Case–control Study of Merkel Cell Polyomavirus Infection and Cutaneous Squamous Cell Carcinoma

Abstract

Merkel cell polyomavirus (MCV) DNA has been reported in 0% to 25% of squamous cell carcinomas (SCC) occurring in immunocompetent individuals. We conducted the first serologic case-control study of MCV and SCC. Patients with histologically confirmed cutaneous SCC (n = 173) were recruited from a university dermatology clinic. Controls were individuals who screened negative for and had no history of skin or other cancers (n = 300). Levels of antibodies against capsid antigens for MCV and another polyomavirus, JC virus (JCV), were determined by fluorescent bead-based multiplex serology. Fresh-frozen tumor tissues were obtained from 145 SCC cases and tested for MCV DNA by multiplexed PCR. Associations between MCV seroreactivity and SCC were estimated by ORs and 95% CIs calculated using logistic regression with adjustment for age and sex. MCV DNA was detected in SCC tumor tissues from 55 (38%) of 145 cases. A statistically significant association was observed between MCV seropositivity and MCV DNA-positive SCC (OR = 2.49, 95% CI = 1.03-6.04), with an almost four-fold association observed when comparing those with MCV antibodies in the fourth versus first quartiles (OR = 3.93, 95% CI = 1.43-10.76, P(trend) = 0.01). No significant associations were observed between MCV seropositivity and MCV DNA-negative SCC (OR = 1.38, 95% CI = 0.76-2.48) or between JCV seropositivity and MCV DNA-positive or DNA-negative SCC. Past exposure to MCV may be a risk factor for SCC. Understanding the role of viral infections in the development of nonmelanoma skin cancer could lead to novel prevention strategies.