Simian virus 40, poliovaccines and human tumors: a review of recent developments

Our plain-English summary of Simian virus 40, poliovaccines and human tumors: a review of recent developments, by M. Carbone, P. Rizzo, H.I. Pass (Oncogene, 1997).

The study

• Authors: M. Carbone, P. Rizzo, H.I. Pass
• Journal: Oncogene
• Published: 1997;15(16):1877-88
• Type of article: Review
• Cited by: 166 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Recently, wild-type SV40 and/or DNA sequences indistinguishable from SV40 have been detected in specific types of human tumors: ependymoma and choroid plexus tumors, mesothelioma, osteosarcoma and sarcoma. The same tumor types will develop in hamsters after injection with SV40. These findings are interesting in themselves for they could shed light on the pathogenesis of these tumors. These findings also have public health implications. SV40 was found to have contaminated the poliovaccines and the adenovaccines from 1955 until 1963, therefore resulting in the inadvertent injection of millions of people with this tumor virus. Moreover, our society pays a high cost for asbestos causality, a carcinogen associated with the development of mesothelioma. In addition to asbestos, the potential impact of finding another possible cause for mesothelioma (i.e., SV40), as well as the possible pathogenic role of the contaminated poliovaccines, has generated considerable public interest and concern. To discuss these recent findings, the NIH (National Institutes of Health) and the FDA (Food and Drug Administration), organized an International Conference at the NIH, Bethesda, MD, January 27-28, 1997. The association of SV40 with human mesothelioma was also discussed in a special session at the IV International Mesothelioma Conference that was held at the University of Pennsylvania, Philadelphia, PA, May 13-16, 1997. The purpose of this review is to summarize data, from the discovery of the contaminated poliovaccines, to the most recent findings presented at the meetings in Bethesda and Philadelphia, to discuss technical and other problems associated with this research, and the potential for using these findings to develop new diagnostic and therapeutic approaches for SV40-associated malignancies.

In plain English

This article was a meeting review, not a new study. The authors summarized research on simian virus 40 (SV40), a monkey virus that contaminated poliovaccines and adenovaccines from 1955 until 1963, and on reports of SV40 in human tumors. This included findings presented at a 1997 NIH conference and at the IV International Mesothelioma Conference. The work reviewed included the authors' own earlier research. In that research, 60% of a control group of hamsters injected with wild-type SV40 into the heart developed pleural mesotheliomas, and SV40-like DNA was found in 29 of 48 human mesotheliomas and in one of 30 non-mesothelioma tissues. One other paper reported negative results. The authors described the epidemiological data on vaccine recipients as mostly incomplete. They noted that at least 20% of mesotheliomas occur in people with no history of asbestos exposure. They also cited their earlier finding that patients who expressed the SV40 T antigen had asbestos in their lungs. They acknowledged that some positive laboratory results could come from contamination. They concluded that any contribution of SV40 to the rise in mesothelioma was unclear and should be carefully investigated.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (meeting review) of published research and of conference presentations on SV40, poliovaccines and human tumors
• Who was studied: Published studies and presentations reviewed, including those at an NIH/FDA international conference in Bethesda (January 1997) and a special session at the IV International Mesothelioma Conference, University of Pennsylvania, Philadelphia (May 1997)
• Exposure: SV40, including SV40 that contaminated poliovaccines and adenovaccines from 1955 until 1963. Asbestos is discussed as a cause of mesothelioma and a possible co-carcinogen with SV40; no fiber types are named.
• Main results:
  • In the authors' earlier hamster experiments, 60% of a control group of hamsters injected intracardially with wild-type SV40 developed pleural mesotheliomas. The authors suggested that the virus reached the pleura on the outside of the needle used during intracardial injection.
  • In those earlier experiments, all hamsters injected with SV40 directly into the pleural space developed mesothelioma within 3 to 6 months
  • Hamsters injected with SV40 through the femoral vein did not develop mesotheliomas
  • In the authors' earlier human study of frozen samples, SV40-like sequences were found in 29 of 48 mesotheliomas and in 1 of 30 non-mesothelioma tissues
  • One paper (Strickler et al., 1996), using 50 archival formalin-fixed, paraffin-embedded samples, reported negative findings for SV40-like sequences in mesothelioma
  • In mesotheliomas reported from Pass's laboratory, 24% of 42 patients showed amplification with all of the primer sets used; positivity varied by primer set
  • In the only long-term follow-up of vaccine recipients the authors cited (Mortimer et al., 1981), 1073 children were followed for 17 to 19 years, and no excess risk of mortality was observed
  • Citing Roggli et al. (1992), at least 20% of mesotheliomas occur in people with no history of asbestos exposure
  • The authors reported their earlier finding that patients who expressed SV40 T antigen had asbestos in their lungs
• The authors' conclusion: The authors concluded that the contribution, if any, of SV40 to the increased incidence of mesothelioma was unclear, and that the hypothesis that SV40 may play a role in mesothelioma or other tumors should be carefully investigated
• Limitations the authors state:
  • Epidemiological data on tumors in recipients of SV40-contaminated vaccines are mostly incomplete
  • Some positive PCR results might be due to laboratory contamination
  • Whether SV40 is present in people without tumors, or in normal tissues of cancer patients, has not been carefully investigated

Topics

Medical terms in this study, explained in our Lexicon: SV40, Mesothelioma, Sarcoma, Discovery.

Related studies

• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Simian virus 40 and human tumors: It is time to study mechanisms — M. Carbone (1999)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)
• The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas — A. De Luca, A. Baldi, et al. (1997)
• Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma — P. Rizzo, M. Carbone, et al. (1999)

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