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Chinese Medical Journal logoLink to Chinese Medical Journal
. 2023 Oct 24;137(3):294–302. doi: 10.1097/CM9.0000000000002841

Global and regional trends in the incidence and mortality burden of endometrial cancer, 1990–2019: Updated results from the Global Burden of Disease Study, 2019

Jianyang Feng 1, Rongjin Lin 1, Haoxian Li 1, Jiayan Wang 2, Hong He 1,
Editor: Yanjie Yin
PMCID: PMC10836881  PMID: 37874032

Abstract

Background:

The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.

Methods:

The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.

Results:

The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, -1.0 to -0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019.

Conclusions:

Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Keywords: Endometrial cancer, Global Burden of Disease, Incidence, Mortality, Trends

Introduction

Endometrial cancer (EC) is the most common gynecological malignancy of the female genital tract in developed countries,[1] and is the second-most-common in China.[2] In terms of mortality of female genital tract cancers, the rate of EC was also second highest worldwide, with an estimated 97,370 deaths and a 1.8 (1/100,000) age-standardized rate (ASR) globally, followed by cervical cancer and ovarian cancer in 2020.[1] However, the incidence and mortality burden of EC vary greatly across different countries and regions.[1,3] For example, the highest estimated age-standardized incidence rate (ASIR) was observed in North America (21.1 per 100,000 person-years), followed by Eastern Europe and Poland (20.2 per 100,000 person-years), while the lowest rate was in Sub-Saharan Africa (2.3 per 100,000 person-years), followed by South Central Asia (2.7 per 100,000 person-years) in 2020.[1] However, in 2020, the most predominant estimated age-standardized mortality rate (ASMR) was detected in Eastern Europe (3.7 per 100,000 person-years), with the lowest in North Africa (0.7 per 100,000 person-years).[1] Therefore, the EC disease burden remains a considerable challenge, and is very different across regions around the world. The Global Burden of Disease (GBD) study has, since 1990, contributed to a wide range of social, economic, and public health issues due to its comprehensive collection and analysis of incidence, mortality, migration, and population for countries, territories, and selected subnational locations on a global scale. When the latest results from the GBD 2019 series of studies were released,[4,5] they allowed an update of the disease burden and trends regarding EC since 1990 across different territories, regions, and countries to facilitate decision-making and resource allocation. In the present study, we reported the results of the GBD 2019 Study on primary EC age-standardized incidence and mortality for five geographic sub-regions and 21 regions in terms of sociodemographic index (SDI) between 1990 and 2019. We additionally estimated the annual percentage change (APC) and average annual percentage change (AAPC) using joinpoint regression analysis to examine the temporal trends of age-standardized incidence and mortality in EC during the same time period.

Methods

Study resource

The Global Health Data Exchange (GHDx) is an open resources platform created and supported by the Institute for Health Metrics and Evaluation (IHME), an independent global health research center at the University of Washington, USA. Specific detailed methods applied to the GBD 2019 series studies are described elsewhere,[4,5] and the defined data from global and regional territories and countries are available electronically. We first categorized the countries and territories into five sub-regions in terms of SDI levels (low, low-middle, middle, high-middle, and high), and then subdivided the world into 21 geographic regions. The annual incident and deceased cases, as well as the age-standardized incidences and mortalities due to EC from 1990 to 2019, were retrieved using the GHDx query tool (available at http://ghdx.healthdata.org/gbd-results-tool). The Human Development Index (HDI) was measured with respect to the basic dimensions of human development across nations worldwide, as described by the United Nations Development Program.

Statistical analysis

ASIR (per 100,000), ASMR (per 100,000), and APC were used to quantify the disease burden of EC. The APC and 95% confidence interval (CI) values were obtained from the linear regression model: log (ASR) = α+βy, where log (ASR) was the natural log of the age-standardized rate in year (y). The AAPC was utilized to summarize the trend measures for a specified fixed-time period interval and was computed as a weighted average of the APCs from the joinpoint model, with the weights equal to the length of the APC interval, using the Joinpoint Regression Program (Version 4.9.0.1, Statistical Methodology and Applications Branch, Surveillance Research Program, National Cancer Institute, Rockville, MD, USA). The estimated APC (EPAC) was calculated as 100{exp[β]-1}. All measures were age-standardized by the standard population provided by the GBD collaborative, and we also estimated the associations between SDI and the disease burden from all national locations by exploiting a generalized linear model with a locally weighted regression (LOESS) smooth adjustment for SDI. All statistics were executed via the R opensource software platform (v4.0.2, R Foundation, Vienna, Austria), and a P-value <0.05 was considered to be statistically significant.

Results

Global and region-specific incidence and mortality burden of EC

The global incident cases of EC increased substantially, from 187,191.1 (with a 95% uncertainty interval [UI] of 174,630.6–196,030.3) in 1990 to 435,041.1 (95% UI, 397,021.1–479,728.7) in 2019, with a rise in ASR (estimated annual percentage change [EAPC] = 0.7; 95% CI, 0.6–0.8) every year over these three decades (8.7 [95% UI, 8.1–9.1] per 100,000 women in 1990 vs. 10.0 [95% UI, 9.1–11.0] per 100,000 women in 2019) [Table 1]. Regionally, the incident cases of EC varied significantly across geographical regions between 1990 and 2019. The highest ASIR was observed in Eastern Europe (20.4 per 100,000 women; 95% UI, 19.6–21.4) in 1990, followed by high-income North America (19.1 per 100,000 women; 95% UI, 18.5–19.7) and Central Europe (13.8 per 100,000 women; 95% UI, 13.3–14.6), while in 2019, high-income North America showed the highest ASIR (27.8 per 100,000 women; 95% UI, 23.1–33.4), followed by Eastern Europe (27.5 per 100,000 women, 95% UI, 23.2–32.6) and Central Europe (20.5 per 100,000 women, 95% UI, 17.7–23.9) [Table 1]. In contradistinction, the lowest ASIR was observed in Western Sub-Saharan Africa both in 1990 (2.1 per 100,000 women; 95% UI, 1.7–3.2) and 2019 (2.6 per 100,000 women; 95% UI, 2.1–3.6), followed by South Asia and Central Sub-Saharan Africa [Table 1]. In addition, the largest increase in ASIR between 1990 and 2019 was observed in the high-income Asian Pacific region (EAPC = 2.4; 95% CI, 2.1–2.6), followed by Southern Sub-Saharan Africa (EAPC = 1.7; 95% CI, 1.6–1.9) and Western Europe (EAPC = 1.7, 95% CI; 1.6–1.9) [Table 1]. Twenty-six countries or territories (including Russia, the USA, the Netherlands, Greece, Italy, and Ireland) reported a very high EC ASIR of >20 per 100,000 women in 2019. The most pronounced increase was noted in Qatar between 1990 and 2019 (1330.1%), followed by Saudi Arabia (1092.3%), with the most notable attenuation observed in Georgia (17.4%). Turkmenistan (EAPC = –2.7; 95% CI; -3.5 to -2.0) showed the most precipitous decline in ASIR from 1990 to 2019.

Table 1.

The incident cases and age-standardized incidence of primary endometrial cancer in 1990 and 2019, and its temporal estimated trends from 1990 to 2019.

Regions/Charateristics 1990 2000 2010 2019 1990–2019
Incident cases ASIR per 100,000 Incident cases ASIR per 100,000 Incident cases ASIR per 100,000 Incident cases ASIR per 00,000 EAPC*
Global 187,191.1 (174,630.6–196,030.3) 8.7 (8.1–9.1) 244,441.1 (223,966.0–253,324.9) 9.1 (8.4–9.5) 358,558.9 (316,915.8–375,355.3) 10.4 (9.2–10.9) 435,041.1 (397,021.1–479,728.7) 10.0 (9.1–11.0) 0.7 (0.6–0.8)
Socio-demographic index
High 77,503 .6 (74,621.9–79,414.9) 13.8 (13.4–14.1) 97,639.5 (94,037.4–100,102 .8) 15.1 (14.7–15.5) 134,225.0 (128,054.2–138,213.2) 17.7 (17.1–18.2) 168,021.2 (148,611.3–188,553.2) 19.2 (16.9–21.5) 1.3 (1.3–1.4)
High-middle 70,517.5 (67,442.1–73,688.2) 11.7 (11.1–12.2) 88,088 (82,546.2–91,433.0) 12.3 (11.5–12.8) 129,017.7 (114,823.5–135,735.9) 14.6 (13.0–15.4) 149,131.3 (133,483.9–165,007.7) 13.9 (12.4–15.4) 0.8 (0.7–1.0)
Middle 25,824.5 (19,856.9–29,471.1) 4.4 (3.5–5.1) 40,100.8 (28,901.5–44,126.7) 5.1 (3.8–5.6) 69,136.5 (46,540.2–77,561.5) 6.5 (4.5–7.3) 78,640.1 (64,686.1–92,029.6) 5.7 (4.7–6.7) 1.1 (0.9–1.4)
Low-middle 9851.3(8012.3–11799.6) 3.1 (2.5–3.7) 13,988.4 (11,097.5–15,983.9) 3.3 (2.8–3.8) 19,717.2 (16,732.0–22,943.7) 3.5 (3.0–4.1) 29,420.8 (25,043.3–35,619.9) 3.9 (3.4–4.8) 0.7 (0.7–0.8)
Low 3387.9(2690.7–4227.3) 2.8 (2.2–3.5) 4459.9 (3612.7–5412.9) 2.9 (2.3–3.6) 6233.8 (5125.5–7650.4) 3.0 (2.5–3.7) 9529.8 (7770.3–11,735 .3) 3.4 (2.8–4.2) 0.7 (0.6–0.7)
Regions

Andean

Latin America

841.1 (668.9–970.7) 7.6 (6.1–8.7) 1320.5 (1042.0–1548.3) 8.4 (6.7–9.9) 2068.6 (1672.5–2539.4) 9.4 (7.6–11.5) 2901.7 (2279.7–3771.7) 9.8 (7.7–12.7) 0.9 (0.8–1.1)
Australasia 1155.5 (1083.5–1227.3) 9.5 (8.9–10) 1637.7 (1539.1–1733.0) 10.9 (10.2–11.6) 2107.7 (1952.9–2244.2) 0 2687.9 (2177.9–3319.6) 11.3 (9.1–13.9) 0.7 (0.6–0.8)
Caribbean 1609.2 (1499.8–1723.7) 11.6 (10.8–12.4) 2786.9 (2636.0–2951.7) 15.6 (14.8–16.6) 3654.5 (3415.4–3921.8) 16.4 (15.3–17.6) 4836.6 (4105.1–5678.2) 17.8 (15.1–21) 1.5 (1.3–1.7)
Central Asia 3052.0 (2881.9–3242.2) 10.8 (10.2–11.4) 3010.4 (2861.1–3173.3) 10.0 (9.5–10.6) 3923.3 (3719.1–4184.7) 10.8 (10.3–11.5) 5456.5 (4862.1–6113.4) 11.7 (10.5–13.1) 0.2 (0.1–0.4)
Central Europe 11,336.8 (10,914.5–11,935.5) 13.8 (13.3–14.6) 14,009 .0 (13,505 .8–14,695 .8) 15.6 (15.0–16.3) 18,364.2 (17,427.6–19,028.6) 18.5 (17.5–19.2) 21,860.3 (18,941.2–25,296.2) 20.5 (17.7–23.9) 1.5 (1.4–1.6)
Central Latin America 1891.9 (1823.0–1963.4) 4.1 (3.9–4.3) 3075.7 (2956.9–3217.6) 4.6 (4.4–4.8) 5075.9 (4868.0–5329.4) 5.2 (5.0–5.5) 8368.1 (7041.1–9916.6) 6.4 (5.4–7.6) 1.5 (1.3–1.6)
Central Sub- Saharan Africa 370.7 (274.8–517.5) 2.8 (2.1–4.0) 456.2 (353.0–620.8) 2.7 (2.1–3.6) 618.6 (461.7–853.0) 2.8 (2.1–3.8) 923.2 (652.9–1,312.7) 3.0 (2.1–4.3) 0.2 (0.1–0.3)
East Asia 25,444.3 (18,943.2–31,280.0) 5.2 (3.9–6.3) 40,329 .9 (27,782 –46,408 .3) 6.1 (4.3–7.0) 77,865.7 (47,769.8–91,740.1) 8.9 (5.5–10.5) 70,916.9 (55,042.0–96,591.0) 6.5 (5.1–8.8) 1.4 (1.0–1.9)
Eastern Europe 34,571.8 (33,206.2–36,185.1) 20.4 (19.6–21.4) 36,968 .4 (36,153 .5–37,836 .0) 21.6 (21.1–22.1) 42,514.0 (41,510.2–43,327.2) 23.7 (23.1–24.1) 52,512.8 (44,704.7–61,826.5) 27.5 (23.2–32.6) 0.9 (0.7–1.1)
Eastern Sub- Saharan Africa 1298.8 (913.2–1601.0) 3.3 (2.3–4.0) 1577.5 (1117.3–1928.6) 3.2 (2.3–3.9) 2113.9 (1528.9–2630.0) 3.3 (2.3–4.1) 3271.4 (2356.6–4076.2) 3.7 (2.6–4.6) 0.3 (0.2–0.4)
High-income Asia Pacific 7419.2 (6588–7791.7) 6.7 (5.9–7.1) 9879.5 (9331.8–1,041 5.4) 7.4 (7.0–7.8) 15,923.9 (14,777.8–16,838.5) 10.8 (10.1–11.3) 17,998.7 (14,655.4–21,639.2) 11.3 (9.2–13.7) 2.4 (2.1–2.6)
High-income North America 35,824.7 (34,358.8–36,831.6) 19.1 (18.5–19.7) 46,479 .0 (44,839 .0–47,712 .3) 22.1 (21.4–22.6) 65,521.3 (63,181.5–67,630.9) 25.4 (24.6–26.2) 86,647.2 (72,240.0–103,729.7) 27.8 (23.1–33.4) 1.4 (1.4–1.5)
North Africa and Middle East 2839.4 (2148.2–3403.3) 3.1 (2.4–3.7) 3932.0 (3266.4–4663.4) 3.2 (2.7–3.8) 7132.7 (5417.9–7919.6) 4.2 (3.3–4.7) 12,514.3 (8,467.2–14,856.9) 5.4 (3.7–6.4) 2.0 (1.8–2.1)
Oceania 112.5 (79.3–140.3) 6.7 (4.8–8.4) 153.9 (106.9–195.8) 7.2 (5.1–9.0) 235.1 (136.8–305.6) 8.0 (4.8–10.3) 344.3 (191.5–461.4) 8.6 (4.9–11.3) 0.8 (0.8–0.9)
South Asia 6021.7 (4711.5–7587.9) 2.2 (1.7–2.7) 9017.4 (7290.8–10,816 .8) 2.4 (1.9–2.9) 12,885.7 (10,855.3–16,234.8) 2.4 (2.0–3.0) 21,825.2 (17,275.2–26,690.4) 2.9 (2.3–3.6) 0.8 (0.7–0.9)
Southeast Asia 7136.6 (4973.8–8350.2) 4.7 (3.4–5.5) 10,531 .1 (6959.4–12,164 .9) 5.2 (3.6–6.0) 15,382.9 (10,147.9–17,733.9) 5.7 (3.8–6.5) 22,135 (14,282.8–26,648.1) 6.2 (4.1–7.5) 0.9 (0.9–0.9)
Southern Latin America 1773.8 (1672.7–1875.7) 7.0 (6.6–7.4) 2256.8 (2123.1–2390.6) 7.4 (6.9–7.8) 2737.2 (2581.9–2896.6) 7.4 (7.0–7.9) 3644.4 (2860.5–4590.0) 8.2 (6.4–10.4) 0.3 (0.2–0.5)
Southern Sub- Saharan Africa 554.7 (450.9–646.2) 3.5 (2.8–4.1) 919.5 (703.9–1045.0) 4.4 (3.4–5.0) 1336.9(960.5–1524.6) 5.2 (3.7–5.9) 1675.4 (1188.3–1951) 5.1 (3.6–5.9) 1.7 (1.6–1.9)
Tropical Latin America 2968.6 (2829.8–3106.1) 5.9 (5.6–6.2) 4566.6 (4368.3–4748.9) 6.5 (6.2–6.7) 6,578.0 (6276.1–6861.8) 6.5 (6.2–6.8) 9347.3 (8723.9–10,021.2) 7.0 (6.5–7.5) 0.4 (0.3–0.5)
Western Europe 40,035.8 (38,525.1–41,247.1) 13.1 (12.7–13.5) 50,316 .7 (48,005 .4–51,856 .3) 14.8 (14.3–15.3) 70,734.7 (66,347.7–73,417.6) 18.6 (17.7–19.3) 82,497.1 (70,937.1–94,175.2) 19.6 (17.0–22.5) 1.7 (1.6–1.9)
Western Sub-Saharan Africa 932.3 (754.8–1359.7) 2.1 (1.7–3.2) 1216.4 (983.1–1714.4) 2.3 (1.8–3.2) 1784.0 (1431.9–2460.9) 2.5 (2.0–3.5) 2677.1 (2146.7–3597.6) 2.6 (2.1–3.6) 0.8 (0.8–0.9)

Data are presented as n (95% UI) or n (95% CI)*. ASIR: Age standardized incidence rate; CI: Confidence interval; UI: Uncertainty interval; EAPC: Estimated annual percentage change.

With respect to SDI and geographical regions, the incidence of EC increased across the five SDI regions, and the higher the SDI, the greater the number of incident cases and the higher the ASIR [Table 1]. However, the EAPCs in the ASIR varied from 0.7 to 1.3 in the third decade of our study period in different SDI areas.

In contrast, the mortality case with EC increased substantially worldwide from 56,130 (95% UI, 51, 103.9–60,198.5) in 1990 to 91,640.7 (95% UI, 82,389.2–101,502.1) in 2019, along with a substantially reduced ASMR (2.7 [95% UI, 2.4–2.9] per 100,000 women in 1990 vs. 2.1 [95% UI, 1.9–2.3] per 100,000 women in 2019) and EAPC (-0.8 [95% CI, -0.8 to -0.7] per year) [Table 2]. Regarding SDI areas, we observed the most significant reduction in ASMR in the high-middle SDI regions (EPAC = -1.2; 95% CI, -1.3 to -1.1), but the low SDI regions regained unchanged from 1990 to 2019 [Table 2]. Of the 21 geographical regions, 15 depicted attenuated mortality and ASMR with commensurate EPAC varying from -1.7 to -0.1 per year during the same period. The largest decline in mortality and ASMR was detected in East Asia (EAPC = -1.7; 95% CI, -2.1 to -1.4); while in the Caribbean, high-income North America, Oceania, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, and Western Europe, deaths and ASMR were augmented and inversely proportional to their SDI levels.

Table 2.

The mortality cases and age-standardized mortality rates of primary endometrial cancer in 1990 and 2019, and its temporal estimated trends from 1990 to 2019.

Regions/Charateristics 1990 2000 2010 2019 1990–2019
Mortality cases ASMR per 100,000 Mortality cases ASMR per 100,000 Mortality cases ASMR per 100,000 Mortality cases ASMR per 100,000 EAPC*
Global 56,130.0 (51,103.9–60,198.5) 2.7 (2.4–2.9) 66,736.1 (59,664.4–70,776.4) 2.5 (2.3–2.7) 79,571.7 (69,249.2–84,065.6) 2.3 (2.1–2.5) 91,640.7 (82,389.2–101,502.1) 2.1 (1.9–2.3) -0.8 (-0.8 to -0.7)
Socio-demographic index
High 16,875.9 (15,873.5–17,408.4) 2.7 (2.6–2.8) 18,693.1 (17,297.1–19,382.0) 2.5 (2.4–2.6) 22,153.1 (20,117.8–23,207.5) 2.5 (2.3–2.6) 26,632.0 (23,999–28,143) 2.5 (2.3–2.6) -0.2 (-0.3 to -0.1)
High-middle 19,519.4 (18,329.5–20,673.5) 3.2 (3.0–3.4) 22,274.3 (20,883.8–23,345.4) 3.1 (2.9–3.2) 24,433.9 (21,976.6–25,759.6) 2.7 (2.4–2.9) 26,425.5 (23,964.8–28,832) 2.3 (2.1–2.5) -1.2 (-1.3 to -1.1)
Middle 11,809.2 (9,280.3–13,506.8) 2.2 (1.8–2.5) 15,340.0 (11,406.6–16,949.6) 2.2 (1.6–2.4) 20,001.2 (14,143.6–21,957.1) 2.1 (1.5–2.3) 20,953.6 (17,525.1–24,330) 1.6 (1.4–1.9) -0.9 (-1.1 to -0.7)
Low-middle 5566.4 (4586.8–6754.4) 1.9 (1.6–2.4) 7420.4 (6119.6–8703.7) 1.9 (1.6–2.3) 9119.3 (7920.0–11,078.7) 1.8 (1.5–2.2) 12,247.2 (10,429.2–15,284.1) 1.7 (1.5–2.2) -0.4 (-0.5 to -0.4)
Low 2322.4 (1838.5–2931.3) 2.1 (1.6–2.6) 2956.6 (2385.7–3667.9) 2.1 (1.7–2.6) 3795.2 (3104.4–4688.4) 2.0 (1.6–2.5) 5295.9 (4320.0–6638.7) 2.1 (1.7–2.6) 0
Regions
Andean Latin America 469.3 (379.5–537.6) 4.5 (3.7–5.2) 608.8 (495.5–714.9) 4.1 (3.3–4.9) 834.0 (678.2–1,033.0) 3.9 (3.2–4.9) 1019.2 (808.1–1339.6) 3.5 (2.8–4.6) -0.8 (-0.9 to -0.8)
Australasia 345.4 (322.1–364.8) 2.6 (2.5–2.8) 435.5 (398.7–460.3) 2.6 (2.4–2.8) 524.4 (472.7–561.0) 2.5 (2.2–2.6) 654.5 (574.5–722.2) 2.4 (2.1–2.6) -0.3 (-0.3 to -0.2)
Caribbean 611.7 (564.2–671.5) 4.5 (4.2–5.0) 916.7 (853.8–989.4) 5.2 (4.9–5.7) 1220.4 (1120.6–1330.7) 5.5 (5.0–6.0) 1564.2 (1341.7–1819.5) 5.7 (4.9–6.6) 0.9 (0.8–1)
Central Asia 1114.3 (1052.6–1179.0) 4.0 (3.8–4.3) 1034.7 (987.6–1086.5) 3.5 (3.3–3.7) 1129.3 (1072.4–1210.4) 3.4 (3.2–3.6) 1350.1 (1210.3–1507) 3.2 (2.9–3.6) -0.8 (-0.9 to -0.7)
Central Europe 3562.9 (3416.9–3772.2) 4.2 (4.1–4.5) 3682.0 (3515.8–3891.9) 3.9 (3.7–4.1) 4153.7 (3893.7–4316.8) 3.8 (3.6–3.9) 4724.0 (4102.3–5428.7) 3.8 (3.3–4.4) -0.4 (-0.5 to -0.3)
Central Latin America 869.7 (832.1–908.7) 2.1 (2.0–2.2) 1131.2 (1071.7–1195.3) 1.8 (1.7–2.0) 1561.2 (1467.7–1676.8) 1.7 (1.6–1.8) 2336.7 (1986.4–2730.4) 1.8 (1.6–2.2) -0.7 (-0.8 to -0.5)
Central Sub-Saharan Africa 251.8 (189.3–348.9) 2.1 (1.6–2.9) 316.5 (245.3–430.8) 2.0 (1.5–2.7) 403.5 (303.1–555.2) 2.0 (1.5–2.7) 548.6 (391.8–783.1) 2.0 (1.4–2.8) -0.3 (-0.3 to -0.2)
East Asia 10,889 .1 (8182.9–13,304 .2) 2.4 (1.8–2.9) 13,333 .9 (9405.9–15,335 .4) 2.2 (1.5–2.5) 16,570.7 (10,561.6–19,169.5) 2.0 (1.3–2.3) 12,931.4 (10,123 .9–17,985 .9) 1.2 (0.9–1.7) -1.7 (-2.1 to -1.4)
Eastern Europe 8056.3 (7722.4–8391.1) 4.5 (4.3–4.6) 8945.0 (8689.1–9193.5) 4.7 (4.6–4.9) 7723.9 (7471.2–7906.3) 3.9 (3.8–4.0) 8439.3 (7308.8–9672.8) 3.9 (3.4–4.5) -0.7 (-0.9 to -0.5)
Eastern Sub-Saharan Africa 904.8 (646.6–1118.0) 2.5 (1.8–3.1) 1076.9 (771.4–1317.8) 2.4 (1.7–2.9) 1356.7 (975.2–1687.0) 2.3 (1.6–2.9) 1917.9 (1344.5–2380.8) 2.4 (1.7–3.0) -0.2 (-0.3 to -0.1)
High-income Asia Pacific 2193.7 (1936.1–2299.4) 1.9 (1.7–2.0) 2355.2 (2133.0–2514.5) 1.5 (1.4–1.6) 3014.4 (2600.9–3239.6) 1.5 (1.4–1.6) 3425.5 (2885.1–3756.2) 1.5 (1.3–1.6) -0.8 (-1 to -0.6)
High-income North America 6137.9 (5753.6–6352.6) 2.9 (2.8–3.0) 6857.7 (6396.4–7108.8) 2.8 (2.7–2.9) 8517.2 (7870.1–8929.3) 3.0 (2.8–3.1) 11,263.6 (10,459.9–11,838.3) 3.2 (3.0–3.4) 0.4 (0.3–0.4)
North Africa and Middle East 1339.6 (1024.6–1621.0) 1.6 (1.3–2.0) 1562.3 (1350.1–1956.1) 1.4 (1.2–1.8) 2250.0 (1810.0–2588.6) 1.5 (1.2–1.7) 3229.1 (2350.4–3810.7) 1.6 (1.2–1.9) -0.2 (-0.3–0)
Oceania 51.7 (35.8–64.9) 3.5 (2.5–4.4) 70.0 (47.1–88.5) 3.7 (2.6–4.7) 105.2 (61.2–137.0) 4.1 (2.5–5.3) 145.6 (81.3–195.1) 4.2 (2.4–5.5) 0.7 (0.7–0.7)
South Asia 3877.8 (3054.5–4919.1) 1.6 (1.2–2.0) 5463.0 (4422.2–6683.9) 1.6 (1.3–2.0) 6879.3 (5807.8–8784.1) 1.4 (1.2–1.8) 10,251.4 (8134.1–13,077.7) 1.5 (1.2–1.9) -0.4 (-0.5 to -0.3)
Southeast Asia 3196.2 (2344.7–3792.4) 2.3 (1.7–2.7) 4457.9 (3137.9–5180.1) 2.4 (1.7–2.8) 5739.4 (4098.6–6619.1) 2.3 (1.7–2.6) 7319.2 (5131.9–8654.3) 2.2 (1.6–2.6) -0.1 (-0.2–0)
Southern Latin America 767.9 (723.6–811.1) 3.0 (2.8–3.2) 902.8 (844.5–959.2) 2.8 (2.6–3.0) 956.4 (888.8–1013.0) 2.4 (2.3–2.6) 1144.9 (1041.3–1252.7) 2.4 (2.2–2.6) -1 (-1.1 to -0.9)
Southern Sub-Saharan Africa 313.3 (250.5–369.5) 2.1 (1.7–2.5) 539.0 (412.3–610.3) 2.7 (2.1–3.1) 761.2 (539.9–863.4) 3.1 (2.2–3.5) 865.6 (604.2–997.6) 2.8 (1.9–3.2) 1.7 (1.5–1.8)
Tropical Latin America 1421.1 (1344.8–1485.1) 3.1 (2.9–3.2) 1886.7 (1773.0–1969.2) 2.8 (2.6–3.0) 2416.7 (2251.8–2532.9) 2.5 (2.3–2.6) 3184.8 (2932.5–3418.6) 2.4 (2.2–2.6) -0.9 (-1 to -0.9)
Western Europe 9114.6 (8560.5–9444.6) 2.6 (2.5–2.7) 10,353.4 (9549.3–10,777.6) 2.5 (2.4–2.6) 12,368.2 (11,102.5–13,023.0) 2.6 (2.4–2.8) 13814 (12,221.0–14,708.9) 2.6 (2.4–2.7) 0.1 (0.1–0.2)
Western Sub-Saharan Africa 640.7 (519.8–951.3) 1.5 (1.2–2.3) 806.8 (652.6–1176.7) 1.6 (1.3–2.3) 1086.1 (885.7–1462.2) 1.7 (1.4–2.3) 1511.4 (1224.8–2049.5) 1.7 (1.4–2.3) 0.4 (0.4–0.4)

Data are presented as n (95% UI) or n (95% CI)*. ASMR: Age standardized mortality rate; CI: Confidence interval; UI: Uncertainty interval; EAPC: Estimated annual percentage change.

Global and region-specific incidence and mortality trends in EC

To investigate the temporal trends in EC associated with age-standardized incidence and mortality from 1990 to 2019, we applied joinpoint regression to estimate the AAPC parameter, which is itself a summary measure of the trend in a variable over a specified fixed interval. When we additionally explored the trends between SDI and ASIR/ASMR with a Loess smoothing model of EC as displayed in Figure 1A and B, we again noted that the ASIR of EC was significantly increased by an average of 0.5% per year from 1990 to 2019 (95% CI, 0.3–0.7, P <0.001) [Table 3 and Figure 1A], while the ASMR decreased by an average of 0.8% per year worldwide (95% CI, -1.0 to -0.7, P <0.001) [Table 4 and Figure 1B], which was consistent with our EAPC estimation [Tables 1 and 2]. We observed four specific temporal trends in ASIR. The ASIR rose by 0.9% per year from 1990 to 1994, declined by 0.6% per year from 1994 to 1997, increased by 1.3% per year during the years 1997–2010, and then decreased by 0.5% per year again from 2010 to 2019 [Figure 2A and Supplementary Table 1, http://links.lww.com/CM9/B708]. In contrast, the ASMR decreased by 0.1–1.8% in consecutive years from 1990 to 2019, with the most notable decline being from 2011 to 2014 (APC = -1.8; 95% CI, -3.0 to -0.5, P = 0.009) [Figure 2B and Supplementary Table 2, http://links.lww.com/CM9/B709].

Figure 1.

Figure 1

The association between (A) ASIRs and SDI, (B) ASMRs and SDIs of different geographical regions. ASIR: Age-standardized incidence rate; ASMR: Age-standardized mortality rate; SDI: Sociodemographic index.

Table 3.

The AAPCs for age-standardized incidence rate (per 100,000) from 1990 to 2019 in endometrial cancer.

Regions/Charateristics AAPC (95% CI) Test statistic P-values
Global 0.5 (0.3–0.7) 5.909 <0.001
Socio-demographic index
High 1.1 (0.8–1.4) 6.928 <0.001
High-middle 0.6 (0.3–1.0) 3.882 <0.001
Middle 0.9 (0.7–1.0) 12.473 <0.001
Low-middle 0.9 (0.8–1.0) 19.769 <0.001
Low 0.7 (0.7–0.8) 23.737 <0.001
Regions
Andean Latin America 0.8 (0.4–1.1) 3.939 <0.001
Australasia 0.7 (0.4–1.0) 4.971 <0.001
Caribbean 1.6 (1.4–1.8) 13.500 <0.001
Central Asia 0.2 (0–0.3) 2.046 0.041
Central Europe 1.3 (1.0–1.7) 7.792 <0.001
Central Latin America 1.8 (1.6–2.0) 19.561 <0.001
Central Sub-Saharan Africa 0.2 (0.1–0.4) 3.056 0.002
East Asia 0.8 (0.6–1.0) 8.251 <0.001
Eastern Europe 1.5 (0.2–2.8) 2.254 0.024
Eastern Sub-Saharan Africa 0.4 (0.3–0.6) 5.822 <0.001
High-income Asia Pacific 1.8 (1.4–2.1) 9.057 <0.001
High-income North America 1.2 (0.7–1.7) 4.644 <0.001
North Africa and Middle East 1.9 (1.7–2.1) 16.770 <0.001
Oceania 0.8 (0.7–1.0) 10.323 <0.001
South Asia 1.1(0.6–1.6) 4.546 <0.001
Southeast Asia 1.0 (0.9–1.1) 18.620 <0.001
Southern Latin America 0.6 (0.4–0.8) 6.292 <0.001
Southern Sub-Saharan Africa 1.3 (0.7–1.9) 4.187 <0.001
Tropical Latin America 0.6 (0.5–0.8) 12.069 <0.001
Western Europe 1.5 (1.2–1.8) 9.595 <0.001
Western Sub-Saharan Africa 0.7 (0.6–0.9) 8.102 <0.001

AAPC: Average annual percent change; CI: Confidence Interval.

Table 4.

The AAPCs for age-standardized mortality rate (per 100,000) from 1990 to 2019 in endometrial cancer.

Regions/Charateristics AAPC (95% CI) Test statistic P-values
Global –0.8 (–1.0 to –0.7) –8.798 <0.001
Socio-demographic index
High –0.3 (–0.4 to –0.2) –5.571 <0.001
High-middle –1.1 (–1.3 to –0.9) –11.357 <0.001
Middle –1.1 (–1.2 to –1.0) –24.152 <0.001
Low-middle –0.3 (–0.4 to –0.2) –6.461 <0.001
Low 0 (0 to 0.1) 1.021 0.307
Regions
Andean Latin America –0.8 (–1.0 to –0.7) –15.587 <0.001
Australasia –0.3 (–0.5–0) –2.330 0.02
Caribbean 1.0 (0.5–1.4) 4.278 <0.001
Central Asia –0.8 (–1.0 to –0.5) –5.930 <0.001
Central Europe –0.4 (–0.6 to –0.1) –2.999 0.003
Central Latin America –0.3 (–0.4 to –0.2) –4.279 <0.001
Central Sub-Saharan Africa –0.3 (–0.3 to –0.2) –9.806 <0.001
East Asia –2.3 (–2.5 to –2.1) –22.651 <0.001
Eastern Europe –0.1 (–0.7–0.5) –0.369 0.712
Eastern Sub-Saharan Africa –0.1 (–0.2–0) –1.986 0.047
High-income Asia Pacific –1.0 (–1.1 to –0.8) –11.074 <0.001
High-income North America 0.3 (0.2–0.5) 5.480 <0.001
North Africa and Middle East –0.1 (–0.3–0.1) –0.887 0.375
Oceania 0.6 (0.5–0.6) 18.343 <0.001
South Asia –0.2 (–0.5–0.1) –1.238 0.216
Southeast Asia –0.2 (–0.3 to –0.1) –3.041 0.002
Southern Latin America –0.8 (–0.9 to –0.6) –11.922 <0.001
Southern Sub-Saharan Africa 1.0 (0.4–1.5) 3.540 <0.001
Tropical Latin America –0.8 (–0.9 to –0.7) –16.347 <0.001
Western Europe 0 (–0.1–0.2) 0.071 0.944
Western Sub-Saharan Africa 0.3 (0.2–0.4) 6.885 <0.001

AAPC: Average annual percent change; CI: Confidence Interval.

Figure 2.

Figure 2

The age-standardized incidence (A) and temporal mortality trends (B) for EC worldwide, 1990–2019. *P <0.05. APC: Annual percentage change; EC: Endometrial cancer.

In terms of the SDI and geographical region categories, our data revealed significantly increasing trends for ASIR with respect to EC per year between 1990 and 2019 [Table 3]. Although the largest increase in ASIR per year was detected in the high SDI territories (AAPC = 1.1; 95% CI, 0.8–1.4, P <0.001) and the North African and Middle Eastern regions (AAPC = 1.9; 95% CI, 1.7–2.1, P <0.001) [Table 3 and Figure 1A], the ASMR for EC principally demonstrated a significantly decreasing tendency during the 1990–2019 period. The largest declining trends for ASMR were observed in the high-middle SDI territories (AAPC = -1.1; 95% CI, -1.3 to -0.9, P <0.001), while low SDI territories showed a non-significant elevation between 1990 and 2019 (P = 0.307) [Table 4 and Figure 1B]. In stark contrast, the ASMR in the Caribbean, high-income North America, Oceania, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, and Western Europe reflected increasing trends while the remaining areas displayed declining trends [Table 4]. Predominantly increasing trends in ASMR were observed for the Southern Sub-Saharan Africa regions (AAPC = 1.0; 95% CI, 0.4–1.5, P <0.001), followed by the Caribbean and Oceania, while the most notable declines were noted for the high-income Asia Pacific regions (AAPC = -1.0; 95% CI, -1.1 to -0.8, P <0.001), followed by Andean Latin American and Tropical Latin American regions [Table 4 and Figure 1B]. We estimated the correlation between SDI and ASMR using a generalized linear model (as shown in Figure 1B) and found that the ASMRs gradually increased between 0.3 and 0.7 in SDI levels, and then rapidly diminished between 0.8 and 0.9. Details of the ASIR and ASMR trends in the SDI and geographical regions in EC from 1990 to 2019 are described in Supplementary Tables 1, http://links.lww.com/CM9/B708 and 2, http://links.lww.com/CM9/B709, respectively.

Association between HDI and disease burden in EC

In order to investigate the association between HDI and EC disease burden, we also evaluated the association between EAPCs and HDIs (2019) at the national level. As illustrated in Figure 3, we observed a significant positive correlation between EAPCs and HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) in incident cases in 2019 [Figure 3B], and conversely observed a negative correlation between EAPCs and HDIs (ρ = -0.13; 95% CI, -0.27 to 0.02; P = 0.09) in mortality cases in the same year. These results indicated that nations with higher HDIs showed commensurate increases in ASIRs with EC between 1990 and 2019.

Figure 3.

Figure 3

The association between EAPCs and HDI in ASIR and ASMR in 2019, respectively. The size of the circle correlates with the cases of EC. The ρ indices and P-values presented in (A) and (B) were derived from Pearson's correlation analysis. ASIR: Age-standardized incidence rate; ASMR: Age-standardized mortality rate; CI: Confidence interval; EAPC: Estimated annual percentage change; EC: Endometrial cancer; HDI: Human Development Index.

Discussion

EC (principally the endometrioid adenocarcinoma phenotype) is the most common gynecological carcinoma in high- and middle-income countries, and the incidence and mortality burden of EC vary across different socioeconomic developmental levels and geographical regions.[1,6] Based on the updated results from the GBD 2019 Study, we conducted an analysis of the age-standardized incidence and mortality burden and estimated the temporal trends of EC from 1990 to 2019 in terms of the global landscape, different SDI levels, and geographical regions.

In general, the estimated ASIR with respect to EC in our study grew significantly worldwide and varied across different SDI levels and geographic regions [Figure 1, Table 1, and Table 3], and this was consistent with previous estimates.[1,3] The estimated ASIR of EC worldwide from the International Agency for Research on Cancer was 8.2 per 100,000 women in 2008, which increased to 8.3 in 2012 and 8.4 in 2018 continuously.[7,8,9] Lortet-Tieulent et al[10] investigated the international patterns and trends in EC incidence from 1978 to 2013 via population-based cancer registries in 43 populations and found that the highest ASRs in all ages were observed in North America and Eastern and Northern Europe in 2006–2007, while the lowest one was in South Africa, followed by India. Data from GLOBOCAN 2012 illustrated the greatest ASR in North America followed by Central and Eastern Europe, while the data showed the lowest ASR in South-Central Asia, followed by North Africa.[9] As estimated in our study in 2019, high-income North America still showed the highest ASIR followed by Eastern Europe and Central Europe, while the lowest ASIR was similarly observed in Western Sub-Saharan Africa followed by South Asia and Central Sub-Saharan Africa. In addition, similar to our study, a decreasing trend of mortality rates in EC was observed globally.[7,9] The estimated ASMR of EC worldwide from GLOBOCAN was 2.0 per 100,000 women in 2008, which decreased to 1.8 in 2012 continuously.[7,9] The lowest mortality rate of EC was detected in North Africa followed by South-Central Asia in 2012,[9] while the highest one was in Melanesia following Central and Eastern Europe and the Caribbean. Consistent with our study, the lowest ASMR was displayed in East Asia and the greatest one was in the Caribbean in 2019.

The variations of disease burden in EC in different territories and regions might be associated with their socioeconomic development status. In our study, the higher the SDI, the greater the number of incident cases and the higher the ASIR, which is also supported by previous studies.[7,8,9] The ASIR was more than 2-fold higher (14.7 vs. 5.5 per 100,000 women) in the more-developed regions (including Northern America, Europe, Australia/New Zealand, and Japan) than the less-developed regions (like Africa) in 2012, and a similar trend in ASMR between more-developed regions and less-developed regions (2.3 vs. 1.5 per 100,000 women) was also observed.[9] We also observed a significant positive correlation between EAPCs and HDIs in incident cases in 2019. According to the estimates from GLOBOCAN in 2018, the estimated ASIR was more than 3-fold higher (11.1 vs. 3.3 per 100,000 women) in high/very high HDI regions than the low/medium ones.[8] Additionally, as illustrated by our study, the analysis of more developed geographic regions such as Europe and high-income North America revealed a marked increase in incident cases consistent with previous studies.[1,3,11,12] The high-SDI and -HDI regions and countries reflected higher prevalence rates of obesity and metabolic syndrome (encompassing diseases such as diabetic mellitus and polycystic ovary syndrome that show epidemiological and biological relationships to EC) than the low-SDI and -HDI territories and African regions.[13,14,15]

There have been increased efforts undertaken recently in risk reduction so as to prevent EC. First, as we mentioned above, a reduction in the prevalence of diseases that increase the risk of developing EC (such as obesity and metabolic syndrome) in the high-SDI/HDI regions is the primary way to prevent EC. Second, abnormal postmenopausal vaginal bleeding remains the most common symptom of EC,[6,16] and measurement of the endometrial thickness via trans-vaginal ultrasonography in symptomatic postmenopausal women facilitates endometrial biopsy in the early detection of EC.[17,18] Third, atypical hyperplasia of the endometrium is considered a precancerous lesion of EC, and hormonal therapy (including medroxyprogesterone acetate [MPA] or megestrol acetate [MA] with or without a gonadotropin-releasing hormone agonist [GnRHa] and a levonorgestrel-releasing intrauterine system [LNG-IUS]) has proven to be an effective treatment option for fertility-sparing women in order to eradicate the lesions.[19,20,21,22] For those women who have completed their childbearing years, total hysterectomy is the standard therapy for atypical hyperplasia of the endometrium so as to prevent disease progress.[6,16] Fourth, two classical histological subtypes (types I and II) of EC based on morphological features are typically identified that involve unfolded heterogenous epidemiological, biological, and prognostic behaviors.[11] According to The Cancer Genome Atlas, EC can be classified into four molecular phenotypes: the POLE mutation subtype, the microsatellite instability subtype, the high somatic copy-number alteration subtype, and a copy-number low group without a specific driver mutation subtype; and these are each characterized by disparate genomic features and distinct prognoses.[23,24] These molecular classifications have now been tailored for diagnostic and precise treatment decisions in EC within routine clinical practice.[25]

Fortunately, although the estimated death cases from EC in 2019 were more than 1.5-fold in 1990 (56,130 vs. 91,640.7), the ASMR significantly declined from 2.7 to 2.1 per 100,000 women worldwide, and six sustained temporal reductions were observed in the ASMR for EC over the entire study period. Figure 2B illustrates two prominent periods of continuous reduction (2011–2014 and 2014–2019) in the ASMR. However, the regions of the Caribbean, high-income North America, Oceania, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, and Western Europe demonstrated augmented ASMRs.

In the present study, we comprehensively investigated the incidence and mortality burden of EC between 1990 and 2019 on the global landscape as well as for different SDI and geographic regions. Distinct temporal trends in age-standardized incidence and mortality of EC were also identified over the entire study period. Thus, these diverse features of disease burden in EC for different SDI and HDI territories will enable us to tailor targeted strategies in preventive and treatment decisions when planning the allocation of medical resources and health services.

We must, however, also acknowledge some limitations concerning the interpretation of results generated from the GBD resource. For example, the cancer registry systems in low-income countries or in some less-developed regions remain under construction, and their cancer statistics might therefore be underestimated. Additionally, according to the cancer statistics reports from the National Cancer Center of China, less than one-third (27.60%) of the national population was covered by the cancer registries data in 2016, and this may thus not have fully reflected the overall disease burden.[2,26]

In conclusion, the incidence and mortality burden of EC vary across different SDIs and geographical regions, with the incidence rates showing a significantly increasing overall temporal trend, and with the death rates declining consecutively from 1990 to 2019 worldwide. In the future, more precise strategies can be implemented and tailored based on the distinct age-standardized incidence and mortality burden in different regions of the world.

Acknowledgments

We gratefully acknowledge the collaborative efforts of the investigators involved in the Global Burden of Disease Study 2019. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

None.

Conflicts of interest

None.

Supplementary Material

SUPPLEMENTARY MATERIAL
cm9-137-294-s001.xlsx (17.5KB, xlsx)
cm9-137-294-s002.xlsx (17.9KB, xlsx)

Footnotes

How to cite this article: Feng JY, Lin RJ, Li HX, Wang JY, He H. Global and regional trends in the incidence and mortality burden of endometrial cancer, 1990–2019: updated results from the Global Burden of Disease Study, 2019. Chin Med J 2024;137:294–302 doi: 10.1097/CM9.0000000000002841

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