How does high-risk HPV cause cancer?

HPV infects epithelial cells. These cells, which are organized in layers, cover the inside and outside surfaces of the body, including the skin, the throat, the genital tract, and the anus.

Once HPV enters an epithelial cell, the virus begins to make the proteins it encodes. Two of the proteins made by high-risk HPVs (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death.

Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results. As the persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth, leading to the formation of an area of precancerous cells and, ultimately, a cancerous tumor.

Other factors may increase the risk that an infection with a high-risk HPV type will persist and possibly develop into cancer.19 These include:

  • Smoking or chewing tobacco (for increased risk of oropharyngeal cancer)
  • Having a weakened immune system
  • Having many children (for increased risk of cervical cancer)
  • Long-term oral contraceptive use (for increased risk of cervical cancer)
  • Poor oral hygiene (for increased risk of oropharyngeal cancer)
  • Chronic inflammation

Researchers believe that it can take between 10 and 30 years from the time of an initial HPV infection until a tumor forms. However, even when severely abnormal cells are seen on the cervix (a condition called cervical intraepithelial neoplasia 3, or CIN3), these do not always lead to cancer. The percentage of CIN3 lesions that progress to invasive cervical cancer has been estimated to be 50% or less.20

References

1. American Cancer Society. Cancer Facts & Figures 2014Exit Disclaimer. Atlanta: American Cancer Society; 2014. Accessed February 25, 2014.

2. Lowy DR, Schiller JT. Reducing HPV-associated cancer globally. Cancer Prevention Research (Philadelphia) 2012;5(1):18-23. [PubMed Abstract]

3. Centers for Disease Control and Prevention. Human papillomavirus-associated cancers—United States, 2004-2008. Morbidity and Mortality Weekly Report 2012; 61(15):258-261. [PubMed Abstract]

4. Satterwhite CL, Torrone E, Meites E, et al. Sexually transmitted infections among US women and men: Prevalence and incidence estimates, 2008. Sexually Transmitted Diseases 2013; 40(3):187-193. [PubMed Abstract]

5. Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sexually Transmitted Diseases 2014; 41(11):660-664. [PubMed Abstract]

6. Hariri S, Unger ER, Sternberg M, et al. Prevalence of genital human papillomavirus among females in the United States, the National Health and Nutrition Examination Survey, 2003–2006. Journal of Infectious Diseases 2011; 204(4):566–573. [PubMed Abstract]

7. Division of STD Prevention (1999). Prevention of genital HPV infection and sequelae: report of an external consultants’ meeting. Atlanta, GA: Centers for Disease Control and Prevention. Retrieved December 27, 2011.

8. Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women. New England Journal of Medicine 2006; 354(25):2645–2654. [PubMed Abstract]

9. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. Journal of Clinical Oncology 2011; 29(32):4294–4301. [PubMed Abstract]

10. Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 2008; 113(10 Suppl):3036-3046. [PubMed Abstract]

11. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infections in 2008: A review and synthetic analysis. Lancet Oncology 2012; 13(6):607-615. [PubMed Abstract]

12. Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. Journal of the National Cancer Institute 2013; 105(3):175-201. [PubMed Abstract]

13. Collins S, Mazloomzadeh S, Winter H, et al. High incidence of cervical human papillomavirus infection in women during their first sexual relationship. British Journal of Obstetrics and Gynaecology 2002; 109(1):96-98. [PubMed Abstract]

14. Winer RL, Feng Q, Hughes JP, et al. Risk of female human papillomavirus acquisition associated with first male sex partner. Journal of Infectious Diseases 2008; 197(2):279-282. [PubMed Abstract]

15. Hildesheim A, Herrero R, Wacholder S, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: A randomized trial. JAMA 2007; 298(7):743–753. [PubMed Abstract]

16. Schiller JT, Castellsague X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012; 30 Suppl 5:F123-138. [PubMed Abstract]

17. Mirghani H, Amen F, Blanchard P, et al. Treatment de-escalation in HPV-positive oropharyngeal carcinoma: Ongoing trials, critical issues and perspectives. International Journal of Cancer 2015;136(7):1494-503 [PubMed Abstract]

18. Urban D, Corry J, Rischin D. What is the best treatment for patients with human papillomavirus-positive and -negative oropharyngeal cancer? Cancer 2014; 120(10):1462-1470. [PubMed Abstract]

19. Shi R, Devarakonda S, Liu L, Taylor H, Mills G. Factors associated with genital human papillomavirus infection among adult females in the United States, NHANES 2007-2010. Biomed Central Research Notes 2014; 7:544. [PubMed Abstract]

20. McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: A retrospective cohort study. Lancet Oncology 2008; 9(5):425-434. [PubMed Abstract]

Source: National Cancer Institute.