Penile Intraepithelial Neoplasia and Squamous Cell Carcinoma: A Contemporary Review of Clinicopathologic Features, Classification, and Prognostication

Penile intraepithelial neoplasia is an uncommon precancerous genital lesion that may progress to invasive penile squamous cell carcinoma in the absence of proper therapeutic management. The recent trend of increasing incidence because of a heightened burden of genital human papillomavirus (HPV) infection emphasizes a need for effective diagnostic and management strategies. This article provides a clinicopathologic overview focusing on updates in tumor classification and prognostication not previously summarized. We examine changes in classification and nomenclature based on the 2022 World Health Organization guidelines and explore differences in pathogenesis and prognosis between HPV-associated and HPV-independent tumors. This article emphasizes the need for more robust molecular genetic studies to further elucidate prognostic biomarkers and explores the increasingly distinct role of immunohistochemistry in stratifying subtypes. Also, we present an illustrative case to highlight the significance of accurate diagnosis and prompt management.