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1.
J Oral Pathol Med ; 53(6): 376-385, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772856

RESUMO

BACKGROUND: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. METHODS: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. RESULTS: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. CONCLUSION: This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.


Assuntos
Proliferação de Células , Curcumina , Fibroblastos , Queratinócitos , Porphyromonas gingivalis , Streptococcus mutans , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Queratinócitos/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Linhagem Celular , Cicatrização/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Candida albicans/efeitos dos fármacos , Lipopolissacarídeos , Técnicas In Vitro , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Géis , Inflamação/tratamento farmacológico , Apoptose/efeitos dos fármacos , Estomatite/tratamento farmacológico , Adesão Celular/efeitos dos fármacos
2.
J Oral Pathol Med ; 53(2): 90-106, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38316046

RESUMO

BACKGROUND: Aberrant epigenetic modifications significantly develop and progress human malignancies including head and neck squamous cell carcinoma (HNSCC). Taking into account issues of late diagnosis and poor prognosis associated with HNSCC, this systematic review is designed to provide an up-to-date insight of epigenetic changes in the management of HNSCC. METHODS: All studies that assessed the diagnostic and prognostic utilities of epigenetic changes (DNA methylation and histone modifications) among patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) were considered for inclusion till June 2023. Pre-defined Medical Subject Headings terms were used to search Web of Science, Pubmed, Scopus and Embase Ovid databases. RESULTS: Twenty-five studies were deemed eligible for inclusion with a total number of 3790 samples (2123 HNSCCs, 334 OPMDs and 1333 as controls). DNA methylation was investigated in 18 studies while the role of histone modifications was assessed in seven studies. The most investigated biomarkers among the studies were H3, DAPK and TIMP3. The diagnostic accuracy of the epigenetic biomarkers in detecting HNSCC was assessed in eight studies where the following biomarkers showed the highest area under the curve values: TIPM3, DCC, DAPK, SEPT9, SHOX9, HOXA9 and TRH. None of the studies assessed the predictability of the epigenetic biomarkers in HNSCC and OPMDs. CONCLUSION: Although initial promising results were seen using the epigenetic biomarkers in the early detection of HNSCC, the limited number of patients and the absence of well-designed longitudinal studies limit the clinical applicability of the outcomes.


Assuntos
Epigênese Genética , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Metilação de DNA , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
3.
Oral Dis ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38946217

RESUMO

OBJECTIVE: Histopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes. METHODS: The review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design. RESULTS: Forty-six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta-analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia. CONCLUSIONS: No significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.

4.
Int J Mol Sci ; 25(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38891785

RESUMO

Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1-20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia.


Assuntos
Queratinas , Leucoplasia Oral , Humanos , Leucoplasia Oral/metabolismo , Leucoplasia Oral/patologia , Leucoplasia Oral/genética , Queratinas/metabolismo , Queratinas/genética , Prognóstico , Biomarcadores Tumorais/metabolismo
5.
J Oral Pathol Med ; 52(1): 29-36, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36459078

RESUMO

BACKGROUND: Cell-free DNA (cfDNA) and cell-free mitochondrial DNA (cf-mtDNA) have been postulated as potential diagnostic and prognostic biomarkers for different human malignancies. Early detection of head and neck malignancies is fundamental for optimal patient management. This study, therefore, aimed to assess the utility of saliva-based liquid biopsy as a noninvasive source of cfDNA and cf-mtDNA for detecting head and neck cancer (HNSCC). METHODS: One hundred thirty-three patients diagnosed with either oral leukoplakia (OLK) or HNSCC were compared with 137 healthy volunteers. An unstimulated whole saliva sample was collected from each participant. The absolute copy numbers of salivary cf-mtDNA and cfDNA were quantified using Multiplex Quantitative PCR. Two diagnostic indices based on the investigated molecules were assessed for their ability to differentiate between different diagnostic categories. RESULTS: The median scores of cfDNA and cf-mtDNA were statistically significantly higher among HNSCC patients (p < 0.05), revealing area under the curve values of 0.758 and 0.826, respectively. The associated accuracy for this test in discriminating HNSCC from other diagnostic categories was 77.37% for the cfDNA-based index and 80.5% for the cf-mtDNA-based index. The median score of cfDNA was statistically significantly higher for patients with severe epithelial dysplasia (OED) compared to those with epithelial keratosis with no OED and mild OED. However, there was no significant difference between controls and OLK individuals. CONCLUSION: cfDNA and cf-mtDNA showed potential for use as precision medicine tools to detect HNSCC. Further multi-centre prospective studies are warranted to assess the prognostic utility of these molecules.


Assuntos
Ácidos Nucleicos Livres , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Saliva , Detecção Precoce de Câncer , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , DNA Mitocondrial/genética , Biomarcadores Tumorais/genética
6.
J Oral Pathol Med ; 52(3): 226-231, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36799652

RESUMO

BACKGROUND: Oral leukoplakia (OL) is one of the most prevalent oral potentially malignant disorders (OPMD). Although there is emerging evidence that quality of life (QoL) is impaired in subjects with OL; studies to date are based on single and heterogenous point-in-time assessments. The aim of this study was to ascertain if QoL scores change over time in individuals diagnosed with OL. METHODS: Forty-one individuals with OL were administered the Short Generic Health Questionnaire (SF-12) and the discipline-specific Oral Potentially Malignant Disorder Questionnaire (OPMDQ) at four points in time: at the time of clinical diagnosis, at the post-biopsy review (confirmed diagnosis), and at 3- and 6-month follow-up appointments. Responses were compared between the four time points. RESULTS: No significant differences were observed in the SF-12 questionnaire scores over time. However, a general improvement in the participants' life quality was evident over the 6-month period under investigation in the domains of psychological and social well-being (p = 0.0027) and effect of treatment on daily life (p = 0.0317) as well as in the total score (p = 0.0005) of the OPMDQ. Age, gender, medical status, tobacco/alcohol use, lesion site, size, the presence of dysplasia and treatment did not impact QoL scores over time. CONCLUSIONS: QoL scores of OL subjects may improve with time. Our results suggest that studies examining QoL in individuals with OL should be controlled for time at which the participants are surveyed.


Assuntos
Doenças da Boca , Qualidade de Vida , Humanos , Estudos Prospectivos , Estudos Longitudinais , Leucoplasia Oral/patologia
7.
J Oral Pathol Med ; 52(6): 504-513, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36908197

RESUMO

BACKGROUND: Dysregulation of the hypoxia-aerobic system has been postulated in various malignancies. Nonetheless, the contribution of hypoxia to oral carcinogenesis is yet to be elucidated. Understanding this mechanism is important for improving diagnostic tools and targeted therapies. This study aimed to assess the dysregulation of hypoxia-related factors during different stages of oral squamous cell carcinoma (OSCC) development. METHODS: Ninety-two patients diagnosed clinically with oral leukoplakia or OSCC were included and classified according to their histopathological diagnoses. A panel of seven hypoxia-related antibodies were used for immunohistochemical staining of each case. Automated quantification of immunostaining was used for objective reporting. Microvessel density was also assessed. RESULTS: Significant associations were reported for non-dysplastic epithelial changes and malignancy for Glut1, HIF-1α, vascular endothelial growth factor, and signal transducer and activator of transcription 3(p < 0.005). Similarly, microvessel density significantly increased with the severity of epithelial disorders. A multiple regression model including the H-score of HIF-1α and microvessel density could statistically significantly predict the grade of epithelial disorder (p < 0.005). The associated diagnostic accuracy of this approach was 88%. CONCLUSIONS: Hypoxia-associated events are observed during early epithelial dysplastic changes and have a potential role in oral carcinogenesis. The level of hypoxia may assist in stratifying the severity of epithelial changes among patients with oral leukoplakia.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Fator A de Crescimento do Endotélio Vascular , Biomarcadores , Carcinoma de Células Escamosas de Cabeça e Pescoço , Leucoplasia Oral/diagnóstico , Hipóxia , Hiperplasia , Carcinogênese
8.
Oral Dis ; 2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38105485

RESUMO

OBJECTIVES: Malnutrition is common among patients with head and neck cancer (HNC) and associated with poorer outcomes. Oral nutritional supplements (ONS) are often prescribed, with concerns raised about their cariogenicity. This study examined ONS use and caries experience in patients with HNC 12 months post-diagnosis. METHODS: Fifty-four patients with HNC referred for pre-radiotherapy dental assessment were recruited. Data collected included: age, gender, residential postcode, smoking, alcohol use, HNC characteristics, dental history, oral hygiene habits, dietary advice and ONS use. Data was collected at diagnosis, during radiotherapy and 6 weeks, three, six- and 12-months post-treatment completion. RESULTS: Fifty-one subjects completed the study. 76.5% of the participants used ONS for an average of 13.8 weeks. Caries developed in 22.9% of ONS users and 11.1% of non-users (p = 0.6585). The mean overall duration of ONS use was 18.7 weeks for the caries group and 8.5 weeks for the caries-free group (p = 0.1507). Lack of collaboration and disconnection was noted between dietary advice given by dieticians and dentists. CONCLUSIONS: ONS use is common among patients with HNC. Larger studies are needed to establish the reasons for caries development and impacts of ONS use on oral health. Importance of multidisciplinary management of malnutrition is highlighted.

9.
Oral Dis ; 29(5): 2256-2264, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35593522

RESUMO

OBJECTIVES: The use of autologous platelet concentrates has shown growing evidence as a promising therapy. We conducted a split-mouth study to evaluate the effectiveness of injectable platelet-rich fibrin (PRF) compared with triamcinolone acetonide (TA) in the treatment of oral lichen planus (OLP). MATERIALS AND METHODS: This split-mouth randomized trial included 12 patients with symptomatic, bilateral OLP lesions. The participants were randomly allocated to receive a 1-ml intralesional PRF injection on one side of the buccal mucosa and a 0.5-ml TA injection on the counterpart side. The application was performed once a week for 4 weeks. The outcomes were measured using a visual analog scale score, REU score, and lesion areas. RESULTS: Both injectable TA and PRF were effective in the management of oral lichen planus. After 4 weeks of treatment, there was an average reduction in the VAS score (68.5% i-PRF, 91% TA) and an average reduction in the REU score (74% i-PRF, 91% TA). There were no statistically significant differences between the two treatment methods (p > 0.05). CONCLUSIONS: Intralesional injection with TA showed more effectiveness than i-PRF in the management of OPL lesions. Although, i-PRF cannot be considered a first-line treatment option, it showed promising alternative therapy choice with no side effects.


Assuntos
Líquen Plano Bucal , Fibrina Rica em Plaquetas , Humanos , Líquen Plano Bucal/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Triancinolona Acetonida/efeitos adversos , Glucocorticoides/uso terapêutico , Administração Tópica
10.
Oral Dis ; 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37427836

RESUMO

OBJECTIVES: This study aimed to compare the effectiveness of carbon dioxide (CO2 ) laser vaporisation versus intralesional injection of triamcinolone acetonide (TA) in the management of oral lichen planus (OLP). METHODS: A randomised clinical trial with a split-mouth design was conducted on 16 patients with bilateral symptomatic OLP lesions. One side was treated with CO2 laser vaporisation, and the counterpart was treated with TA intralesional injection. The reticular-erythematous-ulcerative (REU) score, Thongprasom sign scoring (TSS), visual analogue scale (VAS) and lesion area were used to evaluate the lesions at weeks 0, 4 and 9. All participants were followed up for 9 months. RESULTS: Reduction in the REU, TSS scores and lesion area from baseline to the end of treatment was significantly greater in the CO2 group than in the TA group (p values were 0.001, 0.002 and 0.048 respectively). However, the reduction in VAS score did not differ between the two groups (p = 0.54). The recurrence rate was significantly higher in the TA group than in the CO2 group (75% vs. 31.1%; p = 0.016). CONCLUSIONS: CO2 laser vaporisation was more effective than TA intralesional injection in managing OLP and decreased recurrence rates.

11.
Oral Dis ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37727932

RESUMO

OBJECTIVE: Proper identification of oral potentially malignant disorders (OPMDs) provides an opportunity for oral cancer prevention. This study aims to assess the competency of dental health professionals in identifying OPMDs and, in turn, reducing the incidence of oral malignancy by early detection. METHODS: A 26-case online questionnaire of oral mucosal lesions was distributed to cohorts of 363 dental health professionals and dental students in Australia. The participants were asked to provide their provisional diagnosis for each case based on the available information. RESULTS: The overall accuracy in identifying oral mucosal lesions was 65.9%. There were no significant differences in the overall diagnostic accuracies between dental specialists, general dental practitioners and final-year dental students (p > 0.05). The lowest diagnostic accuracies were associated with normal mucosal variations and OPMDs. The predoctoral dental curriculum showed statistically significant values in terms of improving skills in diagnosing oral mucosal lesions. CONCLUSIONS: Lack of adequate knowledge in identifying OPMDs was evident among the participants, highlighting a non-promising figure in reducing the incidence of oral cancers in Australia. Comprehensive modifications of the current continuing professional development system are required to ensure adequate knowledge among dental health providers in Australia.

12.
Oral Dis ; 29(8): 3034-3048, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35801385

RESUMO

Head and neck cancers are a heterogeneous group of neoplasms, which together comprise the sixth most common cancer globally. Breath biopsies are a non-invasive clinical investigation that detect volatile organic compounds (VOCs) in exhaled breath. This systematic review examines current applications of breath biopsy for the diagnosis of head and neck squamous cell carcinoma (HNSCC), including data on efficacy and utility, and speculates on the future uses of this non-invasive detection method. Medline, PubMed, Web of Science, Cochrane and Scopus, as well as the grey literature were searched using a search strategy developed to identify relevant studies on the role of breath biopsy in the diagnosis of HNSCC. All included studies were subject to a thorough methodological quality assessment. The initial search generated a total of 1443 articles, 20 of which were eligible for review. A total of 660 HNSCC samples were investigated across the included studies. 3,7-dimethylundecane and benzaldehyde were among several VOCs to be significantly correlated with the presence of HNSCC compared to healthy controls. We show that current breath biopsy methods have high accuracy, specificity and sensitivity for identifying HNSCC. However, further studies are needed given the reported poor quality of the included studies.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Expiração , Biópsia , Testes Respiratórios
13.
Int J Mol Sci ; 24(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36835505

RESUMO

This study aimed to develop an in vitro three-dimensional (3D) cell culture model of oral carcinogenesis for the rapid, scalable testing of chemotherapeutic agents. Spheroids of normal (HOK) and dysplastic (DOK) human oral keratinocytes were cultured and treated with 4-nitroquinoline-1-oxide (4NQO). A 3D invasion assay using Matrigel was performed to validate the model. RNA was extracted and subjected to transcriptomic analysis to validate the model and assess carcinogen-induced changes. The VEGF inhibitors pazopanib and lenvatinib were tested in the model and were validated by a 3D invasion assay, which demonstrated that changes induced by the carcinogen in spheroids were consistent with a malignant phenotype. Further validation was obtained by bioinformatic analyses, which showed the enrichment of pathways associated with hallmarks of cancer and VEGF signalling. Overexpression of common genes associated with tobacco-induced oral squamous cell carcinoma (OSCC), such as MMP1, MMP3, MMP9, YAP1, CYP1A1, and CYP1B1, was also observed. Pazopanib and lenvatinib inhibited the invasion of transformed spheroids. In summary, we successfully established a 3D spheroid model of oral carcinogenesis for biomarker discovery and drug testing. This model is a validated preclinical model for OSCC development and would be suitable for testing a range of chemotherapeutic agents.


Assuntos
Antineoplásicos , Biomarcadores Tumorais , Carcinogênese , Técnicas de Cultura de Células em Três Dimensões , Neoplasias Bucais , Esferoides Celulares , Humanos , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinógenos/farmacologia , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Ensaios de Seleção de Medicamentos Antitumorais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células Tumorais Cultivadas , Antineoplásicos/farmacologia
14.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36982316

RESUMO

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.


Assuntos
Fator XIIIa , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Subunidade alfa de Receptor de Interleucina-3 , Leucoplasia Oral , Macrófagos/patologia , Transformação Celular Neoplásica/patologia
15.
Mod Pathol ; 35(9): 1151-1159, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35361889

RESUMO

Oral epithelial dysplasia (OED) is a precursor state usually preceding oral squamous cell carcinoma (OSCC). Histological grading is the current gold standard for OED prognostication but is subjective and variable with unreliable outcome prediction. We explore if individual OED histological features can be used to develop and evaluate prognostic models for malignant transformation and recurrence prediction. Digitised tissue slides for a cohort of 109 OED cases were reviewed by three expert pathologists, where the prevalence and agreement of architectural and cytological histological features was assessed and association with clinical outcomes analysed using Cox proportional hazards regression and Kaplan-Meier curves. Within the cohort, the most prevalent features were basal cell hyperplasia (72%) and irregular surface keratin (60%), and least common were verrucous surface (26%), loss of epithelial cohesion (30%), lymphocytic band and dyskeratosis (34%). Several features were significant for transformation (p < 0.036) and recurrence (p < 0.015) including bulbous rete pegs, hyperchromatism, loss of epithelial cohesion, loss of stratification, suprabasal mitoses and nuclear pleomorphism. This led us to propose two prognostic scoring systems including a '6-point model' using the six features showing a greater statistical association with transformation and recurrence (bulbous rete pegs, hyperchromatism, loss of epithelial cohesion, loss of stratification, suprabasal mitoses, nuclear pleomorphism) and a 'two-point model' using the two features with highest inter-pathologist agreement (loss of epithelial cohesion and bulbous rete pegs). Both the 'six point' and 'two point' models showed good predictive ability (AUROC ≥ 0.774 for transformation and 0.726 for recurrence) with further improvement when age, gender and histological grade were added. These results demonstrate a correlation between individual OED histological features and prognosis for the first time. The proposed models have the potential to simplify OED grading and aid patient management. Validation on larger multicentre cohorts with prospective analysis is needed to establish their usefulness in clinical practice.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Lesões Pré-Cancerosas , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/patologia , Humanos , Hiperplasia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Prognóstico
16.
J Oral Pathol Med ; 51(6): 563-572, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35460123

RESUMO

BACKGROUND: This study assessed the efficacy of using oral liquid-based brush cytology (OLBC) coupled with immunostained cytology-derived cell-blocks, quantified using machine-learning, in the diagnosis of oral lichen planus (OLP). METHODS: Eighty-two patients diagnosed clinically with either OLP or oral lichenoid lesion (OLL) were included. OLBC samples were obtained from all patients before undergoing surgical biopsy. Liquid-based cytology slides and cell-blocks were prepared and assessed by cytomorphology and immunocytochemistry for four antibodies (Ki-67, BAX, NF-κB-p65, and AMACR). For comparison purposes, a sub-group of 31 matched surgical biopsy samples were selected randomly and assessed by immunohistochemistry. Patients were categorized according to their definitive diagnoses into OLP, OLL, and clinically lichenoid, but histopathologically dysplastic lesions (OEDL). Machine-learning was utilized to provide automated quantification of positively stained protein expression. RESULTS: Cytomorphological assessment was associated with an accuracy of 77.27% in the distinction between OLP/OLL and OEDL. A strong concordance of 92.5% (κ = 0.84) of immunostaining patterns was evident between cell-blocks and tissue sections using machine-learning. A diagnostic index using a Ki-67-based model was 100% accurate in detecting lichenoid cases with epithelial dysplasia. A BAX-based model demonstrated an accuracy of 92.16%. The accuracy of cytomorphological assessment was greatly improved when it was combined with BAX immunoreactivity (95%). CONCLUSIONS: Cell-blocks prepared from OLBC are reliable and minimally-invasive alternatives to surgical biopsies to diagnose OLLs with epithelial dysplasia when combined with Ki-67 immunostaining. Machine-learning has a promising role in the automated quantification of immunostained protein expression.


Assuntos
Líquen Plano Bucal , Erupções Liquenoides , Neoplasias Bucais , Biópsia , Humanos , Antígeno Ki-67 , Líquen Plano Bucal/patologia , Erupções Liquenoides/diagnóstico , Erupções Liquenoides/patologia , Neoplasias Bucais/patologia , Proteína X Associada a bcl-2
17.
Clin Oral Investig ; 26(3): 2317-2334, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35066686

RESUMO

PURPOSE: To investigate the global prevalence of the JP2 genotype of Aggregatibacter actinomycetemcomitans (Aa). METHODS: A comprehensive electronic search of databases, PUBMED, MEDLINE, EMBASE, BIOSIS, and SCOPUS, was conducted up to August 2021. All published articles and studies were considered, excluding animal studies, editorials, personal opinions, letters to editor, conference abstracts, posters, and those studies without full text. The primary objective of this systematic review was to determine the presence of the JP2 genotype of Aa in the world population. RESULTS: A total of 295 articles were identified, of which 62 were preselected, and 51 were finally included in this review. Due to variable study designs and high heterogeneity, a meta-analysis was not conducted. A total of 9744 subjects were screened for the presence of the JP2 genotype of Aa worldwide, and only 621 cases were found positive. CONCLUSIONS: A relatively high presence of JP2 genotype of Aa was found in subjects from South America, North America, and Africa. There were no studies estimating the presence of the JP2 genotype of Aa in the Oceania region. The heterogeneity and quality of the included publications suggest that caution should be exercised when interpreting the data and that there remains an important need for additional evidence. CLINICAL RELEVANCE: Periodontitis is a highly prevalent inflammatory oral disorder with substantial aesthetic, functional, and psychological implications for patients. The JP2 genotype of Aa is implicated in the pathogenesis of periodontitis. To the best of our knowledge, there is a lack of systematic reviews estimating the presence of the JP2 genotype of Aa in the global population. We identified a relatively high presence of the JP2 genotype of Aa in specific geographic areas of the world, and we propose that cross-sectional and longitudinal studies are lacking in the Oceania region and need to be conducted to estimate the presence of the JP2 genotype of Aa in this region.


Assuntos
Aggregatibacter actinomycetemcomitans , Aggregatibacter actinomycetemcomitans/genética , Estudos Transversais , Genótipo , Humanos , Periodontite/microbiologia , Prevalência
18.
BMC Oral Health ; 22(1): 381, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064693

RESUMO

BACKGROUND: Oral cancer is frequently characterized with an aggressive behavior and an unfavorable prognosis; however, it is generally associated with promising prognosis if detected early. Therefore, this study aimed to assess knowledge, practices, and attitudes toward oral cancer prevention among dental students and interns; and to investigate the factors that influence their practices of oral cancer screening or prevention. MATERIAL AND METHODS: A cross-sectional questionnaire-based survey was conducted between March and April of 2022 on the fourth- and fifth-year undergraduate dental students and interns in the College of Dentistry at Arab American University in Palestine. A 48-item questionnaire which has 4 sections: demographics, knowledge, practices, and attitudes toward oral cancer prevention and early detection was sent to all eligible participants (N = 570). RESULTS: The response rate was 68.7% (N = 351). About 66.8% of the respondents had poor knowledge about oral cancer and its risk factors, and 85.5% had a poor practice of oral cancer early detection and prevention; however, the majority of the respondents (81.1%) had shown favorable attitudes toward oral cancer prevention. Interns had significantly better knowledge and attitude scores compared to the undergraduate dental students (P < 0.05). Lack of training, time, confidence, and effectiveness were stated among the barriers to oral cancer screening. CONCLUSIONS: Most of the participants surveyed in this study appeared to lack adequate knowledge and skills in oral cancer prevention and early detection; however, they seemed to have good motivation and a good attitude toward oral cancer prevention training.


Assuntos
Neoplasias Bucais , Estudantes de Odontologia , Árabes , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/prevenção & controle , Inquéritos e Questionários
19.
J Oral Pathol Med ; 50(3): 287-298, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981238

RESUMO

BACKGROUND: The malignant transformation (MT) potential of oral lichen planus (OLP) has sparked heated debates for almost a century, despite the fact that global figures of OLP prevalence and oral cancer incidence do not support an association mathematically. In this study, we performed a systematic review and meta-analysis, using strict inclusion criteria, to more precisely assess the malignant potential rate of OLP and the influence of associated risk factors. METHODS: All reports that documented MT of OLP and published in the English language until January 2020 were included if they met the following strict criteria: (a) the presence of a properly verified OLP diagnosis, (b) a clear description of the cancerous lesion developing at the same site as the verified OLP lesion; and (c) a follow-up period of a minimum of 6 months prior to carcinoma development. RESULTS: Thirty-three studies were included in this analysis with a total of 12 838 OLP patients. Of these, 151 cases were initially considered to have progressed to carcinoma (1.2%). However, after applying strict criteria, only 56 cases were considered to have undergone MT from OLP (0.44%). The risk of MT was significantly higher among OLP patients who smoked (OR = 4.62), consumed alcohol (OR = 3.22), were seropositive for HCV (OR = 3.77) and/or displayed a red OLP subtype (OR = 0.37). CONCLUSIONS: Our results suggest that the reported OLP malignant transformation rates are exaggerated, and these do not reflect the actual clinical course of the disease according to strict clinical and histopathological criteria.


Assuntos
Carcinoma de Células Escamosas , Líquen Plano Bucal , Neoplasias Bucais , Transformação Celular Neoplásica , Humanos , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/epidemiologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/epidemiologia , Fatores de Risco
20.
J Oral Pathol Med ; 50(9): 946-953, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34358361

RESUMO

BACKGROUND: Oral lichen planus (OLP) is a relatively common oral disorder which shares clinical and histopathological features with other lichenoid lesions, leading to considerable inter-observer disagreement. This negatively impacts understanding of the pathogenesis and malignant transformation potential of this condition. METHODS: Artificial intelligence was employed to create a machine-learning artificial neural network to identify and quantify mononuclear cells and granulocytes within the inflammatory infiltrates in digitized hematoxylin and eosin microscopic slides. Twenty-four regions of interest were extracted from OLP cases for learning purposes and validated on a retrospective cohort of 130 cases. All cases were related to patients with confirmed diagnoses of OLP, oral lichenoid lesions (OLLs), or oral epithelial dysplasia (OED) with lichenoid host response. RESULTS: The number of inflammatory cells was statistically significantly higher in OLP compared to OLLs or OED with lichenoid host response (p < 0.0005). The proposed machine-learning method was reliably capable of detecting OLP cases based on the number of inflammatory cells and the number of mononuclear cells with an area under the curve of 0.982 and 0.988, respectively. Identifying a cut-off point between OLP and other lichenoid conditions based on the number of mononuclear cells showed a sensitivity of 100% and an accuracy of 94.62%. CONCLUSION: Artificial intelligence has shown promising outcomes and provides a robust approach to enhance the accuracy of anatomical pathologists in accurately diagnosing OLP using features of disease pathogenesis.


Assuntos
Líquen Plano Bucal , Doenças da Boca , Inteligência Artificial , Humanos , Líquen Plano Bucal/diagnóstico , Aprendizado de Máquina , Estudos Retrospectivos
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