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1.
J Proteome Res ; 23(6): 2148-2159, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38785273

ABSTRACT

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.


Subject(s)
Mouth Neoplasms , Proteome , Saliva , Humans , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Saliva/chemistry , Saliva/metabolism , Proteome/analysis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/diagnosis , Female , Biomarkers, Tumor/metabolism , Male , Lymphatic Metastasis , Protein Conformation , Middle Aged , Prognosis , Proteomics/methods , Transketolase/metabolism , Aged , Mass Spectrometry , Salivary Proteins and Peptides/metabolism , Salivary Proteins and Peptides/analysis
2.
Anal Chem ; 96(3): 1223-1231, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38205554

ABSTRACT

Oral squamous cell carcinoma (OSCC) has become a global health problem due to its increasing incidence and high mortality rate. Early intervention through monitoring of the diagnostic biomarker levels during OSCC treatment is critical. Extracellular vesicles (EVs) are emerging surrogates in intercellular communication through transporting biomolecule cargo and have recently been identified as a potential source of biomarkers such as phosphoproteins for many diseases. Here, we developed a multiple reaction monitoring cubed (MRM3) method coupled with a novel sample preparation strategy, extracellular vesicles to phosphoproteins (EVTOP), to quantify phosphoproteins using a minimal amount of saliva (50 µL) samples from OSCC patients with high specificity and sensitivity. Our results established differential patterns in the phosphopeptide content of healthy, presurgery, and postsurgery OSCC patient groups. Notably, we discovered significantly increased salivary phosphorylated alpha-amylase (AMY) in the postsurgery group compared to the presurgery group. We hereby present the first targeted MS method with extremely high sensitivity for measuring endogenous phosphoproteins in human saliva EVs.


Subject(s)
Carcinoma, Squamous Cell , Extracellular Vesicles , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/diagnosis , Biomarkers, Tumor/analysis , Saliva/chemistry , Mouth Neoplasms/diagnosis , Extracellular Vesicles/pathology , Squamous Cell Carcinoma of Head and Neck , Phosphoproteins/analysis
3.
Clin Oral Investig ; 28(7): 364, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38849649

ABSTRACT

OBJECTIVES: Diagnosing oral potentially malignant disorders (OPMD) is critical to prevent oral cancer. This study aims to automatically detect and classify the most common pre-malignant oral lesions, such as leukoplakia and oral lichen planus (OLP), and distinguish them from oral squamous cell carcinomas (OSCC) and healthy oral mucosa on clinical photographs using vision transformers. METHODS: 4,161 photographs of healthy mucosa, leukoplakia, OLP, and OSCC were included. Findings were annotated pixel-wise and reviewed by three clinicians. The photographs were divided into 3,337 for training and validation and 824 for testing. The training and validation images were further divided into five folds with stratification. A Mask R-CNN with a Swin Transformer was trained five times with cross-validation, and the held-out test split was used to evaluate the model performance. The precision, F1-score, sensitivity, specificity, and accuracy were calculated. The area under the receiver operating characteristics curve (AUC) and the confusion matrix of the most effective model were presented. RESULTS: The detection of OSCC with the employed model yielded an F1 of 0.852 and AUC of 0.974. The detection of OLP had an F1 of 0.825 and AUC of 0.948. For leukoplakia the F1 was 0.796 and the AUC was 0.938. CONCLUSIONS: OSCC were effectively detected with the employed model, whereas the detection of OLP and leukoplakia was moderately effective. CLINICAL RELEVANCE: Oral cancer is often detected in advanced stages. The demonstrated technology may support the detection and observation of OPMD to lower the disease burden and identify malignant oral cavity lesions earlier.


Subject(s)
Leukoplakia, Oral , Lichen Planus, Oral , Mouth Neoplasms , Precancerous Conditions , Humans , Mouth Neoplasms/diagnosis , Precancerous Conditions/diagnosis , Lichen Planus, Oral/diagnosis , Leukoplakia, Oral/diagnosis , Sensitivity and Specificity , Photography , Diagnosis, Differential , Carcinoma, Squamous Cell/diagnosis , Male , Female , Photography, Dental , Image Interpretation, Computer-Assisted/methods
4.
Clin Oral Investig ; 28(2): 131, 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38308109

ABSTRACT

OBJECTIVES: The occurrence and causes of primary professional delay in diagnosis of oral squamous cell carcinoma (OSCC) were examined. MATERIALS AND METHODS: Factors related to initial diagnosis or malignancy suspicion were evaluated in patients with primary OSCC. The outcome variable was primary professional delay for missed suspicion of malignancy or wrong diagnosis or delayed referral. The primary predictor variable was active care-seeking. Secondary predictor variables were patients' symptoms and clinical findings. RESULTS: Primary professional delay was found in 9.5% of the 528 patients included. Professional delay was 6.6 times more likely to occur in patients actively seeking care than in those whose tumor was an incidental finding (95% CI 1.58-27.58, p = 0.010). Pain (OR = 2.0, 95% CI 1.07-3.87, p = 0.031), ulceration (OR = 2.3, 95% CI 1.29-4.19, p = 0.005), denture fit problem (OR = 3.1, 95% CI 1.25-7.56, p = 0.014), and unhealed tooth extraction socket (OR = 29.6, 95% CI 8.89-98.71, p < 0.001) were significant predictors for primary professional delay. CONCLUSIONS: OSCC patients seek care actively. Primary professional delay affects the care of every tenth OSCC patient. CLINICAL RELEVANCE: The role of health care professionals is essential for early OSCC diagnosis, especially in urgent care. Clinicians' knowledge of the typical symptoms and findings of OSCC should be improved.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Patient Acceptance of Health Care
5.
Med Oral Patol Oral Cir Bucal ; 29(4): e533-e536, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38615259

ABSTRACT

BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a diferential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Iincisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.


Subject(s)
Carcinoma, Squamous Cell , Paracoccidioidomycosis , Tongue Neoplasms , Humans , Male , Retrospective Studies , Female , Middle Aged , Cross-Sectional Studies , Paracoccidioidomycosis/diagnosis , Aged , Carcinoma, Squamous Cell/diagnosis , Diagnosis, Differential , Tongue Neoplasms/diagnosis , Oral Ulcer/diagnosis , Oral Ulcer/microbiology , Oral Ulcer/etiology , Tongue Diseases/diagnosis , Tongue Diseases/microbiology , Adult , Aged, 80 and over
6.
Med Oral Patol Oral Cir Bucal ; 29(1): e36-e43, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37330964

ABSTRACT

BACKGROUND: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma (OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study, we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specific Spanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosis measures. MATERIAL AND METHODS: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospital centre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival were calculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression). RESULTS: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) and alcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailed the 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were 39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC cases referred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with an oral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatment. CONCLUSIONS: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prognosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights the better survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and the dental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the early diagnosis and multidisciplinary management of this malignant neoplasm.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Male , Aged , Female , Prognosis , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/therapy , Retrospective Studies , Mouth Neoplasms/diagnosis , Mouth Neoplasms/epidemiology , Mouth Neoplasms/therapy , Follow-Up Studies , Spain/epidemiology
7.
Proteomics ; 23(9): e2200321, 2023 05.
Article in English | MEDLINE | ID: mdl-36625099

ABSTRACT

Globally, oral cavity squamous cell carcinoma (OSCC) is one of the most common fatal illnesses. Its high mortality is ascribed to the fact that the disease is often diagnosed at a late stage, which indicates an urgent need for approaches for the early detection of OSCC. The use of salivary autoantibodies (autoAbs) as OSCC biomarkers has numerous advantages such as easy access to saliva samples and efficient detection of autoAbs using well-established secondary reagents. To improve OSCC screening, we identified OSCC-associated autoAbs with the enrichment of salivary autoAbs combined with affinity mass spectrometry (MS). The salivary IgA of healthy individuals and OSCC patients was purified with peptide M-conjugated beads and then applied to immunoprecipitated antigens (Ags) in OSCC cells. Using tandem MS analysis and spectral counting-based quantitation, the level of 10 Ags increased in the OSCC group compared with the control group. Moreover, salivary levels of autoAbs to the 10 Ags were determined by a multiplexed bead-based immunoassay. Among them, seven were significantly higher in early-stage OSCC patients than in healthy individuals. A marker panel consisting of autoAbs to LMAN2, PTGR1, RAB13, and UQCRC2 was further developed to improve the early diagnosis of OSCC.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Biomarkers, Tumor/analysis , Autoantibodies/analysis , Immunoglobulin A/analysis , Saliva/chemistry , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Tandem Mass Spectrometry , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , rab GTP-Binding Proteins/analysis
8.
Anal Chem ; 95(19): 7753-7760, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37130010

ABSTRACT

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.


Subject(s)
Carcinoma, Squamous Cell , Extracellular Vesicles , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck , Saliva/metabolism , Annexin A5 , Extracellular Vesicles/metabolism , Head and Neck Neoplasms/pathology , ErbB Receptors/metabolism
9.
Proc Natl Acad Sci U S A ; 117(28): 16167-16173, 2020 07 14.
Article in English | MEDLINE | ID: mdl-32601197

ABSTRACT

Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Metabolomics , Mouth Neoplasms/diagnosis , Saliva/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Female , Humans , Machine Learning , Male , Middle Aged , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Neoplasm Staging , Point-of-Care Testing , Reproducibility of Results , Spectrometry, Mass, Electrospray Ionization
10.
Sensors (Basel) ; 23(21)2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37960614

ABSTRACT

For the progress of point-of-care medicine, where individual health status can be easily and quickly monitored using a handheld sensor, saliva serves as one of the best-suited body fluids thanks to its availability and abundance of physiological indicators. Salivary biomarkers, combined with rapid and highly sensitive detection tools, may pave the way to new real-time health monitoring and personalized preventative therapy branches using saliva as a target matrix. Saliva is increasing in importance in liquid biopsy, a non-invasive approach that helps physicians diagnose and characterize specific diseases in patients. Here, we propose a proof-of-concept study combining the unique specificity in biomolecular recognition provided by surface-enhanced Raman spectroscopy (SERS) in combination with molecular dynamics (MD) simulations, which give leave to explore the biomolecular absorption mechanism on nanoparticle surfaces, in order to verify the traceability of two validated salivary indicators, i.e., interleukin-8 (IL-8) and lysozyme (LYZ), implicated in oropharyngeal squamous cell carcinoma (OSCC) and oral infection. This strategy simultaneously assures the detection and interpretation of protein biomarkers in saliva, ultimately opening a new route for the evolution of fast and accurate point-of-care SERS-based sensors of interest in precision medicine diagnostics.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Mouth Neoplasms/diagnosis , Point-of-Care Systems , Carcinoma, Squamous Cell/diagnosis , Head and Neck Neoplasms/diagnosis , Biomarkers/analysis , Saliva/chemistry , Spectrum Analysis, Raman , Biomarkers, Tumor/analysis
11.
J Oral Implantol ; 49(1): 25-28, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-34412118

ABSTRACT

Proper staging and diagnosing of mucosal head and neck cancers is necessary given important differences in tumor behaviors that lead to different standards of treatment. We report the unusual case of a 65-year-old woman who is a former smoker with an implant-supported upper denture who developed an isolated nasal mass on examination, which was confirmed after resection to be a squamous cell carcinoma originating from the hard palate. Although this is a rare scenario, an oral cavity cancer should be taken into consideration in the differential diagnosis of a nasal cavity mass in the setting of a fixed upper dental implant.


Subject(s)
Carcinoma, Squamous Cell , Dental Implants , Head and Neck Neoplasms , Mouth Neoplasms , Female , Humans , Aged , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgery , Mouth Neoplasms/diagnosis , Mouth Neoplasms/surgery , Dentures , Dental Prosthesis, Implant-Supported
12.
BMC Oral Health ; 23(1): 994, 2023 12 12.
Article in English | MEDLINE | ID: mdl-38087258

ABSTRACT

BACKGROUND: Early detection and diagnosis of malignant tumors is critical for improving the survival rate and treatment outcomes of oral cancer. Thus, the current prospective investigation was designed to verify the role, sensitivity, and specificity of salivary LINC00657 and miRNA-106a as diagnostic markers in oral squamous cell carcinoma patients as compared to oral lichen planus (as an example of oral potentially malignant disorders) and normal individuals, and to show LINC00657 relation to miR-106a. METHODS: A total of 36 participants were included, subdivided into 3 groups: Group I: 12 patients diagnosed with oral squamous cell carcinoma (OSCC). Group II: 12 patients diagnosed with oral lichen planus (OLP). Group III: 12 systemically free individuals with no oral mucosal lesions. Unstimulated salivary samples were collected from all participants to evaluate level of LINC00657 and miR-106a in different groups using quantitative real-time PCR. RESULTS: OSCC showed the highest LINC00657 and lowest miR-106a fold change among included groups. Receiver Operating Characteristic (ROC) curve analysis of the two biomarkers for detecting OSCC revealed that LINC00657 had higher diagnostic accuracy (DA) (83.3%) compared to miR-106a (80.4%). As for detecting OLP, ROC analysis showed that miR-106a had higher (DA) (61%) compared to LINC00657 (52.5%). To discriminate OSCC from OLP, the diagnostic accuracy of both markers is the same (75%). Moreover, differentiating OSCC grades II and III, ROC analysis showed that miR-106a had lower (DA) (60%) compared to LINC00657 (DA) (83.3%). CONCLUSIONS: Salivary LINC00657 and miR-106a could be promising diagnostic markers for oral squamous cell carcinoma. Salivary LINC00657 may differentiate oral squamous cell carcinoma from oral potentially malignant disorders with considerable diagnostic accuracy. Moreover, low levels of salivary miR-106a could have the potential to indicate malignancy. TRIAL REGISTRATION: The study was retrospectively registered on clinicaltrial.gov with NCT05821179 (first trial registration in 26/3/2023), date of registration: 19/4/2023.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Lichen Planus, Oral , MicroRNAs , Mouth Neoplasms , Precancerous Conditions , Humans , Biomarkers , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Lichen Planus, Oral/diagnosis , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Saliva/chemistry , Squamous Cell Carcinoma of Head and Neck
13.
Med Oral Patol Oral Cir Bucal ; 28(4): e301-e309, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37330954

ABSTRACT

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.


Subject(s)
Carcinoma, Squamous Cell , Gingival Neoplasms , Oral Ulcer , Male , Humans , Aged , Middle Aged , Female , Gingival Neoplasms/pathology , Brazil/epidemiology , Ulcer/diagnosis , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Diagnosis, Differential , Retrospective Studies
14.
Med Oral Patol Oral Cir Bucal ; 28(5): e474-e486, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37099710

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. MATERIAL AND METHODS: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". RESULTS: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. CONCLUSIONS: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Cytokines/analysis , Tumor Necrosis Factor-alpha , Interleukin-6/analysis , Interleukin-8 , Reproducibility of Results , Biomarkers, Tumor/analysis , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Prognosis , Saliva/chemistry
15.
J Oral Pathol Med ; 51(5): 429-435, 2022 May.
Article in English | MEDLINE | ID: mdl-35416334

ABSTRACT

BACKGROUND: Differences in cell-free DNA (cfDNA) fragments have been described as a valuable tool to distinguish cancer patients from healthy individuals. We aim to investigate the concentration and integrity of cfDNA fragments in saliva from oral squamous cell carcinoma (OSCC) patients and healthy individuals in order to explore their value as diagnostic biomarkers. METHODS: Saliva samples were collected from a total of 34 subjects (19 OSCC patients and 15 healthy controls). The total concentration of salivary cfDNA (scfDNA) was determined using a fluorometry method and quantitative real-time polymerase chain reaction (qPCR). To evaluate the scfDNA quantity and integrity, qPCR targeting Arthobacter luteus (ALU) sequences at three amplicons of different lengths (60, 115, and 247 bp, respectively) was carried out. ScfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) were calculated as the ratio between the absolute concentration of the longer amplicons 115 bp and 247 bp and the total scfDNA amount (amplicon 60 bp). RESULTS: The total scfDNA concentration (ALU60) was higher in OSCC than in healthy donors, but this trend was not statistically significant. The medians of scfDNA integrity indexes, ALU115/ALU60 and ALU247/ALU60, were significantly higher in OSCC, showing area under the curve values of 0.8211 and 0.7018, respectively. CONCLUSION: Our preliminary results suggest that scfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) have potential as noninvasive diagnostic biomarkers for OSCC.


Subject(s)
Carcinoma, Squamous Cell , Cell-Free Nucleic Acids , Mouth Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Humans , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Saliva
16.
Oral Dis ; 28(3): 541-558, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33423350

ABSTRACT

OBJECTIVES: This study aims to determine the diagnostic test accuracy (DTA) of hypermethylated DNA biomarkers in saliva and oral swabs for oral squamous cell carcinoma (OSCC) detection from the prevalidation studies available. MATERIALS AND METHODS: Electronic database searching of PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and LILACS was conducted to identify relevant articles that were published between January 1, 2000, and August 1, 2020. RESULTS: Meta-analysis was conducted based on 11 of 20 studies selected for review. Included studies had high bias concerns on the QUADAS-2 study assessment tool. We found that salivary and oral swab hypermethylation markers had better specificity than sensitivity for oral cancer detection. Summary sensitivity and specificity (95% CI) of hypermethylation panels were 86.2% (60-96.2) and 90.6% (85.9-93.9) while for individual markers, summary sensitivity and specificity (95% CI) were 70% (56.9-80.5) and 91.9% (80.3-96.9), respectively. Respective positive and negative likelihood ratios for combined markers were 9.2 (5.89-14.36) and 0.15 (0.05-0.5), and 8.61 (3.39-21.87) and 0.33 (0.22-0.49) for single-application biomarkers. CONCLUSION: DNA hypermethylation biomarkers especially in combination have acceptable DTA that warrants further optimization with rigorous biomarker evaluation methods for conclusive determination of their efficacy.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Biomarkers , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , DNA , Humans , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Saliva , Sensitivity and Specificity
17.
Cytopathology ; 33(3): 374-379, 2022 05.
Article in English | MEDLINE | ID: mdl-34995373

ABSTRACT

OBJECTIVE: Although class III beta-tubulin (TUBB3) is not expressed in normal epithelium, its expression in cancers of some organs has been reported. Herein, we investigated the expression pattern and expression levels of TUBB3 in oral squamous cell carcinoma (SCC), and assessed whether TUBB3 immunostaining could improve the diagnostic accuracy of oral scraping liquid-based cytology (LBC). METHODS: Paraffin sections of biopsies from 107 patients with primary SCC and 30 patients with squamous papilloma of the tongue or gingiva were immunostained for TUBB3. In addition, 15 LBC samples obtained from the study participants with SCC were immunostained for TUBB3. Seven LBC samples were false-negative. The TUBB3 expression level in each sample was evaluated and classified as 3+, 2+, 1+, or 0. RESULTS: TUBB3 expression was confirmed in 91.6% of paraffin-embedded SCC specimens. Clear and diffuse positivity (2+ or above) was observed in 77.6% of the total cases. In the well-differentiated type, tumour cells in the middle layer of the parenchyma specifically expressed TUBB3. In almost LBC samples, cancerous intermediate cells showed immunopositivity similar to that of paraffin samples, even if cellular atypia was not clear in Papanicolaou staining. CONCLUSIONS: TUBB3 immunostaining is useful for diagnosing oral SCC in scraping LBC, especially when samples consist of intermediate cells with little morphological change. Moreover, TUBB3 immunostaining could improve the diagnostic accuracy of oral scraping LBC by reducing false-negatives.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Humans , Mouth Neoplasms/diagnosis , Paraffin , Squamous Cell Carcinoma of Head and Neck , Tubulin/genetics
18.
Lasers Med Sci ; 37(3): 1821-1827, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34637056

ABSTRACT

Head and neck cancer detection using fluorescence spectroscopy from human saliva is reported here. This study has been conducted on squamous cell carcinoma (SCC), and dysplastic (precancer) and control (normal) groups using an in-house developed compact set-up. Fluorescence set-up consists of a 375-nm laser diode and optical components. Spectral bands of flavin adenine dinucleotide (FAD), porphyrins, and Raman are observed in the spectral range of 400 to 800 nm. Presence of FAD and porphyrin bands in human saliva is confirmed by the liquid phantoms of FAD and porphyrin. Significant differences in fluorescence intensities among all the three groups are observed. Three spectral ranges from 455 to 600, 605 to 770, and 400 to 800 nm are selected for each group and area values under each spectral range are computed. To differentiate among the groups, receiver operating characteristic (ROC) analysis is employed on the area values. ROC differentiates among the groups with accuracies of 98%, 92.85%, and 81.13% respectively in the spectral ranges of 400 to 800 nm. However, in other two spectral ranges (455 to 600 and 605 to 770 nm), low accuracy values are found. Obtained accuracy values indicate that selection of human saliva for head and neck cancer detection may be a good alternative.


Subject(s)
Carcinoma, Squamous Cell , Saliva , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Head , Humans , ROC Curve , Spectrometry, Fluorescence/methods
19.
Clin Oral Investig ; 26(11): 6653-6659, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35881238

ABSTRACT

OBJECTIVES: Oral brush biopsies are a well researched index for early detection of oral cancer in specialised centers. But the performance of the exfoliative biopsy is not yet researched in daily dental routine. METHODS: Private dentists and private oral surgeons in Germany took brush biopsies out of 814 suspicious lesions from 670 patients using the Orcellex brush while regular dental appointments. The analyses of the biopsies were performed by the Cytological Laboratory of Bonn (CLB) using liquid-based cytology. RESULTS: The final results were 74 oral squamous cell carcinomas and one verrucous carcinoma, histological proven, 232 cases of leukoplakia, 242 cases of lichen planus, 17 cases of erythroplakia, 259 cases of benign inflammatory, traumatic or hyperplastic oral lesions. The sensitivity for the detection of cancer cells using brush biopsy archived 100%, the specificity for the detection of non-neoplastic cells was 86.5%. The positive predictive value was 43.1%, the negative predicative value was at 100%. CONCLUSION: The oral brush biopsy seems to be a sufficient tool for early cancer detection in private dental offices. CLINICAL RELEVANCE: Generally, practicing dentists do not see various oral squamous cell carcinomas in their careers, so the experience in identifying oral squamous cell carcinomas as such is very low. The brush biopsy might help them in cases of doubt to prevent tumors from expansive growth.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Mouth Neoplasms/diagnosis , Mouth Neoplasms/pathology , Biopsy/methods , Early Detection of Cancer/methods , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Sensitivity and Specificity
20.
J Craniofac Surg ; 33(3): e279-e281, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35727656

ABSTRACT

ABSTRACT: Oropharyngeal squamous cell carcinoma is the most common neoplasm of head and neck cancers related to the presence of human papillomavirus (HPV). in the dental, maxillofacial and ENT fields, the finding of mediated HPV lesions is quite common. The diagnostic techniques currently available are different and can be more or less invasive depending on the type of lesion and the need for the clinician. In this study, two clinical cases subjected to a double diagnostic technique were considered in order to exclude any possible risk of false negatives. The polymerase chain reaction (PCR) technique showed a lower sensitivity or in any case dictated by a limited number of HPV strains analyzed. Histological examination nowadays turns out to be the best diagnostic method despite requiring a surgical phase.


Subject(s)
Alphapapillomavirus , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , DNA, Viral/analysis , Humans , Oropharyngeal Neoplasms/diagnosis , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis
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