宫颈癌早期诊断中细胞学p16^INK4a检测的价值  

The value of p16^INK4a cytology for early diagnosis of cervical cancer

作　　者：段律芳[1] 杜辉[1] 肖爱民[1] 王纯[1] 闫培莎 黄霞 吴瑞芳[1] Duan Lüfang;Du Hui;Xiao Aimin;Wang Chun;Yan Peisha;Huang Xia;Wu Ruifang(Department of Gynecology and Obstetrics,Peking University Shenzhen Hospital,Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases,Shenzhen 518036,China)

机构地区：[1]北京大学深圳医院妇产科暨深圳女性重大疾病早期诊断技术重点实验室,518036

出　　处：《中华病理学杂志》2020年第8期812-815,共4页Chinese Journal of Pathology

基　　金：深圳市卫计委2017临床研究项目(SZLY2017005);深圳市政府"三名"工程(SZSM201412010);深圳市妇科重点学科(深卫计教科[2018]61号)。

摘　　要：目的探讨细胞学p16INK4a免疫化学染色用于宫颈癌早期诊断的临床价值。方法募集2018年3—8月深圳周边地区902名25~60岁有性生活非妊娠期女性进行宫颈癌筛查,同时行宫颈新柏氏薄层液基细胞学(TCT)、高危型人乳头状瘤病毒(HPV)检测和细胞学p16INK4a检测。任一检测结果阳性者均行阴道镜下宫颈四象限定点+随机活检+宫颈管搔刮方案,由2位细胞病理学主任医师对TCT和细胞学p16INK4a进行判读阅片,评价p16INK4a早期诊断宫颈上皮内瘤变(CIN)2+的效率和判读一致性。结果筛查人群中HPV、p16INK4a和TCT≥低级别鳞状上皮内病变(LSIL)/不典型腺细胞(AGC)阳性率分别为8.1%(73/902)、6.8%(61/902)和4.7%(42/902),任一筛查结果阳性者共137例,阴道镜回叫率79.6%(109/137),组织病理诊断为5例CIN2、5例CIN3。HPV阳性、p16INK4a阳性和TCT≥LSIL/AGC诊断CIN2+的灵敏度分别为100.0%、90.0%和80.0%,特异度分别为94.4%、95.3%和96.8%,差异均无统计学意义(均P>0.05)。两位细胞病理学医师对p16INK4a和TCT判读的Kappa值分别0.944和0.425。结论在宫颈癌筛查中,p16INK4a检测具有与HPV、TCT检测相近的灵敏度和特异度,而且细胞病理学医师对p16INK4a判读的主观差异小,提示p16INK4a检测作为新的宫颈癌筛查方法具有一定优势。Objective To investigate the use of p16INK4a immuno-stained cytology as the primary screening for cervical cancer prevention.Methods From March to August 2018,902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test(TCT),cobas4800 HPV test,and p16INK4a co-test.Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women,any of whose tests was positive.Two senior cytopathologists interpreted TCT and p16INK4a test.The performance of p16INK4a for early detection of CIN2+and inter-observer reproducibility of the interpretation of p16INK4a were evaluated.Results The positive rates of HPV test,p16INK4a co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1%(73/902),6.8%(61/902)and 4.7%(42/902),respectively.Colposcopy referring rate was 79.6%(109/137),among which 10 cases were diagnosed as CIN2+(5 cases of CIN2 and 5 cases of CIN3).The sensitivity and specificity for CIN2+of p16INK4a test,TCT(LSIL/AGC or higher grade)and HPV test were 90.0%,80.0%,100.0%and 90.9%,91.9%,82.5%,respectively.Compared to TCT and HPV test,there was no significant difference in sensitivity and specificity between p16INK4a and TCT/HPV test(P>0.05).The Kappa value of the 2 cytopathologists in interpreting p16INK4a and TCT was 0.944 and 0.425,respectively(P<0.05).Conclusions p16INK4a for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists′interpretation of p16INK4a is small.Therefore,p16INK4a can be used as a new cervical cancer screen method for its better diagnostic performance.

关 键 词：宫颈肿瘤 宫颈上皮内瘤样病变 细胞周期蛋白依赖激酶抑制剂p16 细胞学技术 免疫化学 

分 类 号：R737.33[医药卫生—肿瘤]