Although this preventive measure can save lives, ensuring widespread usage presents a unique challenge for practitioners.
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. According to the Centers for Disease Control and Prevention, sexually active men and women have a lifetime risk of at least 50% of acquiring HPV infection. An estimated 9.2 million sexually active young adults aged 15 to 24 are infected; in fact, 74% of new HPV infections occur among young people in this age group. Although cervical cancer is the most serious manifestation of the virus, most HPV-related morbidity is associated with cervical dysplasia or genital warts.
In June 2006, the FDA approved quadrivalent HPV 6, 11, 16, and 18 recombinant vaccine.1 Indicated for young girls and women aged 9 to 26, Gardasil is the first vaccine approved to prevent transmission of HPV types 16 and 18, which are responsible for approximately 70% of cervical cancer cases, and HPV types 6 and 11, which cause approximately 90% of genital warts. (A bivalent HPV 16/18 vaccine called Cervarix is expected to be approved by the FDA shortly.) Produced in recombinant yeast and adsorbed on an aluminum-containing adjuvant, Gardasil is administered as three injections over a 3-month period. Because the vaccine does not protect women who have been infected before vaccination, cervical cancer screening via Pap smears remains critical in detecting precancerous changes in the cervix.
Although Gardasil has been proven effective in preventing HPV transmission, mandating its use is somewhat controversial. In March, 2007, The Advisory Committee on Immunization Practices (ACIP) of the CDC recommended that the vaccine be administered routinely to 11- and 12-year-old girls and to nonvaccinated females aged 13 to 26 years, noting that physicians could start vaccination in girls as young as 9 years.2 A total of 24 states and the District of Columbia have proposed legislation that would make vaccination mandatory for girls entering the sixth grade but to date only Virginia has passed such a mandate. Proposals in many other states, including Texas and Georgia, were contentiously defeated or were amended to only provide parents with educational material.3 In addition, the American Academy of Family Physicians, the American Academy of Pediatrics, and other groups argue that legislating use of the vaccine is premature, given that long-term safety and accessibility issues have not yet been resolved.
Targeting women before exposure
Four prospective randomized trials conducted in more than 20,000 women between the ages of 16 and 26 demonstrated the efficacy of Gardasil. In all these trials, Gardasil was effective in reducing the incidence of cervical intraepithelial neoplasia (CIN) 1, 2, 3, adenocarcinoma-in situ, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, and genital warts caused by infection with HPV 6, 11, 16, and/or 18.1,4 Although the vaccine showed no benefit in reducing HPV-related lesions that previously infected the patient, the vaccine reduced infection of the other HPV types targeted by the vaccine. For example, if the patient was infected with HPV 16, the vaccine did not reduce HPV 16-associated lesions but did decrease HPV 6, 11, and 18 lesions.
IN TWO IMMUNOGENICITY studies, the immune response to the vaccine was as good in young women between ages 9 and 15 as it was in women between the ages of 16 and 26, inferring that the vaccine would be as effective in younger women as it is in the older group. Ongoing studies are evaluating the efficacy of this vaccine in women older than 26 and in men. The results of these studies may support a more universal vaccination program. Despite the vaccine's advantages, adverse effects associated with Gardasil in clinical trials included pain (84%); erythema (25%); swelling (25%); and pruritis (3%).1
To move toward universal acceptance of the HPV vaccine by the general population, controversial issues, including teen sex, parental control, and the role of government in health-care policy, must be addressed. In discussing the vaccine's usefulness, for example, health-care providers might encounter resistance from individuals or groups concerned about the government mandating a vaccine for a virus contracted through sexual activity or who worry that vaccination will encourage sexual activity among teens.
DATA FROM SEVERAL STUDIES, however, support vaccination of young women before they become sexually active. The highest rates of developing HPV occur in women between the ages of 18 and 28. It is estimated that 24% of 15-year-old girls, 40% of 16-year-old girls, and 70% of 18-year-old women have had sexual intercourse.2 In addition, those at increased risk for cervical cancer, including minorities and women in low socioeconomic groups, frequently begin sexual activity at a young age.
In a group of 603 female university students assessed at 4-month intervals between 1990 and 2000, the cumulative incidence of HPV infection in women who were sexually active was 39% at 24 months. Predictors of an increased risk of infection included intercourse with a new partner 5 to 8 months before a study visit, intercourse with a partner known to be the student for less than 8 months before sex occurred (especially one who has had multiple sex partners), smoking, and oral contraceptive use.5
In another study, an estimated 74% of new HPV infections that developed in 2000 occurred among those aged 15 to 24. In the 2003 Youth Risk Behavior Surveillance summary, the CDC reported that 62.3% of females in the United States have had sexual intercourse by grade 12; 27.9% by grade 9; and 4.2% before the age of 13.6
The role of education
Realizing that education is critical to acceptance of the vaccine, our group at The University of Texas M. D. Anderson Cancer Center conducted a pilot analysis of women's opinion of vaccination. We interviewed 200 women with children between the ages of 8 and 14 to determine if they would accept the HPV vaccine for themselves and their daughters and sons. (We included boys in the analysis even though current indications do not include males.) In our survey, women expressed a general willingness to be vaccinated themselves (77%). In addition, 67% who had a daughter and 66% who had a son said they would consent to have their children vaccinated. In this cohort, the respondents' reasons for not wanting to use the vaccine included lack of efficacy, adverse effects of vaccinations, and unwillingness to vaccinate their sons because the boys were not considered high risk for such HPV-associated diseases as penile cancers and genital warts.7
SEVERAL STUDIES ILLUSTRATE the importance of educating patients about the full benefits of HPV vaccination. One study evaluated a similar population of parents, whose children ranged in age from 10 to 15 years old).8 The investigators found that 55% of the parents were willing to accept the HPV vaccine for their children. After an educational intervention, however, 20% of those who initially did not want the vaccine were willing to have their children receive the injection. Of interest, parents who opposed the vaccination believed their children would be more likely to be sexually active if they received the vaccine.
In a population-based study in Cuernavaca, Mexico, researchers educated a group of mothers with adolescent daughters about HPV preventive measures and then surveyed them about the acceptability of the vaccination.9 After receiving an explanation that the HPV vaccine might prevent cervical cancer, 84% of the women said they would allow their teenage daughter to be vaccinated.
In several years, physicians will be able to better identify factors associated with the acceptance or refusal of the vaccine. In the past, researchers have found that understanding that a disease is sexually transmitted is a main determinant of whether a vaccine against that disease will be accepted. The hepatitis B vaccine, for example, was successfully launched and accepted by the general population. Most cases of hepatitis B are transmitted through sexual contact, despite the perception that it is a disease typically contracted by health-care workers and hospitalized patients. In a study regarding the acceptance of the hepatitis B vaccine, researchers found that one of the main factors associated with the acceptance of the vaccine was the perception of the risk of contracting hepatitis B through nonsexual means.10
DESPITE THE POTENTIAL social and cultural barriers to a universal HPV vaccination program, our study and others indicate a willingness among many women to accept the vaccine for their daughters. Obstetricians and gynecologists, who are responsible for treating most cases of cervical, vulvar, and vaginal dysplasia and genital warts, must be proactive in educating and discussing benefits of vaccination. We should also educate our patients that the vaccine is most effective in HPV-naïve women and is most effective prior to HPV or possible HPV exposure, meaning prior to sexual activity. Future studies need to evaluate public health issues that arise once the HPV vaccination programs have been established more extensively.
1. Gardasil [package insert]. Whitehouse Station, NJ: Merck and Co., Inc.; 2006.
2. Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm?s_cid=rr5602a1_eAccessed May 20, 2007.
3. McCaffrey S. States back cancer vaccine mandate. Available at: http://www.forbes.com/feeds/ap/2007/05/20/ap3739648.html . Accessed May 20, 2007.
4. U.S. Food and Drug Administration. New vaccine prevents cervical cancer. FDA Consumer Magazine, Sept-Oct 2006. Available at: http:// http://www.fda.gov/fdac/features/2006/506_cervical.html. Accessed May 20, 2007.
5. Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218-226.
6. Centers for Disease Control and Prevention. Division of STD Prevention. HPV and HPV Prevention: Information for Health Care Providers. Revised August 2006. Available at http:// http://www.cdc.gov/std/HPV/STDFact-HPV-vaccine-hcp.htm . Accessed June 2, 2007. Centers for Disease Control and Prevention. Youth Risk Behavior Survey-United States, 2005. MMWR. 2006;55(S S05):1-112.
7. Slomovitz BM, Sun CC, Frumovitz M, et al. Are women ready for the HPV vaccine? Gynecol Oncol. 2006;103:151-154.
8. Davis K, Dickman ED, Ferris D, et al. Human papillomavirus vaccine acceptability among parents of 10- to 15-year-old adolescents. J Low Genit Tract Dis. 2004;8:188-194.
9. Arillo-Santillan E, Lazcano-Ponce E, Rivera L, et al. Acceptability of a human papillomavirus (HPV) trial vaccine among mothers of adolescents in Cuernavaca, Mexico. Arch Med Res. 2001;32:243-247.
10. Bodenheimer H, Fulton J, Kramer P. Acceptance of hepatitis B vaccine among hospital workers. Am J Public Health. 1986;76:252-255.