Establishment of an Early Warning Screening System for High Risk Population in High Incidence Area of Esophageal Cancer, Gansu province, northwestern China: A Retrospective Population-Based Study

Establishment of an Early Warning Screening System for High Risk Population in High Incidence Area of Esophageal Cancer, Gansu province, northwestern China: A Retrospective Population-Based Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Establishment of an Early Warning Screening System for High Risk Population in High Incidence Area of Esophageal Cancer, Gansu province, northwestern China: A Retrospective Population-Based Study Duojie Zhu, Chengyun Li, Yinggang Che, Huijuan Cheng, Yumin Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5753089/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective The medical treatment of cancer patients has caused a huge burden on the financial expenditure of the government, so it is crucial to evaluate whether the financial expenditure of public medical care. The aim of this study was to identify risk populations of esophageal cancer (EC) in Liangzhou through epidemiological data and evaluate the feasibility and cost-effectiveness of early screening in these populations. Methods We collected data on EC incidence and follow-up from 2009 to 2021 in the regions of Liangzhou and Jingtai in Gansu Province. We used spatial analysis and regional investigation the incidence data of EC reporting area to analyze the prevalence of EC within Liangzhou and Jingtai, the impact of lifestyle, heavy metals and nitrosamines on EC. Subsequently, we conducted a health economics assessment based on the Chinese government's regional investment in EC screening in Gansu Province in the past five years, with a view to optimizing cancer prevention measures in areas with high incidence of EC. Results From 2009 to 2021, the incidence of EC in Liangzhou remained high with an average annual incidence of 45.23 per100,000, there were 8 communities and townships with the incidence of EC higher than 70/100,000 in Liangzhou. Drinking alcohol, intake of red meat, salted food, dried food, fried food and dry thinness were risk factors for EC. The trace elements ( iron, copper and zinc) and NMEA, NDEA and NDPA in drinking water of Liangzhou were higher than those in Jingtai County, suggested that the residents of Liangzhou District are exposed to higher environmental carcinogenic risk. In the systematic health economics evaluation of the EC screening, we found that the screening cost amounted to 1,1407200 yuan, and the benefit totaled 1,9763200 yuan, resulting in a cost-benefit ratio (CBR) of 1:1.73. Conclusions This study identified high-incidence areas and key populations of EC. This approach guided the implementation of targeted EC screening in specific area, proving to be a cost-effective and efficient screening method. The adoption of this approach should be widely applied in the prevention and control of EC in the future, and provides an important basis for the clinical benefit and early screening of patients with EC. Esophageal cancer Spatial epidemiology Risk factors Screening Health economics evaluation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Esophageal cancer (EC), ranking as the seventh most prevalent and sixth most fatal cancer globally, represents a prevalent malignant tumor in the digestive tract, posing a formidable menace to human well-being( 1 ). The incidence of EC has surged notably by 56% from 1990 to 2019, leading to increased public healthcare expenditures and household financial burdens( 2 ). The rural areas exhibit approximately double the incidence and mortality rates compared to urban areas, signifying a glaring regional disparity( 3 ). Despite advancements in EC treatment, the anticipated outcome remained limited, with a meager five-year survival rate below 20%( 4 ). Encouragingly, timely detection and intervention in EC patients have shown substantial promise in reducing mortality rates( 5 ). The occurrence and progression of EC are influenced by a multitude of factors. Socioeconomic status, particularly low educational attainment and lower economic levels, have been identified as risk factors for EC development( 6 ). Furthermore, the risk of EC is significantly elevated in smokers compared to non-smokers, with the risk decreasing upon smoking cessation( 7 ). Excessive alcohol consumption has also been demonstrated to markedly increase the risk of EC( 8 ). Additionally, the consumption of hot foods and beverages associated with risk of EC( 9 ). Conversely, studies have indicated that a diet rich in fruits, vegetables, and dietary fiber can potentially reduce the risk of EC( 10 ). Projections suggest a substantial increase in the burden of EC in the future( 11 ). However, the efficacy of early screening and interventions for EC patients remains uncertain, with inconclusive evidence regarding the potential benefits for the Chinese population and unclear cost-effectiveness of early screening. Nonetheless, the implementation of a standardized screening protocol has the potential to yield significant benefits, particularly in high-risk regions and among targeted populations( 12 ). Studies conducted in high-risk regions of China have demonstrated that early screening programs for EC can effectively reduce mortality rates among patients( 13 ). In this comprehensive study, we systematically gathered and analyzed data concerning the incidence and longitudinal follow-up of EC cases from 2009 to 2021 in the regions of Liangzhou and Jingtai situated in Gansu Province. Specifically, we performed an intricate spatial analysis focusing on the high prevalence of EC within Liangzhou District and Jingtai County. Furthermore, our study delved into the nuanced interplay of various demographic and lifestyle factors with the incidence of EC in the aforementioned regions. Moreover, we investigation encompassed an assessment of the impact of heavy metals and nitrosamines on the geographical areas at heightened risk for EC. Through the lens of health economics, we rigorously scrutinized the cost-effectiveness and cost-benefit profiles associated with early screening protocols for individuals afflicted with EC. Remarkably, our findings underscored the significant role of early screening initiatives as a pivotal strategy to curtail national expenditures on EC while conferring substantial benefits to affected individuals. Materials and methods 1. Sources of data and quality control The Information Center of Gansu Provincial Health Commission and Liangzhou and Jingtai (Gansu province, China ) Cancer Registry provided esophageal cancer incidence data and demographic information from the target regions. Data collected from 2009 to 2021 included Liangzhou and Jingtai EC incidence data, classified by the International Classification of Diseases (ICD)-10 codes. As per the International Association of Cancer Registries (IACR) and NCCR requirements of cancer registration data, our data evaluation met the quality control criteria for tumor follow-up registration, Liangzhou and Jingtai esophageal cancer incidence data were included in the annual report of the Chinese Tumor Registry, from 2009 to 2021. 2. To identify the EC trends in prevalence The average annual percent change (EAPC) to assess trends with regard to changes in Wuwei and Jingtai EC incidence rates from 2009 to 2021. The EAPC calculation included the independent variable, years, and a logarithmic transformation on the incidence rates. We fit the EAPC to a straight line, Y = b + aX and Y = Ln (incidence rate), where X represents the year. With the final equation being EAPC = (10a-1)×100%, explained observed annual variation trends. 3. Visual analysis of the population with high incidence of EC in the region This part of the study utilized geographical epidemiology and geographic information system analysis to examine the low incidence of EC in Jingtai County and the high incidence in Liangzhou District. GIS10.0 software was empolyed for mapping the incidence of EC and conducting spatial autocorrelation analysis using Moran index (Moran's I), Moran's I scatter plots, local aggregation, and outliers (LISA). Spatio-temporal scanning statistics were utilized to identify high-value clusters of EC incidence in Liangzhou and Jingtai (Gansu province, China ). 4. To investigate the lifestyle and behavior of people in areas with high incidence of EC In order to understand the risk factors of EC in Liangzhou District, Wuwei City, Gansu Province, this study investigated the basic situation and lifestyle of 223 patients with esophageal cancer in Liangzhou District and 538 normal control groups in 5 towns and townships in Jingtai County,. The contents of the investigation mainly include the basic information of the subjects and the relevant information such as living and eating habits. For the design of the epidemiological questionnaire, refer to the Technical Plan for Screening and Early Diagnosis and Treatment of Upper Gastrointestinal Cancer (2020 edition). Epidemiological questionnaire for early diagnosis and treatment of upper gastrointestinal cancer. The contents of the investigation mainly include the basic information of the subjects (gender, age, anxiety, education, personality, whether they have mental trauma and often sulk, etc.) and lifestyle information (smoking, drinking alcohol, drinking tea, drinking water sources, whether they exercise, intake of pickled and dried food, intake of fried food, intake of fast food and convenience food, intake of cold and hot food and dry food, etc.). The epidemiological questionnaire was completed by face-to-face interview. 5. Detection of heavy metals and nitrites in drinking water The concentration of heavy metals and nine N-nitrosamines in drinking water was determined by atomic absorption technique and solid phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS). The concentration of 6 N-nitrosamines in drinking water was determined by SPE-GC-MS. 6. Study on health economic regarding the screening of EC in Liangzhou high risk area The cost data were obtained from the Wuwei Tumor Hospital of Gansu (Wuwei, China) finance department and from surveys of patients and relatives. The annual per capita income is obtained by the financial department of the local government at the screening site. This study examined both direct medical costs and indirect costs (earnings due to missed work for screening and treatment). The benefits include direct benefits (savings in routine medical costs) and indirect benefits (benefits resulting from reduced missed work due to avoided deaths and treatments). Because the screening work has a certain time span and the medical market price changes greatly, the screening cost, medical cost and benefit are discounted to the price level of 2020, and the discount rate is determined according to the national retail price index and the consumer price index. In addition, 107 esophageal cancer patients’ information mainly included: (1) the first page of medical records: gender, age, date of birth, date of admission, date of discharge, length of stay, department of treatment, hospital grade, medical insurance payment method, hospital nature, and operation; (2) Hospitalization cost information: total hospitalization cost, treatment cost, medicine cost, consultation fee, examination fee, laboratory fee, bed fee, nursing fee, operation fee. The outliers excluded include: there are obvious logical errors between the inpatient expenses and the total inpatient expenses; The length of hospitalization is less than 1 day and more than 100 days; Duplicate cases based on medical record number; Basic information missing cases; Cases with abnormal total hospital expenses. Additional missing values include: age based on date of birth and date of discharge, length of stay derived from date of discharge and date of admission, etc. 7. Statistical analysis The original case data of patients with esophageal cancer were obtained according to the ICD-X. The qualified data was assessed based on the ‘guideline of Chinese cancer registration’ and referred to the criteria listed under the ‘cancer incidence in five continents volume’ outlined by IACR. The data were stratified by years and crude incidence rates were calculated. Analysis of Chi-square test, or non-parametric tests were employed as appropriate for data comparisons. Data analysis was performed using IBM SPSS Statistics 26.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 8.0 (La Jolla, CA, USA). Statistical significance was defined as P < 0.05. Results Selection of high incidence area of EC, Gansu province, northwestern China Since the scope of tumor registry monitoring in China is not full coverage of the whole population, this work cannot reflect the overall situation of some regions.? In the early stage of this study, the data of EC patients in Gansu province in the past ten years were collected from the Information Center of Gansu Provincial Health Commission. The cumulative number of patients was 18,252, and the average annual incidence of the whole population was 7.3/100,000. However, the incidence of EC in some regions far exceeded the national average of 18.24 per 100,000 in 2018. According to tumor registration data, Liangzhou District, Wuwei City, Gansu Province, and Jingtai County, Baiyin City, Gansu Province, belong to the areas under long-term surveillance (Figure 1). From 2009 to 2021, the incidence of EC in Liangzhou District, Wuwei City, Gansu Province remained at a high level for a long time, with an average annual incidence of 45.23/100,000. The average annual incidence of EC in Jingtai County was 9.83/100,000, and the incidence of male EC was more than twice that of female cancer (Figure 2-3). EAPC assess trends in Wuwei and Jingtai EC incidence rates from 2009 to 2021 showed a decreasing trend in Liangzhou District and Jingtai County (Figure 4). The overall analysis data suggest that the incidence of EC in Liangzhou district is at a high level, which belongs to the high incidence area in Gansu Province. Geographical epidemiology and the application of geographic information system were used to analyze the low incidence of esophageal cancer in Jingtai County and the high incidence in Liangzhou District, and carries out a more detailed spatial analysis. According to the detailed monitoring data of local EC from 2009 to 2021, we found that in Liangzhou District, there were 8 communities and townships with the incidence of EC higher than 70/100,000, including Dizhixincun street, Yangxiaba town, Fafang town, Siba town, Xiashuang town, Qingshui town, Wuhe town, and Jingshan town. Among them, the average incidence of EC in Dizhixincun street was 93.55/100,000, more than five times the national average incidence. In addition, Jingtai County is a drop-incidence area of EC, with an average incidence of 9.83/100,000 from 2009 to 2021, among which the incidence of EC in Yitiaoshan town in Jingtai County is the lowest, at 3.47/100,000. The specific geographical distribution information is shown in detail in Figure 5 and Figure S1 a-j. Risk factors for EC in a high incidence area of Liangzhou area One of the goals of the study was to look for differences in the risk of EC, so we investigated the basic situation and lifestyle of 223 patients with EC in Liangzhou District and 538 normal control groups in 5 towns and townships in Jingtai County, which had a low incidence of EC. The contents of the investigation mainly include the basic information of the subjects and the relevant information such as living and eating habits. Chi-square test analysis results showed that among the collected basic data, personality characteristics, marital status were risk factors for EC (P<0.05) . The analysis of relevant data of life habits found that drinking alcohol, intake of red meat, intake of salted and dried food, intake of fried food, cold and hot degree, and dry thinness were risk factors for EC (P<0.05) (Table 1). In addition, drinking water of residents in Jingtai County and Liangzhou District was collected and tested. Environmental drinking water quality monitoring showed that the iron, copper and zinc elements in drinking water of people with high incidence of EC in Liangzhou District were higher than those in Jingtai County with EC low incidence. In addition, we found that the NMEA, NDEA and NDPA in drinking water samples Liangzhou were significantly higher than those in Jingtai, suggesting that the comprehensive exposure level assessment of nitrosamines in the external environment can effectively predict the health risk of nitrosamine exposure (Figure 6). The cost-effectiveness analysis of EC screening in the high incidence area of EC in Liangzhou District Table 2 shows the direct cost of EC screening in high-incidence area of of EC in Liangzhou District 8 towns (including: Dizhixincun street, Yangxiaba town, Fafang town, Siba town, Xiashuang town, Qingshui town, Wuhe town, and Jingshan town). There were 17546 cases participate EC screening, we found 107 cases of EC (including 90 early EC and 17 advanced EC). Assuming that 90 cases of EC in the screening group did not participate in screening at the early stage, the cost of treating one case of EC according to the advanced diagnosis is 120000.00 yuan, and a total cost of 10800000 yuan is required. The additional cost of screening measures is 10800,000-6300000 =4500000 yuan, and each additional cost of 4500000/90=50000 yuan can reduce one case of EC from early avoidance to advanced stage (Table 3). The cost-benefit analysis of EC screening in the high incidence area of EC in Liangzhou District Table 4 shows the direct cost of EC screening in high-incidence area of of EC in Liangzhou District. Statistics show that the total cost of screening and diagnosis for 107 cases of EC is 8340,000 yuan. The indirect cost mainly takes into account the income loss caused by missed work due to screening and treatment, and the amount is calculated according to the annual per capita annual income of the screening site of 20,000 yuan (the average income in 2023, discounted), the total indirect cost was 644,000 yuan. In addition, the direct benefit (conventional treatment cost) is that the cost of diagnosing and treating one case of advanced EC is 120000.00 yuan, and 107 cases require a total cost of 12840000yuan. Indirect benefits mainly consider the benefits generated by avoiding treatment and accompanying care, preventing loss of life and thus reducing missed work; The amount is calculated based on the annual per capita annual income of 20,000 yuan (the average income in 2023, discounted) at the screening site. It is estimated that the average survival of patients with early esophageal cancer is 5 years, the average survival of patients with advanced EC is 2 years, and the number of years lost is 3 years. The total indirect benefit is 6,923,200.00 yuan (Table 5). The total benefit is 19763200 yuan. Cost: benefit =11407200:19763200=1:1.73. As a result, the benefits outweigh the costs, so screening measures are economical and can create greater economic benefits. Discussion Esophageal cancer (EC) ranks among the most common malignant tumors worldwide. According to the International Agency for Research on Cancer (IARC) World Cancer Report 2020, new cases and deaths of EC constitute for 3.10% and 5.50% of all malignant tumors globally, with incidence and death rates were 6.3/100,000 and 5.6/100,000, respectively( 14 ). It ranks seventh and sixth in the global incidence and death spectrum of malignant tumors. Epidemiological investigation showed that the incidence of EC varies significantly among different populations, countries and regions, with 70% of cases occurring in developing countries and about 50% of patients in East Asia( 15 ).In China, the incidence and mortality of EC have remained high in certain areas for an extended period. The prevalence of EC in China is higherer among men than women, in rural areas compared to in urban areas, and higher in western regionss than in eastern regions( 16 ). Currently, EC in China exhibits regional clustering, high morbidity and mortality rates, low rates of radical surgical treatment, and a low 5-yuear survival rate( 17 , 18 ). Therefore, focusing on prevention and treatment of high-risk groups in areas with a high incidence of EC can facilitate early diagnosis and treatment, thus positively impacting EC prevention and treatment efforts. With the advent of the information age and the continuous progress of population monitoring through big data, such as the ongoing advancement of tumor follow-up registration in China( 19 ), there is potential to identify specific small areas with high incidence of EC through refined disease monitoring for population prevention and control, and to evaluate the effectiveness of prevention and control measures. Based on this concept, this study utilized the long-term tumor registration data to identify specific areas where the high-incidence population of EC is located, and analyzed the recent trends in EC incidence. Using the spatial epidemiology methods, we created comparison maps of high and low EWC incidence areas through geographic information systems(GIS), highlighting towns or villages with the highest EC incidence rates. In addition, extensive medical research and clinical practice have confirmed that cancer screening and early diagnosis and treatment in high-incidence areas are effective measures for EC control. Screening can detect precancerous lesions and early-stage cancer, allowing for effective treatment to halt the progression of lesions and cure early-stage cancer, thereby reducing the occurrence of advanced cancer( 20 – 22 ). This represents a crucial measure to advance cancer prevention and control efforts and enhance their efficiency.. However, detailed etiological investigation and health economic utility and effectiveness evaluation of screening in the high incidence population of EC in western China have not been reported. The systematic analysis explored the population-based incidence of EC cases in Liangzhou and Jingtai from 2009 to 2021s, revealing that the incidence of EC in Liangzhou District was much higher than that in Jingtai County. These findings suggest that health administrative and scientific research departments should intensify efforts in health education, environmental improvement, and pre-cancer screening for digestive system diseases while enhancing research into the etiology of EC. Using the EAPC, this study analysized the changing trend of the incidence of EC in residents of Liangzhou District from 2009 to 2021, showing an overall increasing trend possible reasons for this trend may include advancements in medical technology and changes in population lifestyle. Studies have indicated that the high incidence of local EC may be related to environmental factors in the region, although the specific factors remain unclear. Therefore, this study employed geographic information system (GIS) technology through spatial epidemiology to identify population with high EC incidence in small areas. Subsequently, through population epidemiological investigation and environmental drinking water quality monitoring, the risk factors affecting the high incidence of EC in Liangzhou district were initially explored, and the results of the case-control study suggested that the occurrence of EC was closely linked to sex, age, personality, interpersonal relationship, mental trauma, drinking, intake of salted and sun-cured food, as well as dietary habits such as temperature and dryness of food. Psychological or spiritual factors such as anxiety, depression, and mental trauma were identified as significant contributors to EC risk. A possible explanion would be chronic stress conditions are easy to lead to the disorder of endocrine function of the body, resulting in the decrease of the activity of immune function cells in the body, and the decline of immune ability ultimately leads to the increase of cancer risk( 23 , 24 ). Research data show that anxiety, depression and mental trauma and other negative events are the main mental factors of EC, and the risk of EC or gastric adenoma in people with long-term depression is 4.54 times that of people without depression( 25 , 26 ). Population studies also have shown that people with mental health have a significantly lower risk of developing EC than people who have experienced psychological trauma( 27 ). Unhealthy lifestyle is closely related to the occurrence of EC, such as smoking, drinking, high-salt diet, fried food, etc., are independent risk factors for EC( 28 – 30 ). This study found that the high incidence of EC in Liangzhou is also related to the above factors, suggesting that the prevention and treatment of EC in this area should pay attention to improving the poor eating habits and diet structure of the local population through health intervention. Environmental drinking water quality monitoring showed that the iron, copper and zinc elements in drinking water of people with high incidence of EC in Liangzhou District were higher than those in Jingtai County with EC low incidence. In addition, Nmor and Npyr in drinking water samples were significantly higher than those in the control group, suggesting that the comprehensive exposure level assessment of nitrosamines in the population can effectively predict the health risk of nitrosamine exposure. Finally, a systematic health economics evaluation of the EC screening conducted in high-incidence townships of Liangzhou District over the past five years demonstrated the feasihbility and benefits of such screening. This evaluation aimed to assess the effectiveness of EC screening in areas with a high incidence of EC in western China and to provide a basis for areas with an EC incidence exceeding 70/100,000. The evaluation of EC screening methods should encompass not only their accuracy and effectiveness, but also their health economics( 31 , 32 ). This comprehensive assessment is crucial for the widespread adoption of the screening method. While many studies abroad have evualated the health economic evaluation of EC screening, there is a lack of reports on health economics evaluation of EC screening in western China. In recent years, Chinese scholars have begun to develop a screening program for EC tailored to China’s economic conditions( 33 ). This study employed two fundamentalmethods of health economics evaluation: cost-effectiveness analysis (CEA) and cost-benefit analysis (CBA). CEA compares the costs of different methods to achieve the same effect( 34 ), while CBA assesses the costs and benefits of a program in monetary terms. A program is deemed feasible if the benefits outweigh the costs. In this study, the cost of ‘reducing death’ in the high-risk population of Liangzhou District was evaluated, with an additional 50,000 yuan allocated for each case of EC detectged( 35 ) ( 36 ). The cost and benefit ratio was calculated by comparing the screening cost to the benefits gained. The screening cost was 1,1407200 yuan, and the benefit was 1,9763200 yuan, resulting in a cost-benefit ratio(CBR) of 1:1.73. As the benefits exceed the costs, it is economically feasible and beneficial to conduct EC screening in townships with a high incidence of EC in Liangzhou District. In summary, EC as one of the major cancers affecting the health level of local people in China, should be a focal point of local chronic disease prevention and control efforts. Taking Liangzhou District as an example, factors such as age, interpersonal relationship, mental trauma, drinking, intake of salted and dried food, as well as dietary temperature and dryness, are potential risk factors for EC incidence among local population. Effectively controlling these factors is crucial for reducing the high incidence of EC in the local population. In addition, this study utilized tumor registration big data and spatial epidemiological methods to identify high-incidence areas and key populations of EC. This approach guided the implementation of targeted EC screening in specific areas, proving to be a cost-effective and efficient screening method. This strategy should be widely adopted in the future for the prevention and control of EC. Declarations ACKNOWLEDGMENTS This study was supported by the Major Science and Technology Project of Gansu Province [22ZD6FA050, 22JR9KA002, 20ZD7FA003] and Project of Gansu Provincial Development and Reform Commission [2020–2024] and the funding of the Fundamental Research Funds for the Central Universities (lzujbky‐2022‐25), Natural Science Foundation of Gansu Province (23JRRA10772) and the Second Hospital of Lanzhou University, Cuiying Science and Technology Innovation Plan Project, No: CY2021-BJ-A19 and Lanzhou City Chengguan district science and technology plan project (2023SHFZ0002). AUTHOR CONTRIBUTIONS Duojie Zhu held the primary responsibility for designing the study and drafting the manuscript, while Chengyun Li was in charge of the analysis and interpretation of the data. Huijuan Cheng and Yinggang Che were responsible for data analysis, and Yumin Li played a crucial role in both the design of the study and its coordination. ETHNIC STATEMENT The study was approved by the Ethics Committee of Lanzhou University Second Hospital (2024A-059). CONFLICT OF INTEREST STATEMENT The authors declare that they have no conflicts of interest. DATA AVAILABILITY STATEMENT The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71:209-49. Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396:1204-22. Zhu H, Ma X, Ye T, Wang H, Wang Z, Liu Q, et al. Esophageal cancer in China: Practice and research in the new era. Int J Cancer. 2023; 152:1741-51. Du QC, Wang XY, Hu CK, Zhou L, Fu Z, Liu S, et al. Integrative analysis of platelet-related genes for the prognosis of esophageal cancer. World J Clin Cases. 2022; 10:12077-88. Wang QL, Xie SH, Li WT, Lagergren J. Smoking Cessation and Risk of Esophageal Cancer by Histological Type: Systematic Review and Meta-analysis. J Natl Cancer Inst. 2017; 109. Xie SH, Lagergren J. Social group disparities in the incidence and prognosis of oesophageal cancer. United European Gastroenterol J. 2018; 6:343-8. Li R, Sun J, Wang T, Huang L, Wang S, Sun P, et al. Comparison of Secular Trends in Esophageal Cancer Mortality in China and Japan during 1990-2019: An Age-Period-Cohort Analysis. Int J Environ Res Public Health. 2022; 19. He F, Sha Y, Wang B. Relationship between alcohol consumption and the risks of liver cancer, esophageal cancer, and gastric cancer in China: Meta-analysis based on case-control studies. Medicine (Baltimore). 2021; 100:e26982. Masukume G, Mmbaga BT, Dzamalala CP, Mlombe YB, Finch P, Nyakunga-Maro G, et al. A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case-control studies. Br J Cancer. 2022; 127:1106-15. Luo H, Ge H. Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies. Front Nutr. 2022; 9:831567. Liu CQ, Ma YL, Qin Q, Wang PH, Luo Y, Xu PF, et al. Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040. Thorac Cancer. 2023; 14:3-11. Sheikh M, Roshandel G, McCormack V, Malekzadeh R. Current Status and Future Prospects for Esophageal Cancer. Cancers (Basel). 2023; 15. Wei WQ, Chen ZF, He YT, Feng H, Hou J, Lin DM, et al. Long-Term Follow-Up of a Community Assignment, One-Time Endoscopic Screening Study of Esophageal Cancer in China. J Clin Oncol. 2015; 33:1951-7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020; 70:7-30. Su B, Zhong P, Xuan Y, Xie J, Wu Y, Chen C, et al. Changing Patterns in Cancer Mortality from 1987 to 2020 in China. Cancers (Basel). 2023; 15. Ma L, Li X, Wang M, Zhang Y, Wu J, He Y, et al. The Incidence, Mortality, and DALYs Trends Associated with Esophageal Cancer - China, 1990-2019. China CDC Wkly. 2022; 4:956-61. Yi H, Li S, Lin Y, Li F, Wang S, Jin D, et al. Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer. J Gastroenterol Hepatol. 2023; 38:930-9. Hong K, Yang Q, Yin H, Wei N, Wang W, Yu B. Comprehensive analysis of ZNF family genes in prognosis, immunity, and treatment of esophageal cancer. BMC Cancer. 2023; 23:301. Kashani F, Schrotzlmair F, Canis M, Haubner F. [An unusual finding in the tumor follow up care]. Laryngorhinootologie. 2019; 98:568-70. Hewitt RJ, Bartlett EC, Ganatra R, Butt H, Kouranos V, Chua F, et al. Lung cancer screening provides an opportunity for early diagnosis and treatment of interstitial lung disease. Thorax. 2022; 77:1149-51. Chongsuwat T, Ibrahim AO, Evensen AE, Conway JH, Zwick M, Oloya W. Health facility assessments of cervical cancer prevention, early diagnosis, and treatment services in Gulu, Uganda. PLOS Glob Public Health. 2023; 3:e0000785. Alsomali H, Palmer E, Aujayeb A, Funston W. Early Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis: A Narrative Review. Pulm Ther. 2023; 9:177-93. Thompson PA, Khatami M, Baglole CJ, Sun J, Harris SA, Moon EY, et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis. 2015; 36 Suppl 1:S232-53. Song M, Rabkin CS, Ito H, Oze I, Koyanagi YN, Pfeiffer RM, et al. Circulating immune- and inflammation-related biomarkers and early-stage noncardia gastric cancer risk. Eur J Cancer Prev. 2022; 31:270-3. Aronsen S, Conway R, Lally P, Roberts A, Croker H, Beeken RJ, et al. Determinants of sleep quality in 5835 individuals living with and beyond breast, prostate, and colorectal cancer: a cross-sectional survey. J Cancer Surviv. 2022; 16:1489-501. Klikovac TD, Petrovic N, Saric D. Assessment of Cancer Patients' Mental Health during the Coronavirus Pandemic in Serbia. Int J Environ Res Public Health. 2023; 20. Shin Y, Kim H, Lee T, Kim S, Lee SB, Kim J, et al. Factors in Parenting Stress in Young Patients With Breast Cancer and Implications for Children's Emotional Development: The PSYCHE Study. JAMA Netw Open. 2023; 6:e2344835. Rafiemanesh H, Maleki F, Mohammadian-Hafshejani A, Salemi M, Salehiniya H. The Trend in Histological Changes and the Incidence of Esophagus Cancer in Iran (2003-2008). Int J Prev Med. 2016; 7:31. Sidhu MS, Paul D, Jain S, Brar GS, Sood S, Jain K. Prognostic factor for recurrence in esophagus cancer patients who underwent surgery for curative intent: A single-institution analysis. J Cancer Res Ther. 2021; 17:1376-81. Xia Y, Lin M, Huang J, Fan L. Cardiovascular disease related death among patients with esophagus cancer: A population-based competing risk analysis. Front Oncol. 2022; 12:976711. Shih YT, Sabik LM, Stout NK, Halpern MT, Lipscomb J, Ramsey S, et al. Health Economics Research in Cancer Screening: Research Opportunities, Challenges, and Future Directions. J Natl Cancer Inst Monogr. 2022; 2022:42-50. Halpern MT, Lipscomb J, Yabroff KR. Cancer Health Economics Research: The Future Is Now. J Natl Cancer Inst Monogr. 2022; 2022:102-6. Xia C, Basu P, Kramer BS, Li H, Qu C, Yu XQ, et al. Cancer screening in China: a steep road from evidence to implementation. Lancet Public Health. 2023; 8:e996-e1005. Babela R, Orsagh A, Ricova J, Lansdorp-Vogelaar I, Csanadi M, De Koning H, et al. Cost-effectiveness of colorectal cancer screening in Slovakia. Eur J Cancer Prev. 2022; 31:415-21. Ramos MC, Passone JAL, Lopes ACF, Safatle-Ribeiro AV, Ribeiro Junior U, de Soarez PC. Economic evaluations of colorectal cancer screening: A systematic review and quality assessment. Clinics (Sao Paulo). 2023; 78:100203. Ghorbani S, Rezapour A, Eisavi M, Barahman M, Bagheri Faradonbeh S. Cost-benefit Analysis of Breast Cancer Screening with Digital Mammography: A Systematic Review. Med J Islam Repub Iran. 2023; 37:89. Tables Tables 1 to 5 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files 1.table1.xlsx Table 1. Basic information of 223 patients with EC (Liangzhou) and 538 healthy controls (Jingtai) 2.table2.xlsx Table 2. Cost of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023 3.table3.xlsx Table 3. Direct cost of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023 4.table4.xlsx Table 4. Indirect cost of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023 5.table5.xlsx Table 5. Indirect benefit of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023 SupplementarymaterialFigureS5.docx FigureS1c.jpg FigureS1d.jpg FigureS1i.jpg FigureS1a.jpg FigureS1g.jpg FigureS1e.jpg FigureS1h.jpg FigureS1b.jpg FigureS1f.jpg FigureS1j.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5753089","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":398372542,"identity":"7088d110-4c70-486c-b16a-071b20c69cab","order_by":0,"name":"Duojie Zhu","email":"","orcid":"","institution":"Department of Thoracic Surgery, The Second Hospital \u0026 Clinical Medical School, Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Duojie","middleName":"","lastName":"Zhu","suffix":""},{"id":398372543,"identity":"c4d79e5f-d9a0-47ce-b42a-3b6d3d37b264","order_by":1,"name":"Chengyun Li","email":"","orcid":"","institution":"Department of Toxicology, School of Public Health, Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Chengyun","middleName":"","lastName":"Li","suffix":""},{"id":398372544,"identity":"d25c921a-3306-4bdb-8c5d-a472e2afd7ef","order_by":2,"name":"Yinggang Che","email":"","orcid":"","institution":"Department of Respiratory Medicine, Air force hospital of western theater command, PLA","correspondingAuthor":false,"prefix":"","firstName":"Yinggang","middleName":"","lastName":"Che","suffix":""},{"id":398372545,"identity":"1e60f7a9-1066-4fb3-8f5d-958f82ab2700","order_by":3,"name":"Huijuan Cheng","email":"","orcid":"","institution":"The Second Hospital \u0026 Clinical Medical School, Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Huijuan","middleName":"","lastName":"Cheng","suffix":""},{"id":398372546,"identity":"877aa7b0-06d6-44dd-974a-06a6f309f16c","order_by":4,"name":"Yumin Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYBACPmYg8aEAzDYgTgsbUAvjDAOStAAxMw9pWth5TDfbGNQlNrA3b5NgqLlDjMN4zG7nGLAlNvAcK5NgOPaMaC08iQ0SOWYSjA2HidRiYSCR2CD/hhQtDAYGQFt4iNbCVnazxyDBuI0nrdgi4RgRWvj5D2+78aOiTraf/fDGGx9qiNDCwMABiQ5QBDEkEKOBgYH9AXHqRsEoGAWjYOQCAB+aLZkLPadHAAAAAElFTkSuQmCC","orcid":"","institution":"Gansu provincial key laboratory of environmental oncology, lanzhou university second hospital.Lanzhou University","correspondingAuthor":true,"prefix":"","firstName":"Yumin","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-01-02 16:08:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5753089/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5753089/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73338943,"identity":"0f658dd3-7dda-413f-8724-59917f1f7d86","added_by":"auto","created_at":"2025-01-09 04:56:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":543693,"visible":true,"origin":"","legend":"\u003cp\u003eGansu Province in China has been a key areas of EC tumor registry monitoring for more than 20 years\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/041227a9823aac5ce7292fc1.jpg"},{"id":73339289,"identity":"42f46d13-12a9-446d-b9d6-8fb59969b1e2","added_by":"auto","created_at":"2025-01-09 05:04:39","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":331221,"visible":true,"origin":"","legend":"\u003cp\u003eGender specific incidence characteristics of EC cases registered in Liangzhou area, 2009–2021\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/95d9227646271a44819c4bf9.jpg"},{"id":73339290,"identity":"105379c2-172d-475f-a03e-473fbe752749","added_by":"auto","created_at":"2025-01-09 05:04:39","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":469084,"visible":true,"origin":"","legend":"\u003cp\u003eGender specific incidence characteristics of EC cases registered in Jingtai area, 2009–2021\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/20e4b213adeaa3421c6819bf.jpg"},{"id":73338966,"identity":"4701346c-91dd-4fdb-9041-009dad2d5fbc","added_by":"auto","created_at":"2025-01-09 04:56:40","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":344131,"visible":true,"origin":"","legend":"\u003cp\u003eTrend change analysis of EC incidence rates in Liangzhou and Jingtai areas (2009-2021) (A: Both genders. B: Male. C: Female. D: EAPC trends)\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/121c73e9081c84d51d1a75c7.jpg"},{"id":73339294,"identity":"c9d488d6-1ba6-40ad-9a91-f02e156b5e47","added_by":"auto","created_at":"2025-01-09 05:04:39","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2155441,"visible":true,"origin":"","legend":"\u003cp\u003eDescription of the spatial distribution of EC cases in two regions, from 2009 to 2021\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/451481a4b33678fae93fb6e3.jpg"},{"id":73338959,"identity":"20ec8155-a636-4ff8-9076-4fb70396f437","added_by":"auto","created_at":"2025-01-09 04:56:40","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003eDrinking water quality detection in Liangzhou District and Jingtai County, Gansu Province (A: Water quality mineral element content detection. B: Water quality NMEA, NDEA and NDPA content detection)\u003c/p\u003e","description":"","filename":"placeholderimage.png","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/89a4074a501c69a519864fbe.png"},{"id":78373654,"identity":"8cea3e5b-685a-4ef2-a0a0-44f68ed26b4f","added_by":"auto","created_at":"2025-03-12 14:31:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4573318,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/89602099-bb6c-4aab-8d09-37d1cafef679.pdf"},{"id":73338944,"identity":"0c3d422b-982c-4986-a794-296c84cec456","added_by":"auto","created_at":"2025-01-09 04:56:39","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14267,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1. Basic information of 223 patients with EC (Liangzhou) and 538 healthy controls (Jingtai)\u003c/p\u003e","description":"","filename":"1.table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/dd23fc71c729e13a7457ed58.xlsx"},{"id":73341241,"identity":"20b671c5-d421-4444-9851-813085c6d02d","added_by":"auto","created_at":"2025-01-09 05:28:39","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10900,"visible":true,"origin":"","legend":"\u003cp\u003eTable 2. Cost of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023\u003c/p\u003e","description":"","filename":"2.table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/42024c4dd1770e088f3dd5f7.xlsx"},{"id":73339293,"identity":"7b1a34d8-f471-4eb1-9714-0fc588f7d941","added_by":"auto","created_at":"2025-01-09 05:04:39","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10782,"visible":true,"origin":"","legend":"\u003cp\u003eTable 3. Direct cost of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023\u003c/p\u003e","description":"","filename":"3.table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/e3900890f34522bcf3872b2b.xlsx"},{"id":73338953,"identity":"011f0c99-7823-4388-a8b7-2711c844567b","added_by":"auto","created_at":"2025-01-09 04:56:39","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":11189,"visible":true,"origin":"","legend":"\u003cp\u003eTable 4. Indirect cost of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023\u003c/p\u003e","description":"","filename":"4.table4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/78215a18c8de05b2d0cdad67.xlsx"},{"id":73338960,"identity":"5eefdc7e-8d81-4c50-be68-9992ed85a44c","added_by":"auto","created_at":"2025-01-09 04:56:40","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":10918,"visible":true,"origin":"","legend":"\u003cp\u003eTable 5. Indirect benefit of EC screening in areas with high incidence of EC in Liangzhou District, Gansu Province, 2019-2023\u003c/p\u003e","description":"","filename":"5.table5.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/3e5909f55714fd617047ecf6.xlsx"},{"id":73338958,"identity":"f9393395-27f4-4576-93bd-169d816ca6b6","added_by":"auto","created_at":"2025-01-09 04:56:40","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":11204,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarymaterialFigureS5.docx","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/36cd3af98526624cc4d380af.docx"},{"id":73338964,"identity":"99558c5f-8a0e-4068-a517-6ca017fd618f","added_by":"auto","created_at":"2025-01-09 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05:04:40","extension":"jpg","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":2115531,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS1h.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/377894749ec2863f3c8598ad.jpg"},{"id":73338962,"identity":"b9ef0f4c-0f27-44fe-a6f3-8e2c744544b5","added_by":"auto","created_at":"2025-01-09 04:56:40","extension":"jpg","order_by":14,"title":"","display":"","copyAsset":false,"role":"supplement","size":2148342,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS1b.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/2b9b69a1efc14e1c8c0b781a.jpg"},{"id":73341245,"identity":"777db14b-7fdc-4a90-be26-0d4cbc5f0064","added_by":"auto","created_at":"2025-01-09 05:28:41","extension":"jpg","order_by":15,"title":"","display":"","copyAsset":false,"role":"supplement","size":2129736,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS1f.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/ca4bee7f0b154b097cc706f4.jpg"},{"id":73338984,"identity":"6b0c65a7-2ca2-4d5b-a401-d6be7e6ffe79","added_by":"auto","created_at":"2025-01-09 04:56:40","extension":"jpg","order_by":16,"title":"","display":"","copyAsset":false,"role":"supplement","size":2111562,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS1j.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5753089/v1/0a59d872778d23fe8976a446.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Establishment of an Early Warning Screening System for High Risk Population in High Incidence Area of Esophageal Cancer, Gansu province, northwestern China: A Retrospective Population-Based Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophageal cancer (EC), ranking as the seventh most prevalent and sixth most fatal cancer globally, represents a prevalent malignant tumor in the digestive tract, posing a formidable menace to human well-being(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The incidence of EC has surged notably by 56% from 1990 to 2019, leading to increased public healthcare expenditures and household financial burdens(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The rural areas exhibit approximately double the incidence and mortality rates compared to urban areas, signifying a glaring regional disparity(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite advancements in EC treatment, the anticipated outcome remained limited, with a meager five-year survival rate below 20%(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Encouragingly, timely detection and intervention in EC patients have shown substantial promise in reducing mortality rates(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe occurrence and progression of EC are influenced by a multitude of factors. Socioeconomic status, particularly low educational attainment and lower economic levels, have been identified as risk factors for EC development(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Furthermore, the risk of EC is significantly elevated in smokers compared to non-smokers, with the risk decreasing upon smoking cessation(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Excessive alcohol consumption has also been demonstrated to markedly increase the risk of EC(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Additionally, the consumption of hot foods and beverages associated with risk of EC(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Conversely, studies have indicated that a diet rich in fruits, vegetables, and dietary fiber can potentially reduce the risk of EC(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Projections suggest a substantial increase in the burden of EC in the future(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, the efficacy of early screening and interventions for EC patients remains uncertain, with inconclusive evidence regarding the potential benefits for the Chinese population and unclear cost-effectiveness of early screening. Nonetheless, the implementation of a standardized screening protocol has the potential to yield significant benefits, particularly in high-risk regions and among targeted populations(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Studies conducted in high-risk regions of China have demonstrated that early screening programs for EC can effectively reduce mortality rates among patients(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this comprehensive study, we systematically gathered and analyzed data concerning the incidence and longitudinal follow-up of EC cases from 2009 to 2021 in the regions of Liangzhou and Jingtai situated in Gansu Province. Specifically, we performed an intricate spatial analysis focusing on the high prevalence of EC within Liangzhou District and Jingtai County. Furthermore, our study delved into the nuanced interplay of various demographic and lifestyle factors with the incidence of EC in the aforementioned regions. Moreover, we investigation encompassed an assessment of the impact of heavy metals and nitrosamines on the geographical areas at heightened risk for EC. Through the lens of health economics, we rigorously scrutinized the cost-effectiveness and cost-benefit profiles associated with early screening protocols for individuals afflicted with EC. Remarkably, our findings underscored the significant role of early screening initiatives as a pivotal strategy to curtail national expenditures on EC while conferring substantial benefits to affected individuals.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003e1. Sources of data and quality control\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Information Center of Gansu Provincial Health Commission and Liangzhou and Jingtai (Gansu province, China ) Cancer Registry provided esophageal cancer incidence data and demographic information from the target regions. Data collected from 2009 to 2021 included Liangzhou and Jingtai EC incidence data, classified by the International Classification of Diseases (ICD)-10 codes. As per the International Association of Cancer Registries (IACR) and NCCR requirements of cancer registration data, our data evaluation met the quality control criteria for tumor follow-up registration, Liangzhou and Jingtai esophageal cancer incidence data were included in the annual report of the Chinese Tumor Registry, from 2009 to 2021.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. To identify the EC trends in prevalence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe average annual percent change (EAPC) to assess trends with regard to changes in Wuwei and Jingtai EC incidence rates from 2009 to 2021. The EAPC calculation included the independent variable, years, and a logarithmic transformation on the incidence rates. We fit the EAPC to a straight line, Y = b + aX and Y = Ln (incidence rate), where X represents the year. With the final equation being EAPC = (10a-1)\u0026times;100%, explained observed annual variation trends.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eVisual analysis of the population with high incidence of EC in the region\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis part of the study utilized geographical epidemiology and geographic information system analysis to examine the low incidence of EC in Jingtai County and the high incidence in Liangzhou District. GIS10.0 software was empolyed for mapping the incidence of EC and conducting spatial autocorrelation analysis using Moran index (Moran\u0026apos;s I), Moran\u0026apos;s I scatter plots, local aggregation, and outliers (LISA). Spatio-temporal scanning statistics were utilized to identify high-value clusters of EC incidence in Liangzhou and Jingtai (Gansu province, China ).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTo investigate the lifestyle and behavior of people in areas with high incidence of EC\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn order to understand the risk factors of EC in Liangzhou District, Wuwei City, Gansu Province, this study investigated the basic situation and lifestyle of 223 patients with esophageal cancer in Liangzhou District and 538 normal control groups in 5 towns and townships in Jingtai County,. The contents of the investigation mainly include the basic information of the subjects and the relevant information such as living and eating habits.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor the design of the epidemiological questionnaire, refer to the Technical Plan for Screening and Early Diagnosis and Treatment of Upper Gastrointestinal Cancer (2020 edition). Epidemiological questionnaire for early diagnosis and treatment of upper gastrointestinal cancer. The contents of the investigation mainly include the basic information of the subjects (gender, age, anxiety, education, personality, whether they have mental trauma and often sulk, etc.) and lifestyle information (smoking, drinking alcohol, drinking tea, drinking water sources, whether they exercise, intake of pickled and dried food, intake of fried food, intake of fast food and convenience food, intake of cold and hot food and dry food, etc.). The epidemiological questionnaire was completed by face-to-face interview.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5. Detection of heavy metals and nitrites in drinking water\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe concentration of heavy metals and nine N-nitrosamines in drinking water was determined by atomic absorption technique and solid phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS). The concentration of 6 N-nitrosamines in drinking water was determined by SPE-GC-MS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6. Study on health economic regarding the screening of EC in Liangzhou high risk area\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e The cost data were obtained from the Wuwei Tumor Hospital of Gansu (Wuwei, China) finance department and from surveys of patients and relatives. The annual per capita income is obtained by the financial department of the local government at the screening site. This study examined both direct medical costs and indirect costs (earnings due to missed work for screening and treatment). The benefits include direct benefits (savings in routine medical costs) and indirect benefits (benefits resulting from reduced missed work due to avoided deaths and treatments). Because the screening work has a certain time span and the medical market price changes greatly, the screening cost, medical cost and benefit are discounted to the price level of 2020, and the discount rate is determined according to the national retail price index and the consumer price index.\u003c/p\u003e\n\u003cp\u003eIn addition, 107 esophageal cancer patients\u0026rsquo; information mainly included: (1) the first page of medical records: gender, age, date of birth, date of admission, date of discharge, length of stay, department of treatment, hospital grade, medical insurance payment method, hospital nature, and operation; (2) Hospitalization cost information: total hospitalization cost, treatment cost, medicine cost, consultation fee, examination fee, laboratory fee, bed fee, nursing fee, operation fee. The outliers excluded include: there are obvious logical errors between the inpatient expenses and the total inpatient expenses; The length of hospitalization is less than 1 day and more than 100 days; Duplicate cases based on medical record number; Basic information missing cases; Cases with abnormal total hospital expenses. Additional missing values include: age based on date of birth and date of discharge, length of stay derived from date of discharge and date of admission, etc.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original case data of patients with esophageal cancer were obtained according to the ICD-X. The qualified data was assessed based on the \u0026lsquo;guideline of Chinese cancer registration\u0026rsquo; and referred to the criteria listed under the \u0026lsquo;cancer incidence in five continents volume\u0026rsquo; outlined by IACR. The data were stratified by years and crude incidence rates were calculated. Analysis of Chi-square test, or non-parametric tests were employed as appropriate for data comparisons. Data analysis was performed using IBM SPSS Statistics 26.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 8.0 (La Jolla, CA, USA). Statistical significance was defined as P \u0026lt; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eSelection of high incidence area of EC, Gansu province, northwestern China\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eSince the scope of tumor registry monitoring in China is not full coverage of the whole population, this work cannot reflect the overall situation of some regions.? In the early stage of this study, the data of EC patients in Gansu province in the past ten years were collected from the Information Center of Gansu Provincial Health Commission. The cumulative number of patients was 18,252, and the average annual incidence of the whole population was 7.3/100,000. However, the incidence of EC in some regions far exceeded the national average of 18.24 per 100,000 in 2018. According to tumor registration data, Liangzhou District, Wuwei City, Gansu Province, and Jingtai County, Baiyin City, Gansu Province, belong to the areas under long-term surveillance (Figure 1). From 2009 to 2021, the incidence of EC in Liangzhou District, Wuwei City, Gansu Province remained at a high level for a long time, with an average annual incidence of 45.23/100,000. The average annual incidence of EC in Jingtai County was 9.83/100,000, and the incidence of male EC was more than twice that of female cancer (Figure 2-3). EAPC assess trends in Wuwei and Jingtai EC incidence rates from 2009 to 2021 showed a decreasing trend in Liangzhou District and Jingtai County (Figure 4). The overall analysis data suggest that the incidence of EC in Liangzhou district is at a high level, which belongs to the high incidence area in Gansu Province.\u003c/p\u003e\n\u003cp\u003eGeographical epidemiology and the application of geographic information system were used to analyze the low incidence of esophageal cancer in Jingtai County and the high incidence in Liangzhou District, and carries out a more detailed spatial analysis. According to the detailed monitoring data of local EC from 2009 to 2021, we found that in Liangzhou District, there were 8 communities and townships with the incidence of EC higher than 70/100,000, including Dizhixincun street, Yangxiaba town, Fafang town, Siba town, Xiashuang town, Qingshui town, Wuhe town, and Jingshan town. Among them, the average incidence of EC in Dizhixincun street was 93.55/100,000, more than five times the national average incidence. In addition, Jingtai County is a drop-incidence area of EC, with an average incidence of 9.83/100,000 from 2009 to 2021, among which the incidence of EC in Yitiaoshan town in Jingtai County is the lowest, at 3.47/100,000. The specific geographical distribution information is shown in detail in Figure 5 and Figure S1 a-j.\u0026nbsp;\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eRisk factors for\u0026nbsp;EC in\u0026nbsp;a\u0026nbsp;high incidence area of\u0026nbsp;Liangzhou area\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eOne of the goals of the study was to look for differences in the risk of EC, so we investigated the basic situation and lifestyle of 223 patients with EC in Liangzhou District and 538 normal control groups in 5 towns and townships in Jingtai County, which had a low incidence of EC. The contents of the investigation mainly include the basic information of the subjects and the relevant information such as living and eating habits. Chi-square test analysis results showed that among the collected basic data, personality characteristics, marital status were risk factors for EC (P\u0026lt;0.05) . The analysis of relevant data of life habits found that drinking alcohol, intake of red meat, intake of salted and dried food, intake of fried food, cold and hot degree, and dry thinness were risk factors for EC (P\u0026lt;0.05) (Table 1).\u003c/p\u003e\n\u003cp\u003eIn addition, drinking water of residents in Jingtai County and Liangzhou District was collected and tested. Environmental drinking water quality monitoring showed that the iron, copper and zinc elements in drinking water of people with high incidence of EC in Liangzhou District were higher than those in Jingtai County with EC low incidence. In addition, we found that the NMEA, NDEA and NDPA in drinking water samples Liangzhou were significantly higher than those in Jingtai, suggesting that the comprehensive exposure level assessment of nitrosamines in the external environment can effectively predict the health risk of nitrosamine exposure (Figure 6). \u0026nbsp;\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cstrong\u003eThe cost-effectiveness analysis of EC screening in the high incidence area of EC in Liangzhou District\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTable 2 shows the direct cost of EC screening in high-incidence area of of EC in Liangzhou District 8 towns (including: Dizhixincun street, Yangxiaba town, Fafang town, Siba town, Xiashuang town, Qingshui town, Wuhe town, and Jingshan town). There were 17546 cases participate EC screening, we found 107 cases of EC (including 90 early EC and 17 advanced EC). Assuming that 90 cases of EC in the screening group did not participate in screening at the early stage, the cost of treating one case of EC according to the advanced diagnosis is 120000.00 yuan, and a total cost of 10800000 yuan is required. The additional cost of screening measures is 10800,000-6300000 =4500000 yuan, and each additional cost of 4500000/90=50000 yuan can reduce one case of EC from early avoidance to advanced stage (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003col start=\"4\"\u003e\n \u003cli\u003e\u003cstrong\u003eThe cost-benefit analysis of EC screening in the high incidence area of EC in Liangzhou District\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTable 4 shows the direct cost of EC screening in high-incidence area of of EC in Liangzhou District. Statistics show that the total cost of screening and diagnosis for 107 cases of EC is 8340,000 yuan. The indirect cost mainly takes into account the income loss caused by missed work due to screening and treatment, and the amount is calculated according to the annual per capita annual income of the screening site of 20,000 yuan (the average income in 2023, discounted), the total indirect cost was 644,000 yuan.\u003c/p\u003e\n\u003cp\u003eIn addition, the direct benefit (conventional treatment cost) is that the cost of diagnosing and treating one case of advanced EC is 120000.00 yuan, and 107 cases require a total cost of 12840000yuan. Indirect benefits mainly consider the benefits generated by avoiding treatment and accompanying care, preventing loss of life and thus reducing missed work; The amount is calculated based on the annual per capita annual income of 20,000 yuan (the average income in 2023, discounted) at the screening site. It is estimated that the average survival of patients with early esophageal cancer is 5 years, the average survival of patients with advanced EC is 2 years, and the number of years lost is 3 years. The total indirect benefit is 6,923,200.00 yuan (Table 5). The total benefit is 19763200 yuan. Cost: benefit =11407200:19763200=1:1.73. As a result, the benefits outweigh the costs, so screening measures are economical and can create greater economic benefits.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEsophageal cancer (EC) ranks among the most common malignant tumors worldwide. According to the International Agency for Research on Cancer (IARC) World Cancer Report 2020, new cases and deaths of EC constitute for 3.10% and 5.50% of all malignant tumors globally, with incidence and death rates were 6.3/100,000 and 5.6/100,000, respectively(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). It ranks seventh and sixth in the global incidence and death spectrum of malignant tumors. Epidemiological investigation showed that the incidence of EC varies significantly among different populations, countries and regions, with 70% of cases occurring in developing countries and about 50% of patients in East Asia(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).In China, the incidence and mortality of EC have remained high in certain areas for an extended period. The prevalence of EC in China is higherer among men than women, in rural areas compared to in urban areas, and higher in western regionss than in eastern regions(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Currently, EC in China exhibits regional clustering, high morbidity and mortality rates, low rates of radical surgical treatment, and a low 5-yuear survival rate(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Therefore, focusing on prevention and treatment of high-risk groups in areas with a high incidence of EC can facilitate early diagnosis and treatment, thus positively impacting EC prevention and treatment efforts.\u003c/p\u003e \u003cp\u003eWith the advent of the information age and the continuous progress of population monitoring through big data, such as the ongoing advancement of tumor follow-up registration in China(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), there is potential to identify specific small areas with high incidence of EC through refined disease monitoring for population prevention and control, and to evaluate the effectiveness of prevention and control measures. Based on this concept, this study utilized the long-term tumor registration data to identify specific areas where the high-incidence population of EC is located, and analyzed the recent trends in EC incidence. Using the spatial epidemiology methods, we created comparison maps of high and low EWC incidence areas through geographic information systems(GIS), highlighting towns or villages with the highest EC incidence rates. In addition, extensive medical research and clinical practice have confirmed that cancer screening and early diagnosis and treatment in high-incidence areas are effective measures for EC control. Screening can detect precancerous lesions and early-stage cancer, allowing for effective treatment to halt the progression of lesions and cure early-stage cancer, thereby reducing the occurrence of advanced cancer(\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). This represents a crucial measure to advance cancer prevention and control efforts and enhance their efficiency.. However, detailed etiological investigation and health economic utility and effectiveness evaluation of screening in the high incidence population of EC in western China have not been reported.\u003c/p\u003e \u003cp\u003eThe systematic analysis explored the population-based incidence of EC cases in Liangzhou and Jingtai from 2009 to 2021s, revealing that the incidence of EC in Liangzhou District was much higher than that in Jingtai County. These findings suggest that health administrative and scientific research departments should intensify efforts in health education, environmental improvement, and pre-cancer screening for digestive system diseases while enhancing research into the etiology of EC. Using the EAPC, this study analysized the changing trend of the incidence of EC in residents of Liangzhou District from 2009 to 2021, showing an overall increasing trend possible reasons for this trend may include advancements in medical technology and changes in population lifestyle.\u003c/p\u003e \u003cp\u003eStudies have indicated that the high incidence of local EC may be related to environmental factors in the region, although the specific factors remain unclear. Therefore, this study employed geographic information system (GIS) technology through spatial epidemiology to identify population with high EC incidence in small areas. Subsequently, through population epidemiological investigation and environmental drinking water quality monitoring, the risk factors affecting the high incidence of EC in Liangzhou district were initially explored, and the results of the case-control study suggested that the occurrence of EC was closely linked to sex, age, personality, interpersonal relationship, mental trauma, drinking, intake of salted and sun-cured food, as well as dietary habits such as temperature and dryness of food. Psychological or spiritual factors such as anxiety, depression, and mental trauma were identified as significant contributors to EC risk. A possible explanion would be chronic stress conditions are easy to lead to the disorder of endocrine function of the body, resulting in the decrease of the activity of immune function cells in the body, and the decline of immune ability ultimately leads to the increase of cancer risk(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eResearch data show that anxiety, depression and mental trauma and other negative events are the main mental factors of EC, and the risk of EC or gastric adenoma in people with long-term depression is 4.54 times that of people without depression(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Population studies also have shown that people with mental health have a significantly lower risk of developing EC than people who have experienced psychological trauma(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Unhealthy lifestyle is closely related to the occurrence of EC, such as smoking, drinking, high-salt diet, fried food, etc., are independent risk factors for EC(\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). This study found that the high incidence of EC in Liangzhou is also related to the above factors, suggesting that the prevention and treatment of EC in this area should pay attention to improving the poor eating habits and diet structure of the local population through health intervention. Environmental drinking water quality monitoring showed that the iron, copper and zinc elements in drinking water of people with high incidence of EC in Liangzhou District were higher than those in Jingtai County with EC low incidence. In addition, Nmor and Npyr in drinking water samples were significantly higher than those in the control group, suggesting that the comprehensive exposure level assessment of nitrosamines in the population can effectively predict the health risk of nitrosamine exposure.\u003c/p\u003e \u003cp\u003eFinally, a systematic health economics evaluation of the EC screening conducted in high-incidence townships of Liangzhou District over the past five years demonstrated the feasihbility and benefits of such screening. This evaluation aimed to assess the effectiveness of EC screening in areas with a high incidence of EC in western China and to provide a basis for areas with an EC incidence exceeding 70/100,000. The evaluation of EC screening methods should encompass not only their accuracy and effectiveness, but also their health economics(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). This comprehensive assessment is crucial for the widespread adoption of the screening method. While many studies abroad have evualated the health economic evaluation of EC screening, there is a lack of reports on health economics evaluation of EC screening in western China. In recent years, Chinese scholars have begun to develop a screening program for EC tailored to China\u0026rsquo;s economic conditions(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study employed two fundamentalmethods of health economics evaluation: cost-effectiveness analysis (CEA) and cost-benefit analysis (CBA). CEA compares the costs of different methods to achieve the same effect(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e), while CBA assesses the costs and benefits of a program in monetary terms. A program is deemed feasible if the benefits outweigh the costs. In this study, the cost of \u0026lsquo;reducing death\u0026rsquo; in the high-risk population of Liangzhou District was evaluated, with an additional 50,000 yuan allocated for each case of EC detectged(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). The cost and benefit ratio was calculated by comparing the screening cost to the benefits gained. The screening cost was 1,1407200 yuan, and the benefit was 1,9763200 yuan, resulting in a cost-benefit ratio(CBR) of 1:1.73. As the benefits exceed the costs, it is economically feasible and beneficial to conduct EC screening in townships with a high incidence of EC in Liangzhou District.\u003c/p\u003e \u003cp\u003eIn summary, EC as one of the major cancers affecting the health level of local people in China, should be a focal point of local chronic disease prevention and control efforts. Taking Liangzhou District as an example, factors such as age, interpersonal relationship, mental trauma, drinking, intake of salted and dried food, as well as dietary temperature and dryness, are potential risk factors for EC incidence among local population. Effectively controlling these factors is crucial for reducing the high incidence of EC in the local population. In addition, this study utilized tumor registration big data and spatial epidemiological methods to identify high-incidence areas and key populations of EC. This approach guided the implementation of targeted EC screening in specific areas, proving to be a cost-effective and efficient screening method. This strategy should be widely adopted in the future for the prevention and control of EC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Major Science and Technology Project of Gansu Province [22ZD6FA050, 22JR9KA002, 20ZD7FA003] and Project of Gansu Provincial Development and Reform Commission [2020\u0026ndash;2024] and the funding of the Fundamental Research Funds for the Central Universities (lzujbky‐2022‐25), Natural Science Foundation of Gansu Province (23JRRA10772) and the Second Hospital of Lanzhou University, Cuiying Science and Technology Innovation Plan Project, No: CY2021-BJ-A19 and Lanzhou City Chengguan district science and technology plan project (2023SHFZ0002).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuojie Zhu held the primary responsibility for designing the study and drafting the manuscript, while Chengyun Li was in charge of the analysis and interpretation of the data. Huijuan Cheng and Yinggang Che were responsible for data analysis, and Yumin Li played a crucial role in both the design of the study and its coordination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHNIC STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Lanzhou University Second Hospital (2024A-059).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71:209-49.\u003c/li\u003e\n\u003cli\u003eDiseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396:1204-22.\u003c/li\u003e\n\u003cli\u003eZhu H, Ma X, Ye T, Wang H, Wang Z, Liu Q, et al. Esophageal cancer in China: Practice and research in the new era. Int J Cancer. 2023; 152:1741-51.\u003c/li\u003e\n\u003cli\u003eDu QC, Wang XY, Hu CK, Zhou L, Fu Z, Liu S, et al. Integrative analysis of platelet-related genes for the prognosis of esophageal cancer. World J Clin Cases. 2022; 10:12077-88.\u003c/li\u003e\n\u003cli\u003eWang QL, Xie SH, Li WT, Lagergren J. Smoking Cessation and Risk of Esophageal Cancer by Histological Type: Systematic Review and Meta-analysis. J Natl Cancer Inst. 2017; 109.\u003c/li\u003e\n\u003cli\u003eXie SH, Lagergren J. Social group disparities in the incidence and prognosis of oesophageal cancer. United European Gastroenterol J. 2018; 6:343-8.\u003c/li\u003e\n\u003cli\u003eLi R, Sun J, Wang T, Huang L, Wang S, Sun P, et al. Comparison of Secular Trends in Esophageal Cancer Mortality in China and Japan during 1990-2019: An Age-Period-Cohort Analysis. Int J Environ Res Public Health. 2022; 19.\u003c/li\u003e\n\u003cli\u003eHe F, Sha Y, Wang B. Relationship between alcohol consumption and the risks of liver cancer, esophageal cancer, and gastric cancer in China: Meta-analysis based on case-control studies. Medicine (Baltimore). 2021; 100:e26982.\u003c/li\u003e\n\u003cli\u003eMasukume G, Mmbaga BT, Dzamalala CP, Mlombe YB, Finch P, Nyakunga-Maro G, et al. A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case-control studies. Br J Cancer. 2022; 127:1106-15.\u003c/li\u003e\n\u003cli\u003eLuo H, Ge H. Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies. Front Nutr. 2022; 9:831567.\u003c/li\u003e\n\u003cli\u003eLiu CQ, Ma YL, Qin Q, Wang PH, Luo Y, Xu PF, et al. Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040. Thorac Cancer. 2023; 14:3-11.\u003c/li\u003e\n\u003cli\u003eSheikh M, Roshandel G, McCormack V, Malekzadeh R. Current Status and Future Prospects for Esophageal Cancer. Cancers (Basel). 2023; 15.\u003c/li\u003e\n\u003cli\u003eWei WQ, Chen ZF, He YT, Feng H, Hou J, Lin DM, et al. Long-Term Follow-Up of a Community Assignment, One-Time Endoscopic Screening Study of Esophageal Cancer in China. J Clin Oncol. 2015; 33:1951-7.\u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020; 70:7-30.\u003c/li\u003e\n\u003cli\u003eSu B, Zhong P, Xuan Y, Xie J, Wu Y, Chen C, et al. Changing Patterns in Cancer Mortality from 1987 to 2020 in China. Cancers (Basel). 2023; 15.\u003c/li\u003e\n\u003cli\u003eMa L, Li X, Wang M, Zhang Y, Wu J, He Y, et al. The Incidence, Mortality, and DALYs Trends Associated with Esophageal Cancer - China, 1990-2019. China CDC Wkly. 2022; 4:956-61.\u003c/li\u003e\n\u003cli\u003eYi H, Li S, Lin Y, Li F, Wang S, Jin D, et al. Risk and prognosis of secondary thoracic cancers after radiation therapy for esophageal cancer. J Gastroenterol Hepatol. 2023; 38:930-9.\u003c/li\u003e\n\u003cli\u003eHong K, Yang Q, Yin H, Wei N, Wang W, Yu B. Comprehensive analysis of ZNF family genes in prognosis, immunity, and treatment of esophageal cancer. BMC Cancer. 2023; 23:301.\u003c/li\u003e\n\u003cli\u003eKashani F, Schrotzlmair F, Canis M, Haubner F. [An unusual finding in the tumor follow up care]. Laryngorhinootologie. 2019; 98:568-70.\u003c/li\u003e\n\u003cli\u003eHewitt RJ, Bartlett EC, Ganatra R, Butt H, Kouranos V, Chua F, et al. Lung cancer screening provides an opportunity for early diagnosis and treatment of interstitial lung disease. Thorax. 2022; 77:1149-51.\u003c/li\u003e\n\u003cli\u003eChongsuwat T, Ibrahim AO, Evensen AE, Conway JH, Zwick M, Oloya W. Health facility assessments of cervical cancer prevention, early diagnosis, and treatment services in Gulu, Uganda. PLOS Glob Public Health. 2023; 3:e0000785.\u003c/li\u003e\n\u003cli\u003eAlsomali H, Palmer E, Aujayeb A, Funston W. Early Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis: A Narrative Review. Pulm Ther. 2023; 9:177-93.\u003c/li\u003e\n\u003cli\u003eThompson PA, Khatami M, Baglole CJ, Sun J, Harris SA, Moon EY, et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis. 2015; 36 Suppl 1:S232-53.\u003c/li\u003e\n\u003cli\u003eSong M, Rabkin CS, Ito H, Oze I, Koyanagi YN, Pfeiffer RM, et al. Circulating immune- and inflammation-related biomarkers and early-stage noncardia gastric cancer risk. Eur J Cancer Prev. 2022; 31:270-3.\u003c/li\u003e\n\u003cli\u003eAronsen S, Conway R, Lally P, Roberts A, Croker H, Beeken RJ, et al. Determinants of sleep quality in 5835 individuals living with and beyond breast, prostate, and colorectal cancer: a cross-sectional survey. J Cancer Surviv. 2022; 16:1489-501.\u003c/li\u003e\n\u003cli\u003eKlikovac TD, Petrovic N, Saric D. Assessment of Cancer Patients\u0026apos; Mental Health during the Coronavirus Pandemic in Serbia. Int J Environ Res Public Health. 2023; 20.\u003c/li\u003e\n\u003cli\u003eShin Y, Kim H, Lee T, Kim S, Lee SB, Kim J, et al. Factors in Parenting Stress in Young Patients With Breast Cancer and Implications for Children\u0026apos;s Emotional Development: The PSYCHE Study. JAMA Netw Open. 2023; 6:e2344835.\u003c/li\u003e\n\u003cli\u003eRafiemanesh H, Maleki F, Mohammadian-Hafshejani A, Salemi M, Salehiniya H. The Trend in Histological Changes and the Incidence of Esophagus Cancer in Iran (2003-2008). Int J Prev Med. 2016; 7:31.\u003c/li\u003e\n\u003cli\u003eSidhu MS, Paul D, Jain S, Brar GS, Sood S, Jain K. Prognostic factor for recurrence in esophagus cancer patients who underwent surgery for curative intent: A single-institution analysis. J Cancer Res Ther. 2021; 17:1376-81.\u003c/li\u003e\n\u003cli\u003eXia Y, Lin M, Huang J, Fan L. Cardiovascular disease related death among patients with esophagus cancer: A population-based competing risk analysis. Front Oncol. 2022; 12:976711.\u003c/li\u003e\n\u003cli\u003eShih YT, Sabik LM, Stout NK, Halpern MT, Lipscomb J, Ramsey S, et al. Health Economics Research in Cancer Screening: Research Opportunities, Challenges, and Future Directions. J Natl Cancer Inst Monogr. 2022; 2022:42-50.\u003c/li\u003e\n\u003cli\u003eHalpern MT, Lipscomb J, Yabroff KR. Cancer Health Economics Research: The Future Is Now. J Natl Cancer Inst Monogr. 2022; 2022:102-6.\u003c/li\u003e\n\u003cli\u003eXia C, Basu P, Kramer BS, Li H, Qu C, Yu XQ, et al. Cancer screening in China: a steep road from evidence to implementation. Lancet Public Health. 2023; 8:e996-e1005.\u003c/li\u003e\n\u003cli\u003eBabela R, Orsagh A, Ricova J, Lansdorp-Vogelaar I, Csanadi M, De Koning H, et al. Cost-effectiveness of colorectal cancer screening in Slovakia. Eur J Cancer Prev. 2022; 31:415-21.\u003c/li\u003e\n\u003cli\u003eRamos MC, Passone JAL, Lopes ACF, Safatle-Ribeiro AV, Ribeiro Junior U, de Soarez PC. Economic evaluations of colorectal cancer screening: A systematic review and quality assessment. Clinics (Sao Paulo). 2023; 78:100203.\u003c/li\u003e\n\u003cli\u003eGhorbani S, Rezapour A, Eisavi M, Barahman M, Bagheri Faradonbeh S. Cost-benefit Analysis of Breast Cancer Screening with Digital Mammography: A Systematic Review. Med J Islam Repub Iran. 2023; 37:89.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 5 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Esophageal cancer, Spatial epidemiology, Risk factors, Screening, Health economics evaluation","lastPublishedDoi":"10.21203/rs.3.rs-5753089/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5753089/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe medical treatment of cancer patients has caused a huge burden on the financial expenditure of the government, so it is crucial to evaluate whether the financial expenditure of public medical care. The aim of this study was to identify risk populations of esophageal cancer (EC) in Liangzhou through epidemiological data and evaluate the feasibility and cost-effectiveness of early screening in these populations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe collected data on EC incidence and follow-up from 2009 to 2021 in the regions of Liangzhou and Jingtai in Gansu Province. We used spatial analysis and regional investigation the incidence data of EC reporting area to analyze the prevalence of EC within Liangzhou and Jingtai, the impact of lifestyle, heavy metals and nitrosamines on EC. Subsequently, we conducted a health economics assessment based on the Chinese government's regional investment in EC screening in Gansu Province in the past five years, with a view to optimizing cancer prevention measures in areas with high incidence of EC.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom 2009 to 2021, the incidence of EC in Liangzhou remained high with an average annual incidence of 45.23 per100,000, there were 8 communities and townships with the incidence of EC higher than 70/100,000 in Liangzhou. Drinking alcohol, intake of red meat, salted food, dried food, fried food and dry thinness were risk factors for EC. The trace elements ( iron, copper and zinc) and NMEA, NDEA and NDPA in drinking water of Liangzhou were higher than those in Jingtai County, suggested that the residents of Liangzhou District are exposed to higher environmental carcinogenic risk. In the systematic health economics evaluation of the EC screening, we found that the screening cost amounted to 1,1407200 yuan, and the benefit totaled 1,9763200 yuan, resulting in a cost-benefit ratio (CBR) of 1:1.73.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study identified high-incidence areas and key populations of EC. This approach guided the implementation of targeted EC screening in specific area, proving to be a cost-effective and efficient screening method. The adoption of this approach should be widely applied in the prevention and control of EC in the future, and provides an important basis for the clinical benefit and early screening of patients with EC.\u003c/p\u003e","manuscriptTitle":"Establishment of an Early Warning Screening System for High Risk Population in High Incidence Area of Esophageal Cancer, Gansu province, northwestern China: A Retrospective Population-Based Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-09 04:56:34","doi":"10.21203/rs.3.rs-5753089/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6c6ee64e-8364-4474-a8e3-b40e4d1906e2","owner":[],"postedDate":"January 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-12T14:23:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-09 04:56:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5753089","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5753089","identity":"rs-5753089","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}