Risk of precancerous cervical lesions in women using a hormone-containing intrauterine device and other contraceptives: a register-based cohort study from Denmark.

Malene Skorstengaard,Pinar Bor,Elsebeth Lynge,George Napolitano,Jan Blaakær

doi:10.1093/humrep/deab066

Abstract

STUDY QUESTIONIs the risk of high-grade precancerous cervical lesions and/or is the risk of lesion progression increased in users of a hormone-containing intrauterine device (HIUD) compared with users of other contraceptive methods.SUMMARY ANSWERWomen starting use of HIUD had the same subsequent risk of cervical intraepithelial neoplasia 3+ (CIN3+) as copper IUD (CIUD) users, and both groups tended to have lower risks than oral contraceptives (OC) users.WHAT IS KNOWN ALREADYHIUDs may cause inflammatory and immunosuppressive changes that may potentially affect the risk of persistent human papillomavirus infection and precancerous cervical lesions.STUDY DESIGN, SIZE, DURATIONA Danish population-based cohort study was conducted using register data from 2008 to 2011 on 26–50-year-old users of HIUD (n = 60 551), CIUD (n = 30 303), or OC (n = 165 627).PARTICIPANTS/MATERIALS, SETTING, METHODSWithin each user group, women were divided into two groups; normal cytology or abnormal diagnosis before start of contraceptive use (baseline). Follow-up histology and cytology diagnoses were registered during the 5 years after baseline. Adjusted relative risks (aRR) and 95% CI were calculated for precancerous cervical lesions in HIUD users compared with CIUD and OC users.MAIN RESULTS AND THE ROLE OF CHANCEWomen with normal cytology at baseline: at follow-up HIUD users had the same risk of CIN3 or higher (3+) as CIUD users; aRR 1.08 (95% CI 0.94–1.22). For the HIUD and CIUD groups compared with OCs, the risks of CIN3+ were lower: aRR 0.63 (95% CI 0.57–0.69) and aRR 0.58 (95% CI 0.52–0.65), respectively. The same was observed for CIN2 risks: aRR 0.86 (95% CI 0.76–0.96) and aRR 0.68 (95% CI 0.58–0.79) for HIUD and CIUD groups, respectively. Women with abnormal diagnosis at baseline: a lower progression risk, except for CIN2+ at baseline, was observed in HIUD users compared with OC users. Similar progression risks were found in HIUD and CIUD users. There were no differences between the three contraceptive groups in persistence or regression of present lesions.LIMITATIONS, REASONS FOR CAUTIONWe adjusted for age, education, and region of residence as a proxy for socio-economic factors. Data on smoking and sexual behavior were not available thus we cannot exclude some differences between the three user groups.WIDER IMPLICATIONS OF THE FINDINGSThese findings suggest that women may safely use HIUDs.STUDY FUNDING/COMPETING INTEREST(S)A.P. Møller Foundation for the Advancement of Medical Science, Else and Mogens Wedell-Wedellborgs Fund, Direktør Emil C. Hertz og Hustru Inger Hertz Fund, and the Fund for Development of Evidence Based Medicine in Private Specialized Practices. EL is principle investigator for a study with HPV-test-kits provided by Roche. The other authors have nothing to declare.TRIAL REGISTRATION NUMBERN/A.

Highlights

Infection with high-risk human papillomavirus (HPV) is a necessary but not a sufficient cause of cervical cancer (Walboomers et al, 1999)
We identified 72 125 hormone-containing intrauterine device (HIUD) users, 39 291 CIUD users, and 236 225 Oral contraceptives (OC) users, of whom, 11 574 (16.1%) were excluded in the HIUD group, 8988 (22.9%) in the CIUD group, and 70 598 (29.9%) in the OC group, mainly due to missing baseline diagnosis
In women with normal cytology at the time of initiating contraceptive use, we found that HIUD and CIUD users over the 5 years had a lower risk of CIN2 and CIN3þ than OC users

Summary

Introduction

Infection with high-risk human papillomavirus (HPV) is a necessary but not a sufficient cause of cervical cancer (Walboomers et al, 1999). HPV is a common sexually transmitted infection, and 75% of sexually active women will become infected in life (Tota et al, 2011). In Danish women, the prevalence of HPV is highest at age 20–23 years (46%) and decreasing to the lowest prevalence at age 65þ years (5.7%) (Kjær et al, 2014). Most women will clear the infection, but for some women it will persist and may cause precancerous cervical lesions and cancer (Stanley, 2006). A hormone-containing intrauterine device (HIUD) is widely used as a preferred contraceptive method and in treatment of irregular bleeding (Hidalgo et al, 2002). Evidence is sparse and diverse on HPV infections and precancerous cervical lesions in women using HIUD compared with women using other contraceptive methods

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