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.

OBJECTIVE: 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).
CONCLUSIONS: 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.

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).
CONCLUSIONS: 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.

OBJECTIVE: Precancer biomarkers help in early detection and management of oral potentially malignant disorders (OPMDs). Interleukin-1β (IL-1β), 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-1β levels in patients with OSMF/oral leukoplakia and in gender- and age-matched healthy individuals.
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-1β 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-1β levels were significantly (P 0.001) lesser in Group I in comparison to Group II. The salivary IL-1β levels remained insignificant between both the groups. However, in both the groups, the salivary IL-1β levels were significantly higher compared to the serum IL-1β levels.
CONCLUSIONS: We found that the serum IL-1β level can be considered as a prospective biomarker for dysplasia, whereas salivary IL-1β alone needs more elaborated studies to account for its application as a potential biomarker in OPMD.

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.
CONCLUSIONS: 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.

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.

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.

BACKGROUND: We aimed to construct an artificial intelligence-based model for detecting oral cancer and dysplastic leukoplakia using oral cavity images captured with a single-lens reflex camera.
METHODS: We used 1043 images of lesions from 424 patients with oral squamous cell carcinoma (OSCC), leukoplakia, and other oral mucosal diseases. An object detection model was constructed using a Single Shot Multibox Detector to detect oral diseases and their locations using images. The model was trained using 523 images of oral cancer, and its performance was evaluated using images of oral cancer (n = 66), leukoplakia (n = 49), and other oral diseases (n = 405).
RESULTS: For the detection of only OSCC versus OSCC and leukoplakia, the model demonstrated a sensitivity of 93.9% versus 83.7%, a negative predictive value of 98.8% versus 94.5%, and a specificity of 81.2% versus 81.2%.
CONCLUSIONS: Our proposed model is a potential diagnostic tool for oral diseases.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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).
CONCLUSIONS: 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.