The Prognostic Role of Human Papillomavirus and p16 Status in Penile Squamous Cell Carcinoma—A Systematic Review

SIMPLE SUMMARY: Penile squamous cell carcinoma (PSCC) is a rare and aggressive cancer. About half of all PSCC cases are thought to be related to human papillomavirus (HPV) or have increased expression of p16 by immunohistochemistry (IHC), a surrogate marker for HPV infection. HPV/p16 positivity is generally a marker of better outcomes in more common squamous cell carcinomas, but the studies evaluating its prognostic value in PSCC are conflicting. In this systematic review, we aim to summarize the existing literature on the impact of these biomarkers on PSCC prognosis and determine their potential value in identifying patients with more favorable biology. ABSTRACT: PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide.