Diagnostic Efficacy of Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Meta-Analysis of 66 Studies

Objectives
The diagnostic efficacy of sentinel lymph node biopsy(SLNB) in early oral squamous cell carcinoma(OSCC) still remains controversial. This meta-analysis was conducted to assess the diagnostic value of SLNB in clinically neck-negative T1-2 OSCC.
Methods
A systematic literature search for relevant literature published up to September 11, 2016 was conducted in PubMed, Embase, Web of Science, Cochrane Library and ClinicalTrials, and the reference lists of eligible studies were examined. Data from different studies were pooled to estimate the summary sentinel lymph node(SLN) identification rate, sensitivity, negative predictive value. Summary receiver operator characteristic curve(SROC) was plotted and area under the SROC curve (AUC) was calculated to evaluate the overall diagnostic efficacy. Threshold effect was assessed with use of the spearman correlation coefficient. Between-study heterogeneity was tested using the Q tests and the I2 statistics. Subgroup analyses were conducted in view of the greater effect of different study characteristics on diagnostic efficacy of SLN. Deeks’ funnel plot asymmetry test was performed to evaluate publication bias. Sensitivity analysis was evaluated through omitting studies one by one and comparing the pooled results of random-effects model and fixed-effects model. All analyses were performed using Review Manager (version 5.3.5), Meta-DiSc (version 1.4), Comprehensive Meta Analysis (version 2.0) and STATA (version 12).
Results
66 studies comprising 3566 patients with cT1-2N0 OSCC were included in this meta-analysis. The pooled SLN identification rate was 96.3%(95% CI: 95.3%-97.0%). The pooled sensitivity was 0.87 (95% CI: 0.85–0.89), pooled negative predictive value was 0.94 (95% CI: 0.93–0.95), and AUC was 0.98 (95% CI: 0.97–0.99). Subgroup analyses indicated that SLN assessment with immunohistochemistry(IHC) achieved a significantly higher sensitivity than without IHC.
Conclusions
This meta-analysis suggests that SLNB has a high diagnostic accuracy in cT1-2N0 oral squamous cell carcinoma, and is an ideal alternative to elective neck dissection. Furthermore, the use of IHC can significantly improve SLNB diagnostic sensitivity for early OSCC.

研究目的：早期口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）患者行前哨淋巴结活检（sentinel lymph node biopsy, SLNB）的诊断效能仍存在争议。本研究旨在评估SLNB对临床颈淋巴结阴性T1-2期OSCC的诊断价值。
研究方法：本研究于2016年9月11日前，在PubMed、Embase、Web of Science、Cochrane图书馆及ClinicalTrials数据库中系统检索相关文献，并核查纳入研究的参考文献列表。合并各项研究的数据，以估算前哨淋巴结（sentinel lymph node, SLN）总检出率、灵敏度及阴性预测值。绘制综合受试者工作特征曲线（summary receiver operator characteristic curve, SROC）并计算其曲线下面积（area under the SROC curve, AUC），以评估整体诊断效能。采用斯皮尔曼相关系数评估阈值效应；通过Q检验及I²统计量检验研究间异质性。鉴于不同研究特征对SLN诊断效能的影响存在差异，本研究开展了亚组分析。采用Deeks漏斗图不对称性检验评估发表偏倚；通过逐一剔除研究并比较随机效应模型与固定效应模型的合并结果，进行敏感性分析。本研究所有分析均借助Review Manager（版本5.3.5）、Meta-DiSc（版本1.4）、Comprehensive Meta Analysis（版本2.0）及STATA（版本12）完成。
研究结果：本Meta分析共纳入66项研究，涉及3566例临床T1-2N0期OSCC患者。合并后的SLN总检出率为96.3%（95%置信区间：95.3%~97.0%）；合并灵敏度为0.87（95%置信区间：0.85~0.89），合并阴性预测值为0.94（95%置信区间：0.93~0.95），AUC为0.98（95%置信区间：0.97~0.99）。亚组分析显示，采用免疫组织化学（immunohistochemistry, IHC）进行SLN评估的灵敏度显著高于未使用IHC的方案。
研究结论：本Meta分析结果表明，SLNB对临床T1-2N0期OSCC具有较高的诊断准确性，可作为选择性颈淋巴结清扫术的理想替代方案。此外，IHC的应用可显著提升早期OSCC患者SLNB的诊断灵敏度。