宫颈细胞内p16/Ki67表达与宫颈癌及癌前病变的关系及其用于HPV阳性人群分流的诊断价值

Expression of p16/Ki67 in Cervical Cancer and Precancerous Tissue and its Diagnostic Value for HPV Positive Women

[目的]探讨p16/Ki67双染技术对宫颈癌及癌前病变的检出能力,比较其用于HPV阳性人群分流的诊断价值。[方法]选取2016年9月至2017年5月山西长治三家三甲医院21～70岁参加宫颈癌筛查的妇女及门诊患者共计497例,所有入组研究对象均进行HPV E6/E7m RNA检测、液基细胞学检测（LBC）与p16/Ki67双染。[结果 ]p16/Ki67双染的阳性率随细胞学诊断及病理诊断的严重程度的增加而升高（P〈0.05）;p16/Ki67对62例宫颈上皮内瘤变2级及以上（CIN2＋）研究对象检出的灵敏度、特异性分别为69.4%、83.6%,HPV E6/E7m RNA检测分别为82.3%、74.6%,LBC检测分别为80.6%、65.2%。对49例CIN3＋研究对象检出的灵敏度、特异性分别为69.4%、81.9%,HPV E6/E7m RNA检测分别为85.7%、73.3%。在CIN2＋/CIN3＋病例中p16/Ki67的灵敏度与LBC均衡可比,但其特异性明显高于LBC和HPV E6/E7m RNA检测。在HPV E6/E7m RNA检测阳性人群中p16/Ki67双染对CIN2＋检出的灵敏度和特异性分别为82.4%和56.9%,LBC检测为90.2%和29.4%;p16/Ki67双染对CIN3＋检出的灵敏度和特异性分别为81.0%和53.2%,LBC检测为88.1%和27.0%。p16/Ki67双染中对CIN2＋及CIN3＋检出的灵敏度与LBC检测相比均无明显差异（P〉0.05）,但其特异性明显高于LBC检测（P〈0.001）。[结论]p16/Ki67双染技术用于HPV阳性人群的分流具有优于LBC的特异性和与LBC检测相似灵敏度的特性。在经济条件允许或者缺乏病理医生的地区,可以考虑使用p16/Ki67代替细胞学用于宫颈癌的初筛或HPV阳性人群的分流。

[Purpose] To investigate the expression of p16/Ki67 in cervical cancer and precancerous tissues and its diagnostic value for HPV positive women. [Methods] A total of 497 women aged 21~70 years were enrolled in this study. The expression of HPV E6/E7 m RNA was detected. Liquid based cytology（LBC） was performed and the p16/Ki67 expression was determined by dual staining immunohistochemistry. [Results] The positive rate of p16/Ki67 dual stain increased with the increase of cytologic and pathologic categories（P0.05）. For diagnosis of CIN2＋,the sensitivity and specificity of p16/Ki67 were 69.4% and 83.6%,those of HPV E6/E7 m RNA were 82.3% and74.6%,those of the LBC were 80.6% and 65.2%,respectively. For diagnosis of CIN3＋,the sensitivity and specificity of p16/Ki67 were 69.4% and 81.9%,those of HPV E6/E7 m RNA were 85.7% and 73.3%,those of LBC were85.75% and 73.3%,respectively. For diagnosis of CIN2＋/CIN3＋,the sensitivity of p16/Ki67 was equal to LBC,but the specificity of p16/Ki67 dual stain was higher than that of LBC and HPV E6/E7 m RNA（P0.05）. In the HPV positive women the sensitivity and specificity of p16/Ki67 were 82.4% and 56.9%,those of LBC were 90.2% and29.4%. Mc Nemar test showed that there was no significant difference in sensitivity for diagnosis of CIN2 ＋/CIN3 ＋between p16/Ki67 and LBC,but the specificity of p16/Ki67 dual staining was higher than that of LBC（P〉0.05）.[Conclusion] In HPV positive women the p16/Ki67 dual stain has a higher specificity than LBC. Therefore p16/Ki67 dual staining can be considered as a screening method for cervical cancer in HPV positive women.