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Meta-Analysis
. 2020 Jul 6;7(7):CD005583.
doi: 10.1002/14651858.CD005583.pub3.

Helicobacter pylori eradication for the prevention of gastric neoplasia

Alexander C Ford  1 , Yuhong Yuan  2 , David Forman  3 , Richard Hunt  2 , Paul Moayyedi  2
Affiliations
Meta-Analysis

Helicobacter pylori eradication for the prevention of gastric neoplasia

Alexander C Ford et al. Cochrane Database Syst Rev. .

Abstract

Background: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear.

Objectives: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer.

Search methods: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials.

Selection criteria: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology.

Data collection and analysis: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy.

Main results: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported.

Authors' conclusions: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

PubMed Disclaimer

Conflict of interest statement

ACF: none known.

YY: none known.

DF: none known.

RH: none known.

PM is a joint co‐ordinating editor of Cochrane Gut, however editorial decisions about this review were made independently by another joint Co‐ordinating Editor of Cochrane Gut (Professor Gordon), and the Senior and Associate Editors of the Cochrane Abdomen and Endocrine network.

Figures

1
1
Study flow diagram: review update
2
2
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
1.1
1.1. Analysis
Comparison 1: H. pylori eradication vs control ‐ main analyses, Outcome 1: Incidence of gastric cancer ‐ modified ITT analysis
1.2
1.2. Analysis
Comparison 1: H. pylori eradication vs control ‐ main analyses, Outcome 2: Incidence of gastric cancer ‐ complete case analysis
1.3
1.3. Analysis
Comparison 1: H. pylori eradication vs control ‐ main analyses, Outcome 3: Death from gastric cancer ‐ modified ITT analysis
1.4
1.4. Analysis
Comparison 1: H. pylori eradication vs control ‐ main analyses, Outcome 4: Death from all causes ‐ modified ITT analysis
1.5
1.5. Analysis
Comparison 1: H. pylori eradication vs control ‐ main analyses, Outcome 5: Incidence of oesophageal squamous cell carcinoma ‐ modified ITT analysis
2.1
2.1. Analysis
Comparison 2: H. pylori eradication vs control ‐ subgroup analysis according to presence or absence of pre‐neoplastic lesions at baseline, Outcome 1: Incidence of gastric cancer according to presence or absence of pre‐neoplastic lesions at baseline
3.1
3.1. Analysis
Comparison 3: H. pylori eradication vs control ‐ subgroup analysis according to use of vitamins or antioxidants, Outcome 1: Incidence of gastric cancer according to use of vitamins or anti‐oxidants
4.1
4.1. Analysis
Comparison 4: H. pylori eradication vs control ‐ sensitivity analyses, Outcome 1: Incidence of gastric cancer ‐ modified ITT analysis substituting the 10‐year follow‐up data from Zhou 2014 with the 5‐year follow‐up data from Leung 2004
4.2
4.2. Analysis
Comparison 4: H. pylori eradication vs control ‐ sensitivity analyses, Outcome 2: Incidence of gastric cancer ‐ complete case analysis substituting the 10‐year follow‐up data from Zhou 2014 with the 5‐year follow‐up data from Leung 2004
4.3
4.3. Analysis
Comparison 4: H. pylori eradication vs control ‐ sensitivity analyses, Outcome 3: Incidence of gastric cancer‐ modified ITT analysis including the two arms of celecoxib from Wong 2012
4.4
4.4. Analysis
Comparison 4: H. pylori eradication vs control ‐ sensitivity analyses, Outcome 4: Incidence of gastric cancer ‐ modified ITT analysis including all randomised patients from Correa 2000 and You 2006 who were found subsequently to be ineligible or did not receive treatment
4.5
4.5. Analysis
Comparison 4: H. pylori eradication vs control ‐ sensitivity analyses, Outcome 5: Incidence of gastric cancer ‐ missing data imputation based on various assumptions
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Choi 2020 {published data only}
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Correa 2000‐Correa 2001 {published data only}
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Leung 2004‐Zhou 2014 {published data only}
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Saito 2005 {published data only}
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Wong 2004 {published data only}
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    1. Wong BCY, Lam S, Wong WM, et al. Eradication of Helicobacter pylori infection significantly slows down the progression of precancerous lesions in high risk populations: a 5 year prospective randomized study. In: Gastroenterology. Vol. 122. 2002:A588. Abstract W1216.
Wong 2012a {published data only}
    1. Feng GS, Ma JL, Wong BC, Zhang L, Liu WD, Pan KF, et al. Celecoxib-related gastroduodenal ulcer and cardiovascular events in a randomized trial for gastric cancer prevention. World Journal of Gastroenterology 2008;14(28):4535-9. - PMC - PubMed
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You 2006 ‐ Li 2019 {published data only}
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    1. Li WQ, Ma JL, Zhang L, Brown LM, Li JY, Shen L, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. Journal of the National Cancer Institute 2014;106(7). [DOI: ] [PMID: ] - PMC - PubMed
    1. Li WQ, Zhang JY, Ma JL, Li ZX, Zhang L, Zhang Y, et al. Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. BMJ 2019;366:l5016. [PMID: ] - PMC - PubMed
    1. Li WQ, Zhang L, Ma JL, Brown L, Li JY, Shen L, et al. Fifteen-year effects of Helicobacter pylori treatment on gastric cancer incidence and mortality among participants with different baseline gastric lesions and ages. American Journal of Epidemiology 2013;177 (Suppl 11):S61.
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References to studies excluded from this review

Choi 2014 {published data only}
    1. Choi J, Kim SG, Yoon H, Im JP, Kim JS, Kim WH, et al. Eradication of Helicobacter pylori after endoscopic resection of gastric tumors does not reduce incidence of metachronous gastric carcinoma. Clinical Gastroenterology and Hepatology 2014;12(5):793-800. - PubMed
Choi 2018a {published data only}
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Choi 2018b {published data only}
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Fischbach 2001 {published data only}
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Fischbach 2009 {published data only}
    1. Fischbach LA, Bravo LE, Zarama GR, Bravo JC, Ojha RP, Priest EL, et al. A randomized clinical trial to determine the efficacy of regimens containing clarithromycin, metronidazole, and amoxicillin among histologic subgroups for Helicobacter pylori eradication in a developing country. Helicobacter 2009;14(2):100-8. - PubMed
Ford 2005 {published data only}
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Fukase 2008 {published data only}
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Hamajima 2002 {published data only}
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Harvey 2004 {published data only}
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Juibari 2003 {published data only}
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Kamangar 2006 {published data only}
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Kim 2008 {published data only}
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Lane 2006 {published data only}
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Leja 2017 {published data only}
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Leung 2018 {published data only}
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Mabe 2009 {published data only}
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Mason 2002 {published data only}
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Miehlke 2001 {published data only}
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Moayyedi 2000 {published data only}
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Ogura 2008 {published data only}
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Ohkusa 2001 {published data only}
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Take 2005 {published data only}
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Take 2007 {published data only}
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Takenaka 2007 {published data only}
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Tang 2010 {published data only}
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Uemura 2001 {published data only}
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Yanaoka 2009 {published data only}
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References to ongoing studies

HELPER study {published data only}
    1. KCT0001262. Helicobacter Pylori Eradication for Gastric Cancer Prevention in the General Population. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001262 . [http://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=5307]
    1. NCT02112214. Helicobacter Pylori Eradication for Gastric Cancer Prevention in the General Population (HELPER). https://clinicaltrials.gov/ct2/show/nct02112214 .
Pan 2016 {published data only}
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References to other published versions of this review

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