Helicobacter pylori persists in pancreatic ductal adenocarcinoma despite eradication therapy

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with global 5-year survival below 12%. Recent molecular analyses have revealed that <i>Helicobacter pylori</i> may persist within the pancreatic ductal microenvironment despite successful gastric eradication. In a 2024 multicenter study, <i>H. pylori</i> DNA was detected in 41.6% of PDAC tissues, including patients with documented eradication. Metagenomic sequencing identified <i>H. pylori</i> 16S rRNA reads comprising up to 2.5% of total microbial DNA, supporting selective intrapancreatic survival. Mechanistically, CagA/VacA-mediated STAT3 and NF-κB activation drives cytokine release, oxidative stress, and mismatch repair suppression, enhancing oncogenic inflammation and genomic instability. Chronic colonization increased pancreatic intraepithelial neoplasia by more than 60% in murine models, underscoring its pathogenic potential. These findings suggest that <i>H. pylori</i> persistence represents a novel microbial co-factor in PDAC, warranting further exploration as a diagnostic biomarker and therapeutic target.