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Vaccine Safety > Issues of Interest
Simian Virus 40 (SV40) and Cancer
Q&A image

Questions answered on this page:

  1. What is SV40 virus?

  2. Why is there so much interest in SV40?

  3. Does polio vaccine contain SV40 virus today?

  4. Who received SV40 contaminated polio vaccine?

  5. Were any other vaccines contaminated with SV40?

  6. What was done to see if SV40 virus affected people's health?

  7. Did SV40 harm anyone who received polio vaccine containing it?

  8. Have studies found an association between SV40 and cancer?

  9. Has there been an increase in incidence of cancer as a result?

  10. What is the bottom line?

  11. If I have one of these rare cancers, does it mean SV40 caused it?

  12. Can I obtain a test for SV40?

  13. What should I do if I received polio vaccine during 1955-1963?

  14. Where can I get more information about SV40?

  1. What is SV40 virus?

Simian virus 40 or SV40 was discovered in 1960. It occurs naturally in some species of monkeys, though it does not typically cause symptoms or illness (cf Shah and Nathanson, 1976) except in cases where the animal has chronic problems with their immune system. In those cases, the animals showed lesions associated with SV40 in their kidney and brain (Newman et al., 1998).

It is important to note that SV40 has no relationship to HIV, the virus that causes AIDS in humans, or simian immunodeficiency virus (SIV), the virus that causes an AIDS-like disease in some monkeys species.

  1. Why is there so much interest in SV40?

Soon after its discovery in 1960, SV40 was identified in polio vaccine. This was because rhesus monkey kidney cells, which contain SV40 if the animal is infected, were used in preparing viral vaccines at that time. Because SV40 was not discovered until 1960, no one was aware that polio vaccine made in the 1950's could be contaminated. In 1961, the virus was found to cause tumors in rodents (Eddy et al., 1961). That same year the federal government required all polio vaccine to be free of SV40.

Interest in SV40 has increased in the last several years because the virus has been found in certain rare forms of cancer tumors in humans, for instance mesotheliomas (Carbone et al., 1994). However, data suggest that SV40 has infected a small percentage of the human population independently of the polio vaccine. A study of German medical students found that 12% had SV40 antibodies in 1952, before the introduction of the polio vaccine (Geissler et al., 1985). Moreover, about 13% of a group of people born after 1962 had SV40 antibodies, a time when contaminated polio vaccine was no longer in circulation. Of those persons born between 1959 and 1961 who were at high risk for receiving SV40 contaminated polio vaccine, 24% had SV40 antibodies (Zimmermann et al., 1983). Thus, it appears that the rate of SV40 antibodies in humans was the same before and after contamination of the polio vaccine.

On January 27-28, 1997, the U.S. Food and Drug Administration, the Centers for Disease Control and Prevention, the National Institutes of Health and the National Vaccine Program Office sponsored an open public meeting with scientists and physicians to discuss research findings on SV40. At the meeting they discussed available data and determined that further research into the field of SV40 is needed (Brown & Lewis, 1998).

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  1. Does polio vaccine contain SV40 virus today?

No. All monkey cell cultures used to produce polio vaccine are screened to assure that SV40 is not present. This screening was implemented in the early 1960s when SV40 was first discovered. There are two varieties of SV40 virus – fast replicating and slow replicating strains. Until recently, it was thought that only the fast replicating strains were present in the polio vaccine prior to the institution of screening. Rizzo et al. (1999) recently presented evidence that both the fast and slow replicating strains could have contaminated the polio vaccine prior to 1963. They also suggested that the methods used to screen the polio vaccine after 1963 may not have been sensitive enough to detect the slow replicating strains of SV40. However, the screening methods evaluated by Rizzo et al. (1999) are different from the ones that are actually used; the ones that are actually used are sensitive enough to detect all strains of SV40. In addition, huge amounts of oral polio vaccine have been periodically tested after 1963, using the most sensitive assays available, and SV40 has never been identified. Furthermore, oral polio vaccine (the polio vaccine used in the United States almost exclusively until recently) has been produced under extremely strict conditions in order to eliminate the possibility of any contamination with SV40. Inactivated polio vaccine (the polio vaccine that is currently recommended and used in the United States) is not produced in monkey cell cultures, and, therefore, contamination with SV40 is not an issue.

  1. Who received SV40 contaminated polio vaccine?

About 10-30 million people who received a polio shot between 1954-1963 could have received a vaccine that contained SV40 (Shah and Nathanson, 1976). In addition, volunteers who received oral polio vaccine between 1959-1961 as part of a test group may have received a vaccine contaminated with SV40. The time period during which SV40 could have contaminated polio vaccine was between 1954 when rhesus monkey kidney cultures first came into general use until early 1963. After this date, all vaccines on the market were free of SV40. Formalin was used in vaccines to kill or inactivate the virus. SV40 was a contaminant of: 1) formalin-inactivated poliovirus vaccines given subcutaneously to millions of people, and 2) test lots of live poliovirus vaccines given orally in small trials to approximately 10,000 people (Shah and Nathanson, 1976).

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  1. Were any other vaccines contaminated with SV40?

Yes. SV40 was a contaminant of respiratory syncytial virus given to a few volunteers in an experimental study of infection with live virus (Shah and Nathanson, 1976). In addition, SV40 was also found in vaccines given to protect young men from respiratory infections in army camps. Formalin-inactivated adenovirus vaccines were given subcutaneously; primarily to more than 100,000 young men in army camps between 1955-1961 (Sherwood et al., 1961).

  1. What was done to see if SV40 virus affected people's health?

When SV40 was discovered in the early 1960's, researchers did not know if SV40 virus could negatively affect health. Many viruses that harm animals have no effect on people because of the biological differences between animals and humans. However, to investigate the possibility, several federally funded studies were carried out during the 1960's, 1970's and 1980's to follow persons who received polio vaccines. Several groups of persons who received a vaccine contaminated with SV40 have been contacted by medical researchers to determine whether they developed any cancers. Please see results of studies under Question 9.

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  1. Did SV40 harm anyone who received polio vaccine containing it?

Based on the available research to date, the Centers for Disease Control and Prevention is not aware of any person who has developed an illness as a result of receiving a polio vaccine that may have been contaminated with SV40. It is possible, however, that future research may show a causative relationship between exposure to SV40 contaminated polio vaccine and ill health, but as yet, no such research exists.

It is important to note that formalin used to inactivate the polio viruses would have helped to inactivate SV40 as well. It is likely that in many contaminated batches where SV40 concentrations were not high, formalin may have inactivated most or all of the SV40 virus (Shah & Nathanson, 1976).

  1. Have studies found an association between SV40 and cancer?

While an association has been found between SV40 and certain rare types of cancer, it is important to emphasize that it has not been determined that SV40 causes these cancers. SV40 was linked with mesothelioma when tumors developed in hamsters injected with SV40 into the lungs, heart and abdomen (Cicala et al., 1993). Mesotheliomas are rare cancerous tumors located in the lungs (pleura) and peritonium (abdomen) and are associated with asbestos exposure. SV40 has been found in 47% to 83% of human mesothelioma tumors (Carbone, 1999).

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  1. Has there been an increase in incidence of cancer as a result?

No. Since the discovery of SV40 in the 1960's several studies have been done to see if persons who received polio vaccine containing SV40 had more health problems than persons who did not receive polio vaccine containing SV40. Several studies have compared cancer rates in a cohort of individuals exposed to SV40 contaminated polio vaccine to rates in a cohort of persons unexposed. A brief description of some of these studies follows:

In 1998, the National Institutes of Health, National Cancer Institute published findings from a study (Strickler et al., 1998) that revealed that after 30 years, there was no increased incidence of cancer in persons who may have received vaccine containing SV40. The study included millions of people exposed to contaminated polio virus and decades of cancer incidence and mortality data. Comparisons of the rates of cancer were made between persons who had received SV40 contaminated vaccine as infants born in 1956-1962 and persons born in 1947-1952 and 1964-1969. This study looked specifically for types of rare cancers that have been found to contain SV40 in recent cellular research (Carbone et al., 1994) and found no significant increased incidence compared to persons who had not received contaminated SV40 vaccine. The rare cancers included ependymomas (cancer of cells found in developing fetal neural tubes from which the brain and spinal cord arise as a baby develops), osteosarcomas (a type of bone cancer), mesotheliomas (a type of cancer that originates in the tissue lining of the lung cavity) and brain cancers.

Olin et al. (1998), conducted a long term follow-up study of 700,000 people in Sweden who received polio vaccine potentially contaminated with SV40 in 1957 as school-age children. Their results revealed no increased cancer incidence between persons who received vaccine containing SV40 and those who did not.

Giessler (1988) analyzed German National Cancer Registry data to compare the incidence of cancer in 885,783 persons born between 1959-1961 who received polio vaccine that may have been contaminated with SV40 and compared it to 891,321 persons born between 1962-1964 who received SV40 free vaccine. These data demonstrated that persons who received polio vaccine possibly contaminated with SV40 virus did not develop more tumors within a 20-year time period than did those who received vaccine that did not contain SV40.

Mortimer (1981) studied cancer deaths of 1073 persons born between 1960-1962 who received oral poliovirus or inactivated poliovirus vaccine that contained SV40 when newborn. The follow-up study over 17-19 years revealed no increased number of deaths from cancer.

Fraumeni et al. (1970) followed 1000 persons who had received SV40 contaminated poliovirus vaccine within a few days after birth. The majority of these people received the SV40-contaminated oral vaccine. At eight years of age no cancer deaths were identified in the exposed group.

Fraumeni et al. (1963) focused on a cohort of children age 6-8 years who received inactivated poliovirus vaccine in 1955. A comparison was made based on whether children received vaccine with high, low or no detectable amount of SV40 contamination. Mortality rates from leukemia and all other cancers from 1950-1959 were compared across the three groups. No differences in cancer rates were found for this time period.

In summary, cohort studies carried out in the United States and in Europe have not shown a relationship between exposure to SV40 contaminated polio vaccine in infancy or childhood and cancer. However, two studies concerning maternal vaccination with SV40 contaminated vaccines and risk of cancer in offspring did report an association.

Heinonen et al. (1973) reported a higher incidence of neural malignancies in children born to mothers who received inactivated poliovirus during pregnancy. The prospective study of over 50,000 women who were pregnant between 1959-1965 identified 24 malignancies in their children during the first 4 years of life. The rate of malignancy was about two-fold greater in children born to mothers immunized during pregnancy when compared to children born to unimmunized mothers. Neural tumors accounted for most of the difference.

Farwell et al. (1979) found that of 15 cases of medulloblastoma in children born in Connecticut between 1956-1962, 10 were born to mothers exposed to SV40 contaminated polio vaccine while 5 were born to mothers unexposed. Interpretation of these results, however, is hampered by the low response rates and uncertain accuracy of vaccination histories by obstetricians (Strickler et al., 1998).

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  1. What is the bottom line?

While the majority of evidence suggests there is no relationship between SV40 exposure in contaminated vaccines and cancer development, more studies are needed. Studies should focus on the long term consequences of SV40 exposure in the cohorts of persons exposed very early in life as some cancers like mesotheliomas typically occur in old age. Moreover, additional studies should focus on the effect of maternal exposures to SV40 contaminated vaccines in children as well as the potential long term effect of SV40 exposure on health outcomes other than cancer (Strickler and Goedert, 1998). It should be emphasized that if indeed a causal relationship is found between SV40 and cancer, the occurrence is rare.

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  1. If I have one of these rare cancers, does it mean SV40 caused it?

No. We do not fully understand the possible role of SV40 in human cancers. Though we do know that cancers have been diagnosed in people who did not receive vaccine containing SV40 (Strickler et al., 1998), so they must have other causes regardless of whether or not they are associated with SV40.

  1. Can I obtain a test for SV40?

No, there is no test for SV40 commercially available at this time.

Research laboratories are currently refining the techniques used to detect SV40. PCR (polymerase chain reaction) assays are currently in use to detect SV40 DNA segments. Because of inconsistent results between laboratories there is a need to develop a standard PCR assay (Levine et al., 1998).

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  1. What should I do if I received polio vaccine during 1955-1963?

There are no recommended treatments or tests for persons that may have been exposed to SV40. If you have concerns about your health, please make an appointment to see your health care provider.

  1. Where can I get more information about SV40?

The Food and Drug Administration has been the federal government lead in answering questions relating to SV40 in polio vaccine. You may call the FDA at the following number: 1-800-835-4709.

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References

Brown F, Lewis AM (eds): Simian virus 40 (SV40): A possible human polyomavirus. Dev Biol Stand. Basel, Karger, 1998, vol 94.

Carbone M, Pass HI, Rizzo P, Marinetti M, Di Muzio M, Mew DJ, Levine AS, Procopio A. Simian virus 40-like DNA sequences in human pleural mesothelioma. Oncogene 1994, 9:1781-90.

Carbone M. Simian virus 40 and human tumors: It is time to study mechanisms. J Cellular Biochemistry 1999, 76: 189-93.

Cicala C, Pompetti, Carbone M. SV40 induces mesotheliomas in hamsters. Am J Pathology 1993, 142:1524-33.

Eddy BE, Borman GS, Berkeley W, Young RD. Tumors induced in hamsters by injection of rhesus monkey kidney cell extracts. Proc. Soc. Exp. Biol. (NY) 1961, 107:191-197.

Farwell JR, Dohrmann GJ, Marrett LD, Meigs JW. Effect of SV40 virus contaminated polio vaccine on the incidence and type of CNS neoplasms in children: a population based study. Trans Am Neurol Assoc 1979, 104:261-264.

Fraumeni JF, Ederer F, Miller RW. An evaluation of the carcinogenicity of simian virus 40 in man. J Am Med Assoc 1963, 185:713-718.

Fraumeni JF, Stark CR, Gold E et al. Simian virus 40 in polio vaccine: follow up of newborn recipients. Science 1970, 167:59-60.

Heinonen OP, Shaprio S, Monson R et al. Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidemiol 1973, 2:229-235.

Geissler E, Konzer P, Scherneck S, Zimmermann W. Sera collected before introduction of contaminated polio vaccine contain antibodies against SV40. Acta Virologica 1985, 29:420-23.

Giessler E, Staneczek. W. SV40 and human brain tumors. Archive fur Geschwulstforschung 1988, 58:129-134.

Levine A, Butel J, Dorries K, Goedert J, Frisque R, Garcea R, Morris A, O’Neill F, Shah K. SV40 as a putative human commensal. Developments in Biological Standardization 1998, 94:245-69.

Mortimer EA, Lepow ML, Gold E, et al. Long-term Follow-up of persons inadvertently inoculated with SV40 as neonates. Medical Intelligence 1981, 305:1517-1518.

Newman JS, Baskin GB, Frisque RJ. Identification of SV40 in brain, kidney and urine of healthy and SIV-infected rhesus monkeys. J NeuroVirology 1998; 4:394-406.

Olin P, Giesecke J. Potential exposure to SV40 in polio vaccines used in Sweden during 1957: no impact on cancer incidence rates 1960 to 1993. Dev Biol Stand. 1998, 94:227-33.

Rizzo P, Resta ID, Powers A, Ratner H, Carbone M. Unique strains of SV40 in commercial poliovaccines from 1955 not readily identifiable with current testing for SV40 infection. Cancer Research 1999;59:6103-6108.

Sherwood RW, Buescher EL, Nitz RE et al. Effects of adenovirus vaccine in acute respiratory disease in US Army recruits. JAMA 178:1125-1127:1961.

Shah K, Nathanson N. Human exposure to SV40: Reviews and Comment.. Am J Epidemiol 1976, 103:11-12.

Strickler HD, Rosenberg PS, Devesa SS, Hertel J, Fraumeni JF, Goedert JJ. Contamination of poliovirus vaccines with simian virus 40 (1955-1963) and subsequent cancer rates. JAMA, January 28, 1998; 279(4):292-295.

Strickler HD, Goedert JJ. Exposure to S40 contaminated poliovirus vaccine and the risk of cancer-A review of the epidemiological evidence. In F Brown and AM Lewis (eds.) Simian Virus 40 (SV40): A possible human polyomavirus. Dev Bio Stand Basel Karger 1998, 94:235-244.

Zimmermann W, Scherneck S, Geissler E. Quantitative determination of papovavirus IgG antibodies in sera from cancer patients, labworkers and several groups of control persons by enzyme-linked immunosorbent assay (ELISA). Zentralblatt Fur Bakteriologie, Mikrobiologie Und Hygiene-1-Abt-Originale A, Medizinische Mikrobiologie, Infektionskrankheiten Und Parasitologie 1983, 254:187-96.

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