【作者】 谢婷；

【导师】 舒宽勇；

【作者基本信息】 南昌大学 ， 妇产科学， 2022， 硕士

【摘要】 目的:本研究主要分析p16/Ki-67细胞学双染及液基细胞学检查(thinprep cytologic test,TCT)检测在高危型人乳头瘤病毒(human papilloma virus,HPV)非16/18型阳性妇女宫颈高级别病变筛查中的应用价值,评价p16/Ki-67细胞学双染在宫颈高级别鳞状上皮病变筛查中的诊断价值。方法:以2019.5至2020.4在赣县区人民医院行宫颈癌筛查的200例高危型HPV非16/18型阳性的患者作为研究对象,所有患者均行TCT检查、高危型人乳头瘤病毒(High-risk HPV,HR-HPV)检测、p16/Ki-67细胞学双染以及阴道宫颈组织病理学诊断检查,以病理学诊断结果作为金标准,分析p16/Ki-67细胞学双染和TCT检测的敏感性和特异性、阳性预测值以及阴性预测值。以假阳性率和敏感性作为横、纵坐标制作受试者工作特征曲线(Receiver operating characteristic curve,ROC),计算p16/Ki-67细胞学双染和TCT检测诊断方法曲线下面积(Area under the curve,AUC),比较p16/Ki-67细胞学双染和TCT检测诊断方法的效果。1.p16/Ki-67细胞学双染检测出HSIL(CIN病变程度为CINⅡ及CINⅢ)的敏感性为92.31%(95%CI:89.16%-95.46%),特异性为72.98%(95%CI:69.75%-76.21%),阴性预测值为98.44%(95%CI:97.56%-99.32%),阳性预测值为33.80%(95%CI:23.38%-44.22%)2.TCT检测结果出HSIL(CIN病变程度为CINⅡ及CINⅢ)的敏感性为84.62%(95%CI:79.77%-89.47%),特异性为77.01%(95%CI:70.83%-83.19%),阴性预测值为97.10%(95%CI:94.72%-99.48%),阳性预测值为35.48%(95%CI:30.91%-40.05%)。3.p16/Ki-67细胞学双染检出HSIL(CIN病变程度为CINⅡ及CINⅢ)的敏感性较TCT高7.69%(P<0.05),p16/Ki-67细胞学双染检测HSIL(CIN病变程度为CINⅡ及CINⅢ)的特异性、阴性预测值以及阳性预测值与TCT相比均无统计学差异(P>0.05)。4.p16/Ki-67细胞学双染检出HSIL(CIN病变程度为CINⅡ及CINⅢ)的ROC曲线下AUC值为0.886,TCT检测诊断方法检出HSIL(CIN病变程度为CINⅡ及CINⅢ)的ROC曲线下AUC值为0.532,p16/Ki-67细胞学的ROC曲线下AUC值明显高于TCT(P<0.05)。5.p16/Ki-67细胞学双染检出LSIL的敏感性为54.5%(95%CI,47.41%-61.59%),特异性为65.6%(95%CI,60.06%-71.14%)。p16/Ki-67细胞学双染检测方法检出HSIL的敏感性为92.31%(95%CI,89.16%-95.46%),特异性为72.98%(95%CI,69.75%-76.21%)。6.p16/Ki-67细胞学双染和TCT检测诊断方法检出HSIL(CIN病变程度为CINⅡ及CINⅢ)的符合率分别为0.755和0.487;p16/Ki-67细胞学双染和TCT检测诊断方法检出HSIL(CIN病变程度为CINⅡ及CINⅢ)的Kappa值分别为0.736和0.247。结论:1.与TCT检测方法相比,p16/Ki-67细胞学双染具有更高的敏感度,可识别宫颈高级别病变;2.在高危型HPV非16/18型阳性筛查中p16/Ki-67细胞学双染与TCT检测相比灵敏度更高,降低了高危型HPV非16/18型阳性筛查漏诊率;3.采用p16/Ki-67细胞学双染操作相对简单,且其与宫颈活检病理结果金标准的一致更高。综上所述,p16/Ki-67细胞学双染可作为高危型HPV非16/18型阳性及宫颈高级别病变患者筛查的新型分子标记物。更多还原

【Abstract】 Objective:This study aimed to explore the adoption of p16/ki-67 dual-staining cytology and thinprep cytology test(TCT)in the screening of high-grade cervical lesions in non-16/18 High-risk HPV positive women and evaluate the diagnostic value of p16/ki-67 dual-staining cytology in the screening of high-grade cervical squamous intraepithel-ial lesions.Method:Two hundred cases of non-16/18 High-risk HPV positive patients receiving cervical cancer screening in Ganxian District People’ s Hospital from 2019.5 to2020.4 were recruited as the research objects.All patients went through TCT,HR-HPV test,p16/ki-67 dual-staining cytology,and histopathological diagnostic examination for cervical tissue.The pathological examination results for cervical tissue of the colposcope were defined as the gold standard,which were compared with the results of p16/ki-67 dual-staining cytology and the TCT.Then,the sensitivity,specificity,positive predictive rate,and negative predictive rate of p16/ki-67dual-staining cytology and the TCT were evaluated.The receiver operating characteristic curve(ROC)was plotted with sensitivity as the Y-axis and the false positive rate as the X-axis.The area under the curve(AUC)of p16/ki-67dual-staining cytology and the TCT diagnostic assay was calculated,and the effects of the two methods were compared.Results:1.The detection sensitivity of HSIL(the degree of CIN lesions were CIN II and CIN III)by p16/ki-67 dual-staining cytology was 92.31%(95% CI: 89.16%-95.46%),and the specificity was 72.98%(95% CI: 69.75%-76.21%).The negative predictive rate was 98.44%(95% CI: 97.56%-99.32%),and the positive predictive rate was33.80%(95% CI: 23.38%-44.22%).2.The detection sensitivity of HSIL(the degree of CIN lesions were CIN II and CIN III)by TCT was 84.62%(95%CI: 79.77%-89.47%),and the specificity was77.01%(95%CI: 70.83%-83.19%).The negative predictive rate was 97.10%(95% CI:94.72%-99.48%),and the positive predictive rate was 35.48%(95% CI: 30.91%-40.05%).3.The detection sensitivity of HSIL(the degree of CIN lesions were CIN II and CIN III)by p16/ki-67 dual-staining cytology was 7.69% higher than that of TCT(P<0.05).The detection specificity,negative predictive rate,and positive predictive rate of HSIL(the degree of CIN lesions were CIN II and CIN III)by p16/ki-67dual-staining cytology were not significantly different from those of TCT(P>0.05).4.The AUC of the ROC of HSIL(the degree of CIN lesions were CIN II and CIN III)detected by p16/ki-67 dual-staining cytology was 0.886.The AUC of the ROC of HSIL(the degree of CIN lesions were CIN II and CIN III)detected by TCT was 0.532.The AUC of the ROC of p16/ki-67 dual-staining cytology was considerably superior to that of TCT(P<0.05).5.The detection sensitivity of LSIL by p16/ki-67 dual-staining cytology was54.5%(95% CI,47.41%-61.59%),and the specificity was 65.6%(95% CI,60.06%-71.14%).The detection sensitivity of HSIL by p16/ki-67 dual-staining cytology was 92.31%(95% CI,89.16%-95.46%),and the specificity was 72.98%(95% CI,69.75%-76.21%).6.The detection coincidence rates of HSIL(CIN lesions were CIN II and CIN III)by p16/ki-67 dual-staining cytology and TCT were 0.755 and 0.487,respectively.The Kappa value of HSIL(CIN lesions were CIN II and CIN III)detected by p16/ki-67 dual-staining cytology and TCT was 0.736 and 0.247,respectively.Conclusion:1.p16/ki-67 dual-staining cytology had higher sensitivity than that of TCT and can identify high-grade cervical lesions.2.p16/ki-67 dual-staining cytology was more sensitive than cytological screening in non-16/18 High-risk HPV positive screening,which reduced the missed diagnosis rate in high-risk HPV Other positive screening.3.The operation of p16/ki-67 dual-staining cytology was relatively simple,and the results were relatively consistent with the gold standard of cervical biopsy pathological results.In summary,p16/ki-67 dual-staining cytology can be used as a new molecular marker for the detection of non-16/18 High-risk HPV positive and high-grade cervical lesions.更多还原