Temporal Trends in Cancer Burden and 27 Subtypes Among Women of Childbearing Age Globally from 1990 to 2021.

Introduction

Cancer poses a substantial challenge to global health in the 21st century, accounting for nearly 10 million deaths in 2022 and ranking as the second leading cause of mortality worldwide 1 , 2 Although advances in prevention, screening, diagnosis, and treatment have improved cancer outcomes, the absolute cancer burden continues to rise, particularly in low- and middle-income countries where delayed diagnosis and limited access to treatment remain common. These trends highlight the urgency of Sustainable Development Goal (SDG) 3, particularly Target 3.4, which aims to reduce premature mortality from non-communicable diseases by one-third by 2030, and Target 3.8, which seeks to achieve universal health coverage. 3

Women of childbearing age (WCBA), generally defined as women aged 15–49 years, represent a clinically and socially important population. Cancer in this age group may affect fertility, pregnancy planning, family health, productivity, and premature mortality. 4 , 5 In addition, cancer patterns among WCBA may differ from those in older women because of differences in reproductive history, hormonal exposure, infection-related risks, screening uptake, lifestyle factors, and health-care access. Therefore, a comprehensive assessment of cancer burden in this population is essential for targeted prevention, early detection, and equitable resource allocation.

Previous studies have examined cancer burden in the general population, among adolescents and young adults, among older adults, or for selected female cancers such as breast, cervical, ovarian, and uterine cancers. 6–9 However, evidence remains limited on the overall burden, temporal trends, cancer-type composition, and socioeconomic inequalities of a broad range of cancers among WCBA at global, regional, and national levels. In particular, few studies have simultaneously assessed incidence, mortality, demographic drivers, and cross-country inequalities across all Global Burden of Disease (GBD) regions and Socio-demographic Index (SDI) levels.

Using modeled estimates from the GBD 2021, this study assessed the burden of total cancer and 27 cancer subtypes among women aged 15–49 years from 1990 to 2021. We estimated age-standardized incidence and mortality rates, evaluated temporal trends using average annual percentage changes (AAPC), quantified the contributions of population growth, age-structure change, and epidemiological change through decomposition analysis, and assessed cross-country inequalities using the slope index of inequality (SII) and concentration index (CIX). These findings may help identify priority cancer types and regions, inform age-specific prevention and screening strategies, and support more equitable cancer control among WCBA.

Methods

Data Sources and Disease Definition

We conducted a secondary analysis utilized the GBD 2021 databases, covering 288 causes of mortality and 371 diseases/injuries across 204 countries and territories from 1990 to 2021. 10–12 All data are publicly accessible via the Global Health Data Exchange online query tool ( https://gbd2021.healthdata.org/gbd-results/ ). 13 Detailed methodologies and modeling strategies have been previously reported in GBD studies. 10–12 For this analysis, the following extraction settings were used: measure, incidence and deaths; metric, number and rate; sex, female; age groups, 15–19, 20–24, 25–29, 30–34, 35–39, 40–44, and 45–49 years; years, 1990 to 2021; locations, global, five SDI regions, 21 GBD regions, and 204 countries and territories; and causes, total malignant neoplasms and 27 cancer subtypes in the GBD cause hierarchy. WCBA were defined as women aged 15–49 years according to the World Health Organization definition. 14 The International Classification of Diseases codes for the 27 cancer subtypes investigated are provided in the Supplementary Appendix ( Table S1 ).

Covering 21 GBD regions and 204 countries/territories, the GBD databases classifies locations according to SDI values ( Tables S2 – 4 ). The SDI, a composite indicator closely tied to health outcomes, is derived from fertility rates in women under 25, average years of schooling among those aged 15 and older, and lag-distributed income per capita, combined through a geometric mean. Ranging from 0 to 1, higher SDI scores reflect greater socioeconomic advancement. For this analysis, countries and regions were classified into five SDI levels (low, low-middle, middle, high-middle, and high) to explore the association between cancer burden and socioeconomic development ( Tables S3 and 4 ).

Statistical Analysis

We first conducted descriptive analyses of cancer incidence and mortality among WCBA from 1990 to 2021 at the global, SDI regional, GBD regional, and national levels. Counts were reported as estimated numbers, and rates were expressed per 100,000 population. To improve comparability across populations and over time, age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were calculated using the direct age-standardization method and the GBD 2021 world standard population. 11 Seven five-year age groups from 15–19 to 45–49 years were included in the age standardization. The age-standardized rate (ASR) was calculated as follows (Formula 1):

In the equation, α i indicates the age-specific rate for the i -th age group, and W i corresponds to the population count for that group. The total number of age groups ( N ) is seven in our study.

Because GBD estimates are model-based rather than directly observed registry counts from all countries, 95% uncertainty intervals (UIs) provided by GBD were extracted and reported for incidence and death counts to describe the uncertainty of the estimated numbers. For ASIRs and ASMRs, 95% confidence intervals (CIs) were calculated after age standardization to assess the precision of rate estimates. These uncertainty measures were used to guide cautious interpretation, particularly for countries or cancer types with sparse source data.

The temporal trend in ASRs were quantified by the AAPC and its 95% CI, estimated with Joinpoint Trend Analysis Software (Version 5.1.0). 15 , 16 Joinpoint models were fitted to annual ASRs from 1990 to 2021 using a log-linear model. A maximum of five joinpoints was allowed. The best-fitting model was selected using the Monte Carlo permutation test, and model selection was based on the minimum number of joinpoints required to adequately characterize significant changes in temporal trends. Annual percentage changes were estimated for each time segment, and AAPCs were calculated as weighted averages of the annual percentage changes over the full study period. An upward trend is indicated when the 95% CI is entirely positive, a downward trend when entirely negative, and stability when the CI includes zero.

Decomposition analysis was performed to quantify the contributions of population growth, age-structure change, and epidemiological change to changes in the absolute numbers of incident cases and deaths between 1990 and 2021. Following Das Gupta’s decomposition method, 17 the difference in cancer counts between 1990 and 2021 was decomposed into three components: changes attributable to the total population size of WCBA, changes attributable to the age distribution within the 15–49-year population, and changes attributable to age-specific cancer rates. The epidemiological component therefore reflects changes in age-specific incidence or mortality rates after accounting for demographic changes. Decomposition analyses were conducted for total cancer globally and by SDI region.

Spearman correlation was used to explore the nonlinear association between SDI and ASRs across geographical regions. To assess cross-country socioeconomic-related inequalities in cancer burden, we calculated the SII and CIX, which are recommended by the World Health Organization for health inequality monitoring. 18 For the SII, countries and territories were ranked by SDI and assigned a relative socioeconomic rank. A weighted regression model was then fitted, with the cancer burden indicator as the dependent variable and the relative SDI rank as the independent variable, weighted by the population size of WCBA. The SII represents the absolute difference in the cancer burden indicator between the highest and lowest ends of the SDI distribution. For the CIX, the relative inequality in cancer burden across the SDI distribution was quantified using a concentration curve, with positive values indicating concentration of the burden in higher-SDI countries and negative values indicating concentration in lower-SDI countries.

Statistical analyses and visualizations were carried out using R software (version 4.4.1; The R Foundation for Statistical Computing, Vienna, Austria) and the Joinpoint Regression Program (version 5.1.0.0; National Cancer Institute, Bethesda, MD, USA).

Results

Burden of Total Cancer

At Global Level

From 1990 to 2021, the global burden of cancer in WCBA experienced a significant rise, with new cases rising from 1,047,101 to 1,904,657 and deaths increasing from 398,342 to 508,564 ( Table 1 ). The ASIR increased slightly from 89.20 (95% CI 83.53 to 94.81) to 93.93 (95% CI 86.99 to 101.18) per 100,000, with an AAPC of 0.16 (95% CI 0.08 to 0.24). In contrast, the ASMR declined from 34.02 (95% CI 31.68 to 36.39) to 25.09 (95% CI 23.14 to 27.18) per 100,000, with an AAPC of −0.97 (95% CI −1.05 to −0.90). Decomposition analyses revealed that from 1990 to 2021, female cancer incidence increased substantially by 81.90%, predominantly due to population growth (51.34%) and aging (23.33%), with a modest contribution from epidemiological changes (7.23%) ( Figure 1 and Table S5 ). Cancer-related deaths rose by 27.67%, driven mainly by population growth (43.30%) and aging (19.72%), offset by epidemiological improvements (−35.35%).

At GBD Regional and National Levels

The cancer incidence and mortality among WCBA exhibited marked disparities across geographical regions. Among the 21 GBD regions, High-income North America reported the highest ASIR of 304.29 (95% CI 271.02 to 342.32) per 100,000 in 2021, while Western Sub-Saharan Africa exhibited the lowest ASIR at 50.71 (95% CI 36.22 to 66.07) per 100,000 ( Figure 2A and Table S6 ). ASMR were highest in Southern Sub-Saharan Africa (43.31 per 100,000, 95% CI 37.03 to 50.30) and lowest in High-income Asia Pacific (16.63 per 100,000, 95% CI 16.08 to 17.24) ( Figure 2B and Table S6 ). Regarding trends from 1990 to 2021, North Africa and the Middle East experienced the greatest annual increase in ASIR (AAPC 1.38, 95% CI 1.28 to 1.48), whereas Central Asia showed the most significant decrease (AAPC −0.71, 95% CI −1.04 to −0.38) ( Figure 2C and Table S6 ). The sharpest decline in ASMR was observed in Western Europe (AAPC −1.85, 95% CI −2.04 to −1.65), contrasting with Southern Sub-Saharan Africa, which demonstrated no significant temporal variation in ASMR (AAPC 0.22, 95% CI −0.73 to 1.18) ( Figure 2D and Table S6 ).

Across 204 countries and territories, the estimated burden of cancer among WCBA varied substantially ( Figure 2 and Table S7 ). In 2021, higher ASIRs were generally observed in high-income settings ( Figure 2A and Table S7 ), whereas higher ASMRs were more frequently observed in countries with lower levels of socioeconomic development ( Figure 2B and Table S7 ). The United States of America had the highest estimated ASIR, while Zimbabwe had the highest estimated ASMR. Temporal trends also differed markedly across countries and territories from 1990 to 2021. Detailed country-specific estimates, including ASIR, ASMR, AAPC, and corresponding uncertainty or confidence intervals, are provided in Table S7 .

At SDI Regional Levels

In 2021, high SDI region exhibited the highest ASIR (174.41 per 100,000, 95% UI 161.99 to 188.94) and the lowest ASMR (18.77 per 100,000, 95% UI 18.22 to 19.35), whereas the low SDI region demonstrated the lowest ASIR (60.76 per 100,000, 95% UI 51.67 to 70.20) and the highest ASMR (30.11 per 100,000, 95% UI 25.58 to 34.85) ( Table S8 and Figure S1 ). Although ASIR increased across all SDI regions, the magnitude varied: middle SDI region had the fastest annual rise in ASIR (AAPC 0.62, 95% CI 0.48 to 0.76), followed by low-middle (AAPC 0.56, 95% CI 0.39 to 0.73), high-middle (AAPC 0.45, 95% CI 0.26 to 0.64), and high SDI (AAPC 0.29, 95% CI 0.16 to 0.43) regions ( Table S8 ). Notably, low SDI region showed a stable ASIR trend (AAPC −0.01, 95% CI −0.11 to 0.10). In contrast, ASMR declined across all SDI regions, with the steepest reduction in high SDI region (AAPC −1.65, 95% CI −1.72 to −1.58), followed by high-middle (AAPC −1.48, 95% CI −1.63 to −1.34), middle (AAPC −1.11, 95% CI −1.24 to −0.98), low SDI (AAPC −0.64, 95% CI −0.75 to −0.53) regions, and the smallest reduction in low-middle SDI region (AAPC −0.3, 95% CI −0.43 to −0.16).

Decomposition analysis of total cancer burden among WCBA from 1990 to 2021 revealed notable variations across SDI regions ( Figure 1 and Table S5 ). Low and low-middle SDI regions experienced significant increases in incidence (approximately 150%) and deaths (ranging from 91.99% to 108.23%), primarily driven by population growth. High SDI regions reported increased incidence (32.20%) mainly due to aging (14.15%), whereas deaths decreased (−27.21%) due to epidemiological improvements (−45.38%). Middle and high-middle SDI regions showed increases in incidence with varied mortality patterns, influenced by both demographic and epidemiological factors. A significant positive correlation between ASIR and SDI was identified globally and across 21 GBD regions from 1990 to 2021 (R = 0.82, P < 0.001) ( Figure S2 ). However, global ASMR was negatively correlated with SDI (R = −0.16, P < 0.001), although the regional pattern was non-linear. Specifically, ASMR decreased initially with increasing SDI, stabilized at mid-range SDI values, and then declined again at higher SDI levels. The analysis of health inequities revealed significant absolute and relative disparities in the ASIR and ASMR of overall cancer globally in 2021. Higher SDI countries exhibited disproportionately higher ASIR (SII: 54; CIX: 0.20 [95% CI 0.16 to 0.24]), whereas lower SDI countries had a disproportionately higher cancer mortality burden (SII: −13; CIX: −0.07 [95% CI −0.09 to −0.05]) ( Figure S3 ).

Burden of 27 Specific Cancer Types

At Global Level

Among the 27 estimated cancer types, breast cancer, cervical cancer, non-melanoma skin cancer, ovarian cancer, and colon and rectum cancer were the most frequently diagnosed in WCBA worldwide in 2021 ( Table 1 and Figure 3 ). The main causes of cancer mortality were breast cancer, cervical cancer, tracheal, bronchus, and lung cancer, colon and rectum cancer, and leukemia ( Table 1 and Figure 4 ). From 1990 to 2021, the most pronounced increases in ASIR were observed for thyroid cancer, lip and oral cavity cancer, and non-melanoma skin cancer ( Table 1 , Figure S4 and Table S9 ). Conversely, the most substantial declines in ASIR were seen in stomach cancer, esophageal cancer, and leukemia. The ASIR of colon and rectum cancer remained stable during this period. In terms of ASMR, only multiple myeloma, lip and oral cavity cancer, and mesothelioma exhibited increasing trends. In contrast, the sharpest declines in ASMR were noted for stomach cancer, nasopharyngeal cancer, and esophageal cancer. The ASMR of malignant neoplasm of bone and articular cartilage remained unchanged ( Table 1 , Figure S4 and Table S9 ).

At GBD Regional and National Levels

Significant geographic variations in ASIR and ASMR profiles were observed among WCBA ( Figures 3, 4 , and Table S10 ). Breast and cervical cancers were the most common cancer types in most regions, while mesothelioma and larynx cancer were generally among the least frequent. Notably, in terms of ASIR, malignant skin melanoma ranked second in Australia and Western Europe, while liver cancer was prominent in some regions of sub-Saharan Africa ( Figure 3 and Table S10 ). Regarding ASMR, ovarian cancer, colon and rectum cancer, stomach cancer, and tracheal, bronchus, and lung cancer were also ranked highly across various regions ( Figure 4 and Table S10 ). Comparative rankings demonstrated that Europe and Northern America exhibited relatively higher ASIRs across most cancer types, with Northern America accounting for the largest number of cancer types ranked first by ASIR ( Figure S5 and Table S10 ). In contrast, Africa experienced higher ASMR, especially in Eastern Sub-Saharan Africa, where more cancer types were ranked first by ASMR ( Figure S6 and Table S10 ). Additionally, breast cancer emerged as the most common cancer among WCBA across most countries, dominating both in ASIR and ASMR ( Figure 5A and Table S11 ). In the remaining countries, cervical cancer, and non-melanoma skin cancer ranked foremost in ASIR, while cervical cancer, liver cancer, and stomach cancer held top positions in terms of ASMR ( Figure 5B and Table S11 ).

At SDI Regional Levels

Across five SDI regions, the five most frequent cancer types comprised more than half of the total estimated incident cases and deaths ( Figure 6 and Table S12 ). Breast cancer was the leading cause of cancer incidence in high-middle SDI (32.96%), middle SDI (33.39%), and low-middle SDI (31.30%) regions. Non-melanoma skin cancer exhibited the highest proportion of incident cases in high SDI region (36.82%), whereas cervical cancer was the predominant cancer in low SDI regions (35.25%). Tracheal, bronchus, and lung cancer ranked in the top five in high, high-middle, and middle SDI regions, while colon and rectum cancer was a key contributor in countries with high to low-middle SDI. Leukemia was a major cause of cancer death in middle, low-middle, and low SDI countries.

Age Pattern of 27 Specific Cancer Burden

An age-related rise in both cancer incidence and mortality was observed among WCBA, with the highest burden recorded at 45 to 49 age group ( Figure 7A and Table S13 ). Age-specific cancer patterns revealed notable differences. Among adolescents (15–19 years), leukemia, ovarian cancer, and brain and central nervous system cancer were most frequently diagnosed ( Figures 7B, 7C and Table S14 ). In women aged 20 to 24 years, cervical and ovarian cancers, along with non-melanoma skin cancer, were the most common. From 25 to 49 years, breast, cervical, and non-melanoma skin cancers were the leading diagnoses. Similarly, cancer-related mortality showed an age-dependent shift. Leukemia, brain and central nervous system cancer, and malignant neoplasm of bone and articular cartilage were the primary causes of death in adolescents. In women aged 20 to 29 years, cervical cancer, leukemia, and breast cancer contributed most to mortality. From age 30 onward, breast and cervical cancers remained leading causes, while stomach cancer emerged in the 35 to 39 age group. In women over 40, tracheal, bronchus, and lung cancer increasingly contributed to mortality alongside breast and cervical cancers.

Discussion

Based on GBD 2021 data, this study presented an updated overview of spatial and temporal trends in ASIR and ASMR of total cancer and 27 cancer subtypes among WCBA, and explored the multifaceted interplay among demographic, epidemiological, and socioeconomic factors. From 1990 to 2021, the global number of incident cancer cases increased by 857,556, and cancer-related deaths rose by 110,222, primarily driven by population growth. The ASIR exhibited a modest annual increase of 0.16%, while the ASMR declined by 0.97% per year. Considerable heterogeneity was observed in cancer burden across regions, countries, cancer types, and age groups. A pivotal finding was the positive correlation between ASIR and SDI, contrasted with an inverse relationship between ASMR and SDI, underscoring that higher SDI countries experienced elevated incidence but lower mortality, while lower SDI countries bore a disproportionate mortality burden. These observations highlighted the imperative for tailored public health strategies to mitigate the cancer burden in this demographic.

Several previous studies on the burden of female cancers (breast, cervical, uterine, and ovarian cancers) have revealed similar upward trends in incidence alongside declining mortality. For instance, a study examining the global burden of female cancers reported around one million new cancer cases, with the estimated annual percentage changes in ASIR of 0.16% and a corresponding annual decline of 0.73% in age-standardized DALY rates between 1990 and 2021. 9 Similarly, age-specific assessments have demonstrated that younger women (aged 15–39 years) experienced increasing ASIR and age-standardized prevalence rates of female cancers, despite improvements in ASMR and age-standardized DALY rates. 19 Our modestly lower AAPC in ASIR (0.10% vs 0.16%) might reflect a broader range of cancers, including those outside of breast and reproductive cancers. In contrast, the sustained reduction in ASMR (−1.14% per year) may reflect improvements in early diagnosis, multidisciplinary management, and supportive care. In the United States, breast cancer mortality has dropped significantly from 33 deaths per 100,000 women in 1989 to 19 deaths per 100,000 in 2022. 20 Likewise, cervical cancer mortality has decreased markedly in areas with national human papillomavirus (HPV) vaccination and organized screening programs, especially in high-income countries. 21 , 22

The correlation between SDI and cancer burden revealed profound disparities. In high-SDI regions, higher estimated ASIRs may partly reflect greater diagnostic capacity, more complete cancer registration, and wider access to screening or early detection services, such as mammography for breast cancer, low-dose computed tomography for lung cancer in selected high-risk populations, and endoscopy for gastrointestinal cancers. At the same time, lower ASMRs in these settings may be consistent with earlier diagnosis and broader access to effective cancer treatment, including surgery, radiotherapy, systemic therapy, targeted therapy, immunotherapy, and multidisciplinary care. However, our ecological analysis could not quantify the independent contribution of each of these factors. In contrast, the relatively higher ASMRs observed in low-SDI regions may reflect delayed diagnosis, limited access to pathology and imaging, restricted availability of surgery, radiotherapy and systemic therapies, fragmented referral systems, and incomplete cancer care coverage. 23 These health-system constraints may contribute to the mismatch between lower estimated incidence and higher mortality in some low-resource settings. Differences in risk-factor profiles may also contribute to the observed SDI-related patterns, although these explanations remain hypothesis-generating. In high-SDI countries, changes in obesity, diet, physical activity, alcohol use, environmental exposures, reproductive patterns, and health-care-seeking behavior may influence cancer incidence. 24 , 25 Later childbearing, lower parity, and shorter breastfeeding duration have been associated with increased breast cancer risk, 26–29 and may partly explain higher estimated breast cancer incidence in some high-SDI settings. In contrast, higher fertility in low SDI countries may provide some protection against breast cancer, though this is offset by a greater burden of infection-related cancers. Higher education levels in high SDI countries correlate with increased healthcare-seeking behavior, leading to higher diagnosis rates. Conversely, in low SDI countries, socioeconomic barriers, including poverty and low education, worsen disparities. Moreover, infection-related cancers, driven by agents such as HPV and Helicobacter pylori, are more common due to restricted access to vaccination and treatment. 30 Population ageing, even within the reproductive age range, may also contribute to the increasing absolute cancer burden, particularly in high-middle and middle SDI regions. These patterns are corroborated by ecological analyses identifying education, income, inequality, and health system performance as critical determinants of cancer outcomes. 31–33

From a policy perspective, our findings reinforced the dual necessity of preventive interventions to curb rising ASIR alongside strategies to sustain and extend reductions in ASMR. In regions with increasing incidence, such as North Africa and the Middle East, stronger primary prevention and early detection strategies may be particularly important. Primary prevention should prioritize tobacco-control measures, obesity prevention programs, alcohol-harm reduction policies and the promotion of healthy reproductive behaviors where culturally appropriate. Furthermore, considering cervical cancer is preventable, broadening the scope of HPV vaccination to all eligible girls and enhancing cervical cancer screening using high-performance diagnostic tests are crucial strategies. In the context of diagnosis and treatment, strengthening early detection services through risk-stratified screening guidelines can optimize resource allocation. In high-ASIR regions such as High-income North America, refining screening intervals and modalities to minimize overdiagnosis while maximizing mortality benefit is critical. Conversely, in high-mortality and resource-limited regions, particularly Southern Sub-Saharan Africa and low-SDI settings, improving access to timely diagnosis, pathology services, surgery, systemic therapy, radiotherapy, and palliative care should be prioritized. Implementing low-cost visual inspection screening for cervical cancer and improved breast examination protocols may also yield substantial gains in such settings. Moreover, ensuring equitable access to essential cancer medicines, radiotherapy and palliative care must be embedded within universal health coverage schemes. 23 , 34 Finally, robust cancer surveillance systems are essential to monitor trends, evaluate program effectiveness and inform policy. Investment in population-based cancer registries, particularly in underrepresented regions, will enhance data quality and enable timely detection of emerging patterns. 35 International collaborations to share best practices, technical expertise and affordable technologies can amplify progress toward the WHO’s global targets for cancer control. 36

Several previous studies have documented the predominance of breast, cervical, and lung cancers among women. GLOBOCAN 2022 reported breast cancer as the most frequent malignancy in females, followed by lung cancer and cervical cancer. 1 Our finding that non-melanoma skin cancer ranked third in ASIR should be interpreted cautiously. This high estimated incidence may partly reflect enhanced dermatologic surveillance, greater diagnostic intensity, and more complete cancer registration in high-SDI regions. Population-based studies from the United States and Europe have reported sustained increases in basal cell carcinoma and squamous cell carcinoma over recent decades, which is broadly consistent with our findings. 37–39 However, these increases may represent a combination of true changes in disease occurrence and detection-related factors. Greater ultraviolet exposure, outdoor activities, and tanning behaviors may contribute to a genuine increase in risk, 40–42 whereas improved access to dermatologic examination and biopsy may increase the detection of early or indolent lesions. The rising burden of non-melanoma skin cancer might not be a true increase in underlying incidence. Breast cancer ASIR in high SDI countries has been driven by both genuine risk-factor shifts and intensive screening programs. Reproductive changes, such as delayed childbearing, lower parity, and shorter duration of lactation, have been linked to elevated breast cancer risk, while widespread mammographic screening facilitates detection of early-stage and indolent lesions. Genetic susceptibility, driven by Breast Cancer Susceptibility Gene 1 and 2 Mutations, is especially pronounced in younger female women. Nevertheless, the steady decline in global breast cancer ASMR (−0.26% annually) underscores advancements in early detection, systemic therapy, and multidisciplinary care. Targeted agents and refinements in surgery and radiotherapy have contributed to five-year survival rates above 80% in most regions, with the highest age-standardized 5-year relative survival rate of 90.2% observed in the USA. 43 , 44 Cervical cancer ranks second in both ASIR and ASMR among WCBA in 2021. Globally, ASIR and ASMR have declined, primarily due to HPV vaccination and screening programs. Especially in Western countries, high-coverage HPV vaccination programs have been shown to significantly reduce cervical cancer incidence and mortality, 30 , 45–47 a finding that is consistent with our data from high-SDI regions. However, low SDI regions face substantial challenges in implementing HPV vaccination, including sociocultural, health system, financial, and political obstacles, which contribute to poor vaccine coverage and the highest cervical cancer burdens. 30 , 48 In sub-Saharan Africa, high ASIR and ASMR of cervical cancer highlight the urgent need for equitable vaccine distribution and affordable point-of-care screening. Lung cancer’s position among the top three ASMR malignancies reflects its lethality even in younger women. Tobacco remains the principal driver, and although smoking prevalence has declined in many high SDI nations, the lagged effects of past smoking patterns continue to influence mortality. 49 Moreover, emerging evidence implicates environmental pollutants, such as fine particulate matter and household air pollution, in lung cancer risk among non-smokers, particularly in middle-SDI countries undergoing rapid urbanization. 50–52

The most pronounced reductions in ASIR and ASMR among WCBA were observed for stomach cancer, esophageal cancer, and nasopharynx cancer. Declines in stomach cancer incidence (–2.46% per year) parallel global improvements in Helicobacter pylori eradication, refrigeration and decreased dietary salt intake, while mortality reductions reflect earlier detection and more effective multimodal treatment protocols. 53–55 Systemic treatment approaches are increasingly being guided by biomarkers, including microsatellite instability, programmed cell death ligand 1, human epidermal growth factor receptor 2, and tumor mutation burden. 55 Esophageal cancer has similarly declined, driven by reduced tobacco and alcohol consumption, though obesity and gastro-esophageal reflux disease remain risk factors in some regions. The decline in ASIR and ASMR of nasopharynx cancer correlates with reduced consumption of salted fish and preserved foods, broader Epstein-Barr Virus -DNA screening in endemic regions, and the implementation of advanced radiation therapies such as intensity-modulated radiation therapy and image-guided radiation therapy. Thyroid cancer showed the most pronounced increase in ASIR, while mortality remained relatively low. This pattern may be strongly influenced by diagnostic intensity and overdiagnosis, particularly through the widespread use of ultrasound that can detect small, indolent thyroid nodules. 56 Although changes in environmental, metabolic, and reproductive risk factors may also contribute to thyroid cancer trends, the divergence between rapidly increasing incidence and low mortality suggests that overdiagnosis is likely to play an important role. The rising ASIR of lip and oral cavity cancer (1.40% per year) was attributable to persistent tobacco and betel-nut usage in South Asia and the accelerating incidence of HPV-related oropharyngeal cancers in Western populations. 57–59 The modest increases in ASMR for multiple myeloma and mesothelioma highlighted the necessity for targeted interventions.

The disease spectrum demonstrated marked variation among WCBA across age groups, predominantly illustrating a shift from childhood cancers, such as leukemia and brain and central nervous system cancer, to adult cancers, like breast and cervical cancers. Our study identified leukemia, brain and central nervous system cancer as the primary causes of incidence and mortality among adolescents aged 15–19 years, corroborating established pediatric oncology data. Despite therapeutic advancements, leukemia and brain and central nervous system cancer persist as leading mortality causes in adolescents. Ovarian cancer in this age group is predominantly germ-cell ovarian tumors, with good prognosis when treated with surgery and chemotherapy. 60 , 61 In contrast, malignant neoplasms of bone and articular cartilage, though relatively rare, may have higher mortality than some more common cancers due to their high aggressiveness and poor treatment response. From age 20 onward, the incidence of breast cancer rises sharply, peaking between ages 45 and 49, which is significantly higher compared with other cancers. Cervical cancer persists as a leading diagnosis through the late 40s, particularly in settings with incomplete HPV vaccine uptake and inadequate cytology infrastructure. Additionally, our finding of non-melanoma skin cancer as a leading incident cancer in this age range further reflects the interplay of environmental exposure and dermatologic surveillance intensity. Several interrelated factors may underlie these age-specific distributions. First, tumor-specific biology dictates age of onset: hematopoietic and embryonal tumors peak in adolescence, whereas epithelial malignancies predominate in later reproductive years. Second, hormonal milieu and reproductive behaviors, such as delayed childbearing and reduced breastfeeding, modulate breast and ovarian cancer risk. Third, infection-related cancers (cervical, stomach) cluster where HPV and Helicobacter pylori prevalence remain high and preventive services are limited. Fourth, lifestyle exposures, including air pollution, ultraviolet radiation, tobacco, and alcohol, accumulate over time, driving non-melanoma skin cancer, lung, and stomach cancers in older subsets. 40 , 49 , 50 , 62

Previous studies have primarily focused on cancer trends in the general population or specific cancer types among WCBA. In contrast, this study is the first to deliver a comprehensive description of the global burden, spatial disparities, and temporal shifts across 27 cancer subtypes among WCBA. The policy implications of these findings are multifaceted, necessitating context-specific interventions. In high SDI countries, primary prevention strategies should focus on lifestyle changes, including reducing obesity, alcohol and tobacco consumption, and preventing excessive exposure to ultraviolet radiation. Additionally, sustained investment in risk stratification screening and genetic counselling for high-risk groups is essential. For low SDI countries, strengthening health systems is essential. This includes implementing national cancer control plans focused on prevention and risk reduction, expanding coverage to ethnic minorities and remote areas with a goal of universal health coverage, training healthcare professionals, and ensuring availability of essential medicines and technologies. 23 Addressing social determinants, such as education and poverty, is critical to narrowing disparities. 63–65 Global collaboration is essential to bridge inequities, particularly by supporting cancer control infrastructure development in resource-limited settings. The WHO’s global strategy to eliminate cervical cancer by 2030 exemplifies the potential of coordinated efforts.

The main contribution of this study is the provision of a comprehensive and internally comparable reference of cancer burden among WCBA across cancer types, regions, countries, and socioeconomic settings. Although the analysis is primarily descriptive, it extends previous work by jointly evaluating total cancer and 27 cancer subtypes, age-specific patterns within the reproductive-age range, demographic drivers of absolute burden, and socioeconomic-related inequalities in incidence and mortality. This integrated approach helps distinguish cancers that account for the greatest mortality burden, cancers with rapidly increasing incidence, and regions where discrepancies between incidence and mortality may reflect unmet needs in diagnosis and treatment. These features may support more targeted prioritization than analyses limited to all-age populations or selected female cancers. Nevertheless, several limitations should be considered when interpreting these findings. First, this study was based on modeled estimates from the GBD 2021 database rather than directly observed cancer registry data from all countries. The quality, completeness, and availability of source data vary substantially across countries and regions. In particular, limited diagnostic capacity, incomplete population-based cancer registries, and insufficient cause-of-death certification in several low- and middle-income countries may lead to underdiagnosis and underreporting of cancer incidence and mortality. Although the GBD modeling framework attempts to adjust for missing or incomplete data using standardized statistical methods and covariates, estimates from settings with sparse primary data, especially low-SDI and low-middle-SDI regions, may still have greater uncertainty and should be interpreted cautiously. Second, because GBD estimates are available mainly at the national level, this study could not evaluate subnational disparities in cancer burden, screening access, diagnostic capacity, treatment availability, or cancer outcomes. This limitation may be particularly relevant for large and socioeconomically heterogeneous countries, where substantial within-country inequalities may exist. Third, this study could not directly incorporate country-specific long-term changes in cancer-related determinants, such as screening coverage, HPV vaccination uptake, diagnostic intensity, cancer registry completeness, treatment availability, health insurance coverage, reproductive patterns, lifestyle exposures, environmental risks, or infection prevalence. These factors may have evolved differently across countries and may partly explain divergent incidence and mortality trends. Therefore, possible explanations related to screening, diagnostic intensity, lifestyle changes, HPV vaccination, treatment access, health-system capacity, and other country-specific determinants should be interpreted as contextual hypotheses rather than directly tested mechanisms, and the country-level patterns observed in this study should be regarded as descriptive and hypothesis-generating rather than as evidence of causal effects of specific national policies or exposures. Fourth, the GBD database does not provide sufficient detail on histological subtype, molecular subtype, tumor stage, treatment patterns, or survival outcomes for all cancer types and countries. These factors are essential for understanding cancer prognosis and health-system performance but could not be incorporated into the present analysis. Finally, estimates for some countries, territories, and rare cancer types may be sensitive to sparse case or mortality data and modeling assumptions, which may affect the stability of AAPC estimates and country-level rankings. Therefore, comparisons involving small populations or cancers with limited data should be interpreted with caution.

Conclusions

In conclusion, the global burden of cancer among WCBA increased substantially from 1990 to 2021, with rising absolute numbers of incident cases and deaths largely driven by population growth and age-structure changes. Although the global ASIR increased slightly, the ASMR declined, suggesting improvements in cancer control while also highlighting persistent inequalities. Marked heterogeneity was observed across regions, countries, SDI levels, and cancer types. Breast, cervical, and lung cancers remained major contributors to mortality, while higher ASIRs were concentrated in high-SDI settings and higher ASMRs in low-SDI settings. These findings underscore the need for targeted prevention, HPV vaccination and cervical screening, breast cancer early detection, and equitable access to timely diagnosis and treatment, particularly in resource-limited settings.

Acknowledgments

We extend our thanks to the Global Burden of Disease Study 2021 collaborators for their high-quality data.

Funding Statement

This work was funded by the Science and Technology Planning Project of Medicine and Health in Zhuji City, Zhejiang Province, China (grant number 2023YW084). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Abbreviations

SDG, Sustainable Development Goal; WCBA, women of childbearing age; ASIR, age-standardized incidence rates; GBD, Global Burden of Disease; SDI, Socio-demographic Index; ASMR, age-standardized mortality rates; AAPC, average annual percentage changes; SII, slope index of inequality; CIX, concentration index; WHO, World Health Organization; ASRs, age-standardized rates; CI, confidence interval; HPV, human papillomavirus.

Data Sharing Statement

The data employed in this research are accessible to the public at: https://gbd2021.healthdata.org/gbd-results/ . 13 The detailed statistical codes involved in this study are available upon request from corresponding author.

Ethical Approval and Informed Consent Statements

This study was a secondary analysis of publicly available, anonymized, and aggregate-level estimates from the Global Burden of Disease Study 2021. No individual-level data, personal identifiers, or patient contact information were accessed. According to Article 32, Items 1 and 2, of the Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects issued by the National Health Commission of the People’s Republic of China on February 18, 2023, research using legally obtained public data without involving identifiable personal information is exempt from institutional ethical review. Therefore, ethics committee approval was not required for this study. Written informed consent was not applicable because no identifiable individual information was included in the analyses.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest in this work.

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Associated Data

Data Availability Statement

The data employed in this research are accessible to the public at: https://gbd2021.healthdata.org/gbd-results/ . 13 The detailed statistical codes involved in this study are available upon request from corresponding author.