Content area
Background
Head and neck cancer (HNC) caused substantial morbidity and mortality. Despite advances in treatment modalities, the evolving burden and risk factor profiles of head and neck cancer may contribute to escalating health inequalities. The primary objective of this study is to quantitatively evaluate the degree of SDI-related health inequalities in head and neck cancer and to analyze the evolution of these health inequality trends between 1992 and 2021.
Methods
Using Global Burden of Disease 2021 data, we extracted disability-adjusted life years (DALYs), DALY rates and age-standardized DALY rates (ASDR) for HNC and its five subtypes across 204 countries/territories (1992–2021). Temporal trends stratified by sex and Sociodemographic Index (SDI) levels were assessed using estimated annual percentage change (EAPC) modeling. Socioeconomic health inequalities were further measured through complementary metrics: the Slope Index of Inequality (SII) and Concentration Index (CIX).
Results
From 1992 to 2021, the global ASDR for HNC declined from 228.1 to 179.37 per 100,000 (EAPC: -0.95, 95% CI: -1.05 to -0.84). The low-middle SDI region exhibited the highest ASDR (294.46 per 100,000), while the high SDI region recorded the lowest ASDR (107.97 per 100,000). The CIX indicated a progressive deterioration, decreasing from − 0.11 (95% CI: -0.15 to -0.08). in 1992 to -0.16 (95% CI: -0.22 to -0.11) in 2021. The inequality was particularly pronounced among females, where CIX values decreased from − 0.21 (95% CI: -0.25 to -0.17) to -0.24 (95% CI: -0.30 to -0.17) during the same period, consistently remaining at a relatively high level.
Conclusion
The persistent and widening inequalities in HNC, particularly those affecting females and low SDI regions, call for equitable global governance. particularly affecting females and low-SDI regions, necessitate equitable global governance. Addressing this issue necessitates the establishment of robust data systems, the implementation of gender- and region-specific interventions, the bridging of technological and resource gaps, and enhanced cross-sectoral collaboration. This integrated approach is essential for disrupting the low-SDI/high-burden cycle and promoting health equity as a fundamental right.
Background
Head and neck cancer (HNC) is anatomically defined as a group of malignant tumors that occur above the clavicles, below the skull base, and in the anterior region of the neck vertebral column [1]. This group includes thyroid cancer (TC), lip and oral cavity cancer (LOC), laryngeal cancer (LC), nasopharyngeal cancer (NPC), and other oropharyngeal cancers (OPCs). As a significant global health threat, data from 2022 indicate that there were 1,712,626 new cases of HNC, accounting for 8.5% of global cancer incidence, and 505,592 deaths, making up 5.2% of total cancer mortality [2]. These malignant tumors not only pose a direct threaten patient survival directly but also severely impact essential physiological functions such as breathing, swallowing, and speaking due to their unique anatomical locations. This results in significant changes in appearance and a substantial decline in quality of life, imposing a heavy physical and psychological burden on patients [3]. Additionally, these diseases contribute to considerable socioeconomic burdens. It is estimated that HNC causes economic losses of up to $535 billion annually between 2018 and 2030, representing a significant challenge to global public health and healthcare systems [4].
The epidemiological burden of HNC is undergoing complex dynamic evolution, intensifying and displaying significant heterogeneity across different genders, geographical regions, socio-demographic indices (SDI), and anatomical subtypes [1, 5, 6, 7, 8–9]. Concurrently, the risk factor composition for HNC is experiencing a critical transition. Traditional risk factors, including smoking, alcohol consumption, and areca nut chewing, continue to exert a major global burden, particularly in specific regions such as South Asia [10, 11, 12, 13, 14–15]. However, in high-income countries, human papillomavirus (HPV) infection has emerged as the predominant cause of oropharyngeal cancer [16, 17, 18–19]. Additionally, emerging factors such as Body Mass Index (BMI) and occupational exposures are gaining recognition [20, 21, 22–23]. Changes in the heterogeneity of these burdens and risk factors, alongside disparities in healthcare access and demographic factors, may exacerbate global health inequalities concerning HNC. These inequalities manifests as considerable gaps in incidence rates, early diagnosis, treatment accessibility, survival rates, and quality of life among diverse populations and genders across various regions [24, 25, 26, 27, 28, 29–30]. Furthermore, these disparities aggravate socioeconomic burdens, inhibit effective disease prevention and control efforts, and entrench existing social injustices, thereby posing significant challenges to global health equity and sustainable development. To respond to these health equity challenges, the World Health Organization (WHO) emphasizes that “knowledge, monitoring, and analysis are central to achieving equitable action”, and calls for the systematic collection, integration, and analysis of health inequality evidence based on equity and gender to inform strategy formulation and implementation aimed at enhancing health equity [31]. With the increasing global focus on health inequalities, more studies are beginning to concentrate on this area. Existing studies have initially revealed the spatiotemporal heterogeneity and inequality issues related to HNC burdens and risks, they mostly focus on single countries, specific regions, or individual subtypes, lacking a comprehensive and multidimensional quantitative assessment of HNC-related health inequalities on a global scale. Such global and multidimensional systemic analyses are essential, as they accurately quantify and compare health disparities among various populations and regions over time, providing crucial scientific evidence for developing fairer and more effective prevention strategies, optimizing resource allocation, and monitoring intervention outcomes.
Consequently, this study aims to utilize the Global Burden of Disease (GBD) 2021 data to systematically analyze health inequalities in global head and neck cancer, along with its major subtypes, from 1992 to 2021. The specific objectives are: (1) to quantitatively assess the degree of health inequality in head and neck cancer in relation to the (SDI), and (2) to analyze the trends in health inequalities pertaining to head and neck cancer from 1992 to 2021.
Methods
Data sources
To comprehensively analyze the burden and regional disparities of HNC, we conducted a secondary analysis using data from the GBD 2021 (accessible at https://vizhub.healthdata.org/gbd-results/). This dataset, part of the regularly updated GBD series, integrates over 100,983 globally representative data sources, including vital registration, scientific literature, disease registries, household surveys, and clinical informatics, curated by an international network of more than 10,000 collaborators across 150 countries [32]– [33]. It provides an in-depth epidemiological evaluation of 371 diseases and 88 risk factors and encompasses seven super-regions. These regions are categorized by geographic and epidemiological similarities and include 21 regions and 204 countries/territories from 1990 to 2021. Burden estimates were generated through a standardized modeling framework: (1) Non-fatal outcomes (incidence/prevalence) were modeled using DisMod-MR 2.1 (Bayesian meta-regression) and ST-GPR (spatiotemporal smoothing); (2) Fatal outcomes (Years of Life Lost, YLLs) were estimated using Cause of Death Ensemble modeling (CODEm) with redistribution of garbage codes; and (3) Years of Disability (YLDs) were calculated by splitting diseases into severity-based sequelae, applying disability weights (on a 0–1 scale), and adjusting for comorbidities via microsimulation. All rates were age-standardized using the GBD global standard population structure, which spans 25 age groups, from 0 to 6 days to 95 + years, with finer granularity for the under-5 cohorts [34]. More information regarding the GBD global standard population structure can be accessed through the Global Health Data Exchange web tool (http://ghdx.healthdata.org/).
We obtained estimates of Disability-Adjusted Life Years (DALYs), DALY rates, and Age-Standardized Death Rates (ASDR) for HNC and its five subtypes (TC, LOC, LC, NPC, and OPCs) across 204 countries and territories from 1992 to 2021, including their 95% uncertainty intervals(UI). Furthermore, we utilized the SDI, a composite measure of overall development pertinent to health outcomes. The SDI is calculated as the geometric mean of three components: lag-distributed income (LDI) per capita, the total fertility rate for women under 25 (TFU25)—an indicator of women’s status—and the average educational attainment for populations aged 15 years and older (EDU15+). Each component is scaled within empirically defined minimum and maximum bounds relevant to health outcomes, resulting in a composite SDI value that ranges from 0 (the theoretical minimum level of development related to health outcomes) to 1 (the theoretical maximum level of development related to health outcomes). Based on the 2021 SDI values, countries and regions were classified into into five groups: low SDI, low-middle SDI, middle SDI, high-middle SDI, and high SDI [34].
Disease definitions
Anatomically, HNC refers to a group of malignant tumors located above the clavicles, below the skull base, and in the anterior part of the neck vertebral column [1]. The GBD 2021 includes five types of cancer: TC, LOC, LC, NPC, and OPCs. The International Classification of Diseases 10 (ICD-10) assigns specific codes: LOC (C00 -- C08.9, D10.0–D10.5, D11–D11.9), NPC (C11–C11.9, D10.6), OPCs (C09–C10.9, C12–C13.9, D10.7), TC (C73–C73.9, D09.3, D09.8, D34–D34.9, D44.0), and LC (C32–C32.9, D02.0, D14.1, D38.0).
Statistical analysis
Description of burden and trend analysis
Descriptive statistics quantified the global, regional, and sex-specific burden of HNC and its subtypes using DALYs, crude DALY rates, and ASDR per 100,000 population. Visualizations included sex-stratified stacked bar charts and choropleth maps of ASDR disparities across countries/territories, generated using R v4.1.0 with the ggplot2 package.
Temporal trends were evaluated using the estimated annual percentage change (EAPC), which was calculated by fitting a linear regression model to the natural logarithm of the ASDR, represented as , where β denotes the slope coefficient [35]. Confidence intervals (CI) for the EAPC were derived from the standard error of β to quantify the uncertainty in the trend estimates. The ASDR was considered to have increased if the lower boundary of the 95% CI for the EAPC exceeded 0, while it was considered to have decreased if this boundary was less than 0. If the 95% CI included zero, the ASDR was regarded as unchanged [36]. The EAPC is calculated as .
Cross-country social inequality analysis
To assess global inequalities in the ASDR of HNC patients according to sex and subtypes, we utilized two complementary measures: the slope inequality index (SII) and the concentration index (CIX). The SII serves as a measure of absolute inequality, quantifying the average absolute difference in ASDR between populations situated at the highest and lowest ends of the socioeconomic spectrum [37]. Conversely, the CIX measures relative inequality, capturing the disproportionate concentration of disease burden in relation to the socioeconomic gradient [38]. Both the SII and CIX are standard univariate metrics recommended by the GBD consortium for assessing health inequalities [39, 40, 41–42]. The SII offers an absolute measure of the health gradient across the entire socioeconomic hierarchy, while the CIX reflects relative inequality independent of average disease rates [43, 44–45]. This dual approach is consistent with the guidelines set forth by the WHO for comprehensive health inequality reporting [46].
The SII was derived by fitting a population-weighted least squares regression model to country-specific ASDR values, regressed against a relative position scale based on the SDI, defined as the midpoint of cumulative population percentiles ranked by the SDI [44]. The SII coefficient represents the estimated absolute ASDR difference (per 100,000 person-years) between the hypothetically highest (relative position = 1) and lowest (relative position = 0) SDI populations. A negative SII indicates a higher ASDR in low-SDI populations, reflecting an inverse association [47].
The CIX was computed by ranking countries by SDI and plotting the cumulative proportion of ASDR for HNC on the y-axis against the cumulative population proportion on the x-axis to construct the Lorenz concentration curve. The CIX was then calculated as twice the area between the curve and the line of equality (the 45° line) using numerical integration via the trapezoidal rule [48]. The index ranges from − 1 to 1; values less than 0 indicate a disproportionate burden in disadvantaged populations, while values of |CIX| greater than 0.2 signify a reasonably high level of relative inequality [46].
For uncertainty analysis, 95% CI for SII and CIX were derived through 1,000 bootstrap replicates of country-level data, accounting for sampling variability in GBD estimates. The robustness of the model was assessed by recalculating indicators using the bounds of the 95% CIs for ASDR, selecting values that minimized (lower bound) or maximized (upper bound) inequality.
Results
Global burden and trend of HNC, 1992–2021
From 1992 to 2021, the number of global DALYs for HNC increased by 52.79%, from 10.21 million (95% UI: 9.56 to 10.59) to 15.60 million (95% UI: 14.18 to 16.95). The ASDR for total HNC decreased globally from 228.10 (95% UI: 213.64 to 244.55) to 179.37 (95% UI: 162.94 to 194.93) per 100,000 people, with an EAPC of −0.95 (95% CI: −1.05 to −0.84) (Table 1). The highest DALY rates appeared in the 60–64-year age group in 1992 and in the 65–69-year age group in 2021 (Fig. 1). However, the highest ASDR for HNC patients was observed in the 55–59-year age group in both 1992 and 2021. All five HNC subtypes showed declining ASDR trends, which is consistent with the overall trend for HNC. The NPC experienced the most significant decline, with a 44.1% reduction in the ASDR (EAPC: −2.29, 95% CI: −2.52 to −2.07). For more detailed information on the burden of HNC and its subtypes across age-stratified groups in 1992 and 2021, please refer to Supplementary Tables S1–12.
In 2021, males accounted for 72.39% of HNC DALYs (Fig. 1). The ASDR for HNC was greater in males than in females, except for TC (Table S13). From 1992 to 2021, the ASDR for HNC tended to decrease in both males (EAPC: −1.02, 95% CI: −1.12 to −0.92) and females (EAPC: −0.75, 95% CI: −0.87 to −0.62) (Table S14). However, ASDR trends for each specific cancer varied between sexes. The LC and NPC tended to decrease in both males and females (EAPC < 0, P < 0.05). For OPCs, males presented a declining trend (EAPC: −0.11, 95% CI: −0.20 to −0.02), whereas females presented an increasing trend (EAPC: 0.09, 95% CI: 0.01 to 0.17). Conversely, TC showed a decreasing trend in females (EAPC: −0.46, 95% CI: −0.49 to −0.43) but an increasing trend in males (EAPC: 0.41, 95% CI: 0.35 to 0.48). For more details on the EAPCs in the ASDRs of HNC patients and its subtypes from 1992 to 2021, please refer to Supplementary Table S14.
Table 1. Global burden of head and neck cancer in 1992 and 2021
DALYS | Crude DALY rates | Age-standardized DALY rates | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
1992 (million) | 2021 (million) | Change (%) | 1992 (/1000000) | 2021 (/1000000) | Change (%) | 1992 (/1000000) | 2021 (/1000000) | Change (%) | EAPC | |
HNC | 10.21 (9.56, 10.95) | 15.60 (14.18, 16.95) | 52.79 | 185.68 (173.93,199.22) | 197.66 (179.70,214.77) | 6.45 | 228.10 (213.64,244.55) | 179.37 (162.94,194.93) | −21.36 | −0.95 (−1.05, −0.84) |
LOC | 3.09 (2.95, 3.25) | 5.87 (5.33, 6.35) | 89.97 | 56.16 (53.61,59.03) | 74.44 (67.50,80.44) | 32.55 | 69.74 (66.49,73.29) | 67.71 (61.32,73.17) | −2.91 | −0.18 (−0.24, −0.12) |
LC | 2.56 (2.40, 2.71) | 3.14 (2.92, 3.38) | 22.66 | 46.48 (43.61,49.37) | 39.83 (37.04,42.88) | −14.31 | 58.66 (54.97,62.31) | 35.80 (33.29,38.54) | −38.97 | −1.84 (−1.93, −1.74) |
TC | 0.68 (0.63, 0.75) | 1.25 (1.09, 1.38) | 83.82 | 12.31 (11.49,13.60) | 15.80 (13.87,17.43) | 28.35 | 15.24 (14.24,16.74) | 14.57 (12.78,16.11) | −4.40 | −0.14 (−0.18 to −0.11) |
NPC | 2.44 (2.24, 2.67) | 2.49 (2.21, 2.78) | 2.04 | 44.36 (40.72,48.59) | 31.56 (28.06,35.21) | −28.85 | 51.74 (47.51,56.67) | 28.91 (25.69,32.24) | −44.12 | −2.29 (−2.52, −2.07) |
OPCs | 1.45 (1.35, 1.57) | 2.84 (2.62, 3.06) | 95.86 | 26.37 (24.51,28.63) | 36.04 (33.23,38.82) | 36.67 | 32.72 (30.43,35.54) | 32.38 (29.85,34.87) | −1.04 | −0.09 (−0.18, 0.00) |
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Fig. 1
Burden of HNC stratified by sex, age, and cancer subtype in 1992 and 2021
Burdens and trends in HNC incidence by SDI region and sex from 1992 to 2021
In 2021, the middle-SDI region recorded the highest HNC DALYs at 4.77 million (95% UI: 4.23 to 5.29), whereas the low-SDI region had the lowest DALYs at 1.37 million (95% UI: 1.14 to 1.64) (Fig. 2, Table S13). After age standardization, the low-middle-SDI region presented the highest ASDR at 294.46 per 100,000 (95% UI: 258.92 to 329.92), whereas the high-SDI region presented the lowest at 107.97 per 100,000 (95% UI: 101.78 to 113.89) (Fig. 3, Table S14). The ASDR decreased across all the SDI regions (EAPC < 0, P < 0.05), with the exception of the low–middle-SDI region (EAPC < 0, P > 0.05), where it significantly increased. Subtypes of HNC showed variation in the ASDR across regions: the NPC had the highest ASDR in the high–middle-SDI region in 2021, while the TC was most prevalent in the low-SDI region, and other HNC subtypes presented the highest ASDR in the low–middle-SDI region. The NPC (across all SDI regions) and TC (in the high-, middle- and high-SDI regions) showed decreasing ASDR trends (EAPC < 0, P < 0.05) during the study period.
The sex-specific distribution trends aligned with the overall patterns (Table S13-14). Specifically, regions with lower SDI values presented greater ASDRs for most types of HNC, whereas regions with higher SDI values presented lower ASDRs. However, for NPC, males had the highest ASDR in the high-middle-SDI region, whereas females experienced the highest ASDR in the low-SDI region. In terms of trends, for OPCs, males presented an increasing ASDR trend in the low/low-middle-SDI regions, whereas females presented an increasing trend in the high-SDI region. Detailed data on DALYs, DALY rates, and ASDRs for all HNC cases across countries, SDI regions, and sex-specific categories are available in the online Supplementary Tables S13–S14 and Figure S1–S5.
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Fig. 2
Burden of HNC stratified by sex, age, and SDI region 2021. (A) HNC, (B) LOC, (C) LC, (D) TC, (E) NPC, (F) OPCs
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Fig. 3
World maps of ASDR of HNC in 2021
Cross-national inequality in HNC burden from 1992 to 2021
Absolute inequality (Slope Index of Inequality, SII)
In 1992, a notable health disparity related to SDI was observed concerning the ASDR for HNC. Specifically, the ASDR for HNC in the highest socioeconomic status group was approximately 51.96 per 100,000 (95% CI: 18.96 to 84.96) higher than that in the lowest socioeconomic status group. However, the overall SII for total HNC in 2021 was 0.79 (95% CI: −27.20 to 28.77), indicating no absolute inequality (Table 2; Fig. 4, S6–S10). Gender stratification analysis revealed that the SII for females decreased from − 23.57 (95% CI: −40.57 to −6.57) to −37.10 (95% CI: −50.28 to −23.93), suggesting an intensifying burden on low-income women. Subtype analysis indicated that NPC was the only subtype for absolute inequality worsened for both sexes; the SII for males changed from − 8.56 (95% CI: −18.88 to 1.75) in 1992 to −14.73 (95% CI: −22.69 to −6.79) in 2021, while for females, it changed from − 8.91 (−13.25 to −4.58) in 1992 to −9.65 (−13.01, −6.29) in 2021.
Table 2. SRIs associated with the global ASDR of HNC and its subtypes in 1992 and 2021 stratified by sex
Global | Slope index of inequality | |
|---|---|---|
1992 | 2021 | |
HNC | ||
Both | 51.96(18.96, 84.96) | 0.79(−27.20, 28.77) |
Female | −23.57(−40.57, −6.57) | −37.10(−50.28, −23.93) |
Male | 137.61(77.04, 198.19) | 36.01(−13.42, 85.44) |
LOC | ||
Both | 8.65(−3.60, 20.90) | −4.77(−15.43, 5.90) |
Female | −15.65(−21.55, −9.74) | −17.25(−22.28, −12.23) |
Male | 36.46(15.43, 57.49) | 8.10(−10.13, 26.33) |
LC | ||
Both | 16.89(4.08, 29.70) | −6.32(−14.10, 1.47) |
Female | −3.17(−6.56, 0.22) | −4.20(−6.50, −1.90) |
Male | 40.69(16.51, 64.87) | −6.93(−22.02, 8.17) |
TC | ||
Both | 5.93(3.09, 8.77) | −2.06(−4.72, 0.60) |
Female | 3.94(0.09, 7.79) | −6.34(−10.05, −2.63) |
Male | 6.72(4.69, 8.75) | 2.54(0.43, 4.65) |
NPC | ||
Both | −9.83(−17.31, −2.34) | −12.21(−17.84, −6.58) |
Female | −8.91(−13.25, −4.58) | −9.65(−13.01, −6.29) |
Male | −8.56(−18.88, 1.75) | −14.73(−22.69, −6.79) |
OPC | ||
Both | 17.11(10.61, 23.60) | 14.13(8.46, 19.79) |
Female | 0.85(−1.33, 3.04) | 1.24(−0.77, 3.26) |
Male | 33.21(21.20, 45.22) | 26.69(16.70, 36.68) |
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Fig. 4
SII of HNC in 1992 and 2021
Relative inequality (Concentration Index, CIX)
Relative inequality, assessed using the CIX, demonstrated a progressive concentration of HNC burden in low SDI countries from 1992 to 2021. The CIX for total HNC worsened from − 0.11 (95% CI: −0.15 to −0.08) to −0.16 (95% CI: −0.22 to −0.11), indicating an increase in relative inequality(Table 3; Fig. 5, S11-15). In 2021, all subtypes exhibited pro-poor inequality, except for NPC, with LOC exhibiting the highest degree of inequality (CIX = −0.23 [95% CI: −0.30 to −0.15]). Gender analysis reveals that females experience greater deprivation across all subtypes, as the CIX for total HNC decreasing from − 0.21(95% CI: −0.25 to −0.17)in 1992 to −0.24 (95% CI: −0.30 to −0.17) in 2021, while females with LOC consistently maintain a high negative value of −0.31(95% CI: −0.41 to −0.21). Although relative inequality among males in total HNC, LOC, and OPCs has intensified, it has not yet reached a reasonably high level (|CIX| < 0.2, P < 0.05).
Table 3. CIX effects on the global ASDR of HNC and its subtypes in 1992 and 2021 stratified by sex
Global | Concentration index | |
|---|---|---|
1992 | 2021 | |
HNC | ||
Both | −0.11(−0.15, −0.08) | −0.16(−0.22, −0.11) |
Female | −0.21(−0.25, −0.17) | −0.24(−0.30, −0.17) |
Male | −0.06(−0.10, −0.02) | −0.13(−0.18, −0.08) |
LOC | ||
Both | −0.19(−0.25, −0.13) | −0.23(−0.30, −0.15) |
Female | −0.31(−0.39, −0.23) | −0.31(−0.41, −0.21) |
Male | −0.12(−0.18, −0.06) | −0.18(−0.24, −0.11) |
LC | ||
Both | −0.03(−0.07, 0.01) | −0.15(−0.19, −0.11) |
Female | −0.12(−0.16, −0.08) | −0.19(−0.24, −0.14) |
Male | 0.01(−0.03, 0.06) | −0.14(−0.18, −0.10) |
TC | ||
Both | 0.00(−0.04, 0.04) | −0.09(−0.13, −0.05) |
Female | −0.05(−0.09, −0.01) | −0.14(−0.18, −0.09) |
Male | 0.07(0.03, 0.10) | −0.01(−0.05, 0.02) |
NPC | ||
Both | −0.11(−0.17, −0.04) | −0.06(−0.11, 0.00) |
Female | −0.16(−0.23, −0.10) | −0.15(−0.20, −0.09) |
Male | −0.07(−0.14, 0.00) | −0.02(−0.08, 0.04) |
OPCs | ||
Both | −0.14(−0.21, −0.07) | −0.17(−0.24, −0.09) |
Female | −0.28(−0.35, −0.21) | −0.24(−0.31, −0.16) |
Male | −0.09(−0.15, −0.02) | −0.15(−0.23, −0.07) |
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Fig. 5
CIX of HNC in 1992 and 2021
Discussion
The findings of this study reveal dynamic inequalities in the burden of HNC across regions with varying SDI levels and between genders. Global analysis shows that the global ASDR for HNC declined from 1992 to 2021. However, aging populations have led to an increase in the total disease burden. Disparities in this burden were significant by gender and region, with males and lower SDI regions experiencing a higher burden. We further utilized the Slope SII and CIX to assess SDI-related inequalities in HNC DALYs. These metrics revealed a progressive concentration of the relative HNC burden in low-SDI countries. Notably, while the CIX for males increased, persistent relative inequalities were observed among females, contributing to entrenched health vulnerabilities in these groups. These geographic and gender-specific inequalities highlight the complexity of addressing health disparities on a global scale. Improvements in healthcare access and treatment may not have proportionally reduced the burden for the most vulnerable populations.
During this period, the global DALYs for HNC increased by 52.8%, while the ASDR showed a declining trend. This finding aligns with results from Zhou et al. based on GBD 2019 [1]. Population aging has emerged as the primary driver of the increase in DALYs. This trend is also common in broader cancer epidemiology: while improvements in treatment reduce mortality rates, population aging concurrently elevates the absolute disease burden [49]. The decline in ASDR signifies enhanced treatment effectiveness. This improvement stems from two key developments. First, the widespread adoption of diagnostic technologies, such as endoscopy for screening and follow-up surveillance, has significantly increased early detection rates and recurrence identification. This advancement effectively delays disease progression to stages associated with higher mortality [50]. Second, multimodal treatment approaches combining surgery, radiotherapy, and chemotherapy have become standard. These approaches have significantly reduced overall mortality, particularly improving outcomes for patients with recurrent or metastatic disease. Studies have confirmed that treatment regimens incorporating immune checkpoint inhibitors (e.g., Pembrolizumab) or combining chemotherapy with targeted agents (e.g., Cetuximab) significantly extend median overall survival in patients with advanced HNC [51, 52]. However, the health gains from these medical advances may be unevenly distributed globally, potentially masking persistent and worsening structural health inequities.
The study revealed significant inequalities in the global distribution of the HNC burden across both sexes and SDI regions. Consistent with prior research, this study observed that males bear a disproportionately higher share of total HNC DALYs [1]. This disparity is likely attributable to greater male exposure to key behavioral risk factors, including tobacco use, alcohol consumption, and occupational carcinogens, coupled with lower levels of protective estrogen compared to females [15, 53, 54–55]. However, TC presented an exception. Females exhibited higher ASDR for TC, although the ASDR declined over time, aligning with previous findings [8, 56, 57]. This pattern may be due to estrogen’s role in increasing thyroid cell mutagenesis, which leads to higher rates of thyroid-related symptoms, such as nodules and hyperthyroidism, among women [58, 59]. Consequently, women tend to seek healthcare more frequently, enhancing detection opportunities [60, 61]. It is noteworthy that the male TC ASDR demonstrated an upward trend, corroborating earlier reports of significantly steeper mortality increases in males relative to females [61]. This phenomenon may be explained by the typically more aggressive tumor biology of male TC, compounded by delayed diagnosis and treatment resulting from lower awareness among men, which collectively worsens prognosis [61, 62]. Further analysis indicated even starker disparities across SDI regions: low-middle SDI regions bore the highest HNC ASDR burden, with no significant decline during the period from 1990 to 2021. In stark contrast, high SDI regions exhibited the lowest ASDR and a sustained downward trend, underscoring profound global inequities in healthcare access. Lower SDI regions face multiple barriers, including scarcity of healthcare resources, financial hardship, and limited access to essential services. Globally, the poorest nations, which typically fall within the low-middle SDI category and are home to over one-third of the global population, account for only 6% of the 313 million surgeries performed annually, highlighting severe surgical shortages and inequitable distribution [63]. Furthermore, even when surgery is accessible, approximately one-quarter of patients incur catastrophic medical expenditures, a burden disproportionately heavy in these countries[63]. Access to critical healthcare services is also severely constrained; for instance, existing screening guidelines for oral cancer have low uptake in these settings [64]. The density of oral and maxillofacial surgeons is drastically lower (0.015 per 100,000) compared to high-income countries (1.087 per 100,000), which directly impedes early diagnosis and effective treatment [65].
To better understand and quantify the sexes and regional disparities in HNC, particularly their association with SDI and spatiotemporal trends, we applied the SII and CIX to assess SDI-related inequalities in HNC DALYs. The analysis indicates that lower SDI countries bear a disproportionately high HNC burden, and this SDI-associated health inequality gap has widened over time. These countries often face a higher burden of infectious diseases, which severely constrains resources allocated to chronic non-communicable diseases (NCDs) like HNC [66]. Economic disparities are a fundamental driver of this inequality. As noted earlier, high SDI countries generally possess more robust primary healthcare systems, while lower SDI countries are trapped in healthcare resource scarcity. This directly leads to delayed HNC diagnosis and inadequate treatment and care, ultimately increasing the DALY burden [67, 68–69]. Concurrently, the control of key risk factors for HNC (e.g., tobacco, alcohol) in lower SDI regions remains insufficient [70, 71]. More critically, gender-stratified analysis revealed that the absolute values of both SII and CIX increased more substantially for female compared to male, indicating a rapid deterioration of SDI-related health inequalities for female HNC patients. The CIX value for female HNC has reached a reasonably high level, particularly pronounced for specific subtypes like LC and OPC [46]. This highlights an increasingly severe and disproportionate HNC burden on female in lower SDI regions, reflecting their dual disadvantage in both healthcare access and risk factor exposure. Firstly, multiple barriers significantly restrict their access to healthcare services. In some lower SDI regions, particularly within East Asian cultural contexts, felmales experience systemic under-empowerment in social institutions, with social norms often relegating their roles to unpaid caregiving and household responsibilities. Prevailing social norms often confine them to unpaid caregiving and domestic responsibilities [72]. This expectation of placing family responsibilities above individual needs, combined with the prevalent burden of medical expenses and difficulties in accessing childcare services, collectively leads to delays in women’s healthcare seeking [73]. At the same time, lower education levels result in their greater involvement in low-income or informal work, which lacks protection. This not only directly limits their purchasing power but also undermines their financial resilience in coping with major illnesses such as cancer, especially in countries with weak social security systems [74, 75–76]. Moreover, inadequate health literacy, limited understanding of diseases, and fatalistic attitudes contribute to a negative perception of cancer screening among certain women [77, 78]. Additionally, the shame and stigma associated with cancer more frequently lead to treatment delays and adverse outcomes for these individuals [79].Second, distinct patterns of risk factor exposure exist. Studies indicate a high prevalence of smokeless tobacco use among women in specific lower-SDI regions, such as South and Southeast Asia [80]. This significantly elevates the risk of oral and pharyngeal cancers, as well as precancerous lesions—particularly among women who use chewing tobacco [13, 81]. Specific practices like “reverse smoking” are also relatively common among women in the Philippines, rural elderly women in India, and women in parts of South and Central America, South Asia, and the Caribbean [82]. These interconnected sociocultural factors collectively form a complex barrier network that hinders women’s access to and effective utilization of healthcare services in lower SDI regions. Consequently, they cannot equally benefit from global advances in cancer prevention and control, perpetuating a vicious cycle of health inequality.
This study leverages the GBD 2021 data to underscore the increasing burden of disease and significant inequalities in HNC. It highlights structural deficiencies within global health systems when addressing complex cancer challenges. However, employing GBD data for global assessments entails considerable limitations. Firstly, the data sources included in the GBD exhibit definitional variations, such as discrepancies in disease diagnostic criteria and cause-of-death coding, necessitating the application of adjustment factors. Nevertheless, these adjustments cannot wholly eliminate bias. Moreover, many countries and regions, especially low-income ones, lack high-quality epidemiological data regarding incidence and prevalence. As a result, models often rely on extrapolated predictions instead of actual observed data. Consequently, data gaps in lower-income regions may lead to a systematic underestimation of the true burden of HNC [83]. This underestimation could directly cause misalignment between international aid and domestic budget al.location relative to actual healthcare needs, potentially exacerbating existing health inequalities.
Despite the WHO promoting gender-sensitive health systems (covering six dimensions like service delivery, information monitoring, and technology access) based on “health as a fundamental human right”, current policies still fail to effectively address the core socioeconomic factors behind the HNC burden. Therefore, building precise and equitable HNC strategies is urgent, requiring systemic, multi-level actions. The first priority is establishing reliable data foundations, especially strengthening cancer registries in lower SDI regions. This enables accurate monitoring of NCDs like HNC, supporting science-based resource allocation based on real disease burden. Building on this, targeted interventions must address significant gender and regional disparities. For men, who bear the main disease burden due to high tobacco/alcohol use and occupational exposure, integrated actions are critical. These include stronger tobacco control laws, strict occupational health enforcement, and screening programs in high-risk industries. Simultaneously, tackling the “triple vulnerability” facing women in low-to-middle SDI regions is essential. This includes poor health literacy from limited education, cultural barriers delaying care, and reduced payment ability due to economic dependence. Solutions require multiple approaches: improving women’s basic education to overcome information gaps; designing culturally appropriate community screening to boost early detection; and including core treatments (like surgery and radiotherapy) in universal health coverage to prevent treatment breaks caused by financial toxicity. Bridging technology and resource gaps is key to improving patient outcomes. This requires international collaboration to fill critical resource shortages (e.g., radiotherapy equipment) in low-to-middle SDI regions. It also requires targeted training of local head and neck surgery specialists to build sustainable capacity. Fundamentally, we must recognize that the social determinants of HNC are rooted in broader areas like agricultural trade policies, local economic models, and industrial regulations. Thus, HNC control strategies must be integrated into wider public health agendas, including tobacco control and HPV vaccination. Strong cross-sector collaboration is needed to dismantle the structural drivers of health inequality at their source.
Looking ahead, future research should prioritize addressing critical knowledge gaps to strengthen the aforementioned strategies. Key priorities include exploring cost-effective methods for establishing and operating cancer registries in low-to-middle SDI regions, thoroughly evaluating the cost-effectiveness and long-term impacts of gender-sensitive interventions across various cultural contexts, systematically investigating sustainable models for technology transfer and local health workforce training in resource-limited settings, and quantifying the contribution of incorporating HNC control into cross-sectoral policies, such as tobacco taxation and HPV vaccination programs, to reduce disease burden and narrow inequality gaps. These efforts will help bridge the evidence gap, promote evidence-based decision-making, and ultimately advance global equity in HNC control.
Conclusion
In summary, this study utilizes data from the GBD 2021 to reveal persistent and growing health inequalities in HNC. Addressing this disparity necessitates the implementation of equitable global governance strategies that focus on establishing robust data foundations, executing targeted interventions that consider gender and regional disparities, bridging divides in technology and resources, and fostering collaboration across sectors. This integrated approach is essential for dismantling the cycle of “lower SDI - high burden - lower development” and for genuinely upholding the global commitment that “health is a fundamental human right.”
Acknowledgements
The GBD 2021 study was supported by the Bill & Melinda Gates Foundation. We appreciate the comprehensive and systematic work by the Global Burden of Disease Study 2021 members.
Declaration of generative AI and AI-assisted technologies in the writing process
Statement: During the preparation of this work the author(s) used Deepseek in order to improve language and readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.
Authors’ contributions
S. S.，M. L. and S. W. contributed to the conception of the study. Y. L., Z. Z., H. W. and L. S. contributed to data curation and methodology, and all authors contributed to the interpretation of data, original drafts and critically revising the manuscript for publication.
Funding
This work was supported by the Anhui Provincial Center for Disease Control and Prevention.
Data availability
All data generated or analysed during this study are included in this published article and its supplementary information files.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Abbreviations
Head and Neck Cancer
thyroid cancer
lip-oral cavity cancer
laryngeal cancer
nasopharyngeal cancer
other pharyngeal cancers
Socio-demographic Index
Human Papillomavirus
Body mass index
World Health Organization
Global Burden of Disease
Years of Life Lost
disability-adjusted life years
age-standardized DALY rates
Uncertainty Intervals
Confidence Intervals
Estimated Annual Percentage Change
Slope Index of Inequality
Concentration Index
The International Classification of Diseases 10
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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