免疫细胞化学p16/Ki-67双染检测对宫颈细胞学阴性且HR-HPV阳性病例的分流作用及组织学LSIL的转归预测价值  

Predictive value of immunocytochemical p16/Ki-67 double staining for cervical cytology negative and HR-HPV positive shunting and histological LSIL prognosis

作　　者：邱晓阳[1] 王少洪[1] 郑璟 吴璇[1] 王媛媛[1] 刘君[3] 叶才果 QIU Xiaoyang;WANG Shaohong;ZHENG Jing;WU Xuan;WANG Yuanyuan;LIU Jun;YE Caiguo(Department of Pathology,Shantou Central Hospital,Shantou 515031,Guangdong Province,China;Department of Clinical Laboratory,Shantou Central Hospital,Shantou 515031,Guangdong Province,China;Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou 510060,Guangdong Province,China;Key Laboratory of Medical Molecular Diagnosis,Guangdong Province Affiliated to Guangdong Medical University,Dongguan 523808,Guangdong Province,China)

机构地区：[1]汕头市中心医院病理科,广东汕头515031 [2]汕头市中心医院检验科,广东汕头515031 [3]中山大学肿瘤防治中心病理科,广东广州510060 [4]广东医科大学广东省医学分子诊断重点实验室,广东东莞523808

出　　处：《中国癌症杂志》2020年第7期512-518,共7页China Oncology

基　　金：国家自然科学基金(81572782)。

摘　　要：背景与目的:目前,临床上仍缺乏对宫颈细胞学阴性且高危型人乳头状瘤病毒(high-risk human papilloma virus,HR-HPV)阳性病例的有效分流措施,同时预测组织学为低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)的病例是否会进展为宫颈高度病变的生物学指标尚不明确。探讨免疫细胞化学p16/Ki-67双染检测对宫颈细胞学阴性且HRHPV阳性病例的分流作用及LSIL的转归预测价值。方法:收集2017年4月—2018年7月于汕头市中心医院和中山大学肿瘤防治中心就诊、宫颈癌筛查细胞学阴性且HR-HPV阳性、30岁以上的708例已婚女性患者为研究对象。患者均进行了初次阴道镜检查和p16/Ki-67双染检测,观察p16/Ki-67双染检测结果与初次阴道镜组织学结果之间的关系,探讨p16/Ki-67双染诊断宫颈上皮内瘤变2/3级(cervical intraepithelial neoplasia 2/3,CIN2/CIN3)的效能,比较p16/Ki-67双染检测阳性率在不同亚型HPV感染组之间的差异。并对初次阴道镜组织学LSIL的223例患者随访1年,分析p16/Ki-67双染检测结果对LSIL转归的预测价值。结果:在生物显微镜下,宫颈细胞p16/Ki-67双染检测结果分为阴性和阳性两类。p16/Ki-67双染阳性患者中CIN2+的发生率[33.33%(55/165)]与p16/Ki-67双染阴性患者中CIN2+的发生率[1.10%(6/543)]相比差异有统计学意义(χ2=166.94,P<0.001)。p16/Ki-67双染阳性患者中CIN3+的发生率[26.06%(43/165)]与p16/Ki-67双染阴性患者中CIN3+的发生率[0.37%(2/543)]相比差异有统计学意义(χ2=140.35,P<0.001)。HPV其他12亚型组、HPV16/18亚型组、同时阳性组对应的p16/Ki-67双染阳性率变化经χ2趋势检验分析得知有递增趋势(χ2=29.119,P<0.001)。三组间两两比较,p16/Ki-67双染阳性率之间差异有统计学意义(P<0.01)。8例LSIL病变进展的患者中,有6例p16/Ki-67双染阳性,2例p16/Ki-67双染阴性,p16/Ki-67双染阳性诊断LSIL病变进展率是p16/Ki-67双染阴性的3倍。22例LSIL病�Background and purpose: At present, there is a lack of effective shunt measures for the patients with negative cervical cytology and positive high-risk human papilloma virus(HR-HPV). At the same time, it is not clear whether the patients with low-grade squamous intraepithelial lesion(LSIL) will progress to high-grade cervical lesions. The purpose of this study was to explore the role of immunocytochemical p16/Ki-67 double staining in the shunt of cervical cytology negative and HR-HPV positive patients and the predictive value of LSIL outcome. Methods: From Apr. 2017 to Jul. 2018, 708 married women over the age of 30 were selected from Shantou Central Hospital and Sun Yat-sen University Cancer Center. Cervical cancer screening was negative, and HR-HPV was positive in those women. All patients underwent primary colposcopy and p16/Ki-67 double staining. The relationship between the results of p16/Ki-67 double staining and the histological results of primary colposcopy was observed. The efficacy of p16/Ki-67 double staining in the diagnosis of cervical intraepithelial neoplasia grade 2/3(CIN2/CIN3) was discussed. The difference in the positive rate of p16/Ki-67 double staining between different HPV subtype infection groups was compared. Two hundred and twenty-three patients with LSIL were followed up for one year. The predictive value of p16/Ki-67 double staining test results for the outcome of LSIL was analyzed. Results: Under biomicroscopy, the results of double staining of p16/Ki-67 in cervical cells were divided into two categories: negative and positive. The incidence of CIN2+ was 33.33%(55/165) in the patients with positive double staining of p16/Ki-67 and 1.10%(6/543) in the patients with negative double staining of p16/Ki-67(χ2=166.94,P<0.001).The incidence of CIN3+ was 26.06%(43/165) in patients with positive double staining of p16/Ki-67 and 0.37%(2/543) in patients with negative double staining of p16/Ki-67(χ2=140.35,P<0.001). χ2 trend test showed the positive rate of p16/Ki-67 in the other 12 subtypes o

关 键 词：免疫细胞化学 p16/Ki-67 双染 宫颈细胞 高危型人乳头状瘤病毒 组织 宫颈上皮内瘤变 

分 类 号：R737.33[医药卫生—肿瘤]