Case–Control Study of Cutaneous Human Papillomaviruses in Squamous Cell Carcinoma of the Skin

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Cutaneous human papillomavirus (HPV) infection may be a risk factor for squamous cell carcinoma (SCC) of the skin. To investigate the association between cutaneous HPV and SCC, a case-control study was conducted, including 173 SCC cases from a university dermatology clinic and 300 controls that screened negative for skin cancer. Serum antibodies against cutaneous HPV types in genera alpha, beta, gamma, mu, and nu were measured. Tumor tissue from 159 SCC cases was tested for the presence of DNA for genus-beta HPV types. Using logistic regression ORs and 95% confidence intervals (CI) were estimated for the associations between SCC and cutaneous HPV infection, adjusting for age and sex. The Bonferroni method was used to account for multiple comparisons. SCC was positively associated with seropositivity to any genus-beta HPV type (OR, 1.93; 95% CI, 1.23-3.02), particularly with types in species-1 (OR, 1.86; 95% CI, 1.22-2.85). Type-specific associations with SCC were observed for HPV 8 (OR, 1.80; 95% CI, 1.14-2.84), 17 (OR, 1.59; 95% CI, 1.02-2.49) and HPV 10 from genus-alpha (OR, 2.24; 95% CI, 1.04-4.85). None of the type-specific associations remained statistically significant after correction for multiple comparisons. When DNA-positive SCC cases were compared with controls, strong serologic associations were observed for HPVs 5 (OR, 3.48; 95% CI, 1.27-9.59), 17 (OR, 3.36; 95% CI, 1.29-8.72), and 24 (OR, 3.79; 95% CI, 1.24-11.5). Genus-beta HPV infections were associated with SCC in our study population. Identifying the role of cutaneous HPV infection in SCC may lead to improved characterization of high-risk individuals and the development of novel prevention strategies.