Cytosponge and Methylation-Based Markers for Detection of Dysplasia in Patients with Barrett's Oesophagus: A Review

Abstract

Barrett's oesophagus is the only established precursor of oesophageal adenocarcinoma, and most people who have it do not know. Endoscopy finds it reliably and cannot be offered to everyone at risk, which is why swallowable sampling devices paired with a biomarker have been developed. Whether they detect dysplasia, as opposed to detecting the metaplasia itself, is a separate question that the evidence answers less completely. Objectives: To review the published evidence on non-endoscopic cell collection combined with trefoil factor 3 immunocytochemistry or DNA methylation markers in Barrett's oesophagus: reported accuracy, how performance varies with segment length and sampling, what has been shown specifically for dysplasia, and where these tests sit against endoscopy.
Material and Methods: Narrative review of device development studies, case-control diagnostic studies, randomised trials, cohort studies of risk stratification, cost-effectiveness analyses and guidelines indexed in PubMed and the major gastroenterology journals. Studies were eligible if they reported the accuracy or acceptability of a non-endoscopic sampling device with a biomarker readout, outcomes from its use in a defined population, or guidance on its place in practice. No new patient data were generated; every accuracy estimate quoted is one published by the original investigators. Results: In a multicentre case-control study of 1,110 participants, 93.9 per cent successfully swallowed the device and no serious adverse events were attributed to it. Sensitivity of Cytosponge-TFF3 for Barrett's oesophagus was 79.9 per cent overall, rising to 87.2 per cent for segments of at least 3 centimetres, which carry the higher cancer risk, and to 89.7 per cent when the device was swallowed twice; specificity was 92.4 per cent, and there was no loss of sensitivity in patients with dysplasia. A separate series reported 90.0 per cent sensitivity and 93.5 per cent specificity for circumferential segments of at least 2 centimetres. A balloon-based device paired with methylated vimentin and cyclin A1 achieved sensitivity and specificity both above 90 per cent. In a pragmatic randomised trial across 109 primary care practices, offering the test increased the number of patients diagnosed with Barrett's oesophagus. Conclusion: Non-endoscopic sampling with either readout detects Barrett's oesophagus well enough to serve as a triage to endoscopy, and a randomised trial has shown it changes how many diagnoses are made. The evidence for detecting dysplasia specifically is thinner: sensitivity is reported as preserved in dysplastic patients rather than measured against dysplasia as the primary target, and the biomarker panels that stratify risk within a known Barrett's segment are a different application again. Abbreviations: BE – Barrett's Oesophagus, EAC – Oesophageal Adenocarcinoma, TFF3 – Trefoil Factor 3, VIM – Vimentin, CCNA1 – Cyclin A1, IM – Intestinal Metaplasia, LGD – Low-Grade Dysplasia, HGD – High-Grade Dysplasia, GORD – Gastro-Oesophageal Reflux Disease, EGD –  Oesophagogastroduodenoscopy, NGS – Next-Generation Sequencing, FFPE – Formalin-Fixed Paraffin-Embedded, NPV – Negative Predictive Value.