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Introduction

Penile cancer is an uncommon malignancy that develops primarily in men age >60.  Most cases (90%-95%) are due to squamous cell carcinoma.  Major risk factors for squamous cell carcinoma are persistent human papillomavirus (HPV) infection and chronic inflammation and irritation of the glans.  Patients typically have a painless nodule or ulcer on the distal penis (glans, foreskin), and the diagnosis is confirmed with biopsy.

Pathogenesis and risk factors

The pathogenesis of penile cancer likely involves a complex interplay of infectious and environmental factors, including:

  • Persistent HPV infection:  Infection with high-risk (ie, oncogenic) HPV genotypes, particularly 16 and 18, is strongly associated with the development of penile cancer.  The virus's oncoproteins (E6 and E7) disrupt tumor suppressor genes (p53, Rb), leading to uncontrolled cell proliferation and the inability to repair damaged DNA.

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