Cervical Cancer Prevention (PDQ®)–Health Professional Version

Overview

Note: Separate PDQ summaries on Cervical Cancer Screening and Cervical Cancer Treatment are also available.

Who Is at Risk?

Carcinogenic types of human papillomavirus (HPV) are the primary, etiologic, infectious agents that cause virtually all cases of cervical cancer. HPV type 16 (HPV-16) and HPV type 18 (HPV-18) are most often associated with invasive disease.[1,2] Because HPV is transmitted during sexual activity, there is an association between an increased risk for cervical cancer, the beginning of sexual activity at a younger age, and with a greater number of lifetime sexual partners.[3] Immunosuppression is another risk factor for cervical cancer; for example, coinfection with human immunodeficiency virus may lead to long-term persistence of viral infection (i.e., failure to clear).[4,5] Once HPV infection occurs, several additional risk factors are associated with a higher risk of the eventual development of cervical cancer. These include high parity, long-term use of oral contraceptives, and active and passive cigarette smoking.[6-8] The risk increases with longer duration and intensity of smoking. Diethylstilbestrol (DES) exposure in utero is also associated with an increased risk of developing cervical dysplasia.[9]

Factors With Adequate Evidence of an Increased Risk of Cervical Cancer

Human papillomavirus (HPV)

Based on solid evidence from observational studies, HPV infection is associated with the development of cervical cancer.

Magnitude of Effect: HPV has been implicated as the primary etiologic infectious agent causing virtually all cases of cervical cancer.

Study Design: Evidence obtained from cohort and case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Immunosuppression

Based on solid evidence, being immunosuppressed is associated with an increased risk of cervical cancer.

Study Design: Evidence obtained from cohort and case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Sexual activity at an early age and with a greater number of partners

Based on solid evidence, sexual activity at a younger age and an increasing number of sexual partners are both associated with an increased risk of HPV infection and subsequent development of cervical cancer.

Magnitude of Effect: Women who experience first sexual intercourse at age 17 years or younger or women who have had six or more lifetime sexual partners have approximately two to three times the risk of squamous cell carcinoma or adenocarcinoma of the cervix, compared with women aged 21 years or older or who have a single sexual partner.[3]

Study Design: Evidence obtained from cohort and case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

High parity

Based on solid evidence, high parity is associated with increased risk of cervical cancer in HPV-infected women.

Magnitude of Effect: Among HPV-infected women, those who have had seven or more full-term pregnancies have approximately four times the risk of squamous cell cancer compared with nulliparous women, and HPV-infected women also have two to three times the risk of women who have had one or two full-term pregnancies.[6]

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Long-term use of oral contraceptives

Based on solid evidence, long-term use of oral contraceptives is associated with increased risk of cervical cancer in HPV-infected women.

Magnitude of Effect: Among HPV-infected women, those who used oral contraceptives for 5 to 9 years have approximately three times the incidence of invasive cancer, and those who used them for 10 years or longer have approximately four times the risk.[7]

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Cigarette smoke exposure

Based on solid evidence, cigarette smoking, both active and passive, is associated with an increased risk of cervical cancer in HPV-infected women.

Magnitude of Effect: Among HPV-infected women, current and former smokers have approximately two to three times the incidence of high-grade cervical intraepithelial neoplasia or invasive cancer. Passive smoking is also associated with increased risk but to a lesser extent.

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Diethylstilbestrol (DES) exposure

Based on solid evidence, DES exposure is associated with an increased risk of developing clear cell adenocarcinoma of the cervix.

Magnitude of Effect: About one in 1,000 women exposed to DES in utero will develop a clear cell adenocarcinoma of the cervix.

Study Design: Evidence obtained from cohort studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Factors With Adequate Evidence of a Decreased Risk of Cervical Cancer

Sexual abstinence

Based on solid evidence, abstinence from sexual activity is associated with a near-total reduction in the risk of developing cervical cancer.

Magnitude of Effect: Sexual abstinence essentially precludes HPV transmission.

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Interventions With Adequate Evidence of a Decreased Risk of Cervical Cancer

Note: Based on solid evidence, screening with the Papanicolaou (Pap) test and screening with the HPV DNA test reduces cervical cancer incidence. These screening tests are covered in the Cervical Cancer Screening summary (refer to the PDQ summary on Cervical Cancer Screening for more information).

HPV vaccination: benefits

Based on solid evidence, vaccination against HPV-16/HPV-18 is effective in preventing HPV infection in HPV-naive individuals and is associated with a reduced incidence of cervical intraepithelial neoplasia 2 and 3. By extrapolation, these vaccines should also be associated with a reduced incidence of cervical cancer.

Magnitude of Effect: Vaccination against HPV-16 and HPV-18 reduces incident and persistent infections with efficacy of 91.6% (95% confidence interval [CI], 64.5%–98.0%) and 100% (95% CI, 45%–100%), respectively. Efficacy beyond 6 to 8 years is not known.

Study Design: Evidence obtained from randomized controlled trials.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

HPV vaccination: harms

Based on solid evidence, harms of HPV vaccines include injection-site reactions, dizziness and syncope, headache, and fever. Vaccination during pregnancy has not been associated with adverse pregnancy outcomes.[10] Allergic reactions occur rarely.

Study Design: Evidence obtained from randomized controlled trials.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Use of barrier protection during sexual intercourse: benefits

Based on solid evidence, the use of barrier methods (e.g., condoms) during sexual intercourse is associated with a decreased risk of cervical cancer.

Magnitude of Effect: Total use of barrier protection decreases cervical cancer incidence (relative risk, 0.4; 95% CI, 0.2–0.9).

Study Design: Evidence obtained from cohort and case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Use of barrier protection during sexual intercourse: harms

Based on fair evidence, the use of barrier methods during sexual intercourse is associated with few serious harms. Barrier methods can break, potentially resulting in unintended pregnancy. Allergic reactions to the barrier material (e.g., natural latex) can occur.

Study Design: Evidence obtained from cohort and case-control studies.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

References

Schiffman M, Castle PE, Jeronimo J, et al.: Human papillomavirus and cervical cancer. Lancet 370 (9590): 890-907, 2007. [PUBMED Abstract]
Trottier H, Franco EL: The epidemiology of genital human papillomavirus infection. Vaccine 24 (Suppl 1): S1-15, 2006. [PUBMED Abstract]
Berrington de González A, Green J; International Collaboration of Epidemiological Studies of Cervical Cancer: Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 120 (4): 885-91, 2007. [PUBMED Abstract]
Abraham AG, D'Souza G, Jing Y, et al.: Invasive cervical cancer risk among HIV-infected women: a North American multicohort collaboration prospective study. J Acquir Immune Defic Syndr 62 (4): 405-13, 2013. [PUBMED Abstract]
Grulich AE, van Leeuwen MT, Falster MO, et al.: Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 370 (9581): 59-67, 2007. [PUBMED Abstract]
Muñoz N, Franceschi S, Bosetti C, et al.: Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 359 (9312): 1093-101, 2002. [PUBMED Abstract]
Moreno V, Bosch FX, Muñoz N, et al.: Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 359 (9312): 1085-92, 2002. [PUBMED Abstract]
Appleby P, Beral V, Berrington de González A, et al.: Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 118 (6): 1481-95, 2006. [PUBMED Abstract]
Hoover RN, Hyer M, Pfeiffer RM, et al.: Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med 365 (14): 1304-14, 2011. [PUBMED Abstract]
Scheller NM, Pasternak B, Mølgaard-Nielsen D, et al.: Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes. N Engl J Med 376 (13): 1223-1233, 2017. [PUBMED Abstract]