The Arc of Cancer Mortality: Half a Century of U.S. Data from the CDC WONDER Database

The Arc of Cancer Mortality: Half a Century of U.S. Data from the CDC WONDER Database | 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 The Arc of Cancer Mortality: Half a Century of U.S. Data from the CDC WONDER Database Faizan Ahmed, Husnain Ahmed, Fenilkumar Kotadiya, Haris Bin Tahir, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7755712/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 Background : Cancer remains a leading cause of death across the United States, accounting for more than 27 million deaths among adults aged 25 and older over the past five decades. However, CDC data from 1968 to 2023 show a notable decline in age-adjusted mortality rates, primarily due to recent advances. Despite this progress, disparities still exist among different strata due to various inequities. Aims: The objective of this study was to examine long-term trends in cancer mortality across the United States from 1968 to 2023 and to assess demographic and regional disparities in age-adjusted mortality rates using nationally representative data. Methodology : We conducted a retrospective analysis using the CDC WONDER database, which contains de-identified mortality and population data from the U.S. We included individuals aged 25 and older, recorded from 1968 to 2023, with cancer as the underlying cause of death. Cancer diagnoses were classified using International Classification of Disease (ICD) codes for malignant neoplasms. Results : Despite recent improvements, disparities persist across different strata, including gender (males vs. females), race (Black vs. White), age (older vs. younger adults), and geographic regions (Northeast vs. South), as highlighted in this novel study. These inequities emphasize the need for targeted interventions, equitable resource allocation, and comprehensive policy efforts to support vulnerable and underserved populations. Conclusion : Through our in-depth CDC study, we aim to guide future public health initiatives and enhance efforts for better cancer care and prevention by highlighting both historical and recent trends in cancer-related deaths. Cancer mortality Age-adjusted mortality rate Temporal trends Epidemiology CDC WONDER United States Disparities Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Cancer is a leading cause of death in the United States and the second most common cause of death worldwide, driven by genetic, environmental, and behavioral factors. The interplay of these elements highlights the need for comprehensive prevention and intervention strategies ( 1 ). Over the past 50 years, advancements in prevention (e.g., tobacco control, HPV vaccination), early detection (e.g., mammography, colonoscopy), and treatment (e.g., immunotherapy) have reshaped mortality trends ( 2 ). Despite these advancements, disparities in cancer mortality persist across demographic and geographic lines. Socioeconomic status, access to healthcare, and racial disparities continue to influence cancer outcomes, yet the full extent of these differences remains incompletely understood ( 3 )( 4 ). Cancer incidence refers to the number of new cases within a population over a set time period, influenced by risk factors, susceptibility, and screening practices. Cancer mortality is shaped by its incidence, biological factors, tumor stage, and treatment response. This study provides a comprehensive overview of CDC mortality data from 1968 to 2023, examining trends in total cancer mortality among individuals aged 25 years and older across multiple demographic strata: gender, race, age groups, and census regions. Our study underscores the critical need for continued efforts to address disparities in cancer mortality, particularly among marginalized populations. By shedding light on the historical and contemporary trends in cancer-related deaths, we hope to inform future public health strategies and enhance efforts toward equitable cancer care and prevention. METHODS We performed a retrospective analysis utilizing the publicly available CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database, which compiles de-identified mortality and population statistics across the United States. All individuals aged 25 years and above, recorded between 1968 and 2023, with any cancer listed as the underlying cause of death were included. Cancer diagnoses were classified via International Classification of Diseases (ICD) codes (Supplementary Table 1), which correspond to malignant neoplasms. Age-adjusted mortality rates (AAMRs) were calculated per million individuals per year, standardized to the 2000 US Standard Population. Joinpoint regression models were employed to estimate changes over time. Annual percentage changes (APCs) and average annual percentage changes (AAPCs) were derived with associated 95% confidence intervals (CIs). Asterisks (*) indicate statistical significance (p < 0.05), and p-values < 0.000001 are reported precisely as given. We further stratified the mortality data by sex (male, female), race (Black or African American, White), age groups [young adults (25–44), middle-aged adults (45–64), old adults (≥ 65)], and Census region (Northeast, Midwest, South, West). Because CDC WONDER data are publicly available and do not contain personally identifiable information, institutional review board approval was not required. The data were further analyzed at the state level, with average AAMRs reported for each region. This state-level analysis provided a deeper understanding of regional disparities in HF mortality. Given the publicly available, de-identified nature of the CDC WONDER database, no institutional review board (IRB) approval was required for this study. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure transparency and rigor in reporting observational research. RESULTS Overall Trends Between 1968 and 2023, 27,876,533 deaths attributed to cancer were recorded among U.S. adults aged 25 years and above. The overall age-adjusted mortality rate (AAMR) began at 3034.59 per million (95% CI 3023.49–3045.68) in 1968 and declined to 2178.61 per million (95% CI 2173.07–2184.16) by 2023 (Fig. 1 ). The highest documented AAMR was 3319.58 per million (95% CI 3310.32–3328.85) in 1990, and the lowest documented AAMR was 2215.64 per million (95% CI 2209.94–2221.34). When examined in discrete intervals, the average AAMR was 3072.99 per million (95% CI 3069.83–3076.15) between 1968 and 1978, 3226.03 per million (95% CI 3223.97–3228.08) from 1978 to 1998, 2623.37 per million (95% CI 2621.91–2624.83) from 1999 to 2020, and 2205.23 per million (95% CI 2201.98–2208.49) from 2021 to 2023. Table 1 presents age-adjusted mortality rates across these discrete time periods, further stratified by sex, race and age group. Additional descriptive data, including annual death counts and subgroup-specific AAMRs (by sex, race, age, region, and state), are presented in Supplementary Tables 2–7. Joinpoint analysis revealed a decreasing trend in the last five decades, with an average annual percentage change (AAPC) of − 0.5779% (95% CI − 0.5939 to − 0.5584; p < 0.000001). Detailed joinpoint regression outputs are provided in Supplementary Table 8. Table 1 Age-adjusted Mortality Rates (AAMRs) per million population with 95% confidence intervals, stratified by sex, race and age group across four time periods Variable 1968–1978 (per million, 95% CI) 1979–1998 (per million, 95% CI) 1999–2020 (per million, 95% CI) 2021–2023 (per million, 95% CI) Overall 3072.99 (3069.83–3076.15) 3226.03 (3223.97–3228.08) 2623.37 (2621.91–2624.83) 2205.23 (2201.98–2208.49) Men 3914.30 (3908.67–3919.94) 4164.51 (4160.78–4168.25) 3174.24 (3171.78–3176.71) 2584.94 (2579.64–2590.24) Women 2495.31 (2491.55–2499.07) 2630.05 (2627.60–2632.49) 2235.98 (2234.17–2237.78) 1924.98 (1920.84–1929.13) Blacks / African Americans 3559.19 (3547.54–3570.84) 4093.77 (4085.88–4101.66) 3082.27 (3077.12–3087.43) 2455.60 (2444.85–2466.34) Whites 3032.26 (3028.96–3035.56) 3166.74 (3164.59–3168.89) 2623.46 (2621.88–2625.03) 2248.03 (2244.40–2251.67) Young Adults (25–44) 373.69 (372.00–375.39) 290.93 (290.03–291.83) 207.15 (206.48–207.82) 175.43 (173.80–177.07) Middle-aged Adults (45–64) 2776.13 (2771.46–2780.79) 2651.73 (2648.54–2654.91) 1851.30 (1849.30–1853.30) 1474.21 (1469.61–1478.81) Old Adults (≥ 65) 9963.27 (9949.91–9976.63) 11160.18 (11151.56–11168.79) 9680.82 (9674.43–9687.20) 8278.85 (8264.82–8292.88) Gender-Specific Trends Over five decades (1968–2023), 14,729,890 cancer-related deaths were recorded among males and 13,146,643 among females. In males, the AAMR declined from 3762.58 per million (95% CI 3243.34–3781.82) in 1968 to 2541.77 per million (95% CI 2579.64–2590.24) in 2023. In females, rates declined from 2504.66 per million (95% CI 2491.29–2518.03) in 1968 to 1906.64 per million (95% CI 1899.56–1913.71) in 2023. Figure 1 shows age-adjusted mortality rates for both males and females between 1968 and 2023. Examined by time intervals, the average AAMR for females and males, respectively, was 2495.31 per million (95% CI 2491.55–2499.07) vs. 3914.3 per million (95% CI 3908.67–3919.94) from 1968 to 1978; 2630.05 per million (95% CI 2627.6–2632.49) vs. 4164.51 per million (95% CI 4160.78–4168.25) from 1979 to 1998; 2235.98 per million (95% CI 2234.17–2237.78) vs. 3174.24 per million (95% CI 3171.78–3176.71) from 1999 to 2020; and 1924.98 per million (95% CI 1920.84–1929.13) vs. 2584.94 per million (95% CI 2579.64–2590.24) from 2021 to 2023. Joinpoint analysis confirmed downward trends for both sexes, yielding an AAPC of − 0.6969% (95% CI − 0.7148 to − 0.6761; p < 0.000001) in males and − 0.4875% (95% CI − 0.5109 to − 0.464; p < 0.000001) in females. Race-Specific Trends When segregated by race, Whites accounted for 24,161,144 cancer deaths, whereas Black or African Americans accounted for 3,116,758. In 1968, Black or African Americans had an AAMR of 3407.91 per million (95% CI 3367.14–3448.67), decreasing to 2410.98 per million (95% CI 2392.78–2429.19) by 2023. Whites saw a drop from 3001.18 per million (95% CI 2989.61–3012.76) in 1968 to 2225.87 per million (95% CI 2219.66–2232.08) in 2023 (Fig. 2 ). Between 1968 and 1978, the average AAMRs were 3559.19 per million (95% CI 3547.54–3570.84) in Black populations and 3032.26 per million (95% CI 3028.96–3035.56) in Whites; between 1979 and 1998, 4093.77 per million (95% CI 4085.88–4101.66) in Blacks vs. 3166.74 per million (95% CI 3164.59–3168.89) in Whites; from 1999 to 2020, 3082.27 per million (95% CI 3077.12–3087.43) vs. 2623.46 per million (95% CI 2621.88–2625.03), respectively; and from 2021 to 2023, 2455.6 per million (95% CI 2444.85–2466.34) vs. 2248.03 per million (95% CI 2244.4–2251.67). Both groups demonstrated declining trends, with AAPCs of − 0.6105% (95% CI − 0.6462 to − 0.5754; p < 0.000001) for Blacks and − 0.5180% (95% CI − 0.5358 to − 0.4971; p < 0.000001) for Whites. Age-Specific Trends Analysis by age groups (25–44, 45–64, ≥ 65) indicated that the most deaths (19,043,159) occurred among individuals aged ≥ 65, followed by 7,823,869 among those aged 45–64, and 1,009,505 among those aged 25–44. From 1968 to 1978, average AAMRs were 373.69 per million (95% CI 372–375.39) at ages 25–44, 2776.13 per million (95% CI 2771.46–2780.79) at ages 45–64, and 9963.27 per million (95% CI 9949.91–9976.63) in those aged ≥ 65. Between 1979 and 1998, these values shifted to 290.93 per million (95% CI 290.03–291.83), 2651.73 per million (95% CI 2648.54–2654.91), and 11160.18 per million (95% CI 11151.56–11168.79), respectively. From 1999 to 2020, the average AAMR was 207.15 per million (95% CI 206.48–207.82) in 25–44-year-olds, 1851.3 per million (95% CI 1849.3–1853.3) for 45–64-year-olds, and 9680.82 per million (95% CI 9674.43–9687.2) for those 65 years and older. Figure 3 shows age-adjusted mortality rates across age groups (25–44, 45–64 and ≥ 65 years) between 1968 and 2023. Between 2021 and 2023, these figures were 175.43 per million (95% CI 173.8–177.07), 1474.21 per million (95% CI 1469.61–1478.81), and 8278.85 per million (95% CI 8264.82–8292.88), respectively. Joinpoint analysis indicated significant declines in all age groups, with AAPCs of − 1.6094% (95% CI − 1.6433 to − 1.5741; p < 0.000001) for ages 25–44, − 1.1679% (95% CI − 1.1869 to − 1.1491; p < 0.000001) for 45–64, and − 0.2791% (95% CI − 0.304 to − 0.2512; p < 0.000001) for ages ≥ 65. Regional Trends (Northeast, Midwest, South, West) Regionally, the South had the largest number of cancer deaths (9,939,398), followed by the Midwest (6,825,079), Northeast (6,003,495), and West (5,108,561). Figure 4 illustrates the long-term regional trends in age-adjusted mortality rates across the four United States census regions. Between 1968 and 1978, average AAMRs were 3305.75 per million (95% CI 3299.19–3312.32) in the Northeast, 3080.29 per million (95% CI 3074.29–3086.29) in the Midwest, 2962.12 per million (95% CI 2956.52–2967.72) in the South, and 2921.02 per million (95% CI 2913.37–2928.66) in the West. From 1979 to 1998, rates climbed to 3351.14 per million (95% CI 3346.71–3355.57) in the Northeast, 3240.08 per million (95% CI 3235.98–3244.19) in the Midwest, 3253.24 per million (95% CI 3249.71–3256.78) in the South, and 3012.5 per million (95% CI 3007.9–3017.1) in the West. Between 1999 and 2020, the AAMRs were 2605.45 per million (95% CI 2602.16–2608.75), 2742.46 per million (95% CI 2739.31–2745.62), 2698.81 per million (95% CI 2696.37–2701.26), and 2386.5 per million (95% CI 2383.5–2389.5) for the Northeast, Midwest, South, and West, respectively. In 2021–2023, these rates decreased further to 2055.82 per million (95% CI 2048.49–2063.15) in the Northeast, 2344.89 per million (95% CI 2337.56–2352.21) in the Midwest, 2296.92 per million (95% CI 2291.54–2302.31) in the South, and 2040.14 per million (95% CI 2033.55–2046.73) in the West. The spatial distribution of cancer mortality by state is further illustrated in Fig. 5 , highlighting regional variation in AAMRs across the United States. All regions demonstrated downward trajectories, with the strongest average annual percentage change in the Northeast (–0.8818%; 95% CI − 0.9001 to − 0.8636; p < 0.000001), followed by the West (–0.6344%; 95% CI − 0.6605 to − 0.6053; p < 0.000001), Midwest (–0.4931%; 95% CI − 0.5085 to − 0.4763; p < 0.000001), and South (–0.4068%; 95% CI − 0.4279 to − 0.3834; p < 0.000001). To provide an integrated overview of the temporal and demographic shifts in cancer mortality, a central illustration (Fig. 6 ) summarizes trends across sex, race, age, and geographic regions between 1968 and 2023. DISCUSSION The findings from this comprehensive CDC WONDER analysis of US cancer mortality from 1968 to 2023 highlight several key trends. First, while cancer remains a significant public health challenge, leading to more than 27 million recorded deaths in the U.S. in the last five decades, age-adjusted mortality rates have shown a sustained decline over time ( 5 )( 6 ). This reduction is consistent with broader epidemiological research attributing mortality decreases to improvements in cancer prevention (e.g., reductions in smoking, increased awareness of physical health), early detection (e.g., screening programs for breast, cervical, and colorectal cancers), and advancements in therapeutic options, including targeted therapies and immunotherapies ( 7 , 8 ). Despite this, the magnitude of decrease varies across demographic subgroups, emphasizing persistent inequities. Strikingly, the male population exhibited higher mortality rates but also demonstrated a faster rate of decline (AAPC − 0.6969%) than females (AAPC − 0.4875%) ( 9 ). Previous studies have noted differences in risk exposure (e.g., higher historical smoking rates in males), genetic predispositions, and health-seeking behaviors that could affect incidence and survivorship patterns ( 10 ). Similarly, race-specific data reveal that Black or African American populations have historically had higher AAMRs, peaking around the late 20th century, which might reflect disparate access to preventive care, later-stage diagnoses, delays in treatment and a disproportionate burden of risk factors (e.g., hypertension, obesity) ( 11 – 13 ). The recent convergence between Black and White mortality rates, while still elevated among the Black population, indicates some progress in addressing these disparities, although ongoing attention to social determinants of health remains crucial ( 14 , 15 ). Age segmentation sheds light on the most profound mortality burden in older adults (≥ 65), a finding in line with the fact that cancer incidence and severity typically intensify with advancing age. However, smaller but faster declines in cancer mortality were observed in the youngest group (25–44) (AAPC − 1.6094%), possibly reflecting earlier interventions, HPV vaccination campaigns for cervical cancer prevention, and robust public health messages on lifestyle modification ( 16 ). The moderate decline among middle-aged adults (45–64) underscores the potential influence of extended screening coverage (e.g., mammography, colonoscopy) and improved therapeutic regimens ( 17 ). Nonetheless, the persistently high absolute number of deaths in older cohorts points to the multifaceted nature of geriatric oncology and the necessity of tailored interventions for comorbidity management and supportive care ( 4 ). Regional variations indicate that the Northeast region demonstrated the greatest reduction (AAPC − 0.8818%), which may correlate with earlier adoption of public health policies (e.g., anti-smoking measures), high coverage of screening programs, and broader access to specialized oncology centers ( 18 ). Conversely, the South has experienced a slower decline (AAPC − 0.4068%), which is consistent with historical patterns of higher tobacco use, lower rates of insurance coverage, and rural healthcare access challenges ( 19 , 20 ). These geographic disparities underscore the importance of localized interventions and continued policy efforts aimed at reducing modifiable risk factors, expanding Medicaid in underserved regions, and bridging gaps in healthcare infrastructure. Overall, while the national-level downward trend in cancer mortality is encouraging, the demographic and regional differences reveal complex underpinnings that require sustained, multifaceted strategies. Continued improvements in risk factor reduction (especially addressing obesity, physical inactivity, and tobacco use), early detection initiatives, and equitable access to cutting-edge treatments are crucial. The integration of personalized medicine, clinical trial expansion, and community-based health promotion may further accelerate the downward trend in mortality and foster more uniform benefits across all population subgroups ( 21 ). LIMITATION Several methodological and practical limitations should be noted. First, the reliance on death certificates is subject to potential misclassification errors regarding underlying cause of death. Additionally, changes in ICD coding practices and evolving diagnostic criteria over five decades may affect data comparability. Second, while CDC WONDER covers the entire United States, local-level variations and critical nuances may remain concealed in these broad analyses. Third, although the analysis incorporates demographic stratifications by age, race, region, and gender, other socioeconomic determinants, such as income, education, or insurance status, could provide further explanatory power but remain unaccounted for in this dataset. Finally, the analysis cannot definitively infer causality behind the observed trends, as complex interactions among prevention measures, healthcare system changes, and population-level behaviors likely contributed to the decreasing mortality rates. CONCLUSION In conclusion, over 55 years of CDC mortality data reveal a substantial burden of cancer, with more than 27 million deaths in the United States adult population aged 25 years and older. Nevertheless, the longitudinal data highlight a pronounced decline in age-adjusted mortality rates, suggesting that advancements in cancer prevention, screening, and treatment have collectively contributed to reduced cancer-related deaths. Despite these gains, marked disparities persist across gender, race, age groups, and geographic regions, underlining the need for ongoing targeted interventions, resource distribution, and policy efforts aimed at vulnerable and underserved populations. Strengthening early detection, promoting lifestyle modifications, ensuring equitable access to state-of-the-art therapies, and expanding public health initiatives will be essential in further reducing the cancer burden and improving outcomes for millions of Americans in the coming decades. Declarations Conflict of Interest Disclosure: The authors declare no conflicts of interest related to this work. All authors have reviewed and approved the final manuscript. Ethics Approval Statement: This study used de-identified, publicly available mortality data from the CDC WONDER database. As no human subjects or identifiable data were involved, institutional review board approval was not required. Patient Consent Statement Not applicable. Informed consent was waived because the study used de-identified, publicly available data. Permission to Reproduce Material from Other Sources Not applicable. No third-party material was reproduced. Clinical Trial Registration Not applicable. Funding Statement: This research did not receive any grants from funding agencies in the public, commercial or not-for-profit sectors. Author Contribution Conceptualization: Faizan Ahmed (F.Ah.), Husnain Ahmed (H.A.)Methodology: F.Ah., H.A., Fenilkumar Kotadiya (F.K.)Data Curation: Haris Bin Tahir (H.B.T.), Ramsha Ali (R.A.), Najam Gohar (N.G.)Formal Analysis: H.B.T., R.A., N.G.Investigation: Kainat Aman (K.A.), Mohamed Bakr (M.B.), Swapnil Patel (S.P.)Resources: F.Ah.Visualization: Mohammad Amir Hossain (M.A.H.), F.K.Writing – Original Draft: F.Ah., H.B.T., K.A., M.B., S.P., M.A.H.Writing – Review & Editing: Fawaz Alenezi (F.Al.), all authorsSupervision: F.K.Project Administration: F.Ah. 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14:46:37","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81684,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/08b6c4ab0e0126589d2525b9.html"},{"id":95307297,"identity":"53df3285-0ff8-430e-8f38-c6c1449d0cd1","added_by":"auto","created_at":"2025-11-06 14:46:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":229533,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverall and Sex-Stratified Age-Adjusted Mortality Rates per Million Due to Cancers among Adults in the United States from 1968-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/4d6379868c7060e6ee164beb.png"},{"id":95307300,"identity":"723694cc-1b37-4952-93df-4700a5d0c725","added_by":"auto","created_at":"2025-11-06 14:46:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":185773,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRace Stratified Age-Adjusted Mortality Rates per Million Due to Cancers among Adults in the United States from 1968-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/5d586970e1761b2ddc9cc74c.png"},{"id":95307298,"identity":"75326156-c3c5-4519-a606-4b7a9db89956","added_by":"auto","created_at":"2025-11-06 14:46:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":221377,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAge-Adjusted Mortality Rates per Million by Age Groups Due to Cancers among Adults in the United States from 1968-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/a29a487dcde256faba2290f5.png"},{"id":95307303,"identity":"71474199-3de8-480b-bec6-dacaa7fc50f7","added_by":"auto","created_at":"2025-11-06 14:46:36","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":236184,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAge-Adjusted Mortality Rates per Million by Census Regions Due to Cancers among Adults in the United States from 1968-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/8f970ac301f7127867fd9ca8.png"},{"id":95307304,"identity":"51ac39f0-2c6f-4bc7-9cab-ba75170a7306","added_by":"auto","created_at":"2025-11-06 14:46:36","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":320835,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAge-Adjusted Mortality Rates per Million by State Due to Cancers among Adults in the United States from 1968-2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/db66ff50fb14aa7177806c74.jpeg"},{"id":95307306,"identity":"2f30dd6b-6b57-4d4b-9aad-df56901d6455","added_by":"auto","created_at":"2025-11-06 14:46:36","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":769943,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCentral Illustration of Cancer Mortality among U.S. adults from 1968 to 2023\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/99e16e6376303cb098bb8b33.png"},{"id":100356090,"identity":"dddb7da2-064f-4a28-adc0-304cd673d05d","added_by":"auto","created_at":"2026-01-16 06:51:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2412232,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/8ff16c38-3238-4bc0-b08f-2d71ff2c5475.pdf"},{"id":95314030,"identity":"80925db6-c290-47d3-968a-a24760677e1b","added_by":"auto","created_at":"2025-11-06 15:52:23","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":60768,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialCancerMortality.docx","url":"https://assets-eu.researchsquare.com/files/rs-7755712/v1/714f73ab4f6a257dd18500aa.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Arc of Cancer Mortality: Half a Century of U.S. Data from the CDC WONDER Database","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCancer is a leading cause of death in the United States and the second most common cause of death worldwide, driven by genetic, environmental, and behavioral factors. The interplay of these elements highlights the need for comprehensive prevention and intervention strategies (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Over the past 50 years, advancements in prevention (e.g., tobacco control, HPV vaccination), early detection (e.g., mammography, colonoscopy), and treatment (e.g., immunotherapy) have reshaped mortality trends (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Despite these advancements, disparities in cancer mortality persist across demographic and geographic lines. Socioeconomic status, access to healthcare, and racial disparities continue to influence cancer outcomes, yet the full extent of these differences remains incompletely understood (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCancer incidence refers to the number of new cases within a population over a set time period, influenced by risk factors, susceptibility, and screening practices. Cancer mortality is shaped by its incidence, biological factors, tumor stage, and treatment response. This study provides a comprehensive overview of CDC mortality data from 1968 to 2023, examining trends in total cancer mortality among individuals aged 25 years and older across multiple demographic strata: gender, race, age groups, and census regions. Our study underscores the critical need for continued efforts to address disparities in cancer mortality, particularly among marginalized populations. By shedding light on the historical and contemporary trends in cancer-related deaths, we hope to inform future public health strategies and enhance efforts toward equitable cancer care and prevention.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eWe performed a retrospective analysis utilizing the publicly available CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database, which compiles de-identified mortality and population statistics across the United States. All individuals aged 25 years and above, recorded between 1968 and 2023, with any cancer listed as the underlying cause of death were included. Cancer diagnoses were classified via International Classification of Diseases (ICD) codes (Supplementary Table\u0026nbsp;1), which correspond to malignant neoplasms. Age-adjusted mortality rates (AAMRs) were calculated per million individuals per year, standardized to the 2000 US Standard Population.\u003c/p\u003e\u003cp\u003eJoinpoint regression models were employed to estimate changes over time. Annual percentage changes (APCs) and average annual percentage changes (AAPCs) were derived with associated 95% confidence intervals (CIs). Asterisks (*) indicate statistical significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.000001 are reported precisely as given. We further stratified the mortality data by sex (male, female), race (Black or African American, White), age groups [young adults (25\u0026ndash;44), middle-aged adults (45\u0026ndash;64), old adults (\u0026ge;\u0026thinsp;65)], and Census region (Northeast, Midwest, South, West). Because CDC WONDER data are publicly available and do not contain personally identifiable information, institutional review board approval was not required.\u003c/p\u003e\u003cp\u003eThe data were further analyzed at the state level, with average AAMRs reported for each region. This state-level analysis provided a deeper understanding of regional disparities in HF mortality. Given the publicly available, de-identified nature of the CDC WONDER database, no institutional review board (IRB) approval was required for this study. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure transparency and rigor in reporting observational research.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eOverall Trends\u003c/h2\u003e\u003cp\u003eBetween 1968 and 2023, 27,876,533 deaths attributed to cancer were recorded among U.S. adults aged 25 years and above. The overall age-adjusted mortality rate (AAMR) began at 3034.59 per million (95% CI 3023.49\u0026ndash;3045.68) in 1968 and declined to 2178.61 per million (95% CI 2173.07\u0026ndash;2184.16) by 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The highest documented AAMR was 3319.58 per million (95% CI 3310.32\u0026ndash;3328.85) in 1990, and the lowest documented AAMR was 2215.64 per million (95% CI 2209.94\u0026ndash;2221.34). When examined in discrete intervals, the average AAMR was 3072.99 per million (95% CI 3069.83\u0026ndash;3076.15) between 1968 and 1978, 3226.03 per million (95% CI 3223.97\u0026ndash;3228.08) from 1978 to 1998, 2623.37 per million (95% CI 2621.91\u0026ndash;2624.83) from 1999 to 2020, and 2205.23 per million (95% CI 2201.98\u0026ndash;2208.49) from 2021 to 2023. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents age-adjusted mortality rates across these discrete time periods, further stratified by sex, race and age group. Additional descriptive data, including annual death counts and subgroup-specific AAMRs (by sex, race, age, region, and state), are presented in Supplementary Tables\u0026nbsp;2\u0026ndash;7. Joinpoint analysis revealed a decreasing trend in the last five decades, with an average annual percentage change (AAPC) of \u0026minus;\u0026thinsp;0.5779% (95% CI \u0026minus;\u0026thinsp;0.5939 to \u0026minus;\u0026thinsp;0.5584; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001). Detailed joinpoint regression outputs are provided in Supplementary Table\u0026nbsp;8.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAge-adjusted Mortality Rates (AAMRs) per million population with 95% confidence intervals, stratified by sex, race and age group across four time periods\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1968\u0026ndash;1978 (per million, 95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1979\u0026ndash;1998 (per million, 95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1999\u0026ndash;2020 (per million, 95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2021\u0026ndash;2023 (per million, 95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3072.99 (3069.83\u0026ndash;3076.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3226.03 (3223.97\u0026ndash;3228.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2623.37 (2621.91\u0026ndash;2624.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2205.23 (2201.98\u0026ndash;2208.49)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMen\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3914.30 (3908.67\u0026ndash;3919.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4164.51 (4160.78\u0026ndash;4168.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3174.24 (3171.78\u0026ndash;3176.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2584.94 (2579.64\u0026ndash;2590.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWomen\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2495.31 (2491.55\u0026ndash;2499.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2630.05 (2627.60\u0026ndash;2632.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2235.98 (2234.17\u0026ndash;2237.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1924.98 (1920.84\u0026ndash;1929.13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBlacks / African Americans\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3559.19 (3547.54\u0026ndash;3570.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4093.77 (4085.88\u0026ndash;4101.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3082.27 (3077.12\u0026ndash;3087.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2455.60 (2444.85\u0026ndash;2466.34)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWhites\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3032.26 (3028.96\u0026ndash;3035.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3166.74 (3164.59\u0026ndash;3168.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2623.46 (2621.88\u0026ndash;2625.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2248.03 (2244.40\u0026ndash;2251.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eYoung Adults (25\u0026ndash;44)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e373.69 (372.00\u0026ndash;375.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e290.93 (290.03\u0026ndash;291.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e207.15 (206.48\u0026ndash;207.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e175.43 (173.80\u0026ndash;177.07)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMiddle-aged Adults (45\u0026ndash;64)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2776.13 (2771.46\u0026ndash;2780.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2651.73 (2648.54\u0026ndash;2654.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1851.30 (1849.30\u0026ndash;1853.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1474.21 (1469.61\u0026ndash;1478.81)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOld Adults (\u0026ge;\u0026thinsp;65)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9963.27 (9949.91\u0026ndash;9976.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11160.18 (11151.56\u0026ndash;11168.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9680.82 (9674.43\u0026ndash;9687.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8278.85 (8264.82\u0026ndash;8292.88)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eGender-Specific Trends\u003c/h3\u003e\n\u003cp\u003eOver five decades (1968\u0026ndash;2023), 14,729,890 cancer-related deaths were recorded among males and 13,146,643 among females. In males, the AAMR declined from 3762.58 per million (95% CI 3243.34\u0026ndash;3781.82) in 1968 to 2541.77 per million (95% CI 2579.64\u0026ndash;2590.24) in 2023. In females, rates declined from 2504.66 per million (95% CI 2491.29\u0026ndash;2518.03) in 1968 to 1906.64 per million (95% CI 1899.56\u0026ndash;1913.71) in 2023. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows age-adjusted mortality rates for both males and females between 1968 and 2023. Examined by time intervals, the average AAMR for females and males, respectively, was 2495.31 per million (95% CI 2491.55\u0026ndash;2499.07) vs. 3914.3 per million (95% CI 3908.67\u0026ndash;3919.94) from 1968 to 1978; 2630.05 per million (95% CI 2627.6\u0026ndash;2632.49) vs. 4164.51 per million (95% CI 4160.78\u0026ndash;4168.25) from 1979 to 1998; 2235.98 per million (95% CI 2234.17\u0026ndash;2237.78) vs. 3174.24 per million (95% CI 3171.78\u0026ndash;3176.71) from 1999 to 2020; and 1924.98 per million (95% CI 1920.84\u0026ndash;1929.13) vs. 2584.94 per million (95% CI 2579.64\u0026ndash;2590.24) from 2021 to 2023. Joinpoint analysis confirmed downward trends for both sexes, yielding an AAPC of \u0026minus;\u0026thinsp;0.6969% (95% CI \u0026minus;\u0026thinsp;0.7148 to \u0026minus;\u0026thinsp;0.6761; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) in males and \u0026minus;\u0026thinsp;0.4875% (95% CI \u0026minus;\u0026thinsp;0.5109 to \u0026minus;\u0026thinsp;0.464; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) in females.\u003c/p\u003e\n\u003ch3\u003eRace-Specific Trends\u003c/h3\u003e\n\u003cp\u003eWhen segregated by race, Whites accounted for 24,161,144 cancer deaths, whereas Black or African Americans accounted for 3,116,758. In 1968, Black or African Americans had an AAMR of 3407.91 per million (95% CI 3367.14\u0026ndash;3448.67), decreasing to 2410.98 per million (95% CI 2392.78\u0026ndash;2429.19) by 2023. Whites saw a drop from 3001.18 per million (95% CI 2989.61\u0026ndash;3012.76) in 1968 to 2225.87 per million (95% CI 2219.66\u0026ndash;2232.08) in 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Between 1968 and 1978, the average AAMRs were 3559.19 per million (95% CI 3547.54\u0026ndash;3570.84) in Black populations and 3032.26 per million (95% CI 3028.96\u0026ndash;3035.56) in Whites; between 1979 and 1998, 4093.77 per million (95% CI 4085.88\u0026ndash;4101.66) in Blacks vs. 3166.74 per million (95% CI 3164.59\u0026ndash;3168.89) in Whites; from 1999 to 2020, 3082.27 per million (95% CI 3077.12\u0026ndash;3087.43) vs. 2623.46 per million (95% CI 2621.88\u0026ndash;2625.03), respectively; and from 2021 to 2023, 2455.6 per million (95% CI 2444.85\u0026ndash;2466.34) vs. 2248.03 per million (95% CI 2244.4\u0026ndash;2251.67). Both groups demonstrated declining trends, with AAPCs of \u0026minus;\u0026thinsp;0.6105% (95% CI \u0026minus;\u0026thinsp;0.6462 to \u0026minus;\u0026thinsp;0.5754; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) for Blacks and \u0026minus;\u0026thinsp;0.5180% (95% CI \u0026minus;\u0026thinsp;0.5358 to \u0026minus;\u0026thinsp;0.4971; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) for Whites.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eAge-Specific Trends\u003c/h3\u003e\n\u003cp\u003eAnalysis by age groups (25\u0026ndash;44, 45\u0026ndash;64, \u0026ge;\u0026thinsp;65) indicated that the most deaths (19,043,159) occurred among individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;65, followed by 7,823,869 among those aged 45\u0026ndash;64, and 1,009,505 among those aged 25\u0026ndash;44. From 1968 to 1978, average AAMRs were 373.69 per million (95% CI 372\u0026ndash;375.39) at ages 25\u0026ndash;44, 2776.13 per million (95% CI 2771.46\u0026ndash;2780.79) at ages 45\u0026ndash;64, and 9963.27 per million (95% CI 9949.91\u0026ndash;9976.63) in those aged\u0026thinsp;\u0026ge;\u0026thinsp;65. Between 1979 and 1998, these values shifted to 290.93 per million (95% CI 290.03\u0026ndash;291.83), 2651.73 per million (95% CI 2648.54\u0026ndash;2654.91), and 11160.18 per million (95% CI 11151.56\u0026ndash;11168.79), respectively. From 1999 to 2020, the average AAMR was 207.15 per million (95% CI 206.48\u0026ndash;207.82) in 25\u0026ndash;44-year-olds, 1851.3 per million (95% CI 1849.3\u0026ndash;1853.3) for 45\u0026ndash;64-year-olds, and 9680.82 per million (95% CI 9674.43\u0026ndash;9687.2) for those 65 years and older. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows age-adjusted mortality rates across age groups (25\u0026ndash;44, 45\u0026ndash;64 and \u0026ge;\u0026thinsp;65 years) between 1968 and 2023. Between 2021 and 2023, these figures were 175.43 per million (95% CI 173.8\u0026ndash;177.07), 1474.21 per million (95% CI 1469.61\u0026ndash;1478.81), and 8278.85 per million (95% CI 8264.82\u0026ndash;8292.88), respectively. Joinpoint analysis indicated significant declines in all age groups, with AAPCs of \u0026minus;\u0026thinsp;1.6094% (95% CI \u0026minus;\u0026thinsp;1.6433 to \u0026minus;\u0026thinsp;1.5741; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) for ages 25\u0026ndash;44, \u0026minus;\u0026thinsp;1.1679% (95% CI \u0026minus;\u0026thinsp;1.1869 to \u0026minus;\u0026thinsp;1.1491; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) for 45\u0026ndash;64, and \u0026minus;\u0026thinsp;0.2791% (95% CI \u0026minus;\u0026thinsp;0.304 to \u0026minus;\u0026thinsp;0.2512; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) for ages\u0026thinsp;\u0026ge;\u0026thinsp;65.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eRegional Trends (Northeast, Midwest, South, West)\u003c/h2\u003e\u003cp\u003eRegionally, the South had the largest number of cancer deaths (9,939,398), followed by the Midwest (6,825,079), Northeast (6,003,495), and West (5,108,561). Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e illustrates the long-term regional trends in age-adjusted mortality rates across the four United States census regions. Between 1968 and 1978, average AAMRs were 3305.75 per million (95% CI 3299.19\u0026ndash;3312.32) in the Northeast, 3080.29 per million (95% CI 3074.29\u0026ndash;3086.29) in the Midwest, 2962.12 per million (95% CI 2956.52\u0026ndash;2967.72) in the South, and 2921.02 per million (95% CI 2913.37\u0026ndash;2928.66) in the West.\u003c/p\u003e\u003cp\u003eFrom 1979 to 1998, rates climbed to 3351.14 per million (95% CI 3346.71\u0026ndash;3355.57) in the Northeast, 3240.08 per million (95% CI 3235.98\u0026ndash;3244.19) in the Midwest, 3253.24 per million (95% CI 3249.71\u0026ndash;3256.78) in the South, and 3012.5 per million (95% CI 3007.9\u0026ndash;3017.1) in the West. Between 1999 and 2020, the AAMRs were 2605.45 per million (95% CI 2602.16\u0026ndash;2608.75), 2742.46 per million (95% CI 2739.31\u0026ndash;2745.62), 2698.81 per million (95% CI 2696.37\u0026ndash;2701.26), and 2386.5 per million (95% CI 2383.5\u0026ndash;2389.5) for the Northeast, Midwest, South, and West, respectively. In 2021\u0026ndash;2023, these rates decreased further to 2055.82 per million (95% CI 2048.49\u0026ndash;2063.15) in the Northeast, 2344.89 per million (95% CI 2337.56\u0026ndash;2352.21) in the Midwest, 2296.92 per million (95% CI 2291.54\u0026ndash;2302.31) in the South, and 2040.14 per million (95% CI 2033.55\u0026ndash;2046.73) in the West.\u003c/p\u003e\u003cp\u003eThe spatial distribution of cancer mortality by state is further illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, highlighting regional variation in AAMRs across the United States. All regions demonstrated downward trajectories, with the strongest average annual percentage change in the Northeast (\u0026ndash;0.8818%; 95% CI \u0026minus;\u0026thinsp;0.9001 to \u0026minus;\u0026thinsp;0.8636; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), followed by the West (\u0026ndash;0.6344%; 95% CI \u0026minus;\u0026thinsp;0.6605 to \u0026minus;\u0026thinsp;0.6053; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), Midwest (\u0026ndash;0.4931%; 95% CI \u0026minus;\u0026thinsp;0.5085 to \u0026minus;\u0026thinsp;0.4763; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), and South (\u0026ndash;0.4068%; 95% CI \u0026minus;\u0026thinsp;0.4279 to \u0026minus;\u0026thinsp;0.3834; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001).\u003c/p\u003e\u003cp\u003eTo provide an integrated overview of the temporal and demographic shifts in cancer mortality, a central illustration (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e) summarizes trends across sex, race, age, and geographic regions between 1968 and 2023.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe findings from this comprehensive CDC WONDER analysis of US cancer mortality from 1968 to 2023 highlight several key trends. First, while cancer remains a significant public health challenge, leading to more than 27\u0026nbsp;million recorded deaths in the U.S. in the last five decades, age-adjusted mortality rates have shown a sustained decline over time (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This reduction is consistent with broader epidemiological research attributing mortality decreases to improvements in cancer prevention (e.g., reductions in smoking, increased awareness of physical health), early detection (e.g., screening programs for breast, cervical, and colorectal cancers), and advancements in therapeutic options, including targeted therapies and immunotherapies (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Despite this, the magnitude of decrease varies across demographic subgroups, emphasizing persistent inequities.\u003c/p\u003e\u003cp\u003eStrikingly, the male population exhibited higher mortality rates but also demonstrated a faster rate of decline (AAPC \u0026minus;\u0026thinsp;0.6969%) than females (AAPC \u0026minus;\u0026thinsp;0.4875%) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Previous studies have noted differences in risk exposure (e.g., higher historical smoking rates in males), genetic predispositions, and health-seeking behaviors that could affect incidence and survivorship patterns (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Similarly, race-specific data reveal that Black or African American populations have historically had higher AAMRs, peaking around the late 20th century, which might reflect disparate access to preventive care, later-stage diagnoses, delays in treatment and a disproportionate burden of risk factors (e.g., hypertension, obesity) (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The recent convergence between Black and White mortality rates, while still elevated among the Black population, indicates some progress in addressing these disparities, although ongoing attention to social determinants of health remains crucial (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAge segmentation sheds light on the most profound mortality burden in older adults (\u0026ge;\u0026thinsp;65), a finding in line with the fact that cancer incidence and severity typically intensify with advancing age. However, smaller but faster declines in cancer mortality were observed in the youngest group (25\u0026ndash;44) (AAPC \u0026minus;\u0026thinsp;1.6094%), possibly reflecting earlier interventions, HPV vaccination campaigns for cervical cancer prevention, and robust public health messages on lifestyle modification (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The moderate decline among middle-aged adults (45\u0026ndash;64) underscores the potential influence of extended screening coverage (e.g., mammography, colonoscopy) and improved therapeutic regimens (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Nonetheless, the persistently high absolute number of deaths in older cohorts points to the multifaceted nature of geriatric oncology and the necessity of tailored interventions for comorbidity management and supportive care (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eRegional variations indicate that the Northeast region demonstrated the greatest reduction (AAPC \u0026minus;\u0026thinsp;0.8818%), which may correlate with earlier adoption of public health policies (e.g., anti-smoking measures), high coverage of screening programs, and broader access to specialized oncology centers (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Conversely, the South has experienced a slower decline (AAPC \u0026minus;\u0026thinsp;0.4068%), which is consistent with historical patterns of higher tobacco use, lower rates of insurance coverage, and rural healthcare access challenges (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These geographic disparities underscore the importance of localized interventions and continued policy efforts aimed at reducing modifiable risk factors, expanding Medicaid in underserved regions, and bridging gaps in healthcare infrastructure.\u003c/p\u003e\u003cp\u003eOverall, while the national-level downward trend in cancer mortality is encouraging, the demographic and regional differences reveal complex underpinnings that require sustained, multifaceted strategies. Continued improvements in risk factor reduction (especially addressing obesity, physical inactivity, and tobacco use), early detection initiatives, and equitable access to cutting-edge treatments are crucial. The integration of personalized medicine, clinical trial expansion, and community-based health promotion may further accelerate the downward trend in mortality and foster more uniform benefits across all population subgroups (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e"},{"header":"LIMITATION","content":"\u003cp\u003eSeveral methodological and practical limitations should be noted. First, the reliance on death certificates is subject to potential misclassification errors regarding underlying cause of death. Additionally, changes in ICD coding practices and evolving diagnostic criteria over five decades may affect data comparability. Second, while CDC WONDER covers the entire United States, local-level variations and critical nuances may remain concealed in these broad analyses. Third, although the analysis incorporates demographic stratifications by age, race, region, and gender, other socioeconomic determinants, such as income, education, or insurance status, could provide further explanatory power but remain unaccounted for in this dataset. Finally, the analysis cannot definitively infer causality behind the observed trends, as complex interactions among prevention measures, healthcare system changes, and population-level behaviors likely contributed to the decreasing mortality rates.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn conclusion, over 55 years of CDC mortality data reveal a substantial burden of cancer, with more than 27\u0026nbsp;million deaths in the United States adult population aged 25 years and older. Nevertheless, the longitudinal data highlight a pronounced decline in age-adjusted mortality rates, suggesting that advancements in cancer prevention, screening, and treatment have collectively contributed to reduced cancer-related deaths. Despite these gains, marked disparities persist across gender, race, age groups, and geographic regions, underlining the need for ongoing targeted interventions, resource distribution, and policy efforts aimed at vulnerable and underserved populations. Strengthening early detection, promoting lifestyle modifications, ensuring equitable access to state-of-the-art therapies, and expanding public health initiatives will be essential in further reducing the cancer burden and improving outcomes for millions of Americans in the coming decades.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest Disclosure:\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflicts of interest related to this work. All authors have reviewed and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eEthics Approval\u0026nbsp;Statement:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThis study used de-identified, publicly available mortality data from the CDC WONDER database. As no human subjects or identifiable data were involved, institutional review board approval was not required.\u003c/p\u003e\n\u003ch2\u003ePatient Consent Statement\u003c/h2\u003e\n\u003cp\u003eNot applicable. Informed consent was waived because the study used de-identified, publicly available data.\u003c/p\u003e\n\u003ch2\u003ePermission to Reproduce Material from Other Sources\u003c/h2\u003e\n\u003cp\u003eNot applicable. No third-party material was reproduced.\u003c/p\u003e\n\u003ch2\u003eClinical Trial Registration\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eFunding Statement:\u003c/h2\u003e\n\u003cp\u003eThis research did not receive any grants from funding agencies in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eConceptualization: Faizan Ahmed (F.Ah.), Husnain Ahmed (H.A.)Methodology: F.Ah., H.A., Fenilkumar Kotadiya (F.K.)Data Curation: Haris Bin Tahir (H.B.T.), Ramsha Ali (R.A.), Najam Gohar (N.G.)Formal Analysis: H.B.T., R.A., N.G.Investigation: Kainat Aman (K.A.), Mohamed Bakr (M.B.), Swapnil Patel (S.P.)Resources: F.Ah.Visualization: Mohammad Amir Hossain (M.A.H.), F.K.Writing \u0026ndash; Original Draft: F.Ah., H.B.T., K.A., M.B., S.P., M.A.H.Writing \u0026ndash; Review \u0026amp; Editing: Fawaz Alenezi (F.Al.), all authorsSupervision: F.K.Project Administration: F.Ah.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eAll data used in this study are publicly available through the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. The authors obtained access in accordance with the CDC\u0026rsquo;s data use guidelines.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSiegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. \u003cem\u003eCA Cancer J Clin\u003c/em\u003e [Internet]. 2023 Jan [cited 2025 Apr 4];73(1):17\u0026ndash;48. Available from:\u0026nbsp;https://doi.org/10.3322/caac.21763\u003c/li\u003e\n \u003cli\u003eWingo PA, Cardinez CJ, Landis SH, Greenlee RT, Ries LAG, Anderson RN, et al. Long-term trends in cancer mortality in the United States, 1930\u0026ndash;1998. \u003cem\u003eCancer\u003c/em\u003e [Internet]. 2003 Jun 15 [cited 2025 Apr 4];97(S12):3133\u0026ndash;3275. Available from:\u0026nbsp;https://doi.org/10.1002/cncr.11380\u003c/li\u003e\n \u003cli\u003eKish JK, Yu M, Percy-Laurry A, Altekruse SF. 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Reporting recommendations for tumor marker prognostic studies (REMARK): an abridged explanation and elaboration. \u003cem\u003eJ Natl Cancer Inst\u003c/em\u003e. 2018 Aug 1;110(8):803\u0026ndash;811.\u003c/li\u003e\n \u003cli\u003eJemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson B, et al. Annual report to the nation on the status of cancer, 1975\u0026ndash;2014, featuring survival. \u003cem\u003eJ Natl Cancer Inst\u003c/em\u003e. 2017 Sep 1;109(9):djx030. doi:10.1093/jnci/djx030\u003c/li\u003e\n \u003cli\u003eEdwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LAG, et al. Annual report to the nation on the status of cancer, 1975\u0026ndash;2002, featuring population-based trends in cancer treatment. \u003cem\u003eJNCI J Natl Cancer Inst\u003c/em\u003e [Internet]. 2005 Oct 5 [cited 2025 Apr 4];97(19):1407\u0026ndash;1427. Available from:\u0026nbsp;https://doi.org/10.1093/jnci/dji278\u003c/li\u003e\n \u003cli\u003eFedewa SA, Ward EM, Stewart AK, Edge SB. Delays in adjuvant chemotherapy treatment among patients with breast cancer are more likely in African American and Hispanic populations: a national cohort study 2004\u0026ndash;2006. \u003cem\u003eJ Clin Oncol\u003c/em\u003e [Internet]. 2010 Sep 20 [cited 2025 Apr 4];28(27):4135\u0026ndash;4141. Available from:\u0026nbsp;https://doi.org/10.1200/JCO.2009.27.2427\u003c/li\u003e\n \u003cli\u003eHoskins PJ, Gotlieb WH. Missed therapeutic and prevention opportunities in women with BRCA-mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: a review of the literature. \u003cem\u003eCA Cancer J Clin\u003c/em\u003e. 2017 Nov;67(6):493\u0026ndash;506.\u003c/li\u003e\n \u003cli\u003eGerend MA, Pai M. 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Geographical and racial disparities in head and neck cancer diagnosis in South-Eastern United States: using real-world electronic medical records data. \u003cem\u003eHealth Equity\u003c/em\u003e. 2020;4(1):43\u0026ndash;51.\u003c/li\u003e\n \u003cli\u003eKeller D, Guilfoyle C, Sariego J. Geographical influence on racial disparity in breast cancer presentation in the United States. \u003cem\u003eAm Surg\u003c/em\u003e. 2011 Jul;77(7):933\u0026ndash;936.\u003c/li\u003e\n \u003cli\u003eJaner G, Sala M, Kogevinas M. Health promotion trials at worksites and risk factors for cancer. \u003cem\u003eScand J Work Environ Health\u003c/em\u003e [Internet]. 2002 Jun [cited 2025 Apr 4];28(3):141\u0026ndash;157. Available from: https://doi.org/10.5271/sjweh.658\u003c/li\u003e\n\u003c/ol\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":"Cancer mortality, Age-adjusted mortality rate, Temporal trends, Epidemiology, CDC WONDER, United States, Disparities","lastPublishedDoi":"10.21203/rs.3.rs-7755712/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7755712/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Cancer remains a leading cause of death across the United States, accounting for more than 27 million deaths among adults aged 25 and older over the past five decades. However, CDC data from 1968 to 2023 show a notable decline in age-adjusted mortality rates, primarily due to recent advances. Despite this progress, disparities still exist among different strata due to various inequities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAims: \u003c/strong\u003eThe objective of this study was to examine long-term trends in cancer mortality across the United States from 1968 to 2023 and to assess demographic and regional disparities in age-adjusted mortality rates using nationally representative data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology\u003c/strong\u003e: We conducted a retrospective analysis using the CDC WONDER database, which contains de-identified mortality and population data from the U.S. We included individuals aged 25 and older, recorded from 1968 to 2023, with cancer as the underlying cause of death. Cancer diagnoses were classified using International Classification of Disease (ICD) codes for malignant neoplasms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Despite recent improvements, disparities persist across different strata, including gender (males vs. females), race (Black vs. White), age (older vs. younger adults), and geographic regions (Northeast vs. South), as highlighted in this novel study. These inequities emphasize the need for targeted interventions, equitable resource allocation, and comprehensive policy efforts to support vulnerable and underserved populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Through our in-depth CDC study, we aim to guide future public health initiatives and enhance efforts for better cancer care and prevention by highlighting both historical and recent trends in cancer-related deaths.\u003c/p\u003e","manuscriptTitle":"The Arc of Cancer Mortality: Half a Century of U.S. Data from the CDC WONDER Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-06 14:46:31","doi":"10.21203/rs.3.rs-7755712/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":"9b79bcf6-4a24-441d-b71f-f3fdc7672d2b","owner":[],"postedDate":"November 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T20:38:52+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-06 14:46:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7755712","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7755712","identity":"rs-7755712","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}