Managing HPV: A New Era in Patient Care – Impact and Epidemiology

(Published June 2009)

Impact

Genital human papillomavirus (HPV) infection is the most commonly diagnosed sexually transmitted infection in the United States and is a necessary cause of cervical cancer.^1,2 HPV also is associated with external genital warts and cancer of the penis, vagina, vulva, anus, and oropharynx.²

Approximately 11,150 women are diagnosed with cervical cancer each year in the United States.³ Most cases of invasive cervical cancer and death due to cervical cancer occur in women who did not receive proper screening.⁴ Cervical cancer screening has not been equally accessible to all women, and the incidence of cervical cancer is higher among ethnic minorities and poor women.⁴

One hundred percent of the cervical cancer cases diagnosed each year are believed to be attributable to HPV.³ This means that essentially all cervical cancers are associated with persistent infection with “high-risk” HPV. High-risk types are associated with cervical and other cancers, whereas low-risk types are associated with external genital warts but not cancer. These HPV types (see Table 1) have been shown to be carcinogenic for the cervix.²

Prevalence

HPV infection is common among sexually active individuals, with a lifetime risk of about 75 percent.⁷ As shown in Figure 1, HPV prevalence varies by age and is highest for young women, decreasing in the middle age range (30 to 60 years old). Prevalence by type varies somewhat by region, for reasons that are not yet known. This figure compares data from cohorts in Portland, Oregon, and Guanacaste, a rural province in Costa Rica.

The high prevalence of HPV infection among young women has been confirmed in several studies. A study of 603 female college students found that 19.7 percent of the women were already HPV DNA positive at study initiation.⁹ Over 2 years of follow-up, 39 percent of the women who were initially HPV DNA negative became HPV DNA positive. High-risk types of HPV such as HPV 16 and 18 were the types most commonly identified in these young college-aged women.

Transmission

Unlike most sexually transmitted infections (STIs), which spread via body fluids, HPV is transmitted through direct genital contact, most commonly by sexual intercourse.¹⁰ Genital contact in the absence of intercourse is a plausible means for HPV transmission, but the risk associated with such contact is much lower than that for intercourse.^10-11 Transmission via inanimate objects such as clothing is thought to be unlikely, but the true risk is unknown.¹⁰

Natural History

Progression to precancer occurs when infection with high-risk HPV persists over time (see Figure 2). In most cases, HPV infection—with either a low- or high-risk type—is cleared by the body. Observational studies have shown that about 90 percent of women infected with a particular HPV type will clear the infection within two years.¹² Less than half of women who develop HPV infection will have persistence of the same HPV type 12 months later.¹ HPV type 16 combines high rates of persistence with carcinogenicity, resulting in a risk of CIN-3 of 40 percent at 5 years.¹²

Risk Factors

In almost all studies of HPV infection, the most consistent predictors of infections are measures of sexual activity. Specific risk factors for HPV infection include:¹⁴

• Multiple partners
• Younger compared to older age at sexual debut
• Lack of condom use

In a study of college women, the strongest risk factor for infection was having a regular sexual partner who had six or more lifetime partners.¹⁵

Risk factors for persistent HPV infection and/or neoplastic progression are slightly different and include:^12,16,17

• Smoking
• HPV type
• Increasing age
• Lack of condom use
• Immunodeficiency (e.g., HIV)
• Possibly other STIs, such as chlamydia
• Possibly oral contraceptive (OC) use

Some studies have suggested that OC use for more than 5 years and the presence of STIs other than HPV may act as weak cofactors in neoplastic progression and/or persistence of HPV infection.^18-20

References:

1. Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine. 2006;24(suppl 1):S1/4-15.
2. Munoz N, Castellsagué X, de Gonzalez AB, Gissmann L. HPV in the etiology of human cancer. Vaccine. 2006; 24(suppl 3):S3/1-10.
3. American Cancer Society. Cancer Facts and Figures. 2007. Available at: www.cancer.org/downloads/STT/CAFF2006PWSecured.pdf. Accessed March 20, 2007.
4. Anhang R, Goodman A, Goldie SJ. HPV communication: review of existing research and recommendations for patient education. CA Cancer J Clin. 2004;54:248-59.
5. Lacey CJN, Lowndes CM, Shah KV. Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24S3:S3/35-41.
6. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsagué X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518-27.
7. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. 1997;102:3-8.
8. Schiffman M, Kjaer SK. Natural history of anogenital human papillomavirus and neoplasia. J Natl Cancer Inst Monogr. 2003;31:14-9.
9. Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218-26.
10. Centers for Disease Control and Prevention. Human Papillomavirus: HPV Information for Clinicians. November 2006.
11. Burchell AN, Winer RL, de Sanjose S, Franco EL. Epidemiology and transmission dynamics of genital HPV infection. Vaccine. 2006;24(suppl 3):S3/52-62.
12. Moscicki AB, Schiffman M, Kjaer S, Villa LL. Updating the natural history of HPV and anogenital cancer. Vaccine. 2006;24S3:S3/42-51.
13. Figure Courtesy of M. Schiffman, National Cancer Institute.
14. Ley C, Bauer HM, Reingold A, Schiffman MH, Chambers JC, Tashiro CJ, et al. Determinants of genital human papillomavirus infection in young women. J Natl Cancer Inst. 1991;83:997-1003.
15. Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423-8.
16. Hogewoning CJ, Bleeker MC, van den Brule AJ, Voorhorst FJ, Snijders PJ, Berkhof J, et al. Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial. Int J Cancer. 2003;107:811-6.
17. Moscicki AB, Ellenberg JH, Farhat S, Xu J. Persistence of human papillomavirus infection in HIV-infected and -uninfected adolescent girls: risk factors and differences, by phylogenetic type. J Infect Dis. 2004;190:37-45.
18. Castellsagué X, Muñoz N. Chapter 3: Cofactors in human papillomavirus carcinogenesis—role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr. 2003(31):20-8.
19. Castle PE, Giuliano AR. Chapter 4: Genital tract infections, cervical inflammation, and antioxidant nutrients—assessing their roles as human papillomavirus cofactors. J Natl Cancer Inst Monogr. 2003(31):29-34.
20. Moreno V, Bosch FX, Muñoz N, Meijer CJ, Shaj KV, Walboomers JM, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet. 2002;359(9312):1085-92.