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Sexually Transmitted Diseases:
doi: 10.1097/01.olq.0000225323.51240.bc
Editorial

Human Papillomavirus: Current Prevalence and Future Protection

Bauer, Heidi M. MD, MPH*; Ault, Kevin MD†

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From the *California Department of Health Services STD Control Branch, Richmond, California; and the †Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia

Correspondence: Heidi M. Bauer, MD, MPH, Chief, Office of Medical and Scientific Affairs, California Department of Health Services, STD Control Branch, 850 Marina Bay Parkway, P-2, Richmond, CA 94804. E-mail: hbauer@dhs.ca.gov

Received for publication April 5, 2006, and accepted April 24, 2006.

LESS THAN 20 YEARS AGO, researchers were still working to establish the etiologic relationship between human papillomaviruses (HPV) and cervical cancer. Now, health and medical communities are on the verge of celebrating a vaccine against HPV that prevents cervical cancer. In this issue of Sexually Transmitted Diseases, Dr. Lisa Manhart and colleagues report the findings of the first population-based estimate of HPV prevalence among young women in the United States, which have clear implications for developing effective vaccination strategies.1 Based on data from 3262 sexually active women aged 18 to 25 years who participated in the National Longitudinal Study of Adolescent Health (Add Health), the weighted prevalence of HPV was 26.9%. Surprisingly, among those with only one lifetime partner, the prevalence was 14.3%. Depending on the true sensitivity of urine tests to detect cervical and lower genital tract HPV infection, actual prevalence may be as high as 33%. Predictors of infection, including certain sexual risk behaviors, were generally consistent with those found in other populations; however, the authors describe intriguing results related to partner characteristics.

To further elucidate the prevalence of HPV, population-based surveys (e.g., National Health and Nutrition Examination Survey) should include genital specimens collected from sexually active men and women of all ages. Furthermore, self-collected vaginal swab specimens would provide test sensitivity more comparable to cervical specimens and improve the accuracy of the prevalence estimates in females.2

Approximately one third of the more than 100 HPV types infect genital and oral mucosa.3 Genital HPV is one of the most common sexually transmitted infections.4 Manhart et al provide data in support of current estimates that 20 million people in the United States are infected with HPV. The majority of HPV infections is asymptomatic and transient, and resolve without causing clinical disease; however, persistent infection with high-risk oncogenic types can progress to anogenital and oral cancers. The most common high-risk types include types 16 and 18, which account for approximately 70% of cervical cancers. Infections with low-risk types can cause genital warts, recurrent respiratory papillomatosis, and low-grade cervical abnormalities. Low-risk types 6 and 11 account for approximately 90% of genital warts.

Worldwide, cervical cancer is the second leading cause of cancer-related death among women. The American Cancer Society predicts that there will be approximately 9710 new cases of invasive cervical cancer in the United States in 2006, and approximately 3700 women will die from this disease.5 Strategies to prevent cervical cancer in the United States, which have relied on the early diagnosis and treatment of precancerous lesions, have decreased rates of cervical cancer by more than 75% since the peak in 1948. However, the current Pap screening program is expensive and, because of the limited specificity of screening tests, too often leads to invasive diagnostic and treatment procedures that do not ultimately prevent death or disability from cervical disease. Worse yet is the potential for unnecessary medical interventions to lead to adverse reproductive health outcomes and complications. Widespread implementation of an HPV vaccine could make an important contribution to preventing morbidity and mortality related to HPV infection.

Several prophylactic HPV vaccines have shown promise in preventing infection and disease.6–10 Two pharmaceutical companies, Merck and Company, Inc. and GlaxoSmithKline (GSK), have developed HPV vaccines, which are composed of DNA-free virus-like particles. Merck developed a quadrivalent vaccine against HPV types 6, 11, 16, and 18, whereas GSK developed a bivalent vaccine against HPV types 16 and 18. Both vaccines prevent over 90% of incident and persistent infections with the specific types included in the vaccine as well as the precancerous cervical lesions associated with those infections. In addition, the quadrivalent vaccine protects against genital warts and other HPV-related diseases of the vulva and vagina.11 The vaccines have been demonstrated to provide protection for at least 4 years and published data indicate only minimal adverse effects from the vaccine. Administration of the vaccine requires 3 doses over a 6-month period. Merck’s application for US Federal Drug Administration (FDA) licensure was approved in June 2006 for females aged 9–26 years; GSK is expected to apply for FDA licensure in 2006.12

Vaccination against HPV types 16 and 18 is expected to ultimately reduce cervical cancer incidence and death, abnormal Pap smears, and subsequent diagnostic and treatment procedures, and probably other HPV-related anogenital cancers. Clearly, implementation of the vaccine in the developing world, where cervical cancer screening programs are rudimentary or nonexistent, would result in the greatest public health benefit. Despite the likelihood of significant reductions in the production costs (similar to current hepatitis B vaccine available to developing countries), many obstacles would need to be overcome to realize this potential.13 In the United States, vaccination for females is predicted to be cost-effective, particularly if it allows a later age of screening initiation and a less frequent screening interval.14–16 However, these assumptions have yet to be studied and proven.

In June 2006, the Advisory Committee on Immunization Practices (ACIP) is expected to make formal recommendations.17 Vaccine trial data indicate that those most likely to benefit from vaccination are females before sexual debut. According to the Manhart study, HPV prevalence was high (14.3%) even among females with only one sexual partner. Because of viral clearance combined with the poor sensitivity of urine specimens, this prevalence is likely an underestimate. According to the 2003 Youth Risk Behavior Surveillance, only 4.2% of females report having had sexual intercourse by the age of 13 years18; thus, routine vaccination of females aged 11 to 12 years would likely strike a good balance between providing immunization before exposure and providing protection for at least several years into adolescence. This approach is further supported by evidence that antibody titers are highest among those vaccinated at younger ages.17

Implementing an HPV vaccine program is not without serious challenges.19,20 First, getting the target population into care for a series of 3 injections will be a challenge; however, the recent recommendations for tetanus/diphtheria/pertussis and meningococcal vaccine in early adolescence support a routine adolescent well-care visit.21,22 Although state laws requiring documentation of hepatitis B vaccination before school entry significantly increased vaccine coverage among adolescents, including HPV vaccine among the school entrance requirements, may be challenging to enforce and politically controversial. Second, the cost of the vaccine series is expected to exceed $300, creating challenges to both public and private vaccine funding. Third, recommendations for vaccination of only females will present challenges. Unfortunately, the vaccine efficacy for males is unknown and the costs of including males may be high. Fourth, until more data on the impact of vaccination are available, maintaining the current Pap screening schedule is paramount.

Improving public and provider knowledge and acceptance of the vaccine will be an essential piece of a vaccine implementation strategy.23,24 Limited research has demonstrated relatively high rates of vaccine acceptance among young women25,26 and parents.27 This should be reassuring to healthcare providers who are concerned about negative responses. However, health educators are still faced with significant gaps in public knowledge about HPV28 and the necessity of conveying complicated messages: “HPV is very common, usually goes away, but can cause cervical cancer; the HPV vaccine protects against cervical cancer, but you still need Pap smears.” Fortunately, provider recommendations and education will likely facilitate vaccine acceptance.29

Many unanswered questions should temper the enthusiasm with which this medical advance is embraced. First, the vaccination protocol must provide protection over decades; thus, cohort studies should continue to assess whether boosters are needed. Second, trials should evaluate the effect of vaccination on other disease end points such as anal cancers. Third, the effect of vaccination on sexual risk and health-seeking behaviors needs to be better understood. Finally, the current vaccine does not protect against all oncogenic types of HPV. Recent clinical trial data on the bivalent vaccine demonstrate some crossprotection against other high-risk HPV types not included in the vaccine.10 Notwithstanding the option of adding more HPV types to the vaccine, there is the possibility of type replacement.30 Viral ecology studies are needed to assess the effect of vaccination on HPV type distribution in the population and in disease. Thus, the long-term impact on cervical cancer screening protocols needs to be studied.

Another challenge worth mentioning is the opposition to the vaccine based on political ideology. This opposition is exemplified by the concern expressed by Bridget Maher of the Family Research Council that “giving the HPV vaccine to young women could be potentially harmful, because they may see it as a license to engage in premarital sex.”31 The basis of the opposition is that a sexually transmitted disease vaccine may undermine abstinence messages. HPV has been exploited because of the lack of data to support the efficacy of condoms for prevention of transmission. Vaccine trial data along with recent data demonstrating that condoms may be up to 70% effective32 clearly indicate that abstinence is not the only means to prevent HPV infection. At the February ACIP meeting, Dr. Nicole Liddon reviewed available behavioral data and concluded that an increase in sexual risk is unlikely to result from vaccination.17 Thus far, opposition to the vaccine has not interfered with the FDA vaccine approval process; however, it is critical that public health policy and programs are created based on science, not political ideology.

Despite the significant challenges of implementation and the decades-long delay to realize true benefits, the HPV vaccine represents one of the most exciting new developments in cancer and sexually transmitted disease prevention.

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References

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2. Palmisano ME, Gaffga AM, Daigle J, et al. Detection of human papillomavirus DNA in self-administered vaginal swabs as compared to cervical swabs. Int J STD AIDS 2003; 14:560–567.

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4. Centers for Disease Control and Prevention. Human Papillomavirus (HPV) Infection. Available at: http://www.cdc.gov/std/hpv/. Accessed March 27, 2006.

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32. Winer RL, Hughes JP, Feng Q, O’Reilly S, Kiviat NB, Koutsky L. The effect of consistent condom use on the risk of genital HPV infection among newly sexually active women. Paper presented at the 16th Biennial Meeting of the International Society for Sexually Transmitted Disease Research (ISSTDR), July 10–13, 2005, Amsterdam, The Netherlands.

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