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Helicobacter pylori (H. pylori) therapy and eradication protected against progression to gastric cancer in Hispanic patients with pre-cancerous lesions, and the protective effect of therapy endured at 20 years, researchers reported.

In the longest prospective study of a Hispanic population after an H. pylori eradication trial, therapy reduced progression of the , for an odds ratio of 0.59 (95% CI 0.38-0.93), according to Maria Blanca Piazuelo, MD, of Vanderbilt University in Nashville, and colleagues.

Furthermore, H. pylori-negative status continued to have a durable beneficial effect on the score over time (P=0.036), they reported in .

H. pylori infection is the main global driver of the precancerous Correa cascade and progression to gastric cancer, they noted, and "The current analysis shows that the protective effect of anti-H. pylori therapy [intention to treat] against progression of precancerous lesions remains after 20 years. Compared to participants who received placebo at baseline, those who were treated had a significant 41% reduction of the risk of progression as assessed by the comprehensive Correa score."

Study Details

The Colombian chemoprevention trial enrolled adult volunteers from two Colombian towns in a for gastric cancer. They underwent upper gastrointestinal endoscopy with biopsy mapping to determine eligibility.

Individuals with pre-cancerous lesions (multifocal atrophic gastritis, intestinal metaplasia, dysplasia) were invited to join a double-blind trial of anti-H. pylori therapy and antioxidant supplementation for preventing histological progression. Participants were randomized to receive 2 weeks of anti-H. pylori therapy, with or without beta-carotene and/or ascorbic acid supplementation, for 6 years or to corresponding placebos. At the end of the 6-year trial, anti-H pylori therapy was offered to previously untreated individuals.

The cohort was followed up with endoscopic visits at 12, 16, and 20 years after enrollment. Additional anti-H. pylori treatments were not part of the study protocol and were not recorded, the authors noted.

The baseline cohort included 800 randomized adults (mean age 51; 46% male). At baseline, 776 (97%) were H. pylori-positive. After gastric biopsy at entry, participants were biopsied at 3, 6, 12, 16, and 20 years and were assessed by Correa score. Over time, the cohort number dropped to 612 at 12 years and 356 at 20 years.

Individuals who were H. pylori-negative at 20 years had a net regression of -0.12 score units (95% CI -0.01 to -0.23, P=0.03) compared with baseline, while those who were still infected at year 20 had a net progression of 0.28 units (95% CI 0.4-0.14).

Clearance of H. pylori led to regression of multifocal atrophic gastritis and reduced the progression of intestinal metaplasia.

Incomplete-type versus complete-type intestinal metaplasia conferred a 13.4-fold higher risk of progression to gastric cancer risk (95% CI 1.8-103.8), according to the authors.

The maximum histological regression achieved by both H. pylori-positive and -negative individuals was observed 12 years after enrollment, and was probably due to the residual effect of interventions. Afterwards, a steady increase in the scores was observed at 16 and 20 years in both groups, but significantly lower in the absence of H. pylori. About 40% were still infected at 20 years.

'In Proper Context'

The study aligns with cited by the researchers, including a study from that showed that H. pylori therapy was associated with decreased rates of metachronous gastric cancer in high-risk patients following endoscopic resection of gastric dysplasia, commented Andrew Y. Wang, MD, of the University of Virginia in Charlottesville.

"The results of the current study are unquestionably important, as they provide new data regarding the long-term incident rates of progression among various premalignant gastric conditions, including progression from complete and incomplete gastric intestinal metaplasia to cancer," said Wang, who was not involved in the study. "It should be remembered, however, that this study's participants were Hispanic patients from an area in Colombia at increased risk for gastric cancer."

He added that the Correa cascade, which delineates progression from chronic gastritis to chronic atrophic gastritis (typically in the presence of H. pylori), to gastric intestinal metaplasia, to dysplasia, and then to non-hereditary, non-cardia gastric adenocarcinoma, is well accepted.

"However, the risk of developing non-hereditary gastric adenocarcinoma is influenced also by race, ethnicity, gender, and environmental factors. Therefore, the results of this study need to be taken in the proper context when they are applied to the heterogeneous U.S. population," Wang stressed.

The authors pointed out that of H. pylori infection in high-risk populations has been proposed and implemented in some populations in order to reduce gastric cancer rates. "However, important concerns remain, such as the increase in antibiotic resistance and alterations of the intestinal microbiota with yet unknown consequences," they wrote.

Wang agreed with the authors that any screen-and-treat mass strategy should be tailored to local conditions. As a first step, clear and strong guidelines on the management of individuals at high risk should be considered, even in countries with overall low- and moderate-risk of gastric cancer, according to Piazuelo's group.

Additional strategies should include careful high-quality endoscopic examinations, optimal handling and processing of biopsy specimens, and adoption of pathology reports reflecting gastric cancer risk, they said.

In 2018, the expert panel that compiled the guidelines noted serious gaps in North America in the testing, treatment, and follow-up of H. pylori infection, which disproportionately impacts ethnic and racial minorities.

Limitations of the current study include a relatively high drop-out rate and the possibility of diagnostic and/or H. pylori status misclassification due to biopsy sampling error. Although H. pylori was assessed in all biopsy samples using a silver stain, false-negative results may have occurred, particularly in individuals with extensive intestinal metaphase.

Other limitations were the lack of complete information on risk factors, such as smoking and other environmental influences, and on anti-H. pylori therapy after the 12-year follow-up.

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