# Presentation: 156107

## Immunization Safety Review

- SV40 Contamination of
- Polio Vaccine and Cancer
- Kathleen Stratton
- NVAC 2-4-03

## Issue Under Review

- Potential for SV40-contaminated polio vaccines in the late 1950s and 1960s to cause cancer

## Scientific Assessment: Causality

- Cancer Incidence (5 ecologic, 2 controlled)
- Fisher et al., 1999
- Strickler et al., 1999
- Strickler et al., 1998
- Olin and Giesecke, 1998
- Geissler, 1990
- Innis, 1968
- Stewart and Hewitt, 1965

## Scientific Assessment: Causality

- Cancer Mortality (2 controlled, 1 uncontrolled)
- Strickler et al., 1998
- Fraumeni et al., 1963
- Follow-up Studies
- Carroll-Pankhurst et al., 2001
- Mortimer et al., 1981
- Fraumeni et al., 1970

## Scientific Assessment: Causality

- Prenatal exposure to SV40 through vaccination of their mothers (2 controlled)
- Farwell et al., 1979
- Heinonen et al., 1973

## Scientific Assessment: Causality

- Limitations
- Ecologic design
- Misclassification bias
- Rarity of Tumors
- Conclusion: **Evidence is inadequate to accept or reject a causal relationship between SV40-containing polio vaccines and cancer.**

## Scientific Assessment: Biological Mechanisms

- The committee was not charged to resolve the full range of uncertainties about the biology of SV40
- The committee reviewed the evidence through 3 key questions

## Scientific Assessment: Biological Mechanisms

- Is SV40 a transforming virus?
- Evidence: studies on rodents, nonhuman primates, cell-culture, and humans
- Conclusion: **The biological evidence is strong that SV40 is a transforming virus**

## Scientific Assessment: Biological Mechanisms

- Can SV40 cause cancer in humans under conditions of natural exposure?
- Inconsistent data on the association between SV40 and human cancers
- Conflicting results in the detection of SV40
- Detection in tumors does not, by itself, demonstrate a causal relationship
- Conclusion: **The biological evidence is moderate  that SV40 exposure could lead to cancer in humans under natural conditions. **

## Scientific Assessment: Biological Mechanisms

- Is contamination of the polio vaccine with SV40 responsible for SV40 infection in humans?
- Exposure to IPV (1955-63) cannot be equated with exposure to live SV40 or to infection with SV40
- Uncertainty about the possible contribution of vaccine-based SV40 exposure to SV40 infection and carcinogenesis b/c of age at which vaccinees were exposed.

## Scientific Assessment: Biological Mechanisms

- (*continued*)
- Other sources of SV40 exposure
- Measures of infection remain problematic
- Conclusion: **The biological evidence is moderate that SV40 exposure from the polio vaccine is related to SV40 infection in humans.  **

## Scientific Assessment: Summary

- The evidence is strong that SV40 contaminated some polio vaccine used from 1955-63
- SV40 has transforming properties in several experimental systems

## Scientific Assessment: Summary (continued)

- It is not clear
- What proportion (if any) of the people exposed to SV40-contaminated polio vaccine were infected
- What proportion (if any) of the human cancers in which SV40 is detected are caused by SV40
- That the sole source of SV40 is due to the contaminated polio vaccine
- That SV40-contaminated polio vaccine did or did not cause cancer in the vaccine recipients.

## Significance Assessment

- Concerns about exposure to SV40 through inadvertent contamination of polio vaccines are significant because
- of the seriousness of cancers as the possible adverse health outcomes
- and because of the continuing need to ensure and protect public trust in the nation’s immunization program

## Recommendations for Public Health Response: Policy Review

- No policy review of polio vaccine by any of the national or federal vaccine advisory bodies on the basis of concerns about cancer risks that might be associated with the exposure to SV40, because the vaccine in current use is free of SV40

## Policy Analysis & Communication Recommendation

- Appropriate federal agencies develop a Vaccine Contamination  Prevention and Response Plan
- Identify procedures already in place or those that need to be developed
- Include strategies for routine assessment of vaccine possible contamination
- Notification of public health officials, health care providers, and the public if contamination occurs.
- Identification of recipients of contaminated vaccine
- Surveillance and research to assess health outcomes associated with the contamination

## Things to Consider

- A program to store samples from each vaccine lot approved for release
- The development of better mechanisms to identify the recipients of vaccine from specific lots

## In Addition:

- The development of the plan should be the subject of broad and open discussion by the regulators, policymakers, manufacturers, researchers, vaccine administrators and the public
- Once a plan is developed, a communication campaign should be undertaken to inform the public and medical practitioners

## Research Recommendations

**Development of sensitive and specific serologic tests for SV40.**
**Development and use of sensitive and specific standardized techniques for SV40 detection.**
- O**nce there is agreement in the scientific community as to the best detection methods and protocols, pre-1955 samples of human tissues should be assayed for the presence or absence of SV40 in rigorous, multicenter studies.**

## Research Recommendations

**Further study of the transmissibility of SV40 in humans.**
**Until some of the technical issues are resolved, the committee does not recommend additional epidemiologic studies of people potentially exposed to the contaminated polio vaccine.**

## Contact Information

- Phone: (202)334-1342
- Email: _[imsafety@nas.edu](mailto:imsafety@nas.edu)_
- Website: _[www.iom.edu/imsafety](http://www.iom.edu/imsafety)_
- Next meeting: March 13, 2003
- Washington, DC