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.
