The role of SV40 in malignant mesothelioma and other human malignancies

Our plain-English summary of The role of SV40 in malignant mesothelioma and other human malignancies, by M.A. Pershouse, S. Heivly, T. Girtsman (Inhalation Toxicology, 2006).

The study

• Authors: M.A. Pershouse, S. Heivly, T. Girtsman
• Journal: Inhalation Toxicology
• Published: 2006;18(12):995-1000
• Type of article: Review
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

SV40 is a DNA tumor virus thrust upon human populations primarily as a contaminant in various vaccine preparations. Some estimates suggest that millions of people are currently infected with the virus. The virus causes primary brain tumors, bone tumors, lymphomas, and mesotheliomas when injected into some rodent models. It has also been detected in a similar spectrum of human tumors. However, epidemiological studies have failed to conclusively demonstrate a higher incidence of disease in affected populations. To date, over 60 reports from 49 different laboratories have shown SV40 sequences in tissues from human cancer patients. Six studies, however, have failed to detect evidence of virus in similar tissues. Some have suggested that SV40 may act as a cocarcinogen with asbestos to cause mesothelioma formation, or that it may be responsible for the 10-20% of mesotheliomas with no reported history of asbestos exposure. This report briefly covers the historical evidence for SV40 carcinogenesis and then covers experiments now underway to better understand the role of SV40 in human mesotheliomas.

In plain English

This review summarized earlier research on whether SV40, a monkey virus that contaminated some early polio vaccines, plays a role in mesothelioma and other cancers. Others have suggested that SV40 acts with asbestos to cause mesothelioma. The authors reported that most of over 60 earlier studies detected SV40 in human tumors, and that most of at least 15 mesothelioma studies found SV40 sequences common. Some studies found none, including a 2005 study in which none of 89 analyzable tumor samples (out of 113) tested positive. The authors noted that two of that study's positive controls also tested negative, suggesting a sensitivity issue. Epidemiologic studies had not conclusively linked vaccinated groups to more tumors, while a 2003 meta-analysis concluded that SV40 was significantly associated with malignant mesotheliomas and other cancers. In hamsters, SV40 injected into the heart or the pleural cavity gave rise to mesotheliomas. The authors cautioned that SV40 testing can be complicated and that population studies are hard to interpret. They described a mouse model their laboratory was developing and hoped better tests would clarify SV40's role.

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 research on SV40 and human cancers, especially malignant mesothelioma, plus a description of experiments planned in the authors' laboratory
• Who was studied: Earlier published studies: analyses of human tumor samples, epidemiological studies, cell (in vitro) studies, hamster experiments and transgenic mouse models. The review does not state a total number of reviewed studies.
• Exposure: SV40 virus, mainly from contaminated polio vaccines given in 1954 to 1963. Asbestos is discussed only through the suggestion that SV40 may act as a cocarcinogen with it. No asbestos fiber types are named.
• Main results:
  • According to the review, most of over 60 earlier studies of human tumors detected evidence of SV40.
  • According to the review, most of at least 15 earlier studies of human mesotheliomas found SV40 sequences to be common in the samples.
  • A 2005 study (Manfredi et al.) analyzed 113 paraffin-embedded tumors. Of these, 89 were suitable for analysis, and none was found positive for SV40.
  • The authors noted that two of the 2005 study's positive controls, previously published as SV40-positive, tested negative, suggesting a sensitivity issue.
  • Two large multi-institutional trials reached different conclusions. One detected SV40 in most tumor specimens, and the other found no evidence of SV40 in a similar set of samples.
  • An Institute of Medicine committee found the epidemiological studies inadequate to evaluate a causal relationship.
  • A 2003 meta-analysis by Vilchez and coworkers concluded that SV40 was significantly associated with brain tumors, bone cancers, malignant mesotheliomas and non-Hodgkins lymphomas.
  • SV40-positive tumors have not been found in Finland, Turkey or Austria, which the review describes as countries that did not use SV40-contaminated polio vaccine.
  • In hamsters, intracardiac and intrapleural injections of SV40 gave rise to mesotheliomas.
  • The authors wrote that transgenic mouse studies suggest SV40 is sufficient for tumor development, but none of these models produced mesothelial-specific tumors. Their laboratory was working toward such a model.
• The authors' conclusion: The authors hoped that experiments in their laboratory and others, together with newer and more specific virus detection methods, would clarify the role of SV40 in human tumors, and specifically in mesotheliomas.
• Limitations the authors state:
  • Epidemiological studies are difficult to interpret because the true rate of SV40 infection in the general population is unknown.
  • Detecting SV40 can be complicated by several factors: antibody cross-reaction with the related BKV and JCV viruses, laboratory contamination with SV40, nonspecific techniques, and low virus levels.
  • Transgenic mouse models do not fully reproduce how the virus causes tumors, partly because they lack viral packaging and immune surveillance.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: SV40, Mesothelioma, Asbestos Exposure, Carcinogenesis.

Related studies

• SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study — A. Cristaudo, R. Foddis, et al. (2005)
• SV40 multiple tissue infection and asbestos exposure in a hyperendemic area for malignant mesothelioma — M. Comar, C. Rizzardi, et al. (2007)
• Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids — F. López-Ríos, P.B. Illei, et al. (2004)
• Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection — M. Suzuki, S. Toyooka, et al. (2005)
• Cellular and molecular parameters of mesothelioma — M.E. Ramos-Nino, J.R. Testa, et al. (2006)
• Simian virus 40 transformation, malignant mesothelioma and brain tumors — F. Qi, M. Carbone, et al. (2011)

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