Human papillomavirus is the cause of malignant melanoma

Abstract

Background:The potential role of human papillomavirus (HPV) in the pathogenesis of malignant melanoma (MM) has been the subject of considerable debate, yet remains poorly investigated compared to other malignancies. The aim of this study is to re-evaluate the relationship between HPV infection and MM through a comprehensive re-analysis of published data.Material and methods:We systematically re-analyzed data from several independent case-control and cross-sectional studies that investigated the prevalence of HPV DNA in melanoma tissue specimens. A total of five studies, encompassing cutaneous, mucosal, and UV-shielded anatomical sites, were included in our analysis. Novel statistical approaches—including formal hypothesis testing for necessary and sufficient conditions—were applied to the aggregated data, with statistical significance set at \( \alpha = 0.05 \). Results:The re-analysis revealed statistically significant associations between HPV presence and MM across all included studies. Specifically, four independent investigations demonstrated that HPV constitutes a sufficient condition for MM (right-tailed p-values ranging from 0.0137 to 0.0294). Furthermore, a matched and controlled study by Ruer et al. provided evidence that HPV is also a necessary condition for MM (right-tailed p = 0.0397). The convergence of evidence for both necessary and sufficient conditions fulfills the classical criteria for causal inference.Conclusion:The accumulated evidence strongly supports the hypothesis that HPV infection is causally implicated in the pathogenesis of malignant melanoma. Given that more than 200 HPV types have been characterized, future research should focus on the precise identification of the specific genotype—or genotypes—responsible for this association, which may have profound implications for prevention, diagnosis, and the development of targeted therapeutic strategies.