Age-specific disease burden of uterine and cervical cancer among reproductive-aged women in China, 1990–2021: a comparison with global trends

Introduction

Cervical and uterine cancers are among the most common malignancies affecting women worldwide, posing serious threats to women’s health and lives (1). According to data from the International Agency for Research on Cancer (IARC), cervical cancer is the fourth most common cancer in women globally, with an estimated 604,000 new cases and 342,000 deaths in 2020, while uterine cancer ranks as the sixth most common, with 417,000 new cases. The disease burden is particularly high in developing countries, where approximately 90% of cervical cancer deaths occur (2).

In recent years, thanks to the widespread implementation of screening programs and the promotion of comprehensive prevention measures such as human papillomavirus (HPV) vaccination, the global and Chinese disease burden of cervical cancer has shown an overall downward trend (3,4). In China, cervical cancer screening programs have been gradually implemented since 2009 under the National Basic Public Health Service Initiative, focusing initially on rural women aged 35–64 years. These programs primarily use cytology and HPV testing. However, screening coverage remains uneven due to disparities in healthcare infrastructure and regional economic development. In contrast, developed countries such as the United States and many European nations have established organized screening programs with high coverage and centralized quality assurance, contributing to more pronounced declines in cervical cancer mortality. Since 2016, China has approved several HPV vaccines, including the bivalent, quadrivalent, and nonavalent types. Vaccination is recommended primarily for girls aged 9–14 years, with catch-up vaccination recommended for women up to 26 or 45 years, depending on the vaccine type. However, national immunization coverage remains low due to limited vaccine supply, out-of-pocket costs, and low public awareness. Efforts to integrate HPV vaccination into the Expanded Program on Immunization are ongoing.

Given China’s large population and accelerating aging process, women of different age groups face distinct health risks and disparities in access to medical resources (5). The age-specific distribution characteristics and long-term evolution trends of the disease burden therefore, require further in-depth analysis (6). Moreover, with changes in lifestyle (7-9), the increasing prevalence of risk factors such as obesity and unsafe sexual behaviors may pose new challenges for disease prevention and control. Although uterine and cervical cancers differ in etiology and prevention strategies, both are major contributors to the female reproductive cancer burden and share overlapping risk factors such as obesity and HPV infection. A joint analysis provides a comprehensive understanding of the evolving disease landscape and supports integrated prevention strategies. However, existing studies predominantly focus on broad regional trends, lacking a comparative age-specific analysis that integrates the impact of emerging risk factors. Bridging this gap is vital for shifting from broad surveillance to precision prevention tailored to China’s reproductive-aged female population. We present this article in accordance with the STROBE reporting checklist (available at https://jphe.amegroups.com/article/view/10.21037/jphe-2025-1-60/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Data sources and variable definitions

Given the significant impact of premature mortality on family structures and the workforce, this study specifically focused on women of reproductive age (15–49 years). This age range was selected to capture the critical transition from peak fertility to the perimenopausal period, allowing for a focused analysis of early-onset disease burden.

This study is a descriptive observational study based on Global Burden of Disease (GBD) 2021 data. The data for this study were obtained from the GBD data regularly released by the Institute for Health Metrics and Evaluation (IHME), which is the Global Health Data Exchange query tool. The data extraction was performed on June 9, 2025. This database analysis incorporated 56,604 data sources, including information from vital registration and verbal autopsy records, surveys, censuses, surveillance systems, and cancer registries, to assess the global burden of 288 causes of death and life expectancy decomposition across 204 countries and territories and 811 subnational locations (10). The GBD study utilizes rigorous modeling (DisMod-MR 2.1) to impute missing values, resulting in a complete dataset. Therefore, no additional missing data handling was required for this analysis.

The primary study variables included: (I) incidence and mortality numbers: the absolute number of new cases and deaths per year; (II) age-standardized rates (ASR): calculated using the GBD world population standard to adjust for population age structures, expressed per 100,000 population; (III) age-specific rates: the incidence or mortality rate calculated specifically for each 5-year age group (from 15 to 49 years), calculated as the number of cases/deaths in that age group divided by the population of that age group, multiplied by 100,000; (IV) risk factors: data on “unsafe sexual behavior” and “high body mass index (BMI)” were extracted to analyze correlations. In the GBD framework, Unsafe sexual behavior is defined as the risk of sexually transmitted infections due to unprotected sexual practices, quantified using the summary exposure value (SEV), which measures the population’s risk exposure severity ranging from 0% to 100%. High BMI is defined as BMI ≥25 kg/m² for adults.

Statistical methods

Descriptive statistical analysis

Age-standardized incidence rates and mortality rates provided by the GBD database were used for analysis, grouped in 5-year intervals starting from the 15–19-year age group. Age-specific measures were operationalized as the number of cases or deaths within each specific 5-year age bracket divided by the total population of that corresponding age bracket, expressed as a rate per 100,000 individuals. This approach allows for the direct observation of disease burden variations across different life stages, independent of the overall population structure. The results were presented as mean ± standard deviation for the number of deaths and mortality rates across age groups in China and globally, with proportional differences calculated. All disease burden indicators were reported with 95% uncertainty intervals estimated by the IHME.

Joinpoint regression analysis

Trend analyses of the standardized incidence rate of cervical cancer were performed using the Joinpoint Regression Program (Version 5.3.0, Statistical Research and Applications Branch, National Cancer Institute) developed by the U.S. National Cancer Institute (11). Joinpoint regression analysis was performed to identify significant trend shifts using a segmented linear regression approach. The model assumes independent Poisson-distributed errors and employs the weighted least squares method to account for heteroscedasticity and ensure optimal model fit. The Monte Carlo Permutation Test was utilized for model selection to determine the number of significant joinpoints and verify trend changes robustness. The annual percentage change (APC) for each segment and the average annual percentage change (AAPC) over the entire study period (12) are estimated, with a two-sided P<0.001 considered statistically significant.

Correlation analysis

The Pearson correlation coefficient was used to quantify the strength of linear associations between specific risk factors and disease burden indicators. For uterine cancer, analyze the number of deaths, mortality rate, and the proportion of deaths among individuals with high BMI, as well as the correlation of these indicators with the corresponding overall uterine cancer indicators. For cervical cancer, the correlations between unsafe sexual behavior and the number of deaths, as well as the mortality rate, were examined. A two-sided significance level of α=0.05 was adopted.

Results

This study reveals distinct epidemiological patterns for uterine and cervical cancers in China compared to global trends. While the absolute number of uterine cancer deaths in China remained lower than the global average, the age-specific mortality rates were significantly higher, particularly in middle-aged women. In contrast, cervical cancer showed a dramatic 70-fold increase in death counts, far exceeding the global rise. Temporal trend analysis identified a peak in uterine cancer incidence around 2010 and a rebound after 2016, whereas cervical cancer incidence surged between 1998 and 2004 before declining post-2016. High BMI was identified as a critical risk factor strongly correlated with uterine cancer burden.

Epidemiological trends of uterine and cervical cancer from 1990 to 2021

Statistical data on uterine and cervical cancer mortality from 1990 to 2021 indicate that both the number of deaths and the mortality rate exhibit an upward trend with increasing age. Longitudinal comparisons revealed that, for uterine cancer, the number of deaths in China was consistently lower than the global average across all age groups, and the gap widened with age. In the 20–24-year age group, the number of deaths in China (48.12±15.39) accounted for 33.8% of the global figure (142.40±10.29), whereas by the 45–49-year age group, this proportion had declined to 30.8% (China: 942.04±147.82 vs. global: 3,054.31±384.28). In contrast, mortality rates displayed an opposite pattern: China’s mortality rate exceeded the global average across all age groups, with the disparity increasing progressively with age, peaking at 1.30 times the global level. Given the differences in population size, these higher mortality rates provide a more accurate reflection of the disease burden severity in China compared to absolute death counts.

For cervical cancer, both the number of deaths and mortality rates in China were consistently lower than the global averages across all age groups. In the 15–19-year age group, the number of deaths in China (55.94±22.82) accounted for only 8.0% of the global figure (701.57±41.49); however, this proportion increased to 15.5% in the 45–49-year age group (China: 3,923.71±850.19 vs. global: 25,384.56±2,429.17). This result indicates that although the gap in the number of deaths widens with age, the increase in deaths in China is significantly higher than the global increase (a 70.2-fold increase in China vs. a 36.2-fold increase globally). A similar pattern was observed for mortality rates, as detailed in Table 1.

Temporal trends and key turning points in disease burden

Trends in mortality rates for uterine and cervical cancer showed a general declining tendency in both China and globally. However, within specific age groups, the data points for China show greater fluctuations, whereas the global data decline more rapidly, remain at a lower level, and display a smoother fitted curve. Details are presented in Figures 1,2.

Figure 1 Age-specific mortality rates of uterine cancer in China and worldwide.

Figure 2 Age-specific mortality rates of cervical cancer in China and worldwide.

The analysis of temporal trends identified multiple significant turning points in the incidence trends of uterine and cervical cancer in China and worldwide from 1990 to 2021. In China, the incidence rate of uterine cancer reached a peak around 2010, followed by a significant decline (APC =−3.75%, P<0.001), and then exhibited a slight rebound starting in 2016 (APC =1.27%, P<0.001). In contrast, the age-standardized incidence rate of cervical cancer showed a period of rapid increase between 1998 and 2004 (APC =3.42%, P<0.001), followed by a mild downward trend after 2016.

On a global scale, both uterine and cervical cancer incidence rates demonstrated a transition from a declining to an increasing trend around 2008. The increasing trend in the age-standardized incidence rate of uterine cancer shows varying rates of growth across different time periods. In contrast, the global age-standardized incidence rate of cervical cancer has risen at a relatively moderate pace, with smaller overall fluctuations. Around 2019, the incidence rates of both diseases showed a significant decline: uterine cancer between 2019 and 2020 (APC =−8.81%, P<0.001), and cervical cancer during the same period (APC =−8.26%, P<0.001). Detailed results are illustrated in Figure 3.

Figure 3 Temporal epidemiological trends and Joinpoint regression analysis of ASIR for uterine and cervical cancer in China and globally from 1990 to 2021. *, APC is significantly different from zero at the alpha =0.05 level. APC, annual percent change; ASIR, age-standardized incidence rate.

Association between risk factors and cancer burden

We examined the association between high BMI populations and uterine cancer mortality, the number of uterine cancer deaths, mortality rate, and proportion of deaths among individuals with high BMI were calculated separately. These indicators were then analyzed for their correlations with the corresponding overall uterine cancer mortality metrics. The results showed that the correlation coefficient between the number of uterine cancer deaths in the high BMI population and the total number of uterine cancer deaths was 0.941 [95% confidence interval (CI): 0.883–0.972, P<0.001], indicating a very strong positive linear relationship where increased high BMI prevalence is closely tracked by rising uterine cancer deaths; the correlation coefficient between the mortality rate and the overall mortality rate was also 0.941 (95% CI: 0.883–0.972, P<0.001) while the correlation coefficient between the proportion of deaths and the overall proportion of deaths was 0.713 (95% CI: 0.486–0.852, P<0.001).

Regarding behavioral factors, the relationships between unsafe sexual behavior, the number of cervical cancer deaths, and the mortality rate were evaluated to explore the potential impact of behavioral factors on the disease burden of cervical cancer. The results indicated that the correlation coefficient between unsafe sexual behavior and the number of cervical cancer deaths was 0.446 (95% CI: 0.119–0.687, P=0.01) while that between unsafe sexual behavior and the mortality rate was 0.450 (95% CI: 0.123–0.690, P=0.009).

Discussion

This study provides a comprehensive age-specific analysis of uterine and cervical cancer burden in China from 1990 to 2021. Our findings highlight a divergent pattern: uterine cancer is characterized by “fewer deaths but higher mortality rates” in perimenopausal age groups compared to global levels, while cervical cancer is marked by a rapid surge in absolute death counts. We also identified distinct temporal turning points linked to public health policies and quantified the strong impact of obesity on uterine cancer mortality. These results underscore the urgent need for precision prevention strategies tailored to women transitioning through the critical reproductive stages.

Regarding uterine cancer, our observation of low absolute mortality but high mortality rate, with the disparity becoming more pronounced with advancing age. This observation suggests that insufficient recognition or delayed reporting of abnormal symptoms among middle-aged individuals may contribute to diagnostic delays (13). Disparities in economic development leading to unequal distribution of primary healthcare resources, along with limited health awareness among high-risk populations (14), may represent the key factors contributing to such diagnostic and treatment delays. This finding aligns with a recent study by Wu et al. (4), which also reported that cancer mortality rates in China’s rural areas are significantly influenced by disparities in diagnostic capacity. Furthermore, Li et al. (15) noted similar age-specific increasing trends, confirming that the disease burden is shifting towards older populations as the demographic structure changes. In contrast, both the number of deaths and the mortality rate from cervical cancer in China are lower than the global averages. However, it is noteworthy that the increase in cervical cancer deaths in China is approximately twice the global rate. As China is rapidly entering an aging society, the population of middle-aged is increasing sharply (16). According to the 2021 National Bulletin on the Development of Undertakings for the Aged, by the end of 2021, the elderly population in China had reached 267 million, accounting for 18.9% of the total population (17). Our data confirms that both death counts and mortality rates peak in this group, serving as a critical early warning for the future disease burden as this cohort ages. Therefore, how to strengthen health education and screening participation rate among women of late reproductive age, especially rural and marginalized groups, while expanding screening coverage, has become a key priority in current cervical cancer prevention and control (18).

Globally, the scatter distribution of global uterine and cervical cancer mortality rates exhibited low variability and a steady downward trend, reflecting the impact of well-established screening systems and healthcare homogenization in high-income countries. In simple terms, the tight clustering of data points globally indicates that progress in reducing mortality has been consistent and predictable across different populations. In contrast, the data from China displayed marked volatility in scatter distribution, particularly among women aged 30–49 years. This observed volatility was significantly more pronounced than in other age cohorts, a phenomenon of high dispersion that further underscores the uneven distribution of primary healthcare resources, where diagnostic delays in less developed regions contribute to greater fluctuations in mortality rates. This phenomenon is consistent with previous research (19), which reported that although the utilization rate of preventive healthcare services among rural residents increased during 2009–2011, a significant urban-rural disparity persisted, and the rate of growth differed between the two groups, resulting in an “unstable coverage” pattern. In contrast, the relatively concentrated scatter observed among younger age groups in China may be attributed to the nationwide implementation of rural screening programs (20). The temporal evolution of disease burden further highlights key policy windows in the evolution of disease burden. The 2010 peak inflection point in uterine cancer incidence rate coincided closely with the nationwide promotion of the ‘Two Cancers Screening’ program under the National Basic Public Health Services initiative launched in 2009 (21), reflecting the protective effect of policy interventions on younger female populations. This temporal coincidence suggests a potential impact, although causality cannot be directly inferred from ecological data. However, the rebound in uterine cancer incidence observed in 2016 reflects significant shortcomings in weight management and lifestyle interventions, suggesting that future prevention and control strategies should place greater emphasis on modifiable risk factors such as obesity (15). Over the past few decades, China, like other developed nations, has undergone rapid economic development as well as cultural and sociodemographic transformations, which have in turn led to substantial lifestyle changes (22,23). Evidence suggests (24) that between 1991 and 2015, overall dietary fat intake among Chinese adults increased significantly with advancing urbanization, particularly in highly urbanized areas, thereby accelerating the nutrition transition and contributing to rising obesity and related health issues. Regarding cervical cancer, a rapid upward trend was observed from 1998 to 2004, corresponding to changes in sexual behavior patterns during China’s period of economic transition. The downward inflection point in 2016 may be associated with the approval of the bivalent HPV vaccine by the China Food and Drug Administration (FDA) in 2016, marking the introduction of the first commercially available HPV vaccine in the country (25). This trend suggests that the introduction of HPV vaccines has begun to show prevention and control effects at the population level, providing important evidence for the subsequent evaluation of the public health impacts of vaccination strategies (26).

Our examination of risk factors provided important evidence regarding risk factors. Both the number of uterine cancer deaths and the mortality rate among individuals with metabolic syndrome showed a strong correlation with the corresponding overall indicators, strongly supporting the view that metabolic syndrome is a key risk factor for uterine cancer, consistent with previous research findings (27,28). In addition, unsafe sexual behavior demonstrated a moderate positive correlation with both the number of cervical cancer deaths and the mortality rate, suggesting a potential influence of behavioral factors on the disease burden of cervical cancer. In summary, although the overall disease burden of uterine and cervical cancers among Chinese women showed a declining trend from 1990 to 2021, several challenges persist compared with global patterns. These include relatively higher mortality rates among middle-aged and elderly populations, a rapid increase in the absolute number of deaths, and an unequal distribution of medical resources. To align with the Healthy China Initiative—Cancer Prevention and Control Action Plan (2023–2030), targeted health education should be reinforced among high-risk groups. Critically, our study identified a strong correlation (r=0.941) between high BMI and uterine cancer mortality, providing compelling evidence for the necessity of obesity control. Based on this finding, personalized weight management guidance should be rigorously provided for high-risk populations, including perimenopausal women, individuals with a family history of cancer, and those undergoing long-term hormone therapy (29-31). It is recommended to adopt the following comprehensive prevention and control strategies: promote the establishment of an ‘age-specific’ screening strategy to enhance risk awareness and regular screening for uterine and cervical cancers among women aged 45–49 years (32); integrate weight management and metabolic health promotion into routine women’s healthcare services, with particular emphasis on strengthening education and awareness of obesity-related cancers within community and primary healthcare settings (33,34); strive to increase HPV vaccine coverage by prioritizing adolescent girls and progressively implementing ‘catch-up’ vaccination programs (35,36); and strengthen the integration and data sharing of national cancer registries and risk factor surveillance systems to provide a scientific basis for dynamic assessment of disease burden and evidence-based precision interventions (37,38). There should be further development of interdisciplinary evidence-based teams, utilizing artificial intelligence and big data methods to continuously optimize early screening and intervention programs, with the aim of effectively reducing the incidence and mortality burden of female reproductive system tumors (39).

Comparatively, the rising uterine cancer burden aligns with other transition economies like Brazil and India, driven by urbanization. However, China’s unique ‘mortality-incidence divergence’ contrasts with high-income nations, likely due to unstable screening coverage and regional healthcare disparities. China’s experience offers critical insights for other developing nations. Consequently, the proposed strategies—integrating weight management and targeted age-specific screening—have broad applicability for middle-income countries undergoing similar demographic transitions.

This study has certain limitations. At the model and data level, as a global model, the GBD study has inherent limitations in both data quality and modeling methods. On one hand, the data integrated by GBD come from diverse sources, and in some countries, cause-of-death registration and disease surveillance systems are incomplete, which may lead to data gaps or reporting bias. On the other hand, its statistical modeling process relies on a series of smoothing, extrapolation, and imputation assumptions, which may not fully capture the unique disease patterns and distribution of risk factors in the Chinese population, thereby introducing uncertainty. The BMI classification used in the GBD is based on the World Health Organization (WHO) standard, which differs from the Chinese standard and may lead to an underestimation of the disease burden. In addition, confounding factors such as smoking, HPV subtype variations, and hormone therapy were not analyzed. Future research based on Chinese population data is needed to more accurately reflect the situation in China.

Conclusions

This study analyzed China’s uterine and cervical cancer burden from 1990 to 2021. While age-standardized incidence and mortality rates showed an overall decline, uterine cancer mortality remained significantly higher than global levels, with cervical cancer death counts rising dramatically. The identified trend inflection points coincided with the implementation of major national screening and vaccination programs, suggesting a potential positive impact of these interventions. Targeted interventions are needed, including enhanced screening, obesity control, and HPV vaccination for high-risk age groups, to address the persistent disparities in disease burden. These findings underscore the necessity for continued age-specific prevention strategies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jphe.amegroups.com/article/view/10.21037/jphe-2025-1-60/rc

Data Sharing Statement: Available at https://jphe.amegroups.com/article/view/10.21037/jphe-2025-1-60/dss

Peer Review File: Available at https://jphe.amegroups.com/article/view/10.21037/jphe-2025-1-60/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jphe.amegroups.com/article/view/10.21037/jphe-2025-1-60/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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