Prevalence and time trends of <scp>human papillomavirus</scp> in penile cancer over 26 years—A comprehensive study of 1040 penile cancer cases from Denmark

Penile cancer is rare. It has been suggested that approximately half are human papillomavirus (HPV) associated, but large-scale studies on HPV prevalence and time trends are limited. We aimed to examine the high-risk HPV (hrHPV) prevalence in a large single-country study of penile squamous cell carcinomas (SCC) during a 26-year period. From the nationwide Danish Pathology Register, we identified all penile SCCs diagnosed during the period 1995-2020 at hospitals covering most regions in Denmark. Histologic slides were evaluated by expert pathologists, and archived tumor tissue was tested for the presence of HPV DNA using the INNO-LiPA assay. We assessed the overall and type-specific HPV prevalence according to calendar period, age, and histology, and estimated the annual percentage change (EAPC) of hrHPV positivity over the entire study period. We included 1040 penile SCCs. The overall HPV prevalence was 54.5% and the hrHPV prevalence was 50.4%. We observed no change in the prevalence of hrHPV over time (EAPC = -0.03% [95% confidence interval: -0.91; 0.85]). HPV16 was the most prevalent genotype (41.1%), and 50.0% of the penile SCCs had an HPV type that would be covered by the nine-valent HPV vaccine (HPV6/11/16/18/31/33/45/52/58). Penile SCCs with HPV-associated histological features had the highest hrHPV prevalence, particularly tumors exhibiting basaloid features (81.8%-87.7%). In this large population-based study, covering most regions in Denmark, we found no substantial change in hrHPV prevalence during 1995-2020. Our findings suggest that prophylactic vaccination with the nine-valent HPV vaccine could prevent a considerable part of penile SCCs in Denmark.