Prevention and Epidemiology Multicenter Study of the Association between Betapapillomavirus Infection and Cutaneous Squamous Cell Carcinoma

Human papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case– control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case–control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR1⁄4 2.8; 95% CI 1.3–5.8) and Italy (OR1⁄4 1.7; 95% CI 0.79–3.6), but not in Australia (OR1⁄4 0.91; 95% CI 0.53–1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR 1⁄4 2.2; 95% CI 1.4–3.3), the Netherlands (OR 1⁄4 2.0; 95% CI 1.2–3.4) and fair-skinned Italians (OR 1⁄4 1.6, 95% CI 0.94– 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma. Cancer Res; 70(23); 1–10. 2010 AACR.