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One Step Forward But Room for Improvement in Reducing Risk of Gastric Cancer by Curing Helicobacter pylori Infection

  • Colin W. Howden
    Correspondence
    Correspondence Address correspondence to: Colin W. Howden, MD, Division of Gastroenterology, 956 Court Avenue, Suite H210, Memphis, Tennessee 38163.
    Affiliations
    University of Tennessee College of Medicine, Division of Gastroenterology, Memphis, Tennessee
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Published:November 12, 2019DOI:https://doi.org/10.1053/j.gastro.2019.11.008
      See “Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study,” by Kumar S, Metz DC, Ellenberg S, et al, on page 527.
      For 2019, the American Cancer Society predicted that there would be 27,510 new cases of gastric cancer in the United States.
      • Siegel R.L.
      • Miller K.D.
      • Jamal A.
      Cancer statistics, 2019.
      This estimate exceeded that for both histologic forms of esophageal cancer combined by a ratio of almost 1.6. However, that imbalance does not reflect the activities of US-based gastroenterologists who are typically more focused on screening for esophageal adenocarcinoma (or, rather, antecedent Barrett’s esophagus) than the identification of patients at risk of gastric cancer. Between 2011 and 2016, the incidence of gastric cancer in the United States was 6.6 per 100,000 with a male preponderance and with the greatest burden of disease falling on the Asian/Pacific Islander, non-Hispanic black, Hispanic, and American Indian/Alaska Native populations.
      • Siegel R.L.
      • Miller K.D.
      • Jamal A.
      Cancer statistics, 2019.
      Helicobacter pylori infection has long been recognized as a major risk factor for the development of gastric cancer, and especially for cancers located in the distal stomach. Within the United States, the burden of H pylori infection mirrors that of gastric cancer with respect to race and ethnicity. Evidence has accumulated, largely from studies conducted in Asia, that treating asymptomatic adults for H pylori infection is associated with a reduced risk of development of gastric cancer.
      • Ford A.C.
      • Forman D.
      • Hunt R.H.
      • et al.
      Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials.
      ,
      • Lee Y.-C.
      • Chiang T.-H.
      • Chou C.-K.
      • et al.
      Association between Helicobacter pylori eradication and gastric cancer incidence: A systematic review and meta-analysis.
      In this issue of Gastroenterology, Kumar et al
      • Kumar S.
      • Metz D.C.
      • Ellenberg S.
      • et al.
      Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: A large cohort study.
      present the results of an important retrospective cohort study conducted within the US Veterans Administration health care system. The detection and successful treatment of H pylori infection was associated with a decreased risk of the subsequent development of nonproximal gastric cancer.
      The authors’ cohort comprised >370,000 patients. Of these, just over 10% had a positive diagnostic test of active H pylori infection; the remainder had been diagnosed serologically or identified upon receiving a prescription for an eradication regimen, or through the use of administrative codes. In a retrospective analysis, patients were followed starting with documentation of H pylori infection. Ultimately, just >1 in 200 infected patients developed gastric adenocarcinoma over a median follow-up of 7.4 years. As would be expected, patients who developed gastric cancer were typically older than those who did not and were more likely to be male, African American, and smokers. Importantly, not all patients with H pylori infection received treatment for it. Fortuitously, therefore, the authors were able to compare gastric cancer incidence between treated and untreated groups. The most important bottom line was that patients who were treated for H pylori infection and who had documented cure of infection had a 76% lower incidence of gastric cancer as compared with untreated individuals (ie, subhazard ratio of 0.24). The effect was seen exclusively among those patients who had a confirmed initial diagnosis of H pylori infection based on histology, a urea breath test, or a fecal antigen test. This finding strengthens the conclusion that effective treatment is protective against gastric cancer development because it is those patients who had the best evidence of active, ongoing infection at study inception—rather than those in whom the diagnosis of infection was made serologically or by a surrogate marker. Furthermore, the authors essentially excluded the misclassification of prevalent to incident cancers by analyzing their results based on excluding patients diagnosed with gastric cancer for up to 3, 6, or 12 months after the diagnosis of H pylori infection.
      This study adds valuable US experience to the body of evidence from overseas
      • Ford A.C.
      • Forman D.
      • Hunt R.H.
      • et al.
      Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials.
      ,
      • Lee Y.-C.
      • Chiang T.-H.
      • Chou C.-K.
      • et al.
      Association between Helicobacter pylori eradication and gastric cancer incidence: A systematic review and meta-analysis.
      that successful treatment of H pylori infection among asymptomatic infected individuals reduces the risk of gastric cancer development. Logically, this also underscores the importance of treating all patients who are found to have the infection—as was emphasized in recent guidelines.
      • Chey W.D.
      • Leontiadis G.I.
      • Howden C.W.
      • et al.
      ACG clinical guideline: Treatment of Helicobacter pylori infection.
      However—and through no fault of the authors—recent practice seems not to be keeping up with recommendations. Just under 75% of the patients with a positive diagnostic test of active H pylori infection received treatment for it. Furthermore, of the patients who were treated, only about 20% had a post-treatment test to document success or failure of eradication. Recent practice guidelines
      • Chey W.D.
      • Leontiadis G.I.
      • Howden C.W.
      • et al.
      ACG clinical guideline: Treatment of Helicobacter pylori infection.
      —admittedly published after the inception of this study cohort—recommend that all patients with a diagnosis of H pylori infection should be offered treatment for it, and that all treated patients should have post-treatment documentation of eradication. Accordingly, Kumar et al have identified important opportunities for education and for practice improvement within the Veterans Administration health care system—and, potentially, beyond. On a more positive note, the eradication rate among patients who were appropriately tested post-treatment was an impressive 90.9%. Unfortunately, we do not have precise information about which regimens were used, when post-treatment testing was performed, or whether patients were always taken off proton pump inhibitors, antibiotics, and bismuth before their post-treatment tests of active infection. However, the reported success rate was higher than recently documented among patients treated with a variety of regimens at academic medical centers in Rhode Island.
      • Alsamman M.A.
      • Vecchio E.C.
      • Shawwa K.
      • et al.
      Retrospective analysis confirms tetracycline quadruple as best Helicobacter pylori eradication regimen in the USA.
      So, we now have evidence from within the United States that treatment of H pylori infection among asymptomatic adults reduces—but does not eliminate—the risk of the subsequent development of gastric cancer. What implications does this hold for contemporary practice? Based on the demographics of the cohort, the results may not be immediately generalizable to the entire US population. H pylori infection is not the next hepatitis C; we are not yet at the stage of recommending universal screening—at least in this country. The prevalence of the infection among people born in the United States is lower than in less developed areas of the world—as is the absolute risk of gastric cancer from the infection. However, evidence is mounting that eradication of H pylori infection is beneficial even in a low prevalence country such as the United States. A wise man once said that, “The only good H pylori is a dead H pylori.” He may well have been right.

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