Guttmacher Policy Review
Winter 2006, Volume 9, Number 1
March 18, 2006
The Public
Health Promise and Potential Pitfalls
of the World's First Cervical Cancer Vaccine
By Cynthia Dailard
After a decade in development, a cervical
cancer vaccine appears poised to become
available to American women later this
year. Given the vaccine’s demonstrated
high level of effectiveness in preventing
transmission of the two strains of human
papillomavirus (HPV) responsible for most
cases of cervical cancer, researchers
believe that widespread vaccination has
the potential to reduce cervical cancer
deaths around the world by as much as
two-thirds. The vaccine, therefore, holds
the promise of being an enormous public
health advance, both for women in the
United States and for women in developing
countries, who disproportionately bear
the global burden of cervical cancer.
Because HPV is sexually transmitted, experts
say the vaccine needs to be administered
to as many young adolescent females as
possible prior to sexual activity to achieve
maximum effectiveness. Adolescents, however,
are typically considered to be a difficult
population to reach through immunization
programs. For the HPV vaccine, moreover,
the politics of teen sex are likely to
exacerbate many of the practical challenges
involved in achieving high vaccination
rates—practical challenges that are
magnified exponentially in developing
countries, where the vaccine is needed
most.
What the Science Says
Virtually all cases of cervical cancer
are linked to HPV, an extremely common
sexually transmitted infection (STI) that
is typically asymptomatic and harmless;
most people never know they are infected,
and most infections typically resolve
on their own. The infection is so common,
in fact, that it is considered virtually
a “marker” for sexual activity;
according to a 1997 American Journal of
Medicine article, nearly three in four
Americans between the ages of 15 and 49
have been infected with HPV at some point
in their life.
Of the 30 known types of HPV that are sexually
transmitted, more than 13 types have the
potential to lead to cervical cancer;
two of these types, HPV 16 and 18, are
associated with 70% of all cases of cervical
cancer. In the United States, notwithstanding
the prevalence of HPV infection, cervical
cancer is relatively rare. This is largely
due to the widespread availability of
Pap tests, which can detect cervical cancer
in its earliest and most treatable stages,
as well as precancerous changes of the
cervix, which can be treated before cervical
cancer sets in. Nonetheless, the American
Cancer Society estimates that in 2006,
almost 10,000 cases of invasive cervical
cancer will occur to American women, resulting
in 3,700 deaths. More than half of all
U.S. women diagnosed with cervical cancer
have not had a Pap test in the last three
years. These women are disproportionately
low-income women and women of color who
lack access to basic health services.
In resource-poor developing countries, the
incidence of cervical cancer is much higher,
and the disease is far more lethal. Of
the 225,000 annual deaths from cervical
cancer globally, 80–85% occur to
women in developing countries. Most of
these deaths occur in Sub-Saharan Africa,
South Asia and Latin America—where
the public health infrastructure is extremely
poor and basic preventive health services
such as Pap smears are largely unavailable.
Because women in these regions typically
do not receive care until their disease
is well advanced, it is usually fatal
(related article, August 2003, page 4).
...the
politics of teen sex are likely
to exacerbate many of the practical
challenges involved in achieving
high vaccination rates...
A cervical cancer vaccine would therefore
represent an enormous step forward for
women’s health. There are actually
two currently under development. Merck
& Company filed an application for
approval of its vaccine, Gardasil, with
the federal Food and Drug Administration
(FDA) in December; it expects an expedited
decision—which is reserved for medications
that treat unmet medical needs—from
the agency in June. It has also submitted
applications to regulatory agencies in
Europe, Australia, Mexico, Brazil, Argentina,
Taiwan and Singapore. GlaxoSmithKline
will be seeking regulatory approval of
its vaccine, Cervarix, in Europe in March
2006 and at the end of the year in the
United States. Both vaccines target HPV
16 and 18, although Merck’s vaccine
also offers protection against two types
of HPV that cause almost all cases of
genital warts. A consortium of agencies
funded by the Bill & Melinda Gates
Foundation, and which includes Harvard
University, the International Agency for
Research on Cancer, PATH and the World
Health Organization, is laying the groundwork
for implementation of the vaccine in the
developing world, expecting that it may
be licensed in selected developing countries
as early as 2007.
Targeting Teens
To become widely available in the United
States, a vaccine must win the endorsement
of the Advisory Committee on Immunization
Practices (ACIP) in addition to FDA approval.
Organized by the federal Centers for Disease
Control and Prevention (CDC), ACIP is
a 15-member panel authorized under federal
law to recommend who should receive a
vaccination, when and how often they should
receive it, and the appropriate dosage.
In deciding whether to recommend a vaccine,
the committee must weigh a host of factors,
including efficacy, benefits and risks,
and cost-effectiveness. It also determines
whether the vaccine should be available
through the federal Vaccines for Children
Program, which provides free vaccines
to doctors serving eligible low-income
children. Although ACIP’s recommendations
are not binding, they are followed closely
by physicians and medical professional
organizations, and ACIP’s endorsement
determines with virtual certainty whether
a vaccine becomes the standard of care
in this country. ACIP recommendations
are also widely relied upon by insurers
for setting reimbursement policy and by
states for public funding purposes.
Perhaps the single most important decision
for ACIP will be the optimal age for administering
an HPV vaccine. While the typical American
female has intercourse for the first time
at age 17, 13% do so prior to age 15,
according to the 2002 National Survey
of Family Growth. Because HPV infection
is so widespread, most cases of HPV are
acquired soon after women become sexually
active, with the peak incidence currently
occurring at age 19. Merck’s trials,
moreover, found that the vaccine produced
a stronger immunological response in adolescents
aged 10–15 than in women aged 16–23.
For these reasons, both Merck and GlaxoSmithKline
are recommending that all girls receive
their vaccines when they are 10–12
years old.
There are other practical reasons for targeting
this age-group. In order to address the
historical lack of emphasis on adolescent
immunization, ACIP, the American Academy
of Pediatrics, the American Association
of Family Physicians and the American
Medical Association in 1996 jointly identified
ages 11–12 as the optimal time for
adolescent immunizations. Currently, the
federal Childhood and Adolescent Immunization
Schedule recommends that every 11–12-year-old
receive two vaccines (a new vaccine for
bacterial meningitis and a combined booster
for tetanus, diphtheria and whooping cough);
it also recommends that they be assessed
for “catch-up” shots at that
time.
If the vaccine is recommended for preadolescent
girls, acceptability among pediatricians
and parents will be key to its success.
Survey results released in October by
researchers from the CDC and the University
of California found that most pediatricians
would be willing to administer the vaccine
to their patients. And, several surveys
of parents published in 2005 in the Journal
of Adolescent Health and elsewhere suggest
that parental acceptance of the vaccine
will in fact be high. Many of those surveyed
who initially expressed reservations about
the vaccine changed their minds when educated
about HPV and cervical cancer, suggesting
the importance of counseling and education
targeting parents during an adolescent
health visit.
Finally, each state decides for itself whether
a particular vaccine will be required
in order for children to enroll in school,
and they typically rely on ACIP recommendations
in making this determination. According
to a 2005 report on adolescent vaccination
by the National Foundation for Infectious
Diseases (NFID), school-based immunization
requirements are by far the most effective
means to ensure rapid and widespread use
of childhood or adolescent vaccines. Adolescents
are typically a hard-to-reach population
for vaccine programs, and adding a vaccine
to the list of those required for school
enrollment boosts vaccination rates considerably—and
far more effectively than guidelines recommending
the vaccine for certain age-groups or
high-risk populations. NFID also notes
that timing an adolescent vaccination
to middle school entry (ages 11–12)
is important given that dropout rates
begin to climb at age 13. Along these
lines, younger dropouts are at particularly
high risk of early sexual activity and
poor sexual and reproductive health outcomes,
suggesting an even greater imperative
for a school-based requirement targeting
11–12-year-olds.
The Politics of Teen Sex
No sooner had Merck publicly announced
the results of its long-term clinical
trials in October 2005 than conservative
activists began suggesting that inoculating
young adolescents against HPV would encourage
teenage sexual promiscuity. The heads
of various “family values” groups
publicly declared that they would not
vaccinate their own children. Vaccination
“sends the wrong message,” asserted
Tony Perkins of the Family Research Council
(FRC). “Our concern is that this
vaccine will be marketed to a segment
of the population that should be getting
a message about abstinence.” This
shot across the bow signaled that the
cervical cancer vaccine could become the
next battlefront in the social conservatives’
crusade to advance an abstinence-only-unless-married
agenda, and that leading activists would
be working to ensure that it would meet
the same regulatory fate as efforts to
bring emergency contraception over the
counter.
Yet, these same groups now appear to be
softening their stance. A statement on
the FRC website now says that “media
reports suggesting that the Family Research
Council opposes all development or distribution
of such vaccines are false” and that
it “welcomes the news that vaccines
are in development.” At the same
time, the statement warns, “we will
seek to ensure that there is full disclosure
to the public of what these vaccines can
and cannot achieve, their efficacy, and
their risks (including side effects) and
benefits. We believe that adults must
be provided with sufficient information
to make an informed, free choice whether
to vaccinate either themselves or their
children for HPV.”
If anything, the challenges in developing
countries are more acute, and overcoming
them may be far more difficult.
Whether the new FRC statement heralds a
genuine change in posture on the part
of social conservatives remains to be
seen. A more likely scenario, perhaps,
is that leaders of that movement have
made a tactical decision not to oppose
federal approval of the cervical cancer
vaccine outright but, rather, to hold
their fire for 50 state battles over whether
the vaccine will be mandatory for middle
and high school students. The public health
ramifications of such a decision could
still be significant. Because universal
uptake of the vaccine will have the most
impact on cervical cancer rates, efforts
designed to prevent mandatory vaccination
programs in the name of “parental
control” may ultimately hinder the
eradication of cervical cancer in the
United States.
Beyond Politics
Beyond these political challenges, the
impending roll-out of a cervical cancer
vaccine raises some very serious practical
challenges, as well as a range of longer-term
scientific, logistical and policy questions
that must be confronted over time (see
box). One immediate challenge, for example,
is successfully providing the vaccine’s
three required doses over a six-month
period to adolescents, who, unlike infants
and toddlers, do not typically make frequent,
successive visits to a doctor’s office
or health care clinic. Moreover, the three-shot
regimen is likely to be relatively expensive—somewhere
in the vicinity of $100–150 per shot,
according to newspaper reports. And since
ongoing clinical trials to date have only
demonstrated the vaccine’s effectiveness
for four years, it may be that booster
shots will be needed—either later
in adolescence or during adulthood.
If anything, the challenges in developing
countries are more acute, and overcoming
them may be far more difficult. These
include raising awareness of the need
for a vaccine where knowledge of HPV is
very low; ensuring acceptability among
parents, providers and policymakers in
cultural and political contexts that are
particularly sensitive to teenage sexuality;
delivering a series of three injections
to a population that often has minimal
contact with health care facilities or
providers; and ensuring that the vaccines
are affordable in extremely-low-resource
settings. While some global health experts,
as in the United States, note the appeal
of school-based vaccination programs as
a means for reaching large numbers of
adolescents, sizeable proportions particularly
of female adolescents in many developing
countries do not enroll in school or leave
school prior to the recommended age of
vaccination.
Despite these considerable challenges, one
thing is certain: widespread vaccination
against HPV in order to prevent cervical
cancer would bring an enormous payoff
to women, both in the United States and
abroad. It can only be hoped that the
politics will not be allowed to sabotage
the promise first.
Key Scientific, Logistical and Policy Questions
About the Cervical Cancer Vaccine
• Should older women who are already
sexually active receive “catch-up”
vaccines at the start of any vaccination
effort?
• Should males be vaccinated, both
to prevent HPV transmission to women and
to protect against HPV-related genital
and anal cancers, as well as genital warts,
in men?
• Could a therapeutic vaccine be developed
to help those who are already infected
with HPV or have a persistent infection?
• Could a vaccine be developed that
targets additional cancer-causing types
of HPV?
• Could the HPV vaccine be combined
with other vaccinations for ease of administration,
and would that help to institutionalize
the adolescent health visit?
• Will uptake of the vaccine prompt
professional medical organizations and
public health entities to change their
recommendations for Pap smears, and what
might longer recommended intervals between
Pap smears mean for women’s health
and health care–seeking behavior?
• Will the uninsured, the underinsured
and those who rely on public programs
for their care be able to access this
relatively expensive vaccine, or will
the vaccine simply widen the cervical
cancer disparities that already exist?
