p16/微小染色体维持蛋白2和p16/Ki-67双重染色对高危型人乳头瘤病毒呈阳性妇女的宫颈病变筛查  

P16/minichromosome maintenance protein 2 and p16/Ki-67 double staining in cervical lesions screening of high-risk human papillomavirus positive women

作　　者：廖光东[1,2] 康乐妮[2,3] 李静[4] 曾玺[1,2] 郄明蓉[1,2] 

机构地区：[1]四川大学华西第二医院妇产科,成都610041 [2]四川大学华西第二医院出生缺陷与相关妇儿疾病教育部重点实验室,成都610041 [3]四川大学华西第二医院全国妇幼卫生监测办公室,成都610041 [4]四川大学华西公共卫生学院环境与职业医学系,成都610041

出　　处：《中华妇幼临床医学杂志（电子版）》2017年第4期425-431,共7页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：国家自然科学基金资助项目(81602504)~~

摘　　要：目的探讨p16/微小染色体维持蛋白(MCM)2和p16/Ki-67免疫组织化学双重染色,对高危型人乳头瘤病毒(HR-HPV)呈阳性妇女宫颈病变的筛查效果。方法选择2015年4月至10月,于四川省成都市双流区招募的符合本研究纳入、排除标准,并且于四川大学华西第二医院进行HPV DNA检测,诊断为HR-HPV呈阳性的62例妇女为研究对象。采集这62例HR-HPV呈阳性受试者的宫颈脱落细胞学标本,均采取新柏薄层液基细胞学检查(TCT)及p16/MCM2、p16/Ki-67免疫细胞化学双重染色。对于HPV-16、-18呈阳性,或其他12种HR-HPV(HPV-31、-33、-35、-39、-45、-51、-52、-56、-58、-59、-66、-68)呈阳性,并且TCT结果为≥未明确意义的非典型鳞状细胞(≥ASCUS)的受试者,均进行阴道镜检查,若阴道镜检查结果异常,再进行宫颈活组织检查。统计学比较p16/MCM2、p16/Ki-67双重染色与TCT,对HR-HPV呈阳性受试者宫颈病变筛查的敏感度、特异度、受试者工作特征(ROC)曲线下面积(AUC),评估p16/MCM2和p16/Ki-67双重染色对HR-HPV呈阳性受试者宫颈病变筛查的有效性。本研究经过四川大学医学伦理委员会批准(批准编号:K2014018)。所有受试者均同意参加宫颈癌筛查,并签署临床研究知情同意书。结果(1)纳入本研究的62例HR-HPV呈阳性受试者中,p16/Ki-67、p16/MCM2阳性率,均随宫颈病变程度增高而呈上升趋势(χ~2=21.947,P<0.001;χ~2=5.268,P=0.022)。TCT阳性率与宫颈病变程度无显著相关性(χ~2=1.850,P=0.174)。(2)HPV-16、-18呈阳性受试者的p16/Ki-67阳性率为69.2%(9/13),显著高于其他12种HR-HPV呈阳性受试者的36.7%(18/49),并且差异有统计学意义(χ~2=4.413,P=0.036)。HPV-16、-18呈阳性受试者与其他12种HR-HPV呈阳性受试者的p16/MCM2阳性率相比较,差异无统计学意义(χ~2=2.510,P=0.113)。(3)TCT及p16/Ki-67、p16/MCM2双重染色,对纳入本研究的62例HR-HPV呈阳性受试者的宫颈病变筛查的敏感度分别为47.1%(8/17)、94.1%Objective To explore the clinical efficacy of p16/minichromosome maintenance protein（MCM）2 and p16/Ki-67 immunocytochemical double staining in screening cervical lesions in high-risk human papilloma virus（HR-HPV）positive women.Methods From April to October,2015,a total of 62 women who were tested as HR-HPV positive in a cervical cancer screening program conducted in Shuangliu County,Chengdu,Sichuan Province and consistent with the inclusion and exclusion criteria of this study were selected as research subjects.The cervical exfoliative cytology specimens of these 62HR-HPV positive women were collected and ThinPrep liquid-based cytology test（TCT）detection,p16/MCM2 and p16/Ki-67 immunocytochemical double staining were performed on the same specimen of each HR-HPV positive woman.Women infected with HPV-16/18,or other 12 types of HR-HPV（HPV-31,-33,-35,-39,-45,-51,-52,-56,-58,-59,-66,-68）with cytological abnormalities in cervical exfoliated cells TCT detection（≥ atypical-squamous cells of undetermined signification,≥ASCUS）were examined by colposcopy.And if the colposcopy result was abnormal,cervical biopsy was then conducted on the woman.The sensitivities,specificities and area under curve（AUC）of the operator characteristic（ROC）curves of p16/MCM2 and p16/Ki-67 double staining in HR-HPV positive women for the detection of cervical lesions were compared with those of cervical exfoliated cells TCT detection by statistical methods,in order to evaluate the efficiency of p16/MCM2 and p16/Ki-67 double staining.This study was approved by the Medical Ethics Committee of Sichuan University（No.K2014018）.All women signed informed clinical research consents.Results（1）Among the 62 HR-HPV positive women,the positive rates of p16/Ki-67 and p16/MCM2 were both significantly increased with the histological severity,and both the differences were statistically significant（χ~2=21.947,P〈0.001;χ~2=5.268,P=0.022）.While the positive rate of cervical exfoliated cells TCT detection had no obvious r

关 键 词：乳头状瘤病毒科 宫颈肿瘤 p16/Ki-67 p16/微小染色体维持蛋白2 免疫细胞化学 双重染色 妇女 

分 类 号：R737.33[医药卫生—肿瘤]