H Pylori Eradication Reduces Gastric Cancer Incidence in High-Risk Populations

Yi-Chia Lee, MD, PhD

A meta-analysis published this month in the journalGastroenterology¹found that treatment of the bacterium Helicobacter pylori (H pylori) with antibiotics in a population at high risk for stomach cancer is associated with a reduced incidence rate of stomach cancer.

The reduction was statistically significant when researchers looked at the effect in high-risk populations (P= .037), or older patients (P= .023). After adjustment for baseline risk, eradication of H pylori was associated with a risk reduction of stomach cancer amounting to approximately 50%, according to lead author Yi-Chia Lee, MD, PhD, attending physician and clinical associate professor at National Taiwan University Hospital in Taipei.

Researchers concluded that past meta-analyses, which found no statistically significant benefit,²were flawed because they did not take into account the extended follow-up time required to determine the results in a population with less risk for stomach cancer.

The topic has been controversial, as the possibility of eradicating H pylori has been intensely studied as a possible strategy for reducing stomach cancer since 2005, when Barry Marshall and Robin Warren received the Nobel Prize for discovering the role of the pathogen in gastritis and peptic ulcer disease.

The bacterium is thought to cause stomach cancer by first giving rise to chronic inflammation of the gut, which develops into multifocal atrophic gastritis (MAG), and eventually intestinal metaplasia—in which the tissue of the stomach resembles colon tissue, leading to frank adenocarcinomas. For this reason, H pylori, which infects half the world’s population, is thought to be a major global public health threat.

In the study, Lee and colleagues performed a review of scientific literature through May 2015 of studies that examined the effect of eradication, using sources such as PubMed, the Cochrane Library, ClinicalTrials.gov, and Digestive Disease Week abstracts. Researchers compiled data on 48,064 individuals with 715 cases of gastric cancer from the studies and abstracts, the article said. Of the studies, 14 were conducted in asymptomatic individuals with H pylori, while 10 studies were done in patients who had undergone endoscopic resection of early gastric cancers.

Looking at the data set as a whole, there was no statistically significant difference in prevalence between those who underwent eradication therapy compared with those who did not (P= .67). But the baseline rate of gastric incidence varied widely between studies, ranging from 34.3 to 10,256.4 per 100,000 person-years, the article said.

But when the researchers looked only at those populations with intermediate or highest tertiles of risk, the reduction in gastric cancer following H pylori eradication was statistically significant.

Applied Research Ongoing Since 2004

The revisitation of H pylori eradication as a possible solution to gastric cancer was spurred by applied research conducted since 2004 on Matsu Island, a rural province of Taiwan.³While the program has been accompanied by a beneficial decrease in other conditions, its effect on gastric cancer has not yet been documented.

“We started from 2004 with the mass eradication program for this high-risk population, and have performed 4 rounds of screening. The level of H pylori infection has declined from more than 60% to about 15%. The rate of atrophic gastritis has also decreased by 77% and the rate of peptic ulcers has decreased by 67%,” explained Lee.

“As there may be a time lag of about 3 years until reporting of incidence data from the National Cancer Registry in Taiwan, we may report the final results in 2018. Meanwhile, in our previous report inGut, we used atrophic gastritis as a surrogate endpoint (noting a 77% reduction, which was significant). For gastric cancer, the reduction was 25%, but not significant,” he added.

In light of a lack of conclusive evidence from past meta-analyses, some researchers have focused almost exclusively on drug development efforts.

“If you look at the meta-analyses on the question of eradicating H pylori, in subjects that have advanced lesions the benefits are not supported. If you look at all comers, including those with earlier lesions, too, there’s a very modest benefit,” said Keith Wilson, M.D., professor of medicine at Vanderbilt University School of Medicine in Nashville, in a keynote lecture he gave at the 2016 ASCO Gastrointestinal Cancers Symposium.

Wilson recently received a grant to research the possible utility of difluoromethylornithine (DFMO), an experimental agent that was the subject of research in leukemia patients in the 1970s, in gastric cancer.

“It’s very possible the disease process in Asia is very different from what we study in Latin America,” he added. “For example, the Lee article talked about how the group that benefits most had early gastric cancers which were removed endoscopically. Then they were treated with drugs to get rid of H pylori. But we don’t see that type of thing. The Lee paper referred to the flaw of using surrogate markers instead of cancer itself. In the cohort we have followed since 1992, we follow the progression of pre-cancerous lesions.”

While one advantage to the eradication strategy is cost (sometimes as low as $70 per treatment), other possible criticisms include development of antibiotic resistance, the possibility of recontamination, and increased rates of esophagitis in those who are treated for the infection.

“For the population that has received eradication, the reinfection rate is very low at around 7 per 1,000 person-years. Additionally, we found that the rate of antibiotic resistance on Matsu Island has not increased,” said Lee.

However, the program has relied on endoscopic screening, which is both invasive and labor intensive. Additionally, researchers speculate that eradication may not help some individuals in whom the oncogenic process has passed the point of no return.

“We may use some biomarker to identify this group of high-risk subjects who may benefit from endoscopic surveillance,” he added, noting that additional tests for identification include Gastropanel and the pepsinogen test.

1) Lee Y., Chiang T., Chou C., et al: Association between Helicobacter pylori eradication and gastric cancer incidence: A systematic review and meta-analysis. Gastroenterology. 2016;150(5):1113—1124.

2) Ford AC, Forman D, Hunt RH, et al. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014;348:g3174.

See also Fuccio L, Zagari RM, Eusebi LH, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151:121—128.

3) Lee Y., Chen T., Chiu H, et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013;62:676—682.