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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
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