P16/Ki-67蛋白双染在未明确意义的非典型鳞状上皮细胞人群中分流作用

Dual Staining of P16/Ki-67 Proteins in Triaging Women with Atypical Squamous Cells of Undetermined Significance

[目的]探讨p16/Ki-67免疫细胞双染法对宫颈细胞学为未明确意义的非典型鳞状上皮细胞(ASCUS)人群的分流效果。[方法]以2016年4月至12月在郑州大学第二附属医院妇科门诊就诊且被诊断为ASCUS的135例妇女为研究对象,收集其宫颈脱落细胞标本,进行14种高危型HPV DNA及p16/Ki-67蛋白检测,所有妇女均进行阴道镜活检和病理学检查。以组织病理学诊断为金标准,分别计算p16/Ki-67双染、高危型HPV(HR-HPV)和HPV16/18检测的敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV)、转诊率及其95%CI。[结果]135例ASCUS妇女平均年龄为(46.48±10.19)岁(23~64岁),其中诊断为宫颈上皮内瘤变(CIN)1级者7例,诊断为CIN2级及以上(CIN2+)者22例。随异常病理结果的严重性增加,p16/Ki-67双染、HR-HPV和HPV16/18检出阳性率均升高(P<0.001)。以CIN2+作为疾病终点指标时,p16/Ki-67双染对ASCUS人群分流的敏感性、特异性、PPV、NPV和转诊率分别为86.4%(95%CI:66.7%~95.3%)、85.8%(95%CI:78.2%~91.1%)、54.3%(95%CI:38.2%~69.5%)、97.0%(95%CI:91.6%~99.0%)和25.9%,与之相比,HR-HPV检测敏感性稍高[95.5%(95%CI:78.2%~99.2%)],但特异性较低[68.1%(95%CI:59.1%~76.0%)],转诊率较高(42.2%),且差异均有统计学意义(P<0.05)。与p16/Ki-67双染法相比,HPV16/18的特异性较高[92.9%(95%CI:86.7%~96.4%)],但敏感性很低[59.1%(95%CI:38.7%~76.7%)]。按照45岁进行年龄分层后,p16/Ki-67双染在≥45岁组ASCUS人群中分流效果要更好,敏感性为81.8%(95%CI:52.3%~94.9%),特异性为95.5%(95%CI:87.5%~98.4%)。[结论]P16/Ki-67双染检测在保持高敏感性的同时,有更高的特异性,因此对ASCUS人群的分流效果优于HR-HPV和HPV16/18。P16/Ki-67双染检测具有简便、客观、高效、易于重复的特点,可为ASCUS人群提供一种新的分流方法。

[Purpose]To evaluate the immunocytochemistry dual staining of p16/Ki-67 proteins in triaging women with atypical squamous cells of undetermined significance(ASCUS).[Methods]A total of 135 women diagnosed as ASCUS in the Second Affiliated Hospital of Zhengzhou University from April to December 2016 were enrolled in the study.HPV DNA detection and p16/Ki-67 dual staining were performed respectively.All patients underwent colposcopy biopsy and pathological examination.The histopathological result was used as the gold standard,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),referral rate of p16/Ki-67 dual staining,high risk HPV(HR-HPV)and HPV 16/18 were calculated.[Results]The mean age of patients was(46.48±10.19)years old(23~64).Seven women were diagnosed as cervical intraepithelial neoplasia 1(CIN1),20 were diagnosed CIN2+.The positive rates of p16/Ki-67 dual staining,HR-HPV DNA and HPV16/18 increased with the grade of pathologic diagnosis(P<0.001).The sensitivity,specificity,PPV,NPV and referral rate of p16/Ki-67 dual staining for predicting CIN2+lesion in women with ASCUS were 86.4%(95%CI:66.7%~95.3%),85.8%(95%CI:78.2%~91.1%),54.3%(95%CI:38.2%~69.5%),97.0%(95%CI:91.6%~99.0%),25.9%,respectively.To compared with p16/Ki-67 dual staining,HR-HPV DNA had higher sensitivity[95.5%(95%CI:78.2%~99.2%)]but lower specificity[68.1%(95%CI:59.1%~76.0%)]and higher referral rate(42.2%);HPV 16/18 had higher specificity[92.9%(95%CI:86.7%~96.4%)]and lower sensitivity[59.1%(95%CI:38.7%~76.7%)].After age stratification,p16/Ki-67 dual staining had a better triage effect in ASCUS patients with age≥45 years old;the corresponding sensitivity and specificity was 81.8%(95%CI:52.3%~94.9%)and 95.5%(95%CI:87.5%~98.4%),respectively.[Conclusion]P16/Ki-67 dual staining is better than HR-HPV DNA and HPV16/18 detection for triaging ASCUS woman under certain conditions,which is simple,objective,efficient and reproductive and can be a new method for triaging ASCUS women.