Potential Chemopreventive Role of Proton Pump Inhibitors in Head and Neck Cancer: Insights from a Nested Case-Control...

Background/Objectives: This study investigated the potential chemopreventive role of proton pump inhibitor (PPI) use in relation to the occurrence of head and neck cancer (HNC) within a national cohort amid concerns of PPI overprescription. Methods: From a cohort of 1,137,861 individuals and 219,673,817 medical claim records collected between 2005 and 2019, 1677 HNC patients were identified and matched 1:4 with 6708 controls after adjusting for covariates. Odds ratios (ORs) for PPI use and its duration in relation to HNC and its subsites were estimated using propensity score overlap-weighted multivariable logistic regression. Additional subgroup analyses were performed based on age, sex, income level, and geographic region. Results: In the crude model, both current (OR 7.85 [95% CI 6.52-9.44]) and past PPI (OR 1.44 [95% CI 1.23-1.70]) use were associated with increased odds for HNC. However, after overlap weighting, this association reversed for both current (aOR 0.14 [95% CI 0.11-0.17]) and past PPI (aOR 0.69 [95% CI 0.60-0.79]). Subsite analysis showed reduced odds for hypopharyngeal (aOR 0.33, [95% CI 0.25-0.43]) and laryngeal cancer (aOR 0.19 [95% CI 0.16-0.22]) in current PPI users and similar results for past users. Conclusions: This study suggests a potential chemopreventive effect of PPIs, particularly in hypopharyngeal and laryngeal cancers. Additional studies are required to investigate the mechanisms underlying the association of the development of HNC with PPI use.