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1.
Biosensors (Basel) ; 14(6)2024 May 30.
Article in English | MEDLINE | ID: mdl-38920585

ABSTRACT

Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We tested the presence of CIP2A in human leukoplakia samples, which can undergo malignant conversion into aggressive oral squamous cell carcinoma. The method used commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection which was five orders lower than that of commercial ELISA kits. A specially designed printed circuit board (PCB) facilitated accurate measurements, and the device's performance was optimized through characteristic tests. Human sample testing validated the biosensor's effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues.


Subject(s)
Biosensing Techniques , Leukoplakia, Oral , Saliva , Humans , Leukoplakia, Oral/diagnosis , Saliva/chemistry , Biomarkers, Tumor/analysis , Membrane Proteins , Mouth Neoplasms/diagnosis , Enzyme-Linked Immunosorbent Assay
2.
Int J Mol Sci ; 25(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38891785

ABSTRACT

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.


Subject(s)
Keratins , Leukoplakia, Oral , Humans , Leukoplakia, Oral/metabolism , Leukoplakia, Oral/pathology , Leukoplakia, Oral/genetics , Keratins/metabolism , Keratins/genetics , Prognosis , Biomarkers, Tumor/metabolism
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.
Hematol Oncol Clin North Am ; 38(4): 813-830, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38705773

ABSTRACT

This article explores the multifaceted landscape of oral cancer precursor syndromes. Hereditary disorders like dyskeratosis congenita and Fanconi anemia increase the risk of malignancy. Oral potentially malignant disorders, notably leukoplakia, are discussed as precursors influenced by genetic and immunologic facets. Molecular insights delve into genetic mutations, allelic imbalances, and immune modulation as key players in precancerous progression, suggesting potential therapeutic targets. The article navigates the controversial terrain of management strategies of leukoplakia, encompassing surgical resection, chemoprevention, and immune modulation, while emphasizing the ongoing challenges in developing effective, evidence-based preventive approaches.


Subject(s)
Head and Neck Neoplasms , Humans , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/etiology , Precancerous Conditions/diagnosis , Precancerous Conditions/genetics , Precancerous Conditions/etiology , Leukoplakia, Oral/diagnosis , Leukoplakia, Oral/therapy , Leukoplakia, Oral/genetics , Leukoplakia, Oral/etiology , Mouth Neoplasms/diagnosis , Mouth Neoplasms/therapy , Mouth Neoplasms/etiology , Genetic Predisposition to Disease
5.
Article in English | MEDLINE | ID: mdl-38760284

ABSTRACT

OBJECTIVES: Proliferative verrucous leukoplakia (PVL) is a rare but highly aggressive variant of oral leukoplakia that almost inevitably progresses to oral squamous cell carcinoma (OSCC). The aims of this study were to perform whole exome sequencing of a cohort of patients diagnosed with PVL and identify potential mutational profiles and pathways in this disorder. STUDY DESIGN: A total of 12 oral cavity mucosal biopsies from 6 patients with oral lesions clinically compatible with PVL were used. Of these, 9 were diagnosed as dysplasia, 1 OSCC, and 2 hyperkeratosis/hyperplasia. Exome sequencing used the Ion AmpliSeq Exome platform. Ion Reporter software was used for variant calling, annotation, and filtering. Analysis and visualization of somatic mutations was carried out using the MAFtools R package. RESULTS: Following exome sequencing and mutational profiling, we analyzed the profiles for cancer associated genes and signatures. Genes previously associated with OSCC, including HYDIN, MUC16, MAML3, CDKN2A, FAT1, and CASP8, were mutated in multiple samples. Several DNA damage repair genes including PARP1 were mutated in PVL samples. NOTCH and Hippo pathways were the most frequently impacted by mutation. CONCLUSIONS: This genome wide characterization of premalignant PVL identifies both known and potentially novel oncogenic mechanisms in this disorder.


Subject(s)
Leukoplakia, Oral , Mouth Neoplasms , Mutation , Humans , Leukoplakia, Oral/genetics , Leukoplakia, Oral/pathology , Female , Male , Middle Aged , Aged , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Exome Sequencing , Biopsy , Adult , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology
6.
BMC Oral Health ; 24(1): 639, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816724

ABSTRACT

BACKGROUND: Proliferative verrucous leukoplakia (PVL), distinguished by its malignant transformation rate of 43.87% to 65.8%, stands as the oral potentially malignant disorder with the highest propensity for malignancy. PVL is marked by distinctive heterogeneity regarding the clinical or histopathological characteristics as well as prognostic factors pertinent to this condition. The purpose of this study is to compile and assess the clinicopathological features, malignant transformation, and associated risk factors in patients diagnosed with PVL. METHODS: This study is a hospital-based retrospective longitudinal study of 36 patients diagnosed with PVL from 2013 to 2023. We conducted complete clinical and histopathological evaluations of the patients. RESULTS: The cohort comprised 16 males and 20 females, yielding a male-to-female ratio of 1:1.25. The follow-up period ranged from 8 to 125 months, with an average of 47.50 months. The most common clinical type of lesion was the verrucous form (58.33%), and the gingiva was the most common site (44.44%). Each patient had between 2 to 7 lesions, averaging 3.36 per patient. During the follow-up period, twelve patients (33.3%) developed oral cancer, with an average time to malignant transformation of 35.75 months. Kaplan-Meier survival analysis indicated that patients with complaints of pain, roughness, or a rough sensation, with diabetes, and the presence of cytologic atypia histologically showed a higher risk of malignant transformation (p < 0.05). In this study, the rate of malignant transformation in the treatment group (5/23) was lower than that in the untreated group (7/13), however, no statistically significant difference (p = 0.05). CONCLUSION: The main complaints of pain, roughness, or foreign body sensation, coupled with cytologic atypia histologically are indicative of an increased risk of malignant transformation in PVL. Further research is needed to elucidate the influence of these clinicopathological parameters on the malignant progression of PVL.


Subject(s)
Cell Transformation, Neoplastic , Leukoplakia, Oral , Humans , Male , Female , Leukoplakia, Oral/pathology , Cell Transformation, Neoplastic/pathology , Retrospective Studies , Middle Aged , Longitudinal Studies , Aged , Adult , Risk Factors , Mouth Neoplasms/pathology , Aged, 80 and over , Precancerous Conditions/pathology
7.
Stomatologiia (Mosk) ; 103(2): 5-11, 2024.
Article in Russian | MEDLINE | ID: mdl-38741528

ABSTRACT

OBJECTIVE: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant¼ diseases of the oral mucosa. MATERIALS AND METHODS: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein. RESULTS: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases. CONCLUSION: To diagnose early manifestations of neoplastic processes in «potentially malignant¼ diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.


Subject(s)
Ki-67 Antigen , Mouth Mucosa , Precancerous Conditions , Humans , Middle Aged , Male , Female , Aged , Adult , Mouth Mucosa/pathology , Aged, 80 and over , Ki-67 Antigen/analysis , Precancerous Conditions/pathology , Precancerous Conditions/diagnosis , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Leukoplakia, Oral/pathology , Leukoplakia, Oral/diagnosis , Tumor Suppressor Protein p53/analysis , Tumor Suppressor Protein p53/metabolism , Cheilitis/pathology , Cheilitis/diagnosis , Human papillomavirus 16/isolation & purification , Human papillomavirus 16/genetics , Cyclin-Dependent Kinase Inhibitor p16/analysis , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Erythroplasia/pathology , Erythroplasia/diagnosis
9.
Phytomedicine ; 129: 155548, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38583347

ABSTRACT

BACKGROUND: Oral leukoplakia (OLK), characterized by abnormal epithelial hyperplasia, is the most common precancerous oral mucosa lesion and is closely related to oxidative stress. Cucurbitacin B (CuB), a tetracyclic triterpenoid molecule derived from plants, has shown promising anti-proliferative and antioxidant effects in preclinical studies. However, whether CuB can play an antiproliferative role in OLK by regulating oxidative stress remains elusive. PURPOSE: To investigate the role of CuB in inhibiting the malignant progression of oral leukoplakia and to further explore its underlying mechanisms of action. METHODS: In vitro, the effect of CuB on the proliferation, migration, apoptosis, and cell cycle of OLK cells DOK was detected. The core genes and key pathways of OLK and CuB were analyzed in the transcriptome database, by using immunofluorescence, qRT-PCR, and Western blot to evaluate the expression levels of the ferroptosis markers ROS, GSH, MDA, Fe2+, and marker genes SLC7A11, GPX4, and FTH1. Immunohistochemistry of human tissue was performed to investigate the expression of the SLC7A11. In vivo, the model of OLK was established in C57BL/6 mice and the biosafety of CuB treatment for OLK was further evaluated. RESULTS: CuB substantially suppressed the proliferation of DOK cells. Bioinformatics analysis showed that the core targets of OLK crossing with CuB include SLC7A11 and that the essential pathways involve ROS and ferroptosis. In vitro experiments indicated that CuB might promote ferroptosis by down-regulating the expression of SLC7A11. We observed a gradual increase in SLC7A11 expression levels during the progression from normal oral mucosa to oral leukoplakia with varying degrees of epithelial dysplasia. In vivo experiments demonstrated that CuB inhibited the malignant progression of OLK by promoting ferroptosis in OLK mice and exhibited a certain level of biosafety. CONCLUSION: This study demonstrated for the first time that CuB could effectively inhibit the malignant progression of OLK by inducing ferroptosis via activating the SLC7A11/ mitochondrial oxidative stress pathway. These findings indicate that CuB could serve as the lead compound for the future development of anti-oral leukoplakia drugs.


Subject(s)
Amino Acid Transport System y+ , Cell Proliferation , Ferroptosis , Leukoplakia, Oral , Mitochondria , Oxidative Stress , Triterpenes , Ferroptosis/drug effects , Leukoplakia, Oral/drug therapy , Animals , Oxidative Stress/drug effects , Triterpenes/pharmacology , Humans , Amino Acid Transport System y+/metabolism , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Cell Proliferation/drug effects , Reactive Oxygen Species/metabolism , Mice, Inbred C57BL , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Male , Cell Movement/drug effects
10.
Niger J Clin Pract ; 27(4): 467-474, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38679769

ABSTRACT

BACKGROUND: Tobacco smoking statistics are alarming and the oral mucosa is the first human part of the body that is exposed to the toxic substances of smoking. AIMS: Considering the high prevalence rate of tobacco-associated problems in the oral cavity and few studies on the Iranian population regarding the effects of smoking on the oral cavity, this study aimed to evaluate the relationship between smoking and oral lesions in the Iranian population. MATERIALS AND METHODS: Observational study. In this observational study, the oral cavities of 200 participants (smokers = 100 and non-smokers = 100) were examined by a trained dental student under the supervision of an oral and maxillofacial medicine expert, and the presence of coated tongue, leukoedema, leukoplakia, smoker's palate, smoker's melanosis, erythroplakia, frictional hyperkeratosis, acute pseudomembranous candidiasis, and erythematous candidiasis were recorded. Xerostomia was evaluated based on participants' self-reporting through a questionnaire. All data were analyzed using T-test, Chi-square test, odd ratio, 95% confidence interval, Fisher's exact test, and Spearman's rank correlation coefficient. RESULTS: The results of this study showed smoking is significantly associated with an increased risk of coated tongue (OR: 1.80, 95% CI: 1.32-3.54, P = 0.005), smoker's melanosis (OR: 6.176, 95% CI: 3.28-11.62, P = 0.00002), and frictional hyperkeratosis (OR: 1.33, 95% CI: 0.68-2.60, P = 0.005). However, no significant association was observed between smoking and leukoedema (OR: 1, 95% CI: 0.51-1.94, P = 1). None of the participants presented smoker's palate, erythroplakia, and candidiasis. CONCLUSIONS: This study's results showed that smokers exhibited a greater chance of developing oral lesions compared to non-smokers.


Subject(s)
Mouth Diseases , Mouth Mucosa , Smokers , Humans , Iran/epidemiology , Male , Female , Mouth Mucosa/pathology , Adult , Middle Aged , Mouth Diseases/epidemiology , Mouth Diseases/etiology , Smokers/statistics & numerical data , Smoking/epidemiology , Smoking/adverse effects , Non-Smokers/statistics & numerical data , Prevalence , Young Adult , Xerostomia/epidemiology , Aged , Leukoplakia, Oral/epidemiology
11.
Cells ; 13(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38667326

ABSTRACT

Precancerous cells in the oral cavity may appear as oral potentially malignant disorders, but they may also present as dysplasia without visual manifestation in tumor-adjacent tissue. As it is currently not possible to prevent the malignant transformation of these oral precancers, new treatments are urgently awaited. Here, we generated precancer culture models using a previously established method for the generation of oral keratinocyte cultures and incorporated CRISPR/Cas9 editing. The generated cell lines were used to investigate the efficacy of a set of small molecule inhibitors. Tumor-adjacent mucosa and oral leukoplakia biopsies were cultured and genetically characterized. Mutations were introduced in CDKN2A and TP53 using CRISPR/Cas9 and combined with the ectopic activation of telomerase to generate cell lines with prolonged proliferation. The method was tested in normal oral keratinocytes and tumor-adjacent biopsies and subsequently applied to a large set of oral leukoplakia biopsies. Finally, a subset of the immortalized cell lines was used to assess the efficacy of a set of small molecule inhibitors. Culturing and genomic engineering was highly efficient for normal and tumor-adjacent oral keratinocytes, but success rates in oral leukoplakia were remarkably low. Knock-out of CDKN2A in combination with either the activation of telomerase or knock-out of TP53 seemed a prerequisite for immortalization. Prolonged culturing was accompanied by additional genetic aberrations in these cultures. The generated cell lines were more sensitive than normal keratinocytes to small molecule inhibitors of previously identified targets. In conclusion, while very effective for normal keratinocytes and tumor-adjacent biopsies, the success rate of oral leukoplakia cell culturing methods was very low. Genomic engineering enabled the prolonged culturing of OL-derived keratinocytes but was associated with acquired genetic changes. Further studies are required to assess to what extent the immortalized cultures faithfully represent characteristics of the cells in vivo.


Subject(s)
Keratinocytes , Leukoplakia, Oral , Mouth Neoplasms , Humans , Keratinocytes/metabolism , Keratinocytes/pathology , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Leukoplakia, Oral/genetics , Leukoplakia, Oral/pathology , Telomerase/genetics , Telomerase/metabolism , Genetic Engineering , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism , CRISPR-Cas Systems/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Mouth Mucosa/pathology , Precancerous Conditions/pathology , Precancerous Conditions/genetics
12.
J Photochem Photobiol B ; 255: 112907, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677259

ABSTRACT

OBJECTIVE: The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines. METHODS: HOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment. RESULTS: OM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased. CONCLUSIONS: OLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.


Subject(s)
Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Epithelial Cells , Leukoplakia, Oral , Mesenchymal Stem Cells , Mouth Mucosa , Mouth Neoplasms , Photochemotherapy , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mouth Mucosa/pathology , Mouth Mucosa/cytology , Leukoplakia, Oral/pathology , Leukoplakia, Oral/therapy , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Movement/drug effects , Cell Movement/radiation effects , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Mouth Neoplasms/therapy , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Photosensitizing Agents/pharmacology , Cell Line, Tumor , Aminolevulinic Acid/pharmacology , Cell Differentiation/drug effects , Transcriptome/drug effects
13.
BMC Oral Health ; 24(1): 434, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594651

ABSTRACT

BACKGROUND: The grading of oral epithelial dysplasia is often time-consuming for oral pathologists and the results are poorly reproducible between observers. In this study, we aimed to establish an objective, accurate and useful detection and grading system for oral epithelial dysplasia in the whole-slides of oral leukoplakia. METHODS: Four convolutional neural networks were compared using the image patches from 56 whole-slide of oral leukoplakia labeled by pathologists as the gold standard. Sequentially, feature detection models were trained, validated and tested with 1,000 image patches using the optimal network. Lastly, a comprehensive system named E-MOD-plus was established by combining feature detection models and a multiclass logistic model. RESULTS: EfficientNet-B0 was selected as the optimal network to build feature detection models. In the internal dataset of whole-slide images, the prediction accuracy of E-MOD-plus was 81.3% (95% confidence interval: 71.4-90.5%) and the area under the receiver operating characteristic curve was 0.793 (95% confidence interval: 0.650 to 0.925); in the external dataset of 229 tissue microarray images, the prediction accuracy was 86.5% (95% confidence interval: 82.4-90.0%) and the area under the receiver operating characteristic curve was 0.669 (95% confidence interval: 0.496 to 0.843). CONCLUSIONS: E-MOD-plus was objective and accurate in the detection of pathological features as well as the grading of oral epithelial dysplasia, and had potential to assist pathologists in clinical practice.


Subject(s)
Deep Learning , Humans , Leukoplakia, Oral/diagnosis
14.
Article in English | MEDLINE | ID: mdl-38653605

ABSTRACT

OBJECTIVE: This study aimed to assess the impact of oral medicine (OM) practitioners on the literature regarding oral potentially malignant disorders (OPMDs), focusing on oral leukoplakia. STUDY DESIGN: Using a bibliometric approach on the Scopus database until September 1, 2022, the top 100 cited articles were analyzed for article type, subtopic, specialty contributions, author metrics, and keywords. The Bibliometrix package for R and VOSviewer were used to evaluate interactions and generate science maps. RESULTS: OM practitioners, comprising 39% of contributors, played a significant role in studies related to nomenclature and screening of OPMDs. Notably, 4 OM specialists ranked among the most prolific authors, demonstrating denser collaboration with OM co-authors compared to other cancer specialists. However, there was a scarcity of OPMD management studies authored by OM practitioners. CONCLUSIONS: Despite the paucity of OM practitioners, the findings underscored the substantial contribution of OM practitioners in developing OPMD nomenclature and classification, emphasizing the need for increased collaboration with cancer specialists to conduct comprehensive clinical trials for OPMD management. The study highlights the importance of standardized criteria in OPMDs research for better data comparison and encourages further efforts from the OM scientific community.


Subject(s)
Bibliometrics , Leukoplakia, Oral , Mouth Neoplasms , Oral Medicine , Humans , Precancerous Conditions
15.
BMC Oral Health ; 24(1): 469, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632580

ABSTRACT

BACKGROUND: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients. METHODS: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention. RESULTS: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects. CONCLUSION: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.


Subject(s)
Laser Therapy , Lasers, Solid-State , Humans , Network Meta-Analysis , Carbon Dioxide/therapeutic use , Patient Comfort , Leukoplakia, Oral , Lasers, Solid-State/therapeutic use
16.
Article in English | MEDLINE | ID: mdl-38553305

ABSTRACT

OBJECTIVES: To analyze the clinical and histopathological characteristics of oral leukoplakia (OL) in the Japanese population and investigate the prevalence and risk factors for epithelial dysplasia (ED) and carcinoma within lesions. STUDY DESIGN: Data, including age, sex, lesion site, and histopathological features, of 676 cases diagnosed with OL over the previous 10 years were analyzed. Dysplasia and carcinoma prevalence were determined. RESULTS: In male patients, the most affected site was the gingiva (42.7%), whereas in females, it was the tongue (47.6%). Moreover, ED was more prevalent in males (41.9%), whereas epithelial hyperplasia was more common in females (44.7%). A significant difference was observed between affected sites with regard to the presence of dysplasia. The ED rates by site were 64.6% and 33.7% for the tongue and gingiva, respectively (P < 0.05). The squamous cell carcinoma rates by site were 23.4%, 5.4%, and 3.4% for the tongue, buccal mucosa, and gingiva, respectively (P < 0.05). Logistic regression analysis revealed a higher prevalence of dysplasia in males than it did in females and that the risk for both dysplasia and carcinoma was highest in the tongue. CONCLUSIONS: Dysplasia is common in OL cases, often showing carcinoma. Early biopsy and interventions are key in OL management.


Subject(s)
Leukoplakia, Oral , Humans , Leukoplakia, Oral/pathology , Leukoplakia, Oral/epidemiology , Male , Female , Middle Aged , Japan/epidemiology , Aged , Prevalence , Risk Factors , Adult , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/epidemiology , Precancerous Conditions/pathology , Precancerous Conditions/epidemiology
17.
Quintessence Int ; 55(5): 412-419, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38526423

ABSTRACT

OBJECTIVE: The goal was to identify the lifestyle risk factors associated with benign and potentially malignant oral disorders. METHOD AND MATERIALS: The study enrolled first-time patients from the Oral Pathology Section, volunteers from Oviedo, and first-time patients from the University of Oviedo dental clinic. Patients underwent a survey that included sociodemographic information, lifestyle habits, and medical history. A comprehensive examination of the oral mucosa was conducted. Univariate and multivariate logistic regression were conducted using R software. RESULTS: Among the 183 participants, the most prevalent lesions were varicose veins (43.20%), cheek/lip biting (34.97%), and coated tongue (33.33%). Among the oral potentially malignant disorders (16.39%) were oral lichen planus (12.64%) and leukoplakia (3.33%). Tobacco was associated with melanotic pigmentation (OR 3.87, P = .001) and coated tongue (OR 5.90, P = .001). Longer intervals since the last check-up were associated with traumatic keratosis (OR 2.95, P = .031). Age and heavy smoking were found to have higher risk of developing an oral potentially malignant disorder (OR 1.04, P = .035, and OR 7.35, P = .028, respectively). CONCLUSIONS: These data should be considered when organizing public health programs focused on the detection and screening of heavy smokers. It is also important to strengthen the oral pathology units in universities as reference centers for students to acquire the necessary knowledge for their diagnosis and treatment, while simultaneously promoting awareness of this risk factor for oral precancer among the general population.


Subject(s)
Precancerous Conditions , Humans , Risk Factors , Spain/epidemiology , Female , Male , Pilot Projects , Prevalence , Precancerous Conditions/epidemiology , Middle Aged , Adult , Mouth Diseases/epidemiology , Mouth Neoplasms/epidemiology , Aged , Life Style , Smoking/epidemiology , Leukoplakia, Oral/epidemiology
18.
Pediatr Dermatol ; 41(3): 476-479, 2024.
Article in English | MEDLINE | ID: mdl-38413200

ABSTRACT

We have observed a distinct phenomenon of transient oral lingual leukoplakia in infancy and report 22 healthy infants with gray-white plaques on the dorsal tongue with sparing of the tip from four medical centers in three countries. The onset of the eruption ranged from 1 week to 7 months of life and resolved in 19 patients (86%, with 3 patients lost to follow-up). None of the eight patients examined at 1 year of age had residual findings. We believe this is a common entity that can be distinguished from oral candidiasis on clinical and/or laboratory examination and name this entity "transient infantile lingual leukoplakia."


Subject(s)
Leukoplakia, Oral , Humans , Male , Infant , Female , Leukoplakia, Oral/diagnosis , Leukoplakia, Oral/pathology , Infant, Newborn , Tongue Diseases/diagnosis , Tongue Diseases/pathology , Tongue/pathology , Diagnosis, Differential
20.
Photodiagnosis Photodyn Ther ; 46: 104026, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38403144

ABSTRACT

OBJECTIVE: To investigate the clinical efficacy of aminovalerate hydrochloride photodynamic therapy (PDT) for oral potentially malignant disorder (OPMD),oral leukoplakia (OLK), along with identifying the influencing factors.Additionally, the study aims to detect the rates of recurrence and malignancy after PDT. METHOD: 60 patients with OPMD who received PDT at our hospital from 2006 to 2021 were included in this study. Relevant patient medical data were collected and analyzed using SAS 9.4 software.The Mann-Whitney U test was used to retrospectively analyze the factors influencing clinical efficacy, as well as recurrence rate and malignant transformation rate (MTR) after treatment. RESULT: Among the 60 OPMD patients receiving PDT, complete remission in 13 (21.67 %), partial remission in 39 (65.00 %), and no remission in eight (13.33 %), resulting in an overall effective rate of 86.67 %.Fifteen patients experienced relapse, leading to a recurrence rate of 25.00 %. Among these relapses,11 patients occurred within one year after treatment, corresponding to an 18.33 % recurrence rate during that period. Moreover, nine patients developed malignant transformation (MT), resulting in an MTR of 15.00 %. Out of these patients, six individuals developed MT within one year after treatment, resulting in a one-year MTR of 10.00 %. CONCLUSION: The study findings indicate that PDT shows promising clinical efficacy in the treatment of OPMD, with relatively limited and tolerable postoperative adverse reactions. However, there remains a certain rate of recurrence and malignancy after treatment. Therefore, close attention should be paid to postoperative monitoring, regular follow-up, and further expansion of the sample size to observe its long-term efficacy.


Subject(s)
Leukoplakia, Oral , Mouth Neoplasms , Photochemotherapy , Photosensitizing Agents , Humans , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Female , Male , Middle Aged , Aged , Retrospective Studies , Adult , Leukoplakia, Oral/drug therapy , Mouth Neoplasms/drug therapy , Aminolevulinic Acid/therapeutic use , Aged, 80 and over , Neoplasm Recurrence, Local/drug therapy
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