Ki-67联合p16检测对HPV持续高危阳性患者子宫颈高级别鳞状上皮内病变的诊断价值

Diagnostic Value of Ki-67 Combined with p16 Test in Cervical High-grade Squamous Intraepithelial Lesions in Patients with Persistent High-risk Positive HPV

目的:分析原癌基因细胞增殖核抗原(Ki-67)联合细胞周期蛋白激酶的抑制因子(p16)检测对人乳头瘤病毒(HPV)持续高危阳性患者子宫颈高级别鳞状上皮内病变的诊断价值。方法:选取新余市人民医院2017年12月—2020年11月收治的慢性子宫颈炎患者134例、子宫颈低级别鳞状上皮内病变131例、子宫颈高级别鳞状上皮内病变129例、HPV持续高危阳性患者118例,分别记为对照1组、对照2组、对照3组、研究组,四组均取病灶组织采用免疫组化二步法检测Ki-67、p16蛋白表达,比较四组病灶组织Ki-67、p16蛋白表达情况及阳性率;比较研究组不同临床病理特征患者病变组织Ki-67、p16蛋白表达阳性率;采用列联表法分析在各组子宫颈高级别鳞状上皮内病变与病灶组织Ki-67、p16蛋白表达的关系,采用受试者操作特征(ROC)曲线分析病变组织标本中Ki-67、p16及联合诊断子宫颈高级别鳞状上皮内病变的价值。结果:四组病灶组织Ki-67、p16蛋白表达分布比较差异均有统计学意义(Z=29.852,P<0.001;Z=25.856,P<0.001),研究组病灶组织Ki-67、p16蛋白表达阳性率均高于其余三组(P<0.01),且对照2组、对照3组病灶组织Ki-67、p16蛋白表达阳性率均高于对照1组(P<0.01),研究组子宫颈高级别鳞状上皮内病变与病灶组织Ki-67、p16蛋白表达均呈正相关(C=0.745、0.641,P<0.01),HPV持续高危阳性患者Ki-67、p16及联合诊断子宫颈高级别鳞状上皮内病变的敏感度分别为65.40%、69.20%、78.90%,特异度分别为71.70%、73.60%、73.60%,AUC分别为0.718、0.729、0.816,联合诊断的AUC值高于Ki-67、p16单一诊断(Z=6.854,P=0.000;Z=6.741,P=0.000)。结论:子宫颈高级别鳞状上皮内病变与HPV持续高危阳性患者病灶组织Ki-67、p16蛋白表达均呈正相关,Ki-67联合p16检测的诊断价值较高。

Objective:To analyze the diagnostic value of proto-oncogene proliferative nuclear antigen(Ki-67)combined with cyclin kinase inhibitor(p16)detection in cervical high-grade squamous intraepithelial lesions in patients with persistent high-risk positive human papillomavirus(HPV).Method:A total of 134 patients with chronic cervicitis,131 patients with low-grade squamous intraepithelial lesions of the cervix,129 patients with high-grade squamous intraepithelial lesions of the cervix and 118 patients with persistent high-risk positive HPV were selected in Xinyu People's Hospital from December 2017 to November 2020,and were recorded as control group 1,control group 2,control group 3 and study group,respectively.The expressions of Ki-67 and p16 protein in the lesion tissues of the four groups were detected by immunohistochemical two-step method,and the expressions and positive rates of Ki-67 and p16 protein in the lesion tissues of the four groups were compared.The positive expression rates of Ki-67 and p16 protein in pathological tissues of patients with different clinicopathological characteristics were compared.The relationship between the expression of Ki-67 and p16 protein in lesion tissues and cervical high-grade squamous intraepithelial lesions in each group was analyzed by using the contingency table method.The value of Ki-67 and p16 in pathological tissue specimens and their combined diagnosis of cervical highgrade squamous intraepithelial lesions was analyzed by ROC curve.Result:There were significant differences in the distribution of Ki-67 and p16 protein in the four groups(Z=29.852,P<0.001;Z=25.856,P<0.001),the positive rates of Ki-67 and p16 protein expression were higher in study group than those in the other three groups(P<0.01),and the positive rates of Ki-67 and p16 protein expression in control group 2 and control group 3 were higher than those in control group 1(P<0.01).In the study group,there was a positive correlation between the expression of Ki-67 and p16 protein and cervical high-grade squamous intraepithelial lesions(C=0.745,0.641,P<0.01).The sensitivity,specificity and AUC of Ki-67,p16 and combined diagnosis of high grade squamous intraepithelial lesions were 65.40%,69.20%,78.90%,71.70%,73.60%,73.60%and 0.718,0.729,0.816,respectively.The AUC value of combined diagnosis was higher than that of Ki-67 and p16 single diagnosis(Z=6.854,P=0.000;Z=6.741,P=0.000).Conclusion:There is a positive correlation between the expression of Ki-67 and p16 protein in patients with persistent high-risk positive HPV and cervical high-grade squamous intraepithelial lesions.Ki-67 combined with p16 detection is of high diagnostic value.