Background: DNA methylation has been widely assessed as a potential biomarker for the early detection of cervical cancer (CC). Herein, we assessed the associations of SOX1 promoter hypermethylation with squamous intraepithelial lesion and CC.

Methods: Published studies and genome-wide methylation datasets were searched from electronic databases (up to April 2019). The associations of SOX1 hypermethylation with high-grade squamous intraepithelial lesion (HSIL) and CC risks were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). The summary receiver operator characteristic test was used to assess the diagnostic value of the SOX1 promoter hypermethylation of CC and intraepithelial neoplasia type III or worse (CIN3+). Trial sequential analysis (TSA) was performed to evaluate the stability of results and estimate the required information size (RIS).

Results: In this meta-analysis of 17 published studies, the SOX1 methylation rates increased among low-grade SIL (LSIL, 27.27%), HSIL (40.75%), and CC (84.56%) specimens. Compared with control specimens, SOX1 promoter hypermethylation progressively increased the risk of HSIL by 4.20-fold (p < 0.001) and CC by 41.26-fold (p < 0.001). The pooled sensitivity of SOX1 methylation was estimated to be 0.85 (95% CI: 0.81–0.88) in differentiating patients with CC, corresponding to a specificity of 0.72 (95% CI: 0.69–0.75) and an area under the curve (AUC) of 0.93. Furthermore, the pooled sensitivity of SOX1 methylation was estimated to be 0.75 (95% CI: 0.72–0.78) in differentiating patients with CIN3+, corresponding to a specificity of 0.71 (95% CI: 0.69–0.73) and an AUC of 0.84. The pooled results of TCGA and GEO datasets showed that all CpG sites in SOX1 were associated with CC and 16 of 19 CpG sites were associated with HSIL. The results of TSA illustrated that the size was sufficient and significant associations were observed.

Conclusion: This meta-analysis indicated that SOX1 promoter hypermethylation might have a potential value in the clinical diagnosis of CC and CIN3+.

背景：DNA甲基化已被广泛评估为早期发现宫颈癌（CC）的潜在生物标记。在这里，我们评估了SOX1启动子甲基化与鳞状上皮内病变和CC的关联。

方法：从电子数据库中搜索已发表的研究和全基因组甲基化数据集（截至2019年4月）。通过比值比（OR）和95％置信区间（CI）评估SOX1甲基化程度高与高度鳞状上皮内病变（HSIL）和CC风险之间的关系。简要的接收者操作员特征测试用于评估CC的SOX1启动子甲基化和III型或更严重的上皮内瘤变（CIN3 +）的诊断价值。进行了试验顺序分析（TSA）以评估结果的稳定性并估计所需的信息量（RIS）。

结果：在对17项已发表研究的荟萃分析中，低级SIL（LSIL，27.27％），HSIL（40.75％）和CC（84.56％）样品中的SOX1甲基化率增加。与对照标本相比，SOX1启动子高甲基化使HSIL的风险逐渐增加4.20倍（p <0.001）和CC到41.26倍（p<0.001）。在区分CC的患者中，SOX1甲基化的合并敏感性估计为0.85（95％CI：0.81-0.88），对应于0.72（95％CI：0.69-0.75）的特异性和曲线下面积（AUC）为0.93。此外，在区分CIN3 +的患者中，SOX1甲基化的合并敏感性估计为0.75（95％CI：0.72-0.78），对应的特异性为0.71（95％CI：0.69-0.73），AUC为0.84。TCGA和GEO数据集的汇总结果显示，SOX1中的所有CpG位点均与CC相关，而19个CpG位点中的16个均与HSIL相关。TSA的结果表明大小足够，并且观察到显着的关联。

结论： 这项荟萃分析表明，SOX1启动子甲基化可能在CC和CIN3 +的临床诊断中具有潜在价值。