Etiology of Penile Cancer

The etiology of penile cancer is still not fully understood. Currently two distinct pathways have been identified; one related to high risk human papilloma virus (hrHPV), the other to irritation and inflammation of the prepuce, for example secondary to lichen sclerosus (LS). Of the HPV subtypes, mainly high risk HPV (hrHPV) 16 and 18 have been detected in penile carcinomas and penile intraepithelial neoplasia (PeIN). Generally it is mainly undifferentiated PeIN and basaloid, warty (condylomatous) and mixed warty-basaloid histological subtypes of cancer correlate with HPV-positivity. Although observational studies report the frequent presence of LS in peritumoral tissue, demonstrating a strong relationship has proved difficult due to the lack of incidence of histologically proven LS in the healthy population. The eventual development of phimosis partially accounts for the relationship with penile cancer as well as the hypothesized immunologic deregulation of chronic inflammatory sites. Other risk factors contribute to either or both of these two pathways. For example, the protective effect of circumcision is explained by a reduction in the surface area susceptible to HPV infection, prevention of phimosis and the development of a keratinized surface replacing the normal mucosa (eukeratinisation). It also effectuates better genital hygiene, less smegma retention, and hence, less chronic irritation and/or inflammation.