Background: Poliovirus vaccines that were used during the late 1950s and early 1960s were contaminated with simian virus 40 (SV40), a monkey virus that is tumorigenic in rodents. SV40 DNA sequences have been detected in some human cancers, especially pleural mesotheliomas, although results are conflicting. We examined the relationship between SV40-contaminated poliovirus vaccine exposure and subsequent rates of pleural mesothelioma in the United States.
Methods: We used data from the Surveillance, Epidemiology, and End Results Program to estimate age- and sex-specific pleural mesothelioma incidence rates per 10(5) person-years (py) from 1975 through 1997 and the Poisson distribution to determine 95% confidence intervals (CIs) for each rate. The prevalence, by birth cohort, of poliovirus vaccine exposure during the period of widespread SV40 contamination was determined from published survey data. Trends in mesothelioma incidence rates were assessed by examining age- and sex-specific rates over calendar periods and with the use of the age-period-cohort model. Trends in mesothelioma incidence were then compared with trends in prevalence of exposure. All statistical tests were two-sided.
Results: The age-standardized pleural mesothelioma incidence rate for 1975 through 1997 was 1.29/10(5) py (95% CI = 1.24/10(5) to 1.34/10(5) py) in males and 0.21/10(5) py (95% CI = 0.20/10(5) to 0.23/10(5) py) in females. The rate in males increased from 0.79/10(5) py (95% CI = 0.62/10(5) to 1.0/10(5) py) in 1975 to a peak of 1.69/10(5) py (95% CI = 1.46/10(5) to 1.95/10(5) py) in 1992. Incidence rates increased the most among males who were 75 years of age or older, the age group least likely to have been immunized against poliovirus. Incidence rates among males in the age groups most heavily exposed to SV40-contaminated poliovirus vaccine remained stable or decreased from 1975 through 1997. Similar age-specific trends were observed among females. The age-period-cohort models for men and women also indicated that the trends in pleural mesothelioma incidence were not related to trends in exposure to SV40-contaminated poliovirus vaccine.
Conclusions: Age-specific trends in U.S. pleural mesothelioma incidence rates are not consistent with an effect of exposure to SV40-contaminated poliovirus vaccine. Nonetheless, given reports of the detection of SV40 genomic DNA sequences in human mesotheliomas, monitoring of vaccine-exposed cohorts should continue.