We chose the year 2012 as the baseline year. The birth rate, all-cause mortality, sex ratio, and standard life expectancy at birth from 2012 to 2019 were collected from the China Statistical Yearbook released by the Bureau of Statistics of China [12]. Infant mortality from 2012 to 2019 was drawn from the Statistical Report of China Children’s Development (2011-2020) [13]. All cohort data for subsequent years were drawn from the World Population Prospects 2019 released by the United Nations Population Division [14]. The birth rate and infant mortality for boys and girls were calculated for both sexes combined according to the sex ratio at birth. All-cause mortality for males and females was computed by the mortality of both sexes combined with the sex ratio of the total population and the risk ratio of all-cause mortality in males compared to females obtained from the Tabulation on the 2010 Population Census of the People’s Republic of China [15].

We used an age-specific population and all-cause mortality, age-specific EC incidence, mortality in 2012, and EC fatalities to estimate the EC prevalence in 2012, average age of onset, and duration of EC through the DisMod model [16]. Age-specific population and all-cause mortality were estimated using the data collected from the 2010 Population Census of the People’s Republic of China. EC incidence and mortality were collected from published data [6,17], whereas the fatality was estimated based on survival data [6]. Additionally, the AAPC of EC incidence and mortality were used to simulate the subsequent yearly incidence and mortality of EC [6,17].

The simulated EC incidence by the model closely matched the input data (Figure S2 in Multimedia Appendix 1). The regression line slope was 1.01 and the R² was 0.99, which demonstrated good consistency between the two estimates.

From 2013 to 2030, the prevalence of EC will increase from 61.00 to 64.5 per 100,000 and peak at 67.9 per 100,000 in 2020. In males, there was a dramatic increase predicted for EC incidence, from 82.0 to 96.4 per 100,000, whereas the incidence is predicted to first increase and then decrease in females, resulting in an overall decrease from 38.9 to 31.6 per 100,000. The total EC cases will increase by 11.5% (from 835,600 to 931,800), and will peak at 961,500 in 2021. The EC cases in males will increase by 22.9% (from 575,500 to 707,500), whereas in females, it will first increase and then decrease, with an overall decrease of 13.8% (from 260,100 to 224,3000). Table 1 summarizes the details.

Figure 1 presents the DALYs due to EC by sex in China between 2013 and 2030. From 2013 to 2030, the total DALYs for both sexes will increase by 21.3% (from 30,034,000 to 36,444,000). DALYs will increase by 32.6% in males (from 21,266,000 to 28,209,000); in contrast, they will decrease overall by 6.1% in females (from 876,800 to 823,500). Significantly, YLL contributed to over 90% of the DALYs for both sexes. Figure 2 displays the DALY rates per 100,000 people by year and sex.

The results of the Joinpoint regression analysis address the statistical significance of the AAPC in DALY rates. From 2013 to 2030, the overall DALY rates per 100,000 will increase from 219.2 to 252.3, and will peak at 262.1 in 2021. The AAPC will be 0.8% (95% CI 0.8%-0.9%). In males, there was an obvious increase from 302.9 to 384.3, with 1.4% (95% CI 1.3%-1.5%) of the AAPC. However, an overall significant downward trend was shown in females (from 131.2 to 115.9), which peaked at 147.4 in 2017. The AAPC will be –0.7% (95% CI –0.8% to –0.7%).

The predicted annual direct medical expenditure for both sexes will increase significantly (Figure 3). From 2013 to 2030, the total annual direct medical expenditure will increase by 128.7% (from US $33.4 billion to US $76.4 billion). The AAGR will be 5.0%, and the annual growth rate will decline from 9.7% to 3.8%. Male patients will have 2.2-3.2 times higher direct medical expenditure than female patients, which will increase by 152.2% and 76.9% (from US $23.0 billion to US $58.0 billion and from US $10.4 billion to US $18.4 billion) in males and females, respectively.

The results of the sensitivity analysis indicated that changes in the AAGR of direct medical expenditure, 5-year survival rate, and AAPC of EC incidence have a substantial impact on the direct medical expenditure of EC, whereas the disability weight, 5-year survival rate, AAPC of EC incidence, risk ratio of all-cause mortality, and birth rate have an obvious impact on the DALYs. Table 2 and Table 3 summarize the changes in the cumulative direct medical expenditure and DALYs due to EC according to the variations in key input data considered in the sensitivity analyses for males and females, respectively.

To the best of our knowledge, this is the first modeling study on the national disease burden of EC in China. According to our estimates, the disease and economic burdens due to EC will increase substantially over the next few decades. From 2013 to 2030, the EC prevalence will increase by 11.5% (from 835,600 to 931,800); the total DALYs will increase by 21.3% (from 30,034,000 to 36,444,000); the DALY rates per 100,000 people will increase from 219.2 to 252.3, with an AAPC of 0.8%; and the direct medical expenditure will increase by 128.7% (from US $33.4 billion to US $76.4 billion), with an AAGR of 5%. Additionally, we found large variations in burdens between sexes: the prevalence and direct medical expenditure was 2.2-3.2 times higher and DALYs were 2.4-3.4 times higher in males than in females.

China ranks close to the top in terms of the highest number of EC incident cases, deaths, and DALYs worldwide [2]. The DALY rates per 100,000 in 2017 were twice as high as those in the rest of the world (222.6 vs 119.9) [2]. This is largely because of the higher aging population, low social demographic index, and high-risk lifestyles related to EC in China. Our estimated DALY rates in 2017 were slightly higher than the estimates provided by the GBD 2017 Esophageal Cancer Collaborators (256.9 vs 222.6). This discrepancy is probably due to the different sources of the data used for calculating the DALYs. Almost all of the DALYs were attributed to YLL due to premature death, which is quite consistent with previous studies [19,25,26]. Additionally, the burden from EC in China has geographic disparities, and high-risk areas cause an almost 4-times higher burden than that estimated at the national level (810.0 vs 219.2 per 100,000) [19].

Despite previous studies indicating a decrease in the incidence and mortality of EC over the past decades, this study suggests a continuous increase in the prevalence of EC, DALYs, and direct medical expenditure. This is driven primarily by the increasing absolute number of EC cases. Additionally, the sensitivity analysis demonstrated that the incidence of EC, 5-year survival rate, and disability weight have a considerable impact on DALYs. Collectively, these findings suggest the significance of reducing the incidence of EC, premature death, and personal direct medical expenditure, and improving the 5-year survival rate and disease health-related quality of life.

Consequently, policymakers should adopt comprehensive effective strategies to reduce the burden caused by EC, possibly focusing on the consciousness of cancer prevention, early detection, early diagnosis, and early treatment, as well as the demand for and access to cancer prevention and treatment knowledge. First, screening should be highly recommended since it is the major strategy for primary and secondary disease prevention, and could detect the disease in the early stage to treat it effectively [27]. Additionally, considering the cost-effectiveness and the large disparities according to age, sex, and other higher-risk behaviors, a finer delineation of strategies should be specified for individuals at different risk levels [28,29]. Second, improving health literacy, including personal health literacy and organizational health literacy, is positively related to awareness of cancer risk and knowledge, health behavior and screening, early cancer symptom recognition, cancer screening behavior, health service resource utilization, treatment compliance, and quality of life [30]. Moreover, educational interventions using social media should be suggested to promote self-management and strengthen health literacy [31,32]. Furthermore, clinical treatment and terminal care should be strengthened to improve the quality of life and 5-year survival rate.

China has suffered a high catastrophic health expenditure (CHE). The total out-of-pocket payment expenses accounted for approximately 30% of the total health expenditure, increasing by 120.6% between 2010 and 2019 [33]. The average incidence of CHE in recent decades was 23.3% (95% CI 21.1%-25.6%) [34], whereas it was 60.1% in cancer patients [27,35]. The overall incidence of CHE in EC patients was 69.2%, followed by colon cancer, breast cancer, and liver cancer [27]. Specifically, CHE is closely linked with health insurance, which reached 73.6% and 100% in patients under the new rural cooperative medical scheme and in patients without coverage by health insurance, respectively [27]. Although the predicted annual growth rate of direct medical expenditure due to EC will decline and the proportion of direct medical expenditure among total health expenditure will decrease from 0.47% to 0.36% between 2013 and 2017, the estimated absolute direct medical expenditure will still increase over the next decades [33]. Thus, EC remains a severe economic burden. Moreover, esophageal squamous cell carcinoma (ESCC) is the dominant histological subtype of EC in China, and studies have shown a strong inverse relationship between ESCC and socioeconomic status [2,36,37]. Financial capability largely determines the treatment and health service utilization for cancer patients in China. The current insurance schemes are insufficient to address these disparities [38]. All of these findings imply that more integrated strategies are needed, including improving a household’s economic level, expanding the breadth of insurance coverage, reinforcing prepayment hospital insurance methods, and strengthening the public assistance system. Additionally, the scope of national drug centralized volume–based procurement should be expanded, since it has substantial importance in reducing medical costs and the expenditure of medical insurance funds, saving procurement funds, and reducing the patients’ burdens due to use of the drug [39,40].

Some limitations should be noted when interpreting our results. First, it is difficult to examine the external validation of our model since there are no comparable published data. However, our model has good face and internal validity because it was developed based on the structure of the DisMod II model, which presents the dynamic development of EC very well, and goodness-of-fit analyses showed the internal validity. Second, our model underestimates the total economic burden of EC, since the indirect and hidden costs were not simulated. Third, the input data were estimated based on past data values, which cannot provide accurate evaluations. However, the sensitivity analysis presented the changes caused by the uncertainty of the inputs. Moreover, the goodness-of-fit analysis showed the good internal validity of the model.

EC still causes serious disease and economic burdens in China, and DALYs and direct medical expenditures will continue to increase over the next decades. Male patients have a higher burden than female patients. YLL account for the majority of DALYs. Comprehensive strategies should be implemented for the improvement of EC prevention and control, including screening, improving health literacy, improving a household’s economic level, expanding the breadth of insurance coverage, reinforcing prepayment hospital insurance methods, strengthening the public assistance system, and expanding the scope of national drug centralized volume–based procurement. In addition, clinical treatment and terminal care should be strengthened to improve quality of life.