Penile Cancer—A Preventable Cause of Death in Elderly Men

Penile cancer (PeCa) is a rare but preventable malignancy that predominantly affects elderly men. Incidence is rising in high-income countries, and mortality is particularly high in those aged 75 years and older. The major, synergistic risk factors are male genital lichen sclerosus (MGLSc) and persistent infection with high-risk human papillomavirus (HPV). This narrative review examines the peer-reviewed evidence on PeCa’s epidemiology, aetiopathogenesis, diagnosis, management, and prevention, with a focus on MGLSc and high-risk HPV, and their implications for disease in older men. Priority was given to high-impact studies, and recent advances relevant to clinical practice. PeCa develops via two principal pathways: an HPV-dependent route, typically leading to undifferentiated penile intraepithelial neoplasia (uPeIN) and related squamous cell carcinoma (SCC) subtypes; and an HPV-independent route, driven by chronic inflammation and scarring from MGLSc, leading to differentiated PeIN (dPeIN) and SCC. Additional modifiable risk factors include phimosis, smoking, and poor genital hygiene. Diagnosis relies on careful clinical examination, dermatoscopy, and histopathology. Management ranges from topical therapy and circumcision to organ-sparing surgery, lymphadenectomy, systemic chemotherapy, and emerging immunotherapies. Prognosis is closely related to lymph node involvement. Preventive strategies, particularly early diagnosis and treatment of MGLSc and PeIN, HPV vaccination, circumcision, and smoking cessation, could substantially reduce disease burden. PeCa remains an under-recognised malignancy in older men despite being largely preventable. Improved public awareness, timely diagnosis of precursor conditions, and broader uptake of preventive interventions are essential to reverse current trends in incidence and mortality.