Definition:

Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare in developed countries but more common in South America and East Africa. Squamous cell carcinoma (SCC) is the predominant tumor type in penile cancer, accounting for 95% of cases. Penile cancers are thought to arise from the progression of precursor lesions and can be subdivided into human papilloma virus (HPV) positive and HPV negative cases. Most common disrupted pathways, both in HPV-mediated and HPV-independent penile carcinogenesis, involve the p14ARF/MDM2/p53 and/or p16INK4a/cyclin D/Rb pathways. HPVs exert their oncogenic effect by expressing the oncoproteins E6 and E7, which bind to and inactivate the p53 and Rb tumor suppressor gene products, respectively. HPV independent mechanisms of pathway inactivation include silencing of the p16INK4a gene by promoter hypermethylation, somatic mutations of the p53 gene, over-expression of MDM2 and mutation of p14ARF. Several other molecular events include alterations in the activity and/or expression of ras and myc genes, cyclo-oxygenase-2 (COX) pathway and prostaglandin E2 synthase. These alterations have been described in both HPV-positive and -negative penile cancers.