Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples

Abstract Background Efficient triage of high-risk human papillomavirus (hrHPV)-positive women is essential to avoid unnecessary referrals and overtreatment. This study evaluates the diagnostic accuracy of the commercially available DNA methylation panel, GynTect® (ASTN1, DLX1, ITGA4, RXFP3, SOX17, a...

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Main Authors: Yifei Ren, Fengjiang Qin, Li Shen, LanFang Li, Qingrong Wu, Ping Yi
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14531-z
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author Yifei Ren
Fengjiang Qin
Li Shen
LanFang Li
Qingrong Wu
Ping Yi
author_facet Yifei Ren
Fengjiang Qin
Li Shen
LanFang Li
Qingrong Wu
Ping Yi
author_sort Yifei Ren
collection DOAJ
description Abstract Background Efficient triage of high-risk human papillomavirus (hrHPV)-positive women is essential to avoid unnecessary referrals and overtreatment. This study evaluates the diagnostic accuracy of the commercially available DNA methylation panel, GynTect® (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671), in cervical cytology samples from 146 women for detecting cervical intraepithelial neoplasia grade 3 (CIN3) or cervical carcinoma (CC). This analysis focuses particularly on the performance of the ZNF671 methylation marker (ZNF671m) within the panel. Results The positive rates of all triage markers—hrHPV, TCT, HPV16/18, GynTect®, and ZNF671m—correlated with increasing severity of CIN lesions (Chi-squared test for trend, P < 0.01). ZNF671m exhibited the highest Area Under the Curve (AUC) of 0.811 (95% CI: 0.734–0.888) for identifying CIN3 + cases, closely followed by GynTect® (AUC 0.800, 95% CI: 0.721–0.878). Among 102 hrHPV-positive women, employing GynTect® or ZNF671m instead of TCT yielded identical sensitivity (0.84; 95% CI: 0.69–1.01) but enhanced specificity (86% and 90%, respectively) for detecting CIN3 +. Adding HPV16/18 to the triage strategy maintained similar outcomes. Additionally, ZNF671m showed a significant risk difference (60.0%; 95% CI 42.8–77.1%) for detecting CIN3 +, on par with GynTect® (57.6%; 95% CI 37.9–71.2%). Conclusion ZNF671m within the GynTect® panel demonstrates robust triage performance in diagnosing CIN3 + cases, with efficacy comparable to the full panel. These findings suggest that ZNF671m could be a promising alternative for cytologic triage, warranting further validation.
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spelling doaj-art-8c8ba4653f534bdba7b2b4d7d143557f2025-08-20T03:05:13ZengBMCBMC Cancer1471-24072025-07-012511910.1186/s12885-025-14531-zTriage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samplesYifei Ren0Fengjiang Qin1Li Shen2LanFang Li3Qingrong Wu4Ping Yi5Department of Obstetrics and Gynecology, Army Medical Center, Daping HospitalDepartment of Obstetrics and Gynecology, Chongqing University Fuling HospitalDepartment of Obstetrics and Gynecology, Chongqing University Fuling HospitalDepartment of Obstetrics and Gynecology, Army Medical Center, Daping HospitalDepartment of Obstetrics and Gynecology, Chongqing University Fuling HospitalDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background Efficient triage of high-risk human papillomavirus (hrHPV)-positive women is essential to avoid unnecessary referrals and overtreatment. This study evaluates the diagnostic accuracy of the commercially available DNA methylation panel, GynTect® (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671), in cervical cytology samples from 146 women for detecting cervical intraepithelial neoplasia grade 3 (CIN3) or cervical carcinoma (CC). This analysis focuses particularly on the performance of the ZNF671 methylation marker (ZNF671m) within the panel. Results The positive rates of all triage markers—hrHPV, TCT, HPV16/18, GynTect®, and ZNF671m—correlated with increasing severity of CIN lesions (Chi-squared test for trend, P < 0.01). ZNF671m exhibited the highest Area Under the Curve (AUC) of 0.811 (95% CI: 0.734–0.888) for identifying CIN3 + cases, closely followed by GynTect® (AUC 0.800, 95% CI: 0.721–0.878). Among 102 hrHPV-positive women, employing GynTect® or ZNF671m instead of TCT yielded identical sensitivity (0.84; 95% CI: 0.69–1.01) but enhanced specificity (86% and 90%, respectively) for detecting CIN3 +. Adding HPV16/18 to the triage strategy maintained similar outcomes. Additionally, ZNF671m showed a significant risk difference (60.0%; 95% CI 42.8–77.1%) for detecting CIN3 +, on par with GynTect® (57.6%; 95% CI 37.9–71.2%). Conclusion ZNF671m within the GynTect® panel demonstrates robust triage performance in diagnosing CIN3 + cases, with efficacy comparable to the full panel. These findings suggest that ZNF671m could be a promising alternative for cytologic triage, warranting further validation.https://doi.org/10.1186/s12885-025-14531-zCervical cancerCINDNA methylationGynTect® testHigh-risk human papillomavirusTriage
spellingShingle Yifei Ren
Fengjiang Qin
Li Shen
LanFang Li
Qingrong Wu
Ping Yi
Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
BMC Cancer
Cervical cancer
CIN
DNA methylation
GynTect® test
High-risk human papillomavirus
Triage
title Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
title_full Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
title_fullStr Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
title_full_unstemmed Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
title_short Triage of women with a positive HPV DNA test: evaluating a DNA methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
title_sort triage of women with a positive hpv dna test evaluating a dna methylation panel for detecting cervical intraepithelial neoplasia grade 3 and cervical cancer in cervical cytology samples
topic Cervical cancer
CIN
DNA methylation
GynTect® test
High-risk human papillomavirus
Triage
url https://doi.org/10.1186/s12885-025-14531-z
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