中国多中心前瞻性研究：在非16/18型高危人乳头瘤病毒阳性女性中，PAX1m/JAM3m筛查在机会性宫颈癌筛查中的性能评估

Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China

Clinical Epigenetics

影响因子:4.4

分区:医学2区 / 遗传学2区肿瘤学2区

发表日期:2024 Aug 16

作者: Xiaojing Chen, Xitong Jin, Linghua Kong, Yuligh Liou, Pei Liu, Zhe Dong, Sijun Zhou, Bingli Qi, Jing Fei, Xiaoyan Chen, Guangwu Xiong, Yuchong Hu, Shikai Liu, Jianwei Zhou, Huafeng Shou, Lei Li

DOI: 10.1186/s13148-024-01731-w

摘要

本研究旨在验证PAX1和JAM3甲基化检测（PAX1m/JAM3m）作为筛查工具，用于检测非16/18型高危人乳头瘤病毒（hrHPV）阳性患者中的宫颈上皮内瘤变三级或更严重（CIN3+）。比较液基细胞学（LBC）和PAX1m/JAM3m检测在CIN3+检测中的表现。共纳入1851名具有宫颈组织学结果的参与者，分析显示，LBC检测（≥ASCUS）和PAX1m/JAM3m检测的敏感性/特异性分别为90.1%/26.7%和84.8%/88.5%。在整个队列中，PAX1m/JAM3m阳性（+）的诊断曲线下面积（AUC）最高，为0.866（95% CI：0.837-0.896）。所有20例癌症均由PAX1m/JAM3m（+）检测出。与LBC（≥ASCUS）相比，PAX1m/JAM3m（+）将需要转诊进行阴道镜检查的患者数减少了57.21%（74.66%比17.45%）。检测CIN3+的优势比（OR）为：LBC≥ASCUS为3.3（95% CI：2.0-5.9），PAX1m/JAM3m（+）为42.6（27.1-69.6）（p<0.001）。联合检测（LBC≥ASCUS或PAX1m/JAM3m（+））略微提高诊断敏感性（98.0%，95% CI：95.8-100%）和转诊率（77.09%），但降低诊断特异性（24.8%，22.7-26.8%）。在非16/18型hrHPV阳性女性中，PAX1m/JAM3m在检测CIN3+方面优于细胞学检测。相较于LBC（≥ASCUS），PAX1m/JAM3m（+）在不影响诊断敏感性的情况下，显著减少了需要转诊的患者数量。

Abstract

In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +).The triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared.In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%).In non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.