宿主多基因甲基化对子宫颈高级别鳞状上皮内病变诊断价值的Meta分析

Meta-Analysis of the Diagnostic Value of the Host Multigene Methylation for High-Grade Squamous Intraepithelial Lesion

目的:系统地评估宿主多基因甲基化在子宫颈高级别鳞状上皮内病变(HSIL)中的诊断价值,为临床诊断提供循证医学依据。方法:检索PubMed、Embase、The Cochrane Library、Web of Science、中国知网(CNKI)、万方、维普(VIP)和中国生物医学文献数据库(CBM)数据库中有关宿主多基因甲基化诊断HSIL的相关文献,检索时限为从建库至2022年1月11日。按照纳入和排除标准,使用QUADAS-2评价文献质量,采用Meta-disc 1.4和Stata15.0软件进行统计学分析及绘图,评估宿主多基因甲基化对子宫颈上皮内瘤变(CIN)2及以上(CIN2^(+))和CIN3及以上(CIN3^(+))的诊断价值。结果:最终纳入8项研究,共3135例患者。Meta分析结果显示,宿主多基因甲基化对诊断CIN2^(+)的合并敏感度为0.80(95%CI 0.76~0.83),合并特异度为0.78(95%CI 0.76~0.80),合并阳性似然比(PLR)为8.01(95%CI 2.54~25.22),合并阴性似然比(NLR)为0.27(95%CI 0.13~0.54),合并诊断比值比(DOR)为37.74(95%CI 11.60~122.79),合并曲线下面积(AUC)为0.9566。对CIN3^(+)的合并敏感度为0.70(95%CI 0.65~0.75),合并特异度0.75(95%CI 0.73~0.76),合并PLR为4.66(95%CI 2.82~7.70),合并NLR为0.37(95%CI 0.24~0.59),合并DOR为16.42(95%CI 8.20~32.88),合并AUC为0.8937。结论:宿主多基因甲基化对诊断CIN2^(+)、CIN3^(+)具有较好敏感度和特异度,有较高的诊断效能,对HSIL有很好的分流作用,该检测有望成为一种稳定、准确、有效的子宫颈癌筛查分流方法。

Objective:To systematically evaluate the performance of host multigene methylation test in the diagnosis of high-grade squamous intraepithelial lesion(HSIL)and provide evidence-based medical basis for clinical diagnosis.Methods:Chinese databases(CNKI,Wanfang,VIP,CBM)and English databases(Pubmed,Embase,The Cochrane Library,Web of Science)were searched for literature related to host multigene methylation testing for the diagnosis of cervical intraepithelial neoplasia,and the search time frame was from the date of database creation to January 11,2022.The quality of the literature was evaluated using QUADAS-2 according to inclusion and exclusion criteria,and the statistical analysis and mapping were performed by Meta-disc 1.4,and Stata15.0 software.Assess the diagnostic value of host polygenic methylation for cervical intraepithelial neoplasia grade 2 and above(CIN2^(+))and grades 3 and above(CIN3^(+)).Results:Eight studies were included,involving a total of 3135 patients.The results of Meta-analysis showed that the combined sensitivity of host polygene methylation for diagnosing CIN2+was 0.80(95%CI 0.76-0.83),with a combined specificity of 0.78(95%CI 0.76-0.80).The positive likelihood ratio(PLR)was 8.01(95%CI 2.54-25.22),and the negative likelihood ratio(NLR)was 0.27(95%CI 0.13-0.54).The diagnostic odds ratio(DOR)was calculated as 37.74(95%CI 11.60-122.79),and the area under the curve(AUC)was 0.9566.For CIN3^(+),the combined sensitivity was 0.70(95%CI 0.65-0.75),with a combined specificity of 0.75(95%CI 0.73-0.76).The PLR and NLR were 4.66(95%CI 2.82-7.70)and 0.37(95%CI 0.24-0.59),respectively.The DOR was 16.42(95%CI 8.20-32.88),and the AUC was 0.8937.Conclusions:The host multigene methylation test shows good sensitivity and specificity for the diagnosis of CIN2^(+)and CIN3^(+)which proves its high diagnostic efficacy,further indicating that it has a good triage effect on HISL.The test is expected to be a stable,accurate and effective screening and triage method for cervical cancer.