S963 Pooled Diagnostic Accuracy of Methylated DNA Biomarker Panels from Nonendoscopic Cell Collection Devices for Barrett’s Esophagus and Neoplasia Detection

Introduction: Barrett’s esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC), a cancer with rising incidence and poor survival. Despite guideline recommendations, screening uptake remains low due to reliance on endoscopy, an invasive and resource-intensive procedure. Minimally invasive, non-endoscopic methods that use esophageal cell collection devices in combination with methylated DNA biomarkers (MDMs) have emerged as promising alternatives for detecting BE and associated neoplastic lesions. We evaluated the pooled diagnostic performance of MDM panels applied to cytologic samples collected via various capsule sponge-based devices for detection of non-dysplastic BE, indefinite for dysplasia (IND), high-grade dysplasia (HGD), and EAC. Methods: We systematically searched MEDLINE, Embase, and Scopus from inception through May 2025 for studies evaluating the diagnostic accuracy of MDM assays for BE and related lesions. Multiple studies used genome-wide methylation profiling to identify and validate hypermethylated genes that differentiate BE from normal epithelium. Candidate MDMs—including CCNA1, VIM, TFPI2, TWIST1, and others—were analyzed via quantitative polymerase chain reaction or next-generation sequencing from cytologic samples collected using swallowable devices such as Cytosponge, EsophaCap, and EsoCheck. The most discriminative panels included combinations such as TFPI2, TWIST1, ZNF345, ZNF569; CCNA1 + VIM; and USP44, TBC1D30, NELL1. Cases included patients with BE or neoplasia confirmed on endoscopy; controls had no evidence of BE or dysplasia. Results: Eight studies were included, encompassing 853 cases and 713 controls. The pooled sensitivity for detecting any lesion (BE, IND, HGD, or EAC) amongst cases was 83.8%, and the pooled specificity for excluding these conditions in controls was 90.0%. Conclusion: Nonendoscopic esophageal cell collection paired with methylated DNA biomarker assays demonstrates high sensitivity and specificity for detecting BE and associated neoplasia. These approaches offer a scalable, patient-friendly alternative to traditional endoscopic screening and may improve early detection and risk stratification. Widespread implementation could address current gaps in screening uptake and aligns with American College of Gastroenterology and American Gastroenterological Association guideline priorities for EAC prevention.