Does contraceptive use impact cancer risk?

Contraceptive use has been reported as a risk factor for cervical cancer1,2; however, since the discovery of the strong link between human papillomavirus (HPV) infection and cervical cancer, evidence has been unclear on its association. Findings from a new study indicate that it may well be HPV infection, rather than use of hormonal contraception, that causes high-grade cervical intraepithelial neoplasia (CIN).3

The new study looked at the relationship of oral contraceptive (OC) use, hormonal contraceptive use, and multiparity as potential risk factors for cervical precancer. More research is needed on the subject, says Philip Castle, PhD, MPH, an investigator with the National Cancer Institute in Bethesda, MD, and lead author of the study. Castle points to such research avenues as:

  • ascertainment of specific contraceptives used and their composition of hormones in epidemiologic studies to assess any dose-response relationships;
  • analyses in cohort studies to examine the stage at which hormonal contraceptive use might influence cervical carcinogenesis: HPV acquisition, HPV persistence, development of cervical precancer, and development of cancer;
  • in vitro models to examine the impact of contraceptive hormones on expression of HPV viral genes.

As Contraceptive Technology points out, research indicates that condoms help provide protection against HPV and other sexually transmitted diseases that are transmitted primarily through skin-to-skin contact.4

To perform the analysis, scientists looked at 5,060 women with minimally abnormal Pap smears who were enrolled in the ASCUS (atypical squamous cells of unknown significance) and LSIL (low-grade squamous intraepithelial lesion) Triage Study (ALTS), a randomized clinical trial designed to evaluate management strategies.

Cervical specimens collected at enrollment were tested for HPV DNA. Scientists then calculated odds ratios developing CIN3 during the two-year study for women who were found to have infections with oncogenic HPV at baseline.

Oral contraceptive use, Norplant use, a history of pregnancy, age at first pregnancy, lifetime numbers of pregnancies, and lifetime numbers of live births were not associated with CIN3, researchers conclude.3 Current use of the contraceptive injectable depot medroxyprogesterone acetate (DMPA, Depo-Provera, Pfizer, New York City) was found to marginally increase the risk of CIN3; however, because other contraceptives did not have the same impact, researchers said further examination is needed.3 Previous studies have not found an association of injectable contraceptive use and cancer.5,6

Screening is vital

Most well-controlled studies, including three case-controlled reports,7-9 have found no association between OC use and CIN, says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville.

In the United States, HPV 16 alone accounts for more than half of all cervical cancer cases, followed by HPV 18, 31, and 45.10 While strides have been made in reducing the impact of cervical cancer in America, 2005 statistics from the American Cancer Society (ACS) estimate about 10,370 cases of invasive cervical cancer to be diagnosed in the United States.11 About 3,710 women will die from cervical cancer in the United States during 2005, according to the ACS.11

"From a public health perspective, the most important risk factors for cervical cancer are persistent HPV infection of a carcinogenic HPV type and failure to be screened," says Castle. "Regular screening will protect women from cervical cancer."

References

  1. Moreno V, Bosch FX, Munoz 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 2002; 359:1,085-1,092.
  2. Smith JS, Green J, Berrington DG, et al. Cervical cancer and use of hormonal contraceptives: A systematic review. Lancet 2003; 361:1,159–1,167.
  3. Castle PE, Walker JL, Schiffman M, et al. Hormonal contraceptive use, pregnancy and parity, and the risk of cervical intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal or mildly abnormal cytology. Int J Cancer 2005; 117:1,007-1,012.
  4. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology: 18th revised edition. New York City: Ardent Media; 2004.
  5. Shapiro S, Rosenberg L, Hoffman M, et al. Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa). Cancer Causes Control 2003; 14:485-495.
  6. Thomas DB, Ray RM, Koetsawang A, et al. Human papillomaviruses and cervical cancer in Bangkok. I. Risk factors for invasive cervical carcinomas with human papillomavirus types 16 and 18 DNA. Am J Epidemiol 2001; 153:723-731.
  7. Kjaer SK, Engholm G, Dahl C, et al. Case-control study of risk factors for cervical squamous-cell neoplasia in Denmark, III: role of oral contraceptive use. Cancer Causes Control 1993; 4:513-519.
  8. Coker AL, McCann MF, Hulka BS, et al. Oral contraceptive use and cervical intraepithelial neoplasia. J Clin Epidemiol 1992; 45:1,111-1,118.
  9. Schiffman M, Bauer HM, Hoover RN, et al. Epidemiologic evidence showing that human papilloma infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 1993; 85:958-964.
  10. Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer — burden and assessment of causality. J Natl Cancer Inst Monogr 2003; 3:3-13.
  11. American Cancer Society. Detailed Guide: Cervical Cancer What Are the Key Statistics about Cervical Cancer? January 2005; accessed at: www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_cervical_cancer_8.asp?sitearea=.