Esophageal cancer (EC) and Stomach cancer (SC) are common malignant tumors of the digestive tract worldwide, posing a serious threat to human health (1–3). According to the latest global cancer statistics GLOBOCAN 2022, EC is the 11th most common cancer and the 7th leading cause of cancer death in the world, while SC is the 5th most common cancer and the 5th leading cause of cancer death in the world (4, 5). Histologically, EC can be classified into two major subtypes: the disease burden of esophageal squamous cell carcinoma (ESCC) significantly exceeds that of esophageal adenocarcinoma (EAC) in most parts of the world (6). The vast majority of gastric cancers are histologically adenocarcinomas. The development of gastric cancer is closely associated with Helicobacter pylori infection (7). A meta-analysis and guidelines have indicated that H. pylori infection shows no association with ESCC, and may even be inversely associated with EAC (8, 9). However, the esophagus and stomach are directly connected anatomically, particularly at the esophagogastric junction, where esophageal adenocarcinoma and gastric cardia cancer exhibit significant overlap in terms of pathogenesis, clinical presentation, and even molecular characteristics. Studies have shown that multiple environmental and behavioral risk factors contribute to the development of both cancers, including smoking, alcohol consumption, high salt intake, consumption of preserved foods, and low fruit and vegetable intake (10). It is worth noting that the burden of esophageal and gastric cancers varies considerably across regions. EC is highly prevalent in economically underdeveloped areas of Asia, Africa, and South America, where dietary habits are often poor. Meanwhile, SC incidence is particularly high in East Asia, Eastern Europe, and South America, regions characterized by lower economic development, unbalanced diets, and high rates of Helicobacter pylori infection (11). Therefore, a combined analysis facilitates a more comprehensive evaluation of their overall burden and its relationship with socioeconomic development.

The GBD study is a comprehensive and systematic analysis of global health trends, offering critical insights into the incidence, prevalence, and mortality rates of various diseases (12, 13). Previous studies have analyzed the disease burden and future trends of SC and EC in China based on GBD 2019 (14), but there are limitations such as insufficient data timeliness, limited to specific regions, lack of discussion on the impact of socio-economic development level, and no analysis of age-period-cohort factors and the impact of aging, epidemiological changes and population growth. Although numerous GBD-based studies on individual cancers exist (15–19), this is the first systematic comparative analysis of EC and SC, which are highly related in public health strategies, using GBD 2021 data. The study not only delineates the burden of each cancer but also emphasizes the similarities and differences in their spatial distribution of co-occurrence patterns, gender disparities, age distribution, and temporal trends. Furthermore, this research projects the disease burden of cancers over the next decade, which is critical for evaluating the impact of public health interventions and guiding strategic directions for future cancer control (20, 21).

Previous studies have indicated that these two cancers share similar epidemiological features (28, 29). Our results demonstrate that the Eastern and Northern Hemispheres represent the regions with the highest concentration of co-occurrence patterns, while the Western and Southern Hemispheres are predominantly characterized by low-burden profiles or patterns dominated by one cancer type. These findings are largely consistent with earlier epidemiological studies focusing on either esophageal or gastric cancer individually, though some discrepancies remain. Most countries are influenced by a combination of multiple factors, and the specific composition and temporal variation of these factors significantly contribute to the global disparities and heterogeneity in the distribution and burden of both cancers. The intertwined effects of these risk factors underscore the importance of multifaceted intervention strategies.

First, cultural habits and medical level. Mongolia’s high co-occurrence burden is driven by a diet heavy in salty foods, frequent consumption of scalding-hot milk tea, limited intake of fresh fruits and vegetables, high prevalence of Helicobacter pylori infection, and widespread tobacco and alcohol use (30). In contrast, Kuwait, an affluent Gulf nation, exhibits the lowest co-occurrence burden, which can be attributed to its diverse and healthy diet, advanced healthcare system, and cultural norms influenced by Islam that prohibit alcohol consumption. Moreover, substantial disparities in the burden of the two cancers can exist within the same country. Malawi, one of Africa’s major tobacco-producing countries, has widespread availability of unfiltered, self-rolled tobacco products. Dietary factors including consumption of high-temperature foods, mycotoxin-contaminated staples, smoked products, and selenium-deficient diets, along with frequent exposure to smoke from wood-burning stoves, contribute to its high incidence of EC (1). Although H. pylori infection rates are high across Africa (31), the associated cancer risk remains relatively low. This phenomenon, often termed the “African enigma,” has been partly attributed to the predominant circulation of the hpAfrica2 strain, which confers lower carcinogenic potential (32, 33). Thus, Malawi is characterized by a high burden of EC but a low burden of SC, a pattern which has been corroborated by data from the Malawi National Cancer Registry (34). Conversely, Guatemala exhibits a high burden of SC alongside a low burden of EC. Latin America as a whole is not a high-risk region for EC, which may be partly explained by shared dietary and environmental conditions that reduce esophageal cancer risk. However, factors such as H. pylori infection, environmental exposures, and genetic susceptibility contribute to elevated SC risk (35), a pattern supported by findings from an ecological study (36). Therefore, adopting healthy lifestyle practices, such as maintaining a balanced diet, ceasing tobacco use, limiting alcohol consumption, and engaging in regular physical activity, can effectively reduce the risk of both cancers.

Second, disease screening and level of public participation. The rapid development of early diagnosis and treatment programs, particularly in the field of upper gastrointestinal cancers, has significantly improved the detection and management of early-stage gastric and esophageal cancers. For instance, national cancer screening programs in Japan and South Korea have achieved early gastric cancer detection rates of 70% and 50%, respectively (37, 38). Although South Korea is affected by common risk factors and represents the higher level in terms of both incidence and mortality under the co-occurrence pattern, it has experienced a remarkable decline in disease burden. This can be largely attributed to the National Cancer Screening Program (NCSP) implemented since 1999, which has facilitated the identification of a substantial number of early-stage cases. Coupled with advanced medical technology and treatment expertise, this initiative has significantly reduced mortality rates (39). Similarly, Japan initiated nationwide screening two decades earlier than South Korea. However, the coverage of endoscopic screening in Japan has been considerably lower. This is partly because Japanese screening guidelines did not recommend endoscopic screening until 2014. By 2015, only 19% of municipalities in Japan employed endoscopic screening, whereas as early as 2011, already 72.55% of participants in South Korea had opted for this method (40, 41). In addition, public participation in screening has been lower in Japan compared to South Korea (42), contributing to a higher burden of EC in Japan. Nevertheless, Japan has been proactive in combating Helicobacter pylori infection. In 2013, Japan became the first country to provide national health insurance coverage for the eradication therapy of H. pylori-associated gastritis (43). This policy is one of the key factors explaining why Japan maintains a lower burden of gastric cancer than South Korea, despite its delayed policy adoption and lower screening participation.

Third, economic development level. Globally, our findings indicate that among double high and upper-middle countries, a considerable number of high-burden regions are located in low or lower-middle-income African nations (25 [46.30%] of 54). In contrast, among double low and lower-middle countries, a significant proportion of low-burden regions are situated in high-income European and Middle Eastern countries (20 [36.36%] of 55). Furthermore, countries most affected by EC and SC exhibit distinct economic characteristics. Nations within EC-dominated or SC-dominated regions are predominantly low or lower-middle-income countries. This pattern of comorbidity across different economic strata underscores that socioeconomic development is a fundamental and primary factor in disease prevention and control. In high-income countries such as the United States, Canada, Singapore, and several developed nations in Europe, enhanced screening efforts have contributed to an approximate 5% improvement in the five-year survival rate for SC (44). Compared to high-incidence regions such as East Asia and high-income Asia-Pacific, regions like Australia and high-income North America demonstrate notable advantages in public health awareness and education. Increased public knowledge regarding the association between Hp infection and SC has facilitated the adoption of preventive measures, effectively reducing SC incidence. Studies indicate that the Hp infection rate in the United States is approximately 36%, significantly lower than the global average of 50% (45, 46). Therefore, strengthening risk factor control and expanding screening coverage are essential strategies for cancer prevention. Although our results suggest a relatively weak correlation between the burden of EC and SC and the SDI, a declining trend in ASIR, ASMR, and ASDR was observed with increasing SDI. Given the economic constraints in low-income regions that hinder large-scale screening, we recommend adopting a high-risk population screening model coupled with low-cost screening technologies. This approach would improve early diagnosis rates while reducing overall screening costs.

From a temporal trend perspective, the global ASR for both cancers have shown a consistent decline, with the most pronounced reduction observed during the period 2004–2007. This trend may be attributed to the following factors: In 1994, the National Institutes of Health (NIH) convened the first global consensus conference on Hp. Based on robust evidence, the Maastricht I Consensus was established in 1997 and subsequently refined, leading to the widespread adoption of eradication therapy in the early 2000s. Additionally, the process of urbanization accelerated globally during the 2000s. Developed regions such as Europe and the United States reached urbanization rates of nearly 80%, entering a mature stage of urban development, while developing countries including China and India underwent rapid urbanization. This period saw increased public awareness of healthy diets and the risks associated with smoking and alcohol consumption. Coupled with advancements in endoscopic technology (37, 38), these developments improved both the detection and treatment outcomes of these cancers. Therefore, the observed decline during this period represents a landmark achievement resulting from the synergistic effects of prevention, diagnostic advances, and progress in therapeutic interventions.

However, despite these encouraging trends, the absolute number of new cases and deaths continues to increase. This apparent contradiction is largely attributable to demographic changes, especially population growth and aging, which have contributed to a rise in the absolute disease burden (47). An exception was identified in the decomposition analysis: in Low SDI regions, population aging was associated with a reduction in disease burden. This may be explained by public health advances in certain countries within these regions (48), such as increased emphasis on infectious disease control and significant improvements in child survival rates. These developments have enabled more people to survive into older age while avoiding substantial years of life lost (YLL) due to premature death, ultimately leading to a reduction in overall disease burden. Nevertheless, public health progress presents a double-edged sword. Although advances in screening and treatment technologies have reduced the relative risk of cancer in many high-income countries, the growing elderly population and widespread adoption of diagnostic techniques have also led to the identification of more cases (49).

Based on national-level data, this study proposes the global co-occurrence pattern of EC and SC for the first time. It classifies 204 countries and territories into three distinct types of co-occurrence regions, delineates the spatial distribution of both cancers within these categories, and interprets their epidemiological characteristics from global, regional, and national perspectives. The results demonstrate a significant declining trend in the burden of both cancers across these 204 countries and regions from 1990 to 2021, with SC showing the most pronounced decrease (DALYs: 172 [84.31%] of 204). Nevertheless, the disease burden of SC remained higher than that of EC in the vast majority of countries (DALYs:147 [72.06%] of 204). Further predictive analysis indicates that the global burden of EC and SC is projected to continue declining significantly by 2031. Although this study provides a comprehensive and in-depth analysis of the disease burden of these two cancers, several limitations should be acknowledged. Despite the extensive coverage of the GBD database, health data remain missing for certain countries and territories, particularly in low and middle-income regions. Moreover, GBD estimates integrate data from multiple sources,including national health departments, international organizations, and medical institutions, which vary in quality and reliability. For example, data from some countries may rely on limited surveys or modeled estimates rather than comprehensive health surveillance systems.