Squamous cell carcinoma (SCC) is a keratinocyte-derived carcinoma that occurs most frequently on sun-exposed areas such as the face and hands. However, SCC may also occur on the male genitalia, where it typically presents in later decades of life. Penile cancer, of which SCC comprises a majority, is a rare entity in the United States. Penile SCC is far more common in developing countries, where it represents up to 10% of cancers in men. The incidence of anal SCC has increased for men in recent decades, too, likely due to growing case numbers in high-risk patients (eg, men who have sex with men, immunosuppressed individuals, HIV-infected individuals).

The clinical presentation is variable. SCC often presents as a hyperkeratotic papule or nodule that may ulcerate, but it may also be smooth, plaque-like, exophytic, or papillomatous. Lesions are often red to skin colored. Secondary changes such as scale, crust, erosion, and ulceration can be present. The progression of lesions over time varies. Some enlarge slowly, while others progress rapidly to grow, infiltrate deeper tissue, and metastasize. Pain and tenderness can be present. Anal carcinomas may also present with rectal bleeding and a sensation of an object in the rectum.

The pathogenesis of SCC is multifactorial. It may evolve from intraepithelial neoplasia (including penile intraepithelial neoplasia or anal intraepithelial neoplasia) or arise de novo. TP53 and NOTCH1 gene mutations have been implicated. Penile SCC occurs almost exclusively in uncircumcised men, and neonatal circumcision is believed to be protective. Penile carcinoma is most often found on the glans (48%), followed by the foreskin (21%), corona (6%), and shaft (< 2%). It is believed that smegma, more commonly present in uncircumcised men, induces chronic inflammation and predisposes to SCC. Any repetitive trauma or insult increases risk of SCC. Additional risk factors for anogenital SCC include smoking, sexually transmitted infections, HIV infection, human papillomavirus (HPV) infection, poor genital hygiene, anogenital injury, chronic balanitis, lichen sclerosus, and erosive lichen planus. Approximately 50% of genital SCC cases are associated with HPV infection.

Men who engage in receptive anal intercourse and men with immunocompromised states such as HIV should undergo regular anal cytology testing.

Related topics: bowenoid papulosis, erythroplasia of Queyrat, squamous cell carcinoma in situ