Association between Helicobacter pylori infection and outcomes of cancer patients receiving immunotherapy: a systematic review and meta-analysis

Abstract

The association between Helicobacter pylori (H. pylori) infection and prognostic outcomes in cancer patients receiving immune checkpoint inhibitors (ICIs) remains controversial. We systematically searched PubMed, Embase, and the Cochrane Library up to September 2025 for studies reporting H. pylori status and outcomes in ICI-treated cancer patients. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR) were calculated using fixed- or random-effects models. Pre-defined exploratory subgroup analyses included cancer subtypes, definition of infection, and line of therapy. Seventeen observational studies comprising 3767 patients were included. At the pan-cancer level, H. pylori infection was associated with worse OS (HR = 1.58, 95% CI 1.21–2.06; I 2 = 59%) and PFS (HR = 1.60, 95% CI 1.18–2.16; I 2 = 73%), but not with ORR (OR = 0.79, 95%CI 0.39–1.60; I 2 = 80%). Cancer subgroup analyses revealed no significant association in gastric cancer across all endpoints. By contrast, potential detrimental associations were suggested in liver cancer, esophageal squamous cell carcinoma, and melanoma based on limited data. The definition of H. pylori infection (current vs. current or past) modified the OS association (p for subgroup difference < 0.01). H. pylori infection is associated with inferior survival outcomes in ICI-treated patients at the pan-cancer level, but not in gastric cancer, suggesting potential cancer-specific patterns. H. pylori might be a candidate prognostic biomarker in cancer immunotherapy, while future prospective validation in specific cancer subgroups is warranted.