Novel devices and biomarkers in screening for esophageal squamous cell cancer

Abstract

Esophageal squamous cell carcinoma (ESCC) remains a significant global health challenge, with high mortality rates primarily due to late-stage diagnosis. Detecting ESCC at an early stage, when still amenable to endoscopic resection, could potentially improve survival outcomes and help reduce the overall disease burden. However, despite being the gold standard for ESCC diagnosis, conventional endoscopy has several limitations that hinder its widespread implementation for screening purposes. These include high-costs, invasiveness, suboptimal sensitivity in identifying precancerous lesions, and prerequisite specialized personnel and facilities. In this review, we aim to discuss the current ESCC screening practices and explore emerging screening methods incorporating novel diagnostic devices and biomarkers.

We first present advancements in endoscopic imaging techniques aimed at improving diagnostic accuracy and reducing operator dependency. These include artificial intelligence (AI)-assisted endoscopy, which enhances lesion detection, and confocal laser endomicroscopy, which enables real-time cellular-level assessment. Next, we explore the available non-endoscopic screening modalities such as swallowable cytology-based sampling devices. These minimally invasive tools, when combined with AI-assisted cytological analysis and molecular biomarkers, offer a viable alternative to conventional biopsy for early ESCC detection. We then provide an overview of circulating biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs, and protein-based markers, summarizing the current state of research on liquid biopsies and their potential role in ESCC screening. Additionally, we discuss breath and salivary diagnostics as emerging cost-effective, non-invasive approaches. Finally, we present the latest insights into tissue biomarkers, highlighting their relevance in identifying precancerous lesions and stratifying risk in ESCC screening.