Two upcoming studies by scientists at the National Cancer Institute (NCI), provide further evidence that exposure to simian virus 40 (SV40) is not associated with cancer in humans.
Some U.S. polio vaccines administered from 1955-1962 were accidentally contaminated with SV40 because the vaccines were grown in monkey kidney tissue. Before the discovery of the virus led to changes in vaccine manufacture, millions of Americans received SV40-contaminated polio vaccines. This has been a significant public health concern, as SV40 has been shown to cause cancer in experimental animals. However, studies in humans have not proved conclusive.
Because some laboratory studies report that SV40 DNA can be detected in various childhood tumors, scientists led by Eric Engels, M.D., M.P.H., an investigator in NCI's Division of Cancer Epidemiology and Genetics, evaluated cancer risk of 54,796 U.S. children whose mothers received polio vaccine during pregnancy that may have been contaminated with SV40. Engels and colleagues hypothesized that mothers who were vaccinated against polio before 1963 might have become infected with SV40 by this route and transmitted the virus to their children. In animals, SV40 is most likely to cause cancer when infection occurs during infancy. The scientists wondered whether transmission of infection from a mother to her child during pregnancy or soon after birth might be related to the later development of childhood cancer.
The researchers compared cancer risk in children whose mothers received pre-1963 polio vaccine with cancer risk in children whose mothers did not receive pre-1963 polio vaccine. They also measured SV40 antibodies in the mothers of 50 of these children who developed cancer and the mothers of 200 children without cancer. One of this study's strengths is the researchers' use of two different means of detecting SV40 antibodies, which are produced by exposure to or infection with the virus. The first method, called a plaque neutralization assay, has long been considered the gold standard. They also used a virus-like particle assay, a newer test with high sensitivity and specificity, allowing researchers to distinguish between SV40 antibodies and those against other related viruses.
Interestingly, the investigators found that the incidence of neural tumors and hematologic malignancies was roughly 2.5 times higher in children whose mothers received pre-1963 vaccine than in children whose mothers did not. However, the pattern of cancers in children whose mothers received the vaccine was not what would be predicted if SV40 caused cancer: the types of cancers varied and did not correspond to the types in which SV40 DNA has reportedly been detected. "It was notable that only one brain tumor of the types in which SV40 DNA has reportedly been detected--an ependymoma--was observed, and that was in a child whose mother had not received pre-1963 polio vaccine," explained Engels. "More cases of the types of cancer hypothesized to be linked to SV40--for example ependyomas, choroid plexus tumors, and osteosarcomas--would be expected if SV40 were the cause of the tumors in these children." Additionally, few women had antibodies to SV40 by either of the antibody tests, and there was no consistent relationship between the development of SV40 antibodies during pregnancy and cancer in children.
The scientists acknowledge that the small number of children and the number of individual cancer types seen were limitations. Nonetheless, as Engels summarized, "Overall, these results argue against an important role for SV40 in childhood cancers."