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Immunization Safety Review:
SV40 Contamination of Polio
Vaccine and Cancer
Immunization to protect children and adults from many infectious diseases
is one of the greatest achievements of public health. Immunization is not without
risks, however. It is well established, for example, that some influenza vaccines
have been associated with a risk of Guillain-Barre syndrome and that vaccines
sometimes produce anaphylactic shock. Given the widespread use of vaccines,
state mandates requiring vaccination of children for entry into school, college, or
day care, and the importance of ensuring that trust in immunization programs is
justified, it is essential that safety concerns receive assiduous attention.
The Immunization Safety Review Committee was established by the Insti-
tute of Medicine (IOM) to evaluate the evidence on possible causal associations
between immunizations and certain adverse outcomes, and to then present con-
clusions and recommendations. The committee's mandate also includes assess-
ing the broader significance for society of these immunization safety issues.
In this fifth report in a series, the committee examines the hypothesis that
exposure to polio vaccine contaminated with simian virus 40 (SV40) can cause
certain types of cancer.
THE CHARGE TO THE COMMITTEE
Challenges to the safety of immunizations are prominent in public and sci-
entific debate. Given these persistent and growing concerns about immunization
19
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20
IMMUNIZATION SAFETY REVIEW
safety, the Centers for Disease Control and Prevention (CDC) and the National
Institutes of Health (NIH) recognized the need for an independent, expert group
to address immunization safety in a timely and objective manner. The IOM has
been involved in such issues since the 1 970s. (A brief chronology can be found
in Appendix C.) In 1999, as a result of IOM's previous work and its access to
independent scientific experts, CDC and NIH began a year of discussions with
IOM to develop the Immunization Safety Review project, which addressed both
emerging and existing vaccine safety issues.
The Immunization Safety Review Committee is responsible for examining a
broad variety of immunization safety concerns. Committee members have ex-
pertise in pediatrics, neurology, immunology, internal medicine, infectious dis-
eases, genetics, epidemiology, biostatistics, risk perception and communication,
decision analysis, public health, nursing, and ethics. While all the committee
members share the view that immunization is generally beneficial, none of them
has a vested interest in the specific immunization safety issues that come before
the group. Additional discussion of the committee composition can be found in
the Foreword written by Dr. Harvey Fineberg, President of the IOM.
The committee is charged with examining three ionization safety hy-
potheses each year during the three-year study period (2001-2003~. These hy-
potheses are selected by the Interagency Vaccine Group, whose members repre-
sent several units of the Department of Health and Human Services (DHHS)-
the National Vaccine Program Office, the National Immunization Program, and
the National Center for Infectious Diseases at the CDC, the National Institute for
Allergy and Infectious Diseases at the NIH, the Food and Drug Administration
(FDA), the National Vaccine Injury Compensation Program at the Health Re-
sources and Services Administration (HRSA), and the Centers for Medicare and
Medicaid Services (CMS, formerly the Health Care Financing Administration),
as well as the Department of Defense and the Agency for International Devel-
opment.
For each topic, the Immunization Safety Review Committee reviews rele-
vant literature and submissions by interested parties, holds an open scientific
meeting, and directly follows the open meeting with a 1- to 2-day closed meet-
ing to formulate its conclusions and recommendations. The committee's find-
ings are released to the public in a brief consensus report 60 to 90 days after its
meeting.
The committee is charged with assessing both the scientific evidence re-
garding the hypotheses under review and the significance of the issues for soci-
ety.
· The scientific c assessment has two components: an examination of the epi-
demiologic and clinical evidence regarding a possible causal relationship
between exposure to the vaccine and the adverse event, and an examination
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S V4 0 CONTAMINA TION OF POLIO VA CCINE AND CA NCER
21
of theory and experimental evidence from human or animal studies regard-
ing biological mechanisms that might be relevant to the hypothesis.
The significance assessment addresses such considerations as the burden of
the health risks associated with the vaccine-preventable disease and with the
adverse event. Other considerations may include the perceived intensity of
public or professional concern, or the feasibility of additional research to
help resolve scientific uncertainty regarding causal associations.
The findings of the scientific and significance assessments provide the basis
for the co~ttee's recommendations regarding the public health response to
the issue. In particular, the committee addresses needs for a review of immuni-
zation policy, for current and future research, and for effective communication
strategies. See Figure 1 for a schematic representation of the committee's
charge.
=;~ ~ Clinical ~ Theory|
~ Duaa ~ ~ Data |
41 1~11~ 41
, , Event (3) Preventable
\ / \ / Diseases(3)
Evidence Base \ / \ / \
~ \\ _ f _ _ _ _ ~ ~ _ _ _/_ ~
' ~ , ~ ~ , ~
Causality ~ ~ I Biolo 3ical Mechanisms I
9~t ' /
Conclusions I Scientific Assessment
/
I
| The Public |
/
/
Significance ~~3
1
Public I lealih Response:
Figure 1: Committee Charge
1 Policy 1 j:3 [I=
Recommendations ~ / \ ~
Recommendations tor tYetion
1) in vitro; animal; Herman
2) wild~type disease; estal>lished pati~ophysiological pathways
3) indiv~'al; societal
THE STUDY PROCESS
The committee held an initial organizational meeting in January 2001. CDC
and NIH presented the committee's charge at the meeting, and the committee
conducted a general review of immunization safety concerns. At this initial
meeting, the committee also determined the basic methodology to be used for
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IMMUNIZATION SAFETY REVIEW
assessing causality for the hypotheses to be considered at subsequent meetings.
A website (www.iom.eduJimsafety) and a listserv were created to provide public
access to information about the committee's work and to facilitate communica-
tion with the committee. The conclusions and recommendations of the commit-
tee's previous reports (see Box 1) are summarized in Appendix A.
For its evaluation of the hypothesis on SV40-contaminated polio vac-
cine and cancer, the committee held an open scientific meeting in July 2002 (see
Appendix B) to hear presentations on issues germane to the topic. The presenta-
tions to the committee at the open meeting are available in electronic form (au-
dio files and slides) on the project website (www.iom.edu/imsafety). In addition,
the committee reviewed an extensive collection of material, primarily from the
published, peer-reviewed scientific and medical literature. A list of the materials
reviewed by the committee, including many items not cited in this report, can be
found on the project's website.
THE FRAMEWORK FOR SCIENTIFIC ASSESSMENT
Causality
The Immunization Safety Review Committee has adopted the framework
for assessing causality developed by previous IOM committees (IOM, 1991,
1994), convened under the congressional mandate of P.L. 99-660 to address
questions of immunization safety. The categories of causal conclusions used by
the committee are as follows:
1. No evidence
2. Evidence is inadequate to accept or reject a causal relationship
3. Evidence favors rejection of a causal relationship
4. Evidence favors acceptance of a causal relationship
5. Evidence establishes a causal relationship.
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SV40 CONTAMINATION OF POLIO VACCINE AND CANCER
23
Assessments begin from a position of neutrality regarding the specific vac-
cine safety hypothesis under review. That is, there is no presumption that a spe-
cific vaccine (or vaccine component) does or does not cause the adverse event in
question. The weight of the available clinical and epidemiologic evidence de-
termines whether it is possible to shift from that neutral position to a finding for
causality ("the evidence favors acceptance of a causal relationship") or against
causality ("the evidence favors rejection of a causal relationship". The commit-
tee does not conclude that the vaccine does not cause the adverse event merely if
the evidence is inadequate to support causality. Instead, it maintains a neutral
position, concluding that the "evidence is inadequate to accept or reject a causal
relationship."
Although no firm rules establish the amount of evidence or the quality of
the evidence required to support a specific category of causality conclusion, the
committee uses standard epidemiologic criteria to guide its decisions. The most
definitive category is "establishes causality," which is reserved for those rela-
tionships where the causal link is unequivocal, as with the oral polio vaccine and
vaccine-associated paralytic polio or with anaphylactic reactions to vaccine ad-
ministration. The next category, "favors acceptance" of a causal relationship,
reflects evidence that is strong and generally convincing, although not firm
enough to be described as unequivocal or established. "Favors rejection" is the
strongest category in the negative direction. The category of "establishes no
causal relationship" is not used because it is virtually impossible to prove the
absence of a relationship with the same surety that is possible in establishing its
presence.
If the evidence is not reasonably convincing either in support of or against
causality, the category "inadequate to accept or reject a causal relationship" is
used. Evidence that is sparse, conflicting, of weak quality, or merely suggestive
either toward or away from causality falls into this category. Some authors of
similar assessments use phrases such as "the evidence does not presently support
a causal association." The committee believes, however, that such language does
not make the important distinction between evidence indicating that a relation-
ship does not exist (category 3) and evidence that is indeterminate with regard to
causality (category 2~. The category of "no evidence" is reserved for those cases
in which there is a complete absence of clinical or epidemiologic evidence.
The sources of evidence considered by the committee in its scientific as-
sessment of causality include epidemiologic and clinical studies directly ad-
dressing the question at hand. That is, the data are specifically related to the ef-
fects of the vaccines under review and the adverse health outcomes) under
review in the case of this report, the effects of SV40 contamination of the po-
lio vaccine and the risk for certain types of cancer.
Epidemiologic studies carry the most weight in a causality assessment.
These studies measure health-related exposures and outcomes in a defined set of
subjects and make inferences about the nature and strength of associations be-
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IMMUNIZATION SAFETY REVIEW
tween exposures and outcomes in the overall population from which the study
sample was drawn. Epidemiologic studies can be categorized as observational or
experimental (clinical trial), and as uncontrolled (descriptive) or controlled (ana-
lytic). Among these various study designs, experimental studies generally have
the advantage of random assignment to exposures and are therefore the most
influential in assessing causality. Uncontrolled observational studies are impor-
tant but are generally considered less definitive than controlled studies. In un-
controlled observational studies, where observations are made over time, con-
founding from factors such as changing case definitions or improving case
detection may affect the apparent incidence and prevalence of the adverse out-
comes studied.
By themselves, case reports and case series are generally inadequate to
establish causality. Despite the limitations of case reports, the causality
argument for at least one vaccine-related adverse event (the relationship between
vaccines containing tetanus toxoid and Guillain-Barre syndrome) was
strengthened most by a single, well-documented case report on recurrence of the
adverse event following re-administration of the vaccine, a situation referred to
as a"rechallenge" (IOM, 1994~.
Biological Mechanisms
Evidence considered in the scientific assessment of biological mechanisms
includes human, animal, and in vitro studies related to biological or pathophysi-
ological processes by which immunizations could cause an adverse event. When
other evidence of causality is available, biological data add supportive evidence,
but they cannot prove causality on their own.
This committee is often faced with a set of circumstances in which the epi-
demiologic evidence is judged inadequate to accept or reject a causal association
between a vaccine exposure and an adverse event of concern. It is then left with
the task of examining proposed or conceivable biological mechanisms that
might be operating if an epidemiologically sound association could be shown
between a vaccine exposure and an adverse event.
In any case, the committee's causality assessments must be guided by the
current understanding of biological processes. In fact, the current thinking on a
possible biological explanation for a relationship between immunization and an
adverse event will influence the design of a good epidemiologic analysis. The
essential consideration of"confounders" in epidemiologic studies depends on an
understanding of the biological phenomena that could underlie or explain the
observed statistical relationship. A statistical observation can be considered as
evidence of causality only when important confounders are considered. How-
~ For a discussion of We evolution of the terminology concerning biological mechanisms, see
Me committee's earlier reports (TOM, 2001a,b, 2002a,b).
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SV40 CONTAMINATION OF POLIO VACCINE AND CANCER
25
ever, without evidence of a statistical association or convincing clinical evi-
dence, biological mechanisms cannot be invoked as proof of causality.
The identification of sound biological mechanisms can also influence the
development of an appropriate research agenda and give support for policymak-
ers, who frequently must make decisions without having complete information
regarding causality. In addition, there is often value in investigating and under-
standing possible biological mechanisms even if the available epidemiologic
evidence suggests the absence of a causal association. A review of biological
data could give support to the negative causality assessment, for example, or it
could prompt a reconsideration or further investigation of the epidemiologic
findings. If new epidemiologic studies were to question the existing causality
assessment, the biological data could gain prominence in the new assessments.
The committee has established three general categories of evidence on bio-
logical mechanisms:
1. Theory only. A reasonable mechanism can be hypothesized that is
commensurate with scientific knowledge and that does not contradict known
physical and biological principles, but has not been demonstrated in whole or in
part in humans or in animal models. Postulated mechanisms by which a vaccine
might cause a specific adverse event but for which no coherent theory exists
would not meet the criteria for this category. Thus, "theoretical only" is not a
default category, but one that requires thoughtful and biologically meaningful
suppositions.
2. Experimental evidence that the mechanism operates in animals, in vitro
systems, or humans. Experimental evidence often describes effects on just one
or a few of the steps in the pathological process required for expression of dis-
ease. Showing that multiple components of the theoretical pathways operate in
reasonable experimental models increases confidence that the mechanisms could
possibly result in disease in humans. lathe evidence can be derived under highly
contrived conditions. For example, achieving the results of interest may require
extensive manipulation of the genetics of an animal system, or in vivo or in vitro
exposures to vaccine antigen that are extreme in terms of dose, route, or dura-
tion. Other experimental evidence is derived under less contrived conditions. For
example, a compelling animal or in vitro model exists whereby administration of
a vaccine antigen under conditions similar to human use results in a pathologic
process analogous to a human disease pathology. Mechanistic evidence also
could come from studies in humans, but this is distinct from the evidence (about
incidence of adverse events following immunization) that derives from random-
ized controlled trials or other population-based epidemiologic studies, which
contribute to the causality assessment.
3. Evidence that the mechanism results in known disease in humans. For
example, the wild-type infection causes the adverse health outcome, or another
vaccine has been demonstrated to cause the same adverse outcome by the same
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IMMUNIZATION SAFETY REVIEW
or a similar mechanism. Data from population-based studies of the effects of the
vaccine administration on the occurrence of the adverse outcomes under review
are not considered evidence regarding the biological mechanisms but rather as
evidence regarding causality.
If the committee identifies evidence of biological mechanisms that could be
operational, it will offer a summary judgment of that body of evidence as weak,
moderate, or strong. Although the committee tends to judge biological evidence
in humans as "stronger" than biological evidence from highly contrived animal
models or in vitro systems, the summary judgment of the strength of the evi-
dence also depends on both the quantity (e.g., number of studies or number of
subjects in a study) and quality (e.g., the nature of the experimental system or
study design) of the evidence. Obviously, the conclusions drawn from this re-
view depend on both the specific data and on scientific judgment. To ensure that
its own summary judgment is defensible, the committee intends to be as explicit
as possible regarding the strengths and limitations of the biological data.
Published and Unpublished Data
Published reports carry the most weight in the committee's assessment be-
cause their methods and findings are laid out in enough detail to be assessed.
Furthermore, published works, which undergo a rigorous peer review, are sub-
ject to comment and criticism by the entire scientific community. In general, the
committee cannot rely heavily on unpublished data in making its scientific as-
sessments (regarding either causality or biological mechanisms) because they
usually lack comment and criticism and must therefore be interpreted with cau-
tion. The committee also relies on editorial and peer review procedures to ensure
the disclosure of potential conflicts of interest that might be related to the source
of funding for the research study. Immunization safety studies and other data
reviewed by the committee are funded by a variety of sources, including NIH,
CDC, vaccine manufacturers, research advocacy organizations, or foundations.
The committee does not investigate the source of funding of the published re-
search reports it reviews, nor does the funding source influence the committee's
interpretation of the evidence.
Unpublished data and other reports that have not undergone peer review do
have value, however, and are often considered by the committee. They might be
used, for example, in support of a body of published, peer-reviewed literature
with similar findings. If the committee concluded that the unpublished data were
well described, had been obtained using sound methodology, and presented very
clear results, the committee could report, with sufficient caveats in the discus-
sion, how the unpublished data fit with the entire body of published literature.
Only in extraordinary circumstances, however, could an unpublished study re-
fute a body of published literature.
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SV40 CONTAMINATION OF POLIO VACCINE AND CANCER
27
The Immunization Safety Review Committee's scope of work includes con-
sideration of clinical topics for which high-quality experimental studies are
rarely available. Many other panels making clinical recommendations using
evidence-based methods are able to require that randomized trials be available to
reach strong conclusions. However, the IOM Committee was convened specifi-
cally to assess topics that are of immediate concern and for which data of any
kind may just be emerging. Thus, given the unique nature of this project, the
committee decided that it was important to review and consider as much infor-
mation as possible, including unpublished information. The committee does not
perform primary or secondary analyses of unpublished data, however. In review-
ing unpublished material, the committee applies generally accepted standards for
assessing the quality of scientific evidence, as described above. (All unpublished
data reviewed by the committee and cited in this report are available in the
form reviewed by the committee through the public access files of the Na-
tional Academies. Information about the public access files is available at 202-
334-3543 or www.national-academies.org/publicaccess.)
UNDER REVIEW:
SV40 CONTAMINATION OF POLIO VACCINE AND
CANCER
Polio vaccines were developed to prevent poliomyelitis, a highly contagious
viral disease that was once common worldwide (See Box 2 for the chronology
of polio vaccines used in the United States). Most infections are asymptomatic,
but the most widely recognized form of polio is an infection of the central nerv-
ous system that results in paralysis of the limbs or respiratory muscles. During
the first half of the 20th century, polio was at epidemic levels in the United
States, peaking at more than 20,000 reported cases of paralytic disease in 1952
(CDC, 2000~. Following the introduction of a vaccine against polio in 19552, the
incidence of the disease rapidly declined. By 1965, only 61 paralytic cases were
reported in the United States (CDC, 2002a). In 1994, the entire Western Hemi-
sphere was declared free of indigenous wild poliovirus (CDC, 1994~.
Despite its great value in controlling a devastating disease, polio vaccine is
a source of concern because at least some of the vaccines used between 1955
and 1963, when more than 98 million persons were vaccinated in the United
States, are known to have been contaminated with SV40. SV40 is a polyomavi-
rus that commonly infects certain species of Asian macaques, especially the
rhesus monkey. Other polyomaviruses, which are generally species-specific,
include the BK and JC viruses of humans. Polyomaviruses are a genus of the
papovavirus family of DNA viruses. This family also includes the papillomavi-
2 IPV was licensed and widely distributed in 1955, however exposure to SV40 may have also
occurred in the 1954 field trial of IPV.
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IMMUNIZATION SAFETY RE VIE W
ruses, of which one human papillomavirus (HP V) is causally associated with
cervical cancer.
(Source: IOM, 1996; Office of Technology Assessment, 1979)
SV40 and other polyomaviruses generally produce inapparent infection in
immunocompetent members of their natural host species. SV40 and the closely
related human polyomaviruses BK and JC typically reside in renal epithelial
cells. These viruses can, however, spread to other tissues and produce pathologi-
cal effects in immunocompromised hosts or in non-host species. 1h fact, the
presence of SV40 in polio vaccine produced from macaque kidney cell cultures
was originally identified because of the cytopathological effects of the contami-
nated vaccine in African green monkey kidney cell cultures (Sweet and Hille-
man, 1960~. As another example, the JC virus is known to cause progressive
multi focal leukoencephalopathy in immunocompromised humans .
With continuing controversy about the role of SV40 in human cancers
(Brown and Lewis, 1998; Klein et al., 2002), the Interagency Vaccine Group
asked the Immunization Safety Review Committee to address the question of
whether exposure to the SV40-contaminated polio vaccine causes cancer in hu-
mans. The very abundance of new and emerging literature on the oncogenic
potential of SV40 and its association with certain cancers suggests that it is not
too late to try to resolve the question of whether SV40 contamination of polio
vaccines could cause cancers in humans. Four forms of human cancer—
mesothelioma, osteosarcoma, ependymoma, and non-Hodgkin's lymphoma
(NHL) have been linked to SV40 in animal studies.
Polio Vaccines and SV40
Efforts to develop a vaccine effective against the three distinct types of the
poliovirus began in the 1930s, but progress was hindered by the difficulty of
producing an adequate supply of virus in the laboratory. The development in
1949 of a technique for growing the virus in tissue cultures (Enders et al., 1949)
was soon followed by successful trials of a trivalent killed-virus vaccine. In
1954, 400,000 of 1.8 million children from the United States, Canada, and
Finland actually received the potentially contaminated inactivated poliovirus
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SV40 CONTAMINATION OF POLIO VACCINE AND CANCER
29
vaccine (IPV) developed by Sale and colleagues (Francis et al., 1957~. The vac-
cine was licensed for use in the United States in 1955. Vaccines that used a live
attenuated virus and were administered orally were also developed, initially in a
monovalent form. The trivalent oral poliovirus vaccine (OPV) known as the
Sabin vaccine was licensed in the United States in 1963.
The tissue cultures used to grow poliovirus for these vaccines came from
kidneys of rhesus and cynomolgus macaques.3 In 1960, Sweet and Hilleman
(1960) reported that these tissues could be infected with SV40, a previously un-
known virus that commonly infects rhesus macaques. Soon after its discovery,
SV40 was shown to be able to produce tumors in hamsters and to transform hu-
man cells in culture (Eddy et al., 1961, 1962; Girardi et al., 1962; Koprowski et
al., 1962; Shein and Enders, 1962a,b). Testing confirmed that some of the tissue
cultures used in producing IPV and OPV were contaminated with SV40. In
1961, the U.S. government established requirements for testing to verify that all
new lots of polio vaccine are free of SV40 (Eg en, 2002~. Potentially contami-
nated vaccine from previously approved lots of IPV was not recalled, however,
and might have been used until early 1963.
IPV administered between 1955 and 1963 to about 98 million children and
adults is assumed to be the primary source of human exposure to SV40 in the
United States.4 In addition, experimental lots of OPV contaminated with SV40
was administered to about 10,000 people participating in clinical trials between
1959 and 1961. Recipients of the oral vaccine, in contrast to those receiving
contaminated IPV, did not develop an antibody response to SV40 (as reviewed
in Shah and Nathanson, 1976~. This suggests that IPV, not OPV, resulted in the
infection of humans with SV40. Nonetheless, concerns about the validity, and in
particular the specificity for SV40, of the serologic testing create some uncer-
tainty about this conclusion.
Details of the level and extent of the contamination of IPV are unavailable.
Because the process used to inactivate the poliovirus was less effective against
SV40, IPV could have included killed or live SV40. Furthermore, manufacturers
used different types of cell cultures, and some were less vulnerable to contami-
nation (Shah and Nathanson, 1976~. Tests of stored samples of the vaccine that
had been administered in the United States from May through July in 1955
found various levels of SV40 contamination, with some vaccine showing no
3 Current formulations of IPV and OPV available in the United States are required by the FDA
to be free of SV40. The IPV produced today uses poliovirus grown on Vero cells, a continuous line
of green monkey kidney cells. OPV is no longer produced in the United States, but as the recom-
mended vaccine to control polio outbreaks, a stockpile of OPV is available for these purposes (CDC,
2000). The OPV was produced in the United States in monkeys raised in colonies free from SV40 or
grown in Vero cells and was screened for viruses, including SV40 (Sutter et al., 1999).
4 During the same period, SV40 also contaminated an experimental respiratory syncytial virus
vaccine given to about 100 adults and a licensed adenovirus vaccine given to about 100,000 military
inductees (Shah and Nathanson, 1976).
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IMMUNIZATION SAFETYREVIEW
and where they are operating, some immunization providers do not submit data
(CDC, 2002b). Even with the benefit of registry data, the challenges of tracing
individuals remain. And in their current form, immunization registries do not
capture information on vaccine given to adolescents or adults.
Research
The committee notes that data are accumulating rapidly on many fronts on
the potential for viruses to cause cancers in humans, particularly if exposure is
early in life. The committee supports continued research in viral oncogenesis
broadly, independent of the question of SV40-contamination of polio vaccine.
However, the research recommendations are focused specifically on the question
of the polio vaccine, in keeping with the charge to the committee.
The committee recommends development of sensitive and specific
serologic tests for SV40. These would be helpful to resolve the question as to
whether or not the SV40 exposure led to infection.
The committee recommends the development and use of sensitive and
specific standardized techniques for SV40 detection. Included in these efforts
should be a documentation that: 1) all test specimens are masked, 2) positive and
negative control tissues are both used and are both subjected to the same
processing procedures as test specimens, 3) samples are tested in replicate, and
4) an adequate sample of tissue is available.
The committee recommends that once there is agreement in the
scientific community as to the best detection methods and protocols, prey
1955 samples of human tissues should be assayed for the presence or
absence of SV40 in rigorous, multicenter studies. These tests would not
address the question of whether or not SV40 can cause cancer, but they could
influence the interpretation of some epidemiologic and clinical analyses. They
also would be relevant for discussion of the relative contribution of
contaminated polio vaccine to the burden of SV40 infection in humans.
The committee recommends further study of the transmissibility of
SV40 in humans. This will help confirm whether and why SV40 or antibodies
specific for SV40 are detected in individuals who have no known exposure to
potentially contaminated polio vaccine, animals or laboratory contact. Resolving
the issue of transmissibility of SV40 is not directly relevant for a causality
assessment, but it would be useful in some of the ancillary debates about the role
of the polio vaccine contamination in the cancer burden.
In addition to the research recommended above, it is important to resolve
the extent of SV40 contamination of past polio vaccine. The uncertainty of
exposure makes interpretation of the epidemiologic studies very problematic. In
addition, concerns that the oral polio vaccine had been more widely
contaminated than assumed require attention. The issue should be resolved
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SV40 CONTAMINATIONOF POLIO VACCINE AND CANCER
75
publicly to the satisfaction of the public as well as the scientific and policy-
malcing communities.
If researchers can pursue these strategies and obtain a better understanding
of SV40 exposure and methods of detection, more meaningful case-control
studies can be undertaken to help resolve the question of causality. Und1 some
of the technical issues are resolved, the committee does not recommend
additional epidemiologic studies of people potentially exposed to the
contaminated polio vaccine.
SUMMARY
Some of the polio vaccine administered from 1955-1963 was contaminated
with simian virus 40 (SV40~. The virus came from the monkey kidney cell
cultures used to produce the vaccine. Most, but not all, of the contamination was
in the inactivated polio vaccine (IPV). Once the contamination was recognized,
steps were taken to eliminate it from future vaccines. There have been many
questions as to the effects on people who received the contaminated vaccine.
SV40 has biological properties consistent with a cancer-causing virus, but
researchers have not conclusively established whether or not it could cause
cancer in humans. Studies of groups of people who received polio vaccine
during 1955-1963 provideevidenceofnoincreasedcancer risk.
However, because these epidemiologic studies are sufficiently flawed, the
Institute of Medicine's Immunization Safety Review Committee concluded that
the evidence was inadequate to conclude whether or not the contaminated polio
vaccine caused cancer. In light of the biological evidence supporting the theory
that SV40-contamination of polio vaccines could contribute to human cancers,
the committee recommends continued public health attention in the form of
policy analysis, communication, and targeted biological research. Box 3
summarizes the committee's conclusions and recommendations.
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samples from a human mesothelioma. Anticancer Res 20(2A):879-84.
Baris D, Zahm SH.2000. Epidemiology of lymphomas. Curr Opin Oncol 12~5~:383-94.
Bergsagel DJ, Finegold MJ, Butel JS, Kupsky WJ, Garcea RL. 1992. DNA sequences similar to
those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N Engl J
Med 326(15):988-93.
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Representative terms from entire chapter:
simian virus
