Human papillomavirus vaccines are a promising technology for primary prevention of cervical cancer and other HPV-related diseases, but achieving high rates of vaccination in the age group targeted for vaccination presents a challenge.
Human papillomavirus (HPV) vaccines are a promising technology for primary prevention of cervical cancer and other HPV-related diseases, but achieving high rates of vaccination in the age group targeted for vaccination presents a challenge.
Although pediatric clinicians play a critical role in the implementation of national recommendations for HPV vaccination for children and adolescents, ob/gyns play a critical role in implementing catch-up vaccination.1 Ob/gyn appointments for adolescents and young adults focus primarily on contraception, sexually transmitted disease prevention and treatment, abnormal bleeding, dysmenorrhea, and preventive guidance. These types of visits for young women offer an opportunity to increase vaccination rates with the potential for decreasing rates of HPV infection and cervical cancer precursors. Ob/gyns may be the primary or only contact that older adolescents and young adults have with the healthcare system, and thus are uniquely positioned to provide vaccinations.2
Although most HPV infections are asymptomatic, a proportion of infected individuals will develop clinical disease. Infection with low-risk types HPV-6 or HPV-11 causes approximately 90% of anogenital warts and recurrent respiratory papillomatosis.6 Infection with high-risk types HPV-16 or HPV-18 causes approximately 50% of cervical intraepithelial neoplasia (CIN) 3 lesions and 70% of cervical cancers.7 Infection with these or other high-risk HPV types is thought to cause virtually 100% of cervical cancers, approximately 90% of anal cancers, at least 50% of vulvar, vaginal, and penile cancers, and a subset of oropharyngeal cancers.8
In the United States, approximately 13,000 women are diagnosed with cervical cancer and approximately 5,200 die each year from the disease.9 Worldwide, cervical cancer is the second most common cancer in women: Approximately 490,000 women are diagnosed and 270,000 die from cervical cancer annually.10 HPV vaccines, therefore, have the potential to significantly affect HPV-related morbidity and mortality domestically and internationally.
The antigen for the quadrivalent and bivalent vaccines is the HPV L1 capsid protein. This protein is expressed using recombinant technology and self-assembles into virus-like particles (VLPs). VLPs are identical morphologically to HPV virions and induce a virus-neutralizing antibody response in the host, but because they contain no viral DNA, they cannot cause infection or cancer. The quadrivalent vaccine contains VLP antigens for HPV-6, -11, -16 and -18, and the bivalent vaccine contains VLP antigens for HPV-16 and -18. Both vaccines use aluminum-containing adjuvants, but neither contains thimerosal or antibiotics. Vaccination is much more immunogenic than natural infection, generating high concentrations of neutralizing antibodies to L1.
Clinical trials in women used surrogate efficacy endpoints for cervical cancer, such as CIN 2/3 and cervical adenocarcinoma in situ, as outcomes. Almost all participants in clinical trials of both vaccines seroconverted, and higher immune responses were observed in the younger age groups than in the older age groups for both women and men.11-16 Although the minimum antibody level that confers protection against infection is unknown, clinical trials have demonstrated that the antibody levels sustained more than 8 years after vaccination appear to be sufficient to prevent HPV infection and CIN.
Both vaccines demonstrated 90% to 100% efficacy in preventing persistent HPV infection, CIN 2/3, and adenocarcinoma in situ caused by HPV-16 and -18 among women who had not previously been infected by those HPV types.11-13,17 The quadrivalent vaccine demonstrated equally high efficacy in preventing anogenital warts and precancerous vaginal and vulvar lesions caused by HPV-6, -11, -16, and -18.18
In women infected with a vaccine-type HPV at the time of vaccination, HPV vaccines do not prevent infection or disease caused by that HPV type.19 There is evidence that in women, both vaccines provide moderate cross protection against additional HPV types (eg, types 31 and 45) that are genetically related to the types targeted by the vaccines, which could broaden protection against cancers caused by HPV types not targeted by the current vaccines.20