No Conclusive Link Seen Between Simian Virus 40 and Human Cancer

In recent years, some studies have suggested that simian virus 40 (SV40), which contaminated some polio vaccines made between 1955 and 1963, may now be passing from person to person and causing certain types of human cancers. A new analysis of many of these studies, however, has now concluded that existing data do not indicate a definitive link between the development of human cancer after exposure to SV40. "Nor do the data support the assertion that SV40 is now spreading in the human population by person-to-person transmission," said author Keerti V. Shah, DrPH, MD, Molecular Microbiology and Immunology, Johns Hopkins School of Public Health. His analysis of the SV40 research was published in the February 2000 issue of Reviews in Medical Virology.

Dr. Shah cited several inconsistencies in studies purporting to show that SV40 is now spread by person-to-person transmission. The SV40 gene sequences that are being found in humans, for instance, are essentially identical to those of SV40 found in monkeys in the wild. "SV40 is a highly species-specific virus," he said. "It is difficult to conceive that this virus would cross the species barrier, become a human infection, and acquire pathogenic potential for causing cancer for the new host, without a significant adaptive change in its genome." Further, Dr. Shah noted that several studies looking for SV40 in human cancers have been negative, and that SV40 has not been detected in human urine, where it would be expected if the virus had adapted to circulate in humans.

The polio virus used in vaccine production between 1955 and 1963 was grown in macaque kidney cell cultures that were sometimes contaminated with SV40. The largest U.S. manufacturer of polio vaccine at that time, however, used a culture system inhospitable to SV40 and so a significant proportion of vaccine lots were probably free of SV40. Further, many of the individuals with SV40-positive tumors were born long after polio vaccines were free of SV40.

The analysis turned up many inconsistencies: Some researchers report SV40 in sperm fluids while others do not. The frequency of detection of SV40 in normal blood cells varies greatly from study to study, from 0 to 23 percent. SV40 T antigen was detected in cancers by some investigators but not by others.

On the molecular level, Dr. Shah noted that although many researchers report finding SV40 sequences in human cancers, SV40 DNA is by no means present in every tumor cell. The amount of SV40 DNA in human cancers is apparently so small that it has been difficult to detect the genome consistently in tumors by technology other than the PCR amplification assay, which is prone to error.

Finally, the report noted that in those human cancers positively proven to be associated with viruses, the virus is always linked specifically to just one particular type of cancer. In contrast, SV40 is ambiguously linked to many types of cancer. Additional studies are needed, said Dr. Shah, to clarify many of these questions.

Dr. Shah summed up by saying, "The possibility that a virus may be involved in the development of a human cancer is strengthened when evidence from many separate lines of enquiry (e.g. epidemiology, pathogenesis, molecular mechanisms) converges to provide a coherent picture of how the infection might lead to cancer. The data on SV40 -human cancer association fall far short of this goal. It is premature to discuss or speculate on the potential role of SV40 in the development of human cancer."

This study was supported in part by funding from the National Cancer Institute.