Cutaneous Alpha, Beta And Gamma Human Papillomaviruses In Relation To Squamous Cell Carcinoma Of The Skin: A Population-Based Study

Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta-analysis of the available literature. In a population-based case-control study from New Hampshire, USA (n=1,408), histologically confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2-5, 7-10, 15, 17, 20, 23, 24, 27b, 36, 38, 48-50, 57, 65, 75-77, 88, 92, 95, 96, 101, 103 and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (p for trend=0.016) with an odds ratio of 1.95 (95% confidence interval (CI)=1.07-3.56) for four or more beta types positive. In a meta-analysis of six case-control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies (meta odds ratio=1.45, CI=1.27-1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population.What's new? Recent work has strengthened the possibility that cutaneous human papillomaviruses (HPVs) may contribute to the development of skin cancers, which worldwide are the most commonly diagnosed malignancies. Here, population-based investigation of alpha, beta, and gamma HPV types in squamous cell carcinoma (SCC) reveals an association between beta HPVs and SCC. Enrichment analyses showed that beta-2 subtypes were specifically associated with elevated risk. These results, together with meta-analysis of previous case-control studies, indicate an increased SCC risk in relation to beta HPV seropositivity across populations.