Cutaneous Human Papillomaviruses and the Risk of Keratinocyte Carcinomas

Cutaneous human papillomavirus (cuHPV) infections may be novel targets for skin cancer prevention and treatment, but critical information regarding the development of virus-positive skin cancers following cuHPV infection has been lacking. In this study, baseline cuHPV infection was measured by serology and viral DNA detection in eyebrow hairs (EBH) and forearm skin swabs (SSW) among 1,008 individuals undergoing routine skin cancer screening exams and followed for incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC). Baseline beta-HPV detection, particularly in SSW, significantly predicted cuSCC (HR = 4.32; 95% confidence interval, 1.00-18.66), whereas serologic evidence of past beta-HPV infection was not associated with cuSCC. Less than 5% of baseline beta-HPV types detected in SSW were present in subsequent cuSCC tumors, and cuHPV detected in SSW with higher mean fluorescence intensity values were more likely to be present in cuSCC compared with those with lower levels (P < 0.001). beta-HPV-positive cuSCC occurred more often in areas of highly sun-damaged skin than did beta-HPV-negative cuSCC. Overall, no clear patterns were observed between baseline beta-HPV detection and subsequent development of BCC, or between baseline gamma-HPV detection and either cuSCC or BCC. Collectively, these results demonstrate that beta-HPV detection in SSW is a significant predictor of cuSCC risk, although evidence suggests only a small subset of cuSCC is etiologically linked to beta-HPV infection. Significance: beta-HPV positivity may he a useful biomarker for identifying individuals who could benefit from increased screening or novel cutaneous squamous cell carcinoma prevention strategies.