(UroToday.com) Penile cancer is a rare genitourinary malignancy that is often associated with HPV infection. HPV infection results in the expression of the viral protein E7, which is capable of inhibiting the cell cycle proteins Rb and p21, leading to an accumulation of the p16 protein. Expression of p16 in penile cancer is associated with a better overall prognosis. The rates of association with HPV vary by histologic subtype within penile cancer, with 100% of the “warty” subtype having detectable HPV, 80% of basaloid tumors, 35% of keratinizing squamous cell carcinomas, and 33% of verrucous carcinomas. The impact of HPV infection status on the outcomes of peri-operative treatments for penile squamous cell cancer involving the lymph nodes is unclear.