Everyone has heard of using immunotherapy to try to treat cancer, but could some vaccines actually have caused cancer? Millions of people were infected with the oncogenic simian virus-40 (SV-40) when they received a contaminated polio vaccine over 40 years ago. SV-40 is able to transform cells in vitro and induce tumours in animals, so what were its effects on these people? Two papers in the 9 March issue of The Lancet associate this virus with non-Hodgkin's lymphoma. Could SV-40 underlie the increased incidence of this cancer over the past few decades?

SV-40 causes B-cell lymphomas in animals and has lymphotropic tendencies in humans, so Regis Vilchez et al. and Narayan Shivapurkar et al. set out on separate investigations to see if it is associated with human lymphoma. SV-40 is a DNA polyomavirus that expresses the T-antigen, which binds and inactivates p53 and Rb, leading to cellular transformation. The two research groups screened various human tissue types for the presence of SV-40 T-antigen DNA sequences.

Both Vilchez et al. and Shivapurkar et al. reached similar conclusions, reporting that SV-40 T-antigen DNA sequences could be detected in 42% and 43% of non-Hodgkin's lymphoma samples, respectively. Viral DNA was only found in a small percentage of Hodgkin's lymphoma, breast or colon cancer samples, and was not observed in lymphoid tissue that was taken from people without cancer. Both groups detected viral DNA most frequently in diffuse large B-cell lymphoma samples, indicating that mature B cells might be more susceptible than precursors to the transforming ability of SV-40.

The main source of known human exposure to SV-40 occurred between 1955 and 1963, when millions of Americans were immunized with SV-40-contaminated polio vaccines. The vaccine was prepared from kidney cells of rhesus monkeys that were naturally infected with the virus, which was unknown at the time. Five of the SV-40-positive non-Hodgkin's lymphoma patients in the study of Vilchez et al. were born after the contaminated poliovirus vaccine was administered, indicating other mechanisms of viral transmission.

SV-40 has previously been associated with solid cancers in humans, including brain tumours, osteosarcomas and malignant mesotheliomas. As it is unlikely that the presence of SV-40 T-antigen alone is sufficient to induce cancer, further work is required to determine exactly how this protein fits in the cascade of transformation events.