Vaccine
Safety > Issues of Interest > Cancer
Simian
Virus 40 (SV40), Polio Vaccine, and Cancer
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At
a glance:
SV40
is a virus found in some species of monkey.
Soon after its discovery in 1960, SV40
was found in polio vaccine.
Over 98 million Americans received
one or more doses of polio vaccine during
the period (1955-1963) when some of the
vaccine was contaminated with SV40. SV40
has been found in certain types of human
cancers, but it has not been determined
that SV40 causes these cancers. The majority
of evidence suggests there is no causal
relationship between receipt of SV40-contaminated
vaccine and cancer; however, some research
results are conflicting and more studies
are needed. |
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Contents
of this page:
- What is SV40?
- Why is there so much
interest in SV40?
- Does polio vaccine
being given in the U.S. today contain SV40?
- What about concerns
that the testing methods used to screen oral polio vaccines could
have missed certain strains of SV40?
- Who received SV40 contaminated
polio vaccine?
- Were any other people
in the U.S. possibly exposed to SV40-contaminated vaccines?
- Is receiving contaminated
vaccine the only way to become infected with SV40? Does it spread
from person-to-person?
- SV40 is known to cause
tumors in rodents. Have research studies found an association
between SV40 and cancer in humans?
- What steps have been
taken by the government to see if SV40-contaminated vaccines affected
people's health?
- What has research
found regarding the health affects of receiving SV40-contaminated
vaccine? Has there been an increase in cancer among people who
received SV40-contaminated polio vaccine?
- Have research studies
looked at the risk of cancer in children whose mothers received
SV40-contaminated polio vaccine?
- If I have one of these
cancers does it mean that SV40 caused it?
- Can I obtain a test
to see if I am infected with SV40?
- What should I do if
I received polio vaccine during 1955-1963?
- Where can I get more
information about SV40?
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What
is SV40?
Simian
virus 40, or SV40, was discovered in 1960. It occurs naturally in
some species of monkeys, though it does not typically cause symptoms
or illness except in cases where the animal has chronic problems
with its immune system (Shah and Nathanson, 1976). In those cases,
the animals develop lesions associated with SV40 in their kidneys
and brains (Newman et al., 1998).
SV40
is not related to HIV, the virus that causes AIDS in humans, or
to simian immunodeficiency virus (SIV), the virus that causes an
AIDS-like disease in some monkey species.
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Why
is there so much interest in
SV40?
Soon
after its discovery in 1960, SV40 was identified in polio vaccine.
It was found in the injected form of the vaccine (IPV), not the
kind given by mouth (OPV). At that time, rhesus monkey kidney cells,
which contain SV40 if the animal is infected, were used in preparing
viral vaccines. Because SV40 was not discovered until 1960, no one
was aware that polio vaccine made in the 1950s could be contaminated.
In 1961, the virus was found to cause tumors in rodents (Eddy et
al., 1961). That same year, the federal government required that
new stocks of polio vaccine be free of SV40. However, existing polio
vaccine stocks were not recalled and were used until 1963. When
SV40 was discovered, researchers did not know if the virus could
negatively affect people's health. Many viruses that harm animals
have no effect on people because of the biological differences between
animals and humans.
Interest
in SV40 has increased in the last several years because the virus
was found in certain forms of cancer in humans, for instance mesotheliomas
(rare tumors located in the lungs), brain, and bone tumors (Carbone
et al., 1994; Jasani et al., 2001). More recently, SV40 has also
been found to be associated with some types of non-Hodgkin's lymphoma
(Shivapurkar et al., 2002; Vilchez et al., 2002).
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Does
polio vaccine being given in the
U.S. today contain SV40?
No,
polio vaccines being used today do not contain SV40.
- SV40
was completely removed from the seed strains of the vaccine
viruses in the early 1960s.
- The polio vaccine currently
used in the U.S. (inactivated polio vaccine, or IPV) is no longer
prepared in primary rhesus monkey kidney cells. It is produced
in human or African green monkey cell lines that have been extensively
tested for contaminants, including SV40.
- The poliovirus used in IPV is
killed with formaldehyde. This procedure also kills viral contaminants,
such as SV40. Formaldehyde was also used in the SV40-contaminated
vaccine, but in 1961 researchers found that the process killed
99.99% of SV40 and 1 in 10,000 SV40 particles survived (Hilleman,
1998).
- Today’s testing methods are
better. Any live SV40 would be detected by these methods.
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- What
about concerns that the testing methods used to screen oral polio
vaccines could have missed certain strains of SV40?
Oral
polio vaccine (OPV, which is no longer recommended for use in the
U.S. but is used elsewhere in the world) differs from IPV because
it contains weakened, rather than killed, poliovirus. Because it
is a live vaccine, formaldehyde or other inactivation agents were
not used in producing OPV. The poliovirus that was used to produce
OPV was grown on monkey kidney cells. Screening for SV40 in the
monkey kidney cells used to produce OPV was implemented in the early
1960s after the virus was first discovered. Manufacturers also treated
the stocks of weakened poliovirus in order to remove any SV40 that
might have been present in them.
A
study (Rizzo et al., 1999) raised concern that some lots of OPV
may have been contaminated with a slow-growing SV40 strain that
would not have been detected with the methods used to test it. However,
this study did not follow the actual testing protocol used to ensure
that vaccine is free of SV40. Subsequent studies (Minor et al.,
2001) confirmed studies from the early 1960s (Melnick) showing that
the testing methods used were sufficient to detect even slower-growing
strains of SV40. In addition, researchers from the FDA used the
very sensitive polymerase chain reaction (PCR) methodology to search
for SV40 DNA in OPV manufactured in the U.S. between 1972 and 1996
(the FDA only tested vaccines produced as far back as 1972, because
there were no existing lots of OPV at FDA that were produced between
1962 and 1972). SV40 DNA sequences were not found in any of the
vaccine lots tested (Sierra Honigmann & Krause, 2000). OPV is
no longer produced in the U.S.; if production were to be resumed,
it would continue to be under extremely strict conditions that eliminate
the possibility of any contamination with SV40.
- Who
received SV40 contaminated polio
vaccine in the U.S.?
Over
98 million Americans received one or more doses of IPV (the injected
form of the polio vaccine) during the period (1955-1963) when some
of the vaccine was contaminated with SV40. However, not all doses
of IPV were contaminated. It has been estimated that 10-30 million
of the 98 million people who received a polio shot actually received
a vaccine that contained SV40 (Shah and Nathanson, 1976). In addition,
about 10,000 volunteers who received an experimental oral polio
vaccine (OPV) between 1959-1961 may have been exposed to SV40 (the
vaccine was later licensed in 1963, subsequent to SV40 removal from
the seed stock). All of the evidence to date indicates that after
1963, all vaccines on the U.S. market were free of SV40.
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Were
any other people in the United States possibly exposed to SV40-contaminated
vaccines?
Yes.
SV40 was a contaminant of respiratory syncytial virus given to a
few volunteers in an experimental study of infection with the live
virus (Shah and Nathanson, 1976). In addition, SV40 was also found
in adenovirus vaccines given to more than 100,000 young men in army
camps in the 1950s and 1960s to protect them from respiratory infections
(Sherwood et al., 1961).
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Is
receiving contaminated vaccine the only way to become infected
with SV40? Does it spread from person-to-person?
Receiving
contaminated vaccine is not the only way to become infected with
SV40. Data suggest that SV40 has infected a small percentage of
the human population independently of the polio vaccine. A study
of German medical students found that 12% had SV40 antibodies in
1952, before the introduction of the polio vaccine (Geissler et
al., 1985). Moreover, SV40 has been identified in people born in
the 1980's and 1990's, well after the elimination of SV40 contamination
from polio vaccines. This has led some to consider that the virus
may spread from person-to-person. Some laboratory workers may have
been exposed to SV40 (Horvath, 1965). It is not known whether people
who live in countries with wild rhesus monkeys also could be exposed
to SV40. Exactly how SV40 is transmitted among humans and how common
it is among people in the U.S. population are unknown.
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SV40
is known to cause tumors in rodents.
Have research studies found an association between SV40 and
cancer in humans?
Yes.
An association has been found between SV40 and certain types of
cancer in humans. However, though the virus or its DNA have been
found in certain types of cancer, it has not been determined that
SV40 causes these cancers. Finding that two events are "associated"
is not the same as establishing that one event caused the other.
SV40
was linked with mesothelioma after tumors developed in hamsters
that were injected with SV40 into the lungs, heart and abdomen (Cicala
et al., 1993). Mesotheliomas are rare cancers usually located in
the lining of the lungs in humans and are associated with asbestos
exposure. SV40 has been found in 47% to 83% of human mesothelioma
tumors (Carbone, 1999). In addition, reports have documented an
association between SV40 and brain and bone tumors (Jasani, 2001).
Two
recent studies also found an association between SV40 and non-Hodgkin's
lymphoma (Shivapurkar et al., 2002; Vilchez et al., 2002). These
studies identified the virus in 42-43 percent of non-Hodgkin's tumors,
while finding no SV40 in tissue from healthy study volunteers. Lymphoma
is a general word for cancers that develop in the lymphatic system
– the tissues and organs that produce, store and carry white blood
cells that fight infection and other diseases. Hodgkin’s disease
is one type of lymphoma; all others are called non-Hodgkin’s lymphoma.
Lymphomas account for about 5 percent of all cases of cancer in
this country (http://www.nci.nih.gov).
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What
steps have been taken by the government
to see if SV40-contaminated vaccines affected people's health?
When SV40
was discovered in 1960, researchers did not know if the virus could
negatively affect health. Many viruses that harm animals have no
effect on people because of the biological differences between animals
and humans. However, to investigate the possibility, several federally
funded studies were carried out during the 1960s, 1970s and 1980s
to follow persons who received polio vaccines (the results from
some of these studies are discussed below). In addition, on January
27-28, 1997, the U.S. Food and Drug Administration, the Centers
for Disease Control and Prevention, the National Institutes of Health,
and the National Vaccine Program Office sponsored an open public
meeting with scientists and physicians to discuss research findings
on SV40. At the meeting they discussed available data and determined
that further research into the field of SV40 was needed (Brown &
Lewis, 1998). To learn how to order the proceedings of this meeting,
go to:
http://www.karger.ch/bookseries/debis/debis094.htm
In
2001, the Centers for Disease Control and Prevention
(CDC) and the National Institutes of Health
(NIH) asked the National Academy of Sciences'
Institute of Medicine (IOM) to establish an
independent expert committee to review hypotheses
about existing and emerging immunization safety
concerns. These reviews involve an assessment
of factors such as the biologic mechanisms
of the hypothesis, alternative hypotheses,
as well as the available scientific evidence
to date. In 2002, the IOM Immunization Safety
Review Committee examined the existing scientific
data on SV40-contaminated polio vaccine and
cancer.
The
committee did not recommend review of the current
polio vaccine recommendations on the basis
of concerns about cancer risks, because the
vaccine in current use is free of SV40. However,
the committee recommended development of sensitive
and specific blood tests for SV40 and techniques
for SV40 detection. When this has been done,
the committee recommends that pre-1955 samples
of human tissue be tested for SV40. They also
recommended further study into how SV40 may
spread among humans, and argued that additional
studies of people who may have received contaminated
vaccine should not be done until technical
(laboratory) issues are resolved. The entire
IOM report on SV40 Contamination of Polio Vaccine
and Cancer at http://www.iom.edu/report.asp?id=4317
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What
has research found regarding the
health affects of receiving SV40-contaminated vaccine? Has there
been an increase in cancer among people who received SV40-contaminated
polio vaccine?
The
majority of evidence suggests there is no causal relationship between
receipt of SV40-contaminated polio vaccine and cancer development;
however, some research results in this area are conflicting and
more studies are needed.
Since
the discovery of SV40, several studies have been done to compare
cancer rates in groups of individuals known or strongly presumed
to have received SV40-contaminated polio vaccine to rates in persons
known or strongly presumed not to have received SV40-contaminated
vaccine. A brief description of some of these studies follows:
- Two studies (De Rienzo et al.,
2002; Emri et al., 2000) examined mesothelioma tissue from a
small number of patients in Turkey, where SV40-contaminated
vaccines were not used, and found no SV40. The researchers also
examined mesothelioma tissue from a small number of patients
in the US and Italy, where SV40-contaminated polio vaccines
were used, and found SV40 in some of the specimens.
- In 1999, Fisher and colleagues
reported increased rates of ependymomas, osteogenic sarcomas,
other bone tumors, and mesotheliomas among people who were potentially
exposed to SV40-contaminated polio vaccine. However, the number
of cases in this study was too small to draw any statistically
valid conclusions.
- In 1998, the National Cancer
Institute published findings from a study (Strickler et al.,
1998) that revealed that, after 30 years, there was no increased
incidence of cancer in persons who may have received vaccine
containing SV40. The study used the National Cancer Institute's
SEER database, which contains information on more than 2.5 million
cancer cases in the U.S., and the Connecticut Tumor Registry,
and included millions of people exposed to contaminated poliovirus
vaccine and decades of cancer incidence and mortality data.
Comparisons of the rates of cancer were made between persons
who had received SV40-contaminated vaccine as infants born in
1956-1962 and persons born in 1947-1952 and 1964-1969. This
study looked specifically for types of rare cancers that have
been found to contain SV40 in recent cellular research (Carbone
et al., 1994) and found no significant increased incidence compared
with persons who had not received contaminated SV40 vaccine.
The rare cancers included ependymomas (cancer of cells found
in developing fetal neural tubes from which the brain and spinal
cord arise as a baby develops), osteosarcomas (a type of bone
cancer), mesotheliomas (a type of cancer that originates in
the tissue lining of the lung cavity) and brain cancers.
- Olin et al. (1998), conducted
a long-term follow-up study of 700,000 people in Sweden who
received polio vaccine potentially contaminated with SV40 in
1957 as school-age children. Their results revealed no increased
cancer incidence between persons who received vaccine containing
SV40 and those who did not.
- Geissler (1988) analyzed German
National Cancer Registry data to compare the incidence of cancer
in 885,783 persons born between 1959-1961 who received polio
vaccine that may have been contaminated with SV40 and compared
it with 891,321 persons born between 1962-1964 who received
SV40 free vaccine. These data demonstrated that persons who
received polio vaccine possibly contaminated with SV40 did not
develop more tumors within a 20-year period than did those who
received vaccine that did not contain SV40.
- Mortimer (1981) studied cancer
deaths of 1073 persons born between 1960-1962 who received oral
poliovirus or inactivated poliovirus vaccine that contained
SV40 when newborn. The follow-up study over 17-19 years revealed
no increased number of deaths from cancer. In 2001, a thirty-five
year follow-up study of this group was published. The study
found no deaths in the group due to tumors of the type that
have been associated with SV40 (Carroll-Pankhurst, 2001).
- Fraumeni et al. (1970) followed
1000 persons who had received SV40 contaminated poliovirus vaccine
within a few days after birth. The majority of these people
received the SV40-contaminated oral vaccine. At eight years
of age, no cancer deaths were identified in the exposed group.
- Fraumeni et al. (1963) focused
on a cohort of children age 6-8 years who received inactivated
poliovirus vaccine in 1955. A comparison was made based on whether
children received vaccine with high, low or no detectable amount
of SV40 contamination. Mortality rates from leukemia and all
other cancers from 1950-1959 were compared across the three
groups. No differences in cancer rates were found for this period.
In
summary, the majority of studies in the U.S. and Europe that compare
persons known or strongly presumed to have received SV40-contaminated
polio vaccine with those known or strongly presumed not to have
received SV40- contaminated polio vaccine have not shown a causal
relationship between receipt of SV40-contaminated polio vaccine
and cancer. It should be noted, however, that SV40 infection has
been found in persons who did not receive SV40-contaminated polio
vaccine and that for some study participants it cannot be known
with certainty whether or not they received SV40-contaminated vaccine.
Because of this, there may be errors in these studies that make
it harder to detect a true increased cancer risk associated with
receipt of SV40-contaminated polio vaccine. In addition, research
is needed that focuses on the long-term consequences of SV40 exposure,
as some cancers like mesotheliomas typically occur later in life
and would not have been detected in several of the studies described
above. Moreover, additional studies are needed which focus on the
potential long-term effect of SV40 exposure on health outcomes other
than cancer (Strickler and Goedert, 1998). Because the CDC takes
this issue very seriously, the agency has asked an expert committee
(described in question 9) to review the existing data on this topic
and provide recommendations for future research.
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Have
research studies looked at the
risk of cancer in children whose mothers received SV40-contaminated
polio vaccine?
Yes,
two studies concerning maternal vaccination with SV40-contaminated
vaccines and risk of cancer in offspring have been conducted. Each
study reported an association.
- Heinonen et al. (1973) reported
a higher incidence of neural malignancies in children born to
mothers who received inactivated poliovirus during pregnancy.
The prospective study of over 50,000 women who were pregnant
between 1959-1965 identified 24 malignancies in their children
during the first 4 years of life. The rate of malignancy was
about two-fold greater in children born to mothers immunized
during pregnancy when compared with children born to unimmunized
mothers or mothers who received influenza or OPV vaccines. Neural
tumors accounted for most of the difference.
- Farwell et al. (1979) found
that of 15 cases of medulloblastoma in children born in Connecticut
between 1956-1962, 10 were born to mothers exposed to SV40 contaminated
polio vaccine while 5 were born to mothers unexposed. Interpretation
of these results, however, is hampered by the low response rates
and uncertain accuracy of vaccination histories by obstetricians
(Strickler et al., 1998).
Additional
studies are needed that focus on maternal vaccination with SV40-contaminated
vaccines and risk of cancer and other health effects in offspring.
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If
I have one of these cancers does
it mean that SV40 caused it?
No.
The possible role of SV40 in human cancers is not fully understood
and is the topic of continued research.
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Can
I obtain a test to see if I am
infected with SV40?
Blood
tests can identify if a person has antibodies to SV40, but there
is no test for SV40 commercially available at this time.
Research
laboratories are currently refining the techniques used to detect
SV40. PCR (polymerase chain reaction) assays are currently in use
to detect SV40 DNA segments. Because of inconsistent results between
laboratories, there is a need to develop a standard PCR assay (Levine
et al., 1998).
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What
should I do if I received polio vaccine during 1955- 1963?
There
are no recommended treatments or tests for persons that may have
been exposed to SV40. If you have concerns about your health, please
make an appointment to see your health care provider.
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Where
can I get more information about
SV40?
The
Food and Drug Administration has been the federal government lead
agency in answering questions relating to SV40 in polio vaccine.
You may call the FDA at the following number: 1-800-835-4709.
Top
Brown F, Lewis AM (eds): Simian virus
40 (SV40): A possible human polyomavirus. Dev Biol Stand. Basel,
Karger, 1998, vol 94.
Carbone M, Pass HI, Rizzo P, Marinetti
M, Di Muzio M, Mew DJ, Levine AS, Procopio A. Simian virus 40-like
DNA sequences in human pleural mesothelioma. Oncogene 1994, 9:1781-90.
Carbone M. Simian virus 40 and human
tumors: It is time to study mechanisms. J Cellular Biochemistry
1999, 76: 189-93.
Carroll-Pankhurst C, Engels EA, Strickler
HD, Goedert JJ, Wagner J, Mortimer EA. Thirty-five year mortality
following receipt of SV40-contaminated polio vaccine during the
neonatal period. Br J Cancer 2001, 85(9):1295-7.
Cicala C, Pompetti, Carbone M. SV40
induces mesotheliomas in hamsters. Am J Pathology 1993, 142:1524-33.
De Rienzo A, Tor M, Sterman DH, Aksoy
F, Albelda SM, Testa JR. Detection of SV40 DNA sequences in malignant
mesothelioma specimens from the United States, but not from Turkey.
J Cell Biochem 2002; 84(3):455-9.
Eddy BE, Borman GS, Berkeley W, Young
RD. Tumors induced in hamsters by injection of rhesus monkey kidney
cell extracts. Proc. Soc. Exp. Biol. (NY) 1961, 107:191-197.
Emri S, Kocagoz T, Olut A, Gungen
Y, Mutti L, Baris YI. Simian virus 40 is not a cofactor in the pathogenesis
of of environmentally induced malignant pleural mesothelioma in
Turkey. Anticancer Res 2000; 20(2A):891-894.
Farwell JR, Dohrmann GJ, Marrett
LD, Meigs JW. Effect of SV40 virus contaminated polio vaccine on
the incidence and type of CNS neoplasms in children: a population
based study. Trans Am Neurol Assoc 1979, 104:261-264.
Fisher SG, Weber L, Carbone M. Cancer
risk associated with simian virus 40 contaminated polio vaccine.
Anticancer Res 1999, 19(3B):2173-2180.
Fraumeni JF, Ederer F, Miller RW.
An evaluation of the carcinogenicity of simian virus 40 in man.
J Am Med Assoc 1963, 185:713-718.
Fraumeni JF, Stark CR, Gold E et
al. Simian virus 40 in polio vaccine: follow up of newborn recipients.
Science 1970, 167:59-60.
Geissler E, Konzer P, Scherneck S,
Zimmermann W. Sera collected before introduction of contaminated
polio vaccine contain antibodies against SV40. Acta Virologica 1985,
29:420-23.
Geissler E, Staneczek. W. SV40 and
human brain tumors. Archive fur Geschwulstforschung 1988, 58:129-134.
Heinonen OP, Shaprio S, Monson R
et al. Immunization during pregnancy against poliomyelitis and influenza
in relation to childhood malignancy. Int J Epidemiol 1973, 2:229-235.
Horvath LB, Incidence of SV40 virus
neutralizing antibodies in sera of laboratory workers. Acta Microbiol
Acad Sci Hung 1965;12(2):201-5.
Jasani B, Cristaudo A, Emri SA, et
al. Association of SV40 with human tumors. Semin Cancer Biol 2001,
11:49-61.
Levine A, Butel J, Dorries K, Goedert
J, Frisque R, Garcea R, Morris A, O’Neill F, Shah K. SV40 as a putative
human commensal. Developments in Biological Standardization 1998,
94:245-69.
Minor PD, Dunn G, Piplin PA. Detection
and growth kinetics of SV40 preparations with different enhancer
element copy number. Vaccine 2001 May 14;19(25-26):3457-71.
Mortimer EA, Lepow ML, Gold E, et
al. Long-term Follow-up of persons inadvertently inoculated with
SV40 as neonates. Medical Intelligence 1981, 305:1517-1518.
Newman JS, Baskin GB, Frisque RJ.
Identification of SV40 in brain, kidney and urine of healthy and
SIV-infected rhesus monkeys. J NeuroVirology 1998; 4:394-406.
Olin P, Giesecke J. Potential exposure
to SV40 in polio vaccines used in Sweden during 1957: no impact
on cancer incidence rates 1960 to 1993. Dev Biol Stand. 1998, 94:227-33.
Rizzo P, Resta ID, Powers A, Ratner
H, Carbone M. Unique strains of SV40 in commercial poliovaccines
from 1955 not readily identifiable with current testing for SV40
infection. Cancer Research 1999;59:6103-6108.
Shah K, Nathanson N. Human exposure
to SV40: Reviews and Comment.. Am J Epidemiol 1976, 103:11-12.
Sherwood RW, Buescher EL, Nitz RE
et al. Effects of adenovirus vaccine in acute respiratory disease
in US Army recruits. JAMA 1961, 178:1125-1127.
Shivapurkar N, Harada K, Reddy J,
Scheuermann RH, Xu Y, et al. Presence of simian virus 40 DNA sequences
in human lymphomas. Lancet 2002 359:851-852.
Sierra Honigmann A, Krause PR. Live
oral poliovirus vaccines do not contain detectable simian virus
40 (SV40) DNA. Biologicals 2000, 28(1):1-4.
Strickler HD, Rosenberg PS, Devesa
SS, Hertel J, Fraumeni JF, Goedert JJ. Contamination of poliovirus
vaccines with simian virus 40 (1955-1963) and subsequent cancer
rates. JAMA, January 28, 1998; 279(4):292-295.
Strickler HD, Goedert JJ. Exposure
to S40 contaminated poliovirus vaccine and the risk of cancer-A
review of the epidemiological evidence. In F Brown and AM Lewis
(eds.) Simian Virus 40 (SV40): A possible human polyomavirus. Dev
Bio Stand Basel Karger 1998, 94:235-244.
Vilchez RA, Madden CR, Kozinetz CA,
Halvorson SJ, et al. Association between simian virus 40 and non-Hodgkin
lymphoma. Lancet 2002, 359: 817-823.
Zimmermann W, Scherneck S, Geissler
E. Quantitative determination of papovavirus IgG antibodies in sera
from cancer patients, labworkers and several groups of control persons
by enzyme-linked immunosorbent assay (ELISA). Zentralblatt Fur Bakteriologie,
Mikrobiologie Und Hygiene-1-Abt-Originale A, Medizinische Mikrobiologie,
Infektionskrankheiten Und Parasitologie 1983, 254:187-96.
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