Abstract 950: Merkel cell polyomavirus infection in cutaneous squamous cell carcinomas
Authors: Rollison Dana E. , Giuliano Anna R. , Messina Jane L. , Fenske Neil A. , Cherpelis Basil S. , Sondak Vernon K. , Roetzheim Richard G. , Iannacone Michelle R. , Fulp William , Michael Kristina M. , Waterboer Tim , Gheit Tarik , Tommasino Massimo , Pawlita Michael 
Published: June 2012

Abstract
Objective: Merkel cell polyomavirus (MCV) DNA has been reported previously in 0-25% of squamous cell carcinomas (SCC) occurring in immunocompetent individuals. No studies have investigated MCV seroreactivity in individuals with SCC. We conducted a clinic-based case-control study to investigate the association between MCV seroreactivity and SCC, overall and stratified by MCV DNA status of the SCC tumor tissue. Methods: Patients with histologically-confirmed cutaneous SCC (n=173) were recruited from a university dermatology clinic. Controls were patients undergoing skin cancer screening exams who screened negative for and had no history of skin or other cancers (n=300). Levels of antibodies against capsid antigens for MCV and other polyomavirus controls (JC virus (JCV) and KI virus (KIV)) were determined by fluorescent bead-based multiplex serology. Fresh-frozen tumor tissues were obtained from 145 SCC cases, and DNA from six polyomaviruses (MCV, JCV, KIV, WU virus (WUV), BK virus (BKV) and simian virus 40 (SV40)) was measured using multiplexed PCR. Polyomavirus seropositivity, based on binary cutpoints, and quartiles of seroreactivity, based on the control distribution, were compared between SCC cases and controls, overall and stratified by the presence or absence of MCV DNA in SCC tumor tissues. Associations were estimated by calculating odds ratios (OR) and 95% confidence intervals (CI) using logistic regression to adjust for age, sex, and skin reaction to the sun. Results: MCV seropositivity was associated with a statistically significant increased risk of SCC (OR=1.80, 95% CI=1.03-3.12), whereas no association was observed for JCV (OR=1.17, 95% CI=0.72-1.92) or KIV (OR=0.88, 95% CI=0.37-2.09) seropositivity. MCV DNA was detected in 55 (38%) of SCC tumor tissues, whereas all tissues were negative for DNA from the other five polyomaviruses. Using controls as the reference group, MCV DNA-positive SCC cases were three times as likely to be MCV seropositive (OR=3.15, 95% CI=1.11-8.92) and almost six times as likely to have MCV antibody levels in the fourth versus first quartile (OR=5.94, 95% CI=1.79-19.74, ptrend=0.001). No associations were observed between MCV seropositivity and MCV DNA-negative SCC (OR=1.40, 95% CI=0.78-2.77) or between JCV or KIV seropositivity and MCV DNA-negative or DNA-positive SCC. Conclusion: SCC patients were significantly more likely than controls to exhibit MCV seroreactivity, particularly if they had MCV DNA in their SCC tumor tissue. This association was specific to MCV, with no associations observed for the other polyomaviruses studied. These results suggest that past exposure to MCV may be a risk factor for SCC in immunocompetent individuals.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 950. doi:10.1158/1538-7445.AM2011-950