Is There a Role for SV40 in Human Cancer?
The debate over whether or not Simian Virus 40 (SV40) can cause human cancer has been one of the most contentious topics in oncology in the last 50 years. The inadvertent exposure of nearly 100 million people in the United States, and many more throughout the world (I’m one of them!) to SV40 through the administration of contaminated poliovirus vaccines, and the subsequent finding of the oncogenic activity of the SV40 viral large and small T antigens, has led to concern over the potential of SV40 to cause cancer in humans. Since its discovery in 1960, thousands of studies investigating the biology of SV40 have been reported.
The discovery of SV40 was reported in 1960 as a contaminant present in polio vaccine stocks. At this time, polio vaccine was being produced in primary kidney cells and tissue harvested from rhesus and cynomolgus macaques. Safety testing of vaccine preparations on cultures of African green monkey kidney cells uncovered the presence of SV40, a “vacuolating agent,” that induced a cytopathic effect in some cultures. SV40 was detected in preparations of both the inactivated, or Salk, poliovirus vaccine and the live attenuated, or Sabin, poliovirus vaccine. In the United States, the Salk inactivated poliovirus vaccine (IPV) was used to inoculate 98 million children and adults between 1955 and 1963, whereas about 10,000 people received the Sabin oral polio vaccine (OPV) through clinical trials between 1959 and 1961. Because OPV was not licensed in the United States until 1963, after the establishment of government regulations requiring all poliovirus vaccine to be free of SV40, vaccination with IPV from 1955 to 1963 is thought to be the primary source of human exposure to SV40 in the United States.
The aim of a newly published review (Poulin DL, DeCaprio JA. Is there a role for SV40 in human cancer? J Clin Oncol. 2006 24: 4356-65) is to give a broad overview of the evidence implicating SV40 in human cancer, and to relate these studies to the biologic mechanism of SV40-mediated transformation.
Conclusion: Although many people may have been exposed to SV40 by polio vaccination, there is inadequate evidence to support widespread SV40 infection in the population, increased tumour incidence in those individuals who received contaminated vaccine, or a direct role for SV40 in human cancer.
Phew!
[...] and human cancerA few months ago, I recorded a podcast about whether there is a role for SV40 in human cancer. A paper just published again confirms the negative conclusion I reached. An unknown proportion of [...]
“… there is inadequate evidence” … Absence of evidence isn’t evidence of absence