Association of SV40 with human tumours

Our plain-English summary of Association of SV40 with human tumours, by B. Jasani, A. Cristaudo, S.A. Emri, et al (Seminars in Cancer Biology, 2001).

The study

• Authors: B. Jasani, A. Cristaudo, S.A. Emri, A.F. Gazdar, A. Gibbs, B. Krynska, C. Miller, L. Mutti, C. Radu, M. Tognon, A. Procopio
• Journal: Seminars in Cancer Biology
• Published: 2001;11(1):49-61
• Type of article: Review
• Cited by: 84 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

SV40 was discovered as a contaminant of poliovirus vaccines that were inadvertently administered to millions of people in Europe and the United States between 1955 and 1963. Shortly afterwards, SV40 was proven to be oncogenic in rodents and capable of transforming human and animal cells in vitro. The possibility that SV40 might cause tumours in humans thus became a subject of scientific and public interest and scrutiny. However, largely due to a lack of significant epidemiological evidence, interest in assessing SV40's potential carcinogenic role in humans diminished. Recently, many laboratories have reported the presence of SV40-like DNA in a high proportion of human mesotheliomas, ependymomas and osteosarcoma (the three main types of tumours caused by virus in hamsters), renewing the question whether SV40 might be a human tumour virus. Molecular data from these studies are reviewed to re-evaluate the potential role of SV40 as a human carcinogen.

Copyright 2001 Academic Press.

In plain English

This article was a review, not a new study, of published evidence on whether simian virus 40 (SV40), which contaminated poliovirus vaccines given to millions in Europe and the United States between 1955 and 1963, is associated with human tumours. They covered pre-PCR studies from 1974 to 1985 and nearly 50 studies using PCR, a DNA detection method, on tumours including pleural mesothelioma. One cited study found SV40 DNA in 61/93 microdissected mesothelioma specimens but only 1/75 microdissected non-tumour lung tissue samples from the same specimens. Two other studies found no SV40 in mesotheliomas, possibly reflecting methodological or demographic differences, the authors suggested. Several cohort studies found no cancer increase in exposed birth cohorts, but another survey recorded an unexpected three-fold mesothelioma increase in potentially exposed infant or child cohorts. The authors noted these studies assumed every 'exposed' person was truly inoculated with the suspect vaccine. The authors concluded that molecular and cellular evidence favoured a pathogenic association, especially for pleural mesothelioma. They also suggested surveys of workers with high pleural mesothelioma rates might help evaluate a possible combined causal role of asbestos and SV40.

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: Narrative review of published laboratory (pre-PCR and PCR-based) studies, with discussion of epidemiological studies and the Bradford Hill criteria
• Who was studied: Published studies of human tumour samples: pre-PCR studies from 1974 to 1985 (mostly brain tumours) and nearly 50 PCR-based studies covering pleural and peritoneal mesotheliomas, brain tumours, bone tumours, thyroid tumours, lymphomas and prostatic tumours
• Exposure: SV40 virus, including exposure through contaminated poliovirus vaccines. Asbestos is mentioned only in the conclusion, as a possible co-factor for future study; no fiber types are named.
• Main results:
  • In a cited study by Shivapurkar et al., 61/93 microdissected mesothelioma specimens tested positive for SV40 DNA, compared with 1/75 microdissected non-neoplastic lung tissue samples from the same specimens
  • Two cited studies found no PCR evidence of SV40 in human mesotheliomas; the authors suggested this may be due to methodological and/or demographic differences
  • Cited studies from Finland and Turkey, countries described as unaffected by SV40-contaminated vaccines, found SV40 DNA-positive pleural mesotheliomas to be much less common than in the US
  • Several epidemiological studies cited by the review (Mortimer et al., Geissler, Olin and Giesecke, Strickler and Goedert) failed to show increased cancer incidence in birth cohorts exposed to the contaminated vaccines
  • A separate cited survey by Strickler et al. recorded an unexpected three-fold increase in mesothelioma incidence in cohorts of infants or children potentially exposed to contaminated vaccines, compared with the corresponding unexposed cohorts
  • The authors judged that the reviewed data supported the Bradford Hill criteria of specificity, consistency, biological plausibility and experimental evidence, especially for pleural mesotheliomas and some brain tumours
• The authors' conclusion: The authors concluded that there appeared to be sufficient molecular and cellular evidence in favour of a pathogenic association of SV40 with human tumours, especially pleural mesotheliomas. They said PCR-based methods had provided evidence of a potentially pathogenic role in mesotheliomas and certain brain tumours, and that retrospective surveys of worker cohorts with high pleural mesothelioma incidence might help evaluate a possible synergistic causal association between asbestos and SV40.
• Limitations the authors state:
  • The authors stated that the cohort studies assumed every member of an 'exposed' cohort had truly been inoculated with the Salk vaccine suspected of containing live SV40
  • The authors stated that there are no data showing which vaccine batches, or what proportion of injected vaccines, contained live SV40, which complicates the epidemiological studies
  • The authors stated that cell line and microdissection approaches may be subject to sampling errors
  • The authors cautioned that the detection rates in their summary table should be interpreted in light of how reproducible and reliable the techniques were
  • The authors stated that the significance of cytoplasmic Tag staining is uncertain

Topics

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

Related studies

• 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)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Asbestos, Simian virus 40 and malignant mesothelioma — S.C. Stenton (1997)
• New molecular and epidemiological issues in mesothelioma: role of SV40 — M. Carbone, S. Fisher, et al. (1999)
• SV40 and the pathogenesis of mesothelioma — P. Rizzo, M. Bocchetta, et al. (2001)
• Prospects for an SV40 vaccine — M.J. Imperiale, H.I. Pass, et al. (2001)

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