EXECUTIVE SUMMARY

Preliminary research suggests that medroxyprogesterone acetate (MPA), the active ingredient in the contraceptive injection DMPA, may be effective in preventing cervical cancer.

Investigators at the University of Houston reported that mice receiving MPA did not develop cervical cancer.

Cervical intraepithelial neoplasia (CIN) was absent in most MPA-treated mice, suggesting that MPA may not only prevent CIN from progressing to invasive cancer, but also may promote its regression.

Other contraceptive methods may be effective against cervical cancer. Research indicates that copper and hormonal IUDs were associated with 30% reduction in incidence of invasive cervical cancer.


Statistics from the American Cancer Society indicated that about 13,170 new cases of invasive cervical cancer would be diagnosed in the United States in 2019, and about 4,250 women will die from the disease.1 Preliminary research suggests that medroxyprogesterone acetate (MPA), the active ingredient in the contraceptive injection DMPA, may be effective in preventing cervical cancer.2

Investigators at the University of Houston reported that mice receiving MPA did not develop cervical cancer. Further, researchers found that cervical intraepithelial neoplasia (CIN) was absent in most MPA-treated mice, suggesting that MPA may not only prevent CIN from progressing to invasive cancer, but also may promote its regression. Study results indicated that MPA inhibited cell proliferation and promoted apoptosis in CIN lesions. Also, data suggested that the preventive effect of MPA was absent in human papillomavirus (HPV) transgenic mice in which the expression of progesterone receptor was genetically prevented.2

Next Steps

What is the next step in research for the University of Houston scientists? According to the paper’s lead author, Sanghyuk Chung, PhD, associate professor in the Center for Nuclear Receptors and Cell Signaling at the university’s department of biology and biochemistry, the focus is on determining how MPA prevents cervical cancer.

“MPA is associated with an increased risk of breast cancer,” notes Chung. “Understanding of the mechanism of MPA will help us develop a better chemopreventive method.”

Chung’s lab is examining the roles that estrogen receptors and progesterone receptors play in cervical cancer. Scientists are using the HPV transgenic mouse model, and the lab’s own orthotopic xenograft mouse model.

Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences in Pomona, CA, notes that research indicated that copper and hormonal IUDs were associated with a 30% reduction in incidence of invasive cervical cancer.3

The 2017 analysis, the first to combine data from multiple studies on IUDs and cervical cancer, included data from 16 observational studies involving more than 12,000 women worldwide. In 2011, a pooled analysis of individual data from two large studies by the International Agency for Research on Cancer and the Institut Català d’Oncologia, a Spanish-based oncology research program, showed similar results.4 In that analysis, IUDs reduced the risk of cervical cancer by 45%, compared with never using one. The protective effect was apparent in the first year of use, and continued for as long as 10 years, the researchers noted.

Authors of the 2011 analysis used data from 10 studies of cervical cancer performed in eight countries, and information from 16 human papillomavirus (HPV) prevalence surveys of women in 14 countries. More thab 2,200 women with cervical cancer and 2,214 matched control women without cervical cancer were included from the case-control studies, and 15,272 healthy women from the HPV survey.4 The authors reported that the likelihood of developing squamous-cell carcinoma was reduced by 44%, with risk for adenocarcinoma or adenosquamous carcinoma reduced by 54%. While study data suggested that IUD use does not modify the likelihood of prevalent HPV infection, it might affect the likelihood of HPV progression to cervical cancer.4

What About HPV Vaccine?

In the United States, the nine-valent HPV vaccine is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58, as well as nononcogenic types 6 and 11 that cause genital warts. According to 2012-2016 data, an average of 43,999 HPV-associated cancers were reported annually in the U.S., with an estimated 34,800 of those cancers attributable to HPV. Of the 34,800 cancers, an estimated 32,100 were attributable to the types targeted by the nine-valent vaccine, with 19,000 occurring among females, and 13,100 among males. The most common were cervical (9,700) and oropharyngeal (12,600) cancers.5

The Advisory Committee on Immunization Practices approved use of the nine-valent HPV vaccine for persons ages 27-45 years. The recommendation is for men and women in the noted age range who previously have not received an HPV vaccine series, and are at risk of infection. The shot is most effective when given during the recommended ages of 11-12.

REFERENCES

  1. American Cancer Society. Key statistics for cervical cancer. Jan. 8, 2019. Available at: https://bit.ly/38tmhic.
  2. Baik S, Mehta FF, Chung SH. Medroxyprogesterone acetate prevention of cervical cancer through progesterone receptor in a human papillomavirus transgenic mouse model. Am J Pathol 2019;189:2459-2468.
  3. Cortessis VK, Barrett M, Brown Wade N, et al. Intrauterine device use and cervical cancer risk: A systematic review and meta-analysis. Obstet Gynecol 2017;130:1226-1336.
  4. Castellsagué X, Díaz M, Vaccarella S, et al. Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: A pooled analysis of 26 epidemiological studies. Lancet Oncol 2011;12:1023-1031.
  5. Senkomago V, Henley SJ, Thomas CC, et al. Human papillomavirus-attributable cancers — United States, 2012-2016. MMWR Morb Mortal Wkly Rep 2019;68:724-728