IUDs and Cervical Cancer Risk

Abstract & Commentary

By Jeffrey T. Jensen, MD, MPH , Leon Speroff, Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: In a large pooled analysis, the ever-use of an intrauterine device was associated with a 45% reduction in the risk of cervical cancer.

Source: Castellsague X, 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. PMID:21917519.

The investigators performed a pooled analysis of individual data from two large studies by the International Agency for Research on Cancer (IARC) and Institut Català d'Oncologia (ICO) research program on human papillomavirus (HPV) and cervical cancer. The results from 10 case-control studies of cervical cancer conducted in eight countries (2205 women with cervical cancer and 2214 matched control women without cervical cancer) and 16 HPV prevalence surveys of 15,272 healthy women from the general population in 14 countries were separately analyzed. In both groups, information on intrauterine device (IUD) use was obtained by personal interview. HPV DNA was tested by PCR-based assays. The primary outcome was the association between IUD use, cervical HPV DNA, and cervical cancer. After adjusting for relevant covariates (including cervical HPV DNA and number of previous Pap smears), a strong inverse association was found between ever use of IUDs and cervical cancer (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.42–0.70). The protective association was noted for both squamous cell (OR 0.56; CI 0.43-0.72) and adenosquamous cell (OR 0.46; CI 0.22-0.97) carcinoma. In contrast, there was no significant relationship between IUD use and detection of cervical HPV DNA (OR 0.68; CI 0.44-1.06). The authors concluded that IUD use might act as a protective cofactor in cervical carcinogenesis and postulated that enhanced cellular immunity triggered by the device might be one of several mechanisms that could explain the findings.

Commentary

Like many of you, I am guilty of having harmed women in the past through Pap smear testing. Until recently, the strategy for cervical cancer prevention may have done more harm than good, as we screened young women soon after the onset of coital activity, and treated low-level HPV infection with ablative or excisional therapy. More significantly, we held women hostage to Pap testing in exchange for hormonal contraception, due to unsupported beliefs that oral contraceptives and other hormonal methods were associated with the development of cervical cancer. Fortunately, we now understand that cervical cancer is caused by the human papilloma virus, and recent guidelines (reviewed in the February 2010 issue of OB/GYN Clinical Alert) no longer recommend screening women under age 21, and incorporate the use of DNA testing for high-risk HPV types. However, since so much effort is spent on evaluating potential health risks of contraceptives, it is always useful to highlight benefits.

The IUD is enjoying a much-deserved renaissance due to the availability of two highly effective medicated systems in the United States. The copper and levonorgestrel systems are important and highly acceptable long-acting reversible methods suitable for use in both parous and nulliparous women. Less well-known by providers and patients are some of the established non-contraceptive benefit of intrauterine contraception. These include a reduction in risk of endometrial cancer for both the levonorgestrel1 and copper devices.2 While the hormonal action of levonorgestrel provides a mechanism for the LNG IUS, the mechanism of protection for copper devices has not been established. Now we see new evidence that supports an almost 50% reduction in the risk of cervical cancer associated with IUD use. Although the current study did not stratify the results by IUD type, most of the devices were probably copper as the data were collected in many developing countries.

The new results by Castellsagué et al suggest that local inflammatory effects may activate the immune system to increase clearance of abnormal cells with oncogenic potential. Several findings demonstrate this effect: 1) IUD use (current or past) was associated with a reduction in the risk of cervical cancer, but not in the risk of HPV infection; 2) There was no durational effect, that is no increase in protection with greater duration of IUD use; and 3) A reduction was seen with both squamous and adenosquamous cell cancers.

One explanation may be that mechanical factors associated with insertion serve to activate an immune response that clears abnormal cells. Obviously, this is just a hypothesis that needs to be tested through well-designed clinical trials. While other explanations not evaluated in this study must be considered, since there was no association between IUD use and high-risk HPV infection, it is unlikely that differences in sexual behavior explain the results.

At this point, we can feel confident that IUD use does not increase the risk of cervical cancer, and likely reduces the risk through an unknown mechanism. This is good news for women and another reason to recommend these highly effective methods.

References

  1. Varma R, et al. Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS)—A systematic enquiry and overview. Eur J Obstet Gynecol Reprod Biol 2006;125:9-28.
  2. Curtis KM, et al. Neoplasia with use of intrauterine devices. Contraception 2007;75:S60-S69.