Serological association of beta and gamma human papillomaviruses with squamous cell carcinoma of the skin

Background: Cutaneous human papillomaviruses (HPVs) may play a role in the development of squamous cell carcinomas (SCC) of the skin. Objectives: Available serological studies on HPV and skin SCC have analysed only few HPV types from the phylogenetic genus beta. The potential association of cutaneous HPV types from the genera alpha, gamma, mu and nu with skin SCC has not been thoroughly analysed so far. Methods: Using multiplex serology, a method that allows analysing sera for antibodies to up to 100 different antigens simultaneously, we re-analysed an SCC case-control study in immunocompetent individuals (43 cases, 77 controls) for antibodies to L1 capsid proteins of 29 cutaneous and two mucosal HPV types from five different genera. Results: Significantly increased SCC risks were observed for the beta HPV types 15, 17 and 38, as well as for the gamma HPV type 50, with type-specific odds ratios (ORs) ranging from 2.6 to 3.4. Significant associations were also found in cases of seropositivity for any type of the beta 2 species (OR 3.3, 95% confidence interval [CI] 1.2-8.7) and for any type of the gamma genus (OR 3.1, 95% CI 1.1-8.6). With regression models that included all HPV types and forward stepwise selection, two gamma HPV types (HPV 95, OR 25, 95% CI 1.2-509; HPV 50, OR 3.6, 95% CI 1.4-9.4) were each significantly associated with skin SCC. Conclusions: Our study confirms a possible role of cutaneous HPV in the development of skin SCC. Future studies should include skin HPV types from more than only the beta genus, especially gamma types.