Spatiotemporal patterns and trends in the proportion of advanced oral cancer at diagnosis in Brazil, 2018–2023

Spatiotemporal patterns and trends in the proportion of advanced oral cancer at diagnosis in Brazil, 2018–2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Spatiotemporal patterns and trends in the proportion of advanced oral cancer at diagnosis in Brazil, 2018–2023 Marcio Borges, Elisa Costa, Vandilson Rodrigues, João Victor Lara, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9181918/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Objective To analyze the spatiotemporal proportion of advanced cases (III and IV) of oral cancer (OC) in Brazil. Methods An ecological observational study was conducted using secondary data from Brazil collected from 2018 to 2023. The units of analysis were health regions, geopolitical macroregions, and Brazil. The indicator of interest was the proportion of advanced cases (III and IV) of OC. The statistical analysis was performed in four stages: (1) choropleth maps, (2) Moran’s I (global) and local (LISA), considering only 2018 and 2023; (3) space–time cube; and (4) Prais–Winsten, spanning from 2018 to 2023. A significance level of 5% was adopted for all analyses. Results In 2018, 34.9% of Brazilian health regions had ≥ 75% OC cases diagnosed in advanced stages, and in 2023, this proportion was 57.7%. In both years, advanced-stage OC was more prevalent in men and in the tongue. In 2018, high–high clusters were observed in the southeast, midwest, and northeast regions; and in 2023, a slight change occurred, with high–high clusters in the same regions and in the north. Distinct spatial patterns were observed, with clusters showing a reduction in the proportion of advanced cases in the northeast, southeast, and south regions and clusters showing an increase in specific areas of the north, northeast, southeast, and south. In the temporal trend analysis by macroregion, the northeast showed a decreasing trend, whereas the southeast showed an increasing trend in the proportion of advanced diagnoses of OC. Conclusion From 2018 to 2023, Brazil presented an alarming scenario of advanced diagnosis of OC in many health regions, constituting a serious public health problem. This trend was more noticeable in men and tongue region and varied geographically, with evident clusters of increase, particularly in the northeast and southeast. Mouth Neoplasm Neoplasm Staging Spatio-Temporal Analysis Cluster Analysis Brazil Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Oral cancer (OC), a disease of the upper aerodigestive tract, affects the lips, labial and buccal mucosa, anterior two-thirds of the tongue, retromolar trigone, floor of the mouth, gum, and hard palate. 1 According to World Health Organization estimates, this malignant neoplasm was responsible for over 389,000 new cases and more than 188,000 deaths worldwide in 2022, representing a 5-year mortality rate close to 50%, which has not decreased substantially in the last 40 years. 2 , 3 This high mortality is mainly caused by the high percentage of OC diagnoses at advanced stages, in which treatment is complex, mutilating, and disabling, 4 and this advanced diagnosis have complex and diverse causes, involving several factors, such as patients, health professionals, and health services. 5 The tumor–node–metastasis (TNM) classification, proposed by the American Joint Committee on Cancer, is the most widely used grading system for malignant head and neck tumors (including OC). In this system, components are combined to classify the tumor into stages I–IV to guide treatment and prognosis. 6 Early (I and II) or advanced (III and IV)-staged diagnosis remains an essential factor for treatment planning and disease prognosis, 7 allowing the application of more appropriate treatment protocols with a better estimate of each patient’s prognosis. 8 A meta-analysis showed that initiating treatment within 30 days improved overall survival by 9% compared with longer intervals. 4 The American Dental Association and the American Academy of Oral Medicine recommend OC screening, particularly for high-risk individuals, such as those with chronic tobacco and alcohol use. 9 Clinical recognition and assessment of oral mucosal lesions can detect up to 99% of oral cancers/pre-malignancies, 10 although diagnosis is challenging because OC is often asymptomatic and presents with diverse morphologies. 11 However, compared with other cancer types that have screening programs (breast, prostate, and colon), early detection of OC has not improved in recent years. 12 Studies point to difficulties in promoting policies and strategies for the diagnosis of OC in early stages, particularly in developing countries, 13 which represents a serious public health problem. 14 Professionals from 21 countries in Latin America and the Caribbean identified the limited implementation of OC control plans, low mandatory reporting of oral lesions and OC, unclear protocols for referral of suspected or confirmed lesions, and a shortage of trained professionals as the main barriers to early diagnosis and adequate treatment of OC. 15 Brazil is the country with the highest absolute number of OC cases in Latin America. 16 This neoplasm is among the most prevalent, with an estimated 5.3 cases per 100,000 inhabitants. 17 More than 9,000 new cases and approximately 4,000 deaths are registered in Brazil annually, 18 and a growing mortality trend is projected in the coming decades. 19 A general dentist in the Brazilian public health system is expected to encounter approximately 675 patients with lesions suspected of being OC during their career. 20 Despite this, diagnosis often occurs at more advanced stages, 21 exceeding 50% across all regions 22 , 23 and delaying treatment initiation. Despite the high prevalence, incidence, and mortality from OC in Brazil, the Oral Health Care Network (RASB, acronym in Portuguese) 24 was only created in 2024;.Although the National Oral Health Policy (PNSB, acronym in Portuguese) existed during that period, it was only registered in 2023. 25 The spatiotemporal trend of the proportion of Brazil population diagnosed with OC in advanced stages has been less explored, and no studies have incorporated data from the most recent years. 17 , 25 Therefore, this study aimed to analyze the spatiotemporal distribution of the proportion of OC cases diagnosed in stages III and IV in Brazil from 2018 to 2023. The study tested the hypotheses that the temporal trends of diagnosis in advanced stages are increasing or stationary, despite the current public policies; significant spatiotemporal differences exist in oral cancer staging at the time of diagnosis; and spatial clusters of cases exist in advanced stages, particularly in territories with greater socioeconomic vulnerability. 2. Methods 2.1. Study design This ecological observational study employed spatial and temporal approaches using secondary data from the Brazilian Unified Health System (SUS, acronym in Portuguese), whose units of analysis were health regions, geopolitical macroregions, and Brazil. 2.2. Study location Brazil is a developing country and the largest Latin American country, presenting worrying inequalities and significant regional differences. 26 In 2023, 5,570 municipalities were organized into 450 health regions, 27 federative units (FUs), and five macroregions, as described: north, northeast, central-west, southeast, and south. The northeast (human development index (HDI): 0.663) and north (HDI: 0.667) face the most adverse conditions, reflected in social, political, economic, environmental, and infrastructure challenges. In contrast, south (HDI: 0.754), central-west (HDI: 0.757), and southeast (HDI: 0.766) demonstrate more favorable development indicators. 27 Brazil is organized into Healthcare Networks (HN), which are polyarchic organizations of health services and are organized horizontally, without hierarchy between the three levels of care (primary, secondary, and tertiary), with primary health care (PHC) being responsible for coordinating care. The main objective of the HN is to provide comprehensive care, encompassing promotional, preventive, curative, rehabilitative, and palliative interventions, efficiently and effectively. 28 To facilitate the integration of the HN, health regions were created, which are a continuous geographic space made up of groups of bordering municipalities, delimited based on cultural, economic, and social identities and shared communication and transportation infrastructure networks, to integrate the organization, planning, and execution of health actions and services. 29 2.3. Study population The study population consisted of all OC cases with available staging information from 2018 to 2023, grouped by health region, macroregion, and Brazil. The outcome was the proportion of OC diagnosed in advanced stages (III and IV). OC was defined as cancer located on the lips and in the oral cavity, according to the International Classification of Diseases, Tenth Revision (ICD − 10 (C00 to C06). Cases without a record of OC staging were excluded from the analysis. 2.4. Data Source Data from the Brazilian Unified Health System Informatics Department (DATASUS, acronym in Portuguese) were compiled. DATASUS is the informatics department of the Brazilian Unified Health System, which collects data from three points—primary healthcare (PHC), secondary healthcare (SHC), and tertiary healthcare (THC)—in Brazilian health regions and manages the country’s health database.30 DATASUS data were collected from the digital platform PAINEL-Oncology. This platform unifies data originating from three national information systems: the Outpatient Information System (SIA, acronym in Portuguese), Hospital Information System (SIH, acronym in Portuguese), and Cancer Information System (SISCAN, acronym in Portuguese). 31 The proportion of advanced-stage OC in relation to the total number of cases was estimated by health region from 2018 to 2023. The following anatomical locations were considered according to ICD-10: malignant neoplasm of the lip (C00), malignant neoplasm of the base of the tongue (C01), malignant neoplasm of other parts and unspecified parts of the tongue (C02), malignant neoplasm of the gum (C03), malignant neoplasm of the floor of the mouth (C04), malignant neoplasm of the palate (C05), and malignant neoplasm of other parts and unspecified parts of the mouth (C06). Additionally, the indicator was calculated by sex, age, and anatomical site. Table 1 presents the source, time period, and description of the indicators are presented. Table 1 Description of study indicators by health region. Indicator Description Source Period 2 Advanced staging (AS) 1 Percentage of cases diagnosed with advanced-stage oral cancer by health region DATASUS 2018–2023 AS: men Percentage of advanced-stage oral cancer cases in men by health region DATASUS 2018 and 2023 AS: women Percentage of advanced-stage oral cancer cases in women by health region DATASUS 2018 and 2023 AS: non-older individuals Percentage of advanced-stage oral cancer cases in non-older individuals (< 59 years) by health region DATASUS 2018 and 2023 AS: older individuals Percentage of advanced-stage oral cancer cases in older individuals 30 (≥ 60 years) by health region DATASUS 2018 and 2023 AS: lip Percentage of advanced-stage lip cancer cases by health region DATASUS 2018 and 2023 AS: tongue Percentage of advanced-stage tongue cancer cases by health region DATASUS 2018 and 2023 AS: gum Percentage of advanced-stage gum cancer cases by health region DATASUS 2018 and 2023 AS: floor of the mouth Percentage of advanced-stage floor of mouth cancer cases by health region DATASUS 2018 and 2023 EA: palate Percentage of advanced-stage palate cancer cases by health region DATASUS 2018 and 2023 1 AS: advanced staging (diagnosis in stages III and IV). DATASUS, Department of Informatics of the Brazilian Unified Health System. 2 Analyses considering diagnosis in advanced stages were performed for the period from 2018 to 2023. However, for analyses stratified by sex, age, and anatomical location of oral cancer, only the beginning and end of the time series (2018 and 2023) were considered. 2.5. Statistical analysis Statistical analyses were performed in four stages, as described below: 2.5.1. Choropleth maps for 2018 and 2023 Choropleth maps were created to assess the proportion of advanced OC cases in Brazil. Choropleth maps are thematic representations that use different shades or patterns of a color to represent the variation of a given phenomenon in geographic areas. In this study, maps were created for 2018 and 2023, detailing the distribution of advanced-stage OC by health region. The variables analyzed included the total cases and cases by sex (male and female), age (non-older and older), and anatomical location (lip, tongue, gum, floor of the mouth, and palate). Choropleth maps were created using QGIS 3.16.1. 2.5.2. Global Moran’s Index and LISA in 2018 and 2023 To investigate the spatial autocorrelation of advanced-stage OC cases, Global Moran’s index (GMI) and Local Indicator of Spatial Association (LISA) maps were created. This analysis sought to verify whether changes in the patterns and spatial heterogeneity of diagnosed cases, by health region, in 2018 and 2023, occurred randomly or whether the incidence in one health region influences the occurrence in neighboring regions. The variables analyzed included advanced-stage OC, sex (male and female), age (non-older and older), and anatomical location (lip, tongue, gum, floor of the mouth, and palate). The analyses were processed on Google Colab using the PySAL library in the Python programming language. The cartographic base of Brazil, detailing the borders of the states and Federal District, was obtained free of charge from the Brazilian Institute of Geography and Statistics (IBGE, acronym in Portuguese) website. 28 To calculate the GMI, which provides a single measure of autocorrelation for the entire dataset, a covariance approach is used based on the product of deviations from the mean. This global index tests whether neighboring areas exhibit greater similarity regarding the studied indicator than would be expected by chance. The spatial weight matrix is ​​crucial in this calculation, as it defines which areas are neighbors and the weight of their influence. The first-order adjacency (which verifies horizontal, vertical, and diagonal interactions) is one of the common options; however, the choice of the most appropriate matrix depends on the analysis context. The GMI result ranges from − to + 1, where positive and negative values ​​indicate positive (similar values ​​grouped together) and negative (dissimilar values ​​grouped together) spatial autocorrelation, respectively. Values ​​close to zero indicate the absence of autocorrelation. LISA performs a spatial autocorrelation that measures the relationship between observations with spatial proximity. It is based on the principle that spatially close observations tend to have similar ​​(positive autocorrelation) or dissimilar ​​(negative autocorrelation/outlier) values and seeks to identify these patterns at the local level. LISA is a statistical tool that generates a significant value for each study area, allowing the visualization of clusters and spatial outliers with regions showing similar values ​​for the analyzed indicator. These patterns are categorized into four main types: high–high, regions with high values ​​surrounded by others with equally high values; low–low, regions with low values ​​surrounded by others also with low values; high–low, a spatial outlier of high value amidst regions with low values; and low–high, another spatial outlier, but of low value surrounded by areas with high values. 2.5.3. Space–Time Cube from 2018 to 2023 A space–time cube analysis was employed to assess the annual spatiotemporal distribution of the proportion of advanced OC from 2018 to 2023. The health region was defined as the unit of analysis. This approach was used to identify patterns of spatial and temporal autocorrelation, categorizing health regions into hot spots (increasing trend), indicating growth in the proportion of cases during the period; cold spots (declining trend), for areas with a decrease; and no pattern detected, for regions where no significance was found. The significance of the patterns was determined by the p-value of each location in the cube. Time units were represented by boxes in the cube, and confidence intervals of 90%, 95%, and 99% were considered in the analysis. The analysis was conducted using the scikit-learn library of the Python programming language, which was processed on Google Colab. 2.5.4 Prais–Winsten regression analysis from 2018 to 2023 Time–trend analysis was performed using Prais–Winsten generalized linear regression, a technique appropriate for time series because it corrects for the autocorrelation of the residuals.32 The monthly proportions of advanced OC (III and IV) were evaluated, aggregated by macroregion and Brazil, for the period from 2018 to 2023. The results were interpreted as stable trend (p > 0.05), increasing trend (p < 0.05 and positive regression coefficient), and decreasing trend (p < 0.05 and negative regression coefficient). The regression coefficient and monthly percentage change were also estimated. Temporal analyses were performed using STATA (version 16.0). 3. Results From 2018 to 2023, 64,448 OC cases were diagnosed in Brazil, with 11,333 (17.5%) lacking staging information. Among those with staging information, 23,914 (45.0%) were diagnosed at an advanced stage. In 2018, 157 health regions (34.9%) had ≥ 75% cases diagnosed at an advanced stage, reaching 260 (57.7%) health regions in 2023. The number of health regions with ≥ 50% of cases diagnosed at an advanced stage in men increased from 120 (26.7%) in 2018 to 274 (60.8%) in 2023. In contrast, the proportion of health regions with advanced cases in women was > 75% in the 0%–25% range in both 2018 and 2023. No notable difference was noted in the proportion of advanced cases between non-older and older individuals (Fig. 1 ). The proportion of health regions increased with ≥ 50% of tongue cancer diagnosed in advanced stages, rising from 67 regions (14.8%) in 2018 to 118 (26.2%) in 2023. For all other anatomical locations, > 90% of health regions remained in the range of 0–25% of cases in advanced stages in 2018 and 2023 (Fig. 2 ). In 2018, high–high clusters (health regions with high proportions of advanced OC cases surrounded by other health regions with high proportions) were observed in the southeast, midwest, and northeast; and in 2023, a slight change occurred, identifying high–high clusters in the same regions and in the north. Regarding sex, in 2018, clusters with a high proportion of advanced cases of high–low OC were observed in the southeast region for men and southeast and northeast regions for women. In 2023, high–low clusters were observed in the southeast, midwest, and north regions for men and in the southeast, northeast, and north regions for women. For the non-older population (< 59 years), the number of high–low clusters increased in the northeast and midwest between 2018 and 2023; whereas in the older group, an increase in both high–low and high–low clusters was observed between 2018 and 2023 (Fig. 3 ). Analysis of anatomical location showed a reduction in low–low clusters and an increase in high–high clusters for lip, tongue, and gum cancers from 2018 to 2023, whereas both clusters increased for floor and palate sites (Fig. 4 ). From 2018 to 2023, clusters with a decreasing trend in the proportion of advanced OC cases were observed in the northeast, southeast, and south regions of Brazil (p < 0.05), and clusters with an increasing trend were observed in the north, northeast, southeast, and south regions (p < 0.05) (Fig. 5 ). From 2018 to 2023, the temporal trend analysis of the proportion of advanced OC in Brazil and its macroregions showed a decreasing trend in the northeast (MPV: −0.105; p = 0.049) and an increasing trend in the southeast (MPV: 0.115; p = 0.017). For other macroregions, the trend was stable (Table 1 ). Table 1 Trend in the proportion of advanced oral cancer by macroregion, Brazil, 2018–2023. Unit β 95% CI P MPV Trend North 0.018 −0.106 to 0.142 0.769 0.043 –– Northeast −0.048 −0.096 to − 0.0001 0.049 −0.105 ↓ Southeast 0.047 0.008 to 0.086 0.017 0.115 ↑ South −0.008 −0.056 to 0.040 0.733 −0.018 –– Central-west 0.058 −0.063 to 0.180 0.342 0.144 –– Brazil 0.015 −0.008 to 0.039 0.216 0.216 –– β, Prais–Winsten regression coefficient; 95% CI, confidence interval; MPV, monthly percentage variation. (––) stationary trend, ( ↓ ) decreasing trend, and ( ↑ ) increasing trend. 4. Discussion From 2018 to 2023, the number of health regions with high proportions of OC cases diagnosed at advanced stages (III and IV) has increased. This increasing trend was also observed in the male population and in cases located on the tongue. Conversely, the proportion of advanced OC cases in the female population remained stagnant and was lower in the study period compared with the male population, and no notable difference was found between non-older and older individuals. Distinct regional patterns and some notable changes in the clusters of advanced OC cases were observed in Brazil between 2018 and 2023. Clusters with an increasing trend of advanced OC were found in 22 health regions (distributed across four geopolitical macroregions and seven states); however, clusters with a decreasing trend were also observed in the south, southeast, and northeast regions. Finally, the trend in the proportion of OC cases diagnosed at advanced stages remained stable in Brazil from 2018 to 2023, although with an increasing trend in the southeast region and a decreasing trend in the northeast. The increase in the proportion of OC diagnosed in the advanced stage in Brazil in 2018 and 2023 represents a serious public health problem, which may affect mortality rates because preventive and early diagnostic procedures were not adequately implemented. 12 , 33 High levels of social inequity, such as low educational level, 32 high unemployment 34 , and low HDI 35 , are associated with this high proportion of diagnoses at an advanced stage. Capacity can be expanded for more effective action by oral screening for early disease detection, 36 improvement of healthcare networks focusing on diagnosis in primary health care 37 , training and continuing education of health professionals, health education campaigns for the population, and improved access to dental and diagnostic services, particularly for disadvantaged populations 35 . The proportion of OC diagnosed in the advanced stage in men increased between 2018 and 2023, and this proportion was consistently higher than that in women. Women are less likely to be diagnosed with stage IV oral cancer 21 , and men tend to have higher mortality and worse survival rates than women. Furthermore, men tend to take less care of their health than women. 33 Accordingly, specific health initiatives aimed at the male population can help reverse this alarming situation. The proportion of diagnoses of OC in the advanced stage was similar between non-older and older individuals. This finding is corroborated by the results of a study that did not find a significant difference in staging between individuals aged > 40 and < 40 years; however, non-older individuals generally have higher survival rates. 38 However, other studies present contradictory results: people aged ≥ 60 have a lower chance of being diagnosed at stage IV, 21 whereas patients aged < 50 have a higher risk of being diagnosed at an advanced stage. 5 Non-older individuals may not be prioritized for screening compared with older individuals because they are not considered risk groups. Conversely, the older group tends to seek health services less often; thus, in both groups, the diagnosis was delayed but for different reasons. The tongue showed the highest proportion of advanced OC cases, consistent with previous years because a study conducted in Brazil between 2000 and 2014 reported that most tongue cancers were diagnosed at stages III and IV. 39 The tongue is a richly vascularized structure, which can favor cancer spread. 40 In addition, macro-determining factors, such as low access to education and lack of access to the healthcare system, historical problems in Brazil, and the less accessible position of most tongue cancers (posterior region and edges), in addition to problems in the training of general dentists, favor a late diagnosis. 5 Analysis of spatial clusters of advanced OC revealed distinct patterns among Brazilian macroregions in 2018 and 2023, both for the general population and segregated by sex. Thus, for the 2 years analyzed, the northeast macroregion presented more high–high clusters, which can be explained by macrodeterminant factors such as the low HDI of this region, 41 healthcare network problems, particularly in medium and high complexity care, cultural issues, and historical inequities compared with other macroregions. A Canadian study reported a high proportion of cases diagnosed at advanced stages in both sexes of people residing in economically more vulnerable regions. 42 High–high spatial clusters of advanced OC were observed in men and women in the 2 years analyzed for the southeast macroregion. Although the southeast region is one of the most developed in Brazil, this microregion is characterized by high rates of diagnoses of OC in the advanced stage 43 and mortality from OC. 44 High–high clusters for OC of the tongue and floor of the mouth were also observed in the north macroregion in 2023. The north region has the second lowest HDI—second only to the northeast region—and shares historical inequalities compared with the other macroregions. 45 Space–time cube analysis revealed that from 2018 to 2023, clusters of health regions showed a decreasing trend in the proportion of advanced OC in the south, southeast, and northeast regions of Brazil. This may indicate improvements in prevention and screening programs, earlier diagnosis, and advances in public policies in these clusters. However, in the same period, certain clusters showed an increasing trend in all regions, except for the central-west region. This reinforces the fact that regardless of the analysis type, problems exist in various regions of Brazil, reflecting inefficiencies in public policies. An analysis considering the entire historical series verified a stationary trend in the proportion of advanced OC in Brazil, a decrease in the northeast macroregion, and an increase in the southeast macroregion. A study conducted between 2000 and 2019 observed that the south and southeast macroregions of Brazil were directly associated with an increase in the diagnosis of OC stage IV. 21 Between 2000 and 2017, 0.29% of cases diagnosed at the advanced stage showed an annual growth trend. 5 This result likely reflects the migration of cases to these more developed regions, a more organized health information system, reducing under-registration and under-notification, as well as better completion of official health system forms and documents. However, PHC has grown more rapidly in the north and northeast than in the southeast, and this may have affected the improvement of active case finding and suspicion of cases in earlier stages. This study has some limitations, such as the possibility of ecological fallacy, a problem inherent in ecological studies, which makes it impossible to attribute associations observed at the population level to the individual level; the absence of data notification by the Brazilian Health System, particularly in the first years of this study, which may generate measurement biases, underestimating cases, particularly in less developed areas. Furthermore, the trends in the data may have been influenced by the COVID-19 pandemic, 46 and future studies may identify different results, given the end of the pandemic. Therefore, some researchers have analyzed the Brazilian Information Systems regarding data coverage and completion, and many inconsistencies persist, particularly in underdeveloped areas. 47 In a study conducted between 1996 and 2018, the redistribution of data reported as “ill-defined causes” increased mortality rates from oral and oropharyngeal cancer, particularly in the north and northeast regions, demonstrating that a significant proportion of data is not recorded adequately. 48 The main strengths of this study include the use of the health region as the unit of analysis, since healthcare network services are configured and distributed according to this unit of analysis. Furthermore, the data analyzed encompass the entire population of diagnosed OC cases in the country, not just a sample. The use of different analytical strategies for spatiotemporal analysis and units of analysis (Brazil, geopolitical macroregions, and health regions) allows for the disaggregation of data into different granularities and a more adequate exploration of spatial inequities. Conclusion This study reveals a worrying scenario regarding OC diagnosis in Brazil between 2018 and 2023, characterized by an increase in the proportion of cases diagnosed in advanced stages (III and IV) in several health regions. This trend was particularly pronounced in the male population and tongue lesions. Spatial analysis identified clusters with a trend of increasing advanced cases in 22 health regions, distributed across four geopolitical macroregions and seven FUs. Conversely, clusters with a decreasing trend were observed in the south, southeast, and northeast regions. The evaluation of the temporal trend demonstrated that although the national proportion of advanced cases remained stationary during the period, an increasing trend in the southeast and a decreasing trend in the northeast were noted. The decreasing number of diagnoses in early stages and the persistence of clusters of high advanced incidence point to failures in the coverage and effectiveness of PHC, as well as deficiencies in the early diagnosis network. Therefore, public policies must be strengthened for screening and early detection, expand access to dental services, promote professional training, and intensify educational actions aimed at the population, with a specific emphasis on the male population and areas of greater vulnerability. Declarations Ethics approval and consent to participate Ethical Approval was not required as this study was a review of publicly available policy documentation Consent for publication All participants, and their parents/carers, signed an informed consent to allow their anonymous data to be published. Availability of data and materials The data supporting the findings of this study are available from the Department of Information and Informatics of the Brazilian Unified Health System (DATASUS) at https://datasus.saude.gov.br/. Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This study was supported in part by the Brazilian Coordination for Improvement in Higher Education (CAPES) [Finance Code 001] and the Foundation for Research and Scientific and Technological Development of Maranhão (FAPEMA). Authors' contributions MVCB, EMC, VPR, and EBAFT contributed to the conception and design. MVCB and EMC were responsible for data extraction. EMC, VPR, and EBAFT were responsible for data analysis. MVCB, JVIL, and EBAFT contributed to the interpretation of the results. MVCB and EMC drafted the paper. JVIL, VPR, and EBAFT contributed to revising the manuscript. All authors approved the final version of the manuscript. Acknowledgements Thank you to all the participants who directly or indirectly contributed to the conclusion of this research project. And thank you to the government of Brazil for making the data used in this study freely available. References World Health Organization (WHO). Oral Health. 2025 Available from: https://www.who.int/news-room/fact-sheets/detail/oral-health. Accessed October 10, 2025. International Agency for Research on Cancer (IARC)/World Heath Organization (WHO). Estimated cancer incidence, mortality and prevalence worldwide - Lip, Oral Cavity. 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J Dent Res . 2021;100(12):1313–1320. https://doi.org/10.1177/00220345211014795 Schussel JL, Villarroel-Dorrego M, Niklander SE. Strengthening Collaborations in Latin America for Advancing Oral cancer research and public health policies. J Clin Exp Dent . 2025;17(7):855–861. https://doi.org/10.4317/jced.62884 Ribeiro-Rotta RF, Rosa EA, Milani V, Dias NR, Masterson D, da Silva EN, et al. The cost of oral cancer: A systematic review. Plos One . 2022;17(4): e0266346. https://doi.org/10.1371/journal.pone.0266346 Martínez-Ramírez J, Saldivia-Siracusa C, González-Pérez LV, Cuadra Zelaya FJM, Gerber-Mora R, Cabrera OFG, et al. Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean. Oral Dis . 2024;30(7):4174–4184. https://doi.org/10.1111/odi.14903 Serna BYH, Betancourt JAO, Soto OPL, Do Amaral RC, Correa MDPC. Trends of incidence, mortality, and disability-adjusted life years of oral cancer in Latin America. Rev Bras Epidemiol . 2022;25:e220034. https://doi.org/10.1590/1980-549720220034 de Oliveira DC da RR, da Paz WS, Bezerra-Santos M, dos Santos PL, Tavares D dos S. Temporal trend and spatial analysis of oral cancer cases in Brazil: Correlation between socioeconomic factors and delay in diagnosis and treatment. Trop Med Int Health . 2025;30(9):908–920. https://doi.org/10.1111/tmi.14141 International Agency for Research on Cancer (IARC)/World Health Organization (WHO). Estimated cancer incidence, mortality and prevalence in Brazil - Lip, Oral Cavity. Global Cancer Observatory (Globocan). 2022 Available from: https://gco.iarc.who.int/media/globocan/factsheets/populations/76-brazil-fact-sheet.pdf Accessed May 19,2025. de Paiva JPG, Jorge J, Dos Santos ES, Migowski A, Cohen-Goldemberg D, Kowalski LP, et al. Estimating the burden of care for oral potentially malignant disorders and oral cancer in Brazilian dental practice. Med Oral Patol Oral Cir Buca l. 2024;29(5):e719–e726. https://doi.org/10.4317/medoral.26701 Oliveira LC de, Rosa KS da C, Bergmann A, Thuler LCS. Temporal trends and factors associated with the cancer diagnosed at stage IV in patients included in the integrated hospital-based cancer registry system in Brazil in two decades. Cancer Epidemiol . 2022;80:102242. https://doi.org/10.1016/j.canep.2022.102242 Soares ÉC, Neto BCB, Santos LP de S. Epidemiological study of oral cancer in Brazil. Arq Med . 2019;64:192–198. https://doi.org/10.26432/1809-3019.2019.64.3.192 Borges MVC, Pereira EM, Santos RTP, de Oliveira ICV, Thomaz EBAF, Rodrigues V. Temporal trends in treatment delays for oral and oropharyngeal cancer in Brazil: An analysis of the national database. J Public Health Dent . 2025 Mar 1;85(1):102–110. https://doi.org/10.1111/jphd.12658 Borges MVC, Costa EM, Rodrigues VP, Thomaz EBAF. Healthcare networks and the waiting time to begin oral cancer treatment: An ecological study. Health Policy Technol . 2025 Dec;14(6):101116. https://doi.org/10.1016/j.hlpt.2025.101116 Brasil. Portaria GM/MS No 6.213, de 19 de dezembro de 2024. Altera a Portaria de Consolidação GM/MS no 3, de 28 de setembro de 2017, para instituir a Rede de Atenção à Saúde Bucal - RASB da Política Nacional de Saúde Bucal - PNSB, no âmbito do Sistema Único de Saúde - SUS. Diário Oficial da União. Brasília; 2024 Dec 19. Costa JFR, Chagas L de D, Silvestre RM. A Política Nacional de Saúde Bucal do Brasil: registro de uma conquista histórica. Brasília: Organização Pan-Americana da Saúde; 2006. Mourao P, Junqueira A. Through the irregular paths of inequality: An analysis of the evolution of socioeconomic inequality in Brazilian states since 1976. Sustainab . 2021;13(4):2356. https://doi.org/10.3390/su13042356 Brasil. Human Development Index (HDI) by health region. AtlasBr; 2014 Available from: http://www.atlasbrasil.org.br/ranking Accessed Jun 22,2024. Brasil. IBGE. Instituto Brasileiro de Geografia e Estatística [Internet]. 2014 Available from: https://www.ibge.gov.br/estatisticas/economicas/contas-nacionais.html Accessed May 9, 2024. Oliveira NR de C. Redes de Atenção à Saúde: a atenção à saúde organizada em redes. São Luís: EDUFMA; 2016. Available from: http://www.unasus.ufma.br/site/files/livros_isbn/isbn_redes01.pdf Brasil. Lei no 10.741, de 1º de outubro de 2003. Dispõe sobre o estatuto do idoso e dá outras providências. Diário Oficial da União. Brasília; 2003 Oct 1. Departamento de Informática do Sistema Único de Saúde do Brasil. DATASUS. Brasília: Ministério da Saúde; 2014. Available from: https://datasus.saude.gov.br/informacoes-de-saude-tabnet/ Mathew A, George PS, Ramadas K, Mathew BS, Kumar A, Roshni S, et al. Sociodemographic Factors and Stage of Cancer at Diagnosis: A Population-Based Study in South India. J Glob Oncol . 2019 Jul;5:1–10. Khurshied S, Shahid Z, Wazir T, Ullah I, Sagheer S, Khurshid N, et al. Delay in the Diagnosis of Patients With Head and Neck Cancer: Impact of Different Patient- and Healthcare Provider-Related Factors. Cureus . 2024;16(9):e68528. https://doi.org/10.7759/cureus.68528 Speight PM, Epstein J, Kujan O, Lingen MW, Nagao T, Ranganathan K, et al. Screening for oral cancer—a perspective from the Global Oral Cancer Forum. Oral Surg Oral Med Oral Pathol Oral Radiol . 2017;123(6):680–687. https://doi.org/10.1016/j.oooo.2016.08.021 FDI World Dental Federation. Access to oral healthcare for vulnerable and underserved populations. Int Dent J . 2020;70(1):15–16. https://doi.org/10.1111/idj.12556 Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol . 2009;45(4–5):309–316. https://doi.org/10.1016/j.oraloncology.2008.06.002 Rubin G, Berendsen A, Crawford SM, Dommett R. The expanding role of primary care in cancer control. Lancet Oncol . 2015;16(12):1231–1272. https://doi.org/10.1016/S1470-2045(15)00205-3 Chen S, Lin Z, Chen J, Yang A, Zhang Q, Xie C, et al. Older age is a risk factor associated with poor prognosis of patients with squamous cell carcinoma of the oral cavity. Eur Arch Otorhinolaryngol . 2020;277(9):2573–2580. https://doi.org/10.1007/s00405-020-05963-3 Cohen Goldemberg D, de Araújo LHL, Antunes HS, de Melo AC, Santos Thuler LC. Tongue cancer epidemiology in Brazil: incidence, morbidity and mortality. Head Neck . 2018;40(8):1834–1844. https://doi.org/10.1002/hed.25166 Chieko M, Uzawa N, Kayamori K, Sonoda I. Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas. Oral Oncol . 2012;48(4):320–34. https://doi.org/10.1016/j.oraloncology.2011.11.014 PNUD Brasil, IPEA. Desenvolvimento humano nas macrorregiões brasileiras [Internet]. Brasília: PNUD; 2016. Available from: https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/desenvolvimento-humano-nas-macrorregioesbrasileiras/ Accessed May 29,2025. Kassirian S, Dzioba A, Hamel S, Patel K, Sahovaler A. Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay. Curr Oncol . 2020;27(5):e467–e477. https://doi.org/10.3747/co.27.6547 Louredo BVR, Vargas PA, Pérez-De-Oliveira ME, Lopes MA, Kowalski LP, Curado MP. Epidemiology and survival outcomes of lip, oral cavity, and oropharyngeal squamous cell carcinoma in a southeast Brazilian population. Med Oral Patol Oral Cir Bucal. 2022;27(3):e274–e284. https://doi.org/10.4317/medoral.25147 Pereira NEB, De Oliveira DCDRR, Santos MB, Santos PL Dos, Tavares DDS. Association of Socioeconomic Status and Oral Cancer Mortality in Brazil: Temporal Trends and Spatial Distribution. Med Princ Pract . 2023;32(1):40–48. https://doi.org/10.1159/000529155 Brasil. Human Development Index in each Federative Unit of Brazil. IBGE - Instituto Brasileiro de Geografia e Estatística; 2020. Available from: https://cidades.ibge.gov.br/brasil/pesquisa/37/30255 Accessed Mar 9, 2024. Araújo IM, Borges MVC, Santos LGS, Rocha JR, Pereira ÉM, Rodrigues VP. Impact of the COVID-19 Pandemic on Delay in Treatment Initiation for Oral Cavity and Oropharyngeal Cancer in Brazil. Pesq Bras Odontop Clin Integr . 2025;25:e240036. https://doi.org/10.1590/pboci.2025.020 Teixeira RA, Naghavi M, Guimarães MDC, Ishitani LH, França EB. Quality of cause-of-death data in Brazil: Garbage codes among registered deaths in 2000 and 2015. Rev Bras Epidemiol . 2019;22:E190002.supl.3. https://doi.org/10.1590/1980-549720190002.supl.3 Cunha AR da, Bigoni A, Antunes JLF, Hugo FN. Impact of redistributing deaths by ill-defined causes in oral and oropharyngeal cancer mortality in Brazil. Braz Oral Res. 2022;36:e117. https://doi.org/10.1590/1807-3107bor-2022.vol36.0117 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 May, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers agreed at journal 21 Apr, 2026 Reviewers invited by journal 21 Apr, 2026 Editor assigned by journal 04 Apr, 2026 Editor invited by journal 27 Mar, 2026 Submission checks completed at journal 26 Mar, 2026 First submitted to journal 26 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9181918","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":631114773,"identity":"763f3719-c251-40c1-ac9a-c0afc345b49f","order_by":0,"name":"Marcio Borges","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYLCCBDACgQoJfjDNAxchqOWMhGQDUVoYYAoY2xgIa9FtP/vww4MKhjx+6eMXH/6cZyGh236A8cHbNoY88wbsWszOpBtLJJxhKJbsyyk25t0mIWF2JoHZcG4bQ7HMARxaDqSxMSS2MSRuOMOTJs24TaLO7EACmzQvUGQGDoeZnX8G15L+8+ccoC3nH7D/xqvlBtwW9mMMvA1ALTcS2Jjxa3nGDPSLRLFkDw+zNM8xkJaHzZJzzkkUS+B0WBrjxx8VNnn8POwPP/6oqQM6LPnghzdlNnm4tEABSJrHAMphbICKEATsD4hRNQpGwSgYBSMQAAA+1FbTvINoagAAAABJRU5ErkJggg==","orcid":"","institution":"Federal Institute of Education, Science and Technology of Maranhão","correspondingAuthor":true,"prefix":"","firstName":"Marcio","middleName":"","lastName":"Borges","suffix":""},{"id":631114776,"identity":"c27e21db-3892-4c12-9ee3-f48e2fa1fa44","order_by":1,"name":"Elisa Costa","email":"","orcid":"","institution":"Federal University of Alagoas","correspondingAuthor":false,"prefix":"","firstName":"Elisa","middleName":"","lastName":"Costa","suffix":""},{"id":631114778,"identity":"e6311809-f278-4ecd-8692-21d155981af0","order_by":2,"name":"Vandilson Rodrigues","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Vandilson","middleName":"","lastName":"Rodrigues","suffix":""},{"id":631114779,"identity":"54e4fd7c-1d52-47b4-a3a5-e8c8136c5152","order_by":3,"name":"João Victor Lara","email":"","orcid":"","institution":"Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"Victor","lastName":"Lara","suffix":""},{"id":631114780,"identity":"eee73649-691a-4cfb-90e9-29df531a49b0","order_by":4,"name":"Erika Thomaz","email":"","orcid":"","institution":"Federal University of Maranhão","correspondingAuthor":false,"prefix":"","firstName":"Erika","middleName":"","lastName":"Thomaz","suffix":""}],"badges":[],"createdAt":"2026-03-20 20:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9181918/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9181918/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108389780,"identity":"751d6cf7-8464-47f6-9fde-d6cf3a74e7e0","added_by":"auto","created_at":"2026-05-04 06:52:11","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":511381,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of advanced (III and IV) oral cancer in Brazil in 2018 and 2023 according to the total population, sex (male and female), and age group (non-older and older) in 2018 and 2023.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9181918/v1/edb80b123b63f721e5e1566a.jpeg"},{"id":108492884,"identity":"30254d90-1ac8-4574-9a65-fa0d27054e63","added_by":"auto","created_at":"2026-05-05 09:58:53","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":490720,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of advanced (III and IV) oral cancer in Brazil according to anatomical location: lip, tongue, gums, floor of the mouth, and palate in 2018 and 2023.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9181918/v1/e6509897862def4200a614f5.jpeg"},{"id":108493367,"identity":"281435bc-5423-4cd0-86e8-959437e48654","added_by":"auto","created_at":"2026-05-05 10:00:04","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":486332,"visible":true,"origin":"","legend":"\u003cp\u003eCluster maps (LISA) of the proportion of advanced (III and IV) oral cancer in Brazil according to the total population, sex (male and female), and age group (non-older and older) in 2018 and 2023.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9181918/v1/a43d71c409d307b83e3a69ee.jpeg"},{"id":108389781,"identity":"426999d5-00ff-4850-889e-51fdf6d15ca9","added_by":"auto","created_at":"2026-05-04 06:52:11","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":503980,"visible":true,"origin":"","legend":"\u003cp\u003eCluster maps of the proportion of advanced (III and IV) oral cancer in Brazil according to anatomical location: lip, tongue, gum, and floor of the mouth and palate in 2018 and 2023.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9181918/v1/f39ff0f33c61ccbca70a7856.jpeg"},{"id":108389782,"identity":"08d77704-144b-46c6-bb39-0f1e3acd7515","added_by":"auto","created_at":"2026-05-04 06:52:11","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":814261,"visible":true,"origin":"","legend":"\u003cp\u003eTrend in the proportion of advanced oral cancer (III and IV) in Brazil between 2018 and 2023\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9181918/v1/641e9c6f2a7d1307bb96b888.jpeg"},{"id":108804184,"identity":"84ea44a8-5d8f-4296-825c-6a23efb608be","added_by":"auto","created_at":"2026-05-08 15:17:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3130624,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9181918/v1/d040248f-5707-4143-9f83-227f99eca7e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Spatiotemporal patterns and trends in the proportion of advanced oral cancer at diagnosis in Brazil, 2018–2023","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOral cancer (OC), a disease of the upper aerodigestive tract, affects the lips, labial and buccal mucosa, anterior two-thirds of the tongue, retromolar trigone, floor of the mouth, gum, and hard palate.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e According to World Health Organization estimates, this malignant neoplasm was responsible for over 389,000 new cases and more than 188,000 deaths worldwide in 2022, representing a 5-year mortality rate close to 50%, which has not decreased substantially in the last 40 years.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e This high mortality is mainly caused by the high percentage of OC diagnoses at advanced stages, in which treatment is complex, mutilating, and disabling,\u003csup\u003e4\u003c/sup\u003e and this advanced diagnosis have complex and diverse causes, involving several factors, such as patients, health professionals, and health services.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe tumor\u0026ndash;node\u0026ndash;metastasis (TNM) classification, proposed by the American Joint Committee on Cancer, is the most widely used grading system for malignant head and neck tumors (including OC). In this system, components are combined to classify the tumor into stages I\u0026ndash;IV to guide treatment and prognosis.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Early (I and II) or advanced (III and IV)-staged diagnosis remains an essential factor for treatment planning and disease prognosis,\u003csup\u003e7\u003c/sup\u003e allowing the application of more appropriate treatment protocols with a better estimate of each patient\u0026rsquo;s prognosis.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA meta-analysis showed that initiating treatment within 30 days improved overall survival by 9% compared with longer intervals.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The American Dental Association and the American Academy of Oral Medicine recommend OC screening, particularly for high-risk individuals, such as those with chronic tobacco and alcohol use.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Clinical recognition and assessment of oral mucosal lesions can detect up to 99% of oral cancers/pre-malignancies,\u003csup\u003e10\u003c/sup\u003e although diagnosis is challenging because OC is often asymptomatic and presents with diverse morphologies.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e However, compared with other cancer types that have screening programs (breast, prostate, and colon), early detection of OC has not improved in recent years.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Studies point to difficulties in promoting policies and strategies for the diagnosis of OC in early stages, particularly in developing countries,\u003csup\u003e13\u003c/sup\u003e which represents a serious public health problem.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Professionals from 21 countries in Latin America and the Caribbean identified the limited implementation of OC control plans, low mandatory reporting of oral lesions and OC, unclear protocols for referral of suspected or confirmed lesions, and a shortage of trained professionals as the main barriers to early diagnosis and adequate treatment of OC.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBrazil is the country with the highest absolute number of OC cases in Latin America.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e This neoplasm is among the most prevalent, with an estimated 5.3 cases per 100,000 inhabitants.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e More than 9,000 new cases and approximately 4,000 deaths are registered in Brazil annually,\u003csup\u003e18\u003c/sup\u003e and a growing mortality trend is projected in the coming decades.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e A general dentist in the Brazilian public health system is expected to encounter approximately 675 patients with lesions suspected of being OC during their career.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Despite this, diagnosis often occurs at more advanced stages,\u003csup\u003e21\u003c/sup\u003e exceeding 50% across all regions\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e and delaying treatment initiation. Despite the high prevalence, incidence, and mortality from OC in Brazil, the Oral Health Care Network (RASB, acronym in Portuguese)\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e was only created in 2024;.Although the National Oral Health Policy (PNSB, acronym in Portuguese) existed during that period, it was only registered in 2023.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e The spatiotemporal trend of the proportion of Brazil population diagnosed with OC in advanced stages has been less explored, and no studies have incorporated data from the most recent years.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Therefore, this study aimed to analyze the spatiotemporal distribution of the proportion of OC cases diagnosed in stages III and IV in Brazil from 2018 to 2023. The study tested the hypotheses that the temporal trends of diagnosis in advanced stages are increasing or stationary, despite the current public policies; significant spatiotemporal differences exist in oral cancer staging at the time of diagnosis; and spatial clusters of cases exist in advanced stages, particularly in territories with greater socioeconomic vulnerability.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study design\u003c/h2\u003e \u003cp\u003eThis ecological observational study employed spatial and temporal approaches using secondary data from the Brazilian Unified Health System (SUS, acronym in Portuguese), whose units of analysis were health regions, geopolitical macroregions, and Brazil.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Study location\u003c/h2\u003e \u003cp\u003eBrazil is a developing country and the largest Latin American country, presenting worrying inequalities and significant regional differences.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e In 2023, 5,570 municipalities were organized into 450 health regions, 27 federative units (FUs), and five macroregions, as described: north, northeast, central-west, southeast, and south. The northeast (human development index (HDI): 0.663) and north (HDI: 0.667) face the most adverse conditions, reflected in social, political, economic, environmental, and infrastructure challenges. In contrast, south (HDI: 0.754), central-west (HDI: 0.757), and southeast (HDI: 0.766) demonstrate more favorable development indicators.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Brazil is organized into Healthcare Networks (HN), which are polyarchic organizations of health services and are organized horizontally, without hierarchy between the three levels of care (primary, secondary, and tertiary), with primary health care (PHC) being responsible for coordinating care. The main objective of the HN is to provide comprehensive care, encompassing promotional, preventive, curative, rehabilitative, and palliative interventions, efficiently and effectively.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e To facilitate the integration of the HN, health regions were created, which are a continuous geographic space made up of groups of bordering municipalities, delimited based on cultural, economic, and social identities and shared communication and transportation infrastructure networks, to integrate the organization, planning, and execution of health actions and services.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Study population\u003c/h2\u003e \u003cp\u003eThe study population consisted of all OC cases with available staging information from 2018 to 2023, grouped by health region, macroregion, and Brazil. The outcome was the proportion of OC diagnosed in advanced stages (III and IV). OC was defined as cancer located on the lips and in the oral cavity, according to the International Classification of Diseases, Tenth Revision (ICD\u0026thinsp;\u0026minus;\u0026thinsp;10 (C00 to C06). Cases without a record of OC staging were excluded from the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Data Source\u003c/h2\u003e \u003cp\u003eData from the Brazilian Unified Health System Informatics Department (DATASUS, acronym in Portuguese) were compiled. DATASUS is the informatics department of the Brazilian Unified Health System, which collects data from three points\u0026mdash;primary healthcare (PHC), secondary healthcare (SHC), and tertiary healthcare (THC)\u0026mdash;in Brazilian health regions and manages the country\u0026rsquo;s health database.30 DATASUS data were collected from the digital platform PAINEL-Oncology. This platform unifies data originating from three national information systems: the Outpatient Information System (SIA, acronym in Portuguese), Hospital Information System (SIH, acronym in Portuguese), and Cancer Information System (SISCAN, acronym in Portuguese).\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe proportion of advanced-stage OC in relation to the total number of cases was estimated by health region from 2018 to 2023. The following anatomical locations were considered according to ICD-10: malignant neoplasm of the lip (C00), malignant neoplasm of the base of the tongue (C01), malignant neoplasm of other parts and unspecified parts of the tongue (C02), malignant neoplasm of the gum (C03), malignant neoplasm of the floor of the mouth (C04), malignant neoplasm of the palate (C05), and malignant neoplasm of other parts and unspecified parts of the mouth (C06). Additionally, the indicator was calculated by sex, age, and anatomical site. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the source, time period, and description of the indicators are presented.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of study indicators by health region.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeriod\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdvanced staging (AS)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of cases diagnosed with advanced-stage oral cancer by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018\u0026ndash;2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: men\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage oral cancer cases in men by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: women\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage oral cancer cases in women by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: non-older individuals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage oral cancer cases in non-older individuals (\u0026lt;\u0026thinsp;59 years) by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: older individuals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage oral cancer cases in older individuals\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e (\u0026ge;\u0026thinsp;60 years) by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: lip\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage lip cancer cases by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: tongue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage tongue cancer cases by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: gum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage gum cancer cases by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS: floor of the mouth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage floor of mouth cancer cases by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEA: palate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage of advanced-stage palate cancer cases by health region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDATASUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018 and\u003c/p\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e1\u003c/sup\u003eAS: advanced staging (diagnosis in stages III and IV). DATASUS, Department of Informatics of the Brazilian Unified Health System.\u003c/p\u003e \u003cp\u003e \u003csup\u003e2\u003c/sup\u003e Analyses considering diagnosis in advanced stages were performed for the period from 2018 to 2023. However, for analyses stratified by sex, age, and anatomical location of oral cancer, only the beginning and end of the time series (2018 and 2023) were considered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed in four stages, as described below:\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.5.1. Choropleth maps for 2018 and 2023\u003c/h2\u003e \u003cp\u003eChoropleth maps were created to assess the proportion of advanced OC cases in Brazil. Choropleth maps are thematic representations that use different shades or patterns of a color to represent the variation of a given phenomenon in geographic areas. In this study, maps were created for 2018 and 2023, detailing the distribution of advanced-stage OC by health region. The variables analyzed included the total cases and cases by sex (male and female), age (non-older and older), and anatomical location (lip, tongue, gum, floor of the mouth, and palate). Choropleth maps were created using QGIS 3.16.1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.5.2. Global Moran\u0026rsquo;s Index and LISA in 2018 and 2023\u003c/h2\u003e \u003cp\u003eTo investigate the spatial autocorrelation of advanced-stage OC cases, Global Moran\u0026rsquo;s index (GMI) and Local Indicator of Spatial Association (LISA) maps were created. This analysis sought to verify whether changes in the patterns and spatial heterogeneity of diagnosed cases, by health region, in 2018 and 2023, occurred randomly or whether the incidence in one health region influences the occurrence in neighboring regions. The variables analyzed included advanced-stage OC, sex (male and female), age (non-older and older), and anatomical location (lip, tongue, gum, floor of the mouth, and palate). The analyses were processed on Google Colab using the PySAL library in the Python programming language. The cartographic base of Brazil, detailing the borders of the states and Federal District, was obtained free of charge from the Brazilian Institute of Geography and Statistics (IBGE, acronym in Portuguese) website.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo calculate the GMI, which provides a single measure of autocorrelation for the entire dataset, a covariance approach is used based on the product of deviations from the mean. This global index tests whether neighboring areas exhibit greater similarity regarding the studied indicator than would be expected by chance. The spatial weight matrix is ​​crucial in this calculation, as it defines which areas are neighbors and the weight of their influence. The first-order adjacency (which verifies horizontal, vertical, and diagonal interactions) is one of the common options; however, the choice of the most appropriate matrix depends on the analysis context. The GMI result ranges from \u0026minus;\u0026thinsp;to +\u0026thinsp;1, where positive and negative values ​​indicate positive (similar values ​​grouped together) and negative (dissimilar values ​​grouped together) spatial autocorrelation, respectively. Values ​​close to zero indicate the absence of autocorrelation.\u003c/p\u003e \u003cp\u003eLISA performs a spatial autocorrelation that measures the relationship between observations with spatial proximity. It is based on the principle that spatially close observations tend to have similar ​​(positive autocorrelation) or dissimilar ​​(negative autocorrelation/outlier) values and seeks to identify these patterns at the local level. LISA is a statistical tool that generates a significant value for each study area, allowing the visualization of clusters and spatial outliers with regions showing similar values ​​for the analyzed indicator. These patterns are categorized into four main types: high\u0026ndash;high, regions with high values ​​surrounded by others with equally high values; low\u0026ndash;low, regions with low values ​​surrounded by others also with low values; high\u0026ndash;low, a spatial outlier of high value amidst regions with low values; and low\u0026ndash;high, another spatial outlier, but of low value surrounded by areas with high values.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.5.3. Space\u0026ndash;Time Cube from 2018 to 2023\u003c/h2\u003e \u003cp\u003eA space\u0026ndash;time cube analysis was employed to assess the annual spatiotemporal distribution of the proportion of advanced OC from 2018 to 2023. The health region was defined as the unit of analysis. This approach was used to identify patterns of spatial and temporal autocorrelation, categorizing health regions into hot spots (increasing trend), indicating growth in the proportion of cases during the period; cold spots (declining trend), for areas with a decrease; and no pattern detected, for regions where no significance was found. The significance of the patterns was determined by the p-value of each location in the cube. Time units were represented by boxes in the cube, and confidence intervals of 90%, 95%, and 99% were considered in the analysis. The analysis was conducted using the scikit-learn library of the Python programming language, which was processed on Google Colab.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e2.5.4 Prais\u0026ndash;Winsten regression analysis from 2018 to 2023\u003c/h2\u003e \u003cp\u003eTime\u0026ndash;trend analysis was performed using Prais\u0026ndash;Winsten generalized linear regression, a technique appropriate for time series because it corrects for the autocorrelation of the residuals.32 The monthly proportions of advanced OC (III and IV) were evaluated, aggregated by macroregion and Brazil, for the period from 2018 to 2023. The results were interpreted as stable trend (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), increasing trend (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and positive regression coefficient), and decreasing trend (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and negative regression coefficient). The regression coefficient and monthly percentage change were also estimated. Temporal analyses were performed using STATA (version 16.0).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eFrom 2018 to 2023, 64,448 OC cases were diagnosed in Brazil, with 11,333 (17.5%) lacking staging information. Among those with staging information, 23,914 (45.0%) were diagnosed at an advanced stage. In 2018, 157 health regions (34.9%) had\u0026thinsp;\u0026ge;\u0026thinsp;75% cases diagnosed at an advanced stage, reaching 260 (57.7%) health regions in 2023. The number of health regions with \u0026ge;\u0026thinsp;50% of cases diagnosed at an advanced stage in men increased from 120 (26.7%) in 2018 to 274 (60.8%) in 2023. In contrast, the proportion of health regions with advanced cases in women was \u0026gt;\u0026thinsp;75% in the 0%\u0026ndash;25% range in both 2018 and 2023. No notable difference was noted in the proportion of advanced cases between non-older and older individuals (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe proportion of health regions increased with \u0026ge;\u0026thinsp;50% of tongue cancer diagnosed in advanced stages, rising from 67 regions (14.8%) in 2018 to 118 (26.2%) in 2023. For all other anatomical locations, \u0026gt;\u0026thinsp;90% of health regions remained in the range of 0\u0026ndash;25% of cases in advanced stages in 2018 and 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn 2018, high\u0026ndash;high clusters (health regions with high proportions of advanced OC cases surrounded by other health regions with high proportions) were observed in the southeast, midwest, and northeast; and in 2023, a slight change occurred, identifying high\u0026ndash;high clusters in the same regions and in the north.\u003c/p\u003e \u003cp\u003eRegarding sex, in 2018, clusters with a high proportion of advanced cases of high\u0026ndash;low OC were observed in the southeast region for men and southeast and northeast regions for women. In 2023, high\u0026ndash;low clusters were observed in the southeast, midwest, and north regions for men and in the southeast, northeast, and north regions for women. For the non-older population (\u0026lt;\u0026thinsp;59 years), the number of high\u0026ndash;low clusters increased in the northeast and midwest between 2018 and 2023; whereas in the older group, an increase in both high\u0026ndash;low and high\u0026ndash;low clusters was observed between 2018 and 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAnalysis of anatomical location showed a reduction in low\u0026ndash;low clusters and an increase in high\u0026ndash;high clusters for lip, tongue, and gum cancers from 2018 to 2023, whereas both clusters increased for floor and palate sites (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFrom 2018 to 2023, clusters with a decreasing trend in the proportion of advanced OC cases were observed in the northeast, southeast, and south regions of Brazil (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and clusters with an increasing trend were observed in the north, northeast, southeast, and south regions (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFrom 2018 to 2023, the temporal trend analysis of the proportion of advanced OC in Brazil and its macroregions showed a decreasing trend in the northeast (MPV: \u0026minus;0.105; p\u0026thinsp;=\u0026thinsp;0.049) and an increasing trend in the southeast (MPV: 0.115; p\u0026thinsp;=\u0026thinsp;0.017). For other macroregions, the trend was stable (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTrend in the proportion of advanced oral cancer by macroregion, Brazil, 2018\u0026ndash;2023.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMPV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTrend\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNorth\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.106 to 0.142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.769\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026ndash;\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNortheast\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.096 to \u0026minus;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026darr;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSoutheast\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.008 to 0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026uarr;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSouth\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.056 to 0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026ndash;\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCentral-west\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.063 to 0.180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026ndash;\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBrazil\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.008 to 0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026ndash;\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eβ, Prais\u0026ndash;Winsten regression coefficient; 95% CI, confidence interval; MPV, monthly percentage variation. (\u0026ndash;\u0026ndash;) stationary trend, (\u003cb\u003e\u0026darr;\u003c/b\u003e) decreasing trend, and (\u003cb\u003e\u0026uarr;\u003c/b\u003e) increasing trend.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eFrom 2018 to 2023, the number of health regions with high proportions of OC cases diagnosed at advanced stages (III and IV) has increased. This increasing trend was also observed in the male population and in cases located on the tongue. Conversely, the proportion of advanced OC cases in the female population remained stagnant and was lower in the study period compared with the male population, and no notable difference was found between non-older and older individuals. Distinct regional patterns and some notable changes in the clusters of advanced OC cases were observed in Brazil between 2018 and 2023. Clusters with an increasing trend of advanced OC were found in 22 health regions (distributed across four geopolitical macroregions and seven states); however, clusters with a decreasing trend were also observed in the south, southeast, and northeast regions. Finally, the trend in the proportion of OC cases diagnosed at advanced stages remained stable in Brazil from 2018 to 2023, although with an increasing trend in the southeast region and a decreasing trend in the northeast.\u003c/p\u003e \u003cp\u003eThe increase in the proportion of OC diagnosed in the advanced stage in Brazil in 2018 and 2023 represents a serious public health problem, which may affect mortality rates because preventive and early diagnostic procedures were not adequately implemented.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e High levels of social inequity, such as low educational level,\u003csup\u003e32\u003c/sup\u003e high unemployment\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e, and low HDI\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e, are associated with this high proportion of diagnoses at an advanced stage. Capacity can be expanded for more effective action by oral screening for early disease detection,\u003csup\u003e36\u003c/sup\u003e improvement of healthcare networks focusing on diagnosis in primary health care\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e, training and continuing education of health professionals, health education campaigns for the population, and improved access to dental and diagnostic services, particularly for disadvantaged populations\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe proportion of OC diagnosed in the advanced stage in men increased between 2018 and 2023, and this proportion was consistently higher than that in women. Women are less likely to be diagnosed with stage IV oral cancer\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, and men tend to have higher mortality and worse survival rates than women. Furthermore, men tend to take less care of their health than women.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e Accordingly, specific health initiatives aimed at the male population can help reverse this alarming situation.\u003c/p\u003e \u003cp\u003eThe proportion of diagnoses of OC in the advanced stage was similar between non-older and older individuals. This finding is corroborated by the results of a study that did not find a significant difference in staging between individuals aged\u0026thinsp;\u0026gt;\u0026thinsp;40 and \u0026lt;\u0026thinsp;40 years; however, non-older individuals generally have higher survival rates.\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e However, other studies present contradictory results: people aged\u0026thinsp;\u0026ge;\u0026thinsp;60 have a lower chance of being diagnosed at stage IV,\u003csup\u003e21\u003c/sup\u003e whereas patients aged\u0026thinsp;\u0026lt;\u0026thinsp;50 have a higher risk of being diagnosed at an advanced stage.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Non-older individuals may not be prioritized for screening compared with older individuals because they are not considered risk groups. Conversely, the older group tends to seek health services less often; thus, in both groups, the diagnosis was delayed but for different reasons.\u003c/p\u003e \u003cp\u003eThe tongue showed the highest proportion of advanced OC cases, consistent with previous years because a study conducted in Brazil between 2000 and 2014 reported that most tongue cancers were diagnosed at stages III and IV.\u003csup\u003e39\u003c/sup\u003e The tongue is a richly vascularized structure, which can favor cancer spread.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e In addition, macro-determining factors, such as low access to education and lack of access to the healthcare system, historical problems in Brazil, and the less accessible position of most tongue cancers (posterior region and edges), in addition to problems in the training of general dentists, favor a late diagnosis.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAnalysis of spatial clusters of advanced OC revealed distinct patterns among Brazilian macroregions in 2018 and 2023, both for the general population and segregated by sex. Thus, for the 2 years analyzed, the northeast macroregion presented more high\u0026ndash;high clusters, which can be explained by macrodeterminant factors such as the low HDI of this region,\u003csup\u003e41\u003c/sup\u003e healthcare network problems, particularly in medium and high complexity care, cultural issues, and historical inequities compared with other macroregions. A Canadian study reported a high proportion of cases diagnosed at advanced stages in both sexes of people residing in economically more vulnerable regions.\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHigh\u0026ndash;high spatial clusters of advanced OC were observed in men and women in the 2 years analyzed for the southeast macroregion. Although the southeast region is one of the most developed in Brazil, this microregion is characterized by high rates of diagnoses of OC in the advanced stage \u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e and mortality from OC.\u003csup\u003e44\u003c/sup\u003e High\u0026ndash;high clusters for OC of the tongue and floor of the mouth were also observed in the north macroregion in 2023. The north region has the second lowest HDI\u0026mdash;second only to the northeast region\u0026mdash;and shares historical inequalities compared with the other macroregions.\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSpace\u0026ndash;time cube analysis revealed that from 2018 to 2023, clusters of health regions showed a decreasing trend in the proportion of advanced OC in the south, southeast, and northeast regions of Brazil. This may indicate improvements in prevention and screening programs, earlier diagnosis, and advances in public policies in these clusters. However, in the same period, certain clusters showed an increasing trend in all regions, except for the central-west region. This reinforces the fact that regardless of the analysis type, problems exist in various regions of Brazil, reflecting inefficiencies in public policies.\u003c/p\u003e \u003cp\u003eAn analysis considering the entire historical series verified a stationary trend in the proportion of advanced OC in Brazil, a decrease in the northeast macroregion, and an increase in the southeast macroregion. A study conducted between 2000 and 2019 observed that the south and southeast macroregions of Brazil were directly associated with an increase in the diagnosis of OC stage IV.\u003csup\u003e21\u003c/sup\u003e Between 2000 and 2017, 0.29% of cases diagnosed at the advanced stage showed an annual growth trend.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e This result likely reflects the migration of cases to these more developed regions, a more organized health information system, reducing under-registration and under-notification, as well as better completion of official health system forms and documents. However, PHC has grown more rapidly in the north and northeast than in the southeast, and this may have affected the improvement of active case finding and suspicion of cases in earlier stages.\u003c/p\u003e \u003cp\u003eThis study has some limitations, such as the possibility of ecological fallacy, a problem inherent in ecological studies, which makes it impossible to attribute associations observed at the population level to the individual level; the absence of data notification by the Brazilian Health System, particularly in the first years of this study, which may generate measurement biases, underestimating cases, particularly in less developed areas. Furthermore, the trends in the data may have been influenced by the COVID-19 pandemic,\u003csup\u003e46\u003c/sup\u003e and future studies may identify different results, given the end of the pandemic. Therefore, some researchers have analyzed the Brazilian Information Systems regarding data coverage and completion, and many inconsistencies persist, particularly in underdeveloped areas.\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e In a study conducted between 1996 and 2018, the redistribution of data reported as \u0026ldquo;ill-defined causes\u0026rdquo; increased mortality rates from oral and oropharyngeal cancer, particularly in the north and northeast regions, demonstrating that a significant proportion of data is not recorded adequately.\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe main strengths of this study include the use of the health region as the unit of analysis, since healthcare network services are configured and distributed according to this unit of analysis. Furthermore, the data analyzed encompass the entire population of diagnosed OC cases in the country, not just a sample. The use of different analytical strategies for spatiotemporal analysis and units of analysis (Brazil, geopolitical macroregions, and health regions) allows for the disaggregation of data into different granularities and a more adequate exploration of spatial inequities.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study reveals a worrying scenario regarding OC diagnosis in Brazil between 2018 and 2023, characterized by an increase in the proportion of cases diagnosed in advanced stages (III and IV) in several health regions. This trend was particularly pronounced in the male population and tongue lesions. Spatial analysis identified clusters with a trend of increasing advanced cases in 22 health regions, distributed across four geopolitical macroregions and seven FUs. Conversely, clusters with a decreasing trend were observed in the south, southeast, and northeast regions. The evaluation of the temporal trend demonstrated that although the national proportion of advanced cases remained stationary during the period, an increasing trend in the southeast and a decreasing trend in the northeast were noted.\u003c/p\u003e \u003cp\u003eThe decreasing number of diagnoses in early stages and the persistence of clusters of high advanced incidence point to failures in the coverage and effectiveness of PHC, as well as deficiencies in the early diagnosis network. Therefore, public policies must be strengthened for screening and early detection, expand access to dental services, promote professional training, and intensify educational actions aimed at the population, with a specific emphasis on the male population and areas of greater vulnerability.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical Approval was not required as this study was a review of publicly available policy documentation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants, and their parents/carers, signed an informed consent to allow their anonymous data to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from the Department of Information and Informatics of the Brazilian Unified Health System (DATASUS) at https://datasus.saude.gov.br/.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported in part by the Brazilian Coordination for Improvement in Higher Education (CAPES) [Finance Code 001] and the Foundation for Research and Scientific and Technological Development of Maranh\u0026atilde;o (FAPEMA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMVCB, EMC, VPR, and EBAFT contributed to the conception and design. MVCB and EMC were responsible for data extraction. EMC, VPR, and EBAFT were responsible for data analysis. MVCB, JVIL, and EBAFT contributed to the interpretation of the results. MVCB and EMC drafted the paper. JVIL, VPR, and EBAFT contributed to revising the manuscript. All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThank you to all the participants who directly or indirectly contributed to the conclusion of this research project. And thank you to the government of Brazil for making the data used in this study freely available.\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eWorld Health Organization (WHO). Oral Health. 2025 Available from: https://www.who.int/news-room/fact-sheets/detail/oral-health. Accessed October 10, 2025.\u003c/li\u003e\n\u003cli\u003eInternational Agency for Research on Cancer (IARC)/World Heath Organization (WHO). Estimated cancer incidence, mortality and prevalence worldwide - Lip, Oral Cavity. Global Cancer Observatory (Globocan). 2022 Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/1-lip-oral-cavity-fact-sheet.pdf Accessed May 19, 2025.\u003c/li\u003e\n\u003cli\u003eWu J, Chen H, Liu Y, Yang R, An N. The global, regional, and national burden of oral cancer, 1990\u0026ndash;2021: a systematic analysis for the Global Burden of Disease Study 2021. \u003cem\u003eJ Cancer Res Clin Oncol\u003c/em\u003e. 2025;151:53. https://doi.org/10.1007/s00432-025-06098-w\u003c/li\u003e\n\u003cli\u003eVillemure-Poliquin N, Fu R, Gaebe K, Kwon J, Cohen M, Ruel M, et al. 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Temporal trend and spatial analysis of oral cancer cases in Brazil: Correlation between socioeconomic factors and delay in diagnosis and treatment. \u003cem\u003eTrop Med Int Health\u003c/em\u003e. 2025;30(9):908\u0026ndash;920. https://doi.org/10.1111/tmi.14141\u003c/li\u003e\n\u003cli\u003eInternational Agency for Research on Cancer (IARC)/World Health Organization (WHO). Estimated cancer incidence, mortality and prevalence in Brazil - Lip, Oral Cavity. Global Cancer Observatory (Globocan). 2022 Available from: https://gco.iarc.who.int/media/globocan/factsheets/populations/76-brazil-fact-sheet.pdf Accessed May 19,2025.\u003c/li\u003e\n\u003cli\u003ede Paiva JPG, Jorge J, Dos Santos ES, Migowski A, Cohen-Goldemberg D, Kowalski LP, et al. Estimating the burden of care for oral potentially malignant disorders and oral cancer in Brazilian dental practice. \u003cem\u003eMed Oral Patol Oral Cir Buca\u003c/em\u003el. 2024;29(5):e719\u0026ndash;e726. https://doi.org/10.4317/medoral.26701\u003c/li\u003e\n\u003cli\u003eOliveira LC de, Rosa KS da C, Bergmann A, Thuler LCS. Temporal trends and factors associated with the cancer diagnosed at stage IV in patients included in the integrated hospital-based cancer registry system in Brazil in two decades. \u003cem\u003eCancer Epidemiol\u003c/em\u003e. 2022;80:102242. https://doi.org/10.1016/j.canep.2022.102242\u003c/li\u003e\n\u003cli\u003eSoares \u0026Eacute;C, Neto BCB, Santos LP de S. Epidemiological study of oral cancer in Brazil. \u003cem\u003eArq Med\u003c/em\u003e. 2019;64:192\u0026ndash;198. https://doi.org/10.26432/1809-3019.2019.64.3.192\u003c/li\u003e\n\u003cli\u003eBorges MVC, Pereira EM, Santos RTP, de Oliveira ICV, Thomaz EBAF, Rodrigues V. Temporal trends in treatment delays for oral and oropharyngeal cancer in Brazil: An analysis of the national database. \u003cem\u003eJ Public Health Dent\u003c/em\u003e. 2025 Mar 1;85(1):102\u0026ndash;110. https://doi.org/10.1111/jphd.12658\u003c/li\u003e\n\u003cli\u003eBorges MVC, Costa EM, Rodrigues VP, Thomaz EBAF. Healthcare networks and the waiting time to begin oral cancer treatment: An ecological study. \u003cem\u003eHealth Policy Technol\u003c/em\u003e. 2025 Dec;14(6):101116. https://doi.org/10.1016/j.hlpt.2025.101116\u003c/li\u003e\n\u003cli\u003eBrasil. Portaria GM/MS No 6.213, de 19 de dezembro de 2024. Altera a Portaria de Consolida\u0026ccedil;\u0026atilde;o GM/MS no 3, de 28 de setembro de 2017, para instituir a Rede de Aten\u0026ccedil;\u0026atilde;o \u0026agrave; Sa\u0026uacute;de Bucal - RASB da Pol\u0026iacute;tica Nacional de Sa\u0026uacute;de Bucal - PNSB, no \u0026acirc;mbito do Sistema \u0026Uacute;nico de Sa\u0026uacute;de - SUS. Di\u0026aacute;rio Oficial da Uni\u0026atilde;o. Bras\u0026iacute;lia; 2024 Dec 19.\u003c/li\u003e\n\u003cli\u003eCosta JFR, Chagas L de D, Silvestre RM. A Pol\u0026iacute;tica Nacional de Sa\u0026uacute;de Bucal do Brasil: registro de uma conquista hist\u0026oacute;rica. Bras\u0026iacute;lia: Organiza\u0026ccedil;\u0026atilde;o Pan-Americana da Sa\u0026uacute;de; 2006.\u003c/li\u003e\n\u003cli\u003eMourao P, Junqueira A. Through the irregular paths of inequality: An analysis of the evolution of socioeconomic inequality in Brazilian states since 1976. \u003cem\u003eSustainab\u003c/em\u003e. 2021;13(4):2356. https://doi.org/10.3390/su13042356\u003c/li\u003e\n\u003cli\u003eBrasil. Human Development Index (HDI) by health region. AtlasBr; 2014 Available from: http://www.atlasbrasil.org.br/ranking Accessed Jun 22,2024.\u003c/li\u003e\n\u003cli\u003eBrasil. IBGE. Instituto Brasileiro de Geografia e Estat\u0026iacute;stica [Internet]. 2014 Available from: https://www.ibge.gov.br/estatisticas/economicas/contas-nacionais.html Accessed May 9, 2024.\u003c/li\u003e\n\u003cli\u003eOliveira NR de C. Redes de Aten\u0026ccedil;\u0026atilde;o \u0026agrave; Sa\u0026uacute;de: a aten\u0026ccedil;\u0026atilde;o \u0026agrave; sa\u0026uacute;de organizada em redes. S\u0026atilde;o Lu\u0026iacute;s: EDUFMA; 2016. Available from: http://www.unasus.ufma.br/site/files/livros_isbn/isbn_redes01.pdf\u003c/li\u003e\n\u003cli\u003eBrasil. Lei no 10.741, de 1\u0026ordm; de outubro de 2003. Disp\u0026otilde;e sobre o estatuto do idoso e d\u0026aacute; outras provid\u0026ecirc;ncias. Di\u0026aacute;rio Oficial da Uni\u0026atilde;o. Bras\u0026iacute;lia; 2003 Oct 1.\u003c/li\u003e\n\u003cli\u003eDepartamento de Inform\u0026aacute;tica do Sistema \u0026Uacute;nico de Sa\u0026uacute;de do Brasil. DATASUS. Bras\u0026iacute;lia: Minist\u0026eacute;rio da Sa\u0026uacute;de; 2014. Available from: https://datasus.saude.gov.br/informacoes-de-saude-tabnet/\u003c/li\u003e\n\u003cli\u003eMathew A, George PS, Ramadas K, Mathew BS, Kumar A, Roshni S, et al. Sociodemographic Factors and Stage of Cancer at Diagnosis: A Population-Based Study in South India. \u003cem\u003eJ Glob Oncol\u003c/em\u003e. 2019 Jul;5:1\u0026ndash;10.\u003c/li\u003e\n\u003cli\u003eKhurshied S, Shahid Z, Wazir T, Ullah I, Sagheer S, Khurshid N, et al. Delay in the Diagnosis of Patients With Head and Neck Cancer: Impact of Different Patient- and Healthcare Provider-Related Factors. \u003cem\u003eCureus\u003c/em\u003e. 2024;16(9):e68528. https://doi.org/10.7759/cureus.68528\u003c/li\u003e\n\u003cli\u003eSpeight PM, Epstein J, Kujan O, Lingen MW, Nagao T, Ranganathan K, et al. Screening for oral cancer\u0026mdash;a perspective from the Global Oral Cancer Forum. \u003cem\u003eOral Surg Oral Med Oral Pathol Oral Radiol\u003c/em\u003e. 2017;123(6):680\u0026ndash;687. https://doi.org/10.1016/j.oooo.2016.08.021\u003c/li\u003e\n\u003cli\u003eFDI World Dental Federation. Access to oral healthcare for vulnerable and underserved populations. \u003cem\u003eInt Dent J\u003c/em\u003e. 2020;70(1):15\u0026ndash;16. https://doi.org/10.1111/idj.12556\u003c/li\u003e\n\u003cli\u003eWarnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. \u003cem\u003eOral Oncol\u003c/em\u003e. 2009;45(4\u0026ndash;5):309\u0026ndash;316. https://doi.org/10.1016/j.oraloncology.2008.06.002\u003c/li\u003e\n\u003cli\u003eRubin G, Berendsen A, Crawford SM, Dommett R. The expanding role of primary care in cancer control. \u003cem\u003eLancet Oncol\u003c/em\u003e. 2015;16(12):1231\u0026ndash;1272. https://doi.org/10.1016/S1470-2045(15)00205-3\u003c/li\u003e\n\u003cli\u003eChen S, Lin Z, Chen J, Yang A, Zhang Q, Xie C, et al. Older age is a risk factor associated with poor prognosis of patients with squamous cell carcinoma of the oral cavity. \u003cem\u003eEur Arch Otorhinolaryngol\u003c/em\u003e. 2020;277(9):2573\u0026ndash;2580. https://doi.org/10.1007/s00405-020-05963-3\u003c/li\u003e\n\u003cli\u003eCohen Goldemberg D, de Ara\u0026uacute;jo LHL, Antunes HS, de Melo AC, Santos Thuler LC. Tongue cancer epidemiology in Brazil: incidence, morbidity and mortality. \u003cem\u003eHead Neck\u003c/em\u003e. 2018;40(8):1834\u0026ndash;1844. https://doi.org/10.1002/hed.25166\u003c/li\u003e\n\u003cli\u003eChieko M, Uzawa N, Kayamori K, Sonoda I. Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas. \u003cem\u003eOral Oncol\u003c/em\u003e. 2012;48(4):320\u0026ndash;34. https://doi.org/10.1016/j.oraloncology.2011.11.014\u003c/li\u003e\n\u003cli\u003ePNUD Brasil, IPEA. Desenvolvimento humano nas macrorregi\u0026otilde;es brasileiras [Internet]. Bras\u0026iacute;lia: PNUD; 2016. Available from: https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/desenvolvimento-humano-nas-macrorregioesbrasileiras/ Accessed May 29,2025.\u003c/li\u003e\n\u003cli\u003eKassirian S, Dzioba A, Hamel S, Patel K, Sahovaler A. Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay. \u003cem\u003eCurr Oncol\u003c/em\u003e. 2020;27(5):e467\u0026ndash;e477. https://doi.org/10.3747/co.27.6547\u003c/li\u003e\n\u003cli\u003eLouredo BVR, Vargas PA, P\u0026eacute;rez-De-Oliveira ME, Lopes MA, Kowalski LP, Curado MP. Epidemiology and survival outcomes of lip, oral cavity, and oropharyngeal squamous cell carcinoma in a southeast Brazilian population. Med Oral Patol Oral Cir Bucal. 2022;27(3):e274\u0026ndash;e284. https://doi.org/10.4317/medoral.25147\u003c/li\u003e\n\u003cli\u003ePereira NEB, De Oliveira DCDRR, Santos MB, Santos PL Dos, Tavares DDS. Association of Socioeconomic Status and Oral Cancer Mortality in Brazil: Temporal Trends and Spatial Distribution. \u003cem\u003eMed Princ Pract\u003c/em\u003e. 2023;32(1):40\u0026ndash;48. https://doi.org/10.1159/000529155\u003c/li\u003e\n\u003cli\u003eBrasil. Human Development Index in each Federative Unit of Brazil. IBGE - Instituto Brasileiro de Geografia e Estat\u0026iacute;stica; 2020. Available from: https://cidades.ibge.gov.br/brasil/pesquisa/37/30255 Accessed Mar 9, 2024.\u003c/li\u003e\n\u003cli\u003eAra\u0026uacute;jo IM, Borges MVC, Santos LGS, Rocha JR, Pereira \u0026Eacute;M, Rodrigues VP. Impact of the COVID-19 Pandemic on Delay in Treatment Initiation for Oral Cavity and Oropharyngeal Cancer in Brazil. \u003cem\u003ePesq Bras Odontop Clin Integr\u003c/em\u003e. 2025;25:e240036. https://doi.org/10.1590/pboci.2025.020\u003c/li\u003e\n\u003cli\u003eTeixeira RA, Naghavi M, Guimar\u0026atilde;es MDC, Ishitani LH, Fran\u0026ccedil;a EB. Quality of cause-of-death data in Brazil: Garbage codes among registered deaths in 2000 and 2015. \u003cem\u003eRev Bras Epidemiol\u003c/em\u003e. 2019;22:E190002.supl.3. https://doi.org/10.1590/1980-549720190002.supl.3\u003c/li\u003e\n\u003cli\u003eCunha AR da, Bigoni A, Antunes JLF, Hugo FN. Impact of redistributing deaths by ill-defined causes in oral and oropharyngeal cancer mortality in Brazil. Braz Oral Res. 2022;36:e117. https://doi.org/10.1590/1807-3107bor-2022.vol36.0117\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Mouth Neoplasm, Neoplasm Staging, Spatio-Temporal Analysis, Cluster Analysis, Brazil","lastPublishedDoi":"10.21203/rs.3.rs-9181918/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9181918/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo analyze the spatiotemporal proportion of advanced cases (III and IV) of oral cancer (OC) in Brazil.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAn ecological observational study was conducted using secondary data from Brazil collected from 2018 to 2023. The units of analysis were health regions, geopolitical macroregions, and Brazil. The indicator of interest was the proportion of advanced cases (III and IV) of OC. The statistical analysis was performed in four stages: (1) choropleth maps, (2) Moran\u0026rsquo;s I (global) and local (LISA), considering only 2018 and 2023; (3) space\u0026ndash;time cube; and (4) Prais\u0026ndash;Winsten, spanning from 2018 to 2023. A significance level of 5% was adopted for all analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn 2018, 34.9% of Brazilian health regions had\u0026thinsp;\u0026ge;\u0026thinsp;75% OC cases diagnosed in advanced stages, and in 2023, this proportion was 57.7%. In both years, advanced-stage OC was more prevalent in men and in the tongue. In 2018, high\u0026ndash;high clusters were observed in the southeast, midwest, and northeast regions; and in 2023, a slight change occurred, with high\u0026ndash;high clusters in the same regions and in the north. Distinct spatial patterns were observed, with clusters showing a reduction in the proportion of advanced cases in the northeast, southeast, and south regions and clusters showing an increase in specific areas of the north, northeast, southeast, and south. In the temporal trend analysis by macroregion, the northeast showed a decreasing trend, whereas the southeast showed an increasing trend in the proportion of advanced diagnoses of OC.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFrom 2018 to 2023, Brazil presented an alarming scenario of advanced diagnosis of OC in many health regions, constituting a serious public health problem. This trend was more noticeable in men and tongue region and varied geographically, with evident clusters of increase, particularly in the northeast and southeast.\u003c/p\u003e","manuscriptTitle":"Spatiotemporal patterns and trends in the proportion of advanced oral cancer at diagnosis in Brazil, 2018–2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 06:52:06","doi":"10.21203/rs.3.rs-9181918/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"22148918034304619391691074952114865059","date":"2026-05-04T12:00:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"159929392046896763059982138751531919241","date":"2026-04-23T14:33:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189099158436134667884294957437443628641","date":"2026-04-21T15:34:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-21T14:31:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-04T17:05:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-27T09:36:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-26T22:36:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Public Health","date":"2026-03-26T22:31:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cef2d4f6-c737-4547-813a-6b6ba23e3943","owner":[],"postedDate":"May 4th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"22148918034304619391691074952114865059","date":"2026-05-04T12:00:25+00:00","index":70,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T06:52:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-04 06:52:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9181918","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9181918","identity":"rs-9181918","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}