Risk of Precancerous Cervical Lesions in Women Using a Hormone-containing Intrauterine Device and Other Contraceptive

A Register-based Cohort Study From Denmark

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

Disclosures

Hum Reprod. 2021;36(7):1796-1807. 

In This Article

Abstract and Introduction

Abstract

Study Question: Is 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 Answer: Women 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 Already: HIUDs may cause inflammatory and immunosuppressive changes that may potentially affect the risk of persistent human papillomavirus infection and precancerous cervical lesions.

Study Design, Size, Duration: A 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, Methods: Within 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 Chance: Women 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 Caution: We 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 Findings: These 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 Number: N/A.

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 65+ 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). Cervical screening aims to find and treat lesions before they progress to cancer.

A hormone-containing intrauterine device (HIUD) is widely used as a preferred contraceptive method and in treatment of irregular bleeding (Hidalgo et al., 2002). In Denmark, the annual number of HIUD sold increased from 15,000 in 2005 to 62,000 in 2017 (Sundhedsdatastyrelsen). Evidence is sparse and diverse on HPV infections and precancerous cervical lesions in women using HIUD compared with women using other contraceptive methods.

One study found that 1 year after insertion, HIUD-users (n = 152) had more persistent HPV infections (P = 0.02) and more new HPV infections (P = 0.056) than CIUD users (n = 150) (Lekovich et al., 2015). In another study, the HPV infection rate was the same in IUD users (n = 295) as in users of other contraceptive methods (Gavrić-Lovrec and Takač, 2010), and HIUD (n = 187) use did not affect risk of positive cervical cytology and high-grade lesions (Lessard et al., 2008). In a study concerning effect of HIUD use on properties of the mucosal immunity of the upper reproductive tract, both inflammatory and immunosuppressive changes were observed although it was uncertain how these changes would affect the risk of viral infections (Shanmugasundaram et al., 2016). All studies were based on relatively small numbers.

The aim of the present study was to investigate the risk of abnormal cervical cytology and histology after use of HIUD compared with use of other contraceptive methods. First, we hypothesized that HIUD use increases the risk of developing a precancerous cervical lesion. Second, we hypothesized that a precancerous cervical lesion will progress after insertion of an HIUD, given the fact that the presence of cervical dysplasia is listed as a contraindication for insertion of a HIUD (Pro.medicin).

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