Cutaneous human papillomaviruses and squamous cell carcinoma of the skin: Nested case-control study

Abstract

Background:Cutaneous human papillomavirus (HPV) types have been associated with non-melanoma skin cancer (NMSC), including a previous nested case-control study using HPV serology with bacterially derived fusion proteins with the major HPV capsid protein L1 (GST-L1). However, HPV serology using conformationally intact pseudovirions has been shown to correlate better with natural infection. Prospective studies using a more valid marker of infection are therefore warranted. Methods: Cancer registry follow-up of large Nordic biobanks identified prediagnostic serum samples from 633 subjects who later developed SCC, 1,990 subjects who developed basal cell carcinoma (BCC). The samples from cases and matched controls were tested for IgG to pseudovirions to 16 different HPV types (3, 5, 6, 11, 15, 16, 18, 31, 32, 33, 38, 45, 52, 58, 68, and 76) and two polyomaviruses (MCPyV and JCPyV). Results: Baseline seropositivitywasnot associated withSCCrisk, and there were only weak associations with BCC risk [HPV-5 (OR, 1.1; 95%confidence interval [CI], 1.0-1.3), HPV-15 (OR, 1.2; 95% CI, 1.0-1.4),HPV-38 (OR, 1.2; 95%CI, 1.0-1.3), andMCPyV (OR, 1.1; 95%CI, 1.0-1.3)]. Acquisition of HPV-5 seropositivity during follow-up was associated with SCCrisk(OR, 3.2; 95%CI, 1.3-7.6). Persistent seropositivity for HPV-15 was weakly associated with BCC (OR, 1.4; 95% CI, 1.0-1.9) and HPV-6 antibody persistence was weakly associated with SCC (OR, 2.2; 95% CI, 1.0-4.8). Conclusion: Considering the large number of viruses tested, the weak associations found do not support any strong links between studied HPV and NMSC, with the possible exception of HPV-5 seroconversion and SCC. Impact: Known alpha and beta papillomaviruses do not appear to be risk factors for NMSC.