Clinico-epidemiological Characteristics of <i>Helicobacter pylori</i>-naïve Undifferentiated Gastric Cancer

Objective Understanding the prevalence of screening targets is essential for optimizing cancer-screening strategies. However, the precise clinicoepidemiological characteristics of Helicobacter pylori-naïve gastric cancer (H. pylori-naïve GC), especially the undifferentiated type, remain unknown. We herein aimed to confirm the clinicopathological characteristics of H. pylori-naïve patients with undifferentiated GC in Japan. Methods This retrospective cross-sectional study used a database of esophagogastroduodenoscopies (EGDs) from 12 Japanese institutions (2016-2022). Patients who underwent EGD as part of their health monitoring were analyzed for the prevalence and clinical characteristics of H. pylori-naïve undifferentiated GC, including pure signet ring cell carcinoma (PSRCC) and por/sig lesions. The previous EGD images were reviewed to estimate the rate of missed lesions. Results Among 222,656 individuals, 35 PSRCC and 7 por/sig lesions were identified (prevalence: 0.020% and 0.003%, respectively). Por/sig lesions were more frequently located in the upper half of the stomach than were PSRCC lesions (71.4% vs. 40.0%, p=0.040). All PSRCC lesions were classified as pT1a, whereas 71.4% of por/sig lesions were pT1b or deeper, and 57.1% required surgery. Furthermore, 44.4% of PSRCC lesions were missed during previous EGDs, whereas none of the por/sig lesions were overlooked. Conclusion The prevalence of undifferentiated H. pylori-naïve GC was low. Compared with PSRCC, por/sig lesions were diagnosed at a more advanced stage and were not identified during previous examinations, highlighting their difficulty in detection during routine EGD screening. These findings underscore the need to revise EGD screening strategies, particularly in populations with a low prevalence of H. pylori infection.