Abstract
Abstract Objective: Several studies have suggested a role for cutaneous beta human papillomaviruses in the development of skin cancers in the general population, and specifically squamous cell carcinoma (SCC). Recent evidence also indicates other cutaneous HPVs, such as the gamma types, may be related to SCC occurrence. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous HPVs including alpha, beta and gamma types on risk of skin cancers, as well as a systematic review and meta-analysis to summarize emerging trends in the published literature. Participants: As part of an expanded analysis of our population-based case-control study from New Hampshire, USA, we examined seropositivity for alpha and gamma cutaneous human papillomaviruses, along with beta papillomaviruses, in relation to newly diagnosed, histologically confirmed SCC and basal cell carcinoma (BCC) of the skin. A total of 2366 histologically confirmed skin cancer cases and controls from the general population aged 25 to 74 years (663 SCC, 898 BCC and 805 controls) on whom plasma samples were available, were tested for L1 antibodies to cutaneous human papillomavirus types 2, 3, 7, 10, 27b, 57, 77 in genus alpha, 5, 8, 9, 15, 17, 20, 23, 24, 36, 38, 49, 75, 76, 92, 96 and 107 in genus beta and 4, 48, 50, 65, 88, 95, 101, 103 in genus gamma using multiplex serology. Results: Prevalence of each of the individual gamma human papillomaviruses assayed was higher among SCC cases than controls; however, the association was only weakly evident among those seronegative for beta HPVs. No association was observed between the cutaneous alpha HPVs and SCC, and none of the HPV types related to BCC. In contrast, a consistent increasing trend in the odds ratios for SCC with number of beta HPVs to which an individual tested positive remained even among those seronegative for the gamma types. Using a gene set enrichment analysis, we found genus beta-2 HPVs to be the most highly represented viral types related to SCC. In a meta-analysis of 6 case-control studies, although varying in magnitude, increased odds ratios of SCC and beta HPV seropositivity were observed across studies, with a summary odds ratio of 1.45 (CI= 1.27, 1.66). Conclusions: In aggregate, we found the association between cutaneous HPVs and skin cancers was specific to squamous cell carcinomas, genus beta HPVs, and possibly beta-2 HPV types in a general US population. Citation Format: Shohreh F. Farzan, Tim Waterboer, Jiang Gui, Heather Nelson, Zhongze Li, Kristina Michael, Ann Perry, Stephen Spencer, Eugene Demidenko, Adele Green, Michael Pawlita, Margaret Karagas. Cutaneous alpha, beta and gamma human papillomaviruses in relation to basal cell and squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2289. doi:10.1158/1538-7445.AM2013-2289
Published Version
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