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Cancer J Clin. 2007;57:7-28.Clinical ContextAccording to a report by Pagliusi published
by the World Health Organization,
cervical cancer is the second most
common cause of cancer death worldwide. In the December 1999 issue of Clinical Obstetrics and
Gynecology, Sawaya and Washington noted that the incidence of cervical
cancer would be 2 to 3 per 100,000 even with optimal screening. HPV
types 16 and 18 cause 70% of cervical cancers, according to Munoz and
colleagues in the February 6, 2003, issue of The New England Journal of Medicine, and 50% to 60% of CIN grade 2 and 3, according to Clifford and colleagues in the July 7, 2003, issue of the British Journal of Cancer.
Two HPV vaccines have been developed to decrease HPV-related
cervical, penile, vulvar, vaginal, and anal precancerous and cancerous
lesions, genital warts, and laryngeal papillomatosis: Gardasil (Merck & Co, Inc) is a quadrivalent
vaccine to prevent HPV types 6, 11, 16, and 18; and Cervarix (GlaxoSmithKline) is a bivalent vaccine to prevent HPV types 16 and 18.
An expert panel organized by the ACS reviewed the published and
unpublished data on HPV vaccines and the prevention of cervical cancer
and precancerous lesions. Panel members put forth expert opinions in
cases of insufficient evidence. The recommendations were discussed and
voted on by the ACS Gynecologic Cancer Advisory Group and the National
Board of Directors. The ACS guidelines focus mainly on Gardasil, which is licensed by the US Food and Drug Administration.
Study HighlightsCervical cancer incidence is higher in some groups because of social, cultural, and healthcare access barriers.Progression from HPV infection to invasive cancer takes an average of 20 years.Genital HPV transmission usually occurs within a few years after onset of vaginal or anal intercourse.Study
enrollment criteria limited the lifetime number of sex partners (mean,
2; maximum, 4) and histories of cervical abnormalities.2 Gardasil
phase 3
efficacy substudies were conducted on women who complied with
vaccine regimen and did not have type-specific HPV infection:Females 15 to 26 years
old had 100% vaccine efficacy in prevention of HPV 16/18-related CIN 2/3 and adenocarcinoma in situ.Females
16 to 23 years old had 100% vaccine efficacy in prevention of HPV
6/11/16/18-related external genital warts, vulvar/vaginal
intraepithelial neoplasia, and cervical lesions with follow-up of 1.5
years.Results from intent-to-treat analyses of Gardasil
included women who received at least a 1 vaccine dose and had current
or past HPV infection, according to polymerase chain reaction or
serology.Cervarix had 100% efficacy in preventing HPV 16/18-related CIN in females 15 to 25 years old followed up to 4.5 yearsSafety results for Gardasil and Cervarix from phase 2b randomized controlled trials:Injection site adverse events were more common and intense in Gardasil vs placebo
subjects (83% vs 73%) and more common in Cervarix vs placebo subjects (94% vs 88%).Most common systemic adverse events occurred in 69% of both Gardasil and placebo subjects and in 86% of both Cervarix and placebo subjects.Serious vaccine-related events occurred in 5 Gardasil and 2 placebo subjects.Up to 0.2% of subjects discontinued study because of adverse events.No vaccine-related deaths occurred in Gardasil or Cervarix subjects.In women who became pregnant within 30 days'' postvaccination, congenital anomalies occurred in 5 of Gardasil group and none of placebo; no data were published for Cervarix subjects.Pregnancy registry postmarketing to further evaluate effects has been proposed.Duration of vaccine-related HPV immunity is not known.Youngest subjects were 9 years old for safety and immunogenicity studies, 16 years old for Gardasil efficacy studies, and 15 years old for Cervarix efficacy studies.Insufficient
evidence exists to recommend for or against routine vaccination for
women 19 to 26 years old, but those who have not had sexual intercourse
would benefit from vaccine. Efficacy data for HPV 16/18-related CIN 2/3
in women with more than 4 lifetime sex partners are lacking.Male subjects 9 to 15 years old were included in Gardasil
safety, immunogenicity, and ongoing efficacy trials; male vaccination
might not be cost-effective in cervical cancer prevention, but might be
more effective in low-vaccination areas.Current cervical cancer screening recommendations should continue.Vaccination
effects on cervical cancer rates will not be apparent until subjects
reach the age of 48 years, the median age of cervical cancer diagnosis.HPV testing before vaccination is not recommended.Recommendations
for vaccine implementation include distribution to underserved areas
through free programs and at routine healthcare visits for girls at age
11 or 12 years.Limitations of HPV vaccines include lack of
protection against all carcinogenic HPV types, noncompliance, and need
for studies in HIV-infected people.
Pearls for PracticeHPV vaccine is recommended routinely for girls 11 and 12 years old
and for catch-up for teenaged girls 13 to 18 years old. It can be given
to girls as young as 9 years. However, data are inadequate to support
universal HPV vaccine for women 19 to 26 years old, but the vaccine is
likely less beneficial in females with more lifetime sexual partners.Females who are vaccinated and unvaccinated with HPV vaccine should
continue to undergo screening for CIN and cancer, as recommended in
current ACS guidelines.
More abstracts about the Guidelines Issued for the Use of HPV Vaccine for Cervical Cancer