Case-control study of simian virus 40 and non-Hodgkin lymphoma in the United States

Background: Recent studies have reported detection of simian virus 40 (SV40) DNA in tumor tissues from 15%-43% of U.S. non-Hodgkin lymphoma (NHL) patients. SV40 accidentally contaminated U.S. poliovirus vaccines that were widely administered from 1955 through 1962. However, epidemiologic data linking SV40 with NHL are lacking. Methods: We obtained serum samples from 724 incident NHL case patients and 622 control subjects from a population-based U.S. case-control study. SV40 serostatus was analyzed by two independent laboratories (designated A and B) using similar virus-like particle (VLP) enzyme immunoassays. Associations with serostatus were assessed with logistic regression, adjusting for sex, race, birth year, and study site. VLPs for the human polyomaviruses; BK and JC were used in competitive inhibition experiments to assess the specificity of SV40 reactivity. Statistical tests were two-sided. Results: SV40 antibody results from the two laboratories were correlated (R = 0.59; P<.001). Laboratories A and B detected SV40 seropositivity in 7.2% and 9.8% of NHL case patients, respectively, and in 10.5% and 9.6% of control subjects, respectively. SV40 seropositivity was not associated with increased NHL risk (laboratory A: adjusted odds ratio [OR] = 0.68, 95% confidence interval [CI] = 0.46 to 1.00; laboratory B: adjusted OR = 1.02, 95% CI = 0.71 to 1.47). SV40 seropositivity was not associated with NHLs of any specific histology or site. Among subjects born before 1963, 1.0%-1.6% showed SV40-specific reactivity, i.e., SV40 reactivity confirmed in competitive inhibition experiments, whereas (based on limited data) none born subsequently demonstrated SV40-specific reactivity. Conclusions: In persons born before 1963, the presence of SV40-specific antibodies, although rare, could reflect exposure to SV40-contaminated vaccines. Nevertheless, NHL risk was unrelated to serologic evidence of SV40 exposure or infection.