In Japan, gastric cancer accounted for almost half of all cancer deaths in the 1960s, but the proportion continues to decline. According to the 2021 cancer statistics forecast of the National Cancer Center Cancer-Information Service, “Cancer Registration and Statistics”, gastric cancer ranked third in the number of deaths after lung cancer and colorectal cancer. The total number of cancer deaths was 11.1% (42,000 people) [11]. The number of gastric cancer deaths has remained at 50,000 per year for the past few decades, and since 2011, it has been declining. However, more than 40,000 people lose their lives to stomach cancer every year. Gastric cancer has the second highest incidence rate at 12.9% (130,500 people), following colorectal cancer. As for the annual transition of gastric cancer, the age-standardized incidence and mortality are steadily decreasing, the number of cases is increasing, and the number of deaths tends to plateau due to an increase in the incidence and deaths caused by gastric cancer in the elderly population.

The International Agency for Research on Cancer designated H. pylori as a clear gastric cancer carcinogenic factor (group 1) in 1994 [27] and recommended prevention by eradication in 2014 [28]. The presence of H. pylori infection is determined by histologic examination, the rapid urease test, serum antibody test, stool antigen test, or 13C-urea breath test. The effectiveness of the eradication treatment on gastric cancer prevention has been shown in a randomized controlled trial [29], and this primary preventive effect of the eradication of gastric cancer has been reported in recent meta-analyses [30,31,32]. Eradication of H. pylori reduces the risk of gastric cancer and mortality [33,34,35,36], but the risk still remains in the second decade after eradication [37]. Moreover, the pathogenicity and carcinogenicity of H. pylori depend on its strain. The East Asian type of H. pylori, which is popular in Japan, is more carcinogenic than the European-type H. pylori [38,39]. In addition, the presence of H. pylori with a positive babA2 gene may contribute to an increased risk of GC, especially in the Asian population [39,40]. In Japan, the eradication treatment for gastric and duodenal ulcers was covered by the National Health Insurance in 2000, and H. pylori-infected gastritis was added as an indication in 2013 [41]. According to recent reports in Japan, the risk of cumulative incidence of gastric cancer was 17.0% in men and 7.7% in women in the H. pylori-infected population, and <1% in the non-infected population [42]. More than 99% of gastric cancers in Japan are associated with H. pylori-infection gastritis [19,20]. Histopathological diagnosis of gastric cancer is performed according to the Japanese Classification of Gastric Carcinoma and the Vienna classification system [43,44]. Although gastric cancer that is not associated with H. pylori infection is extremely rare, gastric is cancer associated with autoimmune gastritis, gastric cancer due to CDH1 gene mutation, fundic gland-type cancer, signet ring cell carcinoma, and cardia cancer are known [45]. Cardia cancer is often discovered at an advanced stage; thus, particular attention should be paid to it [46]. Moreover, the main risk factors of cardia cancer, which include gastroesophageal reflux disease and obesity, are different from those of gastric cancer associated with H. pylori [47].

As mentioned above, in Japan, the age-standardized incidence and mortality rate of gastric cancer has decreased over the past few decades due to a decrease in the incidence of H. pylori infection [4,5,6,7,8,9,10,11,12,13,14,15]. H. pylori infection rates in the 1960s, 1970s, and 1980s or later were 30%, 20%, and <10%, respectively [7]. A meta-analysis of the Japanese population shows that H. pylori infection rate is high in patients born in the 1940s; however, the infection rate decreased in patients who were born later, in the 1950s [9]. Although the morbidity rate of gastric cancer has continued to decrease due to the reduced H. pylori infection rates and the preventative effect of the H. pylori eradication therapy, the prevalence of H. pylori eradication has increased remarkably in recent years [8]. In the midst of dynamic changes in the incidence of H. pylori infection, it is considered to be important to pay attention to the high-risk groups in gastric cancer screening.

Annual radiographic screening for everyone >40 years of age in Japan was implemented in the 1960s as a secondary preventive measure for gastric cancer [12,14]. Gastric cancer screening using radiographic examination has proven to reduce mortality. It has an excellent mass-processing ability, and good accuracy, and is safe and cost-effective [48,49]. Furthermore, in recent case-control studies in Japan and South Korea, the effect of radiographic screening on mortality reduction was limited [50,51]. The Japan Society of Gastroenterological Cancer Screening formulated a revised version of the new gastric radiography guidelines (2011) [52]. The ability to view lesions by gastric radiographic examination has been greatly improved with the use of high-concentration, low-viscosity barium preparations and the advent of digital X-ray devices. Consequently, the rate of early detection of gastric cancer has exceeded 70% [53]. In addition, gastric cancer screening has been performed using imaging and AI to detect H. pylori-infected gastritis and gastric mucosal atrophy [54]. However, due to aging and immobilization of patients, radiation exposure, and lack of reading physicians and aging facilities, the rate of participation has been sluggish. Although endoscopic examinations have been approved by the revised 2014 Japanese Guidelines for Gastric Cancer Screening [13], it is impossible to replace all conventional radiography with endoscopic examinations due to problems relating to the capacity of endoscopy, budget, and access to examinees [14,15]. In population-based gastric cancer screening, it will be necessary to continue to utilize radiographic examinations with high processing capacity as a safety net.

Radiographic examination is a screening method limited to Japan, but there is a growing international interest in endoscopic screening [55]. In Korea, in response to the results of domestic research, gastric cancer screening has been limited to endoscopic examinations [55,56].

In 2013, a case-control study was conducted in Japan and Korea. The research conducted in Japan involved a study on the population of Goto Islands in Nagasaki Prefecture [57] and a study on the population of Tottori Prefecture and Niigata City [58]. Although the sample size is small in the Nagasaki study, the mortality rate of gastric cancer was significantly decreased by 79% in participants of endoscopic screening (odds ratio [OR]: 0.206, 95% confidence interval [CI]: 0.044–0.965) [57]. In 2013, a case-control study that was conducted in Niigata City and four cities in Tottori Prefecture reported that the mortality rate was significantly lower by approximately 30% in people who underwent endoscopy 36 months before the date of gastric cancer diagnosis (OR: 0.695, 95% CI: 0.489–0.986) [58]. The studies that were conducted in Korea were large-scale research based on national databases. When the gastroscopic examination was performed even once in the past, the effect of reducing the gastric cancer mortality rate was confirmed to be 47% in individuals aged 40–74 years old (OR: 0.53, 95% CI: 0.51–0.56) [56]. Based on these results, a gastroscopy was recommended as a population-based screening method according to the revised 2014 Japanese Guidelines for Gastric Cancer Screening [13]. At the same time, it has changed from once a year for individuals aged >40 to once every 2 years for individuals aged >50 years, reflecting the recent decline in gastric cancer mortality by age group. In 2015, a study of Tottori Prefecture showed that endoscopic screening reduced the gastric cancer mortality rate by 67% compared with radiographic screening [50]. Zhang et al. conducted a meta-analysis that included 342,013 individuals in the six-cohorts and four-case-control studies that were previously published. This analysis demonstrated that endoscopic examination showed a 40% reduction in gastric cancer mortality rate (relative risk: 0.60, 95% CI: 0.49–0.73) [59].

According to reports from the area where endoscopic examinations were introduced, the gastric cancer detection rate was 0.05–0.32% for gastric X-ray examination and 0.30–0.87% for gastroscopic examinations [8,60]. Further, the gastric cancer detection rate of endoscopy was reported to have been approximately three times higher than that of X-ray examination. In Japanese studies, the proportion of early-stage cancer was approximately 70% in the radiographic screening group and >80% in the endoscopic screening group. Similarly, Hosokawa et al. previously reported that the detection rate of early cancer was higher in the endoscopic screening group than in the radiographic screening group [61]. However, the effectiveness of gastric cancer screening should be evaluated by the mortality reduction, and not by the detection rate.

Endoscopy can diagnose early-stage cancers that can be treated by endoscopic surgical dissection. Endoscopic surgical dissection has been performed for approximately half of early-stage cancers detected by endoscopic screening [62]. It seems to contribute to the maintenance of the quality of life after treatment. Moreover, recent development and widespread use of IEE and magnifying endoscopy have improved the endoscopic diagnosis of gastric cancer [23]. IEE is useful for diagnosing gastric cancer after eradication, which is usually difficult to detect [63]. In a recent study, we showed that photodynamic endoscopic diagnosis—based on the fluorescence of photosensitizers that accumulate in tumors—may be useful in the diagnosis of early gastric cancer regardless of the endoscopist’s experience and is useful for tumor detection; however, its usefulness has not been established because no prospective studies evaluating its usefulness have been performed [64].

As the participation rate in gastric cancer screening has decreased, its impact on mortality reduction has become limited. Although the participation rate in radiographic screening for gastric cancer has sunk below 10% [65], it is possible to improve the participation rate by introducing endoscopic screening as a method of gastric cancer screening. Notably, the participation rate is approximately 25% in municipalities that have already undergone endoscopic screening [66,67]. Thus, endoscopy is now the first choice for gastrointestinal tract examination instead of X-ray examination.