Helicobacter pylori Eradication in the United States: A Deeper Exploration of Demographics, Strain Variations, and Clinical Implications

A retrospective study in the United States by Li et al1Li D. et al.Gastroenterology. 2023; 165: 391-401Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar demonstrated a notable reduction in gastric cancer risk after 8 years of Helicobacter pylori (HP) eradication, with a hazard ratio of 0.37 (95% confidence interval, 0.14–0.97). Although the study underscores the relevance of HP eradication in curbing noncardia gastric adenocarcinoma, several aspects merit deeper analysis. First, regional differences in gastric cancer incidence among HP-positive individuals in this study demand attention. HP exhibits strain differences, with the East Asian CagA-positive variant more likely causing gastric mucosal lesions and contributing to the carcinogenesis of gastric cancer.2Yamaoka Y. et al.Intern Med. 2008; 47: 1077-1083Crossref PubMed Scopus (183) Google Scholar Because of the high prevalence of this strain, gastric cancer is particularly common in East Asia. The United States, however, reports fewer of these strains. Thus, the question arises whether the infection identified in this study should be considered a CagA-negative HP infection. As noted in the text, the incidence of gastric cancer in this cohort was 1.7 to 3.9 times higher in Black, Hispanic, Asian, Native American, and Alaskan native populations than in White populations. These differences may reflect variations in HP strains within a given community. The racial disparities in gastric cancer development could be instrumental in framing preventive strategies. This study provides urban, suburban, and rural classifications of where the subjects live; however, it provides little geographic information, such as whether the incidence is skewed by region. Similar to the regional differences in the distribution of HP strains worldwide, there may also be regional differences in the distribution of strains in the United States. Because there are clear regional differences in the racial composition of the population of the United States, it is possible that regional differences in strains may be a confounding factor leading to racial differences in gastric cancer incidence. Further detailed regional analyses of the subjects may provide useful information. Second, analyzing the effect of eradication based on more specific age brackets could be enlightening. Early eradication of HP potentially minimizes cancer risk because of its role in chronic inflammation and subsequent gastric dysplasia. Asian countries, with a high gastric cancer incidence, are pioneering eradication efforts among youth. Specifically, Japan, recognizing the potential of early HP eradication, offers screenings to all junior and senior high school students in a given school year.3Saito H. et al.J Gastrointest Cancer. 2021; 52: 489-497Crossref PubMed Scopus (6) Google Scholar As of 2019, over 80 municipalities in Japan have been providing such screenings to adolescents. This surge in municipal initiatives has underscored the growing interest in the potential effects of HP eradication at a younger age. However, limited studies address the efficacy of early eradication in younger age groups. To truly understand the implications, a deeper exploration of the demographics of those aged 18–40 years, which was uniformly classified in the present study, is crucial. Finally, the external validity of this study warrants careful consideration. Whether the generalizability of this study, as the authors discussed, can be used in general practice in the United States should be carefully debated. Notably, the prevalence of HP infection is low in the United States, and routine screening in asymptomatic individuals is typically not recommended, except when there are additional risk factors such as family history. General practitioners and gastroenterologists in the United States tend not to test for HP in cases deemed to have a low risk of gastric cancer.4Shah S.C. et al.Gut Liver. 2018; 12: 38-45Crossref PubMed Scopus (11) Google Scholar However, in the present cohort, a notably low percentage (2.5%) reported a family history of gastric cancer; thus, it is crucial to understand the context in which HP tests were conducted in this cohort. The population of HP-positive individuals in this study may have had gastrointestinal diseases or symptoms at the time of testing. Even though a comorbidity score was provided, a more detailed investigation into the conditions faced by the patients is warranted to further evaluate the representativeness of the population. Notably, the advisability to eradicate HP can differ between those with and without gastrointestinal symptoms and diseases. Clarifying the specific clinical context in which the results of this study can be effectively applied becomes crucial. Effect of Helicobacter pylori Eradication Therapy on the Incidence of Noncardia Gastric Adenocarcinoma in a Large Diverse Population in the United StatesGastroenterologyVol. 165Issue 2PreviewHelicobacter pylori eradication therapy was associated with a significant reduction in the risk of developing noncardia gastric adenocarcinoma based on results from a large, diverse, community-based population. These findings support the potential for substantial gastric cancer prevention through testing and eradication of Helicobacter pylori in the United States. Full-Text PDF ReplyGastroenterologyPreviewWe appreciate the comments and suggestions by Dr Uchiyama and colleagues regarding our recent study published in Gastroenterology.1 We concur with their comments regarding the increased carcinogenic risk associated with certain CagA strains of Helicobacter pylori.2–4 Testing for CagA and differentiating its subtypes (such as East Asian CagA vs Western CagA) are not routinely performed in clinical practice in the United States, including in our study population. Accordingly, population-based data on the prevalence of CagA strains and subtypes in the United States overall and stratified by race and ethnicity remain very limited. Full-Text PDF