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.

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

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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.

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 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.

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).

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).

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