An STD expert explores the questions and issues that patients will be raising about the new human papillomavirus vaccine, Gardasil.

Elizabeth, a 20-year-old college student, presents for a “gyn checkup.” After reviewing her history and completing an examination, you move on to a discussion of preventive health issues, recommending that she start the human papillomavirus (HPV) vaccine series. Elizabeth initially seems ambivalent. She vaguely recalls reading about HPV in a women’s magazine and wonders whether the vaccine is really necessary.

HPV infections are common among adolescents and young adults. An estimated 75% of sexually active men and women have been exposed to HPV at some point in their lives.1 The prevalence of HPV infections in the United States is thought to exceed 20 million, while the incidence of HPV infections acquired via intercourse is upward of 5.5 million cases annually.2

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Studies among adolescent girls and young adult women have reported HPV prevalence rates ranging from 28% to 82%.3,4 Prevalence rates among male adolescents and young men can range from 29% to 48%.5 Thus, males and females appear to have comparable rates of infection.

Elizabeth wonders whether HPV is sexually transmitted. She is not currently sexually active but has had four lifetime partners.

While intercourse likely represents the most efficient method of infection, HPV can also be transmitted though any skin-to-skin contact. In one study, the cumulative incidence of HPV infection within 36 months of first intercourse reached 50% among female college students who were HPV-negative at enrollment.6 There is a linear relationship between the number of sexual partners and the likelihood of HPV infection; among women reporting four or more lifetime partners, rates of HPV exceeded 50%, reaching nearly 70% among those reporting 10 or more sexual partners7 (Figure 1).

But won’t condoms prevent HPV infection?
Condoms will decrease the risk but not eliminate it. A recent study found that the risk of genital HPV infection among women reporting consistent condom use with their male partners was reduced by 70%.8

Is infection that a big deal? What happens?
HPV infections can result in genital warts; Pap smear cytologic abnormalities; cancers of the cervix, vagina, vulva, and anus; as well as precursor lesions for these malignancies.

The family of HPV includes more than 100 distinct types that can be subdivided based on their trophism for infecting mucosal or cutaneous epithelial tissues. HPV viral types are generally classified using a numbering system, for example, HPV 6. HPV infections involving cutaneous surfaces result in flat warts or plantar warts. The approximately 40 types of mucosotrophic HPV include both “high-risk” and “low-risk” types based on the disease outcomes resulting from infection.

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High-risk HPV infection (e.g., HPV 16, 18, 31, 33, etc.) manifest as Pap-smear abnormalities—low-grade intraepithelial lesions, high-grade intraepithelial lesions, cervical cancers, and other malignancies of the anogenital region. Nearly all cervical cancer specimens demonstrate detectable high-risk HPV DNA, and the International Agency for Research on Cancer (IARC) has identified a dozen high-risk HPV types as human carcinogens. The IARC considers persistent infection with high-risk HPV necessary for development of cervical cancer. In addition, persistent infection with high-risk HPV has been implicated in the development of anal, penile, and head and neck cancers. Thus, HPV-related disease constitutes a significant clinical burden for both men and women alike.

Infection with low-risk HPV types (e.g., HPV 6, 11, etc.) manifests as low-grade Pap-smear abnormalities and genital warts. While these abnormalities are largely reversible, the process of dealing with them is distressing to patients as well as to their families and sexual partners. Among women exposed to HPV 6 or 11, roughly two thirds will develop genital warts within 36 months.9 HPV 6 and 11 are also responsible for recurrent respiratory papillomatosis, in which obstructive papillomas form on the larynx and vocal cords, causing considerable morbidity among affected infants and young children. There is also an adult-onset form of recurrent respiratory papillomatosis.

The emotional effects of HPV infection are considerable and include feelings of anxiety, rejection, shame, loss of sexual interest, and fears about developing cancer.

Though most HPV infections will clear on their own, chronic and persistent infection with high-risk HPV is associated with the development of malignancies and precursor lesions. At this time, there is no way to identify those at risk of developing persistent infection.

OK, so it’s pretty serious, Elizabeth concedes. But how effective is the HPV vaccine?
The quadrivalent HPV vaccine—marketed by Merck under the name Gardasil—protects against types 16, 18, 6, and 11, with 90%-100% efficacy. Trial results provide consistent evidence confirming high levels of efficacy against incident and persistent HPV infection, cytologic abnormalities, histologic changes, and HPV-related disease, including cancers and precursor lesions. Studies among children aged 9-15 years provide evidence of immunologic responses comparable with those among young women.

Is the vaccine safe?
Yes. Most patients will probably experience localized arm soreness and possibly some transient swelling and redness. Severe reactions are rare.

How long will the vaccine’s protection last?
At this point it is not known whether, or when, booster doses might be needed. Follow-up data extending out to about five years show continued efficacy and immunogenicity. Gardasil is approved for girls and women aged 9-26 years as a three-dose series (initial dose followed by a second dose two months later and a third dose six months after the first). Provisional recommendations from the CDC’s Advisory Committee on Immunization Practices (ACIP) include routine administration of Gardasil among girls during the “preadolescent visit” (age 11-12). This visit is meant to serve as an opportunity to emphasize health promotion and prevention ,a href=”http://(” target=”_blank”> Accessed February 7, 2007).

Clinicians may opt to vaccinate girls as young as 9 years as part of a systematic approach to vaccination. The vaccine should also be made available to girls and women aged 13-26 years as part of a catch-up vaccination strategy.Recommendations from ACIP are included in the updated adult immunization schedule and have been endorsed by the American Academy of Family Physicians, the American Academy of Pediatrics, the Society for Adolescent Medicine, and the American College of Obstetrics and Gynecology.

Elizabeth has friends her age who have been treated for genital warts and abnormal Pap smears. Should they also receive the HPV vaccine?
The greatest benefit will be among those who have not yet been exposed to the HPV types covered by the vaccine.

The ACIP recommendations call attention to special situations, including women who have a history of equivocal or abnormal Pap smears, are HPV-positive, or have a history of genital warts. Women who fall into one or more of these categories have likely been exposed to at least one type of HPV, but the vaccine would still provide protection against those HPV types to which they have not yet been exposed.

Immunocompromised women should also be offered this vaccine, although the immune response and effectiveness are uncertain. These special situations warrant a discussion of potential risks and benefits with patients as part of an informed decision-making process.While lactating women may receive the HPV vaccine, immunization should be deferred in pregnant women. Vaccination should also be deferred for those with a moderate or severe acute illness. Those with an allergy to any component in the HPV vaccine should not be offered vaccination.

How much does the vaccine cost?
Merck charges $120 a dose, or $360 for the series. Because the vaccine is recommended for routine use in targeted groups, the expense is expected to be covered by nearly all health-insurance plans. The vaccine is also included as part of the government’s Vaccines for Children program, assuring access for adolescent women younger than 19 years old. For the benefit of women aged 19-26 years who lack health insurance and/or coverage for the vaccine, Merck has created a patient assistance program.

Elizabeth wonders whether her sister, age 28, should also get the vaccine.The vaccine has not been studied in women aged 27 years and older, but clinical trials focusing on mid-adult-age women are ongoing. Off-label use is relatively common. Decisions about off-label use should include a consideration of the standard of care, along with a full discussion of potential risks and benefits with the patient. Additionally, health-plan coverage for off-label use of the vaccine is uncertain, so patients should be warned of the potential cost.

What about protecting boys and men?
The vaccine is not currently approved for males but may be in the future. While men and women transmit HPV infections back and forth, the focus on female populations is consistent with the greater burden of HPV-related clinical disease among women compared with men. One trial reported robust HPV antibody levels among boys and girls aged 9-15 years following vaccination.10 Seroconversion rates >99% were observed, with persistent seropositivity in 92% of subjects at month 18.

Elizabeth wonders whether she will need to continue with Pap smears after completing the HPV vaccine series.Girls and women who are vaccinated should continue with regular Pap-smear screening and gynecologic care. Use of the vaccine will reduce but not eliminate the risk of cervical cancer, so screening and early detection remain important.11

Is there a therapeutic vaccine for women with persistent HPV infections?
No, but various immunologic approaches to the development of a therapeutic HPV vaccine are being investigated.

Dr. Mahoney is associate professor of oncology at the Roswell Park Cancer Institute, Buffalo, N.Y., and associate professor of family medicine and public health at the State University of New York at Buffalo.


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2. Cates W Jr. Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. American Social Health Association Panel. Sex Transm Dis. 1999;26(4 Suppl):S2-S7.

3. Burk RD, Ho GY, Beardsley L, et al. Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women. J Infect Dis. 1996;174:679-689.

4. Brown DR, Shew ML, Qadadri B, et al. A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women. J Infect Dis. 2005;191:182-192.

5. Kataoka A, Claesson U, Hansson BG, et al. Human papillomavirus infection of the male diagnosed by Southern-blot hybridization and polymerase chain reaction: comparison between urethra samples and penile biopsy samples.J Med Virol. 1991;33:159-164.

6. 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.

7. Ley C, Bauer HM, Reingold A, et al. Determinants of genital human papillomavirus infection in young women. J Natl Cancer Inst. 1991;83:997-1003.

8. Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med. 2006;354:2645-2654.

9. Winer RL, Kiviat NB, Hughes JP, et al. Development and duration of human papillomavirus lesions, after initial infection. J Infect Dis. 2005;191:731-738.

10. Reisinger KS, Block SL, Lazcano E, et al. A randomized controlled trial to evaluate the safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine in preadolescents and adolescents. Presented at ESPID; May 3-5, 2006; Basel, Switzerland.

11. Garnett GP, Kim JJ, French K, Goldie SJ. Chapter 21: Modelling the impact of HPV vaccines on cervical cancer and screening programmes. Vaccine. 2006;24 Suppl 3:S178-186.