Abstract

Introduction: High-risk human papilloma virus (HPV) has been associated with 30-50% of penile squamous cell carcinomas (SCC).  However, there is a paucity of literature regarding underlying HPV genotypes. We aimed to assess the frequency of specific subtypes and evaluate correlations with tumor morphology.

Materials and methods: From a single-institution North American cohort of predominantly white patients who underwent penectomy for SCC between 2000 and 2022 (n=121), cases with discrepant results of morphology, p16 immunohistochemistry, and HPV in situ hybridization (ISH) were selected for metagenomic sequencing using a panviral capture panel. Additional low-risk HPV–positive and high-risk HPV–positive cases (diagnosed using ISH) were analyzed as controls.

Results: 26 cases were included. At least one HPV genotype was detected in 24 cases (92.3%).  The most common HPV genotype was HPV 16, identified in 17 of 26 cases (65.4%), followed by HPV 33 and 35 (2 cases each, 7.7%).  Two cases with HPV 16 had a co-infection with another HPV genotype (HPV 42 and 76, respectively). Both cases with a medullary morphology were positive for HPV 16, whereas among the 5 cases with a warty morphologic component only 2 were positive for HPV 16 (40%). HPV 11 and 33 were exclusively seen in cases with a warty component.

Discussion: The most frequent HPV subtypes in our study (16, 33, and 35) are concordant with the literature. More studies are needed to gain further insight into the global HPV landscape of penile SCC, and also to guide development of vaccination programs.