Introduction

Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a significant proportion of the global cancer burden, with substantial temporal and geographic variations in incidence and mortality1. Analysis of global trends reveals a nuanced epidemiological profile. Between 1990 and 2017, the global incidence of lip and oral cavity cancers exhibited a slight increase, whereas the incidence of nasopharyngeal cancers decreased significantly2. South Central Asia reports age-standardized incidence rates as high as 12.7 per 100,000 males. In countries such as Bangladesh, India, Pakistan, and Sri Lanka, where oral cancer accounts for one-third of all reported cancer cases, smoking plays a significant role in its etiology3.

In the United States, mortality rates from these cancers have remained stable since 2009, although variations persist across cancer subtypes and demographic groups4. In Australia, the incidence of lip cancer has declined, whereas oropharyngeal cancers have demonstrated a steady rise since the 1990s5. Conversely, Brazil has reported increased mortality rates for oral cavity, base of tongue, and lip cancers among women from 1980 to 2018, with pronounced regional disparities6.

The analysis of incidence, mortality, and survival rates for oral cavity cancer highlights concerning disparities in prognosis and survival globally. These cancers impose a disproportionate burden on low- and middle-income countries, driven by risk factors such as tobacco and alcohol consumption, poverty, and infections. Recent GLOBOCAN estimates (2022) report that oral cavity cancers, while contributing less to global cancer mortality compared to other upper gastrointestinal cancers, remain a significant challenge, with 188,438 annual deaths frequently linked to tobacco and alcohol use7. In Brazil, projections from the National Cancer Institute for 2023 to 2025 indicate alarming incidence rates, particularly for oral cavity cancer (International Classification of Diseases (ICD)-10 C00–C10). The age-standardized incidence rate is estimated at 7.64 cases per 100,000 men and 2.61 cases per 100,000 women. Following data from the Mortality Information System (SIM), mortality rates in Brasil in 2020 were 4.60 per 100,000 men and 1.32 per 100,000 women. Sergipe, a less developed state, shows some of the highest rates in the country—12.20 cases per 100,000 men and 4.10 cases per 100,000 women, making it the fourth most incident cancer in the state8.

In South America, incidence and mortality rates of oral cavity cancer have been high but vary considerably across countries, primarily due to the limited number of population-based cancer registries, which continue to be updated in the region9. In 2012, the estimated mean age-standardized incidence rate for lip and oral cavity cancer across South American regions was 3.8 per 100,000, while in Brazil, it was significantly higher at 7.2 per 100,00010. In 2016, cancer registries series in males reported higher age-standardized rates in Ecuador, Peru and Chile, while French Guyana and Brazil demonstrated lower rates, ranging from 19.0 to 5.0 per 100,000 among males11. Across the Brazilian regions, age-standardized incidence rates for oral cavity cancer (C00-C10) in males for the years 2023–2025 were estimated to range from 10.37 per 100,000 in the Southeast to 6.21 per 100,000 in the North12.

Geospatial analyses of LOCP cancers are critical for identifying high-incidence clusters and guiding targeted interventions. In the United States, significant clusters of high incidence and mortality have been identified, even after adjusting for risk factors such as diabetes, alcohol consumption, and obesity13. Globally, Australia reports the highest incidence rates of lip cancer, whereas India exhibits the highest rates of oral cavity and tongue cancers14,15,16. Within Europe, Eastern countries, particularly Hungary, bear the highest LOCP cancer burden17. A geographic analysis of Centers of Dental Specialties in Brazil revealed a higher concentration in the Southeast, South, and Midwest, which may contribute to the increased incidence rates of LOCP cancer in these regions18.

The temporal and spatial trends in LOCP cancers underscore the heterogeneity in their epidemiology, shaped by geographic, demographic, and behavioral risk factors. Understanding these variations is imperative for the development of tailored prevention and treatment strategies that address region-specific needs. This study is thus justified in elucidating the temporal evolution and identifying areas requiring targeted public health interventions.

Methods

This study was conducted in Sergipe, the smallest state in Brazil, with a total area of 21,938.188 km², located in the country’s Northeast region. Sergipe comprises 75 municipalities, organized into seven administrative health regions (HR), with a population of 2.2 million and a population density of 100.74 inhabitants per km², 1.1% of Brazil’s total population. The population is distributed as 48.20% male and 51.80% female, with life expectancies of 72 years for males and 79 years for females, respectively19.

Sergipe’s Human Development Index (HDI) is 0.702, with its capital, Aracaju (population 672,614), being the only municipality classified as having a high HDI (0.770)19. Aracaju offers superior access to healthcare, education, social services, formal employment, and urban infrastructure, while many interior municipalities face persistent challenges, including low adherence to the Family Health Strategy (FHS), the primary entry point to the healthcare system.

Study population and data sources

The study population included de-identified individuals diagnosed with malignant neoplasms, classified by ICD-10 codes C00 to C14 (excluding C07 and C08), retrieved from the Aracaju Cancer Registry (ACR) between 1996 and 2017. C07 (malignant neoplasm of the parotid gland) and C08 (malignant neoplasm of other major salivary glands) were excluded due to differing etiologies and risk factors20. Morphological classifications followed ICD-O-3 standards. The ACR, established in 1998, retrospectively collected data starting in 1996 and initially covered the population of Aracaju, with efforts underway to expand statewide coverage; however, for LOCP cancer the expansion process has already been completed.

Mortality data were sourced from the Mortality Information System (SIM) and included individuals who died from LOCP cancers between 1996 and 2022. Timeframes for analysis were based on the availability of data for incidence (1996–2017) and mortality (1996–2022).

Statistical analyses

Age-specific incidence and mortality rates were calculated using case counts as numerators and population data from the 1991, 2000, and 2010 censuses, as well as annual intercensal estimates from the Brazilian Institute of Geography and Statistics (IBGE) as denominators21, per 100,000 persons-year. We defined the age groups 15–44, 45–54, 55–64, 65–74, 75+, and all ages, following the International Cancer Survival Standards (ICSS)22. This breakdown allows for the analysis of age-related incidence, mortality and comparison with survival analysis. Age-standardized rates were calculated by direct standardization applied from the observed age-specific rates to the World Standard Population23.

The Mortality-to-Incidence Ratio (MIR) was computed as the ratio of cancer-related deaths to new cancer cases during specific periods. Its complement, 1 - MIR, was used as a proxy for five-year survival estimates, particularly in resource-limited settings lacking detailed survival data24. While informative, MIR-based survival estimates must be interpreted cautiously, as they are affected by non-cancer-related mortality, diagnostic variability, treatment accessibility, and demographic heterogeneity25,26,27,28,29.

Trend analysis

Temporal trends were evaluated using the Joinpoint Regression Program (version 5.3.0)30, with the calendar year as the independent variable and age-standardized incidence and mortality rates as dependent variables. Annual Percent Change (APC) values quantified rate changes in stable intervals, while Average Annual Percent Change (AAPC) provided a summary metric for the entire study period. A positive and statistically significant trend between two joinpoints indicates that the trend is increasing in that period; a negative and statistically significant trend between two joinpoints indicates that the trend is decreasing in that period; and a trend that is not statistically significantly different from zero (the 95% confidence interval includes zero) indicates that the trend is stable. Monte Carlo permutation simulations with 95% confidence intervals were employed to assess statistical significance31,32.

Spatial analysis

Spatial analyses employed cartographic data from IBGE, a public and freely accessible source. Maps were generated using QGIS version 3.32 and referenced to the Geocentric Reference System for the Americas SIRGAS 2000/UTM 24 S33. Geographic data visualization and manipulation were performed with TerraView 4.2.234.

Local Empirical Bayesian Smoothing methods were applied to stabilize incidence and mortality rates by reducing random variability associated with areas of small population size and to identify spatial clusters.

Empirical Bayesian Kriging was used for interpolation in data-scarce regions by leveraging patterns from neighboring areas35. Parameters such as the number of neighboring points and search radius were adjusted for accuracy. Outputs from QGIS provided spatial variations in incidence and mortality rates, offering critical insights into regional disparities and patterns.

Ethics statement

All methods adhered to relevant guidelines and regulations. The experimental protocol was approved by the Research Ethics Committee of the Federal University of Sergipe under CAAE Reference: 67599723.8.0000.5546, authorization no. 6.125.667. Since only anonymized patient databases were used, informed consent was impractical and was waived by the Research Ethics Committee of the Federal University of Sergipe.

Results

Incidence trends

Between 1996 and 2017, 2,945 incident cases of lip, oral cavity, and pharyngeal cancer were recorded in Sergipe, with 70% of cases occurring in males and 30% in females. Age-standardized rates (ASRs) ranged from 12.8 per 100,000 in 1996–2005 to 11.3 per 100,000 in 2013–2017, which reflect a reduction in the magnitude of the rates rather than a true declining trend in incidence. Among females, ASRs declined from 4.8 per 100,000 in 1996–2005 to 3.4 per 100,000 in 2013–2017. Age-specific analyses identified the highest incidence rates among men aged over 55 years across all periods (Table 1). Incidence and mortality rates by five-year age groups are provided in Supplementary Table S1, while retained broader ICSS-aligned groups to ensure rate stability and comparability with international cancer studies, particularly given the low frequency of LOCP cancers in younger age groups.

Table 1 Number of incident cases (N), average age-standardized rates (ASR) for all ages and age-specific rates for specified age-groups, with 95% confidence intervals (CI), for lip, oral cavity, and pharyngeal cancer in men and women, across three defined time periods, state of sergipe, brazil.
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Joinpoint regression analysis revealed stability in incidence among males (AAPC: − 0.5%; 95% CI: − 1.5 to 0.4), whereas a decrease was observed among females (AAPC: − 2.3%; 95% CI: − 4.1 to − 0.4). Incidence trends showed stabilization in all age groups in males. Females aged 65–74 years experienced the most significant decrease in incidence rates (AAPC: − 3.9%; 95% CI: − 6.4 to − 1.5) (Supplementary Table S2, Fig. 1).

Mortality trends

From 1996 to 2022, 1,614 deaths from LOCP cancer were recorded, with 78% occurring in males and 22% in females. ASRs among males increased from 3.8 per 100,000 in 1996–2005 to 6.1 per 100,000 in 2013–2022. For females, ASRs ranged from 1.0 per 100,000 in 1996–2005 to 1.3 per 100,000 in 2013–2022 (Table 2).

Table 2 Number of deaths (N), average age-standardized rates (ASR) for all ages and age-specific rates for specified age-groups, with 95% confidence intervals (CI), for lip, oral cavity, and pharyngeal cancer in men and women, across three defined time periods, state of sergipe, brazil.
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Fig. 1
Fig. 1The alternative text for this image may have been generated using AI.
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Graphical representation of incidence trends for lip, oral cavity, and pharyngeal cancer in men (A) and women (B), from 1996 to 2017, based on age-standardized rates for all ages and age-specific rates for specified age groups, state of Sergipe, Brazil. APC, annual percent change. * Indicates that the APC is statistically different from zero at an alpha level of 0.05.

Fig. 2
Fig. 2The alternative text for this image may have been generated using AI.
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Graphical representation of mortality trends for lip, oral cavity, and pharyngeal cancer in men (C) and women (D), from 1996 to 2022, based on age-standardized rates for all ages and age-specific rates for specified age groups, state of Sergipe, Brazil. APC, annual percent change. * Indicates that the APC is statistically different from zero at an alpha level of 0.05.

Temporal trends in mortality varied significantly between sexes. Among males, mortality rates increased sharply from 1996 to 2005 (APC: 16.1%; 95% CI: 9.6 to 22.9) before showing stabilization until 2022 (-1.0%; 95% CI: -2.3 to 0.2). In females, mortality showed stabilization from 1996 to 2022 in all age groups. Notably, males aged 55–64 years experienced a mortality increase from 1996 to 2005 (APC: 14.8%; 95% CI: 6.0 to 24.3), followed by a decrease in 2005–2022 (APC: -2.0%; 95% CI: -3.7 to -0.3); and males aged 65–74 increased mortality from 1996 to 2007 (APC: 15.0%; 95% CI: 1.8 to 29.9) (Supplementary Table S3, Fig. 2).

Mortality-to-Incidence ratio (MIR) and survival estimates

Analysis of the mortality-to-incidence ratio (MIR) revealed declining survival probabilities over the study period. For males, five-year survival estimates decreased from 70.31% in 1996–2005 to 46.02% in 2013–2017, with the most significant decline observed among individuals aged 75 + years (70.5–38.10%). Among females, five-year survival decreased from 79.17% in 1996–2005 to 61.76% in 2013–2017, with the steepest decline noted in the 75 + age group (75.93–50.90%) (Supplementary Table S4).

Spatial distribution

Spatial analysis identified distinct geographic clusters of high LOCP cancer incidence and mortality within Sergipe. Urban areas, particularly the capital city of Aracaju, exhibited higher incidence and mortality rates compared to rural regions. Bayesian smoothing reduced variability observed in smaller municipalities with lower population counts. Empirical Bayesian Kriging revealed regional disparities, with certain clusters persisting even after adjusting for population differences.

Figure 3 illustrates the geographic distribution of age-standardized incidence (C) and mortality (D) rates for females in Sergipe over the past decade. Incidence rates were highest in the health regions of Nossa Senhora do Socorro, Aracaju, and Nossa Senhora da Glória, ranging from 6.4 to 8.0 per 100,000. Additionally, incidence rates between 3.5 and 4.2 per 100,000 were recorded in the southern and northeastern regions of the state. Mortality rates were most pronounced in the HR of Estância, particularly in the municipalities of Tomar do Geru, Cristinápolis, and Umbaúba. Notable heterogeneity in mortality distribution was observed, with the municipality of Canindé de São Francisco exhibiting a high mortality rate despite a moderate incidence rate (4.2–5.2 per 100,000).

Figure 3 also depicts findings for males over the same period. Statewide, LOCP cancer incidence (A) and mortality (B) rates were high during the study period. Over the last decade, incidence rates in the northern regions of Sergipe were relatively low, with a notable homogeneity across municipalities. However, the HRs of Nossa Senhora do Socorro and Lagarto demonstrated elevated incidence rates. Regarding mortality, the northern region exhibited low rates overall, while HRs of Estância and Aracaju showed significant concentrations, with high mortality rates particularly notable in the municipalities of Itaporanga D’Ajuda and São Cristóvão.

Fig. 3
Fig. 3The alternative text for this image may have been generated using AI.
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Spatial distribution of lip, oral cavity, and pharynx (LOCP) cancer incidence (2008–2017) and mortality (2013–2022) in Sergipe, Brazil. Age-standardized incidence (A) and mortality (B) in males; incidence (C) and mortality (D) in females.

Maps were created using QGIS v3.32 (https://qgis.org) with shapefiles from IBGE (https://www.ibge.gov.br), and spatial smoothing and interpolation performed in TerraView v4.2.2 (http://www.dpi.inpe.br/terralib5/), using Local Empirical Bayesian and Empirical Bayesian Kriging methods.

Discussion

This study utilized a descriptive design with aggregated database analyses to provide a comprehensive evaluation of trends, patterns, and spatial distribution of lip, oral cavity, and pharyngeal (LOCP) cancers in Sergipe, Brazil. Population-based studies of this nature are instrumental in identifying critical public health needs, guiding the formulation of targeted interventions aimed at reducing the cancer burden.

The findings indicate a higher risk of LOCP cancer and related mortality in Sergipe’s population. Temporal trends demonstrated a decrease in incidence rates among women. Among men, trends showed stabilization and continued featuring high rates in older men. Mortality trends showed an overall increase, most prominently among men, with a decrease observed in women in recent years. The mortality-to-incidence ratio (MIR) analysis revealed a progressive decline in survival estimates, underscoring the urgent need for improved cancer control measures. These findings highlight geographic clusters with disproportionately high incidence and mortality rates, suggesting opportunities for focused public health interventions.

The incidence rates of lip, oral cavity and pharynx cancer in Sergipe differ from national Brazilian trends, where stomach cancer predominates among upper gastrointestinal malignancies. Mortality rates, however, remain lower than those typically reported for stomach cancer. The observed gender differences, with higher incidence and mortality rates in males, are consistent with data from other regions and high-income countries, where similar patterns have been reported since 201536,37,38,39.

The etiology of LOCP cancers is multifactorial, with well-established risk factors including tobacco use, excessive alcohol consumption, diets low in fruits and vegetables, and human papillomavirus (HPV) infections. Genetic predisposition, pre-existing medical conditions and radiation exposure may further contribute by impairing cellular repair mechanisms, thereby initiating carcinogenesis40. Conversely, dietary patterns rich in fruits and vegetables and reduced animal fat intake are associated with a lower risk of LOCP cancers41.

Changes in incidence and mortality trends may reflect evolving population behaviors, economic fluctuations, and government policies that influence healthcare access, nutrition, and lifestyle habits. For instance, dietary shifts, such as increased consumption of processed foods, could contribute to observed patterns42. Additionally, higher alcohol and tobacco consumption, particularly among Brazilian males, has been linked to increased gastrointestinal cancer incidence43,44.

Increased incidence among younger adults raises concerns regarding exposure to specific risk factors, such as human papillomavirus (HPV) infection, which has been associated with LOCP cancers. Young individuals are at greater risk due to unprotected sexual activity and limited healthcare engagement for information, diagnosis, and treatment45. Early initiation of alcohol and tobacco use, which frequently transitions into long-term habits, significantly contributes to cancer development. Combined alcohol and tobacco use increases the likelihood of precancerous lesions in the oral cavity, lips, tongue, and pharynx by up to 60%46.

The role of HPV vaccination programs in reducing oral cavity and oropharyngeal cancer incidence is particularly critical, especially among younger populations. Complementary public health measures, including anti-smoking campaigns and alcohol control policies, can further influence incidence and mortality trends, particularly in remote areas with limited healthcare access.

In Sergipe, health regions such as Lagarto, Nossa Senhora da Glória, and Propriá demonstrated the highest incidence rates among males aged 75 years and older. Similar trends have been reported globally, with studies noting significant increases in oral cavity cancer incidence among elderly populations47,48,49. The potential decline in the incidence of this disease could result from improved access to healthcare, quality education, and socioeconomic improvements, which could be observed over time. These strategies could be effective, like the observed decline in esophageal cancer rates, where the primary risk factors include smoking, alcohol consumption, unhealthy dietary habits associated with poorly hygienic or overly spicy foods, reflux, and genetic predisposition50.

Therefore, adopting strategies to contain future cases is crucial. One such initiative is the “Cancer Moonshot,” which aims to reduce cancer cases by 50% by 2047 through improved healthcare services, research investment, and professional training51. Socioeconomic factors, reflected in the state’s low Human Development Index (HDI) in rural areas, contribute significantly to disparities in cancer incidence and outcomes. Higher HDI regions typically exhibit improved access to healthcare and better cancer survival rates52,53.

Over the years, Sergipe has seen a decline in LOCP cancer cases, which could be linked to changes in lifestyle and exposure to well-known risk factors, especially smoking and alcohol consumption. Surveys like Vigitel54, which primarily tracks health trends in Brazilian capital cities including Aracaju, have documented a steady drop in smoking rates among adults over the past two decades. Likewise, data from the National Health Survey (PNS)55 indicate that fewer people are smoking, and though alcohol abuse has also decreased, the trend hasn’t been as consistent. This shift in behavior likely develops from a mix of national anti-smoking laws, public health campaigns, and local efforts to raise awareness. However, some areas might still struggle with heavy drinking, particularly among men - the group most affected by LOCP cancers. To better understand how these lifestyle changes influence cancer rates, future studies should integrate more local epidemiological data. Doing so would help uncover regional differences and long-term trends, ultimately giving a clearer picture of the evolving cancer burden.

Early detection of LOCP cancer has been the focus of the State Government within the “Smile Sergipe” program. The initiative, which is led by the State Health Department (SES), has already served some municipalities throughout the state. The goal is to provide information on the treatment and prevention of oral cancer. Besides, it offers oral health education and assessment for people over 12 years of age. The program is implemented through an itinerant project “Sergipe is Here”56. However, it is still incipient and should be implemented thoroughly across the state.

Healthcare access is a critical determinant of outcomes, with delayed diagnosis and treatment often exacerbating mortality57. Most of Sergipe’s healthcare infrastructure is concentrated in the capital, Aracaju, creating significant barriers for rural populations. Basic Health Units and Family Health Strategy clinics play a vital role in early detection and preventive care, but these resources are insufficiently distributed across the state.

The observed geographical divergence between incidence and mortality patterns for LOCP cancers across Sergipe likely reflects a complex interplay of diagnostic capacity, health system access, and less probably registry completeness. Higher incidence coupled with lower mortality in certain areas, such as the capital Aracaju, may indicate better access to diagnostic and treatment services, allowing for earlier detection and improved survival. Conversely, municipalities with lower incidence but higher mortality may be experiencing delayed diagnosis, limited access to specialist care, or underreporting of new cancer cases. Variations in exposure to risk factors - such as tobacco and alcohol use, sun exposure in rural areas (for lip cancer), and socioeconomic inequalities - may further influence regional disparities. Finally, differences in the quality of cancer registration versus mortality reporting systems would also contribute to the mismatch, as cancer registries might undercapture cases in more remote regions, while mortality data from SIM is typically more comprehensive.

The declining survival probabilities may be due to the limitations of the method, and the pronounced geographic disparities emphasize the need for robust public health strategies. Effective interventions should include equitable resource distribution, expansion of HPV vaccination programs, and targeted lifestyle campaigns to reduce tobacco and alcohol consumption. In addition, infrastructure improvements in under-resourced regions are necessary to ensure timely diagnosis and treatment.

The observed increase in the mortality-to-incidence ratio over the temporal series highlights the need for implementing public policies for LOCP cancer control and improving the management of diagnosed cases in the studied region. Population-based survival studies, a gold standard in high-income countries, remain scarce in low- and middle-income countries (LMICs). Although the MIR complement provides an alternative, its limitations highlight the need for more robust survival analysis methodologies in LMIC settings26,58,59,60. Future research should prioritize stratification by socioeconomic factors and cancer stage to enhance the understanding of disparities and guide interventions effectively.

This study’s strengths include the use of a long temporal series from validated databases12,61, providing a robust foundation for evaluating trends and patterns. However, certain limitations should be noted, including outdated incidence data, the absence of stratification by cancer stage, and the lack of risk factor prevalence data. Although the mortality-to-incidence ratio (MIR) has been employed as a crude proxy for population-level cancer survival, its methodological limitations must be acknowledged. MIR is a cross-sectional measure that does not reflect the actual survival time of individuals, nor does it track outcomes within the same cohort. The inherent lag between diagnosis and death can distort interpretations, particularly in cancers where survival is prolonged. Moreover, MIR is sensitive to data quality: underascertainment of incident cases or inaccuracies in cause-of-death attribution can lead to substantial bias. Finally, MIR is unable to account for key prognostic variables such as stage at diagnosis or treatment accessibility. Therefore, while MIR may offer broad insights into cancer control effectiveness, it should be interpreted with caution and not considered a substitute for properly estimated net survival using individual-level follow-up data. Continuous improvements in data collection systems are essential to address these gaps and enhance the reliability of future analyses.

Conclusions

This study highlights concerning trends in LOCP cancer incidence and mortality in Sergipe, with particularly high rates among men and older populations. Declining survival probabilities and significant geographic disparities underscore the urgency for targeted interventions. Future strategies should include expanding HPV vaccination programs, improving healthcare access, and implementing public health initiatives to reduce tobacco and alcohol consumption. Further longitudinal studies are necessary to evaluate the impact of policy changes and to explore the relationship between dietary habits, lifestyle factors, and cancer incidence. Addressing these issues is essential for reducing the burden of LOCP cancer and improving outcomes for affected populations.