Chen, Mei-JyhMei-JyhChenFang, Yu-JenYu-JenFangChen, Chien-ChuanChien-ChuanChenChen, Chieh-ChangChieh-ChangChenLuo, Jiing-ChyuanJiing-ChyuanLuoBair, Ming-JongMing-JongBairChen, Po-YuehPo-YuehChenChou, Chu-KuangChu-KuangChouLee, Ji-YuhJi-YuhLeeYang, Tsung-HuaTsung-HuaYangYu, Jian-JyunJian-JyunYuKuo, Chia-ChiChia-ChiKuoChiu, Min-ChinMin-ChinChiuChen, Chi-YiChi-YiChenShun, Chia-TungChia-TungShunHu, Wen-HaoWen-HaoHuTsai, Min-HornMin-HornTsaiHsu, Yao-ChunYao-ChunHsuTseng, Cheng-HaoCheng-HaoTsengChang, Chi-YangChi-YangChangLin, Jaw-TownJaw-TownLinEl-Omar, Emad MEmad MEl-OmarLee, Yi-ChiaYi-ChiaLeeWu, Ming-ShiangMing-ShiangWuLiou, Jyh-MingJyh-MingLiou2025-12-152025-12-152025https://scholars.lib.ntu.edu.tw/handle/123456789/734623Population-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.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.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.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.enHelicobacter pyloriaccuracydiagnosisscreeningserology[SDGs]SDG3journal article10.1111/hel.7007440976884