Abstract
Merkel cell polyomavirus (PyV) is causally related to Merkel cell carcinoma, a rare skin malignancy. Little is known about the serostability of other PyVs over time or associations with cutaneous squamous cell carcinoma (SCC). As part of a U.S. nested case-control study, antibody response against the PyV VP1 capsid proteins of BK and John Cunningham virus (JC) was measured using multiplex serology on 113 SCC cases and 229 gender, age, and study center-matched controls who had a prior keratinocyte cancer. Repeated serum samples from controls and both pre and postdiagnosis samples from a subset of SCC cases were also tested. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using conditional logistic regression. Among controls, BK and JC seroreactivity was stable over time, with intraclass correlation coefficients of 0.86 for BK and 0.94 for JC. Among cases, there was little evidence of seroconversion following SCC diagnosis. JC seropositivity prior to diagnosis was associated with an elevated risk of SCC (OR = 2.54; 95% CI, 1.23-5.25), and SCC risk increased with increasing quartiles of JC (Ptrend = 0.004) and BK (Ptrend = 0.02) seroreactivity. PyV antibody levels were stable over time and following an SCC diagnosis. A history of PyV infection may be involved in the occurrence of SCC in a population at high risk for this malignancy. A single measure of PyV seroreactivity appears a reliable indicator of long-term antibody status, and PyV exposure may be a risk factor for subsequent SCC. Cancer Epidemiol Biomarkers Prev; 25(5); 736-44. ©2016 AACR.
Highlights
The human polyomavirus (PyV) is a nonenveloped virus with an icosahedral capsid containing a circular double-stranded DNA genome [1, 2]
We investigated intraindividual changes in PyV seroreactivity over time using repeated measures taken after baseline by calculating the intraclass correlation coefficient (ICC; ref.53) for continuous median fluorescence intensity (MFI) values, and stratified analyses by randomization arm of the original trial
Among participants with a history of keratinocyte cancer (KC), we found an increased risk of subsequent squamous cell carcinoma (SCC) associated with John Cunningham virus (JC) seropositivity, as well as with increasing quartiles of BK and JC seroreactivity, in serum samples collected prior to SCC diagnosis
Summary
The human polyomavirus (PyV) is a nonenveloped virus with an icosahedral capsid containing a circular double-stranded DNA genome [1, 2]. The genome of the Polyomaviridae family encodes three capsid proteins (VP1, VP2, and VP3), as well as small and large T antigens (TAg; refs. ). Little is known about intraindividual PyV antibody stability over time in the general population [12], but repeated measures of PyV seroreactivity collected from individuals with a compromised immune system [13,14,15,16,17,18,19,20] suggest antibody levels may be consistent longitudinally. Little is known about the serostability of other PyVs over time or associations with cutaneous squamous cell carcinoma (SCC)
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