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.