Non-Hodgkin lymphoma comprises a biologically diverse group of blood malignancies with clinical courses ranging from indolent to highly aggressive. During the past 30 years, the reported incidence and death rate of the disease have increased strikingly, nearly doubling since 1970.

About 55 000 new cases of non-Hodgkin lymphoma are estimated to be diagnosed annually in the USA

Deaths related to the disorder are ranked fourth and fifth among all cancer deaths in women and men, respectively. Although the reasons for the increase in incidence are not fully understood, a substantial number of cases of non-Hodgkin lymphoma are linked to the HIV-1 epidemic. Indeed, non-Hodgkin lymphoma is a common malignancy in HIV-1-infected patients and the incidence can be up to 300 times higher than in HIV-1-negative individuals.

No obvious risk factors have emerged for non-Hodgkin lymphoma in the general population, but a viral cause has been postulated. Some cases of non-Hodgkin lymphoma in HIV-1-infected patients have been attributed to deficient immune surveillance of oncogenic herpesviruses, such as Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8), or perhaps to chronic antigenic stimulation and defective immune regulation.

The small DNA-containing polio viruses (simian virus 40 [SV40], JC virus, and BK virus) are known to infect human beings, to have cancer causing potential, and to be associated with some human cancers. SV40 DNA sequences have been found repeatedly in some brain and bone cancers and mesotheliomas.

Polio viruses are known to induce tumor formation in animals, including the production of B-cell lymphomas by SV40. The major types of tumors induced by SV40 in laboratory animals are the same as the human cancers found to contain SV40 DNA, with the exception of lymphomas.

Studies have reported the detection of SV40 DNA sequences in non-Hodgkin lymphoma from HIV-1-infected and HIV-1-uninfected patients.

These findings suggest a possible role for polio viruses in lymphoproliferative disorders, but the small size of the study populations.

This study showed that polio virus SV40 T antigen DNA sequences are significantly associated with non-Hodgkin lymphoma in HIV-1-infected and HIV-1-uninfected patients. This finding sheds new light on the possible cause of an important group of malignant disorders.

Overall, 42% of non-Hodgkin lymphomas tested here contained SV40 DNA sequences -- a frequency similar to that found in an independent study (43%).

The cancer causing potential of polio virus SV40 has been established in laboratory animals. In studies in which hamsters were inoculated intravenously with SV40, lymphomas developed among 72% of the animals in the inoculated group and none of the control group.

Polio virus SV40 has been associated with specific types of solid cancers in human beings, including brain tumors, osteosarcomas, and malignant mesotheliomas. These are the types of malignant disorders caused by the virus in laboratory animals -- a finding that emphasizes the predictive value of the animal studies. Recent reports provide persuasive evidence that the presence of polio virus SV40 is meaningful in the development of those human cancers.

The major source of known human exposure to polio virus SV40 was immunization with SV40-contaminated polio vaccines.

Inactivated and live, attenuated forms of the polio vaccine were prepared in primary rhesus monkey kidney cells, some of which were from animals naturally infected with SV40 -- a virus that was unknown at the time. Studies showed that residual infectious SV40 survived the vaccine inactivation treatments, and millions of people were inadvertently exposed to live SV40 from 1955 until early 1963

In the USA, vaccine lots received by about 20 states are estimated to have contained 075-097 mL contaminated vaccine per child, lots from about 15 states were thought to have contained 001-074 ml contaminated vaccine per child, and about 15 states were believed to have received lots that were free from SV40.

The Lancet March 9, 2002