The most important risk factor for penile cancer is non-circumcision of the penis. Penile cancer is rarely seen in populations who routinely practice circumcision during the neonatal or childhood period.7-10 The protective effect of circumcision has also been found in developing countries with a high incidence of penile cancer, such as Nigeria and India. In these countries the disease is rare in subpopulations that ritually practice circumcision after birth.10

The positive effect of circumcision is mainly explained by preventing conditions such as poor penile hygiene, smegma retention, and phimosis, which have been reported as risk factors for penile cancer.71011 Phimosis (or narrowness of the opening of the foreskin) leads invariably to retention of the normally desquamated epidermal cells and urinary products (smegma) resulting in conditions of chronic irritation with or without bacterial inflammation of the prepuce and the glans. The frequency of phimosis in men with penile carcinoma is between 44% and 85% and in case-control studies a 65-fold increased relative risk for penile cancer was recorded among males with phimosis.1011 When performing statistical analyses after exclusion of phimosis as a risk factor, the presence of a foreskin did not increase the risk of penile cancer.11 Although carcinogenesis has been attributed to chronic inflammation due to the irritating effects of smegma, to date a carcinogenic agent has not been identified and isolated within smegma.1213 Inflammation appears to be a critical component for the development of penile cancer as these cancers commonly arise at sites of infection, chronic irritation, or injury. The inner prepuce of uncircumcised men consists of a mucosal surface which may be more vulnerable to infection by the human papillomavirus (HPV). The glans and prepuce of circumcised men is covered by keratinized stratified squamous epithelium which provides more resistance to viral entry.

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