What is HPV?

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Infection with HPV is common, and it is estimated that 291 million women worldwide have HPV, with the incidence being highest among young women aged 20 to 29 years.^1–3

It is transmitted between humans via skin-to-skin or mucosal-to-mucosal contact with sexual intercourse as the primary route of infection.^2,4,5 Risk of infection from other routes, such as oral sexual contact or digital-genital contact, is minimal and there is currently not enough data to support that contact with HPV-DNA positive fomites definitively establishes infection.^2,6 Once infected, HPV can persist from 4 to 14 months, making it possible that infection from an earlier sexual relationship can persist in the context of a new sexual relationship.^7–9

There are more than 80 types of HPV and HPV type is important in determining the risk of development of cervical cancer. A 2003 study published in the New England Journal of Medicine demonstrated that 6 HPV types (6, 11, 40, 42, 43, 44) are low-risk and 15 HPV types, specifically HPV 16 and 18, are high-risk.¹⁰ Of the over 1,900 women with cervical cancer who were tested, 90.7% tested positive for HPV. Of these, 95% had a high-risk HPV type.

HPV can cause a range of conditions from benign genital warts (HPV types 6 and 11) to precancerous lesions, and cancer itself (HPV types 16 and 18). It is the single greatest risk factor for developing cervical cancer. HPV prevalence in cervical cancer specimens is greater than 90%.^11,12 HPV initially infects cells at the transformation zone of the cervix and produces oncoproteins which disrupt the normal cell cycle, initiating cervical carcinogenesis.^5,13 While HPV infections can be transient and cleared by the immune system, persistent infections are associated with an increased risk of the development of precancerous lesions.^7–9,14 Even with normal screening, patients who are HPV positive have a 10-year risk of developing precancerous lesions or cancer of up to 20%.¹⁵ HPV testing increases the sensitivity of detection of grade 3 cervical intraepithelial lesions or worse, and the risk of developing invasive cancer after a negative test is significantly lower.¹⁶ Risk factors for persistent HPV infection include smoking, immunosuppression, HIV infection, older age, infection with multiple types of HPV, and infection with a high-risk type of HPV.^7,17

^References

1. Dunne EF, Unger ER, Sternberg M, et al. Prevalence of HPV infection among females in the United States. JAMA. 2007;297(8):813-819. doi:10.1001/jama.297.8.813
2. Burchell AN, Winer RL, de Sanjosé S, Franco EL. Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine. 2006;24 Suppl 3:S3/52-61. doi:10.1016/j.vaccine.2006.05.031
3. Centers for Disease Control and Prevention. Genital HPV Infection - Fact Sheet. 2019. https://www.cdc.gov/std/hpv/stdfact-hpv.htm. Accessed February 15, 2021.
4. Collins SI, Mazloomzadeh S, Winter H, et al. Proximity of first intercourse to menarche and the risk of human papillomavirus infection: a longitudinal study. Int J Cancer. 2005;114(3):498-500. doi:10.1002/ijc.20732
5. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890-907. doi:10.1016/S0140-6736(07)61416-0
6. Liu Z, Rashid T, Nyitray AG. Penises not required: a systematic review of the potential for human papillomavirus horizontal transmission that is non-sexual or does not include penile penetration. Sex Health. 2016;13(1):10-21. doi:10.1071/SH15089
7. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338(7):423-428. doi:10.1056/NEJM199802123380703
8. Franco EL, Villa LL, Sobrinho JP, et al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis. 1999;180(5):1415-1423. doi:10.1086/315086
9. Giuliano AR, Harris R, Sedjo RL, et al. Incidence, prevalence, and clearance of type-specific human papillomavirus infections: The Young Women’s Health Study. J Infect Dis. 2002;186(4):462-469. doi:10.1086/341782
10. Muñoz N, Bosch FX, de Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348(6):518-527. doi:10.1056/NEJMoa021641
11. Bosch FX, Manos MM, Muñoz N, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995;87(11):796-802. doi:10.1093/jnci/87.11.796
12. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12-19. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
13. Münger K, Basile JR, Duensing S, et al. Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene. 2001;20(54):7888-7898. doi:10.1038/sj.onc.1204860
14. Schlecht NF, Kulaga S, Robitaille J, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA. 2001;286(24):3106-3114. doi:10.1001/jama.286.24.3106
15. Kjaer S, Høgdall E, Frederiksen K, et al. The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res. 2006;66(21):10630-10636. doi:10.1158/0008-5472.CAN-06-1057
16. Ronco G, Giorgi-Rossi P, Carozzi F, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol. 2010;11(3):249-257. doi:10.1016/S1470-2045(09)70360-2
17. Castle PE, Schiffman M, Herrero R, et al. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis. 2005;191(11):1808-1816. doi:10.1086/428779