Background/Objectives: Oral cancers in patients with proliferative verrucous leukoplakia (PVL-OSCC) exhibit different clinical and prognostic outcomes from those seen in conventional oral squamous cell carcinomas (cOSSCs). The aim of the present study is to compare the genome-wide DNA methylation signatures in fresh frozen tissues between oral squamous cell carcinomas in patients with PVL and cOSCC using the Illumina Infinium MethylationEPIC BeadChip. Methods: This case–control study was carried out at the Stomatology and Maxillofacial Surgery Department of the General University Hospital of Valencia. For the epigenomic study, unsupervised exploratory bioinformatic analyses were performed using principal component and heatmap analysis. Supervised differential methylation analyses were conducted using a rank-based regression model and a penalized logistic regression model to identify potential prognostic biomarkers. Results: The unsupervised analyses of the global methylation profiles did not allow us to differentiate between the distinct oral cancer groups. However, the two supervised analyses confirmed the existence of two oral carcinoma phenotypes. We identified 21 differentially methylated CpGs corresponding to 14 genes. Among them, three CpGs had not been previously assigned to any known gene, and the remaining were associated with genes unrelated to oral cancer. The AGL, WRB, and ARL15 genes were identified as potential prognostic biomarkers. Conclusions: This study emphasizes the significant role of epigenetic dysregulation in OSCC, particularly in cases preceded by PVL. We have provided data on differential methylation genes that could be involved in the molecular carcinogenesis of PVL-OSCC.

Background and objective Early diagnosis is paramount in the effective management of oral cancer, offering numerous benefits including improved treatment outcomes, reduced morbidity and mortality, preservation of function and appearance, cost-effectiveness, and enhanced quality of life for patients. Transformer-based models, increasingly used in medical image analysis, are the focus of our study. We aim to compare a vision transformer (ViT) classification method with a fully automated radiomics approach. This involves using object detection and segmentation algorithms to effectively classify oral lesions in both cancer and control cases. A combined approach is also presented. Methods The analysis included 322 patients with oral lesions, comprising 120 cancer cases and 202 controls, with standard JPG images. Pretrained transformer-based algorithms like DEtection TRansformer (DETR), Segment Anything (SAM), and Vision Transformers (ViT) were used to explore different pipelines for lesion classification. For the ViT approach, images were inputted in three configurations: the entire image, a bounding box around the lesion, and a lesion delineation. The radiomics approach involved pipelines with bounding boxes and lesion segmentations. Additionally, a ViT-Radiomics combined approach was proposed, using ViT attention maps as radiomics masks. To validate the models, a five-fold cross validation was used. Results The combined ViT-radiomics model demonstrated superior performance for small training sets, achieving specificity = 0.97 ± 0.04, sensitivity = 0.96 ± 0.05, and accuracy = 0.97 ± 0.02 for the 100 % of the training set. When analyzed independently, the ViT approach using the entire image achieved the best results with specificity = 0.99 ± 0.02, sensitivity = 0.96 ± 0.05, and accuracy = 0.96 ± 0.02. Following closely was the pipeline using automatically obtained segmentations, while the one with bounding boxes had the least favourable outcomes. In the radiomics approach, the most effective classifier used the attention masks from the ViT classifier (derived from the entire image), achieving specificity = 0.97 ± 0.05, sensitivity = 0.95 ± 0.08, and accuracy = 0.94 ± 0.03. Manual segmentations yielded the best results for both approaches, indicating potential for performance enhancement through improved lesion segmentation. Conclusions The ViT classification surpassed the radiomics-based approach yet combining ViT with radiomics yielded similar results. However, the attention maps generated by ViT tend to associate oral lesions in cancer patients with regions distant from the lesions in control patients. For tasks requiring the examination and comparison of features within cancer and control oral lesions, utilizing the radiomics approach with an automatic lesion segmentation algorithm is recommended.

INTRODUCTION:Severe recurrent aphthous stomatitis (RAS) represents a therapeutic challenge because of its impact on the patient's quality of life. Additionally, no approved systemic therapies are available. Roflumilast, a phosphodiesterase-4 inhibitor, has shown promise in other inflammatory dermatological conditions. This study aimed to assess the characteristics, effectiveness, and safety of roflumilast in treating RAS in routine clinical practice. METHODS:This is a single cohort ambispective observational study conducted in five Spanish centers. Twenty-two patients with RAS treated with roflumilast participated. Data collection included demographic, clinical, and outcome variables. Statistical analysis compared the outcomes of 12 weeks of roflumilast treatment with a similar prior period without treatment. RESULTS:During treatment with roflumilast, a significant reduction in flare-ups (88%) and oral ulcers (94%) was observed compared to the untreated period. A reduction in pain (66%) and ulcer duration (63%) was observed. Adverse effects (AEs) occurred in 13 patients, predominantly headache and gastrointestinal disturbances. Most of these were self-limiting or manageable with dose adjustment. Treatment was withdrawn in three cases, mainly because of AEs. CONCLUSIONS:This study suggests that roflumilast may effectively treat RAS by reducing the number of flare-ups and ulcers, their duration, and the symptomatology produced by the ulcers. In addition, roflumilast has a good safety profile, is well tolerated at low doses, and does not require close monitoring. These characteristics and its favorable economic profile make roflumilast a promising therapeutic option in this pathology.

ObjectiveProliferative verrucous leukoplakia (PVL) is considered a clinically distinct entity from other oral leucoplakias (OLs) due to its clinical presentation and evolution. However, molecular differences between them remain unclear. We aimed to determine whether there are methylation differences between PVL and other forms of OLs.Materials and MethodsOral biopsies from 12 patients with PVL, eight patients with homogeneous leucoplakia (HL), and 10 healthy individuals were obtained for a genome-wide DNA methylation analysis via the Infinium EPIC Platform.ResultsA total of 1815 differentially methylated CpGs were found between PVL and HL, with a prominent state of hypermethylation in HL patients. CpGs covered 813 genes with distinct roles, including cell adhesion, extracellular matrix organization, and cell and synaptic signaling. 43% of these genes had been previously described in cancer and associated with prognosis. We developed a multinomial logistic regression model able to differentiate HL, PVL, and control samples. The model had a cross-validated estimate of 73% and included differentially methylated cancer-related genes between the pathological conditions and the healthy donors, including ADNP, BRCA2, CDK13, GNB1, NIN, NUMB, PIK3C2B, PTK2, SHISA4, THSD7B, WWP1, and ZNF292. It also included CpGs covering differentially methylated genes in HL (MEN1 and TNRC6B) and PVL (ACOXL, ADH1B, CAMTA1, CBFA2T3, CPXM2, LRFN2, SORCS2, and SPN).ConclusionsPVL and HL present differential methylation patterns that could be linked to their differential clinical behavior. Our findings show the potential of methylation markers and suggest novel diagnostic biomarkers.

INTRODUCTION:Mucocutaneous Behcet's disease is often a therapeutic challenge. Roflumilast has shown promise in other inflammatory dermatological conditions. The objective of this study is to evaluate the characteristics, effectiveness and safety of roflumilast in the treatment of Behçet's Disease-associated aphthosis in routine clinical practice. METHODS:Single cohort ambispective observational study. 11 patients with Behçet disease treated with roflumilast participated. Data collection included demographic, clinical and outcome variables. Statistical analysis compared 12 weeks of treatment with roflumilast with a previous period without treatment and with a period with the previous treatment. RESULTS:During treatment with roflumilast, a reduction in flare-ups and oral ulcers was observed compared to the untreated period and the previous treatment period. A reduction in genital ulcers, pain and ulcer duration was observed between the Whitout treatment period and the Roflumilast treatment period.Adverse effects occurred in 54% of patients, most of which were self-limiting or manageable with dose adjustment. No patient withdrew treatment. DISCUSSION:Roflumilast appears a promising option in the treatment of Behçet's disease with favourable effectiveness, safety and tolerability profiles. Although further research is needed, roflumilast offers a promising treatment option for Behçet's Disease-associated aphthosis, which could improve patients' quality of life and address unmet therapeutic needs.

OBJECTIVE:Proliferative verrucous leukoplakia (PVL) has high rates of malignant transformation into oral squamous cell carcinoma (OSCC), but the clinical and evolutionary pattern of OSCC from PVL (PVL-OSCC) is more favorable than that of OSCC not preceded by PVL (OSCC). Here, we aimed to explore the pathophysiologic differences between PVL-OSCC and OSCC through transcriptomic and DNA methylation analyses. MATERIALS AND METHODS:In this case-control study, oral biopsies from 8 PVL-OSCC and 10 OSCC patients were obtained for global sequencing using RNAseq and a genome-wide DNA methylation analysis via the Infinium EPIC Platform (graphical abstract). RESULTS:One hundred and thirty-three differentially expressed genes (DEGs) were detected, 94 of them upregulated in OSCC. Most of these genes were previously described in cancer and associated with prognosis. The integrative analysis revealed 26 DEGs, corresponding to 37 CpGs, whose promoters were regulated by DNA methylation. Twenty-nine of the CpGs were found as hypermethylated in PVL-OSCC. Only 5 of the genes that were aberrantly methylated and differentially expressed were upregulated in PVL-OSCC patients, whereas 21 were underexpressed. CONCLUSIONS:PVL-OSCC patients presented lower expression of cancer-related genes. Hypermethylation of the promoter region of many genes was also noticed, indicating that DNA methylation could be a regulatory mechanism.

el odontólogo juega un papel fundamental en el diagnóstico y tratamiento del dolor orofacial, sobre todo en el dolor de origen pulpar o periodontal (odontogénico). En el caso del dolor clasificado habitualmente como crónico (no odontogénico), un elevado porcentaje de estudiantes de Odontología se sienten «en absoluto» o «algo» preparados para afrontar su diagnóstico y tratamiento. proponer una breve guía para diferenciar clínicamente el dolor odontogénico del dolor orofacial, que sea de utilidad tanto para el estudiante de Odontología como para el profesional. se elaboró un vídeo educativo de apoyo a la docencia dentro de un proyecto de innovación docente de la Universidad de Valencia titulado «El dolor orofacial para estudiantes del grado de Odontología: dolor agudo frente a dolor crónico» (UV-SFPIE_PID-1640062. Núm. Registro: 64155). Se establecieron 11 características fundamentales del dolor odontogénico y otras 11 del no odontogénico, que pretenden servir de orientación para el diagnóstico en situaciones en las que el dolor no presenta las características habituales. la proyección del vídeo tuvo una buena acogida por parte de los estudiantes, entendiéndolo como una herramienta atractiva de aprendizaje que favorece la motivación y la adquisición de responsabilidades. El 75,3% consideró que era «muy interesante», otorgando la máxima puntuación. con los datos disponibles actualmente en la literatura científica en relación a las características del dolor facial atípico, consideramos que la guía aportada en este proyecto puede ser de utilidad en el diagnóstico de estos procesos. Dentists play a fundamental role in the diagnosis and treatment of orofacial pain, especially in pain of pulp or periodontal (odontogenic) origin. In the case of pain usually classified as chronic (non-odontogenic), a high percentage of dental students feel “not at all” or “somewhat” prepared to carry out a diagnosis and treatment. To propose a brief guide to clinically differentiate odontogenic pain from orofacial pain, which is clinically useful for both dental students and professionals. An educational video was developed to support teaching within a teaching innovation project at the University of Valencia entitled “Orofacial Pain for Dentistry Degree Students: Acute Pain Versus Chronic Pain” (UV-SFPIE_PID-1640062. Reference No.: 64155). Eleven fundamental characteristics of odontogenic pain and another 11 of non-odontogenic pain were established, which are intended to serve as guidelines for the diagnosis in situations in which the pain does not present the usual characteristics. The video was well accepted among students and it was understood to be an attractive learning tool that enhances motivation and the acquisition of responsibilities. 75.3% considered it to be “very interesting”, giving it the highest score. According to the data currently available in the scientific literature regarding the characteristics of atypical facial pain, we believe that the guidelines provided in this project may be useful in the diagnosis of these processes.

Please confirm that an ethics committee approval has been applied for or granted: Yes: I’m uploading the Ethics Committee Approval as a PDF file with this abstract submission Application for ESRA Abstract Prizes: I don’t wish to apply for the ESRA Prizes Background and Aims Temporomandibular disorders (TMDs) are a frequent cause of orofacial pain, causing functional disability and a negative impact on quality of life. Incobotulim toxin A -Xeomin®- (BTX-A) injection in lateral pterygoid muscle (LPM) is one of the treatment modalities proposed, but the blind puncture guided by EMG carries a risk of vascular puncture or diffusion of the toxin to nearby muscles. We describe an ultrasound-guided approach and show the results of a retrospective study of thirty patients. Methods Thirty patients with unilateral temporomandibular myofascial pain were treated. An out-of-plane approach was performed using a convex probe, injecting 20 U of BTX-A (2.5 unit/0.1 ml solution – 0.8 ml) into the LPM. Before puncture, using colour Doppler mode, the maxillary artery was located to avoid its puncture. Results Compared with baseline, patients manifested significant improvement in pain (VAS) at rest and at mandibular movement a month after treatment (p<0.05). Temporomandibular joint (TMJ) click was present prior to treatment in twenty-four patients, disappearing in 16 of them a month after injection (66.7%). No complications were detected during or after treatment. Conclusions An ultrasound-guided approach for the injection of BTX-A into the LPM could be considered a successful and safe treatment for myofascial pain related to TMD and TMJ clicking. Therefore, further studies with larger sample sizes and longer follow-up periods are needed to study the effect of BTX and its long-term effects. Attachment CEIM.pdf

The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL (n = 9), PVL (n = 12), OSCC (n = 10), PVL-OSCC (n = 8), and healthy (n = 11) donors were obtained. The sequence of the V3-V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and Fusobacteriota constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of Campilobacterota and lower Proteobacteria than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in Streptococcus parasanguinis, Streptococcus salivarius, Fusobacterium periodonticum, Prevotella histicola, Porphyromonas pasteri, and Megasphaera micronuciformis; PVL is enriched in Prevotella salivae, Campylobacter concisus, Dialister pneumosintes, and Schaalia odontolytica; OSCC is enriched in Capnocytophaga leadbetteri, Capnocytophaga sputigena, Capnocytophaga gingivalis, Campylobacter showae, Metamycoplasma salivarium, and Prevotella nanceiensis; and PVL-OSCC is enriched in Lachnospiraceae bacterium, Selenomonas sputigena, and Prevotella shahii. There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed.

Our main purpose and research question were to analyze and quantify whether there were significant differences in the time to develop cancer among patients with oral leukoplakia (OL), comparing the more susceptible cases to those with the least susceptibility to malignancy. We followed 224 cases of OL after surgical or CO2 laser treatment for a mean time of 6.4 years. A Bayesian mixture cure model based on the Weibull distribution was used to model the relationship between our variables and cancer risk. In this model type, the population is considered a mixture of individuals who are susceptible or non-susceptible to developing cancer. The statistical model estimates the probability of cure (incidence model) and then infers the time to malignancy. The model was adjusted using the R-package INLA using default priors. Histology type (moderate or severe dysplasia) and tongue location showed hazard ratios (HR) of 3.19 (95% CI [1.05–8.59]) and 4.78 (95% CI [1.6–16.61]), respectively. Both variables increased the risk of malignant transformation, thus identifying a susceptible subpopulation with reduced time required to develop cancer, as with non-homogeneous leukoplakias. The median time for cancer development was 4 years and 5 months, with a minimum of 9 months after the diagnosis of OL and a maximum of 15 years and 2 months. Susceptible patients with non-homogeneous leukoplakia, dysplasia, or leukoplakia in the tongue develop cancer earlier than those with homogeneous OL and those without dysplasia. The novel contribution of this research is that, until now, the time it took for oral leukoplakias to develop cancer based on whether they were homogeneous or non-homogeneous, and if they have or not epithelial dysplasia, had not been comparatively described and quantified. As a final result, the time to malignant transformation in non-homogeneous and dysplastic leukoplakias is significantly shorter.

Objectives: To estimate the probability of malignancy of an oral leukoplakia lesion using Deep Learning, in terms of evolution to cancer and high-risk dysplasia. Materials and Methods: A total of 261 oral leukoplakia lesions with a mean of 5.5 years follow-up were analysed from standard digital photographs. A deep learning pipeline composed by a U-Net based segmentation of the lesion followed by a multi-task CNN classifier was used to predict the malignant transformation and the risk of dysplasia of the lesion. An explainability heatmap is constructed using LIME in order to interpret the decision of the model for each output. Results: A Dice coefficient of 0.561 was achieved on the segmentation task. For the prediction of a malignant transformation, the model provided a sensitivity of 1 with a specificity of 0.692. For the prediction of high-risk dysplasia, the model achieved a specificity of 0.740 and a sensitivity of 0.928. Conclusion: The proposed model using deep learning can be a helpful tool for predicting the possible malignant evolution of oral leukoplakias. The generated heatmap provides a high confidence on the output of the model and enables its interpretability.

Background: Nearly two decades have passed since a paradoxical reaction in the orofacial region to some bone modifying agents and other drugs was recognized, namely medication-related osteonecrosis of the jaw (MRONJ). Purpose: The aim of this manuscript was to critically review published data on MRONJ to provide an update on key terminology, concepts, and current trends in terms of prevention and diagnosis. In addition, our objective was to examine and evaluate the therapeutic options available for MRONJ. Methods: The authors perused the most relevant literature relating to MRONJ through a search in textbooks and published articles included in several databases for the years 2003–2021. Results and conclusions: A comprehensive update of the current understanding of these matters was elaborated, addressing these topics and identifying relevant gaps of knowledge. This review describes our updated view of the previous thematic blocks, highlights our current clinical directions, and emphasizes controversial aspects and barriers that may lead to extending the accumulating body of evidence related to this severe treatment sequela.

Background: We sought to determine the most appropriate method for measuring salivary flow to aid the diagnosis of Sjogren's syndrome (SS). Specifically, we compared the unstimulated whole salivary flow rate (UWSFR) with the stimulated whole salivary flow rate (SWSFR). Material and Methods: This case-control study comprised one group of 103 patients with SS and a control group of 50 healthy people. We measured the UWSFR and SWSFR in both groups according to the guidelines established by Navacet (1993). Results: The UWSFR and SWSFR were significantly lower in the patient group compared with the controls (p < 0.01). Among the participants in the patient group, we found a decreased UWSFR in 84 individuals (81.5%) and a decreased SWSFR in 90 individuals (87.4%). We encountered difficulties obtaining saliva in 37 (35.9%) patients during the UWSFR test, and in 12 (11.7%) patients during the SWSFR test. There was no significant statistical difference in the UWSFR or SWSFR between patients with primary and secondary SS. Conclusions: Compared with the UWSFR, the SWSFR is a more suitable and effective method for measuring salivary flow in patients with SS, as well as for qualitative analysis of the obtained saliva.

AIMSto discuss the terminology to define and classify actinic cheilitis (AC); and to build a consensus on the diagnostic and therapeutic approaches to AC.METHODSTwo-round Delphi study using a questionnaire including 34 closed sentences (9 on terminology and taxonomy, 5 on potential for malignant transformation, 12 on diagnostic aspects, 8 on treatment) and 8 open questions. Experts' agreement was rated using a Likert scale (1-7).RESULTSA consensus was reached on 24 out 34 statements (73.5%) and on 5 out of 8 (62.5%) close-ended questions. The response rate was identical in both rounds (attrition of 0%). AC is the term with the highest agreement (median of 7 (strongly agree; IQR: 6-7) and the lowest dispersion (VC=21.33). "Potentially malignant disorder" was the preferred classification group for AC (median of 7) and 85.6% of participants showing some level of agreement (CV<50). Experts (66.75%) consider AC a clinical term (median: 7; IQR: 4-7) and believe definitive diagnosis can be made clinically (median: 6; IQR: 5-7), particularly by inspection and palpation (median: 5; IQR: 4-6). Histopathological confirmation is mandatory for the management of AC (median: 5; IQR: 2.5-7), even for homogeneous lesions (median: 5; IQR: 3.5-6). Consensus was reached on all treatment statements (VC<50).CONCLUSIONSAC is a potentially malignant disorder with a significant lack of agreement on diagnostic criteria, procedures, biopsy indications, and the importance of techniques to assist in biopsy. A consensus was reached on nomenclature and management of this disorder.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term “potentially malignant disorders of the oral mucosa” (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with “oral lichenoid lesions” and among those diagnosed with oral manifestations of ‘chronic graft-versus-host disease’. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

Objectives: To explore the pathophysiology of proliferative verrucous leucoplakia (PVL) through a methylated DNA immunoprecipitation and high-throughput sequencing (MeDIP-seq) case-control study. Materials and & nbsp; Methods: Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their epigenetic patterns. Network biology methods and integrative analyses of MeDIP-seq and RNAseq data were applied to investigate functional relations among differentially methylated genes (DMGs). The value of selected genes as malignant biomarkers was evaluated in a large cohort of oral squamous cell carcinoma (OSCC) patients from TCGA.& nbsp; Results: A total of 4647 differentially methylated regions were found, with a prominent state of hypermethylation in PVL patients. At the gene level, differentially methylated regions (DMRs) covered 826 genes with distinct roles, including transcription factors and binding proteins with functions in cell adhesion, migration, proliferation, regulation of transcription, bone morphogenesis, and cell signalling. Network analysis revealed three major hubs, two of them collecting proteins related to the response of the patients to PVL and treatment and one hub collecting proteins related to PVL and cancer. The integrative analysis revealed 8 genes (ARTN, CD8A, GATA3, HOXD10, MYO7A, OSR2, PLCB1, and SPOCK2) significantly upregulated in PVL compared to control and 5 genes (ANKRD6, DLG2, GPX3, PITX2, and ZNF736) significantly downregulated. The status of de-regulation found for PVL patients was concordant with what was found for OSCC samples compared to normal adjacent tissue.& nbsp; Conclusion: Our findings show the potential of methylation markers in PVL and suggest novel OSCC diagnostic biomarkers which may boost the development of novel epigenetic-based therapies.

This study aimed to investigate the role of a panel of salivary cytokines as biomarkers for early detection oral squamous cell carcinoma (OSCC), comparing their levels among healthy individuals, patients with oral leukoplakia (OL), and malignant lesions. Cytokine profiling analysis performed in a minimally invasive sample was correlated with clinicopathological variables in our patient cohorts. Unstimulated saliva was obtained from subjects with OSCC at early (n = 33) and advanced (n = 33) disease, OL with homogeneous (n = 33) and proliferative verrucous (n = 33) clinical presentations, and healthy controls (n = 25). Salivary IL-1α, IL-6, IL-8, IP-10, MCP-1, TNF-α, HCC-1, and PF-4 levels were analyzed by a sensitive bead-based multiplex immunoassay. Mean levels of IL-6, IL-8, TNF-α, HCC-1, MCP-1, and PF-4 differed significantly between OSCC, OL, and control saliva (p < 0.05). We found notably higher IL-6 and TNF-α in advanced compared to early OSCC stages. The area under the curve (AUC) for OSCC vs. control was greater than 0.8 for IL-6, IL-8, TNF-α, and HCC-1, and greater than 0.7 for PF-4. The presence of neck metastases (NM) was associated with increased IL-6 and TNF-α levels. Our findings suggest that salivary IL-6, IL-8, TNF-α, HCC-1, and PF-4 may discriminate between OSCC, OL, and healthy controls. IL-6 and TNF-α may indicate OSCC progression, being distinctive in the presence of NM.