Background

The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques.

Methods

In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508.

Findings

7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44–0·79] and CKC: 0·63 [0·50–0·81]) and increased for laser ablation (1·69 [1·27–2·24]) and cryotherapy (1·84 [1·33–2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68–1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70–3·02]; laser conisation: 1·77 [1·29–2·43]; and LLETZ: 1·37 [1·16–1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78–1·41]; cryotherapy: 1·01 [0·35–2·92]; and cold coagulation: 0·67 [0·02–29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low.

Interpretation

More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning.

Funding

National Institute for Health and Care Research: Research for Patient Benefit.

中文翻译：

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宫颈上皮内瘤变和 IA1 期宫颈癌局部治疗的有效性和早产风险比较：系统评价和网络荟萃分析

背景

宫颈上皮内瘤变（CIN）不同治疗方法的比较有效性和生殖发病率之间的权衡仍不清楚。我们旨在确定与各种治疗技术相关的治疗失败和早产的风险。

方法

在这项系统评价和网络荟萃分析中，我们搜索了 MEDLINE、Embase 和 Cochrane 对照试验中央注册数据库，以获取从数据库开始到 2022 年 3 月 9 日报告 CIN 治疗后肿瘤学或生殖结果的随机和非随机研究，没有语言限制。我们纳入了对患有 CIN、腺上皮内瘤变或 IA1 期宫颈癌的女性进行了切除（冷刀锥切术 [CKC]、激光锥切术和转化区大环切除术 [LLETZ]）或消融（根治性透热疗法、激光消融、冷凝和冷冻疗法）。我们排除了接受子宫切除术治疗的女性。主要结局是任何治疗失败（定义为任何异常组织学或细胞学）和早产（<37 孕周）。早产网络还包括未经治疗的 CIN 女性（未经治疗的阴道镜检查组）。主要参考组是 LLETZ 治疗失败和未经治疗的阴道镜组早产。对于随机对照试验，我们提取了组级汇总数据，对于观察性研究，我们提取了针对潜在混杂因素进行调整的相对治疗效果估计值（如果有），并且我们进行了随机效应网络荟萃分析以获得优势比 (ORs) 95% 置信区间。我们使用 Cochrane 工具评估了研究内和研究间的偏倚风险。该系统评价已在 PROSPERO、CRD42018115495 和 CRD42018115508 注册。对于随机对照试验，我们提取了组级汇总数据，对于观察性研究，我们提取了针对潜在混杂因素进行调整的相对治疗效果估计值（如果有），并且我们进行了随机效应网络荟萃分析以获得优势比 (ORs) 95% 置信区间。我们使用 Cochrane 工具评估了研究内和研究间的偏倚风险。该系统评价已在 PROSPERO、CRD42018115495 和 CRD42018115508 注册。对于随机对照试验，我们提取了组级汇总数据，对于观察性研究，我们提取了针对潜在混杂因素进行调整的相对治疗效果估计值（如果有），并且我们进行了随机效应网络荟萃分析以获得优势比 (ORs) 95% 置信区间。我们使用 Cochrane 工具评估了研究内和研究间的偏倚风险。该系统评价已在 PROSPERO、CRD42018115495 和 CRD42018115508 注册。

发现

7880 条潜在引文被确定为治疗失败的结果，4107 条用于早产的结果。在筛选和删除重复项后，治疗失败网络包括 71 项研究（随机 25 项）的 19240 名参与者，早产网络包括 29 项研究（两项随机）的 68817 名参与者。与 LLETZ 相比，其他切除方法的治疗失败风险降低（激光锥切术：OR 0·59 [95% CI 0·44–0·79] 和 CKC：0·63 [0·50–0·81]）激光消融 (1·69 [1·27–2·24]) 和冷冻疗法 (1·84 [1·33–2·56]) 增加。冷凝与 LLETZ (1·09 [0·68–1·74]) 的比较没有发现差异，但直接数据仅基于两项小型研究。与未经治疗的阴道镜组相比，所有切除技术的早产风险均增加（CKC：2·27 [1·70–3·02]；激光锥切术：1·77 [1·29–2·43]；LLETZ：1·37 [1 ·16–1·62]），而消融方法没有发现差异（激光消融：1·05 [0·78–1·41]；冷冻疗法：1·01 [0·35–2·92]；和冷凝：0·67 [0·02–29·15]）。证据主要基于观察性研究，存在固有的偏倚风险，许多比较的可信度很低。

解释

更彻底的切除技术可降低治疗失败的风险，但会增加随后早产的风险。尽管存在不确定性，但消融治疗可能不会增加早产风险，但与切除技术相比，失败率更高。尽管我们发现 LLETZ 具有平衡的有效性和生殖发病率，但治疗选择应取决于女性的年龄、病变的大小和位置以及未来的计划生育。

资金

国家健康与护理研究所：患者福利研究。