TY - JOUR
T1 - Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women
AU - Jiang, Yunhui
AU - Zhu, Chengyi
AU - He, Dan
AU - Gao, Qinglei
AU - Tian, Xun
AU - Ma, Xin
AU - Wu, Jun
AU - Das, Bhudev C.
AU - Severinov, Konstantin
AU - Hitzeroth, Inga Isabel
AU - Debata, Priya Ranjan
AU - Liu, Rong
AU - Zou, Liang
AU - Shi, Long
AU - Xu, Hua
AU - Wang, Kaixiu
AU - Bao, Yuxian
AU - Ka-Kit, Leung Ross
AU - You, Zeshan
AU - Cui, Zifeng
AU - Hu, Zheng
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/7
Y1 - 2019/7
N2 - 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 +.
AB - 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 +.
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U2 - 10.1016/j.tranon.2019.04.012
DO - 10.1016/j.tranon.2019.04.012
M3 - Article
AN - SCOPUS:85065609705
SN - 1944-7124
VL - 12
SP - 959
EP - 967
JO - Translational Oncology
JF - Translational Oncology
IS - 7
ER -