Abstract
王海瑞,廖光东,江宇,李雨聪,乔友林,陈汶.p16/mcm2双染在宫颈上皮内瘤变的诊断价值及其与高危型HPV感染的关系[J].Chinese journal of Epidemiology,2017,38(9):1241-1245
p16/mcm2双染在宫颈上皮内瘤变的诊断价值及其与高危型HPV感染的关系
Diagnostic value of p16/mcm2 dual staining in cervical intraepithelial neoplasia and its association with high-risk HPV infection
Received:January 26, 2017  
DOI:10.3760/cma.j.issn.0254-6450.2017.09.020
KeyWord: p16  mcm2  宫颈上皮内瘤变  人乳头瘤病毒  宫颈癌筛查
English Key Word: p16  mcm2  Cervical intraepithelial neoplasia  HPV  Cervical cancer screening
FundProject:
Author NameAffiliationE-mail
Wang Hairui School of Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China  
Liao Guangdong Department of Gynecology and Obstetrics, the West China Second University Hospital, Sichuan University, Chengdu 610041, China  
Jiang Yu School of Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China  
Li Yucong Department of Gynecological Oncology, Chongqing Cancer Center/Cancer Hospital, Chongqing 400030, China  
Qiao Youlin Department of Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China  
Chen Wen Department of Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China chenwen@cicams.ac.cn 
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Abstract:
      目的 研究p16/mcm2免疫细胞化学双染在宫颈病变中的表达及其与HPV感染的关联,并探讨其在宫颈癌筛查中的应用价值。方法 将2015年5-12月参加宫颈癌筛查并行高危型HPV(HR-HPV)检测和液基细胞学检查的1 127名女性纳入研究,对留存细胞学标本进行p16/mcm2免疫细胞化学双染检测,并与宫颈组织病理学结果进行比较。结果 p16/mcm2在HPV16/18阳性组和其他HR-HPV阳性组的表达风险均高于HPV阴性组,OR值分别为15.95(95%CI:9.59~26.51)、10.53(95%CI:7.41~14.98);p16/mcm2阳性率随宫颈上皮内瘤变(CIN)级别的升高而升高,且在CIN2组、CIN3组中均高于良性病变组(P<0.05);p16/mcm2阳性者中检出CIN2及以上(CIN2+)和CIN3及以上(CIN3+)病变的灵敏度分别为86.1%、92.0%,特异度分别为46.1%、44.4%;在细胞学诊断为非典型鳞状细胞和低度鳞状上皮内病变人群中检出CIN2+和CIN3+病变的灵敏度分别为85.7%、87.5%,特异度分别为45.5%、44.1%。结论 p16/mcm2双染灵敏度高于细胞学检查,特异度优于HPV检测,可识别宫颈高度病变和指导CIN的分级,有望成为新的宫颈癌筛查标志物。
English Abstract:
      Objective To study the expression of p16/mcm2 immunocytochemical dual staining in cervical lesions and its association with high-risk HPV infection, and discuss its clinical value in cervical cancer screening. Methods From May to December 2015, a total of 1 127 women receiving cervical cancer screening, high-risk HPV (HR-HPV) test and liquid-based cytology test were included in the study. p16/mcm2 immunocytochemical dual staining was performed on residual cytology specimens and the results were compared with histopathology results. Results p16/mcm2 had a higher expression risk in HPV16/18 group and other HR-HPV group compared with HPV negative group, with OR of 15.95 (95%CI:9.59-26.51) and 10.53 (95%CI:7.41-14.98), respectively. The positive rate of p16/mcm2 increased with cervical intraepithelial neoplasia (CIN) severity, and was higher in both CIN2 group and CIN3 group than in benign lesion group (P<0.05). The overall sensitivity of p16/mcm2 to detect CIN2+ and CIN3+ lesions were 86.1% and 92.0%, respectively, and the overall specificity were 46.1% and 44.4%, respectively. In group with cytologic diagnoses of atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL), the sensitivity to detect CIN2+ and CIN3+ lesions were 85.7% and 87.5%, respectively, and the specificity were 45.5% and 44.1%, respectively. Conclusions p16/mcm2 dual staining has higher sensitivity than cytology test and better specificity than HPV test. It can identify high-grade cervical lesions and guide the classification of CIN. p16/mcm2 might be used as an innovative biomarker for cervical cancer screening.
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