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.
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。.
Keywords: Cervical cancer screening; Cervical intraepithelial neoplasia; HPV; mcm2; p16.