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Published on: March 11, 2014
p16 Overexpression and Human Papillomavirus Positivity in More Than 1000 Penile Cancers
Marianne Gardar Stærk1, Birgitte Grønkær Toft2,3, Christina Stilling4
1Unit of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark.
Abstract:
Penile cancer is a severe disease, and a large proportion is related to high-risk (hr) human papillomavirus (HPV). P16 is used as an immunohistochemical marker of HPV in clinical diagnostics. Population-based data on the prevalence of p16 in penile cancer is scarce. We investigated the prevalence of p16 positivity, and p16 in combination with hrHPV DNA, in a large population of Danish penile squamous cell carcinomas (SCC). Cases diagnosed during 1995-2020 were identified in the Danish Pathology Databank, and tumor samples were tested for HPV DNA (INNO-LiPA assay). After immunohistochemical p16-staining, the slides were evaluated by expert pathologists. p16 prevalence was calculated and the combined p16 and hrHPV DNA status (double positivity, double negativity, p16 positive only, and hrHPV DNA positive only) was assessed according to calendar time and histology. Time trends were assessed by calculating estimated annual percentage changes. Of 1028 penile SCCs, 42.8% were p16 positive and 37.8% were double positive. We found no significant changes in prevalences over the study period. The highest prevalence of double positivity was observed in SCCs with HPV-associated histological features, especially basaloid (63.6%-87.5%). hrHPV genotypes covered by the 9-valent HPV-vaccine (HPV16/18/31/33/45/52/58) were detected in 97.9% of double positive SCCs. Based on this large population-based study, we demonstrate a good correlation between p16 and hrHPV DNA and no substantial changes in the prevalences over time (1995-2020). Nearly all double positive SCCs harbored a hrHPV genotype that could potentially be prevented by vaccination, pointing to a likely future decrease in penile cancer in Denmark.
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