Point-of-Care CagA Antibody Positivity and Its Association with Precancerous Gastric Changes

Early detection efforts in gastric carcinoma focus on identifying those with gastric premalignant conditions (GPMC), as they may benefit from secondary prevention. Noninvasive identification of persons with GPMC is an ideal avenue, but currently, no such strategy exists. Although persons with cytotoxin-associated gene A (CagA; the most well-known virulence factor in Helicobacter pylori infection) may be more prone to GPMC, CagA has traditionally been limited to research settings. Recently, a novel point-of-care (POC) test for CagA was developed. In this study, we report on the clinical utility of this test. We evaluated samples from adults undergoing preplanned endoscopy between 2023 and 2025 for benign indications to evaluate the association between GPMC and CagA antibody positivity. Among 95 persons, we found that 40% had H. pylori infection, 14% had GPMC, and 41% had CagA antibody positivity. There was a nonsignificant association between CagA antibody positivity and GPMC [odds ratio (OR) = 1.68; 95% confidence interval (CI), 0.48-5.85; P = 0.42]. In those without active H. pylori, the OR for CagA antibody positivity was 0.78 (95% CI, 0.13 to 4.73; P = 0.79), whereas in those with H. pylori, the OR for CagA antibody positivity was 3.46 (95% CI, 0.29 to 41.52; P = 0.33). We found nonsignificant associations between CagA antibody positivity and GPMC and active H. pylori infection may represent an important effect modifier. Our data suggest that although larger-scale validation is needed, a risk-guided screening strategy could include first testing for active H. pylori infection (e.g., breath or stool test), and if positive, POC testing for CagA antibodies.

Early detection of gastric cancer is sorely needed, and a risk-stratified approach to detecting which persons are likely to have gastric premalignant lesions and may benefit from endoscopy is the optimal secondary surveillance strategy.