Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case-control study.

The first evidence of an association between HPV and non-melanoma skin cancer comes from patients with epidermodysplasia verruciformis (EV). EV is a rare heritable disease characterized by cutaneous warts that display not only a high rate of progression to squamous cell carcinoma on sun-exposed sites, but also a strong predisposition to infection by beta-HPVs, for which HPV 5 and 8 predominate. Two EV genes (EVER1 and EVER2) have been identified, and we tested the hypothesis that variation in the EVER2 gene (rs7208422) is related to seropositivity to HPV (of the genus beta types) and risk of squamous cell carcinoma in a population-based case-control study of SCC (n = 239 cases and 432 controls). Among controls, variant genotype was associated with beta-HPV seropositvity (OR = 2.3, 95%CI = 1.2-4.3), specifically HPV5 or 8 seropositivity (OR = 2.4, 95%CI = 1.1-5.1) and seropositivity for multiple beta-HPV types (OR = 2.7, 95%CI = 1.1-6.6). Furthermore, variant genotype was also related to SCC risk [adjusted OR for homozygous variant versus homozygous wild type for the EVER2 polymorphism 1.7, 95% CI 1.1-2.7]. These data provide evidence for a role of genetic variation in the EVER2 gene in beta-HPV infection and risk of SCC, shedding light on the link between HPVs and skin cancers. (c) 2008 Wiley-Liss, Inc.