Malignant salivary gland tumors in Brazil: epidemiology, treatment patterns, and survival outcomes in public Brazilian population

Introduction

Salivary gland carcinomas (SGC) comprise a group of rare malignant neoplasms characterized by diverse histology and heterogeneous biological behavior arising from the parotid, submandibular, sublingual, or minor salivary glands (1). In the United States, SGCs represent 5% of all head and neck cancers (2). According to Globocan Observatory, in 2020, there were 53,583 new cases of salivary gland cancer globally, with a higher incidence rate in countries with a very high human development index (HDI) (3). There were 22,778 deaths, with a higher number of deaths observed in countries with a moderate HDI. The most recent World Health Organization (WHO) classification of SGCs is the fifth edition, published in 2022 (4). Major changes include the integration of molecular data, such as recurrent gene fusions and mutations, for diagnostic purposes; the introduction of a grading system for specific tumor types like mucoepidermoid carcinoma and adenoid cystic carcinoma, and the addition of new entities. The classification now defines over 20 histotypes, some of which are now characterized by their specific genomic alterations, enabling better diagnosis, identification of prognostic factors, and potential targets for personalized therapies.

Real-world evidence has become an important tool for generating insights into clinical practice and outcomes, particularly for cancer patients treated outside of clinical trials. Such data can be obtained from multiple sources, including electronic health records, claims and billing databases, and disease registries. The resulting information have even been used to support regulatory drug approvals, especially in the case of orphan indications (5). This data is especially valuable for uncommon diseases, such as SGCs with their heterogeneous and rare subtypes. In this setting, single-institution cohorts may lack sufficient power to yield meaningful conclusions, whereas nationwide databases can provide more robust information (6).

Despite their clinical relevance, SGC evidence from low- and middle-income countries remain limited, particularly regarding epidemiological distribution, treatment patterns, and survival outcomes. In Brazil, the availability of robust cancer registries at both the national and state levels offers a unique opportunity to generate comprehensive evidence on these tumors. Such information is essential to identify disparities in access to care, better understand prognostic patterns, and guide health policies in oncology. In this context, our study aims to describe the epidemiological profile, treatment strategies, survival outcomes, and prognostic factors of malignant salivary gland tumors in Brazil using real-world data. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-553/rc).

Methods

This study uses secondary data from two publicly available complementary sources. A cross-sectional national-level dataset obtained from the Brazilian Hospital Cancer Registry Integrator (Integrador RHC) describes epidemiological aspects, while a retrospective longitudinal study was performed to assess overall survival (OS) using data from the São Paulo State Cancer Registry [Fundação Oncocentro de São Paulo (FOSP)]. Therefore, approval from an Ethics Committee was not required. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

All patients diagnosed with malignant salivary gland neoplasms between 2005 and 2018 recorded in the database of the Integrador RHC as of July 10, 2023, were eligible for the epidemiological study. The Integrador RHC is an online platform created by the Brazilian National Cancer Institute [Instituto Nacional do Câncer (INCA)] that centralizes and makes publicly available the data submitted by hospitals across the country. The submission and regular updating of information in this platform are mandatory for hospitals officially accredited in Specialized Oncology Care within the Brazilian public health system [Sistema Único de Saúde (SUS)], whereas participation is optional for institutions that do not meet this requirement. Hospital-based cancer registries in Brazil have a well-established legal framework since 1993, following Ministry of Health Ordinance No. 171, which defined their implementation as necessary to improve the quality of hospital information (7). A limitation of the Integrador RHC is the absence of follow-up data, which precludes survival analyses. However, the RHC in São Paulo, the most populous state in Brazil, maintains a parallel platform that includes follow-up data that is actively carried out by participating hospitals. Therefore, for survival analyses, we used FOSP data extracted from its homepage (8) on March 2, 2025.

All patients with a diagnosis classified under International Classification of Diseases (ICD) codes C07 (malignant neoplasm of parotid gland) or C08 (malignant neoplasm of other and unspecified major salivary glands) between 2005 and 2018 were included, provided they were aged between 18 and 99 years at diagnosis. Specifically, C08 subcategories comprised C08.0 (submandibular gland), C08.1 (sublingual gland), C08.8 (overlapping lesion of major salivary glands), and C08.9 (major salivary gland, unspecified). Histological types were grouped into five main categories: acinic cell carcinoma, “adeno-ductal carcinomas” [including salivary duct carcinoma, adenocarcinoma not otherwise specified (NOS), and other high-grade adenocarcinomas], “biphasic tumors” (comprised adenoid cystic carcinoma, myoepithelial carcinoma, and related biphasic neoplasms characterized by dual epithelial-myoepithelial differentiation), mucoepidermoid carcinomas, and NOS. Cases with morphology codes corresponding to squamous cell carcinoma were excluded, to avoid inclusion of tumors of likely cutaneous or mucosal origin. Histological classification was based on morphology codes recorded in the registry at the time of diagnosis. No retrospective reclassification according to the 2022 WHO classification was performed. Finally, clinical stage at diagnosis was recorded according to the tumor-node-metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC), 7th edition, consistent with the registry period analyzed [2005–2018].

Statistical analysis

Cohorts were described using absolute and relative frequencies, and age was summarized by mean, standard deviation (SD) and age categories. Missing data were described at the descriptive tables. For patients with available OS data, the Kaplan-Meier method was applied to estimate median survival and 2- and 5-year OS rates, while the median follow-up time was calculated using the reverse Kaplan-Meier method.

Cox regression models, including interaction terms, were used to assess the association between potential prognostic factors (age, sex, clinical stage—AJCC 7th ed., histology, level of education, and health coverage) and OS, considering a maximum follow-up time of five years. Age was categorized into clinically meaningful groups (<50, 50–64, and ≥65 years) to facilitate clinical interpretability and reflect commonly adopted epidemiological thresholds in oncologic research. A forward stepwise selection method was applied to build the multivariable regression model, based on statistical significance criteria. A forward selection strategy was used to obtain a parsimonious model, considering clinical relevance and statistical stability, particularly given the relatively small size of certain histological subgroups. The proportional hazards assumption was verified through visual inspection of log-log survival plots. Sensitivity analyses were performed by excluding cases with missing values in key covariates to assess the robustness of the results. All statistical analyses were performed using R software, and a two-sided significance level of 5% (P<0.05) was considered.

Results

After applying the eligibility criteria, the national Brazilian cohort comprised 4,283 patients diagnosed with malignant salivary gland tumors between 2005 and 2018. In parallel, the São Paulo State cohort included 1,238 patients within the same period. The detailed case selection process, including exclusions and histological grouping, is presented in Figure 1.

Figure 1 Flowchart of case selection for patients with malignant salivary gland tumors included in the study. The national cohort was obtained from the Brazilian Hospital Cancer Registry Integrator (Integrador RHC), and the state cohort was retrieved from the São Paulo State Cancer Registry (FOSP). Reasons for exclusion are detailed at each step. FOSP, Fundação Oncocentro de São Paulo; NOS, not otherwise specified.

Patient characteristics—national Brazilian cohort (Integrador RHC)

The mean age at diagnosis was 57 years (SD 16.5), with most patients between 50 and 64 years (33.3%) and a slight male predominance (51%). Regarding educational level, nearly three-quarters of patients (71.9%) had eight years of schooling or less. In terms of marital status, 57.4% were married or in a union, whereas 25.5% were single.

The parotid gland was the most common primary site (74.9%), followed by the submandibular gland (14.4%). Histological subtypes were distributed as follows: acinic cell carcinoma (7.0%), adenocarcinomas/ductal carcinomas (23.5%), biphasic tumors (21.2%), mucoepidermoid carcinoma (20.4%), and NOS (27.9%). Clinical staging information was frequently missing, but among patients with available data, 39.9% were diagnosed with early-stage disease (I–II) and 32.8% with stage IVA–IVB.

Treatment patterns varied, with surgery alone (33.9%) being the most frequent modality, followed by surgery combined with radiotherapy (23.6%). Radiotherapy alone accounted for 14.2% of cases, while chemotherapy, immunotherapy, or androgen deprivation therapy were used in a minority of patients. Table 1 provides a complete summary of sociodemographic, clinical, and treatment-related characteristics for the national cohort.

Patient characteristics—São Paulo State cohort (FOSP)

The mean age at diagnosis was 57.3 years (SD 16.6), with 31.9% aged <50 years, 31.3% aged 50–64 years, and 36.8% aged ≥65 years. The sex distribution was balanced, with 49.2% male. Educational attainment was low in most patients, as two-thirds (66.7%) had completed eight years of schooling or less.

The parotid gland was also the most frequent primary site (73.8%), followed by the submandibular gland (14.1%) and other major glands NOS (10.7%). The sublingual gland was rarely affected (1.4%). Histological distribution was: acinic cell carcinoma (6.4%), adenocarcinomas/ductal carcinomas (21.7%), biphasic tumors (23.3%), mucoepidermoid carcinoma (23.1%), and NOS (25.5%). Clinical stage at presentation was available for most patients: 40.9% had early-stage disease (I–II), 20.6% were stage III, 29.1% were diagnosed with advanced-stage disease (IVA–IVB) and 5.7% had metastatic disease.

Regarding treatment, surgery alone (34.3%) was the most common modality, followed by surgery combined with radiotherapy (26.8%). Multimodal strategies including chemotherapy, hormonal therapy, or even immunotherapy were used less frequently, while 6.2% of patients did not receive treatment. Table 2 presents detailed baseline characteristics, treatment patterns, and clinical stage distribution for the FOSP cohort.

OS (FOSP cohort)

The median follow-up time for the entire cohort was 8.41 years [95% confidence interval (CI): 8.05–8.88]. When stratified by histological subtype, the median follow-up was 6.71 years (95% CI: 5.48–8.46) for acinic cell carcinoma, 9.05 years (95% CI: 8.14–9.88) for adenocarcinomas/ductal carcinomas, 8.34 years (95% CI: 7.79–9.45) for biphasic tumors, 9.92 years (95% CI: 8.88–12.36) for tumors NOS, and 7.79 years (95% CI: 7.25–8.64) for mucoepidermoid carcinoma. Kaplan-Meier survival curves demonstrated significant differences in OS among histological subtypes (P<0.0001) (Figure 2).

Figure 2 Kaplan-Meier OS curves according to histological subtype of malignant salivary gland tumors in the São Paulo State Cancer Registry (FOSP, 2005–2018). Significant differences in survival were observed across histological groups (P<0.0001). For the period 2005–2018, 1-year and 5-year OS rates were as follows: acinic cell carcinoma, 100% and 88% (95% CI: 81–96%); adeno/ductal carcinoma, 81% (95% CI: 76–86%) and 51% (95% CI: 45–57%); biphasic tumors, 93% (95% CI: 90–96%) and 65% (95% CI: 59–71%); mucoepidermoid carcinoma, 86% (95% CI: 81–90%) and 66% (95% CI: 61–72%); and NOS, 71% (95% CI: 66–76%) and 35% (95% CI: 30–41%). CI, confidence interval; FOSP, Fundação Oncocentro de São Paulo; NOS, not otherwise specified; OS, overall survival.

Prognostic factors (FOSP cohort)

In the univariable Cox regression, several factors were significantly associated with OS, including histological subtype, age at diagnosis, sex, educational level, clinical stage, type of healthcare coverage, and year of diagnosis.

When adjusted in multivariable models (Table 3), histology remained a strong prognostic determinant: tumors NOS had the highest risk of death from any cause [adjusted hazard ratio (HRa) =3.15; 95% CI: 1.53–6.46], followed by adenocarcinomas/ductal carcinomas (HRa =2.58; 95% CI: 1.25–5.34), mucoepidermoid carcinomas (HRa =2.29; 95% CI: 1.11–4.76), and biphasic tumors (HRa =2.10; 95% CI: 1.01–4.37), compared with acinic cell carcinoma (reference group).

Older age was independently associated with worse outcomes: patients aged 65–96 years had more than a threefold (HRa =3.19; 95% CI: 2.42–4.20) and those aged 50–64 years had more than a twofold (HRa =2.03; 95% CI: 1.52–2.71) increased risk of death compared with those younger than 50 years. Male sex (HRa =1.27; 95% CI: 1.05–1.53) was also an adverse prognostic factor.

Clinical stage at diagnosis strongly impacted survival: stage IV–C tumors carried the worst prognosis (HRa =8.45; 95% CI: 6.22–11.47), followed by stage IVA–IVB (HRa =4.14; 95% CI: 3.20–5.36), and stage III (HRa =1.73; 95% CI: 1.27–2.36), compared with early-stage disease (I–II).

Low educational level and treatment costs covered by the public healthcare system, which were significantly associated with higher risk of death in the univariable models, were not significant in the multivariable model. Finally, cases diagnosed in 2005–2012 had worse prognosis compared with those diagnosed in 2013–2018 (HRa =1.30; 95% CI: 1.08–1.55).

Discussion

We present comprehensive epidemiological evidence from an upper-middle-income country with a large and diverse population, where reliable data on these rare neoplasms have been extremely limited. By analyzing over 4,000 cases nationwide and more than 1,200 with long-term follow-up in São Paulo, we were able to identify substantial variability in OS across histological subtypes, with acinic cell carcinoma showing the most favorable prognosis and tumors NOS the worst. This represents the largest population-based evaluation of SGC in Latin America to date, thereby filling a critical gap in global oncology literature. Importantly, we also observed that social determinants, such as educational level and type of health coverage, were associated with survival in univariable analyses, although they did not remain significant after multivariable adjustment, while well-established prognostic factors such as age, sex, stage, and histology retained their strong influence on outcomes.

International studies consistently show that malignant salivary gland tumors are rare, accounting for less than 5% of all head and neck cancers, with an estimated incidence of 0.4–2.6 cases per 100,000 population (9). Large multicenter cohorts confirm that the parotid gland is the most frequent primary site, while submandibular and sublingual glands have a higher proportion of malignancy compared with parotid tumors (10,11). Globally, the most common histological subtypes are mucoepidermoid carcinoma and adenoid cystic carcinoma, although their relative frequencies vary across regions (12). The age distribution typically peaks between the fifth and seventh decades, and a slight female predominance has been reported in some series (10). Our Brazilian population-based data align with several of these international observations, particularly regarding the predominance of parotid tumors and the relevance of mucoepidermoid, adenoid cystic, and acinic cell carcinomas. However, the relative distribution of histologies differed from global averages, and the absolute case volume was considerably higher, reflecting both Brazil’s large population and the comprehensive capture of national registries. These findings underscore the importance of incorporating data from upper-middle-income countries, which remain underrepresented in the global epidemiological literature on salivary gland cancers.

Within Brazil, our population-based analysis complements and extends patterns reported in multicenter, pathology-based series. de Silva et al. (13) evaluated a multicenter pathology series, over a 20-year period, comprising 2,292 cases, and identified that parotid tumors predominate and mucoepidermoid carcinoma emerged as the leading malignant subtype—trends also confirmed in our study. By relying on registry-based data rather than pathology reports alone, our study captured a broader care spectrum and enabled survival analyses by histologic grouping, enhancing external validity.

At the national level, Cohen Goldemberg et al. (14) integrated a population-based incidence registry with another hospital morbidity/mortality database and likewise demonstrated that the parotid was the most frequent major site and that advanced stage at presentation was common. Our findings align with these national observations while adding granularity: we quantify OS across grouped histologies and document wide survival variability by subtype. Taken together, both studies provide a coherent epidemiological profile—incidence concentrated in older adults, parotid predominance, and substantial stage IV burden—while our study uniquely contributes survival estimates adjusted for demographic, clinical, and socioeconomic variables. It is important to note that, in contrast to some population-based series, cases of squamous cell carcinoma were deliberately excluded from our analysis, as these tumors are generally considered to arise from cutaneous or mucosal epithelium (metastasis) rather than true salivary gland origin. Differences in inclusion criteria across studies may partially account for variations in histological distribution and survival estimates reported in the literature.

Compared with single-institution and regional series (15-18), our findings corroborate the demographic profile typically reported in the Brazilian literature, with a peak incidence in middle-to-older age groups and predominance of parotid gland tumors. Histologically, the recurrent prominence of mucoepidermoid and adenoid cystic carcinomas in these studies is also consistent with our results. However, the scope and analytical depth of our investigation differ substantially. While institutional and pathology-based studies provide valuable insight into clinical presentation and histological diversity, they are inherently constrained by limited representativeness. In contrast, our population-based cohorts derived from the national database and the state-level FOSP registry encompass a wider spectrum of patients, enabling standardized survival estimates and robust multivariable analyses. Within this framework, age, sex, stage, and histology emerged as independent prognostic factors, thereby offering a more comprehensive and externally valid perspective on salivary gland cancers in Brazil. Prognostic determinants of SGC have been consistently reported across large cohorts and population-based studies, with advanced age, male sex, histological subtype, and stage at diagnosis emerging as robust predictors of survival (9,11,19). Our findings are in line with these reports: in our multivariable analysis, older patients (particularly those over 65 years), men, and those presenting with stage III–IV disease had markedly worse survival outcomes, while acinic cell carcinoma carried a significantly more favorable prognosis compared to other histologies. Similar results have been observed in international series, including SEER-based studies of submandibular gland cancers, which demonstrated that advanced stage and high-grade histologies were strongly correlated with poorer survival (11). Moreover, systematic reviews focusing on adenoid cystic carcinoma confirm the long-term detrimental impact of advanced stage and tumor site on outcomes, reinforcing the clinical significance of these well-established prognostic markers (20). Taken together, these data highlight the consistency of prognostic factors across populations, while our study contributes by confirming their relevance in the largest Brazilian cohort to date.

While socioeconomic and healthcare-related variables such as education and public versus private coverage were significant in univariable models, they did not retain independent prognostic value in multivariable analysis. This contrasts with studies in other oncologic contexts that highlight structural inequities as powerful determinants of outcome but is consistent with the broader salivary gland cancer literature, in which such variables are rarely explored or are absent altogether (20). Although some reports from low- and middle-income settings have described socioeconomic or access-related variables in salivary gland tumor cohorts (21), their incorporation into multivariable survival prognostic models remains uncommon. In this context, our registry-based analysis adds population-level evidence by evaluating education and health coverage alongside established clinical predictors.

Given the rarity and heterogeneity of SGC, a nuanced approach to treatment planning is crucial. The observed differences in survival rates among subtypes, particularly the more favorable prognosis for acinic cell carcinoma versus the poorer outcomes for ‘NOS’ tumors, underscore the need for histology-driven treatment protocols. This is especially pertinent in a resource-constrained environment where optimizing treatment efficacy and minimizing unnecessary interventions are paramount. Future research should focus on developing and validating risk stratification models tailored to the Brazilian population, which can guide clinicians in selecting appropriate treatment intensities, from conservative management to aggressive multimodal therapies.

This study has several limitations that should be acknowledged. First, the use of secondary registry data may lead to underreporting and incomplete information, particularly regarding staging and treatment variables in the national dataset. Second, survival analyses were only possible using the São Paulo State Cancer Registry (FOSP), which may not fully reflect outcomes across the entire country, although it covers the most populous Brazilian state. Third, the heterogeneous grouping of rare histological subtypes into broad categories, including the NOS group, may have obscured more granular prognostic differences. This grouping strategy was necessary due to registry coding structure and the relatively small number of certain individual histological subtypes. However, it may limit direct comparability with studies reporting outcomes for specific entities analyzed separately. In addition, some tumors that were not true salivary gland neoplasms—such as metastatic lesions or other malignancies misclassified within this category—may have been erroneously included under the NOS group. Fourth, the databases analyzed did not include immunohistochemistry or molecular profiling data, which are increasingly relevant for accurate diagnosis and for guiding treatment decisions in line with contemporary precision oncology approaches. Finally, the study design does not allow for patient-level causal inference, and potential confounders not captured in the registries could influence the associations observed. In particular, treatment patterns were described descriptively, as therapeutic decisions are strongly influenced by tumor stage, histological subtype, and clinical factors not fully captured in the registry. Therefore, comparative analyses of treatment modalities and survival outcomes would be highly susceptible to confounding by indication and were beyond the scope of this study. Although statistical significance was assessed using P values, interpretation of the findings was primarily guided by the magnitude and precision of the hazard ratios (HRs), as reflected by their 95% CIs, emphasizing clinical relevance rather than statistical thresholds alone.

Despite these limitations, this study provides robust population-based evidence on malignant salivary gland tumors in Brazil, encompassing more than 4,000 patients across national and state registries. We demonstrated substantial variation in survival according to histological subtype. Associations between social and healthcare inequities and survival were observed in univariable analyses, although they were not retained as independent prognostic factors in multivariable models. These findings underscore the need for strengthening cancer registration, improving access to specialized care, and further investigating the role of social determinants in larger prospective datasets. Future studies integrating molecular profiling and prospective clinical data may refine prognostic models and guide personalized therapeutic strategies. In parallel, collaborative efforts to expand high-quality cancer registries in low- and middle-income countries will be essential to inform equitable cancer control policies worldwide.

On the other hand, our findings provide robust, population-based evidence that can directly inform national oncology policies coordinated by SUS and INCA. The identification of substantial variations in survival by histological subtype and the persistence of social disparities in access to diagnosis and treatment validate the urgent need for equitable resource allocation and the strengthening of regional cancer registries. Integrating such epidemiological data into national cancer control strategies can support evidence-based planning, optimize referral pathways for salivary gland tumors, and guide the implementation of standardized diagnostic and treatment protocols within the Brazilian public health system.

While our study reinforces the importance of traditional prognostic factors, the evolving landscape of salivary gland carcinoma management increasingly relies on molecular insights, such as TRK fusions and HER2 amplification, which can guide the use of targeted therapies (22). In a country like Brazil, where access to advanced diagnostic and therapeutic modalities may vary, integrating molecular profiling into routine clinical practice presents both challenges and opportunities. Future efforts should aim to establish centralized molecular testing facilities or collaborative networks to ensure equitable access to these crucial diagnostic tools. Furthermore, research initiatives should focus on characterizing the molecular landscape of SGC in the Brazilian population, which may reveal unique genetic alterations or prevalence patterns relevant to local treatment strategies. This integration of precision oncology approaches, while challenging, holds the potential to significantly improve outcomes by enabling more tailored and effective treatments, moving beyond broad histological classifications towards a truly personalized medicine paradigm for Brazilian patients.

Conclusions

In summary, this nationwide analysis provides the most comprehensive characterization of malignant SGC in Brazil to date, encompassing more than 4,000 patients and offering robust survival estimates across histological subtypes. Our findings reaffirm the prognostic significance of age, sex, stage, and histology, while underscoring the need for improved data granularity to clarify the contribution of social determinants. By demonstrating marked variability in survival among histological groups, this study emphasizes the necessity of histology-driven management strategies and the development of tailored risk stratification models in upper-middle-income countries. Looking forward, the integration of molecular profiling with population-based evidence holds the potential to transform care delivery, advancing precision oncology and informing equitable cancer control policies in Brazil and beyond.

Acknowledgments

The authors are grateful to Cintia Kurokawa La Scala de Oliveira, from Roche Pharmaceuticals, by her support to conclude this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-553/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-553/prf

Funding: This research was funded by Roche Pharmaceuticals. The funder had no role in the design of the study, data collection, analysis, interpretation, or in the decision to submit the manuscript for publication.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-553/coif). A.L.F.C. reported that Roche funded statistical analysis support and publication-related expenses for this manuscript through direct payments to service providers. A.L.F.C. also received speaker honoraria from MSD, Knight, and Dr. Reddy’s, travel support from MSD and Dr. Reddy’s, and served on advisory boards for MSD, Knight, Dr. Reddy’s, and Danone. L.L.M. received honoraria for lectures from MSD. G.d.C.J. served as a local institutional principal investigator for an AstraZeneca-sponsored clinical trial. L.T.M. received personal payments for lectures from Merck Sharp Dohme and Merck Serono. L.T.M. also served as the unpaid coordinator of the Educational Committee of the Brazilian Head and Neck Cancer Group (GBCP), as an unpaid member of the Head and Neck Tumors Committee of the Brazilian Society of Clinical Oncology (SBOC), and reported holding stocks in Thermo Fisher Scientific, Bristol Meyers Squibb, and Pfizer. W.N.W.Jr. received support for statistical analysis from Roche and received honoraria for lectures or presentations from Roche, AstraZeneca, BMS, Pfizer, Janssen, Daiichi Sankyo, Sanofi, Takeda, Knight, and Merck. W.N.W.Jr. also received travel and meeting support from Dr. Reddy’s, Merck, Pfizer, and Roche. The other authors have no conflicts of interest to declare.

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

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

References

1. Speight PM, Barrett AW. Salivary gland tumours. Oral Dis 2002;8:229-40. [Crossref] [PubMed]
2. Carvalho AL, Nishimoto IN, Califano JA, et al. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005;114:806-16. [Crossref] [PubMed]
3. IARC. Global Cancer Observatory: Salivary Glands. World Health Organization; 2022. Available online: https://gco.iarc.who.int/media/globocan/factsheets/cancers/2-salivary-glands-fact-sheet.pdf
4. Skálová A, Hyrcza MD, Leivo I. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Salivary Glands. Head Neck Pathol 2022;16:40-53.
5. Feinberg BA, Gajra A, Zettler ME, et al. Use of Real-World Evidence to Support FDA Approval of Oncology Drugs. Value Health 2020;23:1358-65. [Crossref] [PubMed]
6. Karanatsios B, Prang KH, Verbunt E, et al. Defining key design elements of registry-based randomised controlled trials: a scoping review. Trials 2020;21:552. [Crossref] [PubMed]
7. INCA. Brasil, Ministério da Saúde. Instituto Nacional do Câncer-Registros hospitalares de câncer: planejamento e gestão. 2nd ed. Rio de Janeiro: INCA; 2010.
8. FOSP. Fundação Oncocentro de São Paulo. 2025. Available online: https://fosp.saude.sp.gov.br
9. Li Y, Hu C. Clinicopathological features and outcomes of major salivary gland mucoepidermoid carcinoma: do they vary in different age groups. Transl Cancer Res 2020;9:6691-9. [Crossref] [PubMed]
10. Alsanie I, Rajab S, Cottom H, et al. Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study. Head Neck Pathol 2022;16:1043-54. [Crossref] [PubMed]
11. Lee RJ, Tan AP, Tong EL, et al. Epidemiology, Prognostic Factors, and Treatment of Malignant Submandibular Gland Tumors: A Population-Based Cohort Analysis. JAMA Otolaryngol Head Neck Surg 2015;141:905-12. [Crossref] [PubMed]
12. Poletto AG, Mello FW, Melo G, et al. Prevalence of mucoepidermoid carcinoma among intraoral minor salivary gland tumors: A systematic review and meta-analysis. J Oral Pathol Med 2020;49:720-6. [Crossref] [PubMed]
13. da Silva LP, Serpa MS, Viveiros SK, et al. Salivary gland tumors in a Brazilian population: A 20-year retrospective and multicentric study of 2292 cases. J Craniomaxillofac Surg 2018;46:2227-33. [Crossref] [PubMed]
14. Cohen Goldemberg D, Alves LDB, Antunes HS, et al. Epidemiology of major salivary gland cancer in Brazil: Incidence, morbidity, and mortality. Oral Dis 2023;29:707-13. [Crossref] [PubMed]
15. de Oliveira FA, Duarte EC, Taveira CT, et al. Salivary gland tumor: a review of 599 cases in a Brazilian population. Head Neck Pathol 2009;3:271-5. [Crossref] [PubMed]
16. Fonseca FP, Carvalho Mde V, de Almeida OP, et al. Clinicopathologic analysis of 493 cases of salivary gland tumors in a Southern Brazilian population. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:230-9. [Crossref] [PubMed]
17. Ito FA, Ito K, Vargas PA, et al. Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. Int J Oral Maxillofac Surg 2005;34:533-6. [Crossref] [PubMed]
18. Vasconcelos AC, Nör F, Meurer L, et al. Clinicopathological analysis of salivary gland tumors over a 15-year period. Braz Oral Res 2016;30:S1806-83242016000100208. [Crossref] [PubMed]
19. He J, Zhao F, Li J, et al. Development and validation of prognostic prediction model for submandibular gland cancer based on the SEER database. Braz J Otorhinolaryngol 2025;91:101654. [Crossref] [PubMed]
20. Li N, Xu L, Zhao H, et al. A comparison of the demographics, clinical features, and survival of patients with adenoid cystic carcinoma of major and minor salivary glands versus less common sites within the Surveillance, Epidemiology, and End Results registry. Cancer 2012;118:3945-53. [Crossref] [PubMed]
21. Akpeh JO, Okechi UC, Ezeanolue BC. Primary minor salivary gland tumors: A retrospective review of cases seen in a tertiary institution in South East Nigeria. Niger J Clin Pract 2022;25:368-72. [Crossref] [PubMed]
22. Broseghini E, Carosi F, Berti M, et al. Salivary Gland Cancers in the Era of Molecular Analysis: The Role of Tissue and Liquid Biomarkers. Cancers (Basel) 2025;17:660. [Crossref] [PubMed]