Immunization Issues

Human Papilloma Viruses (HPVs)

Updated: February 1, 2007

Human papillomaviruses (HPVs) are a group of more than 120 different viruses. They are called papillomaviruses because certain types may cause warts, or papillomas, which are benign (non-cancerous) tumors. Some HPV types are spread by casual skin-to-skin contact with another person; for example, Type 1 causes plantar warts on the feet and types 2 and 3 cause warts on the fingers.1 Others are acquired by intimate sexual contact.

Genital HPVs

Approximately 40 HPV types are primarily sexually transmitted from person to person (for example, genital-genital contact, oral-genital contact and sexual intercourse), infecting the oral, anal or genital areas of both men and women.2 Genital HPV infections are very common: by 50 years of age, 70-80% of women will have acquired genital HPV infection.

The Centers for Disease Control and Prevention (CDC) estimates that 6.2 million Americans get a new genital HPV infection each year.3 Sexually active adolescents and young adults are most likely to acquire genital HPV infection. Genital HPV infections are often acquired within a few months after beginning sexual activity. The prevalence declines with age after 25, but increases again in women about the time of menopause.4 Genital infection with more than one type of HPV is common.

  • The risk of acquiring HPV infection is increased by
    • younger age at sexual initiation,
    • the number of sexual partners, and
    • the number of the partner’s prior sexual partners.
  • Studies suggest that among young sexually active women who are free of genital HPV, as many as 3 out of every 100 will acquire genital HPV infection each month.4
  • With each new sex partner the chances of getting genital HPV increases
    • The rate of acquisition of genital HPV has been estimated to be between 5 and 100% per act of sexual intercourse among college women with a new sex partner.5
  • Twenty percent of women 18-25 years of age participating in a vaccine trial had already been infected with HPV 16, the most common type associated with cervical cancer, before the study began.6

Some of these viruses can cause genital warts and others can cause anogenital cancers:

  • Types 6 and 11 may cause genital warts. These two types of HPV are responsible for more than 90% of genital warts. While it is rare, these types may also spread from mother to infant during delivery and can cause warts in the upper respiratory tract (throat, larynx) of the child.
  • Types 16 and 18 and others, known collectively as “high-risk” HPV types, may cause abnormal Pap tests and cervical cancer in women as well as a number of other cancers in both men and women (such as the vulva, vagina, anus, or penis). Although there are a number of other risk factors for cervical cancer, being infected with a high-risk type HPV appears to be a necessary factor for cervical cancer development.7
  • High-risk HPV infections are also thought to cause 85% of anal cancers, 50% of other anogenital cancers, 20% of cancers of the throat and mouth and 10% of cancers of the larynx (voice box) and esophagus.4

Outcomes of genital HPV infection

The vast majority of people recover from genital HPV infection uneventfully. Most genital HPV infections cause no symptoms and are cleared by the immune system within a few weeks or months. Because most persons with HPV infection do not show any symptoms,

  • they do not realize that they are infected.
  • they do not realize that they can infect their sex partner.

However, some people develop persistent genital HPV infection.

  • Persistent infection with some types of HPV can lead to genital warts in some people.
  • Persistent infection with high-risk types of HPV can lead to pre-cancerous changes on pap smears in some women.
    • These precancerous changes can lead to carcinoma-in-situ (localized cervical cancer), which can progress to invasive cervical cancer in some people, if not treated.

High-risk HPVs can cause cancer. Although the vast majority of women recover uneventfully from high-risk genital HPV infection, some develop persistent infections with high-risk HPVs which can lead to cancer.

  • The vast majority of people with high-risk type HPV infections clear the infection and do not develop cervical cancer.78
  • But some develop persistent (on-going) HPV infection. Persistent cervical infection with a high-risk HPV type does not usually lead to cervical cancer in all women but it does in a small fraction of women.
    • HPV-16 causes approximately 50-60% of cervical cancers.
    • HPV-18 causes another 10-20% of these cancers.
    • The American Cancer Society estimated that in 2002 about 13,000 women in the US developed invasive cervical cancer and about 4,100 women died from this disease.9
    • Globally, HPV causes about 470,000 cases of cervical cancer per year.10
  • Among HPV infected women, other factors (such as cigarette smoking, long term use of oral contraceptives, and co-infection with other sexually transmitted agents) influence the risk of progression to precancerous changes and to invasive cancer.
  • Persistent high-risk HPV infection is a necessary step for the development of cervical and other anogenital cancers. The statistical associations between high-risk HPVs and cervical cancer are some of the strongest there are in cancer epidemiology. In other words, essentially all cervical cancers are associated with high-risk HPVs.

Detection of genital HPV infection

In developed countries, most women are diagnosed with HPV infection on the basis of abnormal Pap tests—the primary cancer-screening tool for cervical cancer. The Pap test screens for changes in cervical cells that are often caused by HPV and may indicate precancerous cells. Pap screening—and then the treatment of any abnormalities that are detected—prevents progression to cervical cancer.

  • Programs to screen for cervical cancer and to treat low-grade lesions before progression to invasive cancer have reduced the incidence of invasive cancer in those countries that are able to afford such programs.9
  • In the US, since the introduction of Pap smear screening, the rates of invasive cervical cancer have fallen by 75% because of early detection.11
    • The sensitivity (likelihood of detecting precancerous cells) of Pap screening is about 50-60% on a single Pap smear but increases when repeated Pap smears are performed.8
    • The most sensitive tests—which are being used more frequently now—for the detection of HPV requires molecular detection of the viral DNA in Pap tests or in cells collected by other means.

It is estimated that 40 million women received Pap smears in the US in 1998 to screen for precancerous lesions and cancer.12 Unfortunately—while widely available for free in the US—many women in the US13 and most women in developing countries11 do not have access to routine screening.

Costs for all HPV-related expenditures from one health plan, extrapolated to the entire US were $3.4 billion of which $2.1 billion was for screening tests.12

The most sensitive tests for the diagnosis of high-risk genital HPV infection involves the detection of viral DNA from cervical or vaginal samples. Many clinicians will perform HPV testing in women with mildly abnormal Pap tests, in order to guide further management. HPV testing along with Pap testing may also be recommended in women over 30 years of age.

These tests have greatly reduced the mortality from cervical cancer by allowing treatment before the cancer develops or in early stages of the cancer. Unfortunately, 50% of newly diagnosed invasive cervical cancers are detected in women who have not been previously screened with Pap smears and another 10% have not had a Pap test in more than 5 years.14

HPV Infection in Men

Much less is known about the epidemiology and natural history of genital HPV infections in men than in women.315 The disease spectrum also ranges from unapparent infection to genital warts and anogenital cancers. Tests for genital HPVs in men have not been well standardized and as a consequence estimates of prevalence vary markedly. However, recent studies suggest that rates of infection in men may be similar to that in women.

HPV Infection in Children

Studies in young children have demonstrated that a small percentage of children 6-11 and 11-12 years of age already have been infected with HPV.1617 The proportion increases with age, peaking in adolescence and young adulthood.

Children can be infected with genital HPV by transmission from mother to newborn at delivery (which is rare), accidental inoculation (such as adult hand to genital contact during bathing) and by sexual abuse.

More Information about HPVs and Cancer

Selected References

  • 1. Harper DM. (2004) Why am I scared of HPV? CA Cancer J Clin 54:245-7.
  • 2. National Cancer Institute (2005). Human Papillomaviruses and Cancer: Questions and Answers.
  • 3. a. b. Centers for Disease Control. (2204). Human Papillomavirus (HPV) Infection.
  • 4. a. b. c. Trottier H, Franco EL. (2006). The epidemiology of genital human Papillomavirus infection. Vaccine, in press.
  • 5. Burchell AN, Richardson H, Mahmud SM, et al. (2006) Modelling the sexual transmissibility of human Papillomavirus infection using stochastic computer simulation and empirical data from a cohort study of young women in Montreal, Canada. Amercian J Epidemiology 163:534-543.
  • 6. Koutsky LA, Ault KA, Wheeler CM (2002). A Controlled Trial of a Human Papillomavirus Type 16 Vaccine. The New England Journal of Medicine, 347(21):1645-1651.
  • 7. a. b. Castellsague X, Diaz M, de Sanjose S, et al. (2006). Worldwide human Papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 98:303-315.
  • 8. a. b. Scheurer ME, Tortolero-Luna G, Adler-Storthz K. ((2005) Human Papillomavirus infection: biology, epidemiology, and prevention. Int J Gynecol Cancer 15:727-46.
  • 9. a. b. Saslow D, Runowicz CD, Solomon D, et al. (2002) American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 52:342-62.
  • 10. Ferlay J, Bray F, Pisani P. (2004) GLOBOCN 2002: cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5. Version 2.0. Lyon: IARC Press.
  • 11. a. b. Katz IT, Wright AA. (2006) Preventing cervical cancer in the developing world. N Engl J Med 354: 11.
  • 12. a. b. Insinga RP, Glass AG, Rush BB. (2004) The health care costs of cervical human Papillomavirus-related disease. Am J Ob Gyn 191:114-20.
  • 13. Adams Hillard PJ, Kahn JA. (2005) Understanding Papillomavirus in adolescence and young adulthood: opportunities for understanding and preventing infection. J Adol Health 37: S1-2.
  • 14. Sawaya GF, Grimes DA. (1999) New technologies in cervical cytology screening: a word of caution. Obstet Gynecol 94:307-10.
  • 15. Partridge JM, Koutsky LA. (2006) Genital human Papillomavirus infection in men. Lancet Infect Dis 6:21-31.
  • 16. Stone KM, Karem KL, Sternberg MR, et al. (2002) Seroprevalence of human Papillomavirus type 16 infection in the United States. J IInfect Dis 186:1396-402.
  • 17. Dunne EF, Karem KL, Sterberg MR, et al. (2005) Seroprevalence of human papillomavirus type 16 in children. J Infect Dis 191:1817-9.