The association between cutaneous squamous cell carcinoma and betapapillomavirus seropositivity: A cohort study

Background: It is currently unclear whether betapapillomaviruses (betaPV) play a role in the etiology of cutaneous squamous cell carcinoma (SCC). We investigated the association between betaPV antibodies and subsequent SCC in a population-based cohort study. Methods: Serum samples were collected in 1992 and/or 1996 from 1,311 participants of the communitybased Nambour Skin Cancer Study. These were tested for the presence of L1 antibodies against 21 different betaPV types. Histologically diagnosed SCCs were ascertained through three full-body skin examinations and linkage with the local pathology laboratories. We used age- and sex-adjusted Cox proportional hazards models to analyze the relationship between betaPV antibodies and SCC occurrence from 1992 until 2007. Results: SCC was newly diagnosed in 150 people. No associations were found between the presence of any betaPV L1 antibodies and the occurrence of SCC (HR = 1.0), and stratification by sex, skin color, and sunburn propensity did not affect these results. However, among people who were less than 50 years old in 1992, the presence of betaPV antibodies was associated with a two-fold increased risk of SCC. There was no significant association between antibodies to any individual betaPV type examined and the later development of SCC. Conclusions: Whether betaPV infection of the skin, and indirectly betaPV antibodies, are involved in the oncogenic process in the general population remains unclear, and this longitudinal study provides only limited support. Impact: This study emphasizes the need for additional longitudinal studies of HPV (human papilloma virus) and SCC, to avoid the possibility of reverse causality in case-control studies