Helicobacter pylori eradication treatment and the risk of gastric and oesophageal cancer

Helicobacter pylori is a strong and well-established risk factor for gastric cancer, but seems to decrease the risk of oesophageal adenocarcinoma. Thus, eradication treatment for Helicobacter pylori may decrease the risk of gastric cancer, and increase the risk of oesophageal adenocarcinoma. The aim of this thesis was to examine how eradication treatment influences the risk of these tumours in various settings and different study designs.

Study I assessed the risk of gastric cancer after Helicobacter pylori eradication treatment in a systematic review and meta-analysis. Relevant literature was collected from PubMed, Web of Science, Embase and the Cochrane Library. The results of eight eligible cohort studies in predominantly Asian populations showed a risk decrease of more than 50% after eradication treatment for Helicobacter pylori (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.32-0.66). Study II described prescription patterns of Helicobacter pylori eradication treatment in the Swedish population based on nationwide data from the Prescribed Drug Registry. From 2005 to 2014 there were 140,391 individuals (1.5% of the Swedish population) receiving eradication treatment, with a decreasing use during the study period. Nearly all eradications (95.4%) used the standard triple therapy with a proton pump inhibitor and the antibiotics clarithromycin and amoxicillin, also for repeated eradication episodes (92.7%). Studies III and IV were Swedish nationwide, population-based cohort studies based on the Prescribed Drug Registry, Cancer Registry, Causes of Death Registry and the Patient Registry. The risks of gastric adenocarcinoma (Study III), as well as oesophageal adenocarcinoma, oesophageal squamous cell carcinoma and the premalignant condition Barrett’s oesophagus (Study IV) in the cohort of individuals who received Helicobacter pylori eradication treatment were compared to the risks in the corresponding Swedish general population. Study III showed a nearly 70% decrease in gastric adenocarcinoma risk from five years after eradication treatment (Standardised Incidence Ratio (SIR) 0.31, 95% CI 0.11-0.67), indicating that this treatment is effective also in a Western population. Study IV showed a decreased risk of oesophageal adenocarcinoma (SIR 0.17, 95% CI 0.00-0.92) and Barrett’s oesophagus (SIR 0.71, 95% CI 0.45-1.05) five years after eradication treatment, which was in contrast to the hypothesis. A decreasing trend was suggested also for oesophageal squamous cell carcinoma.

In conclusion, this thesis has indicated that eradication treatment for Helicobacter pylori prevents gastric cancer development both in Asian populations and in the Swedish population. There was no evidence that eradication treatment increases the risk of oesophageal adenocarcinoma, Barrett’s oesophagus or oesophageal squamous cell carcinoma

List of scientific papers

I. Doorakkers E, Lagergren J, Engstrand L, Brusselaers N. Eradication of Helicobacter pylori and gastric cancer: a systematic review and meta-analysis of cohort studies. Journal of the National Cancer Institute. 2016 Jul;108(9):djw132.
https://doi.org/10.1093/jnci/djw132

II. Doorakkers E, Lagergren J, Gajulapuri VK, Callens S, Engstrand L, Brusselaers N. Helicobacter pylori eradication in the Swedish population. Scandinavian Journal of Gastroenterology. 2017 Jun-Jul;52(6-7):678-685.
https://doi.org/10.1080/00365521.2017.1303844

III. Doorakkers E, Lagergren J, Engstrand L, Brusselaers N. Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population. Gut. 2018 Dec;67(12):2092-2096.
https://doi.org/10.1136/gutjnl-2017-315363

IV. Doorakkers E, Lagergren J, Engstrand L, Brusselaers N. Helicobacter pylori eradication treatment and the risk of Barrett’s esophagus, esophageal adenocarcinoma and esophageal squamous cell carcinoma. [Submitted]