Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women

Yunhui Jiang, Chengyi Zhu, Dan He, Qinglei Gao, Xun Tian, Xin Ma, Jun Wu, Bhudev C. Das, Konstantin Severinov, Inga Isabel Hitzeroth, Priya Ranjan Debata, Rong Liu, Liang Zou, Long Shi, Hua Xu, Kaixiu Wang, Yuxian Bao, Leung Ross Ka-Kit, Zeshan You, Zifeng CuiZheng Hu

Research output: Contribution to journalArticle

Abstract

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 +.

Original languageEnglish (US)
Pages (from-to)959-967
Number of pages9
JournalTranslational Oncology
Volume12
Issue number7
DOIs
StatePublished - Jul 2019

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Biomarkers
Triage
Area Under Curve
ROC Curve
Sensitivity and Specificity
Cervical Intraepithelial Neoplasia
Solar System
Cell Biology
Cross-Sectional Studies
Logistic Models
Immunohistochemistry
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jiang, Yunhui ; Zhu, Chengyi ; He, Dan ; Gao, Qinglei ; Tian, Xun ; Ma, Xin ; Wu, Jun ; Das, Bhudev C. ; Severinov, Konstantin ; Hitzeroth, Inga Isabel ; Debata, Priya Ranjan ; Liu, Rong ; Zou, Liang ; Shi, Long ; Xu, Hua ; Wang, Kaixiu ; Bao, Yuxian ; Ka-Kit, Leung Ross ; You, Zeshan ; Cui, Zifeng ; Hu, Zheng. / Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women. In: Translational Oncology. 2019 ; Vol. 12, No. 7. pp. 959-967.
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title = "Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women",
abstract = "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 +.",
author = "Yunhui Jiang and Chengyi Zhu and Dan He and Qinglei Gao and Xun Tian and Xin Ma and Jun Wu and Das, {Bhudev C.} and Konstantin Severinov and Hitzeroth, {Inga Isabel} and Debata, {Priya Ranjan} and Rong Liu and Liang Zou and Long Shi and Hua Xu and Kaixiu Wang and Yuxian Bao and Ka-Kit, {Leung Ross} and Zeshan You and Zifeng Cui and Zheng Hu",
year = "2019",
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pages = "959--967",
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Jiang, Y, Zhu, C, He, D, Gao, Q, Tian, X, Ma, X, Wu, J, Das, BC, Severinov, K, Hitzeroth, II, Debata, PR, Liu, R, Zou, L, Shi, L, Xu, H, Wang, K, Bao, Y, Ka-Kit, LR, You, Z, Cui, Z & Hu, Z 2019, 'Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women', Translational Oncology, vol. 12, no. 7, pp. 959-967. https://doi.org/10.1016/j.tranon.2019.04.012

Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women. / Jiang, Yunhui; Zhu, Chengyi; He, Dan; Gao, Qinglei; Tian, Xun; Ma, Xin; Wu, Jun; Das, Bhudev C.; Severinov, Konstantin; Hitzeroth, Inga Isabel; Debata, Priya Ranjan; Liu, Rong; Zou, Liang; Shi, Long; Xu, Hua; Wang, Kaixiu; Bao, Yuxian; Ka-Kit, Leung Ross; You, Zeshan; Cui, Zifeng; Hu, Zheng.

In: Translational Oncology, Vol. 12, No. 7, 07.2019, p. 959-967.

Research output: Contribution to journalArticle

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

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

VL - 12

SP - 959

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JO - Translational Oncology

JF - Translational Oncology

SN - 1936-5233

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