Disease | Penile Cancer |
Epidemiology | Penile carcinoma is an uncommon malignant disease, with an incidence of 0.1-7.9 per 100,000 males. In Europe and the USA, the incidence is 0.1-0.9 per 100,000 rising to 19 per 100 000 in some areas of Asia, Africa and South America. Penile cancer tends to be a disease of uncircumcised men, with an increase in incidence of men in their sixties; incidence peaks in men aged 80 years. The frequency of penile carcinoma varies according to hygienic practices, cultural and religious beliefs. Penile cancer has been associated with the presence of herpes virus infection and human papilloma viruses (HPV). HPV is thought to be strongly associated with the generation of insitu and invasive cancers of epithelial tumours (Walboomers et al., 1999). The prevalence of HPV DNA in penile carcinoma is 40-45%. HPV infection also correlates with penile cancer basaloid subtypes, however verrucous tumours tend to be negative for HPV. HPV 16 and 18 are found in 60-75% of insitu and invasive carcinomas whereas HPV 6 and 11 are found in lower risk condylomas. |
Clinics | Non healing ulcer, painless penile mass, phimosis. |
Pathology | Grading and staging: graded by the degree of cellular atypia (G1->G3), Staged by TNM classification (see above). |
Treatment | Non surgical treatments for premalignant lesions include laser therapy, Moh's micrographic surgery, topical 5-FU. Penis-preserving surgery is recommended for premalignant lesions such as carcinoma in situ and also Ta-T1 lesions. Penis preserving surgery is suitable for T2 lesions confined to the glans. More extensive lesions involving the corpus cavernosum or urethra require a partial or total amputation. Local disease recurrence may require partial or total amputation. In those with a high risk of metastases and non palpable nodes, modified or radical lymphadenectomy is recommended, for those with an intermediate or low risk, the options include surveillance or dynamic sentinel node biopsy or modified inguinal lymphadenectomy. If patients have palpable pathological nodes then radical inguinal lymphadenectomy is the standard recommendation. Pelvic lymphadenectomy is performed in those patients with greater than two positive inguinal nodes. |
Evolution | Penile carcinoma is one of the few solid tumours in which lymphadenectomy can provide a high cure rate even when lymph nodes are involved. Most relapses occur during the first 2 years; late recurrences, though uncommon, may occur. |
Prognosis | The mean time until death from cancer is 66.6 months for those with CIS, 50.1 months for those with localized disease, 32.4 months for those with regional disease and 7.4 months for those with distant metastases. The most powerful prognostic factor in patients with SCC of the penis is involvement of the lymph nodes in the groin. 5-year cancer-specific survival probabilities were 93% for N0 patients, 80% for N1, and 50% for N2 patients. Mutant p53 protein has been detected in 67.6% of patients with lymph node metastases, while only 39.6% of patients with metastases had the wild-type protein. Low levels of E-cadherin were present in 59.5% of patients with groin metastases, while high levels of the protein were detected in 61.7% of the patients without nodal involvement (P = 0.032). More interestingly, MMP-9 immunoreactivity was shown to be an independent predictor of disease recurrence as was the presence of urethral infiltration and lymph node metastasis, which had an important prognostic role. |
E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients. |
Campos RS, Lopes A, Guimaraes GC, Carvalho AL, Soares FA. |
Urology. 2006 Apr;67(4):797-802. Epub 2006 Mar 29. |
PMID 16566971 |
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Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. |
Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, de Sanjose S, Eluf-Neto J, Ngelangel CA, Chichareon S, Smith JS, Herrero R, Moreno V, Franceschi S; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. |
N Engl J Med. 2002 Apr 11;346(15):1105-12. |
PMID 11948269 |
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Evidence for at least three alternative mechanisms targeting the p16INK4A/cyclin D/Rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus. |
Ferreux E, Lont AP, Horenblas S, Gallee MP, Raaphorst FM, von Knebel Doeberitz M, Meijer CJ, Snijders PJ. |
J Pathol. 2003 Sep;201(1):109-18. |
PMID 12950023 |
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Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma. |
Gregoire L, Cubilla AL, Reuter VE, Haas GP, Lancaster WD. |
J Natl Cancer Inst. 1995 Nov 15;87(22):1705-9. |
PMID 7473819 |
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Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts. |
Gross G, Pfister H. |
Med Microbiol Immunol. 2004 Feb;193(1):35-44. Epub 2003 Jun 28. |
PMID 12838415 |
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Molecular and genetic pathways in penile cancer. |
Kayes O, Ahmed HU, Arya M, Minhas S. |
Lancet Oncol. 2007 May;8(5):420-9. |
PMID 17466899 |
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Squamous cell carcinoma antigen: a role in the early identification of nodal metastases in men with squamous cell carcinoma of the penis. |
Laniado ME, Lowdell C, Mitchell H, Christmas TJ. |
BJU Int. 2003 Aug;92(3):248-50. |
PMID 12887477 |
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A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c-rasHa activation in malignant progression. |
Leis PF, Stevens KR, Baer SC, Kadmon D, Goldberg LH, Wang XJ. |
Cancer. 1998 Jul 1;83(1):122-9. |
PMID 9655301 |
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Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis. |
Masih AS, Stoler MH, Farrow GM, Wooldridge TN, Johansson SL. |
Mod Pathol. 1992 Jan;5(1):48-55. |
PMID 1311839 |
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Cytogenetic analysis of an invasive, poorly differentiated squamous cell carcinoma of the penis. |
Ornellas AA, Ornellas MH, Simoes F, Soares R, Campos MM, Harab RC, Silva ML. |
Cancer Genet Cytogenet. 1998 Feb;101(1):78-9. |
PMID 9460507 |
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Immunohistochemical expression of Mdm2 and p53 in penile verrucous carcinoma. |
Ouban A, Dellis J, Salup R, Morgan M. |
Ann Clin Lab Sci. 2003 Winter;33(1):101-6. |
PMID 12661905 |
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Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. |
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. |
J Pathol. 1999 Sep;189(1):12-9. |
PMID 10451482 |
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