Overall and Stratified Accuracies of H. pylori Serology Testing: A Multicenter Study of 8497 Screening‐Naïve Adults

Background Population‐based Helicobacter pylori screening is a promising strategy for gastric cancer prevention in high‐prevalence regions. Although serology is recommended for treatment‐naïve individuals, its accuracy in large‐scale screening remains uncertain. This multicenter study evaluated serology against biopsy‐based tests and assessed the influence of age and atrophic status to inform stratified screening policies. Materials and Methods In this multicenter diagnostic study, 8497 treatment‐naïve adults undergoing upper endoscopy across nine hospitals in Taiwan were tested for H. pylori using serology, rapid urease test (RUT), histology, and culture. Serum pepsinogen I and II levels were measured to define serological atrophic gastritis (AG). Diagnostic performance was assessed against a composite reference standard (≥ 2 positive results among RUT, histology, and culture), with subgroup analyses by age and AG status. Results Serology showed a sensitivity of 94.5% (95% CI: 93.7–95.4) and specificity of 86.0% (95% CI: 85.0–87.0), with a diagnostic odds ratio (DOR) of 106.4. RUT, histology, and culture had higher specificities (97.1%, 94.3%, and 98.2%, respectively) but lower sensitivities (88.6%, 92.3%, and 90.2%, respectively). In individuals aged ≤ 45 years, serology demonstrated 95.2% sensitivity, 93.1% specificity, and a DOR of 268.9 (95% CI: 183.4–394.3). Among participants with AG, serologic specificity declined to 62.4% (95% CI: 53.3–71.5) versus 87.2% (95% CI: 86.0–88.5) in those without AG. The overall negative likelihood ratio was 0.06, and 0.05 among younger adults. Conclusions Serology is an accurate, non‐invasive tool for H. pylori detection in younger, treatment‐naïve adults without gastric atrophy in high‐prevalence regions. In older individuals or those with atrophic gastritis, confirmatory testing is warranted, supporting age‐atrophy–based algorithms to optimize screening strategies.