CORRESPONDENCE

Re: Trends in U.S. Pleural Mesothelioma Incidence Rates Following Simian Virus 40 Contamination of Early Poliovirus Vaccines

Regis A. Vilchez, Janet S. Butel

Affiliations of authors: R. A. Vilchez (Departments of Medicine and Molecular Virology and Microbiology), J. S. Butel (Department of Molecular Virology and Microbiology), Baylor College of Medicine, Houston, TX.

Correspondence to: Regis A. Vilchez, M.D., Department of Medicine, Section of Infectious Diseases, One Baylor Plaza, BCM-286, Rm. N1319, Houston, TX 77030 (e-mail: rvilchez{at}bcm.tmc.edu).

We read with interest the recent article in the Journal by Strickler et al. (1), in which the authors performed a retrospective age–period–cohort analysis to estimate the incidence of pleural mesothelioma in individuals potentially exposed to simian virus 40 (SV40) -contaminated poliovirus vaccines. The authors concluded that "Age-specific trends in U.S. pleural mesothelioma incidence rates are not consistent with an effect of exposure to SV40-contaminated poliovirus vaccine" and suggested that "monitoring of vaccine-exposed cohorts should continue." We wish to raise two issues about this and similar studies (24) that address "exposure" to SV40-contaminated polio vaccines and the incidence of human cancers. First, although a cohort study is recognized as the best design to identify incidence and natural history of disease (with a known exposure) and may be used to assess multiple outcomes after a single exposure (5), the prevalence of SV40 infections in the human population is not known, and the available data about prevalence are limited and inconclusive (24). Second, an important confounding factor in the epidemiologic assessment of malignant mesothelioma is that the actual number of people infected with SV40 through the use of contaminated polio vaccines is not known and may be less than the "exposed" population size assumed in the study by Strickler et al. (1). For example, in the United States, not all vaccine lots were contaminated with SV40, formalin inactivation was expected to reduce the titer of live SV40 in the lots that were contaminated, and successful infection rates by live SV40 are unknown (24). Therefore, an inability to identify the population that was actually infected with SV40 through the use of contaminated polio vaccines precludes a meaningful calculation of cancer incidence in relation to exposure to those vaccines. Furthermore, the Institute of Medicine (IOM) Immunization Safety Review Committee found that epidemiologic studies of cancer rates in people potentially "exposed" to SV40-contaminated vaccines, such as the analysis by Strickler et al. (1), are inadequate to evaluate a causal relationship between exposure and disease (2). These limitations led the IOM to "not recommend additional epidemiological studies of people potentially exposed to contaminated polio vaccine" (2). However, the IOM concluded that "the biological evidence is strong that SV40 is a transforming virus" and that "the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions" (2). Future studies are needed to determine the prevalence of SV40 infections in different human populations. The IOM recognized that gaps in our understanding of the pathogenesis of SV40 in humans are important and recommended "targeted biological research," including "further study of the transmissibility of SV40 in humans" (2).

NOTES

R. A. Vilchez is the recipient of the 2001 Junior Faculty Development Award from GlaxoSmithKline and the 2002 Translational Research Award from the Leukemia and Lymphoma Society.

REFERENCES

1 Strickler HD, Goedert JJ, Devesa SS, Lahey J, Fraumeni JF Jr, Rosenberg PS. Trends in U.S. pleural mesothelioma incidence rates following simian virus 40 contamination of early poliovirus vaccines. J Natl Cancer Inst 2003;95:38–45.[Abstract/Free Full Text]

2 Stratton K, Almario DA, McCormick MC, editors. Immunization safety review: SV40 contamination of polio vaccine and cancer. Washington (DC): The National Academies Press. In press 2003. Available at: http://www.nap.edu/books/0309086108/html/index.html. [Last accessed: 03/07/2003.]

3 Vilchez RA, Kozinetz CA, Butel JS. Conventional epidemiology and the link between SV40 and human cancers. Lancet Oncol 2003;4:188–91.[CrossRef][Medline]

4 Rollison DE, Shah KV. The epidemiology of SV40 infection due to contaminated polio vaccines: relation of the virus to human cancer. In: Khalili K, Stoner GL, editors. Human polyomaviruses: molecular and clinical perspectives. New York (NY): Wiley-Liss, Inc.; 2001. p. 561–84.

5 Grimes DA, Schultz KF. Cohort studies: marching towards outcomes. Lancet 2002;359:341–5.[CrossRef][Medline]



             
Copyright © 2003 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement