Pathophysiology
Clinical meaning
Penile cancer is predominantly squamous cell carcinoma (>95%) arising from the epithelium of the glans, prepuce, or penile shaft. HPV types 16 and 18 are implicated in approximately 50% of cases, with viral E6/E7 oncoproteins inactivating p53 and Rb tumor suppressors respectively. Phimosis creates a chronic inflammatory microenvironment beneath the foreskin where smegma accumulation and poor hygiene promote carcinogenesis. Staging follows the TNM system: T1 (subepithelial invasion), T2 (corpus spongiosum/cavernosum), T3 (urethral invasion), T4 (adjacent structures). Inguinal lymph node involvement is the most important prognostic factor, with 5-year survival dropping from 85% (node-negative) to 29% (bilateral nodal disease).