郭 珍,赵冬梅,贾漫漫.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[J].中国肿瘤,2021,30(8):635-640.
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
中文关键词  修订日期:2020-11-09
DOI:10.11735/j.issn.1004-0242.2021.08.A010
中文关键词:  人乳头瘤病毒  p16  Ki-67  未明确意义的非典型鳞状上皮细胞  分流
英文关键词:human papilloma virus  p16  Ki-67  atypical squamous cells of undetermined significance  triage
基金项目:国家自然科学基金(81502475),河南省科技攻关计划项目(192102310105),河南省高等学校重点科研项目计划(20A330005)
作者单位
郭 珍 郑州大学附属肿瘤医院/河南省肿瘤医院 
赵冬梅 郑州大学附属肿瘤医院/河南省肿瘤医院 
贾漫漫 郑州大学附属肿瘤医院/河南省肿瘤医院 
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中文摘要:
      摘 要:[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。
英文摘要:
      Abstract:[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.
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