CORRESPONDENCE

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

Howard D. Strickler, James J. Goedert, Susan S. Devesa, Philip S. Rosenberg

Affiliations of authors: H. D. Strickler, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY; J. J. Goedert, S. S. Devesa, P. S. Rosenberg, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Correspondence to: Howard Strickler, M.D., M.P.H., Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Belfer 1308, Bronx, NY 10461 (e-mail: Strickle{at}aecom.yu.edu).

We thank Dr. Puntoni and his colleagues and Drs. Vilchez and Butel for their interest in our study of pleural mesothelioma risk subsequent to immunization with simian virus 40 (SV40)-contaminated poliovirus vaccine. Widespread SV40 contamination of poliovirus vaccine manufactured between 1955 and 1963 resulted in a massive single-source exposure. As of 1961, most U.S. residents under the age of 40 years and nearly 90% of those under the age of 20 years had been injected with poliovirus vaccine potentially containing live SV40. Published estimates (1) indicate that approximately 10%–30% of vaccine lots [some published data (2) place the figure higher ] contained live SV40. Because vaccinees received multiple immunizations (a series of three injections and a booster), a high percentage of those immunized with poliovirus vaccine between 1955 and 1963 were injected at least once with live SV40. The inability to precisely identify those, if any, who became infected does not invalidate our comparison of cancer rates according to probability of exposure, which ranged from very high (e.g., >90%) to very low (e.g.,<5%), based on the year of birth.

We observed that pleural mesothelioma incidence rates were not associated with exposure to SV40-contaminated poliovirus vaccine. Could SV40 be a major independent cause of mesothelioma nonetheless? For this possibility to be so, alternative routes of exposure to SV40 would have to exist, and SV40 would have to be circulating in the general population. In any case, the persistent rarity of pleural mesothelioma cases among women suggests that the cumulative independent effects of known and hypothesized SV40 exposures on rates of pleural mesothelioma have, to date, been negligible.

Could SV40 be in circulation in the general population and interact with other risk factors, particularly asbestos, to cause mesothelioma? We think this is an open question. However, as reviewed in our paper (3), detection of SV40 DNA in approximately equal numbers of asbestos-positive and asbestos-negative mesothelioma tumors argues against such an interaction.

We agree with Puntoni et al. that the latency period for malignancies can be very long, even decades. Nonetheless, most readers are probably reassured that we found no association between mesothelioma and SV40-contaminated poliovirus vaccine in 40 years of follow-up data. Their suggestion, to discard the most recent data (1995–1997) for the youngest age group (25–44 years), would have no impact on our overall results or conclusions. Moreover, their comments do not take into account our age–period–cohort analyses, in which the contribution of each age group and calendar period was weighted by the size of the group, and exposure trends were assessed by individual year of birth.

In our opinion, achieving the Institute of Medicine’s primary research recommendation—development of sensitive, specific, and reproducible tests for detection of SV40 antibodies as well as DNA (4)—will ultimately help resolve remaining questions about the role of SV40 infection in the etiology of human cancer.

REFERENCES

1 Shah K, Nathanson N. Human exposure to SV40: review and comment. Am J Epidemiol 1976;103:1–12.[Medline]

2 Fraumeni JF Jr, Ederer F, Miller RW. An evaluation of the carcinogenicity of Simian virus 40 in man. JAMA 1963;185:713–8.

3 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]

4 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: 03/07/2002.]



             
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