联合应用DAPKⅠ、RARβ甲基化和高危型HPV检测筛查宫颈癌及癌前病变的研究

Research of hypermethylation detection of DAPKⅠand RARβ combined with high-risk type HPV test in early diagnosis of cervical cancer and precursor lesions

目的:探讨患者宫颈脱落细胞中DAPKⅠ和RARβ甲基化和高危型HPV感染对宫颈癌及癌前病变的筛查意义。方法:选择2008年9月至2009年7月在南通大学附属医院就诊的宫颈炎患者48例、宫颈轻度鳞状上皮内瘤变(CINⅠ)患者11例,宫颈中度鳞状上皮内瘤变(CINⅡ)患者16例,重度鳞状上皮内瘤变患者患者(CINⅢ)14例,宫颈浸润性鳞癌(ICC)患者30例,采集患者的宫颈脱落细胞,用甲基化特异性聚合酶链反应(MSP)检测DAPKⅠ、RARβ甲基化情况,用HPV分型检测法检测高危型HPV感染情况。结合TCT筛查结果,统计单方法和多方法联合检测宫颈癌及癌前病变的灵敏度、特异度、阳性预测值和阴性预测值。结果:单基因甲基化检测的敏感度低,特异性高。DAPKⅠ、RARβ两基因联合HPV检测浸润性宫颈癌的敏感度、特异度、阳性预测值和阴性预测值分别为93.33%、97.92%、96.55%和95.92%。检测Ⅱ级以上宫颈上皮样瘤变的敏感度、特异度、阳性预测值和阴性预测值分别为66.67%、97.92%、95.24%和82.46%。结论:单方法检测的优越性不及联合检测法。DAPKⅠ、RARβ两基因甲基化联合HPV检测具有较高的敏感度、特异度、阳性预测值和阴性预测值。

Objective：To study the role of DNA hypermethylation of DAPKⅠand RARβ combined with high-risk type HPV detection in early diagnosis of cervical cancer and precursor lesions.Methods：We collected exfoliated cells from 48 patients of cervicitis,11 patients of CINⅠ,16 patients of CINⅡ,14 patients of CINⅢ,30 patients of invasive cervical cancer from Sep.2008 to July 2009 at Affiliated Hospital of Nantong University.Methylation Specific PCR was performed to detect the hypermethylation of DAPKⅠand RARβ while HPV type-differentia detection to test high-risk type HPV infection.Combining with the TCT results of these patients,we compared the sensitivity,specificity,PPV and NPV of single screening and conjoined screening.Results：One gene hypermethylation detection had a low sensitivity and a high specificitiy.But the two genes＇ hpermethylation combined with HPV infection detection in screening invasive cervical cancer showed the sensitivity,specificity,PPV and NPV of 93.33%,97.92%,96.55% and 95.92%,and of 66.67%,97.92%,95.24% and 82.46% when screening CINⅡand CINⅢ.Conclusion：The conjoined screening method was more effective than the single screening technique.Detection of the two-gene hypermethylation combined with HPV infection test show a better sensitivity,specificity,PPV and NPV in screening cervical cancer.