GERD and Upper Aerodigestive Tract Cancer Risk: A Systematic Review and Meta-Analysis.

Abstract

Gastroesophageal reflux disease (GERD) is highly prevalent, yet its association with upper aerodigestive tract (UADT) cancers beyond esophageal adenocarcinoma remains incompletely defined. This systematic review and meta-analysis aimed to quantify the risk of specific UADT cancers in individuals with GERD. A comprehensive search of PubMed, Embase, Scopus, the Cochrane Library, and CINAHL was conducted for studies published from January 2000 to October 2024. Observational studies (cohort or case-control) evaluating GERD as a risk factor for UADT cancers in adults were included, following PRISMA guidelines (PROSPERO: CRD42024602545). Esophageal adenocarcinoma was excluded due to its well-established association with GERD. Study quality was assessed using the Newcastle-Ottawa scale. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. Seventeen studies (12 case-control, 5 cohort), encompassing 1,768,394 participants, met inclusion criteria. GERD was significantly associated with laryngeal cancer (RR = 1.65, 95% CI = 1.19-2.31). No significant associations were found for pharyngeal, oropharyngeal, hypopharyngeal, or esophageal squamous cell carcinoma. Subgroup analysis showed stronger associations in U.S.-based studies (RR = 1.61) and in studies using ICD-coded GERD (RR = 1.93). GERD is associated with an increased risk of laryngeal cancer. Findings support further investigation into reflux-related carcinogenesis in the UADT, particularly in high-risk populations.