Efficacy of PPI-containing <i>Helicobacter pylori</i> Eradication Regimens and Gastric Cancer Risk Associated with Long-term PPI Use: A Meta-analysis and Network Meta-analysis

Background: Helicobacter pylori (H.pylori) is a significant risk factor for gastric cancer (GC), and proton pump inhibitors (PPIs) are commonly used as part of H. pylori eradication regimens.This study aims to systematically synthesize existing evidence on the efficacy and risks of PPI use in GC prevention.Methods: Individual studies were extracted from relevant systematic reviews published between 2020 and 2024, identified through searches in PubMed, Embase, and Web of Science, and an updated search was conducted to include original articles published between 2022 and August 2025.A random-effects model was used to estimate the overall effect size of PPI-containing regimens compared to non-PPI regimens.A network meta-analysis was conducted to compare the efficacy and risks among various PPIs.Results: Total of 60 original studies were included in the final analysis.Meta-analysis showed that H. pylori eradication was associated with a 43% reduction in GC (pooled OR/HR=0.57,95% CI=0.49-0.66).In network meta-analysis, triple therapies with lansoprazole and esomeprazole exhibited the highest treatment efficacy.In contrast, overall PPI use was associated with a 62% increased risk of gastric cancer GC (pooled OR/HR=1.62,95% CI=1.13-2.31),particularly with long-term use.In treatment ranking, overall PPI use ranked less favorably; however, among individual regimens, lansoprazole appeared to show comparatively lower gastric cancer risk relative to other PPIs.Conclusions: This study highlights the importance of careful selection of PPI regimens, particularly those based on lansoprazole, for H. pylori eradication and GC prevention, while also considering the potential risks associated with prolonged PPI use.