo |date=4 May 2010 |title=A meta-analysis of alcohol drinking and oral and pharyngeal cancers. Part 1: Overall results and dose-risk relation |url=https://linkinghub.elsevier.com/retrieve/pii/S1368837510001363 |journal=Oral Oncology |language=en |volume=46 |issue=7 |pages=497–503 |doi=10.1016/j.oraloncology.2010.03.024|pmid=20444641 |url-access=subscription }}</ref><ref>{{Cite journal |last1=Bagnardi |first1=V |last2=Rota |first2=M |last3=Botteri |first3=E |last4=Tramacere |first4=I |last5=Islami |first5=F |last6=Fedirko |first6=V |last7=Scotti |first7=L |last8=Jenab |first8=M |last9=Turati |first9=F |last10=Pasquali |first10=E |last11=Pelucchi |first11=C |last12=Galeone |first12=C |last13=Bellocco |first13=R |last14=Negri |first14=E |last15=Corrao |first15=G |date=25 November 2014 |title=Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis |journal=British Journal of Cancer |language=en |volume=112 |issue=3 |pages=580–593 |doi=10.1038/bjc.2014.579 |issn=0007-0920 |pmc=4453639 |pmid=25422909}}</ref> Alcohol use following a diagnosis of head and neck cancer also contributes to other negative outcomes. These include physical effects such as an increased risk of developing a second primary cancer or other malignancies,<ref>{{Cite journal |last1=Leoncini |first1=Emanuele |last2=Vukovic |first2=Vladimir |last3=Cadoni |first3=Gabriella |last4=Giraldi |first4=Luca |last5=Pastorino |first5=Roberta |last6=Arzani |first6=Dario |last7=Petrelli |first7=Livia |last8=Wünsch-Filho |first8=Victor |last9=Toporcov |first9=Tatiana Natasha |last10=Moyses |first10=Raquel Ayub |last11=Matsuo |first11=Keitaro |last12=Bosetti |first12=Cristina |last13=La Vecchia |first13=Carlo |last14=Serraino |first14=Diego |last15=Simonato |first15=Lorenzo |date=19 May 2018 |title=Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium |journal=European Journal of Epidemiology |language=en |volume=33 |issue=12 |pages=1205–1218 |doi=10.1007/s10654-018-0409-5 |pmid=29779202 |pmc=6290648 |issn=0393-2990}}</ref><ref>{{Cite journal |last1=Chuang |first1=Shu-Chun |last2=Scelo |first2=Ghislaine |last3=Tonita |first3=Jon M. |last4=Tamaro |first4=Sharon |last5=Jonasson |first5=Jon G. |last6=Kliewer |first6=Erich V. |last7=Hemminki |first7=Kari |last8=Weiderpass |first8=Elisabete |last9=Pukkala |first9=Eero |last10=Tracey |first10=Elizabeth |last11=Friis |first11=Soren |last12=Pompe-Kirn |first12=Vera |last13=Brewster |first13=David H. |last14=Martos |first14=Carmen |last15=Chia |first15=Kee-Seng |date=2008-11-15 |title=Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries |url=https://onlinelibrary.wiley.com/doi/10.1002/ijc.23798 |journal=International Journal of Cancer |language=en |volume=123 |issue=10 |pages=2390–2396 |doi=10.1002/ijc.23798 |pmid=18729183 |issn=0020-7136|url-access=subscription }}</ref> cancer recurrence,<ref>{{Cite journal |last1=Cadoni |first1=G. |last2=Giraldi |first2=L. |last3=Petrelli |first3=L. |last4=Pandolfini |first4=M. |last5=Giuliani |first5=M. |last6=Paludetti |first6=G. |last7=Pastorino |first7=R. |last8=Leoncini |first8=E. |last9=Arzani |first9=D. |last10=Almadori |first10=G. |last11=Boccia |first11=S. |date=December 2017 |title=Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy |url=http://www.actaitalica.it/issues/2017/6-2017/03_CADONI.pdf |journal=Acta Otorhinolaryngologica Italica |volume=37 |issue=6 |pages=458–466 |doi=10.14639/0392-100X-1246 |pmid=28663597 |pmc=5782422 |issn=0392-100X}}</ref> and worse prognosis<ref>{{Cite journal |last1=Sawabe |first1=Michi |last2=Ito |first2=Hidemi |last3=Oze |first3=Isao |last4=Hosono |first4=Satoyo |last5=Kawakita |first5=Daisuke |last6=Tanaka |first6=Hideo |last7=Hasegawa |first7=Yasuhisa |last8=Murakami |first8=Shingo |last9=Matsuo |first9=Keitaro |date=2017-01-26 |title=Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study |journal=Cancer Science |language=en |volume=108 |issue=1 |pages=91–100 |doi=10.1111/cas.13115 |pmid=27801961 |pmc=5276823 |issn=1347-9032}}</ref> in addition to an increased chance of having a future [[feeding tube]] placed and [[osteoradionecrosis]] of the jaw. Negative social factors are also increased with sustained alcohol use after diagnosis including unemployment and work disability.<ref name=":5">{{Cite journal |last1=Marziliano |first1=Allison |last2=Teckie |first2=Sewit |last3=Diefenbach |first3=Michael A. |date=27 November 2019 |title=Alcohol-related head and neck cancer: Summary of the literature |journal=Head & Neck |volume=42 |issue=4 |pages=732–738 |doi=10.1002/hed.26023 |issn=1097-0347 |pmid=31777131}}</ref><ref>{{Cite journal |last1=Simcock |first1=R. |last2=Simo |first2=R. |date=2016-04-16 |title=Follow-up and Survivorship in Head and Neck Cancer |url=https://linkinghub.elsevier.com/retrieve/pii/S0936655516300061 |journal=Clinical Oncology |language=en |volume=28 |issue=7 |pages=451–458 |doi=10.1016/j.clon.2016.03.004|pmid=27094976 |url-access=subscription }}</ref>

The way in which alcohol contributes to cancer development is not fully understood. It is thought to be related to permanent damage of DNA strands by a metabolite of alcohol called [[acetaldehyde]]. Other suggested mechanisms include nutritional deficiencies and genetic variations.<ref name=":5" />

[[Tobacco smoking]] is one of the main risk factors for head and neck cancer. Cigarette smokers have a lifetime increased risk for head and neck cancer that is 5 to 25 times higher than the general population.<ref>{{cite journal |vauthors=Andre K, Schraub S, Mercier M, Bontemps P |date=September 1995 |title=Role of alcohol and tobacco in the aetiology of head and neck cancer: a case-control study in the Doubs region of France |journal=European Journal of Cancer, Part B |volume=31B |issue=5 |pages=301–309 |doi=10.1016/0964-1955(95)00041-0 |pmid=8704646}}</ref> The ex-smoker's risk of developing head and neck cancer begins to approach the risk in the general population 15 years after [[smoking cessation]].<ref>{{cite journal |vauthors=La Vecchia C, Franceschi S, Bosetti C, Levi F, Talamini R, Negri E |date=April 1999 |title=Time since stopping smoking and the risk of oral and pharyngeal cancers |journal=Journal of the National Cancer Institute |volume=91 |issue=8 |pages=726–728 |doi=10.1093/jnci/91.8.726a |pmid=10218516 |hdl-access=free |hdl=2434/520105}}</ref> In addition, people who smoke have a worse prognosis than those who have never smoked.<ref>{{Cite journal |last1=Fortin |first1=André |last2=Wang |first2=Chang Shu |last3=Vigneault |first3=Éric |date=2008-11-25 |title=Influence of Smoking and Alcohol Drinking Behaviors on Treatment Outcomes of Patients With Squamous Cell Carcinomas of the Head and Neck |url=https://linkinghub.elsevier.com/retrieve/pii/S0360301608034998 |journal=International Journal of Radiation Oncology*Biology*Physics |language=en |volume=74 |issue=4 |pages=1062–1069 |doi=10.1016/j.ijrobp.2008.09.021|pmid=19036528 |url-access=subscription }}</ref> Furthermore, people who continue to smoke after diagnosis of head and neck cancer have the highest probability of dying compared to those who have never smoked.<ref>{{Cite journal |last1=Merlano |first1=Marco Carlo |last2=Denaro |first2=Nerina |last3=Galizia |first3=Danilo |last4=Abbona |first4=Andrea |last5=Paccagnella |first5=Matteo |last6=Minei |first6=Silvia |last7=Garrone |first7=Ornella |last8=Bossi |first8=Paolo |date=20 April 2023 |title=Why Oncologists Should Feel Directly Involved in Persuading Patients with Head and Neck Cancer to Quit Smoking |url=https://karger.com/OCL/article/doi/10.1159/000528345 |journal=Oncology |language=en |volume=101 |issue=4 |pages=252–256 |doi=10.1159/000528345 |pmid=36538910 |issn=0030-2414|url-access=subscription }}</ref><ref>{{Cite journal |last1=von Kroge |first1=Patricia R. |last2=Bokemeyer |first2=Frederike |last3=Ghandili |first3=Susanne |last4=Bokemeyer |first4=Carsten |last5=Seidel |first5=Christoph |date=18 September 2020 |title=The Impact of Smoking Cessation and Continuation on Recurrence and Survival in Patients with Head and Neck Cancer: A Systematic Review of the Literature |url=https://karger.com/ORT/article/doi/10.1159/000509427 |journal=Oncology Research and Treatment |language=en |volume=43 |issue=10 |pages=549–558 |doi=10.1159/000509427 |pmid=32950990 |issn=2296-5270|url-access=subscription }}</ref> This effect is seen in patients with HPV-positive head and neck cancer as well.<ref>{{Cite journal |last1=Descamps |first1=Géraldine |last2=Karaca |first2=Yasemin |last3=Lechien |first3=Jérôme R |last4=Kindt |first4=Nadège |last5=Decaestecker |first5=Christine |last6=Remmelink |first6=Myriam |last7=Larsimont |first7=Denis |last8=Andry |first8=Guy |last9=Hassid |first9=Samantha |last10=Rodriguez |first10=Alexandra |last11=Khalife |first11=Mohammad |last12=Journe |first12=Fabrice |last13=Saussez |first13=Sven |date=2016-07-01 |title=Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients |journal=Journal of Cancer Research and Clinical Oncology |language=en |volume=142 |issue=10 |pages=2185–2196 |doi=10.1007/s00432-016-2203-7 |issn=0171-5216 |pmc=5018052 |pmid=27370781}}</ref><ref>{{Cite journal |last1=Desrichard |first1=Alexis |last2=Kuo |first2=Fengshen |last3=Chowell |first3=Diego |last4=Lee |first4=Ken-Wing |last5=Riaz |first5=Nadeem |last6=Wong |first6=Richard J |last7=Chan |first7=Timothy A |last8=Morris |first8=Luc G T |date=2018-12-01 |title=Tobacco Smoking-Associated Alterations in the Immune Microenvironment of Squamous Cell Carcinomas |url=https://academic.oup.com/jnci/article/110/12/1386/4968036 |journal=JNCI: Journal of the National Cancer Institute |language=en |volume=110 |issue=12 |pages=1386–1392 |doi=10.1093/jnci/djy060 |issn=0027-8874 |pmc=6292793 |pmid=29659925}}</ref><ref>{{Cite journal |last1=Ang |first1=K. Kian |last2=Harris |first2=Jonathan |last3=Wheeler |first3=Richard |last4=Weber |first4=Randal |last5=Rosenthal |first5=David I. |last6=Nguyen-Tân |first6=Phuc Felix |last7=Westra |first7=William H. |last8=Chung |first8=Christine H. |last9=Jordan |first9=Richard C. |last10=Lu |first10=Charles |last11=Kim |first11=Harold |last12=Axelrod |first12=Rita |last13=Silverman |first13=C. Craig |last14=Redmond |first14=Kevin P. |last15=Gillison |first15=Maura L. |date=2010-06-07 |title=Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer |journal=New England Journal of Medicine |language=en |volume=363 |issue=1 |pages=24–35 |doi=10.1056/NEJMoa0912217 |pmid=20530316 |pmc=2943767 |issn=0028-4793}}</ref> It has also been demonstrated that [[passive smoking]], both at work and at home, increases the risk of head and neck cancer.<ref name=":6" />

A major carcinogenic compound in [[tobacco smoke]] is [[acrylonitrile]].<ref name="Cunningham">{{cite journal | vauthors = Cunningham FH, Fiebelkorn S, Johnson M, Meredith C | title = A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants | journal = Food and Chemical Toxicology | volume = 49 | issue = 11 | pages = 2921–2933 | date = November 2011 | pmid = 21802474 | doi = 10.1016/j.fct.2011.07.019 }}</ref> Acrylonitrile appears to indirectly cause [[DNA damage]] by increasing [[oxidative stress]], leading to increased levels of [[8-oxo-2'-deoxyguanosine]] (8-oxo-dG) and [[DNA-formamidopyrimidine glycosylase|formamidopyrimidine]] in DNA.<ref name="pmid19546159">{{cite journal | vauthors = Pu X, Kamendulis LM, Klaunig JE | title = Acrylonitrile-induced oxidative stress and oxidative DNA damage in male Sprague-Dawley rats | journal = Toxicological Sciences | volume = 111 | issue = 1 | pages = 64–71 | date = September 2009 | pmid = 19546159 | pmc = 2726299 | doi = 10.1093/toxsci/kfp133 }}</ref> (see image). Both 8-oxo-dG and formamidopyrimidine are [[mutagen]]ic.<ref name="pmid16679449">{{cite journal | vauthors = Kalam MA, Haraguchi K, Chandani S, Loechler EL, Moriya M, Greenberg MM, Basu AK | title = Genetic effects of oxidative DNA damages: comparative mutagenesis of the imidazole ring-opened formamidopyrimidines (Fapy lesions) and 8-oxo-purines in simian kidney cells | journal = Nucleic Acids Research | volume = 34 | issue = 8 | pages = 2305–2315 | year = 2006 | pmid = 16679449 | pmc = 1458282 | doi = 10.1093/nar/gkl099 }}</ref><ref name="pmid23934915">{{cite journal | vauthors = Jena NR, Mishra PC | title = Is FapyG mutagenic?: Evidence from the DFT study | journal = ChemPhysChem | volume = 14 | issue = 14 | pages = 3263–3270 | date = October 2013 | pmid = 23934915 | doi = 10.1002/cphc.201300535 }}</ref> [[DNA glycosylase]] [[NEIL1]] prevents [[mutagenesis]] by 8-oxo-dG<ref name="pmid20197241">{{cite journal | vauthors = Suzuki T, Harashima H, Kamiya H | title = Effects of base excision repair proteins on mutagenesis by 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) paired with cytosine and adenine | journal = DNA Repair | volume = 9 | issue = 5 | pages = 542–550 | date = May 2010 | pmid = 20197241 | doi = 10.1016/j.dnarep.2010.02.004 | hdl-access = free | hdl = 2115/43021 | s2cid = 207147128 }}</ref> and removes formamidopyrimidines from DNA.<ref name="pmid20955798">{{cite journal | vauthors = Nemec AA, Wallace SS, Sweasy JB | title = Variant base excision repair proteins: contributors to genomic instability | journal = Seminars in Cancer Biology | volume = 20 | issue = 5 | pages = 320–328 | date = October 2010 | pmid = 20955798 | pmc = 3254599 | doi = 10.1016/j.semcancer.2010.10.010 }}</ref>

[[Smokeless tobacco]] (including products where tobacco is [[Chewing tobacco|chewed]]) is a cause of [[oral cancer]]. Increased risk of oral cancer caused by smokeless tobacco is present in countries such as the United States but particularly prevalent in [[Southeast Asia|Southeast Asian countries]] where the use of smokeless tobacco is common.<ref name="Aupérin 178–186" /><ref>{{cite journal |display-authors=6 |vauthors=Wyss AB, Hashibe M, Lee YA, Chuang SC, Muscat J, Chen C, Schwartz SM, Smith E, Zhang ZF, Morgenstern H, Wei Q, Li G, Kelsey KT, McClean M, Winn DM, Schantz S, Yu GP, Gillison ML, Zevallos JP, Boffetta P, Olshan AF |date=November 2016 |title=Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the INHANCE Consortium |journal=American Journal of Epidemiology |volume=184 |issue=10 |pages=703–716 |doi=10.1093/aje/kww075 |pmc=5141945 |pmid=27744388}}</ref><ref name=":7">{{Cite journal |last1=Hecht |first1=Stephen S. |last2=Hatsukami |first2=Dorothy K. |date=3 January 2022 |title=Smokeless tobacco and cigarette smoking: chemical mechanisms and cancer prevention |journal=Nature Reviews Cancer |language=en |volume=22 |issue=3 |pages=143–155 |doi=10.1038/s41568-021-00423-4 |pmid=34980891 |pmc=9308447 |issn=1474-175X}}</ref> Smokeless tobacco is associated with a higher risk of developing head and neck cancer  due to the presence of the tobacco-specific carcinogen [[N-Nitrosonornicotine|N'-nitrosonornicotine]].<ref name=":7" />

[[Cigar]] and [[pipe smoking]] are also important risk factors for oral cancer.<ref>{{Cite journal |last1=Wyss |first1=Annah |last2=Hashibe |first2=Mia |last3=Chuang |first3=Shu-Chun |last4=Lee |first4=Yuan-Chin Amy |last5=Zhang |first5=Zuo-Feng |last6=Yu |first6=Guo-Pei |last7=Winn |first7=Deborah M. |last8=Wei |first8=Qingyi |last9=Talamini |first9=Renato |last10=Szeszenia-Dabrowska |first10=Neonila |last11=Sturgis |first11=Erich M. |last12=Smith |first12=Elaine |last13=Shangina |first13=Oxana |last14=Schwartz |first14=Stephen M. |last15=Schantz |first15=Stimson |date=2013-09-01 |title=Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium |journal=American Journal of Epidemiology |language=en |volume=178 |issue=5 |pages=679–690 |doi=10.1093/aje/kwt029 |pmid=23817919 |pmc=3755640 |issn=1476-6256}}</ref> They have a dose dependent relationship with more consumption leading to higher chances of developing cancer.<ref name=":6" /> The use of [[electronic cigarette]]s may also lead to the development of head and neck cancers due to the substances like [[propylene glycol]], [[glycerol]], [[nitrosamine]]s, and metals contained therein, which can cause damage to the airways.<ref name="ReferenceB">{{cite journal | vauthors = Ralho A, Coelho A, Ribeiro M, Paula A, Amaro I, Sousa J, Marto C, Ferreira M, Carrilho E | display-authors = 6 | title = Effects of Electronic Cigarettes on Oral Cavity: A Systematic Review | journal = The Journal of Evidence-Based Dental Practice | volume = 19 | issue = 4 | article-number = 101318 | date = December 2019 | pmid = 31843181 | doi = 10.1016/j.jebdp.2019.04.002 | s2cid = 145920823 }}</ref><ref name="Aupérin 178–186" /> Exposure to e-vapour has been shown to reduce cell viability and increase the rate of [[cell death]] via [[apoptosis]] or [[necrosis]] with or without nicotine.<ref>{{Cite journal |last1=Esteban-Lopez |first1=Maria |last2=Perry |first2=Marissa D. |last3=Garbinski |first3=Luis D. |last4=Manevski |first4=Marko |last5=Andre |first5=Mickensone |last6=Ceyhan |first6=Yasemin |last7=Caobi |first7=Allen |last8=Paul |first8=Patience |last9=Lau |first9=Lee Seng |last10=Ramelow |first10=Julian |last11=Owens |first11=Florida |last12=Souchak |first12=Joseph |last13=Ales |first13=Evan |last14=El-Hage |first14=Nazira |date=23 June 2022 |title=Health effects and known pathology associated with the use of E-cigarettes |journal=Toxicology Reports |language=en |volume=9 |pages=1357–1368 |doi=10.1016/j.toxrep.2022.06.006 |pmc=9764206 |pmid=36561957|bibcode=2022ToxR....9.1357E }}</ref> This area of study requires more research, however.<ref name="ReferenceB" /><ref name="Aupérin 178–186" /> Similarly, additional research is needed to understand how [[Cannabis (drug)|marijuana]] possibly promotes head and neck cancers.<ref name="Gallagher 2024">{{Cite journal |last1=Gallagher |first1=Tyler J. |last2=Chung |first2=Ryan S. |last3=Lin |first3=Matthew E. |last4=Kim |first4=Ian |last5=Kokot |first5=Niels C. |date=2024-08-08 |title=Cannabis Use and Head and Neck Cancer |journal=JAMA Otolaryngology–Head & Neck Surgery |volume=150 |issue=12 |pages=1068–1075 |doi=10.1001/jamaoto.2024.2419 |pmid=39115834 |pmc=11310842 |issn=2168-6181}}</ref> A 2019 meta-analysis did not conclude that marijuana was associated with head and neck cancer risk.<ref>{{Cite journal |last1=Ghasemiesfe |first1=Mehrnaz |last2=Barrow |first2=Brooke |last3=Leonard |first3=Samuel |last4=Keyhani |first4=Salomeh |last5=Korenstein |first5=Deborah |date=2019-11-27 |title=Association Between Marijuana Use and Risk of Cancer: A Systematic Review and Meta-analysis |journal=JAMA Network Open |language=en |volume=2 |issue=11 |pages=e1916318 |doi=10.1001/jamanetworkopen.2019.16318 |issn=2574-3805 |pmc=6902836 |pmid=31774524}}</ref> Yet individuals with cannabis use disorder were more likely to be diagnosed with such cancers in a large study published 2024.<ref name="Gallagher 2024" />

===Diet===
Many dietary nutrients are associated with cancer protection and its development. Generally, foods with a protective effect with respect to oral cancer demonstrate [[antioxidant]] and [[Anti-inflammatory|anti-inflammatory effects]] such as fruits, vegetables, [[curcumin]] and [[green tea]]. Conversely, pro-inflammatory food substances such as [[red meat]], [[processed meat]] and fried food can increase the risk of developing head and neck cancer.<ref name=":6" /><ref>{{Cite journal |last1=Rodríguez-Molinero |first1=Jesús |last2=Migueláñez-Medrán |first2=Blanca del Carmen |last3=Puente-Gutiérrez |first3=Cristina |last4=Delgado-Somolinos |first4=Esther |last5=Martín Carreras-Presas |first5=Carmen |last6=Fernández-Farhall |first6=Javier |last7=López-Sánchez |first7=Antonio Francisco |date=2021-04-15 |title=Association between Oral Cancer and Diet: An Update |journal=Nutrients |language=en |volume=13 |issue=4 |page=1299 |doi=10.3390/nu13041299 |doi-access=free |pmid=33920788 |pmc=8071138 |issn=2072-6643}}</ref> An increased adherence to the [[Mediterranean diet]] is also related to a lower risk of cancer mortality and a reduced risk of developing multiple cancers including head and neck cancer.<ref>{{Cite journal |last1=Morze |first1=Jakub |last2=Danielewicz |first2=Anna |last3=Przybyłowicz |first3=Katarzyna |last4=Zeng |first4=Hongmei |last5=Hoffmann |first5=Georg |last6=Schwingshackl |first6=Lukas |date=April 2021 |title=An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer |journal=European Journal of Nutrition |language=en |volume=60 |issue=3 |pages=1561–1586 |doi=10.1007/s00394-020-02346-6 |issn=1436-6207 |pmc=7987633 |pmid=32770356}}</ref> Elevated levels of [[nitrite]]s in preserved meats and [[salted fish]] have been shown to increase the risk of nasopharyngeal cancer.<ref name=":8">{{Cite journal |last1=Barsouk |first1=Adam |last2=Aluru |first2=John Sukumar |last3=Rawla |first3=Prashanth |last4=Saginala |first4=Kalyan |last5=Barsouk |first5=Alexander |date=2023-06-13 |title=Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma |journal=Medical Sciences |language=en |volume=11 |issue=2 |page=42 |doi=10.3390/medsci11020042 |doi-access=free |issn=2076-3271 |pmc=10304137 |pmid=37367741}}</ref><ref>{{Cite journal |last=Lian |first=Mei |date=30 January 2022 |title=Salted fish and processed foods intake and nasopharyngeal carcinoma risk: a dose–response meta-analysis of observational studies |url=https://link.springer.com/10.1007/s00405-021-07210-9 |journal=European Archives of Oto-Rhino-Laryngology |language=en |volume=279 |issue=5 |pages=2501–2509 |doi=10.1007/s00405-021-07210-9 |pmid=35094122 |issn=0937-4477|url-access=subscription }}</ref> Overall, a poor nutritional intake (often associated with alcoholism) with subsequent [[Vitamin deficiency|vitamin deficiencies]] is a risk factor for head and neck cancer.<ref name=":8" /><ref name="ridge" />

In terms of nutritional supplements, antioxidants such as [[vitamin E]] and [[Β-Carotene|beta-carotene]] might reduce the toxic effect of radiotherapy in people with head and neck cancer but they can also increase recurrence rates, especially in smokers.<ref>{{Cite journal |last=Harvie |first=Michelle |date=2014-05-30 |title=Nutritional Supplements and Cancer: Potential Benefits and Proven Harms |url=https://ascopubs.org/doi/10.14694/EdBook_AM.2014.34.e478 |journal=American Society of Clinical Oncology Educational Book |language=en |issue=34 |pages=e478–e486 |doi=10.14694/EdBook_AM.2014.34.e478 |pmid=24857143 |issn=1548-8748}}</ref>

===Betel nut===
[[Betel nut chewing]] is associated with an increased risk of head and neck cancer.<ref name="NCI" /><ref>{{cite journal | vauthors = Jeng JH, Chang MC, Hahn LJ | title = Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives | journal = Oral Oncology | volume = 37 | issue = 6 | pages = 477–492 | date = September 2001 | pmid = 11435174 | doi = 10.1016/S1368-8375(01)00003-3 }}</ref> When chewed with additional tobacco in its preparation (like in [[gutka]]), there is an even higher risk, especially for oral and oropharyngeal cancers.<ref name=":6" />

=== Genetics ===
People who develop head and neck cancer may have a [[genetic predisposition]] for the condition. There are seven known genetic variations ([[Locus (genetics)|loci]]) which specifically increase the chances of developing oral and pharyngeal cancer.<ref>{{Cite journal |last1=Lesseur |first1=Corina |last2=Diergaarde |first2=Brenda |last3=Olshan |first3=Andrew F |last4=Wünsch-Filho |first4=Victor |last5=Ness |first5=Andrew R |last6=Liu |first6=Geoffrey |last7=Lacko |first7=Martin |last8=Eluf-Neto |first8=José |last9=Franceschi |first9=Silvia |last10=Lagiou |first10=Pagona |last11=Macfarlane |first11=Gary J |last12=Richiardi |first12=Lorenzo |last13=Boccia |first13=Stefania |last14=Polesel |first14=Jerry |last15=Kjaerheim |first15=Kristina |date=17 October 2016 |title=Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer |journal=Nature Genetics |language=en |volume=48 |issue=12 |pages=1544–1550 |doi=10.1038/ng.3685 |pmid=27749845 |pmc=5131845 |issn=1061-4036}}</ref><ref>{{Cite journal |last1=Shete |first1=Sanjay |last2=Liu |first2=Hongliang |last3=Wang |first3=Jian |last4=Yu |first4=Robert |last5=Sturgis |first5=Erich M. |last6=Li |first6=Guojun |last7=Dahlstrom |first7=Kristina R. |last8=Liu |first8=Zhensheng |last9=Amos |first9=Christopher I. |last10=Wei |first10=Qingyi |date=2020-06-15 |title=A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck |journal=Cancer Research |language=en |volume=80 |issue=12 |pages=2451–2460 |doi=10.1158/0008-5472.CAN-19-2360 |issn=0008-5472 |pmc=7299763 |pmid=32276964}}</ref> Family history, that is having a first-degree relative with head and neck cancer, is also a risk factor. In addition, genetic variations in pathways involved in [[Ethanol metabolism|alcohol metabolism]] (for example [[alcohol dehydrogenase]]) have been associated with an increased head and neck cancer risk.<ref name=":6" />

=== Radiation ===
It is known that prior exposure to [[Ionizing radiation|radiation]] of the head and neck is associated with an increased risk of cancer, particularly thyroid, salivary gland and squamous cell carcinomas, although there is a time-delay of many years and the overall risk is still low.<ref name=":8" />

===Infection===
====Human papillomavirus====
Some head and neck cancers, and in particular [[oropharyngeal cancer]], are caused by the [[human papillomavirus]] (HPV),<ref name="NCI" /><ref name=":9">{{Cite journal |last1=El Hussein |first1=Mohamed Toufic |last2=Dhaliwal |first2=Simreen |date=October 2023 |title=HPV vaccination for prevention of head and neck cancer among men |url=https://journals.lww.com/10.1097/01.NPR.0000000000000099 |journal=The Nurse Practitioner |language=en |volume=48 |issue=10 |pages=25–32 |doi=10.1097/01.NPR.0000000000000099 |pmid=37751612 |issn=0361-1817|url-access=subscription }}</ref> and 70% of all head and neck cancer cases are related to HPV.<ref name=":9" /> Risk factors for [[HPV-positive oropharyngeal cancer]] include multiple sexual partners, anal and oral sex and a weak immune system.<ref name=":8" /> HPV-related head and neck cancer (throat and mouth) can affect both females and males. Increasing HPV-cancer rates in males in the United Kingdom resulted in the [[HPV vaccine]] being offered to adolescent boys between 12 and 13 (previously only offered to girls between this age due to [[cervical cancer]] risks) and men under 45 [[Men who have sex with men|who have sex with men]].<ref>{{Cite journal |last1=Merriel |first1=Samuel WD |last2=Nadarzynski |first2=Tom |last3=Kesten |first3=Joanna M |last4=Flannagan |first4=Carrie |last5=Prue |first5=Gillian |date=2018-08-30 |title='Jabs for the boys': time to deliver on HPV vaccination recommendations |journal=British Journal of General Practice |language=en |volume=68 |issue=674 |pages=406–407 |doi=10.3399/bjgp18X698429 |issn=0960-1643 |pmc=6104855 |pmid=30166370}}</ref><ref>{{Cite web |date=2024-03-06 |title=HPV vaccine |url=https://www.nhs.uk/vaccinations/hpv-vaccine/ |access-date=2024-05-28 |publisher=NHS |language=en}}</ref>

Over 20 different high-risk HPV subtypes have been implicated in causing head and neck cancer. In particular, HPV-16 is responsible for up to 90% of oropharyngeal cancer in North America.<ref name=":8" />  Approximately 15–25% of head and neck cancers contain genomic DNA from HPV,<ref>{{cite journal | vauthors = Kreimer AR, Clifford GM, Boyle P, Franceschi S | title = Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 14 | issue = 2 | pages = 467–475 | date = February 2005 | pmid = 15734974 | doi = 10.1158/1055-9965.EPI-04-0551 | doi-access = free }}</ref> and the association varies based on the site of the tumor.<ref name="Andrew W 2012">{{cite journal | vauthors = Joseph AW, D'Souza G | title = Epidemiology of human papillomavirus-related head and neck cancer | journal = Otolaryngologic Clinics of North America | volume = 45 | issue = 4 | pages = 739–764 | date = August 2012 | pmid = 22793850 | doi = 10.1016/j.otc.2012.04.003 }}</ref> In the case of [[HPV-positive oropharyngeal cancer]], the highest distribution is in the [[tonsils]], where HPV DNA is found in 45–67% of the cases,<ref>{{cite journal | vauthors = Perez-Ordoñez B, Beauchemin M, Jordan RC | title = Molecular biology of squamous cell carcinoma of the head and neck | journal = Journal of Clinical Pathology | volume = 59 | issue = 5 | pages = 445–453 | date = May 2006 | pmid = 16644882 | pmc = 1860277 | doi = 10.1136/jcp.2003.007641 }}</ref> and it is less often in the hypopharynx (13–25%), and least often in the oral cavity (12–18%) and larynx (3–7%).<ref>{{cite journal | vauthors = Paz IB, Cook N, Odom-Maryon T, Xie Y, Wilczynski SP | title = Human papillomavirus (HPV) in head and neck cancer. An association of HPV 16 with squamous cell carcinoma of Waldeyer's tonsillar ring | journal = Cancer | volume = 79 | issue = 3 | pages = 595–604 | date = February 1997 | pmid = 9028373 | doi = 10.1002/(SICI)1097-0142(19970201)79:3<595::AID-CNCR24>3.0.CO;2-Y | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hobbs CG, Sterne JA, Bailey M, Heyderman RS, Birchall MA, Thomas SJ | title = Human papillomavirus and head and neck cancer: a systematic review and meta-analysis | journal = Clinical Otolaryngology | volume = 31 | issue = 4 | pages = 259–266 | date = August 2006 | pmid = 16911640 | doi = 10.1111/j.1749-4486.2006.01246.x | url = http://www.drchrishobbs.com/uploads/8/2/1/2/8212308/hpv__hnscc.pdf | url-status = live | s2cid = 2502403 | archive-url = https://web.archive.org/web/20170811041708/http://www.drchrishobbs.com/uploads/8/2/1/2/8212308/hpv__hnscc.pdf | archive-date = 2017-08-11 }}</ref>

Positive HPV16 status is associated with an improved prognosis over HPV-negative oropharyngeal cancer due to better response to [[Radiation therapy|radiotherapy]] and [[chemotherapy]].<ref name=":10">{{Cite journal |last1=Sabatini |first1=Maria Elisa |last2=Chiocca |first2=Susanna |date=2020-02-04 |title=Human papillomavirus as a driver of head and neck cancers |journal=British Journal of Cancer |language=en |volume=122 |issue=3 |pages=306–314 |doi=10.1038/s41416-019-0602-7 |issn=0007-0920 |pmc=7000688 |pmid=31708575}}</ref>

HPV can induce tumors by several mechanisms:<ref name=":10" /><ref>{{cite journal | vauthors = Schmitz M, Driesch C, Beer-Grondke K, Jansen L, Runnebaum IB, Dürst M | title = Loss of gene function as a consequence of human papillomavirus DNA integration | journal = International Journal of Cancer | volume = 131 | issue = 5 | pages = E593–E602 | date = September 2012 | pmid = 22262398 | doi = 10.1002/ijc.27433 | s2cid = 21515048 }}</ref>
# E6 and E7 oncogenic proteins.
# Disruption of [[tumor suppressor gene]]s.
# High-level DNA amplifications, for example, [[oncogene]]s.
# Generating alternative nonfunctional transcripts.
# Interchromosomal rearrangements.
# Distinct host genome methylation and expression patterns, produced even when the virus is not integrated into the host genome.

There are observed biological differences between HPV-positive and HPV-negative head and neck cancer, for example in terms of [[mutation]] patterns. In HPV-negative disease, genes frequently mutated include ''[[P53|TP53]], [[CDKN2A]]'' and ''[[P110α|PIK3CA]]''.<ref>{{Cite journal |last1=Stransky |first1=Nicolas |last2=Egloff |first2=Ann Marie |last3=Tward |first3=Aaron D. |last4=Kostic |first4=Aleksandar D. |last5=Cibulskis |first5=Kristian |last6=Sivachenko |first6=Andrey |last7=Kryukov |first7=Gregory V. |last8=Lawrence |first8=Michael S. |last9=Sougnez |first9=Carrie |last10=McKenna |first10=Aaron |last11=Shefler |first11=Erica |last12=Ramos |first12=Alex H. |last13=Stojanov |first13=Petar |last14=Carter |first14=Scott L. |last15=Voet |first15=Douglas |date=2011-08-26 |title=The Mutational Landscape of Head and Neck Squamous Cell Carcinoma |journal=Science |language=en |volume=333 |issue=6046 |pages=1157–1160 |doi=10.1126/science.1208130 |issn=0036-8075 |pmc=3415217 |pmid=21798893|bibcode=2011Sci...333.1157S }}</ref> In HPV-positive disease, these genes are less frequently mutated, and the tumour suppressor gene p53 and [[Retinoblastoma protein|pRb]] (protein retinoblastoma) are commonly inactivated by HPV oncoproteins E6 and E7 respectively.<ref>{{Cite journal |last1=van Kempen |first1=Pauline MW |last2=Noorlag |first2=Rob |last3=Braunius |first3=Weibel W |last4=Stegeman |first4=Inge |last5=Willems |first5=Stefan M |last6=Grolman |first6=Wilko |date=29 Oct 2013 |title=Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: A systematic review |journal=Epigenetics |language=en |volume=9 |issue=2 |pages=194–203 |doi=10.4161/epi.26881 |issn=1559-2294 |pmc=3962529 |pmid=24169583}}</ref> In addition, viral infections such as HPV can cause aberrant [[DNA methylation]] during cancer development. HPV-positive head and neck cancers demonstrate higher levels of such DNA methylation compared to HPV-negative disease.<ref>{{Cite journal |last1=Nakagawa |first1=Takuya |last2=Kurokawa |first2=Tomoya |last3=Mima |first3=Masato |last4=Imamoto |first4=Sakiko |last5=Mizokami |first5=Harue |last6=Kondo |first6=Satoru |last7=Okamoto |first7=Yoshitaka |last8=Misawa |first8=Kiyoshi |last9=Hanazawa |first9=Toyoyuki |last10=Kaneda |first10=Atsushi |date=2021-04-10 |title=DNA Methylation and HPV-Associated Head and Neck Cancer |journal=Microorganisms |language=en |volume=9 |issue=4 |page=801 |doi=10.3390/microorganisms9040801 |doi-access=free |issn=2076-2607 |pmc=8069883 |pmid=33920277}}</ref>

E6 sequesters p53 to promote p53 degradation, while E7 inhibits pRb. Degradation of p53 results in cells being unable to respond to checkpoint signals that are normally present to activate [[apoptosis]] when DNA damage is signalled. Loss of pRb leads to deregulation of [[cell proliferation]] and apoptosis. Both mechanisms therefore leave cell proliferation unchecked and increase the chance of [[carcinogenesis]].<ref>{{Cite journal |last=Hickman |first=E |date=2002-02-01 |title=The role of p53 and pRB in apoptosis and cancer |url=https://linkinghub.elsevier.com/retrieve/pii/S0959437X01002659 |journal=Current Opinion in Genetics & Development |volume=12 |issue=1 |pages=60–66 |doi=10.1016/S0959-437X(01)00265-9|pmid=11790556 |url-access=subscription }}</ref>

====Epstein–Barr virus====
[[Epstein–Barr virus]] (EBV) infection is associated with [[nasopharyngeal carcinoma|nasopharyngeal cancer]]. Nasopharyngeal cancer caused by EBV commonly occurs in some countries of the Mediterranean and Asia, where EBV [[antibody titer]]s can be measured to screen high-risk populations.<ref>{{cite web |title=Risks and causes {{!}} Nasopharyngeal cancer |publisher=Cancer Research UK |url=https://www.cancerresearchuk.org/about-cancer/nasopharyngeal-cancer/risks-causes |access-date=4 December 2019}}</ref><ref>{{Cite journal |last1=Li |first1=Wenting |last2=Duan |first2=Xiaobing |last3=Chen |first3=Xingxing |last4=Zhan |first4=Meixiao |last5=Peng |first5=Haichuan |last6=Meng |first6=Ya |last7=Li |first7=Xiaobin |last8=Li |first8=Xian-Yang |last9=Pang |first9=Guofu |last10=Dou |first10=Xiaohui |date=2023-01-11 |title=Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma |journal=Frontiers in Immunology |volume=13 |article-number=1079515 |doi=10.3389/fimmu.2022.1079515 |doi-access=free |issn=1664-3224 |pmc=9875085 |pmid=36713430}}</ref>

===Gastroesophageal reflux disease===
The presence of [[gastroesophageal reflux disease]] (GERD) or laryngeal reflux disease can also be a major factor. [[Stomach acid]]s that flow up through the [[esophagus]] can damage its lining and raise susceptibility to throat cancer.{{citation needed|date=September 2024}}

===Hematopoietic stem cell transplantation===
People after [[hematopoietic stem cell transplantation]] (HSCT) are at a higher risk for oral cancer. Post-HSCT oral cancer may have more aggressive behavior and a poorer prognosis when compared to oral cancer in non-HSCT patients.<ref name="HSCT">{{cite journal | vauthors = Elad S, Zadik Y, Zeevi I, Miyazaki A, de Figueiredo MA, Or R | title = Oral cancer in patients after hematopoietic stem-cell transplantation: long-term follow-up suggests an increased risk for recurrence | journal = Transplantation | volume = 90 | issue = 11 | pages = 1243–1244 | date = December 2010 | pmid = 21119507 | doi = 10.1097/TP.0b013e3181f9caaa | doi-access = free }}</ref> This effect is supposed to be due to continuous, lifelong [[immune system|immune]] suppression and chronic oral [[graft-versus-host disease]].<ref name="HSCT" />

===Other risk factors===
Several other risk factors have been identified in the development of head and neck cancer. These include occupational environmental [[carcinogen]] exposure such as [[asbestos]], [[Sawdust|wood dust]], [[mineral acid]], [[Sulfuric acid|sulfuric acid mists]] and metal dusts. In addition, weakened immune systems, age greater than 55 years, poor [[Socioeconomic status|socioeconomic factors]] such as lower incomes and occupational status, and low [[body mass index]] (<18.5&nbsp;kg/m2) are also risk factors.<ref name=":8" /><ref>{{Cite journal |last1=Khlifi |first1=Rim |last2=Hamza-Chaffai |first2=Amel |date=2010-10-15 |title=Head and neck cancer due to heavy metal exposure via tobacco smoking and professional exposure: A review |url=https://linkinghub.elsevier.com/retrieve/pii/S0041008X10002760 |journal=Toxicology and Applied Pharmacology |language=en |volume=248 |issue=2 |pages=71–88 |doi=10.1016/j.taap.2010.08.003|pmid=20708025 |bibcode=2010ToxAP.248...71K |url-access=subscription }}</ref><ref name=":6" /> Poor [[oral hygiene]] and chronic [[Stomatitis|oral cavity inflammation]] (for example secondary to [[Chronic periodontitis|chronic gum inflammation]]) are also linked to an increased head and neck cancer risk.<ref>{{Cite journal |last1=Bosetti |first1=Cristina |last2=Carioli |first2=Greta |last3=Santucci |first3=Claudia |last4=Bertuccio |first4=Paola |last5=Gallus |first5=Silvano |last6=Garavello |first6=Werner |last7=Negri |first7=Eva |last8=La Vecchia |first8=Carlo |date=2020-08-15 |title=Global trends in oral and pharyngeal cancer incidence and mortality |url=https://onlinelibrary.wiley.com/doi/10.1002/ijc.32871 |journal=International Journal of Cancer |language=en |volume=147 |issue=4 |pages=1040–1049 |doi=10.1002/ijc.32871 |pmid=31953840 |issn=0020-7136|hdl=2434/705176 |hdl-access=free }}</ref><ref>{{Cite journal |last1=Miranda-Filho |first1=Adalberto |last2=Bray |first2=Freddie |date=25 January 2020 |title=Global patterns and trends in cancers of the lip, tongue and mouth |url=https://linkinghub.elsevier.com/retrieve/pii/S1368837519304610 |journal=Oral Oncology |language=en |volume=102 |article-number=104551 |doi=10.1016/j.oraloncology.2019.104551|pmid=31986342 |url-access=subscription }}</ref> The presence of [[leukoplakia]], which is the appearance of white patches or spots in the mouth, can develop into cancer in about 1⁄3 of cases.<ref name="ridge" />

==Diagnosis==
{{multiple image
| direction         = vertical
| width             = 200
| image1            = PET-CT scanning of lymph node metastases in cancer 2.jpg
| image2            = PET-CT scanning of lymph node metastases in cancer.jpg
| footer            = Left inferior internal jugular node metastases with extranodal invasion, two years after [[brachytherapy]] for [[oral cancer|tongue cancer]]. [[PET-CT]] scanning of a male in his 30s, 64 minutes after [[Fluorodeoxyglucose (18F)|fludeoxyglucose (<sup>18</sup>F)]] was administered, shows some fluff around the tumor.
}}
A significant proportion of people with head and neck cancer will present to their physicians with an already advanced stage disease.<ref name=":14">{{Cite journal |last1=Johnson |first1=Daniel E. |last2=Burtness |first2=Barbara |last3=Leemans |first3=C. René |last4=Lui |first4=Vivian Wai Yan |last5=Bauman |first5=Julie E. |last6=Grandis |first6=Jennifer R. |date=2020-11-26 |title=Head and neck squamous cell carcinoma |journal=Nature Reviews Disease Primers |language=en |volume=6 |issue=1 |page=92 |doi=10.1038/s41572-020-00224-3 |pmid=33243986 |pmc=7944998 |issn=2056-676X}}</ref> This can either be down to patient factors (delays in seeking medical attention), or physician factors (such as delays in referral from primary care, or non-diagnostic investigation results).<ref>{{Cite journal |last1=Karp |first1=Emily E. |last2=Yin |first2=Linda X. |last3=Moore |first3=Eric J. |last4=Elias |first4=Anna J. |last5=O'Byrne |first5=Thomas J. |last6=Glasgow |first6=Amy E. |last7=Habermann |first7=Elizabeth B. |last8=Price |first8=Daniel L. |last9=Kasperbauer |first9=Jan L. |last10=Van Abel |first10=Kathryn M. |date=26 January 2021 |title=Barriers to Obtaining a Timely Diagnosis in Human Papillomavirus–Associated Oropharynx Cancer |url=https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1177/0194599820982662 |journal=Otolaryngology–Head and Neck Surgery |language=en |volume=165 |issue=2 |pages=300–308 |doi=10.1177/0194599820982662 |pmid=33494648 |issn=0194-5998|url-access=subscription }}</ref>

A person usually presents to the physician complaining of one or more of the typical symptoms. These symptoms may be site specific (such as a laryngeal cancer causing [[hoarse voice]]), or not site specific (earache can be caused by multiple types of head and neck cancers).<ref name=":11" />

The physician will undertake a thorough history to determine the nature of the symptoms and the presence or absence of any risk factors. The physician will also ask about other illnesses such as heart or lung diseases as they may impact their fitness for potentially curative treatment. Clinical examination will involve examination of the neck for any masses, examining inside the mouth for any abnormalities and assessing the rest of the pharynx and larynx with a [[Nasoendoscopy|nasendoscope]].<ref>{{Cite journal |last1=Schache |first1=Andrew |last2=Kerawala |first2=Cyrus |last3=Ahmed |first3=Omar |last4=Brennan |first4=Peter A. |last5=Cook |first5=Florence |last6=Garrett |first6=Matthew |last7=Homer |first7=Jarrod |last8=Hughes |first8=Ceri |last9=Mayland |first9=Catriona |last10=Mihai |first10=Radu |last11=Newbold |first11=Kate |last12=O'Hara |first12=James |last13=Roe |first13=Justin |last14=Sibtain |first14=Amen |last15=Smith |first15=Maria |date=3 March 2021 |title=British Association of Head and Neck Oncologists (BAHNO) standards 2020 |journal=Journal of Oral Pathology & Medicine |language=en |volume=50 |issue=3 |pages=262–273 |doi=10.1111/jop.13161 |pmid=33655561 |issn=0904-2512|doi-access=free }}</ref>

Further investigations will be directed by the symptoms discussed and any abnormalities identified during the exam.{{citation needed|date=September 2024}}

[[Neck mass]]es typically undergo assessment with [[ultrasound]] and a [[fine-needle aspiration]] (FNA, a type of needle biopsy). Concerning [[lesion]]s that are readily accessible (such as in the mouth) can be biopsied with a [[Local anesthetic|local anaesthetic]]. Lesions less readily available can be biopsied either with the patient awake or under a [[general anaesthetic]] depending on local expertise and availability of specialist equipment.<ref>{{Cite journal |last1=Marcus |first1=Sonya |last2=Timen |first2=Micah |last3=Dion |first3=Gregory R. |last4=Fritz |first4=Mark A. |last5=Branski |first5=Ryan C. |last6=Amin |first6=Milan R. |date=19 February 2018 |title=Cost Analysis of Channeled, Distal Chip Laryngoscope for In-office Laryngopharyngeal Biopsies |url=https://linkinghub.elsevier.com/retrieve/pii/S0892199717305222 |journal=Journal of Voice |language=en |volume=33 |issue=4 |pages=575–579 |doi=10.1016/j.jvoice.2018.01.011|pmid=29472150 |url-access=subscription }}</ref>

The cancer will also need to be [[Cancer staging|staged]] (accurately determine its size, association with nearby structures, and spread to distant sites). This is typically done by scanning the patient with a combination of [[magnetic resonance imaging]] (MRI), [[CT scan|computed tomography]] (CT) and/or [[positron emission tomography]] (PET). Exactly which investigations are required will depend on a variety of factors such as the site of concern and the size of the tumour.<ref name=":12">{{Cite journal |last1=Homer |first1=Jarrod J |last2=Winter |first2=Stuart C |last3=Abbey |first3=Elizabeth C |last4=Aga |first4=Hiba |last5=Agrawal |first5=Reshma |last6=ap Dafydd |first6=Derfel |last7=Arunjit |first7=Takhar |last8=Axon |first8=Patrick |last9=Aynsley |first9=Eleanor |last10=Bagwan |first10=Izhar N |last11=Batra |first11=Arun |last12=Begg |first12=Donna |last13=Bernstein |first13=Jonathan M |last14=Betts |first14=Guy |last15=Bicknell |first15=Colin |date=14 March 2024 |title=Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition |journal=The Journal of Laryngology & Otology |language=en |volume=138 |issue=S1 |pages=S1–S224 |doi=10.1017/S0022215123001615 |pmid=38482835 |issn=0022-2151|doi-access=free }}</ref>

Some people will present with a neck lump containing cancer cells (identified by [[Fine-needle aspiration|FNA]]) that have spread from elsewhere, but with no identifiable primary site on initial assessment. In such cases people will undergo additional testing to attempt to find the initial site of cancer, as this has significant implications for their treatment. These patients undergo MRI scanning, [[PET-CT]] and then [[Endoscopy|panendoscopy]] and [[Biopsy|biopsies]] of any abnormal areas. If the scans and panendoscopy still do not identify a primary site for the cancer, affected people will undergo a bilateral [[tonsillectomy]] and tongue base [[mucosectomy]] (as these are the most common subsites of cancer that spread to the neck). This procedure can be done with or without [[Robot-assisted surgery|robotic assistance]].<ref>{{Cite journal |last1=Ye |first1=Wenda |last2=Arnaud |first2=Ethan H. |last3=Langerman |first3=Alexander |last4=Mannion |first4=Kyle |last5=Topf |first5=Michael C. |date=1 May 2021 |title=Diagnostic approaches to carcinoma of unknown primary of the head and neck |journal=European Journal of Cancer Care |language=en |volume=30 |issue=6 |article-number=e13459 |doi=10.1111/ecc.13459 |pmid=33932056 |issn=0961-5423|doi-access=free }}</ref>

Once a diagnosis is confirmed, a multidisciplinary discussion of the optimal treatment strategy will be undertaken between the [[radiation oncologist]], [[surgical oncology|surgical oncologist]], and [[medical oncology|medical oncologist]]. A [[Histopathology|histopathologist]] and a [[Radiology|radiologist]] will also be present to discuss the biopsy and imaging findings.<ref name=":12" /> Most (90%) cancers of the head and neck are [[squamous cell]]-derived, termed "head-and-neck squamous-cell carcinomas".<ref name="Vug2015" />

===Histopathology===
Throat cancers are classified according to their [[histology]] or cell structure and are commonly referred to by their location in the oral cavity and neck. This is because where the cancer appears in the throat affects the prognosis; some throat cancers are more aggressive than others, depending on their location. The stage at which the cancer is diagnosed is also a critical factor in the prognosis of throat cancer. Treatment guidelines recommend routine testing for the presence of HPV for all oropharyngeal squamous cell carcinoma tumors.<ref>{{cite web|title=Routine HPV Testing in Head and Neck Squamous Cell Carcinoma. EBS 5-9|url=https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=279838|access-date=22 May 2017|date=May 2013|url-status=live|archive-url=https://web.archive.org/web/20160930155638/https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=279838|archive-date=30 September 2016}}</ref>
Accurate prognostic stratification as well as segmentation of Head-and-Neck Squamous-Cell-Carcinoma (HNSCC) patients can be an important clinical reference when designing therapeutic strategies. Study <ref>{{cite conference |url=https://link.springer.com/chapter/10.1007/978-3-031-27420-6_23 |title=Deep Learning and Machine Learning Techniques for Automated PET/CT Segmentation and Survival Prediction in Head and Neck Cancer |book-title=Head and Neck Tumor Segmentation and Outcome Prediction (HECKTOR 2022) |last1=Salmanpour |first1=Mohammad R. |last2=Hajianfar |first2=Ghasem |last3=Hosseinzadeh |first3=Mahdi |last4=Rezaeijo |first4=Seyed Masoud |last5=Hosseini |first5=Mohammad Mehdi |last6=Kalatehjari |first6=Ehsanhosein |last7=Harimi |first7=Ali |last8=Rahmim |first8=Arman |date=18 March 2023 |publisher=Springer |pages=230–239
|series=Lecture Notes in Computer Science|doi=10.1007/978-3-031-27420-6_23|url-access=subscription }}</ref> developed a deep learning framework combining PET/CT fusion imaging with Hybrid Machine Learning Systems (HMLS) for automated tumor segmentation and recurrence-free survival prediction in HNSCC patients. They set to enable automated segmentation of tumors and prediction of recurrence-free survival (RFS) using advanced deep learning techniques and Hybrid Machine Learning Systems (HMLSs).

====Squamous-cell carcinoma====
[[Squamous-cell carcinoma]] is a [[cancer]] of the [[squamous cell]], a kind of [[epithelial]] cell found in both the [[skin]] and [[mucous membrane]]s. It accounts for over 90% of all head and neck cancers,<ref name=Haines-2013 /> including more than 90% of throat cancer.<ref name=ridge /> Squamous cell carcinoma is most likely to appear in males over 40 years of age with a history of heavy alcohol use coupled with smoking.{{citation needed|date=September 2024}}

All squamous cell carcinomas arising from the oropharynx, and all neck node [[Metastasis|metastases]] of unknown primary should undergo testing for HPV status. This is essential to adequately stage the tumour and adequately plan treatment. Due to the different biology of HPV positive and negative cancers, differentiating HPV status is also important for ongoing research to determine the best treatments.<ref>{{Cite web |date=2016-02-10 |title=Cancer of the upper aerodigestive tract: assessment and management in people aged 16 and over - Recommendations |url=https://www.nice.org.uk/guidance/NG36/chapter/Recommendations |access-date=2024-05-28 |website=NICE}}</ref>

[[Nasopharyngeal carcinoma]]s, or neck node metastases possibly arising from the nasopharynx will also be tested for Ebstein Barr virus.<ref>{{Cite web |last1=Helliwell |first1=Tim |last2=Woolgar |first2=Julia |date=November 2013 |title=Standards and datasets for reporting cancers. Dataset for histopathology reporting of salivary gland neoplasms |url=https://www.rcpath.org/static/3d46a973-a5fd-49f5-87dc074b90a69b72/Dataset-for-histopathology-reporting-of-salivary-gland-neoplasms.pdf |access-date=2024-05-28 |publisher=Royal College of Pathologists}}</ref>

The tumor marker Cyfra 21-1 may be useful in diagnosing squamous cell carcinoma of the head and neck (SCCHN).<ref>{{cite journal | vauthors = Wang YX, Hu D, Yan X | title = Diagnostic accuracy of Cyfra 21-1 for head and neck squamous cell carcinoma: a meta-analysis | journal = European Review for Medical and Pharmacological Sciences | volume = 17 | issue = 17 | pages = 2383–2389 | date = September 2013 | pmid = 24065233 }}</ref>

====Adenocarcinoma====
[[Adenocarcinoma]] is a cancer of the epithelial tissue that has [[gland]]ular characteristics. Several head and neck cancers are adenocarcinomas (either of intestinal or non-intestinal cell types).<ref name=Haines-2013>{{cite book| vauthors = Haines III GK | veditors = Radosevich JA |title= Head & Neck Cancer: Current Perspectives, Advances, and Challenges|chapter-url=https://books.google.com/books?id=iaFEAAAAQBAJ&pg=PA267|date=24 May 2013|publisher=Springer Science & Business Media|isbn=978-94-007-5827-8|pages=257–87|chapter=Pathology of Head and Neck Cancers I: Epithelial and Related Tumors|url-status=live|archive-url=https://web.archive.org/web/20160107225436/https://books.google.com/books?id=iaFEAAAAQBAJ&pg=PA267|archive-date=7 January 2016}}</ref>

==Prevention==
Avoidance of risk factors (such as smoking and alcohol) is the single most effective form of prevention.<ref name=":8" />

Regular dental examinations may identify pre-cancerous lesions in the oral cavity.<ref name="NCI" /> While [[Cancer screening|screening]] in the general population does not appear to be useful, screening high-risk groups by examination of the throat might be useful.<ref name="WCR2014" /> Head and neck cancer is often curable if it is diagnosed early; however, outcomes are typically poor if it is diagnosed late.<ref name="WCR2014" />

When diagnosed early, oral, head, and neck cancers can be treated more easily, and the chances of survival increase tremendously.<ref name="NCI" /> The [[HPV vaccine]] helps to prevent the development of HPV-related oropharyngeal cancer.<ref name=":13">{{Cite journal |last1=Macilwraith |first1=Philip |last2=Malsem |first2=Eve |last3=Dushyanthen |first3=Sathana |date=2023-04-24 |title=The effectiveness of HPV vaccination on the incidence of oropharyngeal cancers in men: a review |journal=Infectious Agents and Cancer |language=en |volume=18 |issue=1 |page=24 |doi=10.1186/s13027-022-00479-3 |doi-access=free |issn=1750-9378 |pmc=10127083 |pmid=37095546}}</ref>

==Management==

Improvements in diagnosis and local management, as well as [[targeted therapy]], have led to improvements in quality of life and survival for people with head and neck cancer.<ref>{{cite journal | vauthors = Al-Sarraf M | title = Treatment of locally advanced head and neck cancer: historical and critical review | journal = Cancer Control | volume = 9 | issue = 5 | pages = 387–399 | year = 2002 | pmid = 12410178 | doi = 10.1177/107327480200900504 | doi-access = free }}</ref>

After a histologic diagnosis has been established and tumor extent determined, such as with the use of PET-CT,<ref>{{Citation |last1=Eyassu |first1=Eyovel |title=Nuclear Medicine PET/CT Head and Neck Cancer Assessment, Protocols, and Interpretation |date=2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK573059/ |work=StatPearls |access-date=2023-11-24 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=34424632 |last2=Young |first2=Michael}}</ref> the selection of appropriate treatment for a specific cancer depends on a complex array of variables, including tumor site, relative morbidity of various treatment options, concomitant health problems, social and logistic factors, previous primary tumors, and the person's preference. Treatment planning generally requires a multidisciplinary approach involving specialist surgeons, medical oncologists, and radiation oncologists. {{Citation needed|reason=no source|date=May 2014}}

Surgical resection and radiation therapy are the mainstays of treatment for most head and neck cancers and remain the standard of care in most cases. For small primary cancers without regional metastases (stage I or II), wide surgical excision alone or curative radiation therapy alone is used. For more extensive primary tumors or those with regional metastases (stage III or IV), planned combinations of pre- or postoperative radiation and complete surgical excision are generally used. More recently, as historical survival and control rates have been recognized as less than satisfactory, there has been an emphasis on the use of various induction or concomitant chemotherapy regimens.{{citation needed|date=September 2024}}

===Surgery===
[[Surgery]] as a treatment is frequently used for most types of head and neck cancer. Usually, the goal is to remove the cancerous cells entirely. This can be particularly tricky if the cancer is near the [[larynx]] and can result in the person being unable to speak. Surgery is also commonly used to resect (remove) some or all of the cervical lymph nodes to prevent further spread of the disease. [[Transoral robotic surgery]] (TORS) is gaining popularity worldwide as the technology and training become more accessible. It now has an established role in the treatment of early stage oropharyngeal cancer.<ref>{{Cite journal |last1=Oliver |first1=Jamie R. |last2=Persky |first2=Michael J. |last3=Wang |first3=Binhuan |last4=Duvvuri |first4=Umamaheswar |last5=Gross |first5=Neil D. |last6=Vaezi |first6=Alec E. |last7=Morris |first7=Luc G. T. |last8=Givi |first8=Babak |date=2022-02-15 |title=Transoral robotic surgery adoption and safety in treatment of oropharyngeal cancers |journal=Cancer |language=en |volume=128 |issue=4 |pages=685–696 |doi=10.1002/cncr.33995 |issn=0008-543X |pmc=9446338 |pmid=34762303}}</ref> There is also a growing trend worldwide towards TORS for the surgical treatment of laryngeal and hypopharyngeal tumours.<ref>{{Cite journal |last1=Lechien |first1=Jerome R. |last2=Fakhry |first2=Nicolas |last3=Saussez |first3=Sven |last4=Chiesa-Estomba |first4=Carlos-Miguel |last5=Chekkoury-Idrissi |first5=Younes |last6=Cammaroto |first6=Giovanni |last7=Melkane |first7=Antoine E. |last8=Barillari |first8=Maria Rosaria |last9=Crevier-Buchman |first9=Lise |last10=Ayad |first10=Tareck |last11=Remacle |first11=Marc |last12=Hans |first12=Stéphane |date=10 June 2020 |title=Surgical, clinical and functional outcomes of transoral robotic surgery for supraglottic laryngeal cancers: A systematic review |journal=Oral Oncology |language=en |volume=109 |article-number=104848 |doi=10.1016/j.oraloncology.2020.104848|pmid=32534362 |doi-access=free }}</ref><ref>{{Cite journal |last1=Lai |first1=Katherine W. K. |last2=Lai |first2=Ronald |last3=Lorincz |first3=Balazs B. |last4=Wang |first4=Chen-Chi |last5=Chan |first5=Jason Y. K. |last6=Yeung |first6=David C. M. |date=2022-04-07 |title=Oncological and Functional Outcomes of Transoral Robotic Surgery and Endoscopic Laryngopharyngeal Surgery for Hypopharyngeal Cancer: A Systematic Review |journal=Frontiers in Surgery |volume=8 |article-number=810581 |doi=10.3389/fsurg.2021.810581 |doi-access=free |issn=2296-875X |pmc=9021537 |pmid=35464886}}</ref>

[[Laser surgery#Equipment|CO<sub>2</sub> laser surgery]] is also another form of treatment. [[Transoral laser microsurgery]] allows surgeons to remove tumors from the voice box with no external incisions. It also allows access to tumors that are not reachable with robotic surgery. During the surgery, the surgeon and pathologist work together to assess the adequacy of excision ("margin status"), minimizing the amount of normal tissue removed or damaged.<ref>{{cite journal | vauthors = Maxwell JH, Thompson LD, Brandwein-Gensler MS, Weiss BG, Canis M, Purgina B, Prabhu AV, Lai C, Shuai Y, Carroll WR, Morlandt A, Duvvuri U, Kim S, Johnson JT, Ferris RL, Seethala R, Chiosea SI | display-authors = 6 | title = Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control | journal = JAMA Otolaryngology–Head & Neck Surgery | volume = 141 | issue = 12 | pages = 1104–1110 | date = December 2015 | pmid = 26225798 | pmc = 5242089 | doi = 10.1001/jamaoto.2015.1351 }}</ref> This technique helps give the person as much speech and swallowing function as possible after surgery.<ref>[http://www.mayoclinic.org/throat-cancer/treatment.html] {{webarchive|url=https://web.archive.org/web/20120305053649/http://www.mayoclinic.org/throat-cancer/treatment.html|date=March 5, 2012}}</ref>

===Radiation therapy===
[[File:radiation-mask.jpg|right|thumb|Radiation mask used in the treatment of throat cancer]]
[[Radiation therapy]] is the most common form of treatment. There are different forms of radiation therapy, including 3D conformal radiation therapy, intensity-modulated radiation therapy, [[Proton therapy|particle beam therapy]], and brachytherapy, which are commonly used in the treatment of cancers of the head and neck. Most people with head and neck cancer who are treated in the United States and Europe are treated with intensity-modulated radiation therapy using high-energy photons. At higher doses, head and neck radiation is associated with [[thyroid]] dysfunction and [[Pituitary gland|pituitary]] axis dysfunction.<ref>{{cite journal | vauthors = Mahmood SS, Nohria A | title = Cardiovascular Complications of Cranial and Neck Radiation | journal = Current Treatment Options in Cardiovascular Medicine | volume = 18 | issue = 7 | article-number = 45 | date = July 2016 | pmid = 27181400 | doi = 10.1007/s11936-016-0468-4 | s2cid = 23888595 }}</ref> Radiation therapy for head and neck cancers can also cause acute skin reactions of varying severity, which can be treated and managed with topically applied creams or specialist films.<ref name="auto">{{Cite journal |last1=Burke |first1=G. |last2=Faithfull |first2=S. |last3=Probst |first3=H. |date=7 January 2022 |title=Radiation induced skin reactions during and following radiotherapy: A systematic review of interventions |journal=Radiography |language=en |volume=28 |issue=1 |pages=232–239 |doi=10.1016/j.radi.2021.09.006|pmid=34649789 |doi-access=free }}</ref>

===Chemotherapy===
[[Chemotherapy]] for throat cancer is not generally used to ''cure'' the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish themselves in other parts of the body. Typical chemotherapy agents are a combination of [[paclitaxel]] and [[carboplatin]]. [[Cetuximab]] is also used in the treatment of throat cancer.{{citation needed|date=September 2024}}

[[Docetaxel]]-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only [[taxane]] approved by the FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced head and neck cancer.<ref>{{cite web |url=http://www.cancer.gov/cancertopics/druginfo/fda-docetaxel |title=FDA Approval for Docetaxel - National Cancer Institute |publisher=Cancer.gov |access-date=2014-08-07 |url-status=live |archive-url=https://web.archive.org/web/20140901172746/http://www.cancer.gov/cancertopics/druginfo/fda-docetaxel |archive-date=2014-09-01}}</ref>

While not specifically a chemotherapy, [[amifostine]] is often administered [[Intravenous therapy|intravenously]] by a chemotherapy clinic prior to [[Radiation therapy#Intensity-modulated radiation therapy (IMRT)|IMRT]] radiotherapy sessions. Amifostine protects the gums and [[salivary gland]]s from the effects of radiation.{{citation needed|date=June 2012}}

There is no evidence that [[erythropoietin]] should be routinely given with radiotherapy.<ref>{{cite journal | vauthors = Lambin P, Ramaekers BL, van Mastrigt GA, Van den Ende P, de Jong J, De Ruysscher DK, Pijls-Johannesma M | title = Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer | journal = The Cochrane Database of Systematic Reviews | issue = 3 | article-number = CD006158 | date = July 2009 | pmid = 19588382 | doi = 10.1002/14651858.CD006158.pub2 }}</ref>

===Photodynamic therapy===
[[Photodynamic therapy]] may have promise for treating mucosal dysplasia and small head and neck tumors.<ref name=ridge /> [[Amphinex]] is showing good results in early clinical trials for the treatment of advanced head and neck cancer.<ref>"Inoperable cancers killed by new laser surgery" The Times. UK. 3-April-2010 p15</ref>

===Targeted therapy===
[[Targeted therapy]], according to the [[National Cancer Institute]], is "a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells." Some [[Targeted therapy|targeted therapies]] used in head and neck cancers include [[cetuximab]], [[bevacizumab]], and [[erlotinib]].{{citation needed|date=September 2024}}

[[Cetuximab]] is used for treating people with advanced-stage cancer who cannot be treated with conventional chemotherapy ([[cisplatin]]).<ref>{{Cite journal |last1=Blick |first1=Stephanie K A |last2=Scott |first2=Lesley J |date=2007 |title=Cetuximab: A Review of its Use in Squamous Cell Carcinoma of the Head and Neck and Metastatic Colorectal Cancer |url=http://link.springer.com/10.2165/00003495-200767170-00008 |journal=Drugs |language=en |volume=67 |issue=17 |pages=2585–2607 |doi=10.2165/00003495-200767170-00008 |pmid=18034592 |s2cid=195690071 |issn=0012-6667|url-access=subscription }}</ref><ref>{{Cite journal |last1=Cantwell |first1=Linda A. |last2=Fahy |first2=Emer |last3=Walters |first3=Emily R. |last4=Patterson |first4=Joanne M. |date=26 November 2020 |title=Nutritional prehabilitation in head and neck cancer: a systematic review |url=https://livrepository.liverpool.ac.uk/3167149/1/Nutritional.prehab.pre-print.pdf |journal=Supportive Care in Cancer |language=en |volume=30 |issue=11 |pages=8831–8843 |doi=10.1007/s00520-022-07239-4 |issn=0941-4355 |pmid=35913625 |s2cid=251221072 |url-access= |via=University of Liverpool Repository}}</ref> However, cetuximab's efficacy is still under investigation by researchers.<ref>{{Cite journal |last1=Muraro |first1=Elena |last2=Fanetti |first2=Giuseppe |last3=Lupato |first3=Valentina |last4=Giacomarra |first4=Vittorio |last5=Steffan |first5=Agostino |last6=Gobitti |first6=Carlo |last7=Vaccher |first7=Emanuela |last8=Franchin |first8=Giovanni |date=10 July 2021 |title=Cetuximab in locally advanced head and neck squamous cell carcinoma: Biological mechanisms involved in efficacy, toxicity and resistance |url=https://linkinghub.elsevier.com/retrieve/pii/S1040842821002122 |journal=Critical Reviews in Oncology/Hematology |language=en |volume=164 |article-number=103424 |doi=10.1016/j.critrevonc.2021.103424|pmid=34245856 |s2cid=235791305 |url-access=subscription }}</ref>

[[Gendicine]] is a [[gene therapy]] that employs an [[Adenoviridae|adenovirus]] to deliver the [[tumor suppressor gene]] [[p53]] to cells. It was approved in China in 2003 for the treatment of head and neck cancer.<ref name=Gend>{{cite journal | vauthors = Pearson S, Jia H, Kandachi K | title = China approves first gene therapy | journal = Nature Biotechnology | volume = 22 | issue = 1 | pages = 3–4 | date = January 2004 | pmid = 14704685 | pmc = 7097065 | doi = 10.1038/nbt0104-3 }}</ref>

The mutational profiles of [[Human papillomavirus infection|HPV]]+ and HPV- head and neck cancer have been reported, further demonstrating that they are fundamentally distinct diseases.
<ref>{{cite journal | vauthors = Lechner M, Frampton GM, Fenton T, Feber A, Palmer G, Jay A, Pillay N, Forster M, Cronin MT, Lipson D, Miller VA, Brennan TA, Henderson S, Vaz F, O'Flynn P, Kalavrezos N, Yelensky R, Beck S, Stephens PJ, Boshoff C | display-authors = 6 | title = Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors | journal = Genome Medicine | volume = 5 | issue = 5 | article-number = 49 | year = 2013 | pmid = 23718828 | pmc = 4064312 | doi = 10.1186/gm453 | doi-access = free }}</ref>{{primary source inline|date=August 2013}}

===Immunotherapy===
[[Immunotherapy]] is a type of treatment that activates the immune system to fight cancer. One type of immunotherapy, immune checkpoint blockade, binds to and blocks inhibitory signals on immune cells to release their anti-cancer activities.{{citation needed|date=September 2024}}

In 2016, the FDA granted accelerated approval to [[pembrolizumab]] for the treatment of people with recurrent or metastatic head and neck cancer with disease progression on or after platinum-containing chemotherapy.<ref>{{Cite journal | author =Center for Drug Evaluation and Research |date=2019-02-09|title=pembrolizumab (KEYTRUDA)|url=https://www.fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda|archive-url=https://web.archive.org/web/20190928103705/https://www.fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda|archive-date=September 28, 2019|journal=FDA|language=en}}</ref> Later that year, the FDA approved [[nivolumab]] for the treatment of recurrent or metastatic head and neck cancer with disease progression on or after platinum-based chemotherapy.<ref>{{Cite journal | author = Center for Drug Evaluation and Research |date=2018-11-03|title=Nivolumab for SCCHN|url=https://www.fda.gov/drugs/resources-information-approved-drugs/nivolumab-scchn|archive-url=https://web.archive.org/web/20190612185113/https://www.fda.gov/drugs/resources-information-approved-drugs/nivolumab-scchn|archive-date=June 12, 2019|journal=FDA|language=en}}</ref> In 2019, the FDA approved [[pembrolizumab]] for the first-line treatment of metastatic or unresectable recurrent head and neck cancer.<ref>{{Cite journal| author = Center for Drug Evaluation and Research | date=2019-06-11|title=FDA approves pembrolizumab for first-line treatment of head and neck squamous cell carcinoma|url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-first-line-treatment-head-and-neck-squamous-cell-carcinoma|archive-url=https://web.archive.org/web/20190928072631/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-first-line-treatment-head-and-neck-squamous-cell-carcinoma|archive-date=September 28, 2019|journal=FDA|language=en}}</ref>

===Treatment side effects===
Depending on the treatment used, people with head and neck cancer may experience various symptoms and treatment side effects depending on the type and site of the treatment used.<ref>{{Cite web |title=Late effects of head and neck cancer treatment |url=https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/late-effects-of-head-and-neck-cancer-treatments |access-date=2025-08-25 |website=Macmillan Cancer Support |language=en}}</ref><ref name=ridge />

==== Difficulties with eating and drinking ====
Even before treatment, tumours themselves may interfere with a person's ability to eat and drink normally<ref>{{Cite web |title=Head and neck cancer symptoms |url=https://www.macmillan.org.uk/cancer-information-and-support/head-and-neck-cancer/signs-and-symptoms-of-head-and-neck-cancer |access-date=2025-08-25 |website=Macmillan Cancer Support |language=en}}</ref><ref name=":02">{{Cite journal |last1=Greco |first1=Elissa |last2=Simic |first2=Tijana |last3=Ringash |first3=Jolie |last4=Tomlinson |first4=George |last5=Inamoto |first5=Yoko |last6=Martino |first6=Rosemary |date=27 April 2018 |title=Dysphagia Treatment for Patients With Head and Neck Cancer Undergoing Radiation Therapy: A Meta-analysis Review |url=https://linkinghub.elsevier.com/retrieve/pii/S0360301618302219 |journal=International Journal of Radiation Oncology*Biology*Physics |language=en |volume=101 |issue=2 |pages=421–444 |doi=10.1016/j.ijrobp.2018.01.097 |pmid=29726363 |url-access=subscription }}</ref> and these may be among the early presenting symptoms.<ref name=":15" /> Some treatments can also lead to difficulty with eating and drinking ([[dysphagia]]).<ref name=":02" /><ref>{{Cite journal |last1=Patterson |first1=Joanne M. |last2=McColl |first2=Elaine |last3=Wilson |first3=Janet |last4=Carding |first4=Paul |last5=Rapley |first5=Tim |date=8 April 2015 |title=Head and neck cancer patients' perceptions of swallowing following chemoradiotherapy |url=http://link.springer.com/10.1007/s00520-015-2715-8 |journal=Supportive Care in Cancer |language=en |volume=23 |issue=12 |pages=3531–3538 |doi=10.1007/s00520-015-2715-8 |pmid=25851803 |issn=0941-4355|url-access=subscription }}</ref> This might lead to feelings of food sticking in the throat, food and drink going down the wrong way ([[Aspiration pneumonia|aspiration]]),<ref>{{Cite journal |last1=Mootassim-Billah |first1=Sofiana |last2=Van Nuffelen |first2=Gwen |last3=Schoentgen |first3=Jean |last4=De Bodt |first4=Marc |last5=Dragan |first5=Tatiana |last6=Digonnet |first6=Antoine |last7=Roper |first7=Nicolas |last8=Van Gestel |first8=Dirk |date=1 May 2021 |title=Assessment of cough in head and neck cancer patients at risk for dysphagia—An overview |journal=Cancer Reports |language=en |volume=4 |issue=5 |article-number=e1395 |doi=10.1002/cnr2.1395 |issn=2573-8348 |pmc=8551981 |pmid=33932152}}</ref> taking a long time to chew and swallow food, a change in taste or appetite, and overall changes in enjoyment of eating and drinking.<ref>{{Cite web |title=Eating and drinking after head and neck cancer treatment |url=https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/eating-and-drinking-after-head-and-neck-cancer-treatment |access-date=2025-08-25 |website=Macmillan Cancer Support |language=en}}</ref><ref>{{Cite journal |last1=Patterson |first1=Joanne M. |last2=Lu |first2=Liya |last3=Watson |first3=Laura-Jayne |last4=Harding |first4=Sam |last5=Ness |first5=Andy R. |last6=Thomas |first6=Steve |last7=Waylen |first7=Andrea |last8=Waterboer |first8=Tim |last9=Sharp |first9=Linda |date=20 May 2021 |title=Trends in, and predictors of, swallowing and social eating outcomes in head and neck cancer survivors: A longitudinal analysis of head and neck 5000 |url=https://linkinghub.elsevier.com/retrieve/pii/S1368837521001676 |journal=Oral Oncology |language=en |volume=118 |article-number=105344 |doi=10.1016/j.oraloncology.2021.105344 |pmid=34023744 |url-access=subscription }}</ref> 

Surgery results in changes to anatomy, altering the function and coordination of key structures involved in eating and drinking. Surgery can also result in damage or bruising to nerves needed to move and provide sensation to the muscles involved in swallowing. Following surgery, a person may experience difficulties with chewing, swallowing and jaw opening. Pain, and [[Edema|oedema]] can be present after surgery, particularly in the early postoperative period.<ref name=":2">{{Cite journal |last1=Stephen |first1=Sarah E. |last2=Murphy |first2=Jennifer M. |last3=Beyer |first3=Fiona R. |last4=Sellstrom |first4=Diane |last5=Paleri |first5=Vinidh |last6=Patterson |first6=Joanne M. |date=9 December 2021 |title=Early postoperative functional outcomes following transoral surgery for oropharyngeal cancer: A systematic review |url=https://onlinelibrary.wiley.com/doi/10.1002/hed.26938 |journal=Head & Neck |language=en |volume=44 |issue=2 |pages=530–547 |doi=10.1002/hed.26938 |pmid=34882886 |issn=1043-3074|url-access=subscription }}</ref> The severity of swallowing issues after surgery depends on the location of the tumour and the volume of tissue removed. Factors such as age, other pre-existing illnesses ([[comorbidity]]) and having any earlier problems with swallowing will also impact swallow outcomes. Transoral surgical techniques remove tumours with minimal disruption to normal tissue. This is an established technique in the management of oropharyngeal cancer, with the aim to improve long-term swallow outcomes. However, difficulties with swallowing are common in the early period following the surgery.<ref name=":2" /> Surgery may involve substituting some anatomy with tissue from other areas of the body (soft tissue or bone flap reconstruction). This can lead to changes in sensation and function of this new tissue.<ref>{{Cite journal |last1=Homer |first1=J J |last2=Fardy |first2=M J |date=12 May 2016 |title=Surgery in head and neck cancer: United Kingdom National Multidisciplinary Guidelines |journal=The Journal of Laryngology & Otology |language=en |volume=130 |issue=S2 |pages=S68–S70 |doi=10.1017/S0022215116000475 |issn=0022-2151 |pmc=4873928 |pmid=27841115}}</ref>

Radiotherapy can lead to inflammation of the mouth or throat ([[mucositis]]), dry mouth ([[xerostomia]]),<ref name="ridge" /> reduced motion of the jaw ([[trismus]]),<ref name=":22">{{Cite journal |last1=Charters |first1=E |last2=Dunn |first2=M |last3=Cheng |first3=K |last4=Aung |first4=V |last5=Mukherjee |first5=P |last6=Froggatt |first6=C |last7=Dusseldorp |first7=Jr |last8=Clark |first8=Jr |date=29 January 2022 |title=Trismus therapy devices: A systematic review |journal=Oral Oncology |volume=126 |article-number=105728 |doi=10.1016/j.oraloncology.2022.105728 |issn=1879-0593 |pmid=35104753}}</ref> [[osteoradionecrosis]],<ref name="ridge" /> changes to [[dentition]], fatigue, oedema [[fibrosis]],<ref>{{Cite journal |last1=Turcotte |first1=Maria C. |last2=Herzberg |first2=Erica G. |last3=Balou |first3=Matina |last4=Molfenter |first4=Sonja M. |date=24 September 2018 |title=Analysis of pharyngeal edema post-chemoradiation for head and neck cancer: Impact on swallow function |journal=Laryngoscope Investigative Otolaryngology |language=en |volume=3 |issue=5 |pages=377–383 |doi=10.1002/lio2.203 |issn=2378-8038 |pmc=6209611 |pmid=30410991}}</ref><ref>{{Cite journal |last1=Jeans |first1=Claire |last2=Ward |first2=Elizabeth C. |last3=Cartmill |first3=Bena |last4=Vertigan |first4=Anne E. |last5=Pigott |first5=Amanda E. |last6=Nixon |first6=Jodie L. |last7=Wratten |first7=Chris |date=25 July 2018 |title=Patient perceptions of living with head and neck lymphoedema and the impacts to swallowing, voice and speech function |url=https://onlinelibrary.wiley.com/doi/10.1111/ecc.12894 |journal=European Journal of Cancer Care |language=en |volume=28 |issue=1 |article-number=e12894 |doi=10.1111/ecc.12894 |pmid=30044023 }}</ref> [[atrophy]].<ref name="auto" /> These changes can impair the movement of key swallowing structures but their severity depends on the dose and site of the radiotherapy.<ref name=":32">{{Cite journal |last1=Duprez |first1=Fréderic |last2=Madani |first2=Indira |last3=De Potter |first3=Bruno |last4=Boterberg |first4=Tom |last5=De Neve |first5=Wilfried |date=2013-02-22 |title=Systematic Review of Dose–Volume Correlates for Structures Related to Late Swallowing Disturbances After Radiotherapy for Head and Neck Cancer |journal=Dysphagia |volume=28 |issue=3 |pages=337–349 |doi=10.1007/s00455-013-9452-2 |pmid=23429941 |issn=0179-051X}}</ref><ref>{{Cite journal |last1=Eisbruch |first1=Avraham |last2=Schwartz |first2=Marco |last3=Rasch |first3=Coen |last4=Vineberg |first4=Karen |last5=Damen |first5=Eugene |last6=Van As |first6=Corina J. |last7=Marsh |first7=Robin |last8=Pameijer |first8=Frank A. |last9=Balm |first9=Alfons J.M. |date=2004-12-01 |title=Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: Which anatomic structures are affected and can they be spared by IMRT? |url=https://linkinghub.elsevier.com/retrieve/pii/S0360301604009411 |journal=International Journal of Radiation Oncology*Biology*Physics |language=en |volume=60 |issue=5 |pages=1425–1439 |doi=10.1016/j.ijrobp.2004.05.050 |pmid=15590174 |url-access=subscription }}</ref><ref>{{Cite journal |last1=Nguyen |first1=N.P. |last2=Moltz |first2=C.C. |last3=Frank |first3=C. |last4=Vos |first4=P. |last5=Smith |first5=H.J. |last6=Karlsson |first6=U. |last7=Dutta |first7=S. |last8=Midyett |first8=F.A. |last9=Barloon |first9=J. |last10=Sallah |first10=S. |date=March 2004 |title=Dysphagia following chemoradiation for locally advanced head and neck cancer |url=https://linkinghub.elsevier.com/retrieve/pii/S0923753419641487 |journal=Annals of Oncology |language=en |volume=15 |issue=3 |pages=383–388 |doi=10.1093/annonc/mdh101 |pmid=14998839 |url-access=subscription }}</ref> Recent advancements in the way radiotherapy is planned and delivered aim to reduce some of these side effects.<ref name=":42">{{Cite journal |last=Patterson |first=J. M. |date=2019-05-21 |title=Late Effects of Organ Preservation Treatment on Swallowing and Voice; Presentation, Assessment, and Screening |journal=Frontiers in Oncology |volume=9 |article-number=401 |doi=10.3389/fonc.2019.00401 |doi-access=free |issn=2234-943X |pmc=6536573 |pmid=31165044}}</ref><ref>{{Cite journal |last1=Roe |first1=Justin W.G. |last2=Carding |first2=Paul N. |last3=Drinnan |first3=Michael J. |last4=Harrington |first4=Kevin J. |last5=Nutting |first5=Christopher M. |date=13 November 2015 |title=Swallowing performance and tube feeding status in patients treated with parotid-sparing intensity-modulated radiotherapy for head and neck cancer |url=https://onlinelibrary.wiley.com/doi/10.1002/hed.24255 |journal=Head & Neck |language=en |volume=38 |issue=S1 |pages=E1436-44 |doi=10.1002/hed.24255 |pmid=26566740 |issn=1043-3074|url-access=subscription }}</ref>

==== Communication ====
Speech may become slurred, hard to understand, or the voice may become hoarse or weak. The impact on communication depends on the site and size of the tumour and the treatments used. The tumour itself may result in changes to the voice, which may be among one of the presenting signs and symptoms.<ref name=":15" />

Surgery can lead to changes in the shape and size of the oral structures (tongue, lips, [[palate]], [[Dental extraction|dental extractions]]) which can impact on how they move to produce speech sounds.<ref>{{Cite journal |last1=Baehring |first1=Erikka |last2=McCorkle |first2=Ruth |date=2012-12-01 |title=Postoperative Complications in Head and Neck Cancer |url=http://cjon.ons.org/cjon/16/6/postoperative-complications-head-and-neck-cancer |journal=Clinical Journal of Oncology Nursing |volume=16 |issue=6 |pages=E203–E209 |doi=10.1188/12.CJON.E203-E209 |pmid=23178363 |issn=1092-1095|url-access=subscription }}</ref>

Surgery may result in changes to anatomy or neurology such as removal of a structure or damage to nerves. For example, removal of the [[larynx]] (voice box) in a [[Laryngectomy|total laryngectomy]] or damage to the [[vagus nerve]] during tumour removal leading to [[Vocal cord paresis|vocal fold paresis]] or palsy.<ref>{{Cite journal |last1=Wang |first1=Hsing-Won |last2=Lu |first2=Cheng-Chieh |last3=Chao |first3=Pin-Zhir |last4=Lee |first4=Fei-Peng |date=2022-10-22 |title=Causes of Vocal Fold Paralysis |url=http://journals.sagepub.com/doi/10.1177/0145561320965212 |journal=Ear, Nose & Throat Journal |language=en |volume=101 |issue=7 |pages=NP294–NP298 |doi=10.1177/0145561320965212 |pmid=33090900 |issn=0145-5613|doi-access=free }}</ref>

If surgery affects the [[Maxilla|upper jaw bone]], then this can also affect the development and resonance of speech sounds, resulting in [[hypernasal speech]] and difficulty in making certain sounds that are dependent on the [[Velopharyngeal inadequacy|velopharyngeal competence]]. [[Dental prosthesis|Dental]] and [[Palatal obturator|speech prosthetics]] can sometimes be provided to compensate for these changes, however there is no effective means to restore normal (pre-surgical) speech sounds.<ref>{{Cite journal |last1=König |first1=János |last2=Kelemen |first2=Kata |last3=Váncsa |first3=Szilárd |last4=Szabó |first4=Bence |last5=Varga |first5=Gábor |last6=Mikulás |first6=Krisztina |last7=Borbély |first7=Judit |last8=Hegyi |first8=Péter |last9=Hermann |first9=Péter |date=26 December 2023 |title=Comparative analysis of surgical and prosthetic rehabilitation in maxillectomy: A systematic review and meta-analysis on quality-of-life scores and objective speech and masticatory measurements |url=https://linkinghub.elsevier.com/retrieve/pii/S0022391323007758 |journal=The Journal of Prosthetic Dentistry |language=en |volume=133 |issue=1 |pages=305–314 |doi=10.1016/j.prosdent.2023.11.023 |pmid=38151428 }}</ref><ref>{{Cite journal |last1=dos Santos |first1=D.M. |last2=de Caxias |first2=F.P. |last3=Bitencourt |first3=S.B. |last4=Turcio |first4=K.H. |last5=Pesqueira |first5=A.A. |last6=Goiato |first6=M.C. |date=2018-04-11 |title=Oral rehabilitation of patients after maxillectomy. A systematic review |url=https://linkinghub.elsevier.com/retrieve/pii/S0266435618300652 |journal=British Journal of Oral and Maxillofacial Surgery |language=en |volume=56 |issue=4 |pages=256–266 |doi=10.1016/j.bjoms.2018.03.001 |pmid=29655661 |hdl=11449/176178 |hdl-access=free }}</ref>

Head and neck cancer treatments can lead to changes in the sound of the voice. The impact of surgery on the voice can depend on the size of the resection and subsequent amount of scarring on the vocal folds.<ref>{{Cite journal |last1=Colizza |first1=Andrea |last2=Ralli |first2=Massimo |last3=D'Elia |first3=Chiara |last4=Greco |first4=Antonio |last5=de Vincentiis |first5=Marco |date=3 May 2022 |title=Voice quality after transoral CO2 laser microsurgery (TOLMS): systematic review of literature |journal=European Archives of Oto-Rhino-Laryngology |language=en |volume=279 |issue=9 |pages=4247–4255 |doi=10.1007/s00405-022-07418-3 |issn=0937-4477 |pmc=9363323 |pmid=35505113}}</ref> Radiotherapy treatment may improve the voice or worsen it, depending on pre-treatment voice function, and the site and dose treatment. This may be short- or long-term depending on the treatment plan.<ref>{{Cite journal |last1=Heijnen |first1=B. J. |last2=Speyer |first2=R. |last3=Kertscher |first3=B. |last4=Cordier |first4=R. |last5=Koetsenruijter |first5=K. W. J. |last6=Swan |first6=K. |last7=Bogaardt |first7=H. |date=19 September 2016 |title=Dysphagia, Speech, Voice, and Trismus following Radiotherapy and/or Chemotherapy in Patients with Head and Neck Carcinoma: Review of the Literature |journal=BioMed Research International |language=en |volume=2016 |pages=1–24 |doi=10.1155/2016/6086894 |pmid=27722170 |pmc=5045989 |doi-access=free |issn=2314-6133}}</ref>

==== Upper airway ====
People may experience changes to their breathing from the tumour itself or from side-effects of head and neck cancer treatments. Both surgery and radiotherapy can cause changes in breathing in either the short- or long-term e.g. through a [[Tracheotomy|tracheostomy tube]] or stoma in the neck ([[laryngectomy]]). The extent of these changes is often dependent on a range of factors including type of surgery, position of the tumour and the individual's tissue response to radiotherapy.<ref>{{Cite web |title=Laryngectomy |url=https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/laryngectomy |access-date=2025-08-25 |website=Macmillan Cancer Support |language=en}}</ref>

==== Shoulder dysfunction ====
[[Neck dissection|Surgical neck dissection]] is the most common component of treatment in both new cancers and in cancers previously treated but with residual neck disease. Shoulder dysfunction is by far the most common side effect after neck dissection.<ref name=":0">{{Cite journal |last1=Chan |first1=Jimmy Yu Wai |last2=Wong |first2=Stanley Thian Sze |last3=Chan |first3=Richie Chiu Lung |last4=Wei |first4=William Ignace |date=2 July 2015 |title=Shoulder Dysfunction after Selective Neck Dissection in Recurrent Nasopharyngeal Carcinoma |url=https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1177/0194599815590589 |journal=Otolaryngology–Head and Neck Surgery |language=en |volume=153 |issue=3 |pages=379–384 |doi=10.1177/0194599815590589 |pmid=26138607 |issn=0194-5998|url-access=subscription }}</ref><ref name=":16">{{Cite journal |last1=Gane |first1=E.M. |last2=Michaleff |first2=Z.A. |last3=Cottrell |first3=M.A. |last4=McPhail |first4=S.M. |last5=Hatton |first5=A.L. |last6=Panizza |first6=B.J. |last7=O'Leary |first7=S.P. |date=17 November 2016 |title=Prevalence, incidence, and risk factors for shoulder and neck dysfunction after neck dissection: A systematic review |url=https://linkinghub.elsevier.com/retrieve/pii/S0748798316309660 |journal=European Journal of Surgical Oncology (EJSO) |language=en |volume=43 |issue=7 |pages=1199–1218 |doi=10.1016/j.ejso.2016.10.026 |pmid=27956321 |url-access=subscription }}</ref> Its symptoms can include shoulder pain, decreased range of motion, and muscle loss.<ref>{{Cite web |title=Shoulder Dysfunction |url=https://www.ahns.info/survivorship_intro/shoulder-dysfunction/ |access-date=2025-08-26 |publisher=American Head & Neck Society |language=en-US}}</ref> The prevalence of shoulder dysfunction varies based on the type of neck dissection and the diagnostic tools used, but it can occur in as many as 50 to 100% of cases.<ref name=":0" /><ref name=":16" /> Over 30% of people still experience shoulder pain and reduced function 12 months after surgery.<ref name=":17">{{Cite journal |last1=Carvalho |first1=Alan PV |last2=Vital |first2=Flávia MR |last3=Soares |first3=Bernardo GO |date=2012-04-18 |editor-last=Cochrane ENT Group |title=Exercise interventions for shoulder dysfunction in patients treated for head and neck cancer |url=http://doi.wiley.com/10.1002/14651858.CD008693.pub2 |journal=Cochrane Database of Systematic Reviews |language=en |volume=2012 |issue=4 |doi=10.1002/14651858.CD008693.pub2 |pmid=22513964 |pmc=11537249 }}</ref> Problems with shoulder and neck movement can reduce people's abilities to return to work, and nearly half of people with shoulder disability cease working.<ref name=":16" />

Treatment for shoulder dysfunction, whether pain, weakness or functional difficulties, is commonly provided through [[Physical therapy|physiotherapy]]. Physiotherapists assess the specific symptoms and then prescribe treatments which are often exercise-based, tailored to individual problems<ref>{{Cite journal |last1=Robinson |first1=M |last2=Ward |first2=L |last3=Mehanna |first3=H |last4=Paleri |first4=V |last5=Winter |first5=S C |date=13 June 2018 |title=Provision of physiotherapy rehabilitation following neck dissection in the UK |url=https://www.cambridge.org/core/product/identifier/S0022215118000671/type/journal_article |journal=The Journal of Laryngology & Otology |language=en |volume=132 |issue=7 |pages=624–627 |doi=10.1017/S0022215118000671 |pmid=29897032 |issn=0022-2151|url-access=subscription }}</ref><ref name=":17" />

==== Nutrition and hydration ====
People may find it hard to eat and drink enough due to the side effects of treatments. These may be associated with chemotherapy, radiotherapy and surgery. This can increase their risk of [[malnutrition]]. People with head and neck cancer need to be screened for malnutrition risk on diagnosis and regularly throughout their treatment and referred to a [[dietitian]].<ref name=":12" /> Dietary counselling or oral nutritional supplements may be required to treat and manage any malnutrition.<ref>{{Cite journal |last=Muscaritoli |first=Maurizio |last2=Arends |first2=Jann |last3=Bachmann |first3=Patrick |last4=Baracos |first4=Vickie |last5=Barthelemy |first5=Nicole |last6=Bertz |first6=Hartmut |last7=Bozzetti |first7=Federico |last8=Hütterer |first8=Elisabeth |last9=Isenring |first9=Elizabeth |last10=Kaasa |first10=Stein |last11=Krznaric |first11=Zeljko |last12=Laird |first12=Barry |last13=Larsson |first13=Maria |last14=Laviano |first14=Alessandro |last15=Mühlebach |first15=Stefan |date=15 March 2021 |title=ESPEN practical guideline: Clinical Nutrition in cancer |url=https://linkinghub.elsevier.com/retrieve/pii/S0261561421000790 |journal=Clinical Nutrition |language=en |volume=40 |issue=5 |pages=2898–2913 |doi=10.1016/j.clnu.2021.02.005|url-access=subscription }}</ref> Some people might be recommended to have [[Feeding tube|enteral feeding]], a method that adds nutrients directly into a person's stomach using a [[Gastric intubation|nasogastric feeding tube]] or a [[Feeding tube|gastrostomy tube]].<ref name=":03">{{cite journal |vauthors=Nugent B, Lewis S, O'Sullivan JM |date=January 2013 |title=Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy |journal=The Cochrane Database of Systematic Reviews |volume=2013 |issue=1 |article-number=CD007904 |doi=10.1002/14651858.CD007904.pub3 |pmc=6769131 |pmid=23440820}}</ref><ref>{{Cite journal |last1=Bossola |first1=Maurizio |last2=Antocicco |first2=Manuela |last3=Pepe |first3=Gilda |date=22 May 2022 |title=Tube feeding in patients with head and neck cancer undergoing chemoradiotherapy: A systematic review |url=https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/jpen.2360 |journal=Journal of Parenteral and Enteral Nutrition |language=en |volume=46 |issue=6 |pages=1258–1269 |doi=10.1002/jpen.2360 |issn=0148-6071|url-access=subscription }}</ref> The type of tube used and when it is placed is decided on a case-by-case basis with guidance from the treating team.<ref>{{Cite journal |last1=Talwar |first1=B |last2=Donnelly |first2=R |last3=Skelly |first3=R |last4=Donaldson |first4=M |date=12 May 2016 |title=Nutritional management in head and neck cancer: United Kingdom National Multidisciplinary Guidelines |journal=The Journal of Laryngology & Otology |language=en |volume=130 |issue=S2 |pages=S32–S40 |doi=10.1017/S0022215116000402 |issn=0022-2151 |pmc=4873913 |pmid=27841109}}</ref> However, for people undergoing radiotherapy or chemotherapy, it is not yet known what the most effective method and timing of enteral feeding is for staying nourished during treatment.<ref name=":032">{{cite journal |vauthors=Nugent B, Lewis S, O'Sullivan JM |date=January 2013 |title=Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy |journal=The Cochrane Database of Systematic Reviews |volume=2013 |issue=1 |article-number=CD007904 |doi=10.1002/14651858.CD007904.pub3 |pmc=6769131 |pmid=23440820}}</ref><ref>{{Cite journal |last1=Ye |first1=Xiaodan |last2=Chang |first2=Yuan-Chin |last3=Findlay |first3=Merran |last4=Brown |first4=Teresa |last5=Bauer |first5=Judy |date=3 June 2021 |title=The effect of timing of enteral nutrition support on feeding outcomes and dysphagia in patients with head and neck cancer undergoing radiotherapy or chemoradiotherapy: A systematic review |url=https://linkinghub.elsevier.com/retrieve/pii/S2405457721001972 |journal=Clinical Nutrition ESPEN |language=en |volume=44 |pages=96–104 |doi=10.1016/j.clnesp.2021.05.017 |pmid=34330518 |url-access=subscription }}</ref>

Chemotherapy can lead to taste changes, [[Chemotherapy-induced nausea and vomiting|nausea and vomiting]]. It can deprive the body of vital fluids (although these may be obtained intravenously if necessary). Chemotherapy-induced nausea and vomiting can lead to impaired kidney function, [[Electrolyte imbalance|electrolyte disturbances]], [[dehydration]], malnutrition and [[Gastrointestinal perforation|gastrointestinal trauma]].<ref>{{Cite journal |last1=Gupta |first1=Kush |last2=Walton |first2=Rebecca |last3=Kataria |first3=S.P. |date=23 December 2020 |title=Chemotherapy-Induced Nausea and Vomiting: Pathogenesis, Recommendations, and New Trends |url=https://linkinghub.elsevier.com/retrieve/pii/S2468294220301131 |journal=Cancer Treatment and Research Communications |language=en |volume=26 |article-number=100278 |doi=10.1016/j.ctarc.2020.100278 |pmid=33360668 |doi-access=free }}</ref> It also causes significant psychological distress.<ref>{{Cite journal |last1=Sommariva |first1=Silvia |last2=Pongiglione |first2=Benedetta |last3=Tarricone |first3=Rosanna |date=4 December 2015 |title=Impact of chemotherapy-induced nausea and vomiting on health-related quality of life and resource utilization: A systematic review |url=https://linkinghub.elsevier.com/retrieve/pii/S1040842815300901 |journal=Critical Reviews in Oncology/Hematology |language=en |volume=99 |pages=13–36 |doi=10.1016/j.critrevonc.2015.12.001 |pmid=26697988 |url-access=subscription }}</ref>

=== Rehabilitation and long-term care ===

==== Oral rehabilitation ====
Oral health, dental pain, chewing and swallowing ability remain common long-term concerns of people who have undergone treatment for head and neck cancer, particularly those who have received radiotherapy to the salivary glands and oral structures.<ref>{{Cite journal |last1=Kanatas |first1=A. |last2=Ghazali |first2=N. |last3=Lowe |first3=D. |last4=Udberg |first4=M. |last5=Heseltine |first5=J. |last6=O'Mahony |first6=E. |last7=Rogers |first7=S. N. |date=29 June 2012 |title=Issues patients would like to discuss at their review consultation: variation by early and late stage oral, oropharyngeal and laryngeal subsites |url=http://link.springer.com/10.1007/s00405-012-2092-6 |journal=European Archives of Oto-Rhino-Laryngology |language=en |volume=270 |issue=3 |pages=1067–1074 |doi=10.1007/s00405-012-2092-6 |pmid=22743645 |issn=0937-4477|url-access=subscription }}</ref><ref>{{Cite journal |last1=Mahmood |first1=R. |last2=Butterworth |first2=C. |last3=Lowe |first3=D. |last4=Rogers |first4=S. N. |date=13 June 2014 |title=Characteristics and referral of head and neck cancer patients who report chewing and dental issues on the Patient Concerns Inventory |url=https://www.nature.com/articles/sj.bdj.2014.453 |journal=British Dental Journal |language=en |volume=216 |issue=11 |pages=E25 |doi=10.1038/sj.bdj.2014.453 |pmid=24923963 |issn=0007-0610}}</ref>

People are at increased risk of long-term xerostomia (dry mouth), thicker saliva, dental pain, dental diseases, and [[osteoradionecrosis]] following head and neck cancer treatment involving radiotherapy. Long-term care necessitates [[Adherence (medicine)|adherence]] to preventative [[oral hygiene]] protocols including [[Fluoride therapy#Toothpaste|high fluoride toothpastes]], [[fluoride varnish]], and more frequent dental examinations.<ref>{{Cite web |date=2 December 2024 |title=Oral healthcare provision for cancer pathways |url=https://www.england.nhs.uk/long-read/oral-healthcare-provision-for-cancer-pathways/ |access-date=2025-08-26 |publisher=NHS England |language=en-US}}</ref><ref>{{Cite web |date=9 November 2021 |title=Delivering better oral health: an evidence-based toolkit for prevention. Chapter 13: Evidence base for recommendations in the summary guidance tables |url=https://www.gov.uk/government/publications/delivering-better-oral-health-an-evidence-based-toolkit-for-prevention/chapter-13-evidence-base-for-recommendations-in-the-summary-guidance-tables |access-date=2025-08-26 |website=GOV.UK |language=en}}</ref>

The oral rehabilitation process can vary significantly. In some cases it is possible to provide individuals with dental prostheses within weeks, however this can also take several years.<ref>{{Cite journal |last1=Butterworth |first1=C. J. |last2=Rogers |first2=S. N. |date=29 July 2017 |title=The zygomatic implant perforated (ZIP) flap: a new technique for combined surgical reconstruction and rapid fixed dental rehabilitation following low-level maxillectomy |journal=International Journal of Implant Dentistry |language=en |volume=3 |issue=1 |article-number=37 |doi=10.1186/s40729-017-0100-8 |doi-access=free |issn=2198-4034 |pmc=5534193 |pmid=28756563}}</ref><ref>{{Cite journal |last1=Seikaly |first1=Hadi |last2=Idris |first2=Sherif |last3=Chuka |first3=Richelle |last4=Jeffery |first4=Caroline |last5=Dzioba |first5=Agnieszka |last6=Makki |first6=Fawaz |last7=Logan |first7=Heather |last8=O'Connell |first8=Daniel A. |last9=Harris |first9=Jeffrey |last10=Ansari |first10=Kal |last11=Biron |first11=Vincent |last12=Cote |first12=David |last13=Osswald |first13=Martin |last14=Nayar |first14=Suresh |last15=Wolfaardt |first15=John |date=26 June 2019 |title=The Alberta Reconstructive Technique: An Occlusion-Driven and Digitally Based Jaw Reconstruction |url=https://onlinelibrary.wiley.com/doi/10.1002/lary.28064 |journal=The Laryngoscope |language=en |volume=129 |issue=S4 |doi=10.1002/lary.28064 |pmid=31241771 |issn=0023-852X|url-access=subscription }}</ref><ref>{{Cite journal |last1=Patel |first1=J. |last2=Antov |first2=H. |last3=Nixon |first3=P. |date=27 May 2020 |title=Implant-supported oral rehabilitation in oncology patients: a retrospective cohort study |url=https://linkinghub.elsevier.com/retrieve/pii/S0266435620302370 |journal=British Journal of Oral and Maxillofacial Surgery |language=en |volume=58 |issue=8 |pages=1003–1007 |doi=10.1016/j.bjoms.2020.05.016 |pmid=32474015 |url-access=subscription }}</ref>

It is important that all people with head and neck cancer receive a specialist dental assessment ([[restorative dentistry]]) prior to the start of treatment, particularly if radiotherapy is planned. The purpose of this assessment is to facilitate an improvement in oral health prior to the start of cancer therapies and thus minimise the risk of long-term side effects such as osteoradionecrosis.<ref>{{Cite web |date=November 2016 |title=Predicting and Managing Oral and Dental Complications of Surgical and Non-Surgical Treatment for Head and Neck Cancer. A Clinical Guideline |url=https://www.restdent.org.uk/uploads/RD-UK%20H%20and%20N%20guideline.pdf |website=Restorative Dentistry UK}}</ref>

==== Speech, voice and swallow function ====
Rehabilitation targeting changes to speech, voice and swallowing aims to optimise function and help manage long-term effects.<ref name=":02" /><ref>{{Cite journal |last1=Banda |first1=Kondwani Joseph |last2=Chu |first2=Hsin |last3=Kao |first3=Ching-Chiu |last4=Voss |first4=Joachim |last5=Chiu |first5=Huei-Ling |last6=Chang |first6=Pi-Chen |last7=Chen |first7=Ruey |last8=Chou |first8=Kuei-Ru |date=11 November 2020 |title=Swallowing exercises for head and neck cancer patients: A systematic review and meta-analysis of randomized control trials |url=https://linkinghub.elsevier.com/retrieve/pii/S0020748920303151 |journal=International Journal of Nursing Studies |language=en |volume=114 |article-number=103827 |doi=10.1016/j.ijnurstu.2020.103827 |pmid=33352439 |url-access=subscription }}</ref> Rehabilitation can consist of therapy exercises and compensation strategies. Therapy exercises may involve muscle strengthening exercises e.g. for the tongue or [[larynx]] (voice box), while compensation strategies can involve texture modification or changes to head postures when swallowing. Swallowing rehabilitation may integrate several therapies using training devices, proactive therapies and intensive bootcamp programmes.<ref>{{Citation |last1=Arrese |first1=Loni C. |title=Dysphagia Management of Head and Neck Cancer Patients: Oral Cavity and Oropharynx |date=2019 |work=Clinical Care and Rehabilitation in Head and Neck Cancer |pages=313–328 |editor-last=Doyle |editor-first=Philip C. |url=http://link.springer.com/10.1007/978-3-030-04702-3_19 |access-date=2024-09-23 |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-030-04702-3_19 |isbn=978-3-030-04701-6 |last2=Schieve |first2=Heidi|url-access=subscription }}</ref><ref>{{Cite journal |last1=Speyer |first1=Renée |last2=Baijens |first2=Laura |last3=Heijnen |first3=Mariëlle |last4=Zwijnenberg |first4=Iris |date=17 September 2009 |title=Effects of Therapy in Oropharyngeal Dysphagia by Speech and Language Therapists: A Systematic Review |journal=Dysphagia |language=en |volume=25 |issue=1 |pages=40–65 |doi=10.1007/s00455-009-9239-7 |issn=0179-051X |pmc=2846331 |pmid=19760458}}</ref><ref name=":22" /><ref>{{Cite journal |last1=Hutcheson |first1=Katherine A. |last2=Barrow |first2=Martha P. |last3=Plowman |first3=Emily K. |last4=Lai |first4=Stephen Y. |last5=Fuller |first5=Clifton David |last6=Barringer |first6=Denise A. |last7=Eapen |first7=George |last8=Wang |first8=Yiqun |last9=Hubbard |first9=Rachel |last10=Jimenez |first10=Sarah K. |last11=Little |first11=Leila G. |last12=Lewin |first12=Jan S. |date=May 2018 |title=Expiratory muscle strength training for radiation-associated aspiration after head and neck cancer: A case series |journal=The Laryngoscope |language=en |volume=128 |issue=5 |pages=1044–1051 |doi=10.1002/lary.26845 |issn=0023-852X |pmc=5823707 |pmid=28833185}}</ref>

Early intervention promoting mobilisation of the swallowing muscles is likely to improve effectiveness.<ref>{{Cite journal |last1=Govender |first1=Roganie |last2=Smith |first2=Christina H. |last3=Taylor |first3=Stuart A. |last4=Barratt |first4=Helen |last5=Gardner |first5=Benjamin |date=10 January 2017 |title=Swallowing interventions for the treatment of dysphagia after head and neck cancer: a systematic review of behavioural strategies used to promote patient adherence to swallowing exercises |journal=BMC Cancer |language=en |volume=17 |issue=1 |article-number=43 |doi=10.1186/s12885-016-2990-x |doi-access=free |issn=1471-2407 |pmc=5223405 |pmid=28068939}}</ref><ref>{{Cite journal |last1=Govender |first1=Roganie |last2=Wood |first2=Caroline E. |last3=Taylor |first3=Stuart A. |last4=Smith |first4=Christina H. |last5=Barratt |first5=Helen |last6=Gardner |first6=Benjamin |date=19 April 2017 |title=Patient Experiences of Swallowing Exercises After Head and Neck Cancer: A Qualitative Study Examining Barriers and Facilitators Using Behaviour Change Theory |journal=Dysphagia |language=en |volume=32 |issue=4 |pages=559–569 |doi=10.1007/s00455-017-9799-x |issn=0179-051X |pmc=5515965 |pmid=28424898}}</ref><ref>{{Cite journal |last1=Rodriguez |first1=Ana Maria |last2=Komar |first2=Alyssa |last3=Ringash |first3=Jolie |last4=Chan |first4=Catherine |last5=Davis |first5=Aileen M. |last6=Jones |first6=Jennifer |last7=Martino |first7=Rosemary |last8=McEwen |first8=Sara |date=2019-08-14 |title=A scoping review of rehabilitation interventions for survivors of head and neck cancer |url=https://www.tandfonline.com/doi/full/10.1080/09638288.2018.1459880 |journal=Disability and Rehabilitation |language=en |volume=41 |issue=17 |pages=2093–2107 |doi=10.1080/09638288.2018.1459880 |pmid=29976091 |issn=0963-8288|url-access=subscription }}</ref>

==== Radiation-induced side effects ====
Radiotherapy can cause delayed [[Fibrosis|tissue fibrosis]],<ref>{{Cite journal |last1=Topkan |first1=Erkan |last2=Kucuk |first2=Ahmet |last3=Somay |first3=Efsun |last4=Yilmaz |first4=Busra |last5=Pehlivan |first5=Berrin |last6=Selek |first6=Ugur |date=2023-04-21 |title=Review of Osteoradionecrosis of the Jaw: Radiotherapy Modality, Technique, and Dose as Risk Factors |journal=Journal of Clinical Medicine |language=en |volume=12 |issue=8 |page=3025 |doi=10.3390/jcm12083025 |doi-access=free |issn=2077-0383 |pmc=10143049 |pmid=37109361}}</ref> lower cranial neuropathy<ref>{{Cite journal |last1=Hutcheson |first1=Katherine A. |last2=Yuk |first2=Maggie |last3=Hubbard |first3=Rachel |last4=Gunn |first4=Gary B. |last5=Fuller |first5=C. David |last6=Lai |first6=Stephen Y. |last7=Lin |first7=Heather |last8=Garden |first8=Adam S. |last9=Rosenthal |first9=David I. |last10=Hanna |first10=Ehab Y. |last11=Kies |first11=Merrill S. |last12=Lewin |first12=Jan S. |date=28 April 2017 |title=Delayed lower cranial neuropathy after oropharyngeal intensity-modulated radiotherapy: A cohort analysis and literature review |journal=Head & Neck |language=en |volume=39 |issue=8 |pages=1516–1523 |doi=10.1002/hed.24789 |issn=1043-3074 |pmc=5511776 |pmid=28452175}}</ref> and osteoradionecrosis of bones included in the fields of radiation. These late changes affect the functions of swallowing, speech, voice, breathing and mouth-opening ([[trismus]]) often necessitating placement of a feeding tube and/or [[Tracheotomy|tracheostomy]]. Symptoms usually present gradually, years after treatment though there is no agreed definition.

Several risk factors have been identified (e.g. tumour site,<ref>{{Cite journal |last1=Dong |first1=Yanqun |last2=Ridge |first2=John A. |last3=Ebersole |first3=Barbara |last4=Li |first4=Tianyu |last5=Lango |first5=Miriam N. |last6=Churilla |first6=Thomas M. |last7=Donocoff |first7=Kathleen |last8=Bauman |first8=Jessica R. |last9=Galloway |first9=Thomas J. |date=8 June 2019 |title=Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer |journal=Oral Oncology |language=en |volume=95 |pages=59–64 |doi=10.1016/j.oraloncology.2019.05.014 |pmc=7747216 |pmid=31345395}}</ref><ref>{{Cite journal |last1=Aylward |first1=Alana |last2=Park |first2=Jihye |last3=Abdelaziz |first3=Sarah |last4=Hunt |first4=Jason P. |last5=Buchmann |first5=Luke O. |last6=Cannon |first6=Richard B. |last7=Rowe |first7=Kerry |last8=Snyder |first8=John |last9=Deshmukh |first9=Vikrant |last10=Newman |first10=Michael |last11=Wan |first11=Yuan |last12=Fraser |first12=Alison |last13=Smith |first13=Ken |last14=Lloyd |first14=Shane |last15=Hitchcock |first15=Ying |date=7 February 2020 |title=Individualized prediction of late-onset dysphagia in head and neck cancer survivors |url=https://onlinelibrary.wiley.com/doi/10.1002/hed.26039 |journal=Head & Neck |language=en |volume=42 |issue=4 |pages=708–718 |doi=10.1002/hed.26039 |pmid=32031294 |issn=1043-3074|url-access=subscription }}</ref> gender,<ref>{{Cite journal |last1=Patterson |first1=J.M. |last2=McColl |first2=E. |last3=Carding |first3=P.N. |last4=Wilson |first4=J.A. |date=12 June 2018 |title=Swallowing beyond six years post (chemo)radiotherapy for head and neck cancer; a cohort study |url=https://linkinghub.elsevier.com/retrieve/pii/S1368837518302148 |journal=Oral Oncology |language=en |volume=83 |pages=53–58 |doi=10.1016/j.oraloncology.2018.06.003|url-access=subscription }}</ref> tumour stage), but the evidence base is conflicting. Reducing the radiotherapy dose to structures critical to swallowing function may improve function in the longer-term.<ref>{{Cite journal |last1=Nutting |first1=Christopher |last2=Finneran |first2=Laura |last3=Roe |first3=Justin |last4=Sydenham |first4=Mark A |last5=Beasley |first5=Matthew |last6=Bhide |first6=Shree |last7=Boon |first7=Cheng |last8=Cook |first8=Audrey |last9=De Winton |first9=Emma |last10=Emson |first10=Marie |last11=Foran |first11=Bernadette |last12=Frogley |first12=Robert |last13=Petkar |first13=Imran |last14=Pettit |first14=Laura |last15=Rooney |first15=Keith |date=6 July 2023 |title=Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial |url=https://linkinghub.elsevier.com/retrieve/pii/S1470204523002656 |journal=The Lancet Oncology |language=en |volume=24 |issue=8 |pages=868–880 |doi=10.1016/S1470-2045(23)00265-6 |pmid=37423227 |doi-access=free }}</ref>
Treatment options for late radiation-associated [[dysphagia]] are limited.<ref>{{Cite journal |last1=Strojan |first1=Primož |last2=Hutcheson |first2=Katherine A. |last3=Eisbruch |first3=Avraham |last4=Beitler |first4=Jonathan J. |last5=Langendijk |first5=Johannes A. |last6=Lee |first6=Anne W.M. |last7=Corry |first7=June |last8=Mendenhall |first8=William M. |last9=Smee |first9=Robert |last10=Rinaldo |first10=Alessandra |last11=Ferlito |first11=Alfio |date=18 July 2017 |title=Treatment of late sequelae after radiotherapy for head and neck cancer |journal=Cancer Treatment Reviews |language=en |volume=59 |pages=79–92 |doi=10.1016/j.ctrv.2017.07.003 |pmc=5902026 |pmid=28759822}}</ref> Some, more severely affected patients, choose to undergo a functional [[laryngectomy]] which can improve how they feel about swallowing and communication<ref>{{Cite journal |last1=Evangelista |first1=Lisa |last2=Nativ-Zeltzer |first2=Nogah |last3=Bewley |first3=Arnaud |last4=Birkeland |first4=Andrew C. |last5=Abouyared |first5=Marianne |last6=Kuhn |first6=Maggie |last7=Cates |first7=Daniel J. |last8=Farwell |first8=D. Gregory |last9=Belafsky |first9=Peter |date=2024-04-01 |title=Functional Laryngectomy and Quality of Life in Survivors of Head and Neck Cancer With Intractable Aspiration |journal=JAMA Otolaryngology–Head & Neck Surgery |language=en |volume=150 |issue=4 |pages=335–341 |doi=10.1001/jamaoto.2024.0049 |issn=2168-6181 |pmc=10921343 |pmid=38451502}}</ref> and can facilitate [[Esophageal speech|tracheosophageal speech]] and removal of feeding tubes though outcomes are variable.
=== Psychosocial ===
Programs to support the emotional and social well-being of people who have been diagnosed with head and neck cancer may be offered.<ref name=":1">{{cite journal | vauthors = Semple C, Parahoo K, Norman A, McCaughan E, Humphris G, Mills M | title = Psychosocial interventions for patients with head and neck cancer | journal = The Cochrane Database of Systematic Reviews | issue = 7 | article-number = CD009441 | date = July 2013 | pmid = 23857592 | doi = 10.1002/14651858.CD009441.pub2 | hdl-access = free | s2cid = 42090352 | hdl = 10026.1/3146 | pmc = 11936101 }}</ref> There is no clear evidence on the effectiveness of these interventions or any particular type of psychosocial program or length of time that is most helpful for those with head and neck cancer.<ref name=":1" />

==Prognosis==
Although early-stage head and neck cancers (especially laryngeal and oral cavity) have high cure rates, up to 50% of people with head and neck cancer present with advanced disease.<ref name="Gourin C, Podolsky R 2006 1093–106">{{cite journal | vauthors = Gourin CG, Podolsky RH | title = Racial disparities in patients with head and neck squamous cell carcinoma | journal = The Laryngoscope | volume = 116 | issue = 7 | pages = 1093–1106 | date = July 2006 | pmid = 16826042 | doi = 10.1097/01.mlg.0000224939.61503.83 | s2cid = 11140152 }}</ref>
Cure rates decrease in locally advanced cases, whose probability of cure is inversely related to tumor size and even more so to the extent of regional node involvement. {{Citation needed|date=November 2021}} HPV-associated oropharyngeal cancer has been shown to respond better to chemoradiation and, subsequently, have a better prognosis compared to non-associated HPV head and neck cancer.<ref name=":3" />

Consensus panels in America ([[American Joint Committee on Cancer|AJCC]]) and Europe ([[Union for International Cancer Control|UICC]]) have established staging systems for head and neck cancers. These staging systems attempt to standardize clinical trial criteria for research studies and define prognostic categories of disease. Head and neck cancers are staged according to the [[TNM staging system|TNM]] classification system, where T is the size and configuration of the tumor, N is the presence or absence of lymph node metastases, and M is the presence or absence of distant metastases. The T, N, and M characteristics are combined to produce a "stage" of the cancer, from I to IVB.<ref>{{cite journal | vauthors = Iro H, Waldfahrer F | title = Evaluation of the newly updated TNM classification of head and neck carcinoma with data from 3247 patients | journal = Cancer | volume = 83 | issue = 10 | pages = 2201–2207 | date = November 1998 | pmid = 9827726 | doi = 10.1002/(SICI)1097-0142(19981115)83:10<2201::AID-CNCR20>3.0.CO;2-7 | doi-access = free }}</ref>

=== Disease recurrence ===
Despite ongoing advances in the treatment of primary disease, recurrence rates remain high. Regardless of site of disease, the overall recurrence rate for advanced stage head and neck cancer is up to 50%.<ref>{{Cite journal |last=Isles |first=M.G. |last2=McConkey |first2=C. |last3=Mehanna |first3=H.M. |date=5 June 2008 |title=A systematic review and meta‐analysis of the role of positron emission tomography in the follow up of head and neck squamous cell carcinoma following radiotherapy or chemoradiotherapy |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1749-4486.2008.01688.x |journal=Clinical Otolaryngology |language=en |volume=33 |issue=3 |pages=210–222 |doi=10.1111/j.1749-4486.2008.01688.x |issn=1749-4478|url-access=subscription }}</ref><ref>{{Cite journal |last=Li |first=Yue |last2=Jiang |first2=Yuliang |last3=Qiu |first3=Bin |last4=Sun |first4=Haitao |last5=Wang |first5=Junjie |date=2022-12-06 |title=Current radiotherapy for recurrent head and neck cancer in the modern era: a state-of-the-art review |journal=Journal of Translational Medicine |language=en |volume=20 |issue=1 |doi=10.1186/s12967-022-03774-0 |doi-access=free |issn=1479-5876 |pmc=9724430 |pmid=36474246}}</ref> For recurrent oropharyngeal cancer, recurrence rates in the original site of the disease vary from 9% for HPV-positive disease to 26% for HPV- negative disease.<ref>{{Cite journal |last=Asheer |first=Jasmin |last2=Jensen |first2=Jakob Schmidt |last3=Grønhøj |first3=Christian |last4=Jakobsen |first4=Kathrine K. |last5=Buchwald |first5=Christian von |date=2020-09-01 |title=Rate of locoregional recurrence among patients with oropharyngeal squamous cell carcinoma with known HPV status: a systematic review |url=https://medicaljournalssweden.se/actaoncologica/article/view/24370 |journal=Acta Oncologica |language=en |volume=59 |issue=9 |pages=1131–1136 |doi=10.1080/0284186X.2020.1759822 |issn=0284-186X|doi-access=free }}</ref> 

Treatments for recurrent disease include potentially curative surgery either open or [[Transoral robotic surgery|transoral robotic]] or re-irradiation which can be associated with significant changes to speech and swallowing function.<ref>{{Cite journal |last=Williamson |first=Andrew |last2=Jashek-Ahmed |first2=Farizeh |last3=Hardman |first3=John |last4=Paleri |first4=Vinidh |date=17 June 2023 |title=Functional and quality-of-life outcomes following salvage surgery for recurrent squamous cell carcinoma of the head and neck: a systematic review and meta-analysis |url=https://link.springer.com/10.1007/s00405-023-08056-z |journal=European Archives of Oto-Rhino-Laryngology |language=en |volume=280 |issue=10 |pages=4597–4618 |doi=10.1007/s00405-023-08056-z |issn=0937-4477|url-access=subscription }}</ref><ref>{{Cite journal |last=Hardman |first=John |last2=Liu |first2=ZiWei |last3=Brady |first3=Grainne |last4=Roe |first4=Justin |last5=Kerawala |first5=Cyrus |last6=Riva |first6=Francesco |last7=Clarke |first7=Peter |last8=Kim |first8=Dae |last9=Bhide |first9=Shreerang |last10=Nutting |first10=Christopher |last11=Harrington |first11=Kevin |last12=Paleri |first12=Vinidh |date=18 February 2020 |title=Transoral robotic surgery for recurrent cancers of the upper aerodigestive tract—Systematic review and meta‐analysis |url=https://onlinelibrary.wiley.com/doi/10.1002/hed.26100 |journal=Head & Neck |language=en |volume=42 |issue=5 |pages=1089–1104 |doi=10.1002/hed.26100 |issn=1043-3074|url-access=subscription }}</ref><ref>{{Cite journal |last=Chen |first=Allen M. |last2=Harris |first2=Jeremy P. |last3=Nabar |first3=Rupali |last4=Tjoa |first4=Tjoson |last5=Haidar |first5=Yarah |last6=Armstrong |first6=William B. |date=16 April 2024 |title=Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer |url=https://linkinghub.elsevier.com/retrieve/pii/S0167814024002007 |journal=Radiotherapy and Oncology |language=en |volume=196 |article-number=110278 |doi=10.1016/j.radonc.2024.110278|doi-access=free }}</ref> Non curative treatment options include [[Cancer immunotherapy|immunotherapy]],<ref>{{Cite journal |last=Aboaid |first=Hazem |last2=Khalid |first2=Taimur |last3=Hussain |first3=Abbas |last4=Myat |first4=Yin Mon |last5=Nanda |first5=Rishi Kumar |last6=Srinivasmurthy |first6=Ramaditya |last7=Nguyen |first7=Kevin |last8=Jones |first8=Daniel Thomas |last9=Bigcas |first9=Jo-Lawrence |last10=Thein |first10=Kyaw Zin |date=2025-06-06 |title=Advances and challenges in immunotherapy in head and neck cancer |journal=Frontiers in Immunology |volume=16 |doi=10.3389/fimmu.2025.1596583 |doi-access=free |issn=1664-3224 |pmc=12179090 |pmid=40547025}}</ref> chemotherapy, and other [[Experimental cancer treatment|emerging therapies]] undergoing scientific investigation.<ref>{{Cite journal |last=Rosenberg |first=Ari J. |last2=Perez |first2=Cesar A. |last3=Guo |first3=Wenji |last4=de Oliveira Novaes |first4=Jose Monteiro |last5=da Silva Reis |first5=Kamilla F. Oliveira |last6=McGarrah |first6=Patrick W. |last7=Price |first7=Katharine A.R. |date=8 May 2024 |title=Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy |url=https://ascopubs.org/doi/10.1200/EDBK_433330 |journal=American Society of Clinical Oncology Educational Book |language=en |volume=44 |issue=3 |doi=10.1200/EDBK_433330 |issn=1548-8748|url-access=subscription }}</ref> Treatment decision making in recurrent head and neck cancer is often challenging.<ref>{{Cite journal |last=Mehanna |first=H |last2=Kong |first2=A |last3=Ahmed |first3=Sk |date=12 May 2016 |title=Recurrent head and neck cancer: United Kingdom National Multidisciplinary Guidelines |url=https://www.cambridge.org/core/product/identifier/S002221511600061X/type/journal_article |journal=The Journal of Laryngology & Otology |language=en |volume=130 |issue=S2 |pages=S181–S190 |doi=10.1017/S002221511600061X |issn=0022-2151|pmc=4873924 }}</ref> Careful pre-treatment counselling and an evaluation of the individual's values and goals should be at the centre of the [[Shared decision-making in medicine|treatment decision-making]].<ref>{{Cite journal |last=Brady |first=Grainne |last2=Roe |first2=Justin |last3=Paleri |first3=Vinidh |last4=Lagergren |first4=Pernilla |last5=Wells |first5=Mary |date=2025-02-01 |title=Patient and Caregiver Experience of Diagnosis, Treatment, and Living With Recurrent Oropharyngeal Cancer |url=https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2827118 |journal=JAMA Otolaryngology–Head & Neck Surgery |language=en |volume=151 |issue=2 |page=97 |doi=10.1001/jamaoto.2024.3757 |issn=2168-6181 |pmc=11583016 |pmid=39570619}}</ref>

=== Mental health ===
Cancer in the head or neck may impact a person's [[Mental health|mental well-being]] and can sometimes lead to [[social isolation]].<ref name=":1" /> This largely results from a decreased ability or inability to eat, speak, or effectively communicate. Physical appearance is often altered by the cancer itself and/or as a consequence of treatment side effects. [[Mental distress|Psychological distress]] may occur, and feelings such as uncertainty and fear may arise.<ref name=":1" /> Some people may also have a changed physical appearance, differences in swallowing or breathing, and residual pain to manage.<ref name=":1" />

==== Caregiver stress ====
[[Caregiver|Caregivers]] for people with head and neck cancer show higher rates of [[caregiver stress]] and poorer mental health compared to both the general population and those caring for people with different diseases.<ref>{{cite journal | vauthors = Longacre ML, Ridge JA, Burtness BA, Galloway TJ, Fang CY | title = Psychological functioning of caregivers for head and neck cancer patients | journal = Oral Oncology | volume = 48 | issue = 1 | pages = 18–25 | date = January 2012 | pmid = 22154127 | pmc = 3357183 | doi = 10.1016/j.oraloncology.2011.11.012 }}</ref> Caregivers show increased rates of [[Depression (mood)|depression]], [[Anxiety disorder|anxiety]] and [[post-traumatic stress disorder]] and physical health decline.<ref>{{Cite journal |last=Benyo |first=Sarah |last2=Phan |first2=Chandat |last3=Goyal |first3=Neerav |date=12 May 2022 |title=Health and Well-Being Needs Among Head and Neck Cancer Caregivers – A Systematic Review |url=https://journals.sagepub.com/doi/10.1177/00034894221088180 |journal=Annals of Otology, Rhinology & Laryngology |language=en |volume=132 |issue=4 |pages=449–459 |doi=10.1177/00034894221088180 |issn=0003-4894 |pmc=9989224 |pmid=35549916}}</ref> Caregivers frequently report loss associated with their caring role, including loss of role, certainty, security, finances, intimacy and enjoyment from social activities.<ref name=":18">{{Cite journal |last=Rogers |first=Simon N. |last2=Tsai |first2=Hao-Hsuan |last3=Cherry |first3=Mary Gemma |last4=Patterson |first4=Joanne M. |last5=Semple |first5=Cherith Jane |date=27 September 2024 |title=Experiences and Needs of Carers of Patients With Head and Neck Cancer: A Systematic Review |url=https://onlinelibrary.wiley.com/doi/10.1002/pon.9308 |journal=Psycho-Oncology |language=en |volume=33 |issue=10 |doi=10.1002/pon.9308 |issn=1057-9249}}</ref>

The high symptom burden patients' experience necessitates complex caregiver roles, often requiring hospital staff training, which caregivers can find distressing when asked to do so for the first time. It is becoming increasingly apparent that caregivers (most often spouses, children, or close family members) might not be adequately informed about, prepared for, or trained for the tasks and roles they will encounter during the treatment and recovery phases of this unique patient population, which span both technical and emotional support.<ref name=":4">{{Cite journal| vauthors = Sherrod AM, Murphy BA, Wells NL, Bond SM, Hertzog M, Gilbert J, Adair M, Parks L, Lydiatt WM, Smith RB, Militsakh O | display-authors = 6 |date=2014-05-20|title=Caregiving burden in head and neck cancer. |journal=Journal of Clinical Oncology |volume=32 |issue=15_suppl |article-number=e20678 |doi=10.1200/jco.2014.32.15_suppl.e20678 |issn=0732-183X}}</ref> Examples of technically difficult caregiver duties include tube feeding, [[Suction (medicine)|oral suctioning]], wound maintenance, medication delivery safe for tube feeding, and troubleshooting home medical equipment. If the cancer affects the mouth or larynx, caregivers must also find a way to effectively communicate among themselves and with their healthcare team. This is in addition to providing emotional support for the person undergoing cancer therapy.<ref name=":4" />

Of note, caregivers who report lower [[quality of life]] demonstrate increased burden and fatigue that extend beyond the treatment phase. Factors promoting coping and [[Psychological resilience|resilience]] among caregivers include access to information and support, supportive mechanisms to aid transition from treatment to recovery and personal attributes such as optimism and perspective.<ref name=":18" />

==== Fear of recurrence ====
Fear of [[Recurrent cancer|recurrence]] can occur in up to 72% of [[Cancer survivor|cancer survivors]] in general.<ref>{{Cite journal |last=Almeida |first=Susana N. |last2=Elliott |first2=Robert |last3=Silva |first3=Eunice R. |last4=Sales |first4=Célia M.D. |date=21 December 2018 |title=Fear of cancer recurrence: A qualitative systematic review and meta-synthesis of patients' experiences |url=https://linkinghub.elsevier.com/retrieve/pii/S0272735817305640 |journal=Clinical Psychology Review |language=en |volume=68 |pages=13–24 |doi=10.1016/j.cpr.2018.12.001|hdl=10216/118758 |hdl-access=free }}</ref> Fear of recurrence can remain with head and neck cancer survivors in the long-term, and it has been highlighted as a frequently reported unmet need and a potential cause for high levels of anxiety.<ref>{{Cite journal |last=Mäkitie |first=Antti A. |last2=Alabi |first2=Rasheed Omobolaji |last3=Pulkki-Råback |first3=Laura |last4=Almangush |first4=Alhadi |last5=Beitler |first5=Jonathan J. |last6=Saba |first6=Nabil F. |last7=Strojan |first7=Primož |last8=Takes |first8=Robert |last9=Guntinas-Lichius |first9=Orlando |last10=Ferlito |first10=Alfio |date=7 August 2024 |title=Psychological Factors Related to Treatment Outcomes in Head and Neck Cancer |url=https://link.springer.com/10.1007/s12325-024-02945-3 |journal=Advances in Therapy |language=en |volume=41 |issue=9 |pages=3489–3519 |doi=10.1007/s12325-024-02945-3 |issn=0741-238X |pmc=11349815 |pmid=39110309}}</ref><ref>{{Cite journal |last=McLaren |first=Oliver |last2=Perkins |first2=Clare |last3=Zhu |first3=Yinan |last4=Smith |first4=Mary |last5=Williams |first5=Richard |date=10 August 2021 |title=Patient perspectives on surveillance after head and neck cancer treatment: A systematic review |url=https://onlinelibrary.wiley.com/doi/10.1111/coa.13846 |journal=Clinical Otolaryngology |language=en |volume=46 |issue=6 |pages=1345–1353 |doi=10.1111/coa.13846 |issn=1749-4478}}</ref>

==== Emotional distress ====
People with head and neck cancer are at increased risk of [[Mental distress|emotional distress]]. Around a fifth of people report symptoms of depression, anxiety, or post-traumatic stress, and more than a third report general emotional distress or [[insomnia]] symptoms. People undergoing primary chemoradiotherapy experience significantly higher anxiety than those undergoing surgery, and people who smoke or have an advanced stage of tumour experience increased distress.<ref name=":19">{{Cite journal |last=Jimenez-Labaig |first=Pablo |last2=Aymerich |first2=Claudia |last3=Braña |first3=Irene |last4=Rullan |first4=Antonio |last5=Cacicedo |first5=Jon |last6=González-Torres |first6=Miguel Ángel |last7=Harrington |first7=Kevin J |last8=Catalan |first8=Ana |date=2024-04-30 |title=A comprehensive examination of mental health in patients with head and neck cancer: systematic review and meta-analysis |url=https://academic.oup.com/jncics/article/doi/10.1093/jncics/pkae031/7664173 |journal=JNCI Cancer Spectrum |language=en |volume=8 |issue=3 |doi=10.1093/jncics/pkae031 |issn=2515-5091 |pmc=11149920 |pmid=38702757}}</ref>

Out of 100,000 individuals with head and neck cancer, around 160 commit suicide per year.<ref name=":19" />

Those who have depression or depressive symptoms before the start of their treatment might have worse rates of [[Survival rate|overall survival]].<ref>{{Cite journal |last=Van der Elst |first=Sarah |last2=Bardash |first2=Yonatan |last3=Wotman |first3=Michael |last4=Kraus |first4=Dennis |last5=Tham |first5=Tristan |date=15 September 2021 |title=The prognostic impact of depression or depressive symptoms on patients with head and neck cancer: A systematic review and meta‐analysis |url=https://onlinelibrary.wiley.com/doi/10.1002/hed.26868 |journal=Head & Neck |language=en |volume=43 |issue=11 |pages=3608–3617 |doi=10.1002/hed.26868 |issn=1043-3074|url-access=subscription }}</ref>

===Others===
Like any [[cancer]], [[metastasis]] affects many areas of the body as the cancer spreads from cell to cell and [[organ (biology)|organ]] to organ. For example, if it spreads to the [[bone marrow]], it will prevent the body from producing enough [[red blood cell]]s and affect the proper functioning of the [[white blood cell]]s and the body's [[immune system]]; spreading to the [[circulatory system]] will prevent oxygen from being transported to all the cells of the body; and throat cancer can throw the [[nervous system]] into chaos, making it unable to properly regulate and control the body.{{citation needed|date=September 2024}}

==Epidemiology==
[[File:Mouth and oropharynx cancers world map - Death - WHO2004.svg|thumb|[[Age adjustment|Age-standardized]] death from oro-pharyngeal cancer per 100,000&nbsp;inhabitants in 2004:<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |publisher=World Health Organization |access-date=Nov 11, 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=2009-11-11}}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|No data}}
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{{div col end}}]]
Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide, with 890,000 new cases documented and 450,000 people dying from the disease.<ref name=":3" />  The risk of developing head and neck cancer increases with age, especially after 50 years. Most people who do so are between 50 and 70 years old.<ref name="ridge" />

In North America and Europe, the tumors usually arise from the oral cavity, oropharynx, or larynx, whereas nasopharyngeal cancer is more common in the Mediterranean countries and in the Far East. In Southeast China and Taiwan, head and neck cancer, specifically [[Nasopharyngeal carcinoma|nasopharyngeal cancer]], is the most common cause of death in young men.<ref>{{cite journal | vauthors = Titcomb CP | title = High incidence of nasopharyngeal carcinoma in Asia | journal = Journal of Insurance Medicine | volume = 33 | issue = 3 | pages = 235–238 | year = 2001 | pmid = 11558403 }}</ref>

=== United States ===
In the United States, head and neck cancer makes up 3% of all cancer cases (averaging 53,000 new diagnoses per year) and 1.5% of cancer deaths.<ref>{{cite journal |vauthors=Siegel RL, Miller KD, Jemal A |date=January 2020 |title=Cancer statistics, 2020 |journal=CA: A Cancer Journal for Clinicians |volume=70 |issue=1 |pages=7–30 |doi=10.3322/caac.21590 |pmid=31912902 |doi-access=free}}</ref> The 2017 worldwide figure cites head and neck cancers as representing 5.3% of all cancers (not including non-melanoma skin cancers).<ref name="pmid31560378">{{cite journal |vauthors=Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, etal |date=December 2019 |title=Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study |url= |journal=JAMA Oncology |volume=5 |issue=12 |pages=1749–1768 |doi=10.1001/jamaoncol.2019.2996 |pmc=6777271 |pmid=31560378 |collaboration=Global Burden of Disease Cancer Collaboration}}</ref><ref name="Aupérin 178–186" />  

Head and neck cancer secondary to chronic alcohol or tobacco use has been steadily declining as less of the population chronically smokes tobacco.<ref name=":3" /> 

[[HPV-positive oropharyngeal cancer]] is rising, particularly in younger people in westernized nations, which is thought to be reflective of changes in oral sexual practices, specifically with regard to the number of oral sexual partners.<ref name="Aupérin 178–186" /><ref name=":3" /> This increase since the 1970s has mostly affected wealthier nations and male populations.<ref name="Gillison_2014">{{cite journal |display-authors=6 |vauthors=Gillison ML, Castellsagué X, Chaturvedi A, Goodman MT, Snijders P, Tommasino M, Arbyn M, Franceschi S |date=February 2014 |title=Eurogin Roadmap: comparative epidemiology of HPV infection and associated cancers of the head and neck and cervix |journal=International Journal of Cancer |volume=134 |issue=3 |pages=497–507 |doi=10.1002/ijc.28201 |pmid=23568556 |s2cid=37877664}}</ref><ref name="Gillison_2015">{{cite journal |vauthors=Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C |date=October 2015 |title=Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma |journal=Journal of Clinical Oncology |volume=33 |issue=29 |pages=3235–3242 |doi=10.1200/JCO.2015.61.6995 |pmc=4979086 |pmid=26351338}}</ref><ref name="Aupérin 178–186" /> This is due to evidence suggesting that transmission rates of HPV from women to men are higher than from men to women, as women often have a higher immune response to infection.<ref name="Aupérin 178–186" /><ref name="pmid25043222">{{cite journal |display-authors=6 |vauthors=Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, Sudenga SL, Monsonego J, Franceschi S |date=June 2015 |title=EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection |journal=International Journal of Cancer |volume=136 |issue=12 |pages=2752–2760 |doi=10.1002/ijc.29082 |pmc=4297584 |pmid=25043222}}</ref> In the United States, the incidence of HPV-positive oropharyngeal cancer has overtaken HPV-positive [[cervical cancer]] as the leading HPV related cancer type.<ref>{{Cite journal |last1=Roman |first1=Benjamin R. |last2=Aragones |first2=Abraham |date=23 September 2021 |title=Epidemiology and incidence of HPV-related cancers of the head and neck |journal=Journal of Surgical Oncology |language=en |volume=124 |issue=6 |pages=920–922 |doi=10.1002/jso.26687 |issn=0022-4790 |pmc=8552291 |pmid=34558067}}</ref> 
* In 2008, there were 22,900 cases of oral cavity cancer, 12,250 cases of laryngeal cancer, and 12,410 cases of pharyngeal cancer in the United States.<ref name="ridge" />
* In 2002, 7,400 Americans were projected to die of these cancers.<ref name="ACS">Cancer Facts and Figures, [http://www.cancer.org/downloads/STT/CancerFacts&Figures2002TM.pdf] {{webarchive|url=https://web.archive.org/web/20070929120429/http://www.cancer.org/downloads/STT/CancerFacts%26Figures2002TM.pdf|date=2007-09-29}}, American Cancer Society 2002.</ref>
* More than 70% of throat cancers are at an advanced stage when discovered.<ref name="NCH">{{cite web |url=http://cancer.nchmd.org/treatment.aspx?id=741 |title=Throat Cancer |access-date=2007-06-17 |archive-url=https://web.archive.org/web/20070701170101/http://cancer.nchmd.org/treatment.aspx?id=741 |archive-date=2007-07-01 | work = Patient information web page | publisher = NCH Healthcare Systems | date = 1999 }}</ref>
* Men are 89% more likely than women to be diagnosed with these cancers and are almost twice as likely to die of them.<ref name="ACS" />
* African Americans are disproportionately affected by head and neck cancer, with younger ages of incidence, increased mortality, and more advanced disease at presentation.<ref name="Gourin C, Podolsky R 2006 1093–106" /> Laryngeal cancer incidence is higher in African Americans relative to white, Asian, and Hispanic populations. There is a lower survival rate for similar tumor states in African Americans with head and neck cancer.<ref name="ridge" />

==Research==
Immunotherapy with immune checkpoint inhibitors is being investigated in head and neck cancers.<ref>{{cite journal | vauthors = Syn NL, Teng MW, Mok TS, Soo RA | title = De-novo and acquired resistance to immune checkpoint targeting | journal = The Lancet. Oncology | volume = 18 | issue = 12 | pages = e731–e741 | date = December 2017 | pmid = 29208439 | doi = 10.1016/s1470-2045(17)30607-1 }}</ref>

== References ==
{{Reflist}}

== External links ==
{{commons}}
* [https://www.medlineplus.gov/headandneckcancer.html Head and Neck Cancer] at [[MedlinePlus]] (National Library of Medicine)
* [https://www.macmillan.org.uk/cancer-information-and-support/head-and-neck-cancer Head and neck cancer] at [[Macmillan Cancer Support]] (UK)
* [http://www.radiologyinfo.org/en/info.cfm?pg=hdneck Head and Neck Cancer Treatment] at [[RadiologyInfo]]
* [http://www.cancer.net/cancer-types/head-and-neck-cancer Head and Neck Cancer] at Cancer.net ([[American Society of Clinical Oncology]])
* [https://hancuk.org/ Head and Neck Cancer UK] (HANCUK)

{{Medical resources
|  DiseasesDB     =
|  ICD10          = {{ICD10|C|07||c|00}}–{{ICD10|C|14||c|00}}<br />{{ICD10|C|32||c|30}}–{{ICD10|C|33||c|30}}
|  ICD9           = {{ICD9|140}}–{{ICD9|149}}
|  ICDO           =
|  OMIM           =
|  MedlinePlus    =
|  eMedicineSubj  =
|  eMedicineTopic =
|  MeshID         = D006258
}}

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{{Tumors of lip, oral cavity and pharynx}}
{{Human papillomavirus}}

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[[Category:Head and neck cancer| ]]
[[Category:Otorhinolaryngology]]
[[Category:Health effects of tobacco]]
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