Gastroesophageal and Laryngopharyngeal Reflux Associated With Laryngeal Malignancy: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: Gastric reflux may lead to chronic mucosal inflammation and contribute to development of laryngeal malignancies, although there is controversy over this association. We performed a systematic review and meta-analysis to assess this relationship and determine the risk of laryngeal malignancy in patients with reflux disease. METHODS: We performed a systematic review and meta-analysis, searching MEDLINE, EMBASE, and Web of Science databases from 1900 through April 9, 2018, for observational studies of adults reporting associations between gastroesophageal reflux disease (GERD) and/or laryngopharyngeal reflux and the risk of having or developing laryngeal malignancies. An itemized assessment of the risk of bias was conducted for each study that met inclusion criteria. The meta-analysis was performed using the Mantel-Haenszel method with random effects to account for heterogeneity. We performed subgroup analyses to determine the effect of reflux type, study design, diagnostic method, and confounding variables on the overall risk. RESULTS: Of the 957 studies that were identified during systematic review, 18 case-control studies met the criteria for analysis. Our meta-analysis showed that reflux disease significantly increased the risk of laryngeal malignancy (odds ratio, 2.47; 95% CI, 1.90-3.21; P <.00001; I-2 = 94%). This association remained when controlling for patient smoking and drinking (odds ratio, 2.07; 95% CI, 1.26-3.41). There was no statistically significant difference in risk of laryngeal malignancies between patients with GERD vs laryngopharyngeal reflux (P=.44). CONCLUSIONS: In a systematic review and meta-analysis, we found a significant association between reflux disease and the presence of laryngeal malignancy. Prospective studies should be performed to examine this relationship.