RoC Review of Helicobacter pylori (H. pylori): Chronic Infection

Q: If I get infected with H. pylori, will I get cancer?
A: People with more severe H. pylori infection are at a greater risk of cancer than those who are asymptomatic. Most infected people do not show symptoms. Whether an infected person develops cancer may depend on characteristics of both the bacteria and the infected person. Studies have shown that certain strains are associated with a higher risk of gastric cancer than other strains. Other studies show that diet, including factors such as high salt, processed food, and red meat, may increase cancer risk in infected people.

A listing in the RoC identifies a substance or exposure circumstance as known or reasonably anticipated to be a human carcinogen and thus indicates that it can cause cancer under certain circumstances. It does not estimate cancer risks to individuals associated with exposures in their daily lives. Many factors affect whether a person will or will not develop cancer, including the carcinogenic potency of the substance, the level and duration of exposure, and an individual’s susceptibility to the carcinogenic action of the substance. For example, people with a compromised immune system may be at a greater risk of cancer.

Q: Are there ways to prevent H. pylori-induced cancer or death?
A: Because of the high public health significance of H. pylori infection, the RoC also reported on the status of activities for preventing H. pylori-induced stomach cancer, and related recommendations by national and international working groups. The strategies and recommendations depend on many factors. Highlights from this review and the expert working group reports include the following:

• The American College of Gastroenterology recommends H. pylori testing for individuals with peptic ulcers and treatment of those who test positive.
• For patients with gastric cancer and for low-grade gastric MALT lymphoma, testing and treatment may be useful.
• Randomized controlled trials, or clinical studies with control groups that receive placebos, show that screening for H. pylori infection and treating infected patients reduces stomach-cancer risk by approximately 35%.
• In the U.S., “screen and treat” programs are not currently recommended. It is unclear whether benefits from screening programs outweigh the potential risks of widespread antibiotic treatment in individuals with a low risk of cancer.
• Many, but not all, expert working groups on H. pylori management recommend “screen and treat” programs for individuals with a high risk of stomach cancer.

Q: Why was chronic infection with H. pylori selected for this report?
A: Previous studies of H. pylori have shown a link to cancer. The RoC provides a concise assessment of evidence in the previously published report from the International Agency for Research on Cancer (IARC).

Prevalence of both stomach cancer and H. pylori is higher among people living in poverty, people of color, and immigrant groups. By listing H. pylori, NTP also seeks to increase awareness in specific groups of people in the U.S. who may have higher rates of infection, and thus may be at a greater risk of cancer.

Q: What studies did NTP use to determine the listing status of chronic infection with H. pylori?
A: NTP relied on the International Agency for Research on Cancer assessment (IARC 2012). There was sufficient evidence that H. pylori can cause stomach cancer based on a large body of epidemiological studies showing that H. pylori infection is associated with an approximately three-fold risk of stomach cancer that cannot be explained by chance. These studies were conducted in different geographical locations and included analyses that combined data from 12 studies and meta-analyses.

Evidence for sufficient evidence of a rare gastric lymphoma primarily comes from intervention studies showing that antibiotic treatment of H. pylori resulted in high rates of cancer remission.

From experimental animal studies, NTP concluded there was sufficient evidence of carcinogenicity. H. pylori infection induces tumors in experimental animals of a similar type to those in humans, adenocarcinoma and lymphoma of the stomach.

Mechanistic studies found that chronic infection of the stomach with H. pylori can lead to cancer by biological pathways that are similar in humans. Factors important in determining whether cancer develops includes the virulence of the H. pylori strain, susceptivity of the infected individual, and the degree of acidity of the stomach, which affects the location in the stomach where gastric lesions occur.

Q: How are conclusions drawn?
A: Substances are listed in the RoC as known or reasonably anticipated to be a carcinogen using established listing criteria. Conclusions are based on scientific judgment, using systematic review methods, with consideration given to all relevant information.

For a substance to have the status of known to be a human carcinogen, there must be sufficient evidence of carcinogenicity from studies in humans, showing a cause-and-effect relationship between exposure to the substance and human cancer. Occasionally, substances are listed in this category based on human studies showing that the substance causes biological effects known to lead to the development of cancer.

For a substance to have the status of reasonably anticipated to be a human carcinogen, at least one of the following three situations must occur:

• Limited evidence of carcinogenicity from studies in humans, which indicates that causal interpretation is credible but that alternative explanations, such as chance, bias, or confounding factors, could not adequately be excluded.
• Sufficient evidence in experimental animals showing a cause-and-effect relationship between exposure to the substance and cancer.
• Member of a class of substances already listed in the RoC, or the substance acts through mechanisms indicating it would likely cause cancer in humans.

Q: What were the results of the peer review of chronic infection with H. pylori?
A: In the summer of 2018, three experts reviewed the draft Report on Carcinogens Monograph on H. pylori and unanimously agreed with NTP’s recommended listing status as known to be a human carcinogen.