|
guest Editorial OCTOBER 2006
Cervical Cancer:
A Vaccine-preventable Malignancy
Michael A. Steller, MD
Vaccinations are among the most significant public health interventions
in human history, sparing millions of people from infectious diseases
that often result in death. Consistent and compelling epidemiologic,
molecular, and clinical evidence indicates that cervical cancer
is caused by a sexually transmitted infection (STI) that can now
be prevented by an effective immunization. Human papillomavirus
(HPV) is detectable in more than 99% of cervical cancers, and several
recent clinical trials1-3 have convincingly demonstrated the efficacy
of vaccination in preventing HPV infection and subsequent cervical
intraepithelial neoplasia.
In the past, some vaccination programs initially attempted to
target "at risk" populations, rather than adopting
universal vaccination strategies de novo. This policy only delayed
the achievement of disease control—in some cases for 10 or
20 years. With the rubella vaccine, for example, several programs
first targeted schoolgirls, susceptible women postpregnancy, and
women at "special" risk. Divergent vaccination policies
were implemented in different countries, with vaccine delivery
targeted at different age groups and sexes. This resulted in equally
divergent epidemiologic consequences with regard to the vaccine’s
purpose: to reduce or eliminate the incidence of rubella syndrome.
Only after mandatory, universal inoculation policies were adopted
to target all preschool-aged children, with booster doses provided
to adolescent girls, did reports of rubella epidemics subside.
A similar process occurred in the United States with the hepatitis
B vaccine. Initially, the Advisory Committee on Immunization Practices
(ACIP) recommended pre-exposure vaccination for populations at
high risk of hepatitis Β infection.4 After several years with this
program, however, there was no reduction in the US incidence of
hepatitis B infection. The ACIP subsequently changed its policy
to focus on universal childhood vaccination, prevention of perinatal
transmission, and other target populations. This resulted in a
dramatic reduction in hepatitis B infection rates, particularly
in highly vaccinated populations. The collective experience with
immunoprophylactic vaccines overwhelmingly indicates that to eliminate
viral transmission, high vaccine coverage rates must be sustained
among infants, children, and adolescents, as well as adults of
both genders at high risk for infection.
To achieve optimal protection, vaccination should ideally be administered
before women begin to engage in sexual behavior. According to the
US Centers for Disease Control and Prevention, sexual behavior
is common among high school students, with 33% of high-school freshmen
and 62% of seniors engaging in sexual intercourse. Nationwide,
7.4% of students had sexual intercourse for the first time before
age 13 years.5 Therefore, parental acceptance will have a profound
impact on the potential effectiveness of a prophylactic HPV vaccine.
Although genital HPV infection carries the stigma of unacceptable
sexual behavior for some, in practical terms it represents a formidable
public health problem that can now be reduced or even prevented
by a successful vaccination program. Public education must be given
high priority to spread the message that genital HPV infection
is extremely common, that it is a sexually transmitted condition,
and that there is a causal link between HPV and cervical cancer.
Parental acceptance of vaccination appears to be influenced by
the recommendations of health care providers, the severity of the
disease in question, and the safety and efficacy of the vaccine.
Theoretically, it would be desirable to vaccinate men as well
as women to reduce viral transmission rates through "herd" immunity.
Clinical experience in inoculating men with a virus-like particle-based
HPV vaccine clearly demonstrates that—as for women—potent
neutralizing antibody responses can be safely and reliably elicited.
However, all clinical trials to date that have assessed the prevention
of epithelial HPV infection have been limited to women. The recently
reported success using the quadrivalent HPV vaccine to prevent
warts from developing on the vulva, where the keratinized epithelium
is similar to that of the penis, suggests that male vaccination
may be efficacious. Although HPV is an STI, remarkably little research
has been conducted on its natural history in men. Given the importance
of the decision to include or exclude men in large-scale vaccination
programs, research to elucidate the effectiveness of HPV vaccines
in men should be accorded very high priority. Assuming that vaccination
of men proves efficacious, the inclusion of men in a universal
vaccination program would provide important advantages—eg,
direct protection from genital warts and promotion of herd immunity
by reducing the circulation of HPV in the general population. It
is of interest that in Australia, the quadrivalent HPV vaccine
has been approved for use in men even without efficacy data.
With the successful development of an effective HPV vaccine comes
the dawn of a new era. In the history of cancer research, only cervical
cancer has been shown to have a necessary causal intermediate: HPV
infection. This association dwarfs the associations of tobacco consumption
with lung cancer and chronic hepatitis B infection with liver cancer—two
of the strongest epidemiologic associations ever identified. The
link between HPV and cervical cancer sets this malignancy apart,
especially now that a preventive vaccine is available. Several factors
have historically contributed to the underutilization of vaccines,
including underestimating the severity of vaccine-preventable diseases
and the benefits of vaccination, and concerns regarding the side
effects of vaccines. In earlier eras, the ravages of diseases such
as smallpox and polio were devastating to both individuals and large
populations. Those who witnessed the successful implementation of
vaccination to prevent these diseases viewed them as miracles. Today,
however, few people have experienced such devastation, thanks to
vaccination programs. When there is no longer an imminent fear of
contracting a disease, the public may forget about the limitations
of medicine, becoming apathetic about prevention. Therefore, it
is of surpassing importance that policy-makers around the world
maintain a sense of urgency as HPV vaccines make their way into
the global health care arena.
Michael A. Steller, MD
Director, Division of
Gynecologic Oncology
Department of Obstetrics
and Gynecology
Caritas Christi Health Care System
Tufts University School of Medicine
Boston, Mass
back
to top
References
- Koutsky LA, Ault KA, Wheeler
CM, et al. A controlled trial of a
human papillomavirus type 16
vaccine. N Engl J Med. 2002;
347(21):1645-1651.
- Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent
L1 virus-like particle vaccine in prevention of infection with human papillomavirus
types 16 and 18 in young women: a randomised controlled trial. Lancet. 2004;
364(9447):1757-1765.
- Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6,
11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind pla-cebo-controlled multicentre phase II efficacy trial. Lancet
Oncol. 2005;6(5):271-278.
- US Centers for Disease Control and Prevention. Hepatitis
B vaccination—United States, 1982-2002. MMWR Morb Mortal Wkly Rep. 2002;51(25):549-552,
563.
- Grunbaum, JA, Kann L, Kinchen S, et al. Youth risk behavior surveillance—United States, 2003.
MMWR Surveill Summ. 2004;
53(2):1-96.
back
to top
|
