Global status and attributable risk factors of breast, cervical, ovarian, and uterine cancers from 1990 to 2021

Abstract

Background

Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively.

Methods

Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project.

Results

From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer.

Conclusions

The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.

Background

According to the latest World Health Organization (WHO) estimates, breast cancer is the most common malignant tumor in women worldwide, accounting for 23.8% of new cases in 2022 [1]. Cervical cancer ranks as the fourth most frequently diagnosed cancer among women (6.8%), followed by uterine (4.3%) and ovarian (3.4%) cancers [1]. Together, these four female-specific cancers represent nearly 40% of all cancers affecting women [1]. Notably, the epidemiological patterns of cancer incidence, mortality, and morbidity exhibit significant geographical variations and temporal shifts [2, 3]. For instance, while breast cancer is the most commonly diagnosed cancer among women in most countries [1], cervical cancer surpasses breast cancer in incidence in certain regions of sub-Saharan Africa, South America, and South-Eastern Asia [1]. This is closely linked to the high prevalence of human papillomavirus (HPV) infection and limited access to cervical cancer vaccination and screening programs [1]. Thus, analyzing the epidemiological characteristics of female-specific cancers is critical to understanding their public health implications across diverse populations.

In our previous work, we systematically analyzed the epidemiological trends of these four female-specific cancers using the Global Burden of Disease 2019 (GBD 2019) database [4]. The burden of all four cancers has increased over the past three decades, with breast cancer being the most prominent. Its high incidence and strong positive correlation with socioeconomic development have posed substantial challenges to global cancer prevention and treatment efforts [4]. In contrast, the incidence of cervical cancer has been effectively controlled in many regions, particularly in developed economies, due to the widespread implementation of HPV vaccination programs and other preventive measures [4]. Nevertheless, two years later, an updated analysis is necessary, especially considering the profound impact of the coronavirus disease 2019 (COVID-19) pandemic on global public health resources.

As the updated version of GBD 2019, GBD 2021 database provides comprehensive epidemiological data on 371 diseases and 88 attributable risk factors across 204 countries and territories, spanning the years 1990 to 2021 [5,6,7]. In this study, we leveraged the latest GBD 2021 database to examine the global and regional epidemiological trends of female-specific cancers. These findings aim to provide a critical foundation for evaluating the global and regional cancer burdens and supporting policymakers in designing targeted public health interventions that address the specific needs of their populations.

Methods

Data acquisition

GBD 2021 is a comprehensive epidemiological study providing data on 371 diseases and injuries worldwide. Its extensive data sources include vital registration systems, epidemiological surveys, disease surveillance systems, cancer registries, police records, and open-source databases. Detailed methodologies for data collection and processing have been described in previous publications [8, 9]. Downstream data analysis is performed using advanced statistical models such as meta-regression-Bayesian, regularized, trimmed (MR-BRT), DisMod-MR 2.1, and spatiotemporal Gaussian process regression (ST-GPR). All disease terms were standardized using International Classification of Diseases (ICD) codes to ensure accuracy and comparability. The project adheres to the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).

This study utilized data from the GBD 2021 database, including the number of incident cases, deaths, and disability-adjusted life years (DALYs) for breast, cervical, ovarian, and uterine cancers from 1990 to 2021, along with their corresponding age-standardized rates (ASRs). These metrics were extracted via the GBD visualization platform (https://vizhub.healthdata.org/gbd-results/). ICD codes for female-specific cancers are listed in Supplementary Table S1.

Moreover, to assess the level of development across regions, the socio-demographic index (SDI) was employed, with values ranging from 0 to 1. This parameter was calculated as the geometric mean of three key indicators: fertility rate, mean years of education, and per capita income. Based on the SDI values, countries and territories were categorized into five distinct groups: low, low-middle, middle, high-middle, and high SDI. These classifications were sourced from the Institute for Health Metrics and Evaluation, covering the period of 1990–2021.

Disease-attributable risk factors

The GBD 2021 database provides a comprehensive evaluation of the impact of risk factor exposure on specific health outcomes [10]. This analysis covers 88 risk factors categorized into four hierarchical levels. At Level 1, risk factors are grouped into environmental and occupational, behavioral, and metabolic categories. Level 2 further subdivides these into 20 specific factors, with additional granularity provided at Levels 3 and 4. For this study, Level 2 risk factors associated with female-specific cancers were summarized as follows: (1) Breast cancer: dietary risks, high alcohol use, high body-mass index (BMI), high fasting plasma glucose, low physical activity, and tobacco; (2) Cervical cancer: tobacco and unsafe sex; (3) Ovarian cancer: high BMI and occupational risks; (4) Uterine cancer: high BMI.

The GBD 2021 database employs advanced statistical models to estimate exposure levels, relative risks, population attributable fractions (PAFs), and disease burden in terms of DALYs and deaths. To address interdependence among risk factors, mediation effects are accounted for to prevent the overestimation of PAFs. This ensures accurate attribution of disease burdens to individual and combined risk factors.

Statistical analysis

Annual incident cases, deaths, and DALYs were analyzed to assess the burden of female-specific cancers. ASRs were used to account for differences in age distribution and population size, enabling meaningful comparisons over time and across regions. To evaluate temporal trends, the estimated annual percentage change (EAPC) of ASRs, including age-standardized incidence rate (ASIR), death rate (ASDR), and DALY rate (ASDALYR) per 100,000 female population, was calculated. The formula Y = αX + β was used, where Y represents the Log10(ASR) value, and X denotes the calendar year. EAPC values were derived from the formula EAPC = 100 × (10^α-1). Positive EAPC values with 95% confidence intervals (CIs) above zero indicated increasing trends, while negative values signified decreases [11, 12]. Statistical analyses were conducted using R software (version 4.4.0), with data visualization performed via the ggplot2 package. A two-tailed P-value < 0.05 was considered statistically significant.

Results

Breast cancer burden

Over the past three decades, breast cancer has consistently been the female-specific cancer with the highest global burden in terms of incidence, mortality, and DALYs (Fig. 1a). Between 1990 and 2021, global incident cases rose from 0.87 million to 2.08 million, with the ASIR increasing from 39.99 to 46.40 (EAPC = 0.40). The highest incidence and ASIR were observed in high SDI countries (Fig. 1b). East Asia reported the largest number of incident cases in 2021, totaling 401,076 (Table 1). However, high-income North America had the highest ASIR at 94.93, nearly double the global average. Nationally, China recorded the highest number of new cases (385,838), followed by the United States (269,012) and India (156,160) (Fig. 2a), collectively accounting for nearly 40% of global incident cases.

Fig. 1

Global and regional trends in female cancer incidences, deaths, and disability-adjusted life years (DALYs). a. The absolute numbers for incidences, deaths, and DALYs across different socio-demographic index (SDI) regions and globally were displayed. b. displays the age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASDALYR), showcasing the varying trends by SDI regions

Table 1 The incidence of breast cancer in 1990 and 2021

Fig. 2

Global distribution of breast cancer incidences, deaths, and disability-adjusted life years (DALYs) in 2021. a. The incidences of breast cancer. b. The breast cancer mortality. c. The breast cancer DALYs

Between 1990 and 2021, breast cancer-related deaths increased from 350,577 to 660,925, although the ASDR declined from 16.60 to 14.55 (EAPC = -0.55) (Table 2). Middle SDI countries recorded the highest number of deaths in 2021 (181,470), surpassing high SDI countries, while low SDI countries had the highest ASDR at 16.00. Significant geographical disparities were observed across the 21 global regions. South Asia reported the highest number of deaths (105,497), while southern sub-Saharan Africa had the highest ASDR at 24.93. Nationally, China (88,107), India (78,879), and the United States (52,869) (Fig. 2b) accounted for approximately 33% of global breast cancer deaths. Interestingly, Palau and the United Arab Emirates had the highest ASDRs globally, while Western European countries and the United States, despite high incidence rates, reported relatively lower ASDRs (Fig. S1a-1b).

Table 2 The death of breast cancer in 1990 and 2021

DALY trends mirrored those of mortality. In 2021, global DALYs for breast cancer reached 20.25 million, with an ASDALYR of 455.56. Middle SDI countries recorded the highest DALYs (6.04 million), whereas low SDI regions had the highest ASDALYR (488.24). South Asia contributed 3.71 million DALYs, while southern sub-Saharan Africa had the highest ASDALYR at 728.94 (Table 3). Nationally, China, India, and the United States had the highest DALYs (Fig. 2c). Notably, American Samoa recorded the highest ASDALYR worldwide in 2021 (Fig. S1c).

Table 3 The DALY of breast cancer in 1990 and 2021

Cervical cancer

Among the four female-specific cancers, cervical cancer ranks second in global cancer burden after breast cancer. The total incidence of cervical cancer remains substantial and continues to grow slowly, reaching 0.67 million cases in 2021. However, when accounting for population size and structure, its ASIR has shown a declining trend, decreasing from 18.11 in 1990 to 15.32 in 2021 (EAPC = -0.54) (Table 4). Stratified by SDI region, middle SDI areas recorded the highest incidence, while low SDI regions had the highest ASIR. Geographically, East Asia reported the largest number of incident cases in 2021, totaling 137,864, while southern sub-Saharan Africa had the highest ASIR at 42.40, nearly three times the global average. At the national level, China, India, and the United States accounted for the highest number of cervical cancer cases globally in 2021, reporting 132,788, 112,103, and 27,262 cases, respectively (Fig. 3a). Conversely, the highest ASIRs were observed in Kiribati and Lesotho (Fig. S2a).

Table 4 The incidence of cervical cancer in 1990 and 2021

Fig. 3

Global distribution of cervical cancer incidences, deaths, and disability-adjusted life years (DALYs) in 2021. a. The cervical cancer incidences. b. The cervical cancer mortality. c. The cervical cancer DALYs

The number of deaths from cervical cancer increased from 211,484 in 1990 to 296,667 in 2021, while the ASDR declined from 9.68 to 6.62 (EAPC = -1.27) (Table 5). Middle SDI regions reported the highest number of deaths, whereas low SDI regions consistently exhibited the highest ASDR over the past three decades. Geographically, South Asia recorded the largest number of cervical cancer deaths in 2021, while central sub-Saharan Africa reported the highest ASDR worldwide. At the national level, China, India, and Brazil had the highest cervical cancer mortality in 2021, with 49,841, 60,041, and 11,248 deaths, respectively (Fig. 3b). Conversely, Kiribati and Lesotho reported the highest ASDRs globally (Fig. S2b).

Table 5 The death of cervical cancer in 1990 and 2021

The trends in cervical cancer DALYs closely mirrored those of cervical cancer mortality. Globally, cervical cancer DALYs increased from 7.42 million in 1990 to 9.91 million in 2021, while the ASDALYR declined from 330.11 to 226.28 (EAPC = -1.27) (Table 6). Low SDI regions consistently exhibited the highest ASDALYR. Geographically, South Asia recorded the highest total DALYs in 2021, while southern sub-Saharan Africa, including countries like Lesotho, reported the highest ASDALYR (Fig. S2c). Notably, southern sub-Saharan Africa remains the only region where cervical cancer ASIR, ASDR, and ASDALYR are still rapidly increasing. At the national level, China, India, and Brazil had the highest cervical cancer DALYs in 2021, with 1.55 million, 2.06 million, and 0.38 million DALYs, respectively (Fig. 3c). Kiribati and Lesotho continued to sustain the highest ASDALYRs worldwide in 2021 (Fig. S2c).

Table 6 The DALY of cervical cancer in 1990 and 2021

Ovarian cancer

From 1990 to 2021, the global incidence of ovarian cancer increased from 159,096 to 298,876 cases, while the ASIR declined from 7.22 to 6.71 (EAPC = -0.38) (Table 7). Middle SDI regions experienced rapid growth in ovarian cancer incident cases, surpassing high SDI regions in 2021 to rank first in total incident cases. However, high SDI regions continued to report the highest ASIR for ovarian cancer. Regionally, South Asia recorded the largest number of cases (49,664) in 2021, while Central Europe reported the highest ASIR at 10.80. Nationally, China accounted for the highest number of new ovarian cancer cases in 2021 (41,236), followed by India (36,777) and the United States (25,213) (Fig. 4a). Collectively, these three countries represented approximately 35% of global new cases. The highest ASIRs were observed in the United Arab Emirates and Seychelles (Fig. S3a).

Table 7 The incidence of ovarian cancer in 1990 and 2021

Fig. 4

Global distribution of ovarian cancer incidences, deaths, and disability-adjusted life years (DALYs) in 2021. a. The incidences of ovarian cancer. b. The ovarian cancer mortality. c. The DALYs of ovarian cancer

In the past 32 years, ovarian cancer-related deaths increased from 100,584 to 185,609, while the ASDR declined from 4.73 to 4.06 (EAPC = -0.62) (Table 8). Mortality increased across all SDI regions, with high SDI regions reporting both the highest number of deaths and the highest ASDR in 2021. Among the 21 global regions, South Asia recorded the largest number of ovarian cancer deaths (30,585), while Central Europe had the highest ASDR at 7.40. Nationally, China led in ovarian cancer deaths (25,144), followed by India (23,219) and the United States (17,229) (Fig. 4b). The United Arab Emirates exhibited the highest ASDR globally (Fig. S3b).

Table 8 The death of ovarian cancer in 1990 and 2021

Ovarian cancer DALYs followed a similar trend, increasing steadily from 1990 to 2021, while the ASDALYR declined (EAPC = -0.59) (Table 9). In 2021, global DALYs reached 5.16 million, with an ASDALYR of 115.15. Population in middle SDI regions sustained the most DALYs in 2021 at 1.42 million, whereas high SDI regions maintained the highest ASDALYR despite a declining trend (EAPC = -1.48). Regionally, South Asia reported the highest number of DALYs (960,208), while Central Europe recorded the highest ASDALYR. Nationally, China had the highest ovarian cancer DALYs in 2021 (750,549), followed by India and the United States (Fig. 4c). The United Arab Emirates continued to report the highest ASDALYR globally (Fig. S3c).

Table 9 The DALY of ovarian cancer in 1990 and 2021

Uterine cancer

Uterine cancer is the fastest-growing female-specific cancer, with the number of cases rising from 191,291 in 1990 to 473,614 in 2021. Correspondingly, the ASIR increased from 8.87 to 10.36 during this period (EAPC = 0.54) (Table 10). High SDI regions reported both the highest number of cases and the highest ASIR, with rates continuing to rise significantly (EAPC = 1.36). Geographically, high-income North America recorded the largest number of cases in 2021, totaling 103,521, and the highest ASIR at 31.78. Nationally, the United States reported the highest number of new cases in 2021 (96,331), followed by China (72,019) and Russia (46,639) (Fig. 5a). Collectively, these three countries accounted for approximately 45% of global new cases. The highest ASIRs were observed in the United Arab Emirates and Russia (Fig. S4a).

Table 10 The incidence of uterine cancer in 1990 and 2021

Fig. 5

Global distribution of uterine cancer incidences, deaths, and disability-adjusted life years (DALYs) in 2021. a. The uterine cancer incidences. b. The uterine cancer mortality. c. The uterine cancer DALYs

Between 1990 and 2021, global deaths from uterine cancer increased from 54,849 to 97,672, while the ASDR declined from 2.60 to 2.11 (EAPC = -0.78) (Table 11). Mortality increased across all SDI regions, with high SDI regions reporting both the highest number of deaths (31,632) and the highest ASDR. In 2021, the East Asia region recorded the largest number of deaths globally, totaling 14,233, while the Caribbean had the highest ASDR at 5.38. Nationally, China recorded the highest number of deaths in 2021 (13,599), followed by the United States (11,886) and Russia (7,356) (Fig. 5b). The United Arab Emirates consistently exhibited the highest ASDR globally (Fig. S4b).

Table 11 The death of uterine cancer in 1990 and 2021

Over the past 32 years, the DALYs for uterine cancer increased from 1.50 million in 1990 to 2.56 million in 2021 (Table 12). Correspondingly, the ASDALYR declined from 69.17 to 56.15 (EAPC = -0.78). High SDI regions reported both the highest DALYs and ASDALYR. In 2021, East Asia recorded the highest DALYs among all regions, totaling 425,142, while the Caribbean had the highest ASDALYR. Nationally, China reported the highest DALYs in 2021 (405,490), followed by the United States and Russia (Fig. 5c). Similarly, the United Arab Emirates recorded the highest ASDALYR globally (Fig. S4c).

Table 12 The DALY of uterine cancer in 1990 and 2021

Correlation between ASRs of female-specific cancers and socio-demographics

To explore the role of socio-economic development (measured by SDI) on the incidence and mortality trends of female-specific cancers, we generated scatter plots to illustrate the dynamic changes in SDI and age-standardized rates (ASIR, ASDR, and ASDALYR) across 21 global regions over the past 32 years. Across most regions, a positive correlation was observed between SDI and the ASIRs of breast and uterine cancers, both of which showed a gradual increase as SDI rose. However, the relationship between SDI and ovarian cancer was more complex: while higher SDI was generally associated with higher ASIR, in regions where SDI exceeded 0.7, such as high-income regions like North America, Western Europe, and Australia, additional increases in SDI were associated with a decline in ASIR. In contrast, the incidence of cervical cancer consistently decreased as SDI increased across different regions (Fig. 6). Additionally, a significant negative correlation was observed between SDI and both ASDR and ASDALYR for cervical cancer, with both indicators decreasing markedly as SDI increased (Fig. S5). For the other three cancers, both ASDR and ASDALYR increased with SDI until it reached 0.7, after which they began to decline.

Fig. 6

Global trends in age-standardized incidence rates (ASIRs) and socio-demographic index (SDI) from 1990 to 2021. The Rho values (Spearman’s rho correlation coefficient) indicate the strength of the correlation between the SDI and ASIRs

Age distribution

Age is a key factor influencing tumor burden. Therefore, we interrogated the age distribution patterns for female-specific cancers globally. Except for the super-elderly population (aged 80 years and older), the incidence, mortality, and DALYs for breast cancer peaked in the 55–59 year age group (Fig. 7a). For cervical cancer, the incidence remained consistently high between the ages of 40 and 59 years, with mortality peaking at 55–59 years and the DALY peak occurring at 50–54 years. In ovarian cancer, the incidence similarly peaked at 55–59 years, while the highest mortality was observed in those aged 80 years and older. The DALY peak for ovarian cancer also occurred in the 55–59 year age group. For uterine cancer, the incidence peaked at 60–64 years, with the highest mortality observed in the population aged 80 years and older, and the DALY peak occurring at 60–64 years.

Fig. 7

Age distribution of incidences, mortality, and disability-adjusted life years (DALYs) for female-specific cancers in 2021. a. Global incidences, deaths, and DALYs for breast, cervical, ovarian, and uterine cancers across different age groups in 2021. b. Global age-standardized rates of incidence, death, and DALYs for breast, cervical, ovarian, and uterine cancers across different age groups in 2021

Overall, the ASIRs, ASDRs, and ASDALYRs for most female-specific cancers increased progressively with age (Fig. 7b). Notably, both the ASIR and ASDALYR for cervical cancer peaked at 55–59 years, while these indicators for uterine cancer reached their highest values at 70–74 years. Additionally, the ASDALYR for ovarian cancer also peaked at 70–74 years. Although the age distribution for cancer in regions with different SDI values might vary slightly from the global trend, the overall pattern remained largely consistent across regions (Fig. S6-S10).

Attributable risk factors

Based on GBD 2021 data, we analyzed the Level 2 attributable risk factors for female-specific cancers. Six Level 2 risk factors were identified for breast cancer mortality, including dietary risks, high alcohol use, high BMI, high fasting plasma glucose, low physical activity, and tobacco use. Among these, dietary risks were the most significant contributor to breast cancer mortality globally and across regions with different SDI values (Fig. 8a). Notably, high alcohol use was a more significant contributor to breast cancer mortality in high than in low SDI regions. For cervical cancer, unsafe sex was the most important risk factor, contributing substantially to cervical cancer mortality. However, in high SDI regions, tobacco exposure also played a role in cervical cancer mortality (Fig. 8b). High BMI and occupational risks were the major risk factors for ovarian cancer mortality. Globally, high BMI contributed more to ovarian cancer mortality, but with increasing SDI levels, the contribution of occupational risks to ovarian cancer mortality gradually increased (Fig. 8c). High BMI was the only Level 2 risk factor for uterine cancer mortality. While its contribution to uterine cancer mortality was higher in high SDI regions, the growth rate was faster in low SDI regions (Fig. 8d). The contribution of risk factors to cancer DALYs was similar to their contribution to cancer mortality (Fig. S11).

Fig. 8

Level 2 risk factors contributing to female-specific cancer-related death. The trends in risk factors contributing to deaths for breast, cervical, ovarian, and uterine cancers globally and across different regions from 1990 to 2021, a. Breast cancer, b. Cervical cancer, c. Ovarian cancer d. Uterine cancer

Discussion

In this study, we report the epidemiological trends and attributable risk factors for four major female-specific cancers: breast, cervical, ovarian, and uterine cancer. The key findings are as follows: First, breast cancer bears the highest global disease burden, followed by cervical, ovarian, and uterine cancer. Over the past three decades, both incidence and mortality for these cancers have consistently increased worldwide. Second, after accounting for population growth and demographic changes, the ASIR reveals distinct patterns. The ASIR for breast and uterine cancer has risen, while that for cervical and ovarian cancer has declined. Simultaneously, ASDR and ASDALYR for all four cancers have decreased. Third, the ASIR for breast, ovarian, and uterine cancer increases with SDI, while cervical cancer follows an inverse trend. Finally, the ASIR and ASDR for all four cancers show a positive correlation with age, highlighting the growing burden in aging populations. The attributable risk factors for these cancers vary significantly, with notable differences between high and low SDI regions.

These findings align with our previous reports [4], notably the steady increase in global breast cancer incidence between 1990 and 2021, while ASDR and ASDALYR continued to decline. This increase in breast cancer incidence can be attributed to the widespread implementation of screening technologies, such as mammography and ultrasound, alongside improvements in cancer registries. These advancements have led to more diagnoses, contributing to the persistent high prevalence of breast cancer. Concurrently, progress in molecular subtyping, targeted therapies, and immunotherapies has markedly improved survival rates [13,14,15]. These developments explain the contrast between rising ASIR and declining ASDR, underscoring the positive impact of early detection and therapeutic innovations.

A close relationship between breast cancer incidence and SDI is evident, with high-income regions such as North America and Western Europe exhibiting breast cancer ASIRs significantly higher than the global average. Additionally, both ASIR and ASDR increase with age, raising concerns as the global population ages. Six Level 2 risk factors, including dietary risks, alcohol use, high BMI, high fasting plasma glucose, low physical activity, and tobacco use, were identified as major contributors to breast cancer mortality. These risk factors are closely associated with modern lifestyles, socio-economic development, and urbanization, consistent with previous studies highlighting the influence of age, fertility, diet, and tobacco exposure on breast cancer mortality [16,17,18].

Cervical cancer, though less burdensome globally than breast cancer, exhibits a higher ASIR than breast cancer in low SDI regions. Fortunately, the ASIR, ASDR, and ASDALYR for cervical cancer are rapidly declining worldwide. As a virus-associated malignancy, cervical cancer is preventable through interventions targeting HPV. The promotion of HPV vaccination, early screening, and treatment of precancerous lesions has led to significant reductions in incidence and mortality [19,20,21]. However, there is a negative correlation between cervical cancer burden and SDI, with lower-income regions bearing a heavier burden due to inadequate public health resources. In certain areas, such as southern sub-Saharan Africa, the incidence of cervical cancer continues to rise, emphasizing the need for expanded international support for vaccination and screening programs, including training healthcare professionals and improving facilities.

Ovarian cancer incidence and mortality have decreased globally, with high SDI regions contributing the most to this decline. In contrast, middle, low-middle, and low SDI regions continue to experience rising ASIR and ASDR. Despite a general positive correlation between ASIR and SDI, ovarian cancer ASIR declines in regions with SDI values above 0.7. As with breast cancer, both ASIR and ASDR for ovarian cancer increase with age. Major risk factors for ovarian cancer-related deaths include high BMI and occupational risks. At the same time, some behaviors, such as breastfeeding and tubal ligation, have been identified as protective factors for ovarian cancer [22, 23]. At the present stage, ovarian cancer remains one of the female-specific cancers with a high mortality rate, with limited effective early diagnostic and screening measures. Recent advancements in genetic testing for patient stratification, neoadjuvant chemotherapy, hyperthermic intraperitoneal chemotherapy, targeted therapy, immunotherapy, and advanced surgical techniques have contributed to reductions in ovarian cancer mortality [24,25,26].

Uterine cancer incidence has steadily increased, particularly in high SDI regions. In fact, the ASIR for uterine cancer shows a positive correlation with SDI, with a notable rise in regions such as high-income North America. High BMI is a key risk factor for uterine cancer death, with overweight or obese women more likely to develop uterine cancer [27,28,29]. A lack of physical activity and the high prevalence of diabetes also contribute to increased risk [30, 31]. Public health initiatives focused on weight management and promoting physical activity could help mitigate the growing burden of uterine cancer.

Over the past 32 years, the disease burden of female-specific cancers has risen rapidly. Given the positive correlation between age and cancer incidence rate, coupled with the aging global population, the burden of these cancers is expected to continue increasing in the coming decades. Projections indicate that the economic burden of female-specific cancers will account for 0.073% of the global gross domestic product (GDP) from 2020 to 2050, further exacerbating economic pressure on individuals and healthcare systems [32]. The emergence of new infectious diseases, such as COVID-19, may further strain already limited public health resources, posing additional challenges to cancer prevention and treatment. Global mobilization of medical resources is crucial to address these challenges, alongside the enhancement of screening strategies, optimization of diagnostic tools, and the development of targeted, personalized therapies.

This study has several limitations. First, data from the GBD 2021 project, while comprehensive and statistically refined, may underestimate cancer burden in underdeveloped regions due to incomplete cancer registries and limited public database resources. Second, there is a paucity of epidemiological statistics of pathological subtype of each cancer, leading to a compromised analysis, exemplified by the lack of data on non-HPV-associated cervical cancer. Third, our analysis focuses on four major female-specific cancers, excluding rarer cancer types. Finally, the analysis of attributable risk factors is based on the available Level 2 risk factors in the GBD 2021 database, which may not capture all clinically relevant factors. Therefore, caution should be exercised in interpreting these results.

Conclusion

The present work provides a comprehensive overview of the global burden and attributable risk factors for four major female-specific cancers: breast, cervical, ovarian, and uterine cancers. Our findings show that breast cancer bears the highest global disease burden, especially in high-SDI regions, while the incidence of cervical cancer remains high in low-income areas, despite declining in most parts of the world. There are rising trends in the incidence of ovarian and uterine cancer, with age and lifestyle-related factors contributing significantly to their burden. Addressing these challenges requires expanding prevention and early detection programs, particularly in resource-limited regions. With the aging global population, there is a pressing need for age-appropriate interventions and improved cancer care infrastructure. This study highlights the importance of targeted policies, lifestyle changes, and ongoing research to reduce the global burden of female-specific cancers and improve outcomes for women worldwide.