GERD Associated with Increased Risk of Laryngeal Cancer in Meta-Analysis

A systematic review and meta-analysis examined the association between gastroesophageal reflux disease (GERD) and the risk of specific upper aerodigestive tract (UADT) cancers, including laryngeal, pharyngeal, oropharyngeal, hypopharyngeal cancers, and esophageal squamous cell carcinoma. The study included a total of 1,768,394 adults, though the specific setting (e.g., population-based, hospital-based) was not reported. The exposure was GERD, defined variably across included studies; the comparator was not reported. The primary outcome was the risk of each UADT cancer type.

For laryngeal cancer, GERD was significantly associated with an increased risk, with a relative risk (RR) of 1.65 (95% CI 1.19-2.31). No significant associations were found for pharyngeal cancer, oropharyngeal cancer, hypopharyngeal cancer, or esophageal squamous cell carcinoma; effect sizes and confidence intervals for these outcomes were not reported. Subgroup analyses revealed stronger associations in U.S.-based studies (RR = 1.61) and in studies using ICD-coded GERD (RR = 1.93), though confidence intervals for these subgroups were not provided.

Safety and tolerability data were not reported, as this was a meta-analysis of observational studies focusing on cancer risk rather than intervention-related adverse events. The study did not report funding sources or conflicts of interest.

Compared to prior research, this meta-analysis extends the investigation of GERD beyond esophageal adenocarcinoma, which has a well-established link, to other UADT cancers. The findings for laryngeal cancer align with some prior studies suggesting a potential role of reflux in laryngeal carcinogenesis, but the null results for other sites highlight the need for further investigation.

Key methodological limitations include the observational nature of the included studies, which precludes causal inference. The association may be confounded by factors such as smoking, alcohol use, or obesity, which were not controlled for in the analysis. Additionally, the definition of GERD varied across studies, and the comparator group was not specified, limiting the ability to assess dose-response or duration effects. The lack of reported effect sizes for non-significant outcomes also limits the ability to compare magnitudes across cancer sites.

Clinically, these findings support further investigation into reflux-related carcinogenesis in the UADT, particularly in high-risk populations. However, given the observational nature, clinicians should interpret the association with caution and not assume a causal relationship. The results do not warrant changes in current screening or treatment practices for GERD based on cancer risk alone.

Unanswered questions include whether GERD treatment reduces laryngeal cancer risk, the role of confounding factors, and the biological mechanisms underlying the association. Future studies should use standardized GERD definitions, adjust for key confounders, and explore potential effect modifiers such as reflux type or duration.