PO.PR01.02 · 预防研究

CervicalMethDx：对高危型HPV样本进行精准风险分层，以减少不必要的阴道镜转诊并提升价值导向医疗的质量

CervicalMethDx : Precision risk stratification of high-risk HPV samples to reduce unnecessary colposcopy referrals and improve the quality of value-based care

编号 5105 展板 19 时间 4/21 09:00–12:00 区域 Section 37 主讲 Yanira González Rodríguez, PhD

分会场 Early Detection and Interception

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作者与单位 Authors & Affiliations

Yanira González Rodríguez¹, Ashley Ramos-Lopez¹, Laura Palmieri², Amanda Garcia-Negron¹, Paola Quinonez-Mendez¹, Guie Beeu Guerrero Hunt², Alvaro Gutierrez Colima³, Carolina Teran⁴, Adhi Guerrero Thillet¹, Mariana Brait², Priscilla Brebi Mieville³, Carmen Ili⁵, Teresa Díaz-Montes⁶, Josefina Romaguera⁷, Bruce Trock⁸, David Sidransky⁹, Carolina Larronde³, Rafael E. Guerrero-Preston¹

¹LifeGene-Biomarks, Inc, San Juan, PR,²Oncology, Johns Hopkins Medical Insts., Baltimore, MD,³Center of Excellence in Translational Medicine (CEMT-BIOREN), Universidad de la Frontera, Temuco, Chile,⁴Facultad de Medicina, Universidad San Francisco Xavier of Chuquisaca,, Sucre, Bolivia, Plurinational State of,⁵Center of Excellence in Translational Medicine (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile,⁶Gynecologic Oncology Center, Mercy Medical Center, Baltimore, MD,⁷Obstetrics and Gynecology, University of Puerto Rico School of Medicine, San Juan, PR,⁸Brady Urological Institute,, Johns Hopkins Medical Insts., Baltimore, MD,⁹Lab Director, Otolaryngology, Johns Hopkins Medical Insts., Baltimore, MD

摘要 Abstract

中文摘要

致癌性人乳头瘤病毒（hrHPV）筛查可识别出许多一过性感染，但仅少数为具有临床意义的癌前病变，从而产生高比例不必要的阴道镜转诊。在美国，因hrHPV阳性而转诊阴道镜的女性中，70%-80%缺乏可采取干预措施的癌前诊断。鉴于超过90%的hrHPV感染会在12-24个月内自然清除，迫切需要客观的分子分诊工具，以优化阴道镜引导下的活检选择并提升价值导向的宫颈癌诊疗。 CervicalMethDx精准甲基化平台采用来自波多黎各、拉丁美洲和美国经IRB批准研究的1,618份样本进行评估。测试了独立数据集和多种标本类型，包括Digene和PreservCyt介质以及自采阴道拭子。在不同CervicalMethDx检测版本（1.0单重、1.5六基因组合、2.0双重）之间比较了诊断性能指标（敏感性、特异性、AUC）。采用相关分析和广义估计方程（GEE）模型评估跨检测的重现性和解剖部位一致性。 CervicalMethDx 1.0在hrHPV阳性Digene样本（n=108，波多黎各大学）中检出2级及以上宫颈上皮内瘤变（CIN2+）病变，敏感性96%、特异性84%、ROC曲线下面积（AUC）0.99。在ESTAMPA拉丁美洲试验（n=759）中，CIN3+检出敏感性67%、特异性59%、AUC 0.65。CervicalMethDx 1.5六基因组合在经CLIA认证的PreservCyt样本（n=377）中识别鳞状上皮内病变（SIL）细胞学，敏感性94%、特异性57%、AUC 0.85。在配对的宫颈拭子与自采阴道拭子（各n=100）之间未观察到显著甲基化差异（p>0.05），显示出强的个体内一致性。ZNF516甲基化在单重与双重检测之间相关（r=0.51，p=0.01）。GEE建模显示配对宫颈与阴道部位之间存在负的Pearson内相关（ρ=−0.64），证实了部位相关变异的一致性与可重现性。 CervicalMethDx为hrHPV阳性样本的风险分层提供了一种稳健的精准甲基化方法，有望减少不必要的阴道镜转诊和活检。该检测在自采与临床采集标本之间的可重现性，支持其整合入居家hrHPV检测流程的潜力，从而推动全球公平且价值导向的宫颈癌筛查。

查看英文原文 English abstract

Oncogenic human papillomavirus (hrHPV) screening identifies many transient infections, but few clinically significant precancers, generating high rates of unnecessary colposcopy referrals. In the United States, 70-80% of women referred for hrHPV-positive colposcopy lack actionable precancerous diagnoses. Given that >90% of hrHPV infections clear naturally within 12-24 months, there is an urgent need for objective molecular triage tools to optimize colposcopy-driven biopsy selection and enhance value-based cervical cancer care. The CervicalMethDx precision methylation platform was evaluated using 1,618 samples from IRB-approved studies across Puerto Rico, Latin America, and the United States. Independent datasets and specimen types were tested, including Digene and PreservCyt media, as well as self-collected vaginal swabs. Diagnostic performance metrics (sensitivity, specificity, AUC) were compared across CervicalMethDx assay versions (1.0 singleplex, 1.5 six-gene panel, 2.0 duplex). Cross-assay reproducibility and anatomic-site concordance were assessed using correlation and generalized estimating equation (GEE) models. CervicalMethDx 1.0 detected cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions with 96% sensitivity, 84% specificity, and an area under the ROC curve (AUC) of 0.99 in hrHPV-positive Digene samples (n = 108, University of Puerto Rico). In the ESTAMPA Latin American trial (n = 759), CIN3+ detection reached 67% sensitivity, 59% specificity, and an AUC of 0.65. The CervicalMethDx 1.5 six-gene panel identified squamous intraepithelial lesion (SIL) cytology with 94% sensitivity, 57% specificity, and an AUC of 0.85 in CLIA-certified PreservCyt samples (n = 377). No significant methylation differences (p > 0.05) were observed between paired cervical and self-collected vaginal swabs (n = 100 each), demonstrating strong intra-individual concordance. ZNF516 methylation correlated across singleplex and duplex assays (r = 0.51, p = 0.01). GEE modeling showed a negative within-Pearson correlation (ρ = −0.64) between paired cervical and vaginal sites, confirming consistent site-dependent variation and reproducibility. CervicalMethDx provides a robust precision-methylation approach for risk stratification of hrHPV-positive samples with the potential to reduce unnecessary colposcopy referrals and biopsies. The assay's reproducibility across self-collected and clinician-collected specimens supports its potential integration into at-home hrHPV testing workflows, advancing equitable and value-based cervical cancer screening worldwide

利益披露 Disclosure

Y. González Rodríguez, None.. A. Ramos-Lopez, None.. L. Palmieri, None.. A. Garcia-Negron, None.. P. Quinonez-Mendez, None.. G. Guerrero Hunt, None.. A. Gutierrez Colima, None.. C. Teran, None.. A. Guerrero Thillet, None.. M. Brait, None.. P. Brebi Mieville, None.. C. Ili, None.. T. Díaz-Montes, None.. J. Romaguera, None.. B. Trock, None.. D. Sidransky, None.. C. Larronde, None.. R. E. Guerrero-Preston, None.

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