To Örebro University

BACKGROUND: Penile squamous cell carcinoma is an uncommon neoplasm that arises via two carcinogenic pathways, one linked to HPV infection and the other to chronic inflammation and p53 alterations.

OBJECTIVE/METHODS: We assessed the distribution of HPV genotypes in penile tumors and subsequent inguinal metastases in a cohort of 343 patients, analyzing their concordance with p16 stain and histological subtype, as well as the predictive significance of HPV tumor status and the immunohistochemical expression of p16 and p53 in inguinal lymph node metastasis (ILNM).

RESULTS: The overall prevalence of HPV in primary penile tumors was 42.9%, with high-risk HPV genotypes detected in 95.2% of HPV-positive cases. HPV16 was the most prevalent genotype identified in both primary tumors and metastases. However, other genotypes, including the low-risk HPV82, were also found in metastatic disease. We observed good concordance between HPV tumor status and histological subtype and very good concordance between HPV tumor status and p16 staining, with Cohen's kappa (κ) values of 0.80 (p-value < 0.001) and 0.83 (p < 0.001), respectively.

CONCLUSIONS: In most HPV-positive metastatic cases, the same HPV genotypes were detected in both the metastasis and the penile tumor. Both p16 staining and histological subtype can serve as surrogates for molecular HPV testing in lower resourced settings. In this dataset, no significant association was found between HPV status, p16 expression, or p53 expression and the presence of ILNM, suggesting their limited utility as predictive markers for ILNM in penile cancer.