p16/Ki-67双染在宫颈癌及癌前病变初筛中的应用价值研究

Evaluation of p16/Ki-67 Dual Staining for Cervical Cancer and Precancerous Screening

目的:评价采用p16/Ki-67双染检测技术作为宫颈癌及癌前病变初筛方法的效果及应用价值。方法:对重庆市万州区982例年龄35~64岁有性生活的妇女进行宫颈癌筛查。每位妇女均接受了人乳头瘤病毒DNA(HPV DNA)检测、Thin Prep液基细胞学检查、p16/Ki-67双染检测,对结果异常者进行阴道镜检查,阴道镜下在可见病变处直接取活检,无可见病变时,行宫颈管搔刮术(ECC)。比较3种方法分别作为初筛手段识别宫颈癌前病变(高级别鳞状上皮内病变)及浸润癌的灵敏度、特异度、阳性预测值和阴性预测值等指标,以受试者工作特征(ROC)曲线下面积(AUC)综合分析3种方法作为宫颈癌初筛手段的应用价值。结果:最终966例妇女进入研究,共检出高级别鳞状上皮内病变及浸润癌患者42例。HPV DNA检测、液基细胞学检查和p16/Ki-67检测对宫颈癌及癌前病变患者的灵敏度分别为97.6%、88.1%、92.9%;特异度分别为84.1%、78.8%、82.8%;阳性预测值分别为21.8%、15.9%、19.7%;阴性预测值分别为99.9%、99.3%、99.6%。p16/Ki-67检测的AUC分别与HPV DNA检测、液基细胞学检查相比,差异均无统计学意义(P>0.05)。结论:p16/Ki-67双染检测初筛宫颈癌及癌前病变的效果与HPV DNA检测及液基细胞学检查相似,因其具有简便、客观、高效、易于重复的特点,p16/Ki-67双染检测为宫颈癌及癌前病变的有效初筛提供了一种新选择。

Objective： To evaluate the accuracy and applicative value of p16/Ki-67 dual stain as primary screening test for cervical cancer and precancerous lesions. Methods ：982 sexual active women between 35 -64 years were screened for cervical cancer in Wanzhou district,Chongqing. All women underwent HPV DNA testing, ThinPrep liquid-based cytology,p16/Ki-67 imrnunohistochemically dual staining. Lesion-targeted biopsy was per- formed under abnormal colposcopy to the patients without normal results. If no visible lesion was found, endocervi- cal curettage（ECC） was performed. The final diagnose was based on pathological findings. The sensitivity,speci- ficity,positive predictive value and negative predictive value of high-grade squamous intraepithelial neoplasia （HSIL） and cervical invasive cancer were compared. The area under receiver operating characteristic curve （ROC） of three methods were obtained to analyzed the applicative value of the three methods. Results ：966 sex- ual active women were included in the study,42 cases of high grade CIN and cervical cancer were diagnosed. The sensitivity of HPV DNA detection, liquid-based cytology and p16/Ki-67 detection was 97.6%, 88. 1% and 92.9% respectively. The specificity were 84. 1% ,78.8% and 82.8% respectively. The positive predictive values were 21.8% ,15.9% and 19.7% respectively. The negative predictive values were 99.9% ,99.3% and 99.6% respectively. No significant difference of the areas under ROC between p16/Ki-67 and HPV DNA detection, or p16/Ki-67 and liquid-based cytology（ P 〉 0.05）. Conclusions ：The accuracy of p16/Ki-67 dual staining for cervical cancer and precancerous lesions screening are similar screening cervical cancer and CIN p16/Ki-67 detection may for cervical cancer and CIN screening. to HPV DNA detection and liquid-based cytology in become a simple,objective, efficient and reproductive