p16/Ki-67蛋白双染检测法在人乳头瘤病毒阳性口咽部鳞状细胞癌诊断中的应用探究  

Evaluation of p16/Ki-67 double-stained immunohistochemistry in diagnosis of human papilloma virus-positive oropharyngeal squamous cell carcinoma

作　　者：张莺[1] 顾挺[1] 钱佳骏 薛俊青 刘胜楠 王丽珍[1] Ying Zhang;Ting Gu;Jiajun Qian;Junqing Xue;Shengnan Liu;Lizhen Wang(Department of Oral Pathology,Shanghai Ninth People′s Hospital,Shanghai Jiao Tong University School of Medicine&College of Stomatology,Shanghai Jiao Tong University&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Shanghai Key Laboratory of Stomatology&Shanghai Research Institute of Stomatology&Research Unit of Oral and Maxillofacial Regenerative Medicine,Chinese Academy of Medical Sciences,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院口腔病理科、上海交通大学口腔医学院、国家口腔医学中心、国家口腔疾病临床医学研究中心、上海市口腔医学重点实验室、上海市口腔医学研究所、中国医学科学院口腔颌面再生医学创新单元,上海200011

出　　处：《中华口腔医学杂志》2023年第3期244-250,共7页Chinese Journal of Stomatology

基　　金：上海交通大学医学院附属第九人民医院教学型医师项目(JXXYS-2018-2)。

摘　　要：目的探讨p16/Ki-67蛋白免疫组织化学双染技术在人乳头瘤病毒(human papilloma virus,HPV)阳性口咽部鳞状细胞癌(oropharyngeal squamous cell carcinoma,OPSCC)诊断中的应用价值,提高HPV检测阳性准确率的最优指数。方法选取上海交通大学医学院附属第九人民医院口腔病理科自2014年5月至2020年5月诊断为OPSCC的患者153例,其中男性130例,女性23例,年龄(58.6±10.0)岁。选择HPV RNA原位杂交法为金标准判断其HPV状态。对所有患者行p16免疫组织化学法、p16/Ki-67蛋白双染法检测及预后分析,并以p16/Ki-67双阳性指数20%、40%、60%为阈值,分别与HPV RNA原位杂交法比较灵敏度、特异度、阳性预测值、阴性预测值及预测患者预后的能力。结果153例OPSCC患者中HPV阴性114例,HPV阳性39例,OPSCC患者的HPV感染率为25.5%(39/153)。单一的p16阳性患者仅58.1%(36/62)为HPV阳性,且无法区分患者5年总体生存率。p16/Ki-67双阳性指数为40%时,HPV诊断能力最高(灵敏度=86.8%,特异度=94.8%,阳性预测值=84.6%,阴性预测值=95.6%,曲线下面积=0.897),且p16/Ki-67双阳性指数<40%与≥40%的患者5年生存率差异有统计学意义(P=0.012)。结论与p16单染相比,p16/Ki-67蛋白双染法可提高HPV阳性诊断准确率,且以双阳性指数40%为阈值判断HPV状态时对HPV阳性OPSCC的诊断最准确。相对于单一的p16染色,p16/Ki-67蛋白免疫组织化学双染技术可以更好地检测HPV。Objective To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus(HPV)-positive oropharyngeal squamous cell carcinoma(OPSCC)and find out the optimal index to improve the accuracy of HPV detection.Methods A total of 153 cases,from May 2014 to May 2020,diagnosed OPSCC in Shanghai Ninth People′s Hospital,Shanghai Jiao Tong University School of Medicine,were selected.This cohort included 130 males and 23 females,aged(58.6±10.0)years.HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status.p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases,and the p16/Ki-67 double positive index including 20%,40%,and 60%were used as the thresholds to compare their sensitivity,specificity,and positive prediction value(PPV),negative prediction value(NPV)and prognosis prediction ability.Results Among the 153 patients with OPSCC,114 were HPV-negative and 39 were HPV-positive,and the HPV infection rate of OPSCC patients was 25.5%(39/153).Only 58.1%(36/62)of single p16 positive cases were HPV-positive,and the prognosis of patients could not be distinguished using p16 immunohistochemistry only.Using p16/Ki-67 double staining,the accuracy of HPV positive diagnosis has been improved.The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40%(sensitivity=86.8%,specificity=94.8%,PPV=84.6%,NPV=95.6%,area under the curve=0.897),which could distinguish the prognosis of patients(P=0.012).Conclusions The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40%as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

关 键 词：免疫组织化学 KI-67抗原 蛋白 P16 人乳头瘤病毒阳性 口咽肿瘤 免疫组织化学双染 

分 类 号：R739.63[医药卫生—肿瘤] R739.8[医药卫生—临床医学]