Recent patterns and trends in global ovarian cancer incidence and mortality in adolescents and young adults

Abstract

Objective

Ovarian cancer in adolescents and young adults (AYAs, aged 15–39 years) presents distinct clinical and epidemiological characteristics, yet comprehensive global epidemiological data remain limited.

Methods

We conducted a comprehensive analysis using 3 International Agency for Research on Cancer databases: GLOBOCAN 2022, Cancer Incidence in Five Continents Plus, and World Health Organization (WHO) mortality database. Age-standardized incidence rates (ASIRs) and mortality rates (ASMRs) per 100,000 women-years were calculated using the WHO World Standard Population. Countries were stratified by Human Development Index (HDI). Temporal trends were analyzed using Joinpoint regression to calculate annual percent change and average annual percent change (AAPC).

Results

In 2022, global ASIRs for AYAs (15–39 years) ovarian cancer demonstrated relative uniformity across regions, with highest rates in Melanesia. ASMRs exhibited an inverse HDI gradient, with low-HDI regions experiencing highest mortality burdens (0.75 per 100,000 women-years) despite lower incidence (2.02 per 100,000 women-years). Analysis of the most recent 5-year period revealed divergent trends, characterized by a significant rise in incidence in Thailand (AAPC=6.62%; 95% confidence interval [CI]=1.84%, 11.52%) across 44 regions and marked mortality elevations in the Syrian Arab Republic (AAPC=15.89%; 95% CI=10.29%, 21.64%) and Venezuela (AAPC=11.08%; 95% CI=8.06%, 14.01%) in 59 regions.

Conclusion

Despite relatively uniform global incidence, mortality from ovarian cancer in AYAs shows pronounced international disparities, with the greatest burden concentrated in low-HDI regions. Evidence from divergent incidence-mortality trajectories indicating that healthcare improvements enhance survival highlights the critical need for targeted interventions to address global disparities in AYA ovarian cancer outcomes.

Synopsis

From 1980 to 2022, adolescents and young adults with ovarian cancer showed similar incidence worldwide but pronounced mortality gaps following an inverse Human Development Index gradient. Health-system advances improved survival despite rising detection. Targeted interventions are needed to reduce global outcome inequities.

INTRODUCTION

Ovarian cancer represents a significant global health burden, with an estimated 324,398 new cases and 206,839 deaths worldwide in 2022 [1]. While the majority of cases occur in postmenopausal women, ovarian cancer in adolescents and young adults (AYAs), defined as those aged 15–39 years, presents unique clinical, biological, and psychosocial challenges that distinguish it from disease in older populations [2,3,4]. Recent global cancer statistics indicate that AYAs experienced 1.32 million new cancer cases and 379,273 cancer deaths in 2022, with ovarian cancer accounting for approximately 43,800 new cases and 13,600 deaths in this age group [1,5]. The distinct presentation of ovarian cancer in AYAs, including higher proportions of non-epithelial histology, better overall prognosis, and critical fertility preservation considerations, necessitates focused epidemiological investigation [6,7,8].

Previously, several studies have investigated the global patterns of ovarian cancer in the AYAs population. Che and Yin [9] examined the global burden of ovarian cancer among adolescents aged 15–24 years using Global Burden of Disease (GBD) 2021 data, focusing on 204 countries from 1990 to 2021. While this study provided valuable insights into disease burden by sociodemographic index regions, it was restricted to a narrower age range and relied solely on modeled GBD estimates rather than actual registry data. Huang et al. [10] analyzed trends in all female cancers (including ovarian) among AYAs aged 15–39 years, also using GBD 2021 data, but did not provide detailed ovarian cancer-specific temporal trends or examine divergent incidence-mortality patterns. Ganiyani et al. [5] analyzed GLOBOCAN estimates for all malignancies in 185 countries, showing cancer burden in AYAs population based on Human Development Index (HDI) and income status. However, they did not disentangle site-specific results or long-term incidence or mortality trends of ovarian cancer [5]. Given the temporal changes in diagnostic capabilities, risk factor profiles, and treatment modalities for ovarian cancer [11,12], along with the limited geographic and methodological scope of these previous investigations [13], comprehensive and updated epidemiological data examining both incidence and mortality patterns specifically for AYAs ovarian cancer across diverse global settings remain urgently needed [14].

To address these limitations, we leveraged three complementary International Agency for Research on Cancer (IARC) databases-GLOBOCAN 2022, Cancer Incidence in Five Continents Plus (CI5plus), and World Health Organization (WHO) mortality database-to provide the first comprehensive analysis of global AYAs ovarian cancer epidemiology. This study quantifies the contemporary (2022) global incidence and mortality of ovarian cancer among adolescents and young adults, stratified by HDI and geographic regions. Furthermore, we characterized recent temporal trends to identify high-risk nations and analyzed long-term trajectories (1980–2021) to detect potential disparities in early detection or therapeutic advances. The resulting evidence is intended to inform data-driven policy, prioritize resource allocation, and shape future research aimed at mitigating the global burden of ovarian cancer in young women.

MATERIALS AND METHODS

1. Data sources

Incidence and mortality statistics for AYAs ovarian cancer (International Classification of Diseases, 10th Revision [ICD-10] code C56) were extracted for 185 countries and territories from the GLOBOCAN 2022 estimates (https://gco.iarc.who.int/today/), curated by the IARC. Long-term incidence patterns and trends data for ovarian cancer were extracted from the CI5plus database for countries or territories that contributed at least 10 years of observations between 1980 and 2021 [15]. When national and sub-national series overlapped for a given country-period, national data were preferentially retained, and registries reporting zero or indeterminate population denominators in any age stratum were excluded. Cancer mortality data between 1980 and 2022 for 59 countries/territories were obtained from the WHO mortality database as compiled by IARC, representing approximately 22% of the global population (https://www.who.int/data/data-collection-tools/who-mortality-database) [16].

2. Statistical analysis

Following data acquisition, the dataset was organized and processed for analysis. The number of incident cases was then stratified by age group and year to facilitate age standardization. Age-standardized incidence rates (ASIRs) per 100,000 women-years and age-standardized mortality rates (ASMRs) per 100,000 women-years for ovarian cancer and specified time period were calculated using the direct standardization method, with the WHO World Standard Population (15–39 age groups) serving as the reference population. This approach allowed for the adjustment of incidence rates according to differences in age distribution between populations, thereby enabling valid comparisons across different demographic groups and over time. Building upon the 2018 HDI compiled by the United Nations Development Programme, nations were classified as exhibiting very-high, high, medium, or low human development [17].

To evaluate temporal trends in ASIRs and ASMRs, we calculated the annual percent change (APC) and the average annual percent change (AAPC) using Joinpoint regression analysis [18]. This method identifies specific time points (joinpoints) where significant changes in trends occur, dividing the study period into distinct linear segments. The APC quantifies the rate of change within each specific segment. To summarize the trend over the entire study period, the AAPC was computed as a weighted average of the segment-specific APCs, with weights corresponding to the duration of each segment. In cases where no joinpoint were detected (i.e., a single continuous trend), the AAPC is equivalent to the APC.

All statistical analyses were executed using R (version 4.3.3; R Foundation for Statistical Computing, Vienna, Austria) and the Joinpoint Regression Program (version 5.3.0.0; IMS Inc., Liverpool, NY, USA), and with a two-tailed p-value threshold of <0.05 considered statistically significant throughout the study. This is a population-based descriptive study conducted in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting statement [19].

RESULTS

1. Global incidence and mortality rates of ovarian cancer in AYAs in 2022

Globally, an estimated 37,703 new cases of ovarian cancer in the AYAs (15–39 years) and 9,846 deaths occurred in 2022 (Table 1). The ASIRs for ovarian cancer were relatively uniform, displaying no pronounced disparities. Notably, Melanesia from Ocean had the highest estimated incidence rate at 4.79 per 100,000 women, followed by Eastern Europe (3.94). In contrast, the lowest incidence rate was observed in Polynesia, which recorded an average rate of 0.73 per 100,000 women. In an analysis of international ASIRs trends by HDI, the most elevated ASIR were observed in regions classified as having very high HDI (2.63), while the lowest ASIR was noted in regions with low HDI values (2.02) (Fig. S1A). Regarding ASMRs, Melanesia reported the highest mortality at 1.68 per 100,000 women, South Eastern Asia followed with 1.10 per 100,000 women. ASMRs showed an inverse HDI gradient: regions with low HDI carried the heaviest mortality burden, whereas very-high-HDI regions experienced the lowest rate (Table 1, Fig. S1B). At the country level, the highest incidence rates were observed in Brunei Darussalam, Fiji, Malta, Solomon Islands, Malaysia, and several countries in Eastern Europe and Africa (Fig. 1A, Table S1). Conversely, mortality rates were highest in the Melanesia, Latin America and the Caribbean, and sub-Saharan African countries, such as Solomon Islands, Papua New Guinea, Haiti, and Honduras, with the lowest rates recorded in many European countries (Fig. 1B, Table S2).

Table 1. Estimated number of new ovarian cancer cases and deaths in adolescents and young adults by world regions for 2022.

Regions		Population	ASIRs	Cases	ASMRs	Deaths
Africa
	Eastern Africa	236,089,051	1.79	1,647	0.63	580
	Middle Africa	95,395,941	1.80	630	0.77	269
	Northern Africa	126,846,614	2.33	1,226	0.79	401
	Southern Africa	35,166,105	1.43	216	0.57	90
	Western Africa	210,108,604	2.07	1,612	0.68	525
Asia
	Eastern Asia	795,669,818	2.57	7,165	0.41	1,206
	South-Central Asia	999,473,292	2.13	9,525	0.66	2,869
	South-Eastern Asia	341,238,367	3.93	5,546	1.10	1,581
	Western Asia	137,405,453	2.00	1,168	0.59	349
Europe
	Eastern Europe	154,548,370	3.94	2,345	0.71	450
	Northern Europe	54,164,287	2.03	396	0.21	46
	Southern Europe	77,501,382	2.83	682	0.32	89
	Western Europe	100,087,764	1.33	432	0.19	73
Latin America/Caribbean
	Caribbean	22,290,154	2.34	213	1.02	92
	Central America	93,685,735	2.71	1,084	0.85	339
	South America	222,273,730	1.97	1,837	0.63	584
North America		188,537,331	2.51	1,749	0.34	244
Oceania
	Australia/New Zealand	15,580,191	1.93	116	0.33	20
	Melanesia	5,653,901	4.79	110	1.68	39
	Micronesia	277,280	2.50	3	0	0
	Polynesia	341,664	0.73	1	0	0
HDI
	Very High	830,163,898	2.63	7,943	0.45	1,388
	High	1,369,268,229	2.62	14,035	0.61	3,313
	Medium	1,109,678,271	2.28	11,053	0.71	3,431
	Low	601,531,860	2.02	4,662	0.75	1,712

ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; HDI, Human Development Index.

Fig. 1. Global geographical distribution of ovarian cancer age-standardized incidence and mortality rates in adolescents and young adults in 2022. (A) ASIRs and (B) ASMRs. Melanesia from Ocean displayed the highest ASIRs and ASMRs. Countries are color-coded to reflect the burden of disease.

ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; IARC, International Agency for Research on Cancer.

2. Recent patterns in ovarian cancer incidence and mortality in AYAs

Figs. 2 and 3 presented ASIRs and ASMRs for ovarian cancer over the past 5 years of available records. Incidence varied almost 11-fold across 61 countries, from 0.74 per 100 000 women in Iceland to 8.36 per 100 000 in Brunei Darussalam. In general, nations in Central-Eastern Europe and Asia recorded the higher incidences-most notably Brunei Darussalam-showed the highest, whereas Asian and African countries showed the lower values. Mortality displayed even larger heterogeneity, spanning nearly 20-fold across 78 countries and territories, with a minimum of 0.34 per 100 000 in Turkey and Spain and a maximum of 6.85 per 100 000 in Belize. The lowest mortality rates were observed predominantly in European and North American populations, while the highest were concentrated in the Latin America (e.g., Belize, Guyana) and parts of Southern Europe.

Fig. 2. Ovarian cancer incidence rates in selected countries and regions in adolescents and young adults. Central-Eastern Europe and Asia recorded the higher incidences.

Source: Cancer Incidence in Five Continents Plus.

ASR, age-standardized rate.

^*Rates are from 2008–2012; ^†Rates are from 2013–2017.

Fig. 3. Ovarian cancer mortality rates in selected countries and regions in adolescents and young adults. Latin America and Southern Europe recorded the higher mortalities.

Source: World Health Organization mortality database.

ASR, age-standardized rate.

^*Rates are from 2013–2017; ^†Rates are from 2014–2018, ^‡Rates are from 2015–2019, ^§Rates are from 2016–2020; ^∥Rates are from 2017–2021.

3. Trends in ovarian cancer incidence and mortality rates

Long-term trends (at least 10 consecutive years) in ovarian cancer incidence and mortality rates, analyzed using Joinpoint regression models, revealed distinct regional and temporal patterns across multiple countries (Fig. 4). In most countries, the incidence curve demonstrated decreasing or stable trends from the beginning of observation period through to the 2010–2020 period. Over the most recent 5-year interval, the AAPC in incidence increased significantly in Thailand with APPC of 6.62% (95% confidence interval [CI]=1.84%, 11.52%), while decreased profoundly in Germany with APPC of −7.42% (95% CI=−13.34%, −1.34%) across 44 regions. The remaining countries all demonstrated relatively stable trends (Table S3).

Fig. 4. Trends in ovarian cancer incidence and mortality rates. (A) Asia, (B) Northern Europe, (C) Western Europe, (D) Southern Europe, (E) North America, (F) Latin America and the Caribbean, (G) Central and Eastern Europe, and (H) Oceania. Age-standardized mortality and incidence curves remained broadly parallel in most nations. Blue represents incidence and red represents mortality. Dots represent observed rates and lines represent tted values based on Joinpoint analyses.

In most nations the age-standardized mortality and incidence curves for ovarian cancer remained broadly parallel. A divergent pattern was observed, however, in several Asian countries (China and Japan) (Fig. 4A), and in Lithuania of Eastern European (Fig. 4D), where incidence rates continued to rise while mortality rates declined. Over the most recent 5-year observation period, mortality rate trends varied across the 59 countries analyzed. A declining trend was observed in eight countries, with AAPC ranging from −21.32% in Austria (2002–2006) to −6.01% in Poland (2011–2015). Conversely, an increasing trend was identified only in 2 countries, including Syrian Arab Republic and Bolivarian Republic of Venezuela with AAPC of 15.89% (95% CI=10.29%, 21.64%) and 11.08% (95% CI=8.06%, 14.01%), respectively. The remaining countries exhibited stable mortality rates with no statistically significant changes (Table S4).

Fig. 5 presented the contemporary trends in ovarian cancer incidence and mortality rates among 34 countries with complete data availability for both indicators. The analysis revealed distinct epidemiological patterns. ASIRs increased in Thailand but decreased in Germany, with ASMRs remaining stable in both countries. A divergent pattern of stable ASIRs accompanied by declining ASMRs was evident in 5 countries (Poland, Denmark, Italy, Austria, and Switzerland). Detailed region- and country-specific analyses of these temporal trends are presented in the following sections.

Fig. 5. AAPC in incidence and mortality rates for the recent 5-year period of available data for selected countries and regions in adolescents and young adults. The analysis revealed distinct epidemiological patterns.

AAPC, average annual percent change.

^*The AAPC is statistically signicantly different from zero.

4. Africa

ASIRs of ovarian cancer were notably various in Africa between 2013 and 2017. This is characterized by specific country patterns, with Seychelles reporting the second highest ASIRs (6.47 per 100,000 person-years) globally. Algeria demonstrated the lowest incidence rate of 1.25 per 100,000 women among African countries. Uganda exhibited medium incidence rate with a stable temporal trend during the most recent 5-year period (Fig. 2, Table S3). Among all studied populations, Mauritius exhibits the 8th highest mortality rate (2.48 per 100,000 person-years), while South Africa exhibited extremely low ASMRs (0.52 per 100,000 person-years) (Fig. 3, Table S4).

5. Asia

Asian countries exhibited substantial variation in incidence rates during the most recent five-year period, with national estimates ranging from 0.95 per 100,000 women in Kuwait to 8.36 per 100,000 women in Brunei Darussalam (Fig. 2). Incidence trends during the most recent five-year period showed continuous increases of 6.62% only in Thailand; while rates were stable in the remaining countries (Table S3). Mortality mirrored the heterogeneity seen in incidence, ranging from 0.34 per 100,000 person-years in Turkey to 5.70 per 100,000 person-years in Brunei Darussalam (Fig. 3). Brunei Darussalam exhibited the highest incidence rate and the 4th highest mortality rate among all studied populations. Temporal trends in ASMRs during this period revealed different patterns: an annual increase of 15.89% were found in Syrian Arab Republic, decreases of 11.06% to 16.67% in Mongolian and Kyrgyzstan, respectively, with remaining countries exhibiting stable rates (Table S4).

6. Central and Eastern Europe

Incidence rates across Central and Eastern Europe ranged from 1.22 to 5.19 per 100,000 women (Fig. 2), with corresponding mortality rates of 0.55–3.40 per 100,000 women (Fig. 3). Latvia exhibited the highest incidence rate (5.19 per 100,000 person-years), with Ukraine, Bulgaria, and Russian Federation demonstrating the 4th, 5th, and 7th highest incidence rates among all studied populations (Fig. 2, Table S4). During the most recent 5-year period, incidence trends across Central and Eastern Europe countries demonstrated stable rates (Fig. 4, Table S3). Mortality rates revealed different patterns: an annual decrease of 6.01% was found in the Poland, decrease of 11.26% in Republic of Moldova, with remaining countries exhibiting stable trends among all studied populations.

7. Northern Europe

Northern European countries exhibited homogeneity in incidence rates across the 7 included populations, with minimal variation from 0.74 per 100,000 women in Iceland to 2.47 in Norway-demonstrating relatively consistent rates across the region (Fig. 2). Furthermore, they exhibited similar heterogeneity in mortality rates across 5 countries, nearly 3-fold variation was observed, with Denmark recording the highest rate (1.13 per 100,000 person-years), constituting the medium mortality rate among all studied populations (Fig. 3). During the most recent 5-year period, mortality rates decreased by 10.80% in Denmark, while both incidence and mortality rates remained stable across the other Northern European countries (Tables S3 and S4).

8. Southern Europe

Incidence rates across Southern Europe ranged from 2.28 per 100 000 women in Spain to 3.70 in Malta, while mortality rates varied from 0.34 per 100,000 women in Spain to 6.11 in Malta (Figs. 2 and 3). During the most recent 5-year period, incidence patterns exhibited downward trends in most countries; however, these decreases were not statistically significant. Of the 10 countries with the highest mortality rates, 2 are situated in Southern Europe (Malta and Cyprus). Mortality trends revealed decreases of 9.66% annually in Italy, with remaining countries demonstrated rate stabilization (Table S4).

9. Western Europe

Western European countries exhibited generally comparable incidence and mortality rates, positioning the region at an intermediate level relative to all populations examined. A notable exception was Luxembourg, which demonstrated the second highest mortality rate globally. Germany exhibited a downward trajectory of approximately 7.42% annually during the most recent 5-year period, while the remaining countries showed rate stabilization (Table S3). Mortality trends revealed decreases of 21.34% and 20.52% annually in Austria and Switzerland, with remaining countries demonstrated rate stabilization (Table S4).

10. Latin America and the Caribbean

Latin America and the Caribbean countries exhibited variability in incidence rates across the 6 included populations, with minimal variation from 0.82 per 100,000 women in Brazil to 3.44 in Ecuador-demonstrating intermediate and relatively low ASIRs across the region (Fig. 2). However, substantial geographic variation was evident across the 16 Latin American and Caribbean countries, with mortality rates ranged from 0.77 per 100,000 women in Mexico to 6.85 in Belize, which demonstrated the highest mortality rate among all studied populations, followed by the 6th- and 8th-highest ASMR countries-Guyana (4.53 per 100,000 person-years) and Trinidad and Tobago (3.11 per 100,000 person-years) (Fig. 3). Recent 5-year mortality trends revealed continued annual increases of 11.08% in Bolivarian Republic of Venezuela with remaining countries maintaining stable rates (Table S4).

11. North America

The United States and Canada demonstrated incidence rates within the highest tertile of all populations studied, yet exhibited markedly lower mortality rates, ranking 7th and 8th from the lowest, respectively (Figs. 2 and 3). Incidence and mortality trends during the most recent 5-year period exhibited stabilization trends in both countries (Tables S3 and S4).

12. Oceania

Australia and New Zealand exhibited comparable global incidence. However, mortality differed between Australia and New Zealand, with rates of 0.38 and 0.83 per 100 000 person-years, respectively. Over the most recent 5-year period, both incidence and mortality rates declined in 2 countries, yet the reductions did not attain statistical significance (Tables S3 and S4).

DISCUSSION

Our comprehensive analysis of ovarian cancer epidemiology in adolescents and young adults across 185 countries reveals striking global disparities that reflect complex interactions between biological, socioeconomic, and healthcare system factors. The estimated age-standardized incidence rates in 2022 were highest in Melanesia (4.79 per 100,000), Eastern Europe (3.94 per 100,000), and several Southeast Asian countries, with Brunei Darussalam exhibiting the highest national rate (8.36 per 100,000). These patterns align with recent global cancer burden analyses demonstrating geographic heterogeneity in AYAs malignancies [20]. The inverse relationship between HDI and mortality rates-despite relatively uniform incidence patterns-underscores fundamental healthcare inequities. Countries with low HDI experienced mortality rates up to 20-fold higher than high-HDI nations, a disparity exceeding that reported for most adult cancers [21]. This finding corroborates the Global Cancer Observatory’s recent analysis showing that healthcare system capacity, rather than disease incidence, primarily determines cancer survival outcomes in resource-limited settings [1].

Contextualizing our findings within the recent literature highlights how the inclusion of young adults in the AYA definition critically influences epidemiological interpretation. While the AYA population is often analyzed as a single entity, distinct oncogenic patterns exist within its subgroups. Recently, Che and Yin [9] characterized the global burden of ovarian cancer strictly in adolescents (10–19 years), reporting a relatively low incidence predominantly driven by germ cell tumors. However, by aggregating young adults (20–39 years) with adolescents, our study unmasks a significant disease burden that remains inconspicuous in adolescent-only analyses. This dramatic escalation in incidence is driven by the early onset of epithelial ovarian cancers in the older segment of the AYA spectrum. This observation aligns with the global surveillance data from Fidler et al. [22], which demonstrated that the 20–39 age group exhibits a distinct cancer profile characterized by a steep rise in carcinomas compared to younger cohorts. Importantly, our use of actual cancer registry data from CI5plus, GLOBOCAN 2022, and WHO mortality database, rather than modeled estimates, provides more reliable trend assessments. Zhang et al. [23] demonstrated that GBD modeling can overestimate cancer burden by 15% in countries with limited registration coverage, particularly affecting rare cancers like AYAs ovarian malignancies. Our methodology, incorporating 3 complementary IARC databases, minimizes these biases while maintaining global coverage.

The epidemiological patterns we observed may align with global shifts in reproductive behaviors, which serve as important contextual factors. The fertility transition occurring in regions like Eastern Europe and East Asia-characterized by delayed childbearing and reduced parity-has been documented in the literature to influence ovarian cancer risk [24,25,26]. Furthermore, geographic variations in the prevalence of oral contraceptive use and the increasing utilization of assisted reproductive technologies in high-income countries may contribute to the heterogeneity in disease burden [27,28], although our aggregate dataset limits the ability to draw direct causal inferences regarding these specific exposures.

The striking global heterogeneity in mortality rates-ranging from a low of 0.34 per 100,000 in Turkey and Spain to a high of 6.85 per 100,000 in Belize-reflects profound disparities in healthcare infrastructure and access to specialized oncology services. Wolfson et al. [29] demonstrated that for AYA patients, treatment at National Cancer Institute-designated comprehensive cancer centers is associated with a statistically significant reduction in mortality compared to community-based settings, highlighting the impact of resource availability. Similarly, the European Society for Medical Oncology and the European Society for Pediatric Oncology emphasize that the lack of centralized, age-appropriate multidisciplinary care infrastructure is a major barrier to improving survival rates for AYA malignancies, advocating for dedicated networks to bridge the gap between pediatric and adult oncology services [30]. In resource-constrained settings, these systemic deficits manifest as delays in symptom recognition and limited access to essential diagnostic tools leading to advanced-stage presentations [31]. The consequences of such systemic fragility are vividly illustrated by our Joinpoint analysis, which identified precipitous mortality increases in regions facing sociopolitical instability. Notably, the steep rise in Venezuela (AAPC=11.08% during 2012–2016) coincides with the country’s severe economic crisis and healthcare collapse, while the upward trend in Syria (AAPC=15.89% during 2006–2010) highlights critical healthcare vulnerabilities preceding the major conflict.

These findings underscore the urgent need for targeted public health interventions in low-HDI settings, where the disease burden remains disproportionately high relative to available resources [22,32]. To mitigate rising mortality rates, strategies must prioritize 3 key areas. First, strengthening population-based cancer registries is fundamental to accurately monitor epidemiological trends and guide resource allocation [22]. Second, improving the accessibility of cost-effective diagnostic modalities-specifically transvaginal ultrasound and basic tumor marker testing-is critical for detecting malignancies at manageable stages in primary care settings [33]. Third, ensuring the availability and affordability of standard chemotherapy regimens (e.g., platinum-based therapies) and surgical oncology services is vital [34]. Ultimately, international collaboration and funding must be directed towards infrastructure development to bridge the widening gap between high- and low-transition countries [32].

This study represents the most comprehensive global analysis of AYAs ovarian cancer epidemiology to date, with several key strengths. We leveraged three complementary high-quality IARC databases (GLOBOCAN 2022, CI5plus, and WHO mortality database) to provide unprecedented geographic coverage across 185 countries providing unprecedented insight into global patterns and temporal trends. The stratification by HDI offers valuable context for interpreting observed disparities and identifying priority areas for intervention. However, several limitations must be acknowledged. Several limitations must be acknowledged. First, while GLOBOCAN 2022 provides global estimates, the availability of high-quality, population-based registry data remains geographically unbalanced. In our long-term trend analyses including countries with at least 10 consecutive years, only 44 and 59 of the 185 countries had sufficient longitudinal data to assess incidence and mortality trends, respectively. The majority of excluded nations are low- and medium-HDI countries in sub-Saharan Africa, Central Asia, and parts of Latin America. Second, for countries without national registries, GLOBOCAN estimates are often modeled based on data from neighboring regions or limited urban sub-national registries [35]. This reliance on modeled data may introduce selection bias, particularly an ‘urban bias,’ where data from better-resourced urban centers are extrapolated to rural populations [36]. This could lead to an overestimation of diagnostic rates (due to better detection in cities) and a potential underestimation of the true mortality burden when applied to the entire national population. Third, these data limitations have critical implications for interpreting disparities in low-HDI regions. The observed ‘lower’ incidence in some developing nations may partially reflect under-diagnosis due to limited access to diagnostic imaging and pathology services, rather than a genuinely lower disease burden. Furthermore, our analysis cannot account for histological subtypes, which significantly influence prognosis and treatment approaches in AYAs ovarian cancer. The lack of stage-specific data prevents assessment of whether observed mortality improvements reflect earlier diagnosis versus therapeutic advances. Notably, neither GLOBOCAN 2022 nor CI5plus captures disability estimates; therefore, subsequent studies utilizing comprehensive datasets are warranted to address this knowledge gap.

This comprehensive global analysis reveals substantial geographic disparities in AYAs ovarian cancer mortality despite relatively uniform incidence rates, with mortality burden disproportionately affecting populations in low-HDI countries. The divergent incidence-mortality patterns observed in several countries provide compelling evidence that healthcare system improvements can successfully enhance survival outcomes even as disease detection increases. These findings underscore the critical importance of global health equity initiatives targeting young women with ovarian cancer.

SUPPLEMENTARY MATERIALS

Table S1

ASIRs per 100,000 women in ovarian cancer in adolescents and young adults by countries in 2022

Table S2

ASMRs per 100,000 women in ovarian cancer in adolescents and young adults by countries in 2022

Table S3

Long- and short-term (5 years) trends in in age-standardized ovarian cancer incidence rates for selected countries and regions in adolescents and young adults

Table S4

Long- and short-term (5 years) trends in in age-standardized ovarian cancer mortality rates for selected countries and regions in adolescents and young adults

Fig. S1

Age-standardized incidence (A) and mortality rates (B) of ovarian cancer in adolescents and young adults by HDI in 2022. Each dot represents a country.