Reply to the letter

We sincerely thank Dr. Nishida for his interest in our study and for his valuable comments. We consider all of the points raised to be important issues in the implementation of screen-and-treat programs for Helicobacter pylori infection among adolescents. First, regarding the informed consent process, our study placed particular emphasis on promoting understanding among students and their guardians prior to screening. To facilitate comprehension, especially among younger participants, illustrated pamphlets were distributed, explanatory videos were made available on the city's official online media, and public lectures for community members were conducted. Through these initiatives, information regarding the H. pylori screening program was disseminated in advance. Indeed, a questionnaire survey targeting guardians showed that 86.4% supported screening for their children, suggesting that this support was underpinned by adequate knowledge of H. pylori infection [1]. Written informed consent was obtained separately for participation in the screening program, secondary testing using the urea breath test, and eradication therapy, as applicable. The consent documents described the outline of the examinations, the expected benefits of eradication in reducing gastric cancer risk, and potential adverse effects of antimicrobial agents. In addition, as the first round screening of the program was provided in a school-based setting, special care was taken to ensure that the program was not perceived as mandatory. We clearly stated that participation was voluntary and that opting out was possible at any stage. Although adolescents generally have limited interest in cancer prevention, we believe it is essential—from the perspective of respecting adolescents' rights—not only to obtain parental consent but also to provide careful, age-appropriate explanations directly to participating students. Second, concern was expressed regarding the administration of antimicrobial agents to asymptomatic adolescents. Although some guidelines advise against regarding antimicrobial exposure in asymptomatic children [2], these discussions primarily concern populations in Europe and North America, where gastric cancer incidence is relatively low. Strategies that take population-level gastric cancer risk into account are crucial [3, 4]. In regions with a high gastric cancer burden, such as China, a family-based consensus report recommends eradication therapy for infected children [5]. Previous studies have shown that adverse effects of eradication therapy in adolescents, such as antibiotic-associated enteritis, are infrequent and generally mild and that alterations in the gut microbiota are transient [4, 6]. Furthermore, studies in adults have demonstrated that eradication at a younger age is most effective for gastric cancer prevention [7]. Crucially, the concept of a “point of no return” in gastric carcinogenesis suggests that the preventive effect of eradication diminishes once chronic inflammation and mucosal atrophy have progressed [8]. Therefore, although the optimal timing remains a subject of debate, such intervention should be framed as a purposeful preventive measure rather than “unnecessary” antimicrobial exposure. In several municipalities in Japan, screen-and-treat programs are implemented at ages when medications approved for adult use can be administered [9]. We believe that careful communication and shared decision-making with both adolescents and their guardians are essential when proceeding with testing and eradication therapy, so decisions are made in a manner consistent with local values, preferences, and community sentiments. Third, regarding cost-effectiveness, previous studies have suggested that screening at age 15 may be the most cost-effective approach [10]. However, as shown in our study, real-world programs involve multiple parameters, including infection prevalence, participation rates, and treatment success. Comprehensive evaluations integrating these factors are essential for informed healthcare policy. Although we did not conduct a formal simulation in the present study, we consider this an important topic for future research. Finally, regarding the analogy to HPV vaccination, we acknowledge that these are biologically distinct. We referred to HPV vaccination because both interventions share the objective of preventing future cancer from an early age. Both involve offering preventive interventions to asymptomatic individuals and require effective risk communication regarding diseases that may develop decades later in adulthood. We believe that careful explanations promoting accurate understanding and clear communication of the significance of early prevention can improve participation and treatment uptake among adolescents. In conclusion, we believe that further international discussion is warranted regarding H. pylori screening for adolescents. The points raised by Dr. Nishida provide a valuable basis for such future dialogue, encompassing communication strategies, the balance of benefits and risks, and broader societal implications. The authors declare no conflicts of interest.