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Head & Neck Oct 2023This prospective observational study investigated the determinants of malignant transformation (MT) in localized oral leukoplakia (OL) and proliferative verrucous... (Observational Study)
Observational Study
BACKGROUND
This prospective observational study investigated the determinants of malignant transformation (MT) in localized oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL).
METHODS
Demographic, clinical, histological, and DNA ploidy status data were collected at enrolment. Survival analysis was performed (MT being the event of interest).
RESULTS
One-hundred and thirty-three patients with OL and 20 patients with PVL entered the study over 6 years (mean follow-up 7.8 years). The presence of OED, DNA ploidy, clinical presentation, and lesion site were associated with MT in patients with OL in a univariate analysis. In a multivariate model, OED was the strongest predictor of MT in patients with OL. Adding DNA ploidy increased the model's predictive power. None of the assessed predictors was associated with MT in patients with PVL.
CONCLUSIONS
DNA ploidy might identify a subset OL with low risk or minimal risk of MT, but it does not seem to be a reliable predictor in patients with PVL.
Topics: Humans; Mouth Neoplasms; Prospective Studies; Leukoplakia, Oral; Ploidies; Cell Transformation, Neoplastic; DNA
PubMed: 37563936
DOI: 10.1002/hed.27483 -
Journal of Cancer Research and... 2017Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is...
CONTEXT
Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is composed of diverse group of metabolites, can aid in diagnosis and prognosis of oral squamous cell carcinoma (OSCC).
AIM
The aim of the present study is to analyze and identify serum metabolites in oral leukoplakia and OSCC as a potential diagnostic biomarker and a predictor for malignant transformation of oral leukoplakia.
SUBJECTS AND METHODS
Serum metabolomic profile of patients diagnosed with oral leukoplakia (n = 21) and OSCC (n = 22) was compared with normal controls (n = 18) using quadrupole time of flight-liquid chromatography-mass spectrometry. MassHunter profile software was used for metabolite identification, and statistical analysis to assess the variation of the metabolites was performed using Mass Profiler Professional software. Statistical significance between the three groups was expressed using ANOVA (P < 0.05), and intergroup comparison was done using Student's t-test (P < 0.05).
RESULTS
Significant upregulation of estradiol-17-beta-3-sulfate, L-carnitine, 5-methylthioadenosine (MTA), 8-hydroxyadenine, 2-methylcitric acid, putrescine, and estrone-3-sulfate was seen in oral leukoplakia and OSCC than in normal controls. Furthermore, significant upregulation of 5,6-dihydrouridine, 4-hydroxypenbutolol glucuronide, 8-hydroxyadenine, and putrescine was evident in OSCC group than in oral leukoplakia.
CONCLUSION
Upregulation of L-carnitine, lysine, 2-methylcitric acid, putrescine; 8-hydroxyadenine; 17-estradiol; 5,6-dihydrouridine; and MTA suggests their diagnostic potential in oral leukoplakia and OSCC. Further, a significant upregulation of putrescine, 8-hydroxyadenine, and 5,6-dihydrouridine in OSCC than in oral leukoplakia indicates their potential role in predicting the malignant transformation of oral leukoplakia.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Female; Humans; Leukoplakia, Oral; Male; Metabolomics; Mouth Neoplasms; Prognosis
PubMed: 28862226
DOI: 10.4103/jcrt.JCRT_1233_16 -
Oral Oncology Sep 2021Oral microbiome plays an important role in oral diseases. Among them, proliferative verrucous leucoplakia (PVL) is an uncommon form of progressive multifocal leukoplakia...
OBJECTIVES
Oral microbiome plays an important role in oral diseases. Among them, proliferative verrucous leucoplakia (PVL) is an uncommon form of progressive multifocal leukoplakia with a worryingly rate of malignant transformation. Here, we aimed to characterize the oral microbiome of PVL patients and compare it with those of healthy controls.
MATERIAL AND METHODS
Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their microbial communities. The sequence of the V3-V4 region of 16S rRNA gene was used as the taxonomic basis to estimate and analyze the composition and diversity of bacterial populations present in the samples.
RESULTS
Our results show that the oral microbial composition and diversity are significantly different among PVL patients and healthy donors. The average number of observed operational taxonomic units (OTUs) was higher for healthy donors than for PVL, proving a loss of diversity in PVL. Several OTUs were found to be more abundant in either group. Among those that were significantly enriched in PVL patients, potential protumorigenic pathogens like Oribacterium sp. oral taxon 108, Campylobacter jejuni, uncultured Eubacterium sp., Tannerella, and Porphyromonas were identified.
CONCLUSION
Oral microbiome dysbiosis was found in patients suffering from PVL. To the best of our knowledge, this is the first study investigating the oral microbiome alterations in PVL and, due to the limited number of participants, additional studies are needed. Oral microbiota-based biomarkers may be helpful in predicting the risks for the development of PVL.
Topics: Biopsy; Cell Transformation, Neoplastic; Humans; Leukoplakia, Oral; Microbiota; Mouth; RNA, Ribosomal, 16S
PubMed: 34225130
DOI: 10.1016/j.oraloncology.2021.105404 -
BioMed Research International 2022PVL (proliferative verrucous leukoplakia) has distinct clinical characteristics. They have a proclivity for multifocality, a high recurrence rate after treatment, and...
PVL (proliferative verrucous leukoplakia) has distinct clinical characteristics. They have a proclivity for multifocality, a high recurrence rate after treatment, and malignant transformation, and they can progress to verrucous or squamous cell carcinoma. AI can aid in the diagnosis and prognosis of cancers and other diseases. Computational algorithms can spot tissue changes that a pathologist might overlook. This method is only used in a few studies to diagnose LB and PVL. To see if their cellular nuclei differed and if this cellular compartment could classify them, researchers used a computational system and a polynomial classifier to compare OLs and PVLs. 161 OL and 3 PVL specimens in the lab were grown, photographed, and used for training and computation. Exam orders revealed patients' sociodemographics and clinical pathologies. The nucleus was segmented using Mask R-CNN, and LB and PVL were classified using a polynomial classifier based on nucleus area, perimeter, eccentricity, orientation, solidity, entropies, and Moran Index (a measure of disorderliness). The majority of OL patients were male smokers; most PVL patients were female, with a third having malignant transformation. The neural network correctly identified cell nuclei 92.95% of the time. Except for solidity, 11 of the 13 nuclear characteristics compared between the PVL and the LB showed significant differences. The 97.6% under the curve of the polynomial classifier was used to classify the two lesions. These results demonstrate that computational methods can aid in diagnosing these two lesions.
Topics: Artificial Intelligence; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Cell Transformation, Neoplastic; Female; Humans; Leukoplakia, Oral; Male; Mouth Neoplasms
PubMed: 35909480
DOI: 10.1155/2022/2363410 -
BMC Oral Health Aug 2023This study aims to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia and explore the subgroup factors that may influence its... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia and explore the subgroup factors that may influence its effectiveness.
METHODS
A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science databases to identify relevant studies. Meta-analysis was performed using Stata15.0 software. Cochran's Q test and I statistics were used to evaluate heterogeneity, egger's test was used to evaluate publication bias.
RESULTS
The analysis of 17 studies included in this study suggests that PDT may be effective in achieving complete response (CR) [ES = 0.50, 95%CI: (0.33,0.66)], partial response (PR) [ES = 0.42, 95%CI: (0.27,0.56)], no response (NR) [ES = 0.19, 95%CI: (0.11,0.27)]in patients with oral leukoplakia. The recurrence rate was also evaluated [ES = 0.13, 95%CI: (0.08,0.18)]. Subgroup analysis showed that various factors such as light source, wavelength, medium, duration of application, clinical and pathological diagnosis classification influenced efficacy of PDT. The lesion areas of the leukoplakia after treatment were reduced by 1.97cm compared with those before treatment.
CONCLUSION
Our findings show that PDT is a viable treatment for oral leukoplakia. However, the effectiveness of the therapy may depend on several factors, as suggested by our subgroup analyses. (Registration no. CRD42023399848 in Prospero, 26/02/2023).
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Leukoplakia, Oral
PubMed: 37574560
DOI: 10.1186/s12903-023-03294-3 -
Clinical and Experimental Dental... Aug 2019Oral leukoplakia is keratinized lesions in the buccal mucosa, tongue, and gingiva. It is the most common oral precancerous lesion; oxidative stresses and irrelevant...
OBJECTIVE
Oral leukoplakia is keratinized lesions in the buccal mucosa, tongue, and gingiva. It is the most common oral precancerous lesion; oxidative stresses and irrelevant autophagy have been reported to be the cause of oncogenesis. p62, a cytoplasmic protein induced by oxidative stress, is an adaptor protein involved in the formation of protein aggregates and induction and inhibition of autophagy. The inhibition of autophagy induces p62 overexpression and promotes oncogenesis via the oncogenic signaling pathway. The aim of the present study was to elucidate the involvement of intracellular expression of p62 in oral leukoplakia and to address its potential clinical implementation as a biomarker to predict malignant transformation.
MATERIAL AND METHODS
Fifty samples from subjects with confirmed oral leukoplakia were evaluated by immunohistochemical staining for the expression of p62, 8-hydroxy-2'-deoxyguanosine (8-OHdG), Ki67, and p53. Univariate and multivariate logistic regression analyses were performed to evaluate the association between p62, 8-OHdG, Ki67, and p53 and clinical characteristics, including epithelial dysplasia.
RESULTS
Significant associations were observed between p62 expression in the nucleus, p62 aggregation, and epithelial dysplasia (adjusted odds ratio [OR] = 5.75; 95% confidence interval [CI]: [1.28, 26.2]; .024 and OR = 6.16; 95% CI: [1.01, 37.4]; .048, respectively). The expression of p62 in the cytoplasm and the levels of 8-OHdG, Ki67, and p53 were not significantly associated with epithelial dysplasia. A significant relationship was found between p62 expression in the nucleus and p53 expression (OR = 3.94; 95% CI: [1.14, 13.6]; .031).
CONCLUSIONS
The results suggested that p62 expression in the nucleus and p62 aggregation can be potential markers to predict the malignant transformation of oral leukoplakia.
Topics: Aged; Biomarkers, Tumor; Cell Nucleus; Cell Transformation, Neoplastic; Female; Humans; Leukoplakia, Oral; Male; Middle Aged; Mouth Mucosa; Protein Aggregates; Sequestosome-1 Protein; Tumor Suppressor Protein p53
PubMed: 31452949
DOI: 10.1002/cre2.193 -
International Dental Journal Jun 2024This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was...
OBJECTIVE
This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS
Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments.
RESULTS
Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001).
CONCLUSIONS
Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.
Topics: Humans; Leukoplakia, Oral; Mouth Neoplasms; Carcinoma, Squamous Cell; Female; Male; Gelatinases; Endopeptidases; Middle Aged; Membrane Proteins; Serine Endopeptidases; Adult; Biomarkers, Tumor; Aged; Immunohistochemistry; Blotting, Western; Mouth Mucosa; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 38278714
DOI: 10.1016/j.identj.2023.12.011 -
BMC Oral Health Apr 2024The 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...
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.
Topics: Humans; Deep Learning; Leukoplakia, Oral
PubMed: 38594651
DOI: 10.1186/s12903-024-04191-z -
Iranian Journal of Immunology : IJI Jun 2021The immune evasion of dysplastic cells plays an important role in suppressing the immune response and progression of malignancy. The role of the complement inhibitors in...
BACKGROUND
The immune evasion of dysplastic cells plays an important role in suppressing the immune response and progression of malignancy. The role of the complement inhibitors in the development of oral epithelial dysplastic lesions and squamous cell carcinoma (SCC) is still unclear.
OBJECTIVE
This study aimed to assess the expression of C4 binding protein (C4BP) as a complement inhibitor in oral squamous cell carcinoma and leukoplakia.
METHODS
In this study, 94 samples were classified into four groups: leukoplakia with mild to moderate dysplasia, leukoplakia with severe dysplasia or carcinoma in situ, early invasive SCC, and invasive SCC. The expression of C4BP marker was evaluated by immunohistochemistry (IHC) and real-time PCR. The results were analyzed by the Kruskal-Wallis, Bonferroni adjusted Dunn's multiple comparison, and one-way ANOVA tests.
RESULTS
The results of IHC revealed the expression patterns of C4BP in oral dysplasia and SCC, and indicated that the C4BP expression was not significantly different between different histopathological grades in epithelial cells and vessels (P=0.157 and P=0.123, respectively) but, it was significantly different in fibroblasts and lymphocytes (P=0.017 and P=0.043, respectively). The real-time PCR showed a significant correlation between the dysplasia grade and expression of C4BP (P<0.05).
CONCLUSION
According to the results, C4BP is expressed in the cancerous tissue by the tumor cells and their surrounding stroma. In addition, upregulation of the C4BP gene as an inhibitor of the complement system is a possible strategy adopted by the tumor cells to evade the immune system.
Topics: Adult; Aged; Aged, 80 and over; Complement C4b-Binding Protein; Female; Humans; Immunohistochemistry; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 34190690
DOI: 10.22034/iji.2021.87031.1782 -
Cancer Prevention Research... Sep 2015Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and...
Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages ≥65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased <3 months after leukoplakia diagnosis (HR, 115), likely representing the diagnosis of prevalent cancers. Nonetheless, risk remained substantially increased in subsequent follow-up [HR ≥ 3 months, 24; 95% confidence interval (CI), 22-27; HR ≥ 12 months, 22, 95% CI, 20-25]. Among OCC cases (N = 8,927), those with prior leukoplakia were less likely to be diagnosed at regional/distant stage (OR, 0.36; 95% CI, 0.30-0.43), and had lower mortality (HR, 0.74; 95% CI, 0.65-0.84) when compared with OCC cases without a prior leukoplakia. Individuals with leukoplakia have substantially elevated risk of OCC. Lower stage and better survival after OCC diagnosis suggest that leukoplakia identification can lead to earlier OCC detection and reduced mortality.
Topics: Aged; Aged, 80 and over; Cohort Studies; Disease Progression; Female; Humans; Incidence; Leukoplakia, Oral; Male; Medicare; Mouth Neoplasms; Proportional Hazards Models; Registries; Regression Analysis; Risk Factors; SEER Program; Survival Rate; Treatment Outcome; United States
PubMed: 26159805
DOI: 10.1158/1940-6207.CAPR-15-0091