A complete course of photodynamic therapy reduced the risk of malignant transformation of oral leukoplakia.

BACKGROUND: Photodynamic therapy (PDT) has shown good short-term efficacy in the treatment of oral leukoplakia (OLK). However, the malignant transformation of OLK was seldom evaluated in most PDT studies. Therefore, this study evaluated the effect of PDT on the risk of malignant transformation of OLK. METHODS: Kaplan-Meier survival analysis, COX regression, and sensitivity analysis were used to evaluate the effects of PDT on the risk of malignant transformation of OLK. Subgroup analyses were performed to explore the role of PDT in OLK patients with different clinical characteristics. RESULTS: OLK patients with older age (HR=1.032, P = 0.018) and non-homogeneous lesion (HR=2.104, P = 0.044) had higher risk of malignant transformation. Patients who had finished a complete course of PDT (HR=0.305, P = 0.006) had a significant lower risk of malignant transformation, while those who hadn't finished a complete course of PDT (HR=0.692, P = 0.352) cannot be considered to have such a protective effect. In the subgroup analyses, complete PDT course showed a significant protective effect on malignant transformation of OLK in patients with female sex, no smoking or drinking habits, non-homogeneous lesions, lesions on oral mucosa outside the dangerous region, and any grade of epithelial dysplasia. CONCLUSIONS: A complete course of PDT could significantly reduce the risk of malignant transformation of OLK, especially in those patients with risk factors of malignant transformation.

Differences in the landscape of colonized microorganisms in different oral potentially malignant disorders and squamous cell carcinoma: a multi-group comparative study.

BACKGROUND: The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs. MATERIALS AND METHODS: Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted. RESULTS: Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris. CONCLUSIONS: Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease.

Efficacy of Aminolevulinic Acid Mediated Photodynamic Therapy in the Treatment of Oral Premalignant Lesions: A Systematic Review.

BACKGROUND: Aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) is considered as an effective treatment option for oral premalignant lesions. ALA is a Food and Drug Administration (FDA) approved second-generation photosensitizer (PS) used both orally as well as topically. OBJECTIVE: This systematic review aims to evaluate the efficacy of ALA-PDT for the treatment of oral premalignant lesions. METHODS: The focused question was, "Is ALA-PDT effective in the treatment of oral premalignant lesions?"A literature search was made in PubMed/Medline and GoogleScholar using different combinations of the following keywords: photodynamic therapy, oral premalignant lesions, oral leukoplakia (OL), erythroplakia, oral erythroleukoplakia (OEL), oral verrucous hyperplasia (OVH); and oral lichen planus (OLP). Review articles, preclinical studies, case-reports, commentaries, letters to the Editor, unpublished articles, studies on photodynamic therapy used in areas other than the oral cavityand, articles published in languages other than English were excluded. The relevant information was summarized. RESULTS: There were initially 64 results for the above parameters; 47 studies were excluded, leaving 17 studies for analysis. Characteristics of the included studies, PS, and PDT protocol were summarized. CONCLUSION: The outcome of the included studies suggested that ALA-PDT is an effective, easy to perform technique, well tolerated treatment with encouraging achievements in the treatment of oral premalignant lesions. No systemic side effects and skin photosensitivity were reported with topical ALA even within initial 48 hours after PDT, and patients were not required to avoid exposure to light following treatment. The clinical outcome of the ALA-PDT application, as reported in the studies, was also very promising, with either diminution in the size of the lesion or complete remission or improvement in signs and symptoms as well as reduced recurrence.

Recurrence in Oral Leukoplakia: A Systematic Review and Meta-analysis.

The management of oral leukoplakia (OL) is challenging because of a high risk for recurrence and malignant transformation (MT), and recurrent OL is associated with a higher risk of MT than nonrecurrent OL. The present meta-analysis aimed to examine the association between OL recurrence and surgical techniques used for their management as well as their clinicopathological factors. Electronic searches were conducted in EMBASE, PubMed, Scopus, and Web of Science to retrieve studies reporting OL recurrence after surgery. The pooled proportion of OL recurrence after surgical excision was estimated. Subgroup analyses were conducted based on the surgical technique, data type, grades of epithelial dysplasia, anatomical subsites, clinical type and size of the lesion, surgical margin, and risk habits. Meta-regression analyses were conducted to identify the association between age, sex, and follow-up duration and OL recurrence. The risk of MT based on the recurrence status was also estimated. A network meta-analysis was performed to determine the surgical modality associated with the least OL recurrence. Eighty studies with a total of 7,614 samples and various surgical modalities (laser-based techniques, conventional scalpel surgery, cryosurgery, and photodynamic therapy) were included in the meta-analysis. A pooled proportion of recurrence of 22% was observed. Laser-based surgeries resulted in fewer OL recurrences than other surgical modalities, and the combination of laser excision and vaporization was identified to be the best treatment approach. OL in the retromolar area and multiple sites, nonhomogeneous OL, advanced age, female sex, inadequate surgical margin, retrospective data, and betel quid chewing habit were significantly associated with higher OL recurrence. Recurrent OL showed a 7.39 times higher risk of MT than nonrecurrent OL. These results suggest that the combination of laser excision and vaporization might reduce OL recurrence. Furthermore, OL in older patients, females, and nonhomogeneous OL need close monitoring after any surgical therapy.

Single-cell RNA sequencing highlights the immunosuppression of IDO1+ macrophages in the malignant transformation of oral leukoplakia.

Rationale: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. Methods: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the in vitro/in vivo experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. Results: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. Conclusions: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR.

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

Potential of photodynamic therapy as a minimally invasive treatment for oral verrucous carcinoma.

Oral verrucous carcinoma (OVC) and proliferative verrucous leukoplakia (PVL) share similar histological characteristics and may have a common origin. When they appear simultaneously, the risk of malignant transformation in PVL increases. In elderly patients with both conditions, a safe, effective, simple, and minimally invasive treatment is preferable. Photodynamic therapy (PDT), a non-invasive treatment, utilizes specific wavelengths of light to activate photosensitizers, generating reactive oxygen species that selectively target malignant tissues with cytotoxic effects. This case report describes an elderly patient with coexisting extensive leukoplakia, PVL, and OVC, who achieved complete remission with no recurrence at 10 months following PDT. The treatment resulted in a satisfactory clinical outcome, preserving both the appearance and function of the oral cavity.

Oral leukoplakia and erythroplakia in young patients: a southern Brazilian multicenter study.

The objective of the present study was to investigate the frequency of oral leukoplakia and oral erythroplakia among young patients from three Brazilian reference centers in Oral and Maxillofacial Pathology. A retrospective study was carried out from 2011 to 2021 on 861 patients diagnosed with oral leukoplakia and oral erythroplakia. Demographic and clinicopathological data were evaluated. Fisher's exact test was used to evaluate the association among sex, age, anatomical location, and histopathological diagnosis. A total of 83 (9.64%) cases involved young patients (aged <40 years). Among these, biopsy records were included in 31 (37.34%) cases, all of which received a clinical diagnosis of oral leukoplakia. Seventeen (54.84%) patients were female, mostly in their fourth decade of life (n = 22/70.97%), and their mean age at diagnosis was 32.61(± 5.21) years. Among informed cases, seven (22.58%) patients were smokers. The lateral border of the tongue (n = 9/29.03%) was the most affected site. In 13 (41.94%) cases, oral leukoplakias showed a homogeneous appearance. The mean size of the lesions was 1.47 cm (0.2-3.0 cm) and the mean time of disease progression was 64.37 (± 65.90) months. The histopathological analysis showed that 11 cases (35.48%) exhibited some degree of epithelial dysplasia. Acanthosis and/or hyperkeratosis were observed in 20 cases (64.52%). No significant associations were observed between sex and anatomical location, age and anatomical location, nor between sex and histological diagnosis (p > 0.05). Oral leukoplakia and oral erythroplakia are uncommon diseases in young patients. In this population, oral leukoplakia shows a slight predilection for women aged between 30 and 39 years.

Oral health-related quality of life in Fanconi anemia: a cross-sectional study.

PURPOSE: To evaluate the oral health-related quality of life (OHRQoL) of individuals diagnosed with Fanconi anemia (FA). METHODS: A cross-sectional study was conducted with FA patients from two Brazilian referral centers. Participants underwent a complete dental, periodontal, and oral mucosa examination, as well as assessment of resting salivary flow. The short version of the Oral Health Impact Profile (OHIP-14) questionnaire was administered. Descriptive and bivariate analyses were performed, followed by multivariate analysis to examine the impact of independent variables on OHRQoL. RESULTS: The study included 20 (57.1%) males and 15 (42.9%) females, with a mean age of 18.9 years. Oral leukoplakia (OL) was found in 18 individuals. The overall OHIP-14 score was 9.9 ± 10.5. Individuals aged ≥ 16 years had higher OHIP-14 scores, indicating worse OHRQoL for physical pain (p = 0.007), psychological discomfort (p = 0.001), physical disability (p = 0.03), psychological disability (p = 0.001), handicap (p = 0.004), and overall score (p = 0.007). Females reported more negative OHRQoL than males for physical pain (p = 0.02), psychological discomfort (p = 0.03), psychological disability (p = 0.009), and overall score (p = 0.02). Individuals with OL had an overall OHIP-14 score 1.83 times higher than those without OL (95% CI: 1.02-3.28; p = 0.04). Lower salivary flow correlated with higher overall OHIP-14 scores (95% CI: 0.14-0.84; p = 0.01). CONCLUSION: This study represents the first attempt to evaluate OHRQoL in individuals with FA. The presence of OL and reduced salivary flow were identified as predictors of a negative impact on OHRQoL. It is imperative to integrate patients' quality of life in the clinical treatment protocols for the FA population.

Effects of artemisinin and cisplatin on the malignant progression of oral leukoplakia. In vitro and in vivo study.

OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.

Diseases with oral malignant potential: Need for change to inform research, policy, and practice.

This manuscript critically examines the current classification of oral potentially malignant disorders, questioning the practicality and implications of labeling such a large population as precancerous, given that the actual progression to oral cancer is significantly low for most disorders. The paper advocates for a revised classification system that accurately reflects the varying malignancy risks associated with different disorders. It suggests a reassessment of the diagnostic and management approaches to mitigate overdiagnosis and alleviate patient burdens. We propose categorizing diseases with oral malignant potential as follows: Oral Precancerous Diseases, encompassing high-risk lesions and conditions like erythroplakia, non-homogeneous leukoplakia, proliferative leukoplakia, and actinic keratosis; Oral Potentially Premalignant Diseases, covering lesions, conditions, and systemic diseases with distinct oral manifestations harboring a limited or undefined risk of transformation, such as homogeneous leukoplakia, oral submucous fibrosis, oral lichenoid diseases, chronic hyperplastic candidosis, keratosis of known aetiology (smokeless tobacco, khat), palatal lesions in reverse smokers, and dyskeratosis congenita; and Systemic Conditions with Oral Malignant Potential including Fanconi's anemia, xeroderma pigmentosum, and chronic immunosuppression (including patients post-bone marrow transplantation), which are associated with an increased risk of oral cancer without preceding precursor lesions. We provide illustrative examples to demonstrate how this framework offers practical guidance for research, policy-making, and clinical practice.

Leukoplakia and erythroplakia in youngers versus older individuals: a clinicopathological retrospective study.

BACKGROUND: The incidence of oral cancer has exhibited a rise within the young population. Considering that oral potentially malignant disorders (OPMDs) can precede the development of oral cancer, it is imperative to conduct studies in this particular younger population. This study aimed to evaluate the frequency and conduct a comparative analysis of the clinical-demographic characteristics of OPMDs in two distinct age groups. MATERIAL AND METHODS: A retrospective analysis was conducted with patients diagnosed with leukoplakia, erythroplakia, and leukoerythroplakia between 1965 and 2020. The individuals were categorized into two groups: those aged up to 40 years (Group Younger) and those aged 41 years and above (Group Older). RESULTS: A total of 640 lesions were subjected to analysis. Among these, patients aged up to 40 years constituted 10.63% of the sample, however, this proportion decreased significantly to 6.9% between 2010 and 2020. A predominant male representation was observed in both groups, with white lesions being the most common in both as well. However, the frequency of red or mixed lesions was significantly higher (p=0.034) in the older group, along with a higher prevalence of dysplastic lesions (26.9% versus 11.8%, p=0.01). Moreover, the older group exhibited a relatively higher percentage of smokers/ex-smokers (78.6%), compared to the younger group (61.5%, p=0.085) and alcohol consumers/ex-consumers (54.9% versus 22.7%, p=0.028). Elderly individuals exhibited an unfavorable progression (p=0.028). However, a logistic regression analysis identified as significant variables associated with malignant transformation, the presence of epithelial dysplasia, and red lesions diagnosed as erythroplakia. CONCLUSIONS: A declining frequency of OPMDs in young adults was observed over the years, whereas in older adults, these disorders exhibited an unfavorable progression.

Serum and salivary interleukin-1ß level in oral precancer: An observational study.

BACKGROUND AND AIM: Precancer biomarkers help in early detection and management of oral potentially malignant disorders (OPMDs). Interleukin-1ß (IL-1ß), a biomarker, is known to be altered in oral submucous fibrosis (OSMF) and oral leukoplakia (OL). Therefore, we evaluated and compared the serum and salivary IL-1ß levels in patients with OSMF/oral leukoplakia and in gender- and age-matched healthy individuals. MATERIALS AND METHODS: An in vivo, prospective, observational study was conducted on 40 subjects. Subjects were divided into two groups with 20 individuals in each group, that is, Group I: OSMF/oral leukoplakia and Group II: control group. Salivary and serum IL-1ß levels were quantitatively estimated using enzyme-linked immunosorbent assay (ELISA). The statistical tests used were unpaired t-test and Chi-square test. RESULTS: The serum IL-1ß levels were significantly (P 0.001) lesser in Group I in comparison to Group II. The salivary IL-1ß levels remained insignificant between both the groups. However, in both the groups, the salivary IL-1ß levels were significantly higher compared to the serum IL-1ß levels. CONCLUSION: We found that the serum IL-1ß level can be considered as a prospective biomarker for dysplasia, whereas salivary IL-1ß alone needs more elaborated studies to account for its application as a potential biomarker in OPMD.

Treatment outcomes of oral leukoplakia on the irradiated or nonirradiated mucosa among survivors of head and neck cancer in the papulation where practice of betel nut chewing and cigarette smoking are widespread.

BACKGROUND: Radiotherapy (RT) has numerous effects on the oral mucosa, primarily genetic alterations and changes in the microenvironment. The characteristics of oral leukoplakia (OL) may differ between patients who have received previous head and neck cancer (HNC) treatment with radiation therapy and those who have not. Due to a lack of data on this scenario, we aimed to investigate the surgical outcomes of OL by comparing these two patient groups. METHODS: This retrospective cohort study enrolled a total of 224 OL lesions in 124 patients who underwent carbon dioxide laser (CO2 laser) surgery from July 2002 to Aug 2021. All patients had received previous treatments for HNC, with 59 patients undergoing only surgical approach, 65 patients undergoing RT, and 46 patients undergoing concurrent chemotherapy during RT. The analysis was performed on a per-lesion basis, not a per-capita basis. We investigated the associations of clinicopathological characteristics and treatment outcomes of OL lesions that developed from irradiated or nonirradiated oral mucosa. RESULTS: The median follow-up time was 5.87 years. Postoperative recurrence of OL occurred in 30 patients. Malignant transformation occurred in 17 patients with the incidence rate 4.19% annually and 13.7% cumulatively. The average time for OL transforming into squamous cell carcinoma was 3.27 ± 3.26 years (median 1.82, range 0.11 - 11.90). In univariate analysis, non-homogeneous morphology (P = 0.042), moderate to high-grade dysplasia (P = 0.041), and nonirradiated oral mucosa (P = 0.0047) were predictors for malignant transformation. However, in the Cox proportional hazard model, only nonirradiated oral mucosa remained an independent prognostic factor related to postoperative malignant transformation of OL (P = 0.031, HR 5.08, CI95 1.16 - 22.25). CONCLUSION: In the population whose OL is strongly aetiologically linked to environmental carcinogens such as betel nut and tobacco, OL lesions that develop on previously irradiated oral mucosa have a lower risk for postoperative malignant transformation compared to those that develop on nonirradiated mucosa. This finding highlights the potential impacts of radiation on OL. Further research is needed to confirm this observation and elucidate the underlying mechanism.

Clinical and mycological analysis of colonization by Candida spp. in oral leukoplakia and oral lichen planus.

OBJECTIVE: This study aims to analyze the prevalence of Candida spp. colonization in oral leukoplakia and oral lichen planus lesions, verify the influence of systemic and local factors, besides identify and determine the in vitro antifungal susceptibility profile of Candida species. MATERIALS AND METHODS: Samples were collected by swabbing from oral lesions and healthy mucosa and cultured on Sabouraud Dextrose and CHROMagar® Candida plates. Species identification was confirmed with MALDI-TOF MS analysis. RESULTS: Candida spp. was found in 36.8% of cases of oral leukoplakia and 18.2% of cases of oral lichen planus. Candida albicans was the only species found in oral lichen planus lesions (n = 2, 100%) and the most prevalent in oral leukoplakia (n = 5, 76.4%). Among the non-albicans Candida species found in oral leukoplakia were C. parapsilosis (n = 2, 25.5%) and C. tropicalis (n = 1, 14.1%). Candida isolates were susceptible to all antifungals tested. CONCLUSION: C. albicans was the most commonly found species in the studied lesions. No correlation was found between systemic and local factors with positive cases of oral lichen planus. However, smoking and alcohol consumption may be associated with positive cases of oral leukoplakia, especially the non-homogeneous clinical form. In addition, there is a possible predisposition to associated Candida colonization in cases of epithelial dysplasia found in oral leukoplakia. The antifungal medications tested showed excellent efficacy against isolates.

Sensitive Detection of Oral Leukoplakia: Analyzing P90 Biomarkers in Saliva and Tissue.

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.

Oral Pre-malignancy: An Update on Novel Therapeutic Approaches.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management. RECENT FINDINGS: Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization's three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation. Additionally, treatments such as surgical interventions, photodynamic therapy, and chemopreventive and molecularly targeted agents are being evaluated for their safety and efficacy as well as, immune checkpoint inhibitors being evaluated as potential preventive strategies to halt the progression of OPMDs. The management of OPMDs remains challenging due to the lack of standardized screening protocols and varied clinical management approaches. Despite this, recent advancements in diagnostic grading and therapeutic interventions provide a framework for improved treatment outcomes. Continued research into the molecular and cellular mechanisms driving development and progression of OPMDs and innovative treatment trials are essential to optimize strategies that prevent malignant progression and thereby reduce the global health burden of oral cancer.

Prx1/PHB2 axis mediates mitophagy in oral leukoplakia cellular senescence.

BACKGROUND: Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC). Peroxiredoxin1(Prx1) has been predicted to bind to Prohibitin2 (PHB2), which confers to affect OLK progression; however, the mechanism of Prx1/PHB2 mediated mitophagy involved in OLK remains unclear. METHODS: This study aimed to explore the mechanism of the Prx1/PHB2 axis on senescence in OLK through mediating mitophagy. The positive rate of Ki67 and the expression of p21, p16, PHB2, and LC3 in human normal, OLK, and OSCC tissues were detected by immunohistochemical staining. The mitophagy and mitochondrial function changes were then analyzed in Prx1 knockdown and Prx1C52S mutations in dysplastic oral keratinocyte (DOK) cells treated with H2O2. In situ Proximity Ligation Assay combined with co-immunoprecipitation was used to detect the interaction between Prx1 and PHB2. RESULTS: Clinically, the positive rate of Ki67 progressively increased from normal to OLK, OLK with dysplasia, and OSCC. Higher p21, p16, PHB2, and LC3 expression levels were observed in OLK with dysplasia than in normal and OSCC tissues. In vitro, PHB2 and LC3II expression gradually increased with the degree of DOK cell senescence. Prx1/PHB2 regulated mitophagy and affected senescence in H2O2-induced DOK cells. Furthermore, Prx1C52S mutation specifically reduced interaction between Prx1 and PHB2. Prx1Cys52 is associated with mitochondrial reactive oxygen species (ROS) accumulated and cell cycle arrest. CONCLUSION: Prx1Cys52 functions as a redox sensor that binds to PHB2 and regulates mitophagy in the senescence of OLK, suggesting its potential as a clinical target.

Advancements in diagnosing oral potentially malignant disorders: leveraging Vision transformers for multi-class detection.

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.

Prediction of the short-term efficacy and recurrence of photodynamic therapy in the treatment of oral leukoplakia based on deep learning.

BACKGROUND: The treatment of oral leukoplakia (OLK) with aminolaevulinic acid photodynamic therapy (ALA-PDT) is widespread. Nonetheless, there is variation in efficacy. Therefore, this study constructed a model for predicting the short-term efficacy and recurrence of OLK after ALA-PDT. METHODS: The short-term efficacy and recurrence of ALA-PDT were calculated by statistical analysis, and the relevant influencing factors were analyzed by Logistic regression and COX regression model. Finally, prediction models for total response (TR) rate, complete response (CR) rate and recurrence in OLK patients after ALA-PDT treatment were established. Features from pathology sections were extracted using deep learning autoencoder and combined with clinical variables to improve prediction performance of the model. RESULTS: The logistic regression analysis showed that the non-homogeneous (OR: 4.911, P: 0.023) OLK and lesions with moderate to severe epithelial dysplasia (OR: 4.288, P: 0.042) had better short-term efficacy. The area under receiver operating characteristic curve (AUC) of CR, TR and recurrence predict models after the ALA-PDT treatment of OLK patients is 0.872, 0.718, and 0.564, respectively. Feature extraction revealed an association between inflammatory cell infiltration in the lamina propria and recurrence after PDT. Combining clinical variables and deep learning improved the performance of recurrence model by more than 30 %. CONCLUSIONS: ALA-PDT has excellent short-term efficacy in the management of OLK but the recurrence rate was high. Prediction model based on clinicopathological characteristics has excellent predictive effect for short-term efficacy but limited effect for recurrence. The use of deep learning and pathology images greatly improves predictive value of the models.