Helicobacter pylori treatment for the prevention of stomach cancer

Review question

Whether testing healthy people for Helicobacter pylori and treating those infected routinely with a course of antibiotics decreases the number of new cases of gastric cancer.

Background

People with H. pylori infection are more likely to develop gastric cancer than people who are not infected with the bacterium. For this reason, H. pylori is classed as carcinogenic (causing cancer) to humans. Many people worldwide die of gastric cancer every year, because by the time those affected seek the opinion of a doctor, the condition is often advanced. However, H. pylori infection is easily treatable with a one-week course of antibiotics.

Study characteristics

A literature search up to December 2013 found 6 trials (containing 6497 participants, 3 trials at low risk of bias). Five of the studies were based in Asia.

Key results

We found that antibiotics for H. pylori have a small benefit in preventing gastric cancer (51 (1.6%) of 3294 participants given treatment developed gastric cancer subsequently, compared with 76 (2.4%) of 3203 given no treatment or a placebo), but it is unclear whether or not they decrease the number of deaths from the disease, increase or decrease the number of deaths due to any cause, or increase or decrease the number of cases of oesophageal cancer. Data about side effects of treatment were poorly reported.

Quality of the evidence

Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. One study was at high risk of bias because no placebo was used for the active eradication therapy regimen, and so this part of the trial was unblinded, and the other study was at high risk of bias due to inconsistencies in data reporting at the two points of follow-up. We were unable to resolve this discrepancy despite contacting the original authors. As a result, we downgraded the quality of evidence from high to moderate due to serious risk of bias.

Authors' conclusions: 

We found limited, moderate-quality evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

Read the full 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 strategy: 

We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 11), MEDLINE (1946 to December 2013), and EMBASE (1974 to December 2013). 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 2013. 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. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Five trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (6 trials, 6497 participants, risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported effect of eradication of H. pylori on development of subsequent oesophageal cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to 21.91). The effect of H. pylori eradication on preventing death from gastric cancer compared with placebo or no treatment was uncertain due to wide confidence intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate-quality evidence). There was no evidence of an effect on all-cause mortality (4 trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality evidence). Adverse events data were poorly reported.

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