Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.
Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.
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DOI：
10.1016/s1470-2045(22)00334-5
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发表时间：
2022-08
期刊：
影响因子：
51.1
通讯作者：
Kyrgiou, Maria
中科院分区：
文献类型：
--
作者：
Athanasiou, Antonios;Veroniki, Areti Angeliki;Efthimiou, Orestis;Kalliala, Ilkka;Naci, Huseyin;Bowden, Sarah;Paraskevaidi, Maria;Arbyn, Marc;Lyons, Deirdre;Martin-Hirsch, Pierre;Bennett, Phillip;Paraskevaidis, Evangelos;Salanti, Georgia;Kyrgiou, Maria
宫颈上皮内瘤变（CIN）不同治疗方法的相对有效性和生殖系统发病率之间的权衡仍不清楚。我们的目的是确定与各种治疗技术相关的治疗失败和早产的风险。在这项系统性综述和网络荟萃分析中，我们检索了MEDLINE、Embase和科克伦中央对照试验登记数据库，以寻找报告自数据库成立至2022年3月9日期间CIN治疗后肿瘤或生殖结局的随机和非随机研究，没有语言限制。我们纳入了接受切除（冷刀锥切[CKC]、激光锥切和转化区大环切除[LLETZ]）或消融（根治性透热疗法、激光消融、冷凝固和冷冻疗法）治疗的CIN、腺上皮内瘤变或IA 1期宫颈癌女性的研究。我们排除了接受子宫切除术的女性。主要结局是任何治疗失败（定义为任何异常的组织学或细胞学）和早产（<37周妊娠）。早产网络还包括未经治疗的CIN妇女（未经阴道镜检查组）。主要参照组为治疗失败的LLETZ和未治疗的阴道镜检查组早产。对于随机对照试验，我们提取了组水平的汇总数据，对于观察性研究，我们提取了针对潜在混杂因素调整的相对治疗效果估计值（如可用），我们进行了随机效应网络荟萃分析，以获得比值比（OR）和95% CI。我们使用科克伦工具评估了研究内和研究间的偏倚风险。该系统性综述已在PROSPERO注册，CRD 42018115495和CRD 42018115508。7880篇潜在引文被确定为治疗失败结局，4107篇为早产结局。在筛选和删除重复项后，治疗失败网络包括71项研究（25项随机化）的19240名参与者，早产网络包括29项研究（2项随机化）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：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]）和冷冻治疗（1·84 [1·33-2·56]）的治疗失败风险增加。冷凝固与LLETZ的比较没有发现差异（1·09 [0·68-1·74]），但直接数据仅基于两项小型研究。与未经阴道镜检查组相比，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：1.77 [1.29 - 2.43]; LLETZ：1.37 [1.16 - 1.62]），而消融方法无差异（激光消融：1.05 [0.78 ~ 1.41];冷冻：1.01 [0.35 ~ 2.92];冷凝固：0.67 [0.02 ~ 29.15]）。证据主要基于观察性研究，具有固有的偏倚风险，许多比较的可信度很低。更激进的切除技术降低了治疗失败的风险，但增加了随后早产的风险。尽管存在不确定性，但消融治疗可能不会增加早产的风险，但与切除技术相比，失败率较高。虽然我们发现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。国家健康与护理研究所：为患者利益进行研究。
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. 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. 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. 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. National Institute for Health and Care Research: Research for Patient Benefit.