Comparative effectiveness and reproductive morbidity of local treatments for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: a systematic review and network meta-analysis

Abstract

Background: In this network meta-analysis, we compared the effectiveness and reproductive morbidity associated with various treatment methods for cervical intraepithelial neoplasia (CIN). Methods: We searched electronic databases (MEDLINE, Embase, CENTRAL) from inception until 9 March 2022 for randomised and non-randomised studies reporting on oncological and reproductive outcomes after excisional or ablative CIN treatments. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks). The network for prematurity included also women with untreated CIN (colposcopy group). We extracted study-level data and conducted random-effects network meta-analyses to obtain odds ratios (ORs) with 95% confidence intervals. Within- and across-study risk of bias was assessed using Cochrane tools. PROSPERO registration: CRD42018115495 and CRD42018115508. Findings: Searches retrieved 11,987 citations. The networks for treatment failure and prematurity included 19,240 and 68,817 participants across 71 (25 randomised) and 29 (two randomised) studies, respectively. Compared to large loop excision of the transformation zone (LLETZ), risk of treatment failure was lower for other excisional (laser conisation: OR=0·59, 0·44–0·79; cold knife conisation [CKC]: OR=0·63, 0·50–0·81) and higher for ablative techniques (laser ablation: OR=1·69, 1·27–2·24; cryotherapy: OR=1·84, 1·33–2·55). Compared to colposcopy group, risk of prematurity was higher for all excisional techniques (CKC: OR=2·27, 1·70–3·02; laser conisation: OR=1·77, 1·29–2·43; LLETZ: OR=1·37, 1·16–1·62), whilst estimates were uncertain for ablative methods. Interpretation: More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Ablative treatments probably do not increase risk of prematurity, although there is uncertainty, but are associated with higher failure rates, particularly in the long term. The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low. Although LLETZ reported balanced effectiveness and reproductive morbidity, treatment choice should rely on woman’s age, lesion and fertility wishes.