Trends of uterine cancer burden in 204 countries and regions from 2000 to 2019 and disease burden prediction

doi:10.21203/rs.3.rs-2251857/v1

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Trends of uterine cancer burden in 204 countries and regions from 2000 to 2019 and disease burden prediction

https://doi.org/10.21203/rs.3.rs-2251857/v1

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Background: Uterine cancer is the most common gynecological malignancy and the fourth most common cancer in women. However, the global burden of uterine cancer has not been estimated, and projections of future disease development are lacking.

Methods: Methods: We collected detailed information on the etiology of uterine cancer between 2000 and 2019 from the 2019 Global Burden of Disease Study. Estimated annual percentage changes (EAPCs) of age-standardized incidence rates (ASR) of uterine cancer by region and etiology were calculated to quantify temporal trends in uterine cancer ASR. Predicting future trends in uterine cancer using the EAPC package.

Results: Globally, uterine cancer cases increased from 244,441 in 2000 to 435,041 in 2019, an increase of 78%. During this period, overall ASR increased by an average of 4% per year. The most pronounced increases are usually seen in countries with high sociodemographic indices, such as the United States. The high body-mass index had a significant effect on disability-adjusted life years(DALYs), Deaths, years lived with disability(YLDs), and years of life lost(YLL)s, and 40.2% of DALYs, 39.8% of Deaths, 43.5% of YLDs, and 39.8% of YLLs were attributed to the high body-mass index. EAPC was significantly correlated with ASR (2000) and Human Development Index (HDI) (2019), respectively. Using BAPC models to predict future uterine cancer incidence will continue to rise

Conclusion: The number of uterine cancer cases is on the rise globally. Overall, we observed a higher incidence trend in countries with higher socio-demographic index. High body-mass index is an important risk factor for uterine cancer. This suggests that current prevention strategies should be repositioned and, in some countries, more targeted and specific strategies should be developed to prevent the increase in uterine cancer.

uterine cancer

disease burden

disease prediction

Global Burden of Diseas

Cancer incidence and mortality are rapidly rising globally, with nearly 19.3 million new cases and 10 million deaths worldwide in 2020[1, 2].Uterine cancer is a common and deadly malignancy. In 2019, more than 400,000 people worldwide were diagnosed with uterine cancer[2, 3]. There is a large body of literature showing that the incidence of uterine cancer varies widely around the world, that both newly diagnosed cases and age-standardized incidence of uterine cancer have increased globally over the past few decades, and that risk factors for uterine cancer are based on numerous elements[4–6]. Heterogeneous patterns of uterine cancer incidence are associated with the prevalence of risk factors in different regions[7]. Understanding the incidence of uterine cancer and predicting the future trend of uterine cancer will help to formulate more targeted prevention strategies, thereby promoting accurate prevention of uterine cancer.

The Global Burden of Disease (GBD) study assessed the burden of uterine cancer in 204 countries and territories worldwide, providing a unique opportunity to understand the current status of uterine cancer. In the current study, we retrieved risk factors for the onset of uterine cancer from the 2019 GBD study. We further assessed the disease burden of uterine cancer by identifying temporal trends in uterine cancer incidence at global, regional, and country levels from 2000 to 2019, and by projecting future uterine cancer incidence.

Study data

Annual incidence cases, age-standardized incidence rates, mortality rates, and DALYs of uterine cancer from 2000 to 2019 were collected from the Global Health Data Exchange (GHDx) query tool, by region and country. These countries and regions are then divided into 5 regions of low, medium, low, medium-high, and high according to the Socio-Demographic Index (SDI). Furthermore,the world is divided into 21 regions in terms of geography, such as East Asia (Table 1). Cancer incidence was looked for from individual cancer registries or aggregated databases of cancer registries such as Cancer Incidence in Five Continents (CI5), NORDCAN. We also collected country-level HDI data from the World Bank.

Table 1

ASR, age standardized rate; CI, confidence interval; EAPC, estimated annual percentage change; UI, uncertainty interval.
Characteristics	2000		2019		2000–2019
Characteristics	Incident cases(95%UI)	ASR per 100,000 No. (95% UI)	Incident cases (95%UI)	ASR per 100,000 No. (95% UI)	EAPC No. (95% UI)
overall	244441.1 (223966-253324.9)	9.1 (8.4–9.5)	435041.1 (397021.1-479728.7)	9.9(9.1–11)	0.48 (0.26–0.7)
Socio-demographic index
Low	4459.9 (3612.7-5412.9)	2.9 (2.3–3.6)	9529.8 (7770.3-11735.3)	3.43(2.8–4.2)	0.8 (0.7–0.91)
Low-middle	13988.4 (11097.5-15983.9)	3.3 (2.8–3.8)	29420.8 (25043.3-35619.9)	3.94(3.4–4.8)	0.75 (0.62–0.88)
Middle	40100.8 (28901.5-44126.7)	5.1 (3.8–5.6)	78640.1 (64686.1-92029.6)	5.7(4.7–6.7)	0.26 (-0.29-0.81)
Middle-high	88088 (82546.2-91433)	12.3 (11.5–12.8)	149131.3 (133483.9-165007.7)	13.87(12.4–15.4)	0.59 (0.3–0.88)
High	97639.5 (94037.4-100102.8)	15.1 (14.7–15.5)	168021.2 (148611.3-188553.2)	19.16(16.9–21.5)	1.48 (1.33–1.63)
Region
Andean Latin America	1320.5 (1042-1548.3)	8.4 (6.7–9.9)	2901.7 (2279.7-3771.7)	9.75(7.7–12.7)	0.6 (0.38–0.82)
Australasia	1637.7 (1539.1–1733)	10.9 (10.2–11.6)	2687.9 (2177.9-3319.6)	11.26(9.1–13.9)	0.19 (0.06–0.32)
Caribbean	2786.9 (2636-2951.7)	15.6 (14.8–16.6)	4836.6 (4105.1-5678.2)	17.83(15.1–21)	0.61 (0.46–0.76)
Central Asia	3010.4 (2861.1-3173.3)	10 (9.5–10.6)	5456.5 (4862.1-6113.4)	11.72(10.5–13.1)	0.86 (0.75–0.98)
Central Europe	14009 (13505.8-14695.8)	15.6 (15-16.3)	21860.3 (18941.2-25296.2)	20.52(17.7–23.9)	1.74 (1.59–1.89)
Central Latin America	3075.7 (2956.9-3217.6)	4.6 (4.4–4.8)	8368.1 (7041.1-9916.6)	6.4(5.4–7.6)	2.05 (1.79–2.31)
Central Sub-Saharan Africa	456.2 (353-620.8)	2.7 (2.1–3.6)	923.2 (652.9-1312.7)	3.0(2.1–4.3)	0.52 (0.44–0.6)
East Asia	40329.9 (27782-46408.3)	6.1 (4.3-7)	70916.9 (55042–96591)	6.66(5.1–8.8)	-0.31 (-1.35-0.73)
Eastern Europe	36968.4 (36153.5-37836)	21.6 (21.1–22.1)	52512.8 (44704.7-61826.5)	27.5(23.2–32.6)	1.52 (1.19–1.85)
Eastern Sub-Saharan Africa	1577.5 (1117.3-1928.6)	3.2 (2.3–3.9)	3271.4 (2356.6-4076.2)	3.7(2.6–4.6)	0.73 (0.6–0.85)
High-income Asia Pacific	9879.5 (9331.8-10415.4)	7.4 (7-7.8)	17998.7 (14655.4-21639.2)	11.32(9.2–13.7)	2.54 (2.1–2.99)
High-income North America	46479 (44839-47712.3)	22.1 (21.4–22.6)	86647.2 (72240-103729.7)	27.82(23.1–33.4)	1.53 (1.34–1.72)
North Africa and Middle East	3932 (3266.4-4663.4)	3.2 (2.7–3.8)	12514.3 (8467.2-14856.9)	5.41(3.7–6.4)	3.19 (3-3.38)
Oceania	153.9 (106.9-195.8)	7.2 (5.1-9)	344.3 (191.5-461.4)	8.58(4.9–11.3)	0.92 (0.86–0.97)
South Asia	9017.4 (7290.8-10816.8)	2.4 (1.9–2.9)	21825.2 (17275.2-26690.4)	2.94(2.3–3.6)	1.17 (0.84–1.5)
Southeast Asia	10531.1 (6959.4-12164.9)	5.2 (3.6-6)	22135 (14282.8-26648.1)	6.23(4.1–7.5)	0.92 (0.87–0.96)
Southern Latin America	2256.8 (2123.1-2390.6)	7.4 (6.9–7.8)	3644.4 (2860.5–4590)	8.23(6.4–10.4)	0.77 (0.55–0.99)
Southern Sub-Saharan Africa	919.5 (703.9–1045)	4.4 (3.4-5)	1675.4 (1188.3–1951)	5.08(3.6–5.9)	1.36 (1.06–1.66)
Tropical Latin America	4566.6 (4368.3-4748.9)	6.5 (6.2–6.7)	9347.3 (8723.9-10021.2)	6.97(6.5–7.5)	0.51 (0.42–0.61)
Western Europe	50316.7 (48005.4-51856.3)	14.8 (14.3–15.3)	82497.1 (70937.1-94175.2)	19.62(17-22.5)	1.45 (1.21–1.7)
Western Sub-Saharan Africa	1216.4 (983.1-1714.4)	2.3 (1.8–3.2)	2677.1 (2146.7-3597.6)	2.64(2.1–3.6)	0.77 (0.67–0.87)

Statistical analysis

We quantified trends in uterine cancer incidence using ASR and EAPC, normalized to compare several populations with different age structures or the same population with corresponding changes in age distribution over time[8]. The ASR (per 100,000 population) of the direct method is calculated by comparing the age-specific ratio of the selected reference standard population (ai, where i represents the ith age group) to the number (or weight) of the same age subgroup i ( wi) are added and then divided by the sum of the standard population weights

ASR=\(\frac{\sum {}_{\text{i}=1}{}^{A}{\text{a}}_{\text{i}}{\text{w}}_{\text{i}}}{\sum {}_{\text{i}=1}{}^{A}{\text{w}}_{\text{i}}}\)×100000

ASR trends can be a appropriate proxy for changes in disease patterns in a population, as well as clues to changing risk factors[9]. Therefore, we can assess the effectiveness of current prevention strategies and, if necessary, establish more targeted strategies based on the analysis in the ASR. EAPC is a summary and widely used measure of ASR trends within a specific interval. A regression line was fitted to the natural logarithm of the rate. EAPC is calculated as 100 × (exp(β) -1), and its 95% confidence interval (CI) can also be obtained from a linear regression model. When the EAPC estimate and its 95% CI lower bound were both > 0, the ASR was considered to be trending upward. Conversely, when the EAPC estimate and its 95% CI upper bound were both < 0, the ASR trended downward. Otherwise, the ASR is considered stable over time[10]. Furthermore, to explore the influencing factors of EAPCs, we assessed the association between EAPCs and ASRs (2000) and HDI (2019) at the national level, respectively. Finally, these countries and regions were divided into 4 categories by hierarchical clustering analysis (a: significant increase; b: slight increase; C: stable or slightly decreased; d: significant decrease) in terms of the time trend of ASR. All statistics were performed using the R program (version 4.2) and p-values less than 0.05 were considered statistically significant.

Global burden of uterine cancer

We first counted the number of uterine cancer cases, age-standardized incidence rates, and temporal trends from 2000 to 2019 in 27 regions in 2000 and 2019 (Table 1). The results show that the overall change in global uterine cancer is on the rise. High-income North America had the highest number of cases in 2000 and 2019, with 46,479 × 103 and 86,447 × 103 cases, respectively. North Africa had the highest EAPC at 3.199 (Fig. 1). Analysed at the country level, the global ASR for uterine cancer varies widely around the world, with the Northern Mariana Islands having the highest ASR (32.8/100,000 in 2019), followed by the Russian Federation (32.6/100,000) (Fig. 2). In absolute numbers, the United States of America recorded 43,116.3128 new cases in 2019, followed by China and the Russian Federation. Globally, the incidence of uterine cancer increased from 244,000 in 2000 to 435,000 in 2019, an increase of 78%. Qatar saw the most significant increase (560%). Taiwan (Province of China) saw the largest increase in ASR (EAPC = 5.35), followed by Iraq and Saudi Arabia. Uterine cancer ASR increased between 2000 and 2019 in all countries and territories. According to the results of cluster analysis (Fig. 3), 3 countries (or regions) were classified as significant growth groups, including Taiwan (Province of China), Iraq, Bulgaria. 57 countries (or territories) were grouped into the small growth group, including Saudi Arabia, Nicaragua, Turkey and Singapore. 125 countries (or territories) were classified as remaining stable or declining slightly. The remaining 19 countries (or territories) were included in the significantly reduced group, including Guatemala Belarus and Iceland.

In terms of SDI regions, the number of uterine cancer cases and ASR increased in 5 SDI regions. As can be seen from Fig. 4, ASR was positively correlated with regional or national SDI, and the ASR was significantly higher in countries with high HDI. In terms of geographic regions, all countries (or territories) except Georgia saw an increase in the absolute number of cases.

Risk Factors For Uterine Cancer

We collected risk factors for uterine cancer from 2000 to 2019 from the GHDx query tool. First, we screened at level 2, including environmental/occupational risks, behavioral risks and metabolic risks. The results found that all risk factors for uterine cancer cases are metabolic risks in in the existing database, and then we screened at level 3, including high fasting plasma glucose, high LDL cholesterol, high systolic blood pressure, high body-mass index, low bone mineral density. The results showed that the main risk factor for uterine cancer was high body-mass index (Fig. 4). So we calculate the proportion of the impact of high body-mass index on DALYs, Deaths, YLDs, and YLLs. It was found that 40.2% of DALYs, 39.8% of Deaths, 43.5% of YLDs, and 39.8% of YLLs were attributed to the high body-mass index. The impact of these risk factors varies by region. For example, the effect of high body-mass index is highest in Eastern Europe (55.2% of DALYs can be attributed to high body-mass index), while it is lowest in East Asia, which may be related to economic level and dietary structure(24.6%).

Factors Affecting Eapc

EAPC was significantly correlated with ASR (2000) and HDI (2019), respectively (Fig. 6). The ASR for uterine cancer in 2000 reflects the disease stock at baseline, while the Human Development Index in 2016 serves as a surrogate for the level and availability of health care in each country. Surprisingly, there was a negative correlation between EAPCs and HDIs (cor − 0.2136244 (95% CI: -0.35782915 -0.05946761) p-value = 0.007037). We found that the magnitude of ASR change in 2000, EAPC, was significantly negatively correlated with baseline ASR. Uterine cancers were more likely to increase for countries with lower ASR in 2000. This result may be: 1) the lower the

Bapc Model Predicts Disease Burden

After reading the data of uterine cancer patients from 2000 to 2019 and the demographic data from 1990 to 2019, we used the BAPC model to calculate the incidence of each age group and the incidence rate of each age group. Age of onset is 55–75 years old. It is predicted that the incidence of uterine cancer will continue to rise in the future. It is estimated that by 2030, the number of people aged 55–70 will reach 258,545. Due to population growth and aging, new cases and deaths are expected to continue to increase over the next 25 years. We need further research to evaluate detection strategies based on individual age and risk factors. We hope to further reduce the incidence of esophageal cancer by trying to change people's lifestyles and detect them as early as possible.

Uterine cancer is the most common gynecological malignancy and the fourth most common cancer in women[11, 12]. The 5-year survival rate for women diagnosed with uterine cancer fell from 85.2% in 2000 to 81.7% in 2006–2012[13], and the disease tends to affect middle-aged and older women who are wealthy, obese, nulliparous or low parity. The average age at diagnosis was 61[14]. As many as 20% of women are premenopausal and about 5% are under 40[15]. Therefore, it is of great clinical significance to understand the temporal and spatial trends of uterine cancer incidence, risk factors, and future incidence prediction.

Statistical results show that there are significant differences in the incidence of uterine cancer around the world, and in the current study, we comprehensively analyzed the temporal trends in the incidence of primary uterine cancer at the global, regional and national levels. Overall, the incidence and cancer cases of uterine cancer increased from 2000 to 2019. In addition, ASR is also related to SDI. Countries with higher SDI have higher ASR, high SDI regions have the highest EAPC value, which is 1.48, indicating that the incidence of uterine cancer is on the rise. We also found that an important risk factor for uterine cancer is high BMI, which may explain the high incidence in high HDI regions, as the diet structure of high HDI regions is mainly high sugar and high fat diet, and high HDI regions have a more pronounced population aging phenomenon[16]. Studies of population BMI and mortality have shown that obese people are at increased risk of death from medical complications such as hypertension[17], type 2 diabetes[18], cardiovascular disease[19] and cancer[20]. Physiological changes such as insulin resistance, lipid abnormalities, hormonal changes, and chronic inflammation are thought to mediate this relationship[21–23].

Worldwide, the burden of cancer caused by obesity, expressed in terms of population attribution ratio, is 11.9% for men and 13.1% for women[24]. Overweight was associated with an increased risk of cancer in at least 13 anatomical sites, including endometrial cancer[25]. There is a strong hypothesis that obese women have more adipose tissue, which increases endogenous steroid synthesis and bioavailability[26], and that more frequent anovulation in obese premenopausal women also contributes to progesterone deficiency and inadequate estrogen exposure[27]. Excess estrogen, unaffected by progesterone, causes endometrial cell proliferation, inhibits apoptosis, and increases DNA replication errors and somatic mutations that can lead to cancer. Obesity is also associated with decreased production of sex hormone-binding globulin in the uterine, which in turn increases the diffusion of bioavailable estrogen into endometrial tissue[28].

Our study also found that the incidence of uterine cancer will increase in the future to 2030, according to the prediction of the incidence of uterine cancer by the BAPC model. Therefore, future research is needed to better elucidate the relationship between obesity and endometrial cancer survival, and to investigate other lifestyle factors that may influence survival. A recent review of body weight, physical activity, diet, and survival in gynecologic cancer patients showed that, in addition to overweight and obesity, there is a lack of relevant observational studies on the impact of lifestyle on endometrial cancer survival, and studies should collect dietary, activity and obesity to analyze whether lifestyle factors alter the risk of developing uterine cancer[29]. In addition, future research should investigate the significance of post-diagnosis BMI, as this knowledge may influence uterine cancer prevention in high-risk groups as well as post-diagnosis cancer care.

This paper has certain limitations, such as not exploring health disparities in uterine cancer. Health disparities refer to preventable differences in the burden of disease, injury, violence, or access to optimal health among vulnerable groups in society[30]. Recent studies have shown marked inequalities in uterine cancer care and outcomes among marginalized groups, and differences in morbidity and mortality across racial and ethnic groups, which may include disease stage at diagnosis, histology differences in socioeconomic status and treatment, therefore, can be factored into health differences in follow-up studies.

Author contributions:

Zhihan Zhao & Li Hong contributed to the conception of the study；

Guotao Huang & Yong He to analysis and manuscript preparation;

Xiaohu Zuo & Wuyue Han helped perform the analysis with constructive discussions.

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Trends of uterine cancer burden in 204 countries and regions from 2000 to 2019 and disease burden prediction

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Version 1

Abstract

Figures

Introduction

Materials And Methods

Study data

Statistical analysis

Results

Global burden of uterine cancer

Risk Factors For Uterine Cancer

Factors Affecting Eapc

Bapc Model Predicts Disease Burden

Discussion

Declarations

References

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