View source for Penile cancer

{{Infobox medical condition (new)
| name            = Carcinoma of the penis
| synonyms        =
| image           = Penile cancer by hariadhi.svg
| caption         =
| pronounce       =
| field           = [[Oncology]]
| symptoms        =
| complications   =
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| causes          =
| risks           =
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| frequency       = 36,068 in 2020<ref name =global2020/>
| deaths          = 13,211 (2020)<ref name =global2020/>
}}
'''Penile cancer''', or '''penile carcinoma''', is a [[cancer]] that develops in the skin or tissues of the [[Human penis|penis]]. Symptoms may include abnormal growth, an [[genital ulcer|ulcer]] or sore on the skin of the penis, and bleeding or foul-smelling discharge.<ref>{{Cite web|url=https://www.cancer.org/cancer/penile-cancer/detection-diagnosis-staging/signs-symptoms.html|title=Signs and Symptoms of Penile Cancer {{!}} Signs Of Penile Cancer|website=www.cancer.org|language=en|access-date=2019-12-18}}</ref>

Risk factors include [[phimosis]] (inability to retract the [[foreskin]] of the penis), chronic [[inflammation]], smoking, [[HPV infection]], [[Condylomata acuminata|condylomata acuminate]], having multiple sexual partners, and early age of sexual intercourse.<ref>{{Cite web|url=https://uroweb.org/guideline/penile-cancer/#note_16|title=EAU Guidelines: Penile Cancer | author = Sumedia-Online |website=Uroweb|language=en-US|access-date=2019-12-18}}</ref>

Around 95% of penile cancers are [[squamous-cell carcinoma]]s. Other types of penile cancer, such as [[Merkel-cell carcinoma]], [[small-cell carcinoma]], and [[melanoma]], are generally rare.<ref name="Bleeker2009">{{cite journal | vauthors = Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ | title = Penile cancer: epidemiology, pathogenesis and prevention | journal = World Journal of Urology | volume = 27 | issue = 2 | pages = 141–50 | date = April 2009 | article-number = 141 | pmid = 18607597 | doi = 10.1007/s00345-008-0302-z | s2cid = 25742226 }}</ref> In 2020, it occurred in 36,000 men and caused 13,000 deaths.<ref name="global2020">{{cite web |title=Penile Cancer Factsheet |url=http://gco.iarc.fr/today/data/factsheets/cancers/26-Penis-fact-sheet.pdf |website=Global Cancer Observatory |access-date=7 January 2022}}</ref>

==Signs and symptoms==
Penile cancer can present as redness and irritation on the penis with a skin thickening on the glans or inner foreskin or an ulcerative, outward growing ([https://www.merriam-webster.com/medical/exophytic#:~:text=Medical%20Definition%20of%20exophytic,used%20of%20tumors%20%E2%80%94%20compare%20endophytic exophytic]) or "finger-like" (papillary) growth.<ref name=":0">{{Cite journal|last1=Turner|first1=Bruce|last2=Drudge-Coates|first2=Lawrence|last3=Henderson|first3=Sarah|date=2013-03-20|title=Penile cancer: diagnosis, clinical features and management|url=http://rcnpublishing.com/doi/abs/10.7748/ns2013.03.27.29.50.e6135|journal=Nursing Standard|language=en|volume=27|issue=29|pages=50–57|doi=10.7748/ns2013.03.27.29.50.e6135|pmid=23634501|issn=0029-6570|url-access=subscription}}</ref><ref name=":1">{{Cite web|title=Signs and Symptoms of Penile Cancer {{!}} Signs Of Penile Cancer|url=https://www.cancer.org/cancer/penile-cancer/detection-diagnosis-staging/signs-symptoms.html|access-date=2020-12-08|website=www.cancer.org|language=en}}</ref> Penile cancer may accompany penile discharge with or without difficulty or burning or tingling while urinating ([[dysuria]]) and bleeding from the penis.<ref name=":0" /><ref name=":1" />

==Risk factors==

===Infections===
* [[HIV infection]]—HIV-positive men have an eight-fold increased risk of developing penile cancer compared to HIV-negative men.<ref name="acs-risk">{{cite web|url=http://www.cancer.org/Cancer/PenileCancer/DetailedGuide/penile-cancer-risk-factors|title=What Are the Risk Factors for Penile Cancer?|website=www.cancer.org|access-date=2 April 2018|archive-date=10 December 2016|archive-url=https://web.archive.org/web/20161210173802/http://www.cancer.org/cancer/penilecancer/detailedguide/penile-cancer-risk-factors|url-status=dead}}</ref><ref name=Bleeker2012>{{Cite book | vauthors = Bleeker MC, Heideman DL, Snijders PJ, Horenblas S, Meijer CJ | doi = 10.1007/978-1-84882-879-7_1 | chapter = Epidemiology and Etiology of Penile Cancer | title = Textbook of Penile Cancer | pages = 1–11 | year = 2011 | isbn = 978-1-84882-878-0 }}</ref>
* [[Human papillomavirus]]—HPV is a risk factor in the development of penile cancer.<ref name="pow-sang-2010"/> According to the [[Centers for Disease Control and Prevention]] (CDC), HPV is responsible for about 800 (about 40%) of 1,570 cases of penile cancer diagnosed annually in the United States.<ref>{{cite web|url=http://www.cancer.gov/cancertopics/types/penile/|title=Penile Cancer|date=1980-01-01|website=National Cancer Institute|access-date=2 April 2018}}</ref><ref>https://www.cdc.gov/cancer/hpv/statistics/penile.htm HPV-Associated Penile Cancer Rates by Race and Ethnicity] [[Centers for Disease Control and Prevention]]</ref> There are more than 120 types of HPV.<ref>{{Cite web|url = http://www.stopcancerfund.org/p-cervical-cancer-hpv/hpv-q-a/|title = HPV: Q&A|date = April 2009|website = Cancer Prevention and Treatment Fund| vauthors = de Bravo BF, DeSoto M, Seu K |access-date = August 13, 2013}}</ref>
* [[Genital warts]]—Genital or perianal warts increase the risk of invasive penile cancer by about 3.7 times if they occurred more than two years before the reference date.<ref name="pow-sang-2010"/> About half of men with penile cancer also have [[genital warts]], which are caused by HPV.<ref name="cruk-risks"/>

===Hygiene and injury===
* Poor [[hygiene]]—Poor hygiene can increase a man's risk of penile cancer.<ref name="minhas-2010">{{cite journal | vauthors = Minhas S, Manseck A, Watya S, Hegarty PK | title = Penile cancer--prevention and premalignant conditions | journal = Urology | volume = 76 | issue = 2 Suppl 1 | pages = S24-35 | date = August 2010 | pmid = 20691883 | doi = 10.1016/j.urology.2010.04.007 }}</ref><ref>{{cite journal | vauthors = Reis AA, Paula LB, Paula AA, Saddi VA, Cruz AD | title = [Clinico-epidemiological aspects associated with penile cancer] | language = pt | journal = Ciencia & Saude Coletiva | volume = 15 | pages = 1105–11 | date = June 2010 | issue = Suppl 1 | pmid = 20640268 | doi = 10.1590/s1413-81232010000700018 | doi-access = free }}</ref>
* [[Smegma]]—Smegma, a whitish substance that can accumulate beneath the foreskin, is associated with a greater risk of penile cancer.<ref name="acs-risk"/><ref>{{cite journal | vauthors = Morris BJ, Gray RH, Castellsague X, Bosch FX, Halperin DT, Waskett JH, Hankins CA | title = The Strong Protective Effect of Circumcision against Cancer of the Penis | journal = Advances in Urology | volume = 2011 | article-number = 812368 | year = 2011 | pmid = 21687572 | pmc = 3113366 | doi = 10.1155/2011/812368 | doi-access = free }}</ref> The American Cancer Society suggests that smegma may not be carcinogenic, but may increase the risk by causing irritation and inflammation of the penis.<ref name="acs-risk"/>
* [[Balanitis]] and penile injury—Inflammation of the [[foreskin]] and/or the [[glans penis]] (balanitis) is associated with about 3.1 times increased risk of penile cancer.<ref name="pow-sang-2010"/> It is usually caused by poor hygiene, [[allergic reactions]] to certain [[soap]]s, or an underlying health condition such as [[reactive arthritis]], infection, or [[diabetes]].<ref name="pubmedhealth">[https://web.archive.org/web/20110208224259/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001865 PubMed Health] [[PubMed]], Last Reviewed: September 16, 2011</ref> Small tears and abrasions of the penis are associated with about 3.9 times increased risk of cancer.
* [[Phimosis]]—Phimosis is a medical condition where the foreskin cannot be fully retracted over the glans. It is considered a significant risk factor in the development of penile cancer ([[odds ratio]] of 38–65).<ref name="pow-sang-2010"/> Phimosis may also be a symptom of penile cancer.<ref name="cruk-symptoms">{{cite web|date=2017-08-30|title=Symptoms of penile cancer - Penile cancer - Cancer Research UK|url=http://cancerhelp.cancerresearchuk.org/type/penile-cancer/about/symptoms-of-penile-cancer|access-date=2 April 2018|website=cancerhelp.cancerresearchuk.org}}</ref>
* [[Paraphimosis]]—Paraphimosis is a medical condition where the foreskin becomes trapped behind the [[Glans penis|glans]]. It is considered a risk factor for the development of penile cancer.<ref name="acs-risk"/>
* [[Circumcision]]—Some studies show that circumcision during infancy or in childhood may provide partial protection against penile cancer, but this is not the case when performed in adulthood.<ref name="larke-2010">{{cite journal | vauthors = Larke NL, Thomas SL, dos Santos Silva I, Weiss HA | title = Male circumcision and penile cancer: a systematic review and meta-analysis | journal = Cancer Causes & Control | volume = 22 | issue = 8 | pages = 1097–110 | date = August 2011 | pmid = 21695385 | pmc = 3139859 | doi = 10.1007/s10552-011-9785-9 }}</ref> It has been suggested that the reduction in risk may be due to reduced risk of [[phimosis]];<ref name="acs-risk"/><ref name="larke-2010"/> other possible mechanisms include reduction in risk of [[smegma]] and [[Human papillomavirus|HPV]] infection.<ref name="acs-risk"/>

===Other===
* Age—Penile cancer is rarely seen in men under the age of 50. About 4 out of 5 men diagnosed with penile cancer are over the age of 55.<ref name="acs-risk"/>
* [[Lichen sclerosus]]—Lichen sclerosus is a disease causing white patches on the skin.  Lichen sclerosus increases the risk of penile cancer.<ref name="minhas-2010"/><ref name=Micali2006>{{cite journal | vauthors = Micali G, Nasca MR, Innocenzi D, Schwartz RA | title = Penile cancer | journal = Journal of the American Academy of Dermatology | volume = 54 | issue = 3 | pages = 369–91; quiz 391–4 | date = March 2006 | pmid = 16488287 | doi = 10.1016/j.jaad.2005.05.007 }}</ref> As the exact cause of lichen sclerosus is unknown, there is no known way to prevent it.<ref name="minhas-2010"/>
* [[Tobacco]]—Chewing or [[smoking]] tobacco increases the risk of penile cancer by 1.5–6 times, depending on the duration of smoking and the daily number of cigarettes.<ref name=Bleeker2009/><ref name="pow-sang-2010">{{cite journal | vauthors = Pow-Sang MR, Ferreira U, Pow-Sang JM, Nardi AC, Destefano V | title = Epidemiology and natural history of penile cancer | journal = Urology | volume = 76 | issue = 2 Suppl 1 | pages = S2-6 | date = August 2010 | pmid = 20691882 | doi = 10.1016/j.urology.2010.03.003 }}</ref><ref name="minhas-2010"/>
* [[Ultraviolet light]]—Men with [[psoriasis]] who have been treated using UV light and a drug known as [[psoralen]] have an increased risk of penile cancer.<ref name="acs-risk"/><ref name="minhas-2010"/>

==Pathogenesis==
Penile cancer arises from [[Precursor cell|precursor]] lesions, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers, this sequence is as follows:<ref name=Bleeker2009/>
# [[Squamous]] [[hyperplasia]];
# Low-grade penile intraepithelial neoplasia (PIN);
# High-grade PIN (carcinoma in situ—[[Bowen's disease]], [[Erythroplasia of Queyrat]] and [[bowenoid papulosis]] (BP));
# Invasive carcinoma of the penis.

However, in some cases, non-[[Dysplasia|dysplastic]] or mildly dysplastic lesions may progress directly into cancer. Examples include flat penile lesions (FPL) and ''[[condylomata acuminata]]''.<ref name=Bleeker2009/>

In [[Human papillomavirus infection|HPV]] negative cancers, the most common precursor lesion is [[lichen sclerosus]] (LS).<ref name=Bleeker2009/>

==Diagnosis==
The International Society of Urological Pathology (ISUP) recommends the use of [[p16]]<sup>INK4A</sup> [[immunostaining]] for the diagnosis and classification of HPV-related penile cancer.<ref>{{cite journal | vauthors = Canete-Portillo S, Velazquez EF, Kristiansen G, Egevad L, Grignon D, Chaux A, Cubilla AL | title = Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers V: Recommendations on the Use of Immunohistochemical and Molecular Biomarkers in Penile Cancer | journal = The American Journal of Surgical Pathology | volume = 44 | issue = 7 | pages = e80–e86 | date = July 2020 | pmid = 32235153 | doi = 10.1097/PAS.0000000000001477 | s2cid = 214766446 }}</ref>

===Classification===
Around 95% of penile cancers are squamous-cell carcinomas. They are classified into the following types:<ref>{{cite web |url= https://www.lecturio.com/concepts/penile-cancer/| title= Penile Cancer
|website=The Lecturio Medical Concept Library |access-date= 3 October 2021}}</ref>
* basaloid (4%)
* warty (6%)
* mixed warty-basaloid (17%)
* verrucous (8%)
* papillary (7%)
* other SCC mixed (7%)
* sarcomatoid carcinomas (1%)
* not otherwise specified (49%)
Other types of carcinomas are rare and may include [[small-cell carcinoma|small-cell]], [[Merkel-cell carcinoma|Merkel-cell]], [[clear-cell adenocarcinoma|clear-cell]], sebaceous-cell or [[basal-cell carcinoma|basal-cell]] tumors. Non-epithelial malignancies such as [[melanoma]]s and [[sarcoma]]s are even rarer.<ref name=Bleeker2009/>

====Staging====
Like many [[cancer]]s, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which cancer spreads in the body. Much less often, it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The extent of tumor invasion, nodal metastasis, and distant metastasis determines the staging of penile cancer.<ref name=cancergov>{{cite web|url=http://www.cancer.gov/cancertopics/pdq/treatment/penile/HealthProfessional/page3|title=Stage Information for Penile Cancer|access-date=3 November 2013|publisher=National Cancer Institute|date=1980-01-01}}</ref>

The T portion of the [[AJCC]] [[TNM staging system|TNM staging]] guidelines are for the primary tumor as follows:<ref name=cancergov/>
* TX: Primary tumor cannot be assessed.
* T0: No evidence of primary tumor.
* Tis: Carcinoma ''in situ''.
* Ta: Noninvasive verrucous carcinoma.
* T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4).
* T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated.
* T2: Tumor invades the corpus spongiosum or cavernosum.
* T3: Tumor invades the urethra or prostate.
* T4: Tumor invades other adjacent structures.

Anatomic Stage or Prognostic Groups of penile cancer are as follows:<ref name=cancergov/>
* Stage 0—Carcinoma ''in situ''.
* Stage I—The cancer is moderately or well-differentiated and only affects the subepithelial connective tissue.
* Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.
* Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.
* Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes.
* Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.

====HPV positive tumors====
[[Human papillomavirus]] prevalence in penile cancers is high and is involved in approximately 40% of penile cancers. [[HPV16]] is the predominant genotype accounting for approximately 63% of HPV-positive tumors. Among warty/basaloid cancers, the HPV prevalence is 70–100% while in other types it is around 30%.<ref name=Bleeker2009/>

== Prevention ==
* [[HPV vaccine]]s such as [[Gardasil]] or [[Cervarix]] may reduce the risk of HPV and, consequently, penile cancer.<ref name=Bleeker2009/><ref name="minhas-2010"/>
* The use of condoms is thought to be protective against HPV-associated penile cancer.<ref name=Bleeker2009/>
* Good genital hygiene, which involves washing the penis, the scrotum, and the foreskin daily with water, may prevent balanitis and penile cancer. However, soaps with harsh ingredients should be avoided.<ref name=Minhas-2013>{{cite journal |vauthors= Shabbir M, Barod R, Hegarty PK, Minhas S |date= 2013|title=  Primary prevention and vaccination for penile cancer|journal= Ther Adv Urol|volume= 5|issue= 3|pages= 161–169|doi= 10.1177/1756287212465456|pmid= 23730331|pmc= 3655354}}</ref>
* Cessation of smoking may reduce the risk of penile cancer.<ref name="pow-sang-2010"/>
* Circumcision during infancy or in childhood may provide partial protection against penile cancer. Several authors have proposed circumcision as a possible strategy for penile cancer prevention;<ref name=Bleeker2009/><ref name="minhas-2010"/><ref>{{cite journal | vauthors = de Souza KW, dos Reis PE, Gomes IP, de Carvalho EC | title = [Prevention strategies for testicular and penile cancer: an integrative review] | language = pt | journal = Revista da Escola de Enfermagem da USP | volume = 45 | issue = 1 | pages = 277–82 | date = March 2011 | pmid = 21445520 | doi = 10.1590/s0080-62342011000100039 | doi-access = free }}</ref> however, the American Cancer Society points to the rarity of the disease and notes that neither the American Academy of Pediatrics nor the Canadian Academy of Pediatrics recommend routine neonatal circumcision.<ref name="acs-risk"/>
* Phimosis can be prevented by practising proper hygiene and by retracting the foreskin regularly.<ref name=Minhas-2013/>
* Paraphimosis can be prevented by not leaving the foreskin retracted for prolonged periods.<ref name=Minhas-2013/>

==Treatment==
Treatment of penile cancer will vary depending on the clinical stage of the tumor at the time of diagnosis.<ref>{{cite book | vauthors = Engelsgjerd JS, LaGrange CA |title=Penile Cancer|date=2020|url=https://www.ncbi.nlm.nih.gov/books/NBK499930/| work = StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29763105|access-date=2020-12-07}}</ref> There are several treatment options for penile cancer, depending on staging. They include [[surgery]], [[radiation therapy]], [[chemotherapy]], and [[biological therapy]]. The most common treatment is one of five types of surgery:
* [[Wide local excision]]—the tumor and some surrounding healthy tissue are removed
* [[Microsurgery]]—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible
* [[Laser surgery]]—laser light is used to burn or cut away cancerous cells
* [[Circumcision]]—cancerous foreskin is removed
* Amputation ([[penectomy]])—a partial or total removal of the penis, and possibly the associated [[lymph nodes]].

The role of radiation therapy includes an organ-sparing approach for early-stage penile cancer at specialized centres. Furthermore, adjuvant therapy is used for patients with locally advanced disease or for symptom management.<ref>{{cite journal | vauthors = Hakenberg OW, Dräger DL, Erbersdobler A, Naumann CM, Jünemann KP, Protzel C | title = The Diagnosis and Treatment of Penile Cancer | journal = Deutsches Ärzteblatt International | volume = 115 | issue = 39 | pages = 646–652 | date = September 2018 | pmid = 30375327 | pmc = 6224543 | doi = 10.3238/arztebl.2018.0646 }}</ref>

==Prognosis==
Prognosis can vary considerably for patients, depending on the person's stage of cancer. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.<ref name=cancergov/>

==Epidemiology==
Penile cancer is a rare cancer in [[developed nations]], with annual incidence varying from 0.3 to 1 per 100,000 per year, accounting for around 0.4–0.6% of all malignancies.<ref name=Bleeker2009/> The annual [[incidence (epidemiology)|incidence]] is approximately 1 in 100,000 men in the United States,<ref>[http://www.cancer.org/Cancer/PenileCancer/DetailedGuide/penile-cancer-key-statistics The American Cancer Society: Penile Cancer: What is penile cancer?] {{Webarchive|url=https://web.archive.org/web/20170114144337/http://www.cancer.org/cancer/penilecancer/detailedguide/penile-cancer-key-statistics |date=2017-01-14 }} [[American Cancer Society]], Last revised: January 8, 2012</ref> 1 in 250,000 in Australia,<ref>[http://www.racp.edu.au The Official Website of the Royal Australasian College of Physicians], Published September 2010</ref> and 0.82 per 100,000 in Denmark.<ref name="pmid8520335">{{cite journal | vauthors = Frisch M, Friis S, Kjaer SK, Melbye M | title = Falling incidence of penis cancer in an uncircumcised population (Denmark 1943-90) | journal = BMJ (Clinical Research Ed.) | volume = 311 | issue = 7018 | page = 1471 | date = December 1995 | pmid = 8520335 | pmc = 2543732 | doi = 10.1136/bmj.311.7018.1471 }}</ref> In the United Kingdom, fewer than 500 men are diagnosed with penile cancer every year.<ref name="cruk-risks">{{cite web|url=http://cancerhelp.cancerresearchuk.org/type/penile-cancer/about/risks-and-causes-of-penile-cancer|title=Risks and causes - Penile cancer - Cancer Research UK|date=2017-08-30|website=cancerhelp.cancerresearchuk.org|access-date=2 April 2018}}</ref><ref>[http://www.cancer.org/Cancer/PenileCancer/DetailedGuide/penile-cancer-key-statistics The American Cancer Society: Penile Cancer: What are the key statistics about penile cancer] {{Webarchive|url=https://web.archive.org/web/20170114144337/http://www.cancer.org/cancer/penilecancer/detailedguide/penile-cancer-key-statistics |date=2017-01-14 }} [[American Cancer Society]], Last revised: January 18, 2012</ref>

In the [[developing world]], penile cancer is much more common. For instance, in [[Paraguay]], [[Uruguay]], [[Uganda]] and [[Brazil]] the incidence is 4.2, 4.4, 2.8 and 1.5–3.7 per 100,000, respectively.<ref name=Bleeker2009/><ref name="pow-sang-2010"/> In some South American countries, Africa, and Asia, this cancer type constitutes up to 10% of malignant diseases in men.<ref name=Bleeker2009/>

{{As of|1997}}, the [[lifetime risk]] was estimated as 1 in 1,437 in the United States and 1 in 1,694 in Denmark.<ref>{{cite journal | vauthors = Cold CJ, Storms MR, Van Howe RS | title = Carcinoma in situ of the penis in a 76-year-old circumcised man | journal = The Journal of Family Practice | volume = 44 | issue = 4 | pages = 407–10 | date = April 1997 | pmid = 9108839 }}</ref>

== See also ==
* [[Male breast cancer]]
* [[Testicular cancer]]
* [[Urethral cancer]]
* [[Vulvar cancer]]

== References ==
{{Reflist}}

== External links ==
{{Medical resources
| DiseasesDB=29392
| ICD10={{ICD10|C|60||c|60}}
| ICD9={{ICD9|187}}
| ICDO=
| OMIM=
| MedlinePlus=001276
| eMedicineSubj=
| eMedicineTopic=
| MeshID=D010412
}}
{{Human papillomavirus}}
{{Male genital neoplasia}}
{{STD/STI}}
{{Authority control}}

{{DEFAULTSORT:Penile cancer}}
[[Category:Male genital neoplasia]]
[[Category:Rare cancers]]
[[Category:Penis disorders|cancer]]
[[Category:Papillomavirus-associated diseases]]
[[Category:Human penis]]