机构：[1]Department of Pathology, Jingmen No.2 People's Hospital/Institute for Cancer Prevention and Treatment，Jingchu University of Technology, Jingmen, Hubei Province, 448000, China[2]Department of Obstetrics & Gynecology, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442008, China[3]Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China神经科中山大学附属第一医院[4]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China华中科技大学同济医学院附属同济医院[5]Central Hospital of Wuhan City, Huazhong University of Science and Technology, PR China[6]Department of Urology, The General Hospital of the People's Liberation Army, Beijing, China[7]School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong Province, China[8]Amity Institute of Molecular Medicine & Stem Cell Research, Amity University Uttar Pradesh, Sector-125, Noida, India[9]Skolkovo Institute of Science and Technology, 100 Novaya str., Skolkovo, Moscow Region, Russia[10]E. Rybicki's Biopharming Research Unit. 11 Clifford Avenue, Vredehoek, 8001, Cape Town, South Africa[11]Department of Zoology, North Orissa University, Baripada, India[12]Jingmen No.2 People’s Hospital, Jingmen, Hubei Province, China.[13]GeneRulor Company, Guangzhou, China[14]School of Public Health, The University of Hong Kong, Hong Kong, SAR, Dongguan Maternal and Child Hospital[15]Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China妇产科妇产科中山大学附属第一医院[16]Department of Obstetrics and Gynecology, Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China妇产科妇产科中山大学附属第一医院
Background: Since human papillomavirus (HPV) DNA testing has been promoted as primary screening strategy, the triage method has also evolved from morphological testing to a molecular biomarker detection to improve screening efficiency. In this study, we investigated the performance of three HPV integration hot-spots, HMGA2, LRP1B, and TP63, as potential triage markers in HPV screening tests. Materials and Methods: This cross-sectional study was conducted from November 2016 to December 2017 in the First Affiliated Hospital of Sun Yat-sen University. Immunocytochemistry was carried out using residual cervical cell samples from 121 HPV-positive cases (23 normal, 24 cervical intraepithelial neoplasia (CIN) 1, and 74 CIN2+). Results: Of the 121 cases, 77 showed completely paired for the three biomarkers. In these 77 cases, receiver operating characteristic (ROC) analysis of HMGA2 showed the best potential for detecting CIN2+ among HPV+ cases (sensitivity 70%; specificity 91.89%; AUC 0.839). TP63 was second most effective biomarker (AUC 0.838; sensitivity 80%; specificity 81.08%). In contrast, LRP1B had the smallest AUC (0.801) among the three biomarkers but had the highest sensitivity (90%) and specificity (56.76%). To test the triage value of combining the three biomarkers, logistic regression was conducted followed by ROC comparison analysis. Promisingly, the combination of the three biomarkers gave the largest AUC of 0.951 with 92.5% sensitivity and 89.1% specificity (P < .0001 compared to liquid-based cytology test by Z-test). Conclusions: A combination of HMGA2, LRP1B, and TP63 as potential biomarkers may be useful for screening during triage of HPV-positive patients, particularly for detecting CIN2 + .
基金：
National Science and Technology Major Project of the Ministry of science and technology of China [2018ZX10301402]; Nature and Science Foundation of China [81,761,148,025, 81,630,060, 81,572,570, 81,772,787, 81,403,166]; National Key Research & Development Program of China [2016YFC0902901]; Guangzhou Science and Technology Programme [201704020093]; Fundamental Research Funds for the Central Universities [17ykzd15]; Three Big Constructions-Supercomputing Application Cultivation Projects - National Supercomputer Center In Guangzhou; Jingmen Key Science and Technology Planning Project [YFZD2016039]
第一作者机构：[1]Department of Pathology, Jingmen No.2 People's Hospital/Institute for Cancer Prevention and Treatment，Jingchu University of Technology, Jingmen, Hubei Province, 448000, China
共同第一作者：
通讯作者：
通讯机构：[4]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China[16]Department of Obstetrics and Gynecology, Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China[*1]The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong Province, 510080, China.
推荐引用方式(GB/T 7714)：
Jiang Yunhui,Zhu Chengyi,He Dan,et al.Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women[J].TRANSLATIONAL ONCOLOGY.2019,12(7):959-967.doi:10.1016/j.tranon.2019.04.012.
APA：
Jiang, Yunhui,Zhu, Chengyi,He, Dan,Gao, Qinglei,Tian, Xun...&Hu, Zheng.(2019).Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women.TRANSLATIONAL ONCOLOGY,12,(7)
MLA：
Jiang, Yunhui,et al."Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women".TRANSLATIONAL ONCOLOGY 12..7(2019):959-967
