Intrauterine Device Use, Cervical Infection With Human Papillomavirus, and Risk of Cervical Cancer

Abstract

There is substantial evidence that use of an intrauterine device (IUD) reduces the risk of endometrial cancer. Little is known about the potential effects of an IUD on the risk of developing cervical cancer or cervical human papillomavirus (HPV) infection. A number of studies have addressed the concern that these devices could cause cervical cancer, but the results have been inconclusive. This study used pooled data from 2 large epidemiologic studies that explored the potential effects of IUD use on the risk of cervical HPV infection and the risk of developing cervical cancer. The 2 studies were conducted by the International Agency for Research on Cancer and Institut Català d'Oncologia research program on HPV and cervical cancer. Data from 1 study were obtained from 10 case–control studies of cervical cancer conducted in 8 countries; the other study included data for 16 HPV prevalence surveys from 14 countries for women in the general population. The final pooled analysis included 2205 women with cervical cancer and 2214 matched control women without cervical cancer from the case–control studies, and 15,272 healthy women from the HPV surveys. Personal interviews with participants provided information on potential risk factors for cervical cancer, including IUD use and duration of polymerase chain reaction-based assays, which were used to detect HPV DNA. Multivariate unconditional logistic regression analysis was used to estimate the associations between IUD use and both cervical HPV DNA and cervical cancer, and to adjust the latter for covariates, including cervical HPV DNA and number of previous Papanicolaou smears. The adjusted data show a strong and consistent inverse association between ever use of an IUD and cervical cancer. The adjusted odds ratio (aOR) was 0.55, with a 95% confidence interval (CI) of 0.42 to 0.70 (P < 0.0001). A protective association was found between IUD use and the cervical cancer histologic subtypes, squamous cell carcinoma (aOR, 0.56; 95% CI, 0.43–0.72; P < 0.0001) and combined adenocarcinoma and adenosquamous carcinomas (aOR, 0.46; 0.22–0.97; P = 0.035) but not for HPV-positive women (aOR, 0.68; 95% CI, 0.44–1.06; P = 0.11). None of the surveys showed an association between IUD use and cervical HPV-DNA detection among women without cervical cancer. These findings show that use of IUDs substantially reduces the risk of cervical cancer. Although the underlying mechanisms in reducing the risk of developing cervical cancer are unclear, the data suggest that IUD use could act as a protective cofactor in cervical carcinogenesis and/or may trigger cellular immunity.