Population‐based screening and mass eradication of Helicobacter pylori infection to prevent gastric cancer: There are more questions than answers

Non-cardia gastric cancer remains one of the most important malignant disease of the digestive tract despite the fact that its incidence is declining with the rapidly declining prevalence of Helicobacter pylori infection. Therefore, the issue of whether or not screening for H. pylori infection should be undertaken in even high-prevalence countries for gastric cancer is a controversial subject that requires careful scrutiny of pros and cons of such policy. In this issue of the journal, a group of top-notched gastroenterologists from China published their consensus report on eradication of H. pylori and prevention of gastric cancer. They announced important statements on prevention of gastric cancer by population-based eradication of H. pylori. These include the following: (i) Eradication of H. pylori can effectively prevent gastric cancer in China, (ii) eradication of H. pylori is a cost-effective measure to prevent cancer in high-risk areas, and (iii) eradication therapy of H. pylori will not cause adverse consequences. These statements, if adopted by health authority of China, will have enormous implications on public health practice and resource allocation of the country. Before we jump into such huge commitment, we should ponder a little bit more. First, the consensus advocates that eradication of H. pylori can effectively prevent cancer in China. There is sufficient evidence that if we eradicate H. pylori early enough, preferably before atrophy and intestinal metaplasia sets in, there is a good chance that we can halt progression of gastric carcinogenesis and prevent gastric cancer. But, when it comes to practice in a massive scale, who should we screen for H. pylori infection? Definitely in the high-prevalence country for H. pylori and high-incidence country for gastric cancer, this strategy should give the best outcome. But at what age should we screen and treat H. pylori infection? Logically, treatment should be given before the premalignant stage of the disease has been reached. Is there a reliable way to detect whether the point-of-no-return has been reached in the stomach? As the prevalence of H. pylori infection has gone down tremendously in recent years, screening for the very young would not be cost-effective. On the other hand, screening for H. pylori too late, when irreversible damage is done in the stomach, will miss the golden opportunity. Second, the consensus claims that eradication therapy of H. pylori is cost-effective. However, a robust study with proof of cost-effectiveness is lacking. Calculation of cost-effectiveness depends on complicated factors including prevalence of H. pylori in the screened population, the choice of tests being used in the mass screening, logistic of implementation, compliance of the targeted population, expected outcome of treatment, and anticipated drop in gastric cancer rate, among others. In general, a non-invasive test such as urea breath test and stool antigen are more acceptable to asymptomatic individuals. Could these tests be arranged in the village and rural areas where health care systems are simple? Besides testing for H. pylori, endoscopic screening of asymptomatic gastric cancer or pre-cancerous lesions may be required in high risk individuals. Should we, or can we, rely on non-invasive test such as serum pepsinogen test? The implementation of screen-and-treat strategy for H. pylori to the whole population is an important decision. From the perspective of the health authority, screening for the infection to prevent gastric cancer has to compete with other diseases that also require resources for screening and prevention, for example, cardiovascular disease, diabetes, and metabolic disorders as well as other common cancers (e.g., colorectal cancer and liver cancer). Third, the consensus group believe that eradication therapy of H. pylori will not cause adverse consequences. This notion needs to be considered with greatest caution. There is evidence that prevalence of antibiotic resistance of H. pylori is rising in Asia. Pool data show that overall mean prevalence of primary resistance in Asia are 17% for clarithromycin, 44% for metronidazole, and 18% for levofloxacin. This rising trend of antibiotic resistance, not just in one but in multiple drugs, seems to escalate more rapidly in the Asia Pacific region over the past decade. Therefore, the choice of drugs in anti-helicobacter therapy has becoming a more challenging decision in the region. Will a mass screening and population-wide use of macrolides and quinolones resulting in more serious antibiotic resistance to emerge in the region? This will not only impact on future use of these drugs in H. pylori treatment but also to many other infections. Furthermore, the effect of treatment of H. pylori in gastro-esophageal reflux is still an unsettled debate. Although most of the studies do not lend support to causal relationship between H. pylori eradication and the onset of new gastro-esophageal reflux disease or relapse of acid reflux symptoms, the quality of evidence is low. On the other hand, after successful eradication of H. pylori, a modest increase in body weight is expected. In order for expert’s opinion to be noted and taken up by health authorities and policy makers for establishing strategy, considering implementation and taking up corresponding actions, consensus statements need to address the issues with solid and robust evidence to support such recommendations, proof of cost and life-saving, and reassurance of no harmful effects or adverse consequences of this new policy. Population screening and treatment of a certain condition have never been an easy decision to be made. At the current status, I believe that there are more questions than answers to make firm recommendations on mass screening and treatment of H. pylori for the prevention of gastric cancer.