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Background Methods Results Conclusion Key points Plain language summary Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral leukoplakia. The etiology of PVL remains unknown. The lesion is characterized by a high rate of malignant transformation. There is no definitive treatment for PVL.This case study presents a patient diagnosed in 2000 with a localized hyperkeratinized/verrucous lesion involving the facial gingivae of teeth #6–#8. Over the next 24 years, the lesion was biopsied five times. Further, two attempts to ablate the lesion with a CO2 laser (10.6 µm wavelength) were performed. Both ablation treatments were unsuccessful as the lesion recurred and progressed to involve more areas of gingival tissue. To date, biopsy has not revealed transformation into verrucous or squamous cell carcinoma (SCCA).This case study demonstrates that two attempts at ablation of PVL using a CO2 laser had no short‐ or long‐term benefit. The patient eventually lost all maxillary teeth due to root caries and inability to maintain adequate oral hygiene. The PVL lesion currently involves the entire maxillary edentulous ridge, extending from the 2nd molar site to the opposite corresponding site. During the 24 years encompassed by this report, the patient has not experienced a malignant transformation.The results of CO2 laser ablation of the PVL lesion in this case provided no short‐ or long‐term benefit. Given the potential for a sinister outcome, PVL patients require frequent clinical evaluation and biopsy for early detection of a malignant transformation into oral verrucous or SCCA. Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin. Currently, there is no reliable and successful treatment for PVL. PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister‐appearing mucosal sites. Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin.Currently, there is no reliable and successful treatment for PVL.PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister‐appearing mucosal sites.Proliferative verrucous leukoplakia (PVL) is a rare disorder that affects the gum tissue around the teeth. PVL is a pre‐cancerous disorder for which the cause is unknown and there is no treatment that yields a consistently successful result. This case study presents a patient diagnosed in 2000 with PVL involving the facial gum tissue of the upper right cuspid, lateral, and central incisor teeth. Over the next 24 years, the lesion was biopsied five times and two attempts to irradicate the lesion with a CO2 laser were performed. All attempts at treatment were unsuccessful and the lesion slowly progressed to involve more areas of gum tissue. The last biopsy taken in February 2024 did not reveal any areas of developing cancer. During the 24 years covered in this report, the patient did not develop oral cancer. However, treatment with the CO2 laser afforded no measurable benefit. Given the potential for developing cancer of the gum tissues, PVL patients should receive frequent oral exams and periodic biopsies for the detection of early cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Materials and Methods Results Conclusion Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder. Forms that affect only one tissue are poorly studied, especially the exclusively gingival PVL (gPVL), which may have a more increased malignant transformation potential. The aim of the present study was to characterise the gPVL and its risk of malignant transformation to better raise awareness of this specific disorder.The systematic review was performed on PubMed, Scopus, Web of Science and Google Scholar. Only articles reporting primary studies, case reports and case series were included. The meta‐analysis was performed for the cancer prevalence, proportion of smokers, age and sex ratio, recurrences of gPVL and mortality.A total of 1298 studies were assessed for eligibility by reading titles and abstracts. Fourteen original articles were included with a total of 58 patients. The malignant transformation rate of gPVL was 47.75%. The mortality was 5.84%. The mean follow‐up duration before malignant transformation was 3 years.gPVL seems to have a faster malignant transformation rate than the other forms of PVL. Finding anatomo‐pathological or genetic markers could be a line of research to predict gPVL malignant transformation and improve its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The article presents interim trial results comparing the effectiveness of diode laser (DL) and traditional scalpel (TS) in treating oral leukoplakia (OL) concerning recurrence and malignant transformation (MT). Topics discussed include the surgical techniques employed, the rates of recurrence and malignancy observed in each treatment group, and the statistical analysis conducted to evaluate the outcomes of the two methods.

Objectives Materials and Methods Results Conclusions To update the current evidence on the malignant transformation of oral leukoplakia (OL), including all studies published worldwide on the subject, selected with the maximum rigor regarding eligibility.MEDLINE, Embase, Web of Science and Scopus were searched for studies published before June‐2024, with no lower date limit. The risk of bias was analyzed using the Joanna Briggs Institute tool for meta‐analyses of proportions. We carried out meta‐analyses, explored heterogeneity across subgroups and identified risk factors with potential prognostic value.Fifty‐five studies (41,231 with OL) were included. The pooled malignant transformation proportion for OL was 6.64% (95% CI = 5.21–8.21). The malignant transformation did not significantly vary by time periods (p = 0.75), 5.35% prior to 1978, 7.06% from 1979 to 2007 and 6.97% during more recent times. The risk factors that significantly had a higher impact on malignant transformation were the non‐homogeneous leukoplakias (RR = 4.23, 95% CI = 3.31–5.39, p < 0.001), the larger size (RR = 2.08, 1.45–2.96, p < 0.001), leukoplakia located on the lateral border of tongue (malignant transformation = 12.71%; RR = 2.09, 95% CI = 1.48–2.95, p < 0.001), smoking (RR = 1.64, 95% CI = 1.25–2.15, p < 0.001), and the presence of epithelial dysplasia (RR = 2.75, 95% CI = 2.26–3.35, p < 0.001).OL presents a considerable malignant transformation probability that is especially increased in large non‐homogeneous lesions in smokers, located on the lateral border of the tongue, with epithelial dysplasia. [ABSTRACT FROM AUTHOR]

ABSTRACT Dyskeratosis congenita (DC) is a rare inherited bone marrow disease that classically presents with the triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. It is most commonly caused by a defect in the DKC1 gene involved in telomere stability. Malignant progression of oral leukoplakia to squamous cell carcinoma (SCC) is rare in DC, especially in younger patients, and cutaneous SCC is only reported in 1.5% of cases of DC. Here we report a case of a 12‐year‐old female with a familial heterozygous RTEL1 (regulator of telomere elongation helicase 1) gene mutation associated with a severe phenotype of DC characterized by multiple cutaneous SCCs. [ABSTRACT FROM AUTHOR]

Telomere biology disorders (TBD) are a complex set of inherited illnesses characterized by short telomeres. Dyskeratosis congenita (DC), which is now considered a severe TBD phenotype, is characterized by reticulated pigmentary changes, nail dystrophy, premalignant oral leukoplakia, and systemic involvement. This case describes a 2‐year‐old female with reticulated pigmentary changes and Terry's nails who was found to have a TERT variant and short telomeres; she lacked other mucocutaneous and systemic features of TBD. This report describes a unique clinical presentation of TBD and highlights the importance of upholding suspicion for TBD in individuals with limited or subtle features of classic DC. [ABSTRACT FROM AUTHOR]

Objective: To identify potential salivary biomarkers for the diagnosis and monitoring of disease progression in oral squamous cell carcinoma and oral leukoplakia. Materials and Methods: An advance search from PubMed and Hindawi was performed with keywords; oral leukoplakia/oral squamous cell carcinoma, salivary biomarker and diagnosis/prognosis. An additional search of articles was done through a manual search from the Google Scholar database. Results: Twenty studies involving salivary biomarkers as diagnostic tools for oral squamous cell carcinoma and/or oral leukoplakia were identified. A narrative review was carried out. Conclusion: Single or multiple salivary biomarkers reported by most studies have shown great potential as diagnostic tools for oral squamous cell carcinoma and oral leukoplakia. However, the validation of sensitivity and specificity should be carried out to ensure the accuracy of the biomarkers. Furthermore, a standardised method for saliva collection should be established to prevent variability in the expression of biomarkers. [ABSTRACT FROM AUTHOR]

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. Subjects and 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. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion This systematic review and meta‐analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites.A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered.Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59–1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09–1.09]) for recurrence was observed when cold‐knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN.There is no difference in recurrence risk post‐surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion We aimed to assess the effectiveness of the use of topical imiquimod for the management of oral leukoplakia (OL).This was a retrospective study. Medical chart reviews were conducted to identify patients with biopsy‐proven OL treated with topical 5% imiquimod. Data included OL characteristics, histopathological diagnosis, treatment outcome, and adverse events (AEs). Treatment response was assessed by measuring the percentage reduction in the size of OL lesions.33 patients (51.5% females; median age: 65 years) with 38 lesions were included. OLs were either localized (23.7%) or multifocal lesions (76.3%), with the majority on the gingiva (86.8%). Pretreatment histopathological diagnoses were dysplasia in 84.2% and nonreactive hyperkeratosis in 15.8%. Most regimens consisted of 60‐minute applications, 5‐days‐a‐week, for 6 weeks. At the end of treatment, 81.6% of 38 lesions showed a reduction in size with 68.4% exhibiting ≥50% reduction in size, and 42.1% exhibiting complete resolution. Application site reactions were the most common with pain/soreness/sensitivity occurring in 86.8%. Fatigue was the most frequently reported systemic AE (28.9%).Two‐thirds of OL lesions had ≥50% reduction in size. Most AEs were temporary and resolved upon treatment discontinuation. Prospective studies are needed to further assess Imiquimod's effectiveness in OL management. [ABSTRACT FROM AUTHOR]

Objectives: This study assessed the validity of nomograms for predicting malignant transformation (MT) among patients with oral leukoplakia (OL) and oral lichen planus (OLP). Materials and Methods: Two nomograms were identified following a systematic search. Variables to interrogate both nomograms were obtained for a retrospective OL/OLP cohort. Then, the nomograms were applied to estimate MT probabilities twice and their average was used to calculate the discriminatory performance, calibration, and potential net benefit of the models. Subgroup analyses were performed for patients with OL, OLP, and oral epithelial dysplasia. Results: Predicted probabilities were mostly significantly higher among OL/OLP patients who developed MT compared to those who did not (p = <0.001–0.034). AUC values and Brier scores of the nomograms were 0.644–0.844 and 0.040–0.088 among OL patients and 0.580–0.743 and 0.008–0.072 among OLP patients. Decision curve analysis suggested that the nomograms had some net benefit for risk stratification. However, the models did not best binary dysplasia grading in discriminatory validity and net benefit among patients with OL and oral epithelial dysplasia. Conclusion: Nomograms for predicting MT may have satisfactory validity among patients with OL than OLP, but they do not outperform binary dysplasia grading in risk stratification of OL. [ABSTRACT FROM AUTHOR]

Objectives: This study explored associations between histological features of dysplasia and malignant transformation, as well as genomic copy number alterations. Materials and Methods: Overall, 201 samples were collected from patients of oral leukoplakia. The associations of dysplastic features with malignant transformation and copy number alterations were investigated by Cox proportional hazards regression analysis and the Mann–Whitney U‐test. Results: Eight individual histological features, such as irregular epithelial stratification (p = 0.001), mitoses high in epithelium (p = 0.033), extension of changes along minor gland ducts (p < 0.001), etc., were associated with greater risk of malignant transformation. A model including histological features and age showed good performance for predicting malignant transformation (area under receiver operating characteristic curve: 0.806). Irregular epithelial stratification (p = 0.007), abnormal nuclear shape (p = 0.005), abnormal cell size (p = 0.004), etc. were associated with greater genomic instability. Conclusions: A Cox proportional hazards model using eight histological features and patient age reliably predicted the malignant potential of oral epithelial dysplasia. Identification of these histological features closely related to malignant transformation may aid the management of oral potentially malignant disorders and early detection of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate whether regular follow‐up of oral leukoplakia (OL) resulted in early detection of malignant transformation (MT). Method: Two hundred and twenty‐two consecutive patients with OL (147 females, 75 males); median follow‐up period of 64 months (range: 12–300). Three groups were distinguished: group A (n = 92) follow‐up at the hospital; group B (n = 84) follow‐up by their dentist; group C (n = 46) lost to follow‐up. Results: OLs in group B compared to group A, were smaller in size (<2 cm; p < 0.001), showed more hyperkeratosis (p < 0.001) and less moderate/severe dysplasia (p < 0.001). MT occurred in 45 (20%) patients: 32 (35%) in group A, five (6%) in group B and eight (17%) in group C. There was no significant difference in clinical tumour size between group A (median: 15 mm, range: 1–40) and group B (median: 10 mm, range: 3–25; p = 0.496). Tumour size was smaller for patients in groups A and B (median: 10 mm, range 1–40) compared to group C (median: 33 mm, range: 3–100; p = 0.003). There was a positive correlation between tumour size and interval between the last visit in all patients (p = 0.022). Conclusion: Regular follow‐up of OL resulted in early detection of MT. If properly selected, follow‐up of OL performed by the dentist seems feasible. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. Methods: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential‐OSCC versus OSCC‐de novo (OSCC‐dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t‐test, and qualitative variables with chi‐square. Results: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC‐dn, while s‐OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. Conclusions: In Latin America, OSCC‐dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon. [ABSTRACT FROM AUTHOR]

Objective: DNA methylation data can be used to derive mitotic indices from complex tissues. Here, we assessed if the DNA methylation‐derived mitotic ageing indices are associated with oral squamous cell carcinoma (OSCC) development and recurrence‐free survival (RFS). Methods: DNA methylation‐based mitotic indices (MitoticAge, TNSC and hypoSC) were derived using algorithms "MitoticAge" and "epiTOC2" for the discovery [non‐malignant (n = 22), premalignant (n = 22) and OSCC (n = 68) tissues] and validation datasets (GSE87053, GSE136704 and TCGA‐HNSCC). Differences in mitotic indices between non‐malignant, premalignant and OSCC tissues were assessed. Finally, the association between estimated mitotic indices and RFS was evaluated in OSCCs. Results: In the discovery and validation datasets, increased mitotic ageing was observed in OSCC compared to non‐malignant and premalignant oral tissues. HPV‐positive HNSCCs had higher mitotic index TNSC. Mitotic age index hypoSC was associated with RFS in OSCC (p = 0.011, HR 2.61, 95% CI 1.24–5.48). Conclusions: DNA methylation‐derived mitotic indices are associated with OSCC development and RFS. Thus, DNA methylation‐derived mitotic indices may be a valuable research tool to reliably estimate the cumulative number of stem cell divisions in malignant and non‐malignant oral tissues. Future research utilizing mitotic indices for predicting clinical outcomes in OSCC is warranted. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures.This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the “wait and see” approach in preventing OSCC onset in patients affected by dysplastic and non‐dysplastic OL.Two Italian referral care centres for oral diseases were involved in this multicenter two‐arm RCT comparing the surgical removal of OL (group A) and the “wait and see” approach (group B), with the aim of reducing oral cancer onset.This report shows preliminary data on the first 161 patients, with a mean follow‐up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision.Within the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B (“wait and see”) compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5‐year follow‐up, in order to achieve conclusive results, in an evidence‐based medicine approach. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusions Proliferative verrucous leukoplakia (PVL) is considered a clinically distinct entity from other oral leucoplakias (OLs) due to its clinical presentation and evolution. However, molecular differences between them remain unclear. We aimed to determine whether there are methylation differences between PVL and other forms of OLs.Oral biopsies from 12 patients with PVL, eight patients with homogeneous leucoplakia (HL), and 10 healthy individuals were obtained for a genome‐wide DNA methylation analysis via the Infinium EPIC Platform.A total of 1815 differentially methylated CpGs were found between PVL and HL, with a prominent state of hypermethylation in HL patients. CpGs covered 813 genes with distinct roles, including cell adhesion, extracellular matrix organization, and cell and synaptic signaling. 43% of these genes had been previously described in cancer and associated with prognosis. We developed a multinomial logistic regression model able to differentiate HL, PVL, and control samples. The model had a cross‐validated estimate of 73% and included differentially methylated cancer‐related genes between the pathological conditions and the healthy donors, including ADNP, BRCA2, CDK13, GNB1, NIN, NUMB, PIK3C2B, PTK2, SHISA4, THSD7B, WWP1, and ZNF292. It also included CpGs covering differentially methylated genes in HL (MEN1 and TNRC6B) and PVL (ACOXL, ADH1B, CAMTA1, CBFA2T3, CPXM2, LRFN2, SORCS2, and SPN).PVL and HL present differential methylation patterns that could be linked to their differential clinical behavior. Our findings show the potential of methylation markers and suggest novel diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants. Methods: Case–control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single‐nucleotides polymorphisms were tested for individuals with and without missing teeth. Results: Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively). Conclusions: Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

The article explores ChatGPT's efficacy in Oral Medicine, focusing on its performance in addressing questions related to oral potentially malignant disorders (OPMDs). Topics discussed include ChatGPT's moderate knowledge base, discrepancies in classifying OPMDs, and conflicting recommendations regarding adjuncts for diagnosis and factors contributing to malignant transformation.

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." [ABSTRACT FROM AUTHOR]

Objective: Proliferative verrucous leukoplakia (PVL) has high rates of malignant transformation into oral squamous cell carcinoma (OSCC), but the clinical and evolutionary pattern of OSCC from PVL (PVL‐OSCC) is more favorable than that of OSCC not preceded by PVL (OSCC). Here, we aimed to explore the pathophysiologic differences between PVL‐OSCC and OSCC through transcriptomic and DNA methylation analyses. Materials and methods: In this case‐control study, oral biopsies from 8 PVL‐OSCC and 10 OSCC patients were obtained for global sequencing using RNAseq and a genome‐wide DNA methylation analysis via the Infinium EPIC Platform (graphical abstract). Results: One hundred and thirty‐three differentially expressed genes (DEGs) were detected, 94 of them upregulated in OSCC. Most of these genes were previously described in cancer and associated with prognosis. The integrative analysis revealed 26 DEGs, corresponding to 37 CpGs, whose promoters were regulated by DNA methylation. Twenty‐nine of the CpGs were found as hypermethylated in PVL‐OSCC. Only 5 of the genes that were aberrantly methylated and differentially expressed were upregulated in PVL‐OSCC patients, whereas 21 were underexpressed. Conclusions: PVL‐OSCC patients presented lower expression of cancer‐related genes. Hypermethylation of the promoter region of many genes was also noticed, indicating that DNA methylation could be a regulatory mechanism. [ABSTRACT FROM AUTHOR]

Objective: Manganese ion (Mn2+) is reported to promote the antitumor immune response by activating the cGAS‐STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. Methods: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP–AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT–PCR, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4‐nitroquinoline oxide (4NQO)‐induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+‐loaded guanosine‐tannic acid hydrogel (G‐TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. Results: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway. Moreover, Mn2+ suppressed the development of 4NQO–induced carcinogenesis in the mouse model. In addition, the G‐TA@Mn2+ hydrogel had better anti‐OLK effects. Conclusions: Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway, and the G‐TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to identify and analyze the existing literature on the utility of podoplanin to predict the risk of malignancy development (MD) in patients previously diagnosed with oral leukoplakia (OL). Methods: A systematic review and meta‐analysis (SRMA) was performed though a search strategy using several electronic databases and a combination of keywords related to podoplanin and MD of OL, until 15 May, 2022 (PROSPERO CRD42022329326). Evaluation of the risk of bias (ROB) was performed using the Quality in Prognosis Studies Tool. The meta‐analyses were estimated using fixed‐effect models. Results: From 421 articles, 6 studies were finally included, that enrolled 546 patients with OL, of whom 125 presented with an oral cancer during follow‐up (32 to 90 months). Some limitations regarding the ROB were identified mostly related to small sample sizes, short follow‐up times, lack of information on covariables in the included studies and lack of accuracy (including sensitivity and specificity). Meta‐analysis of 6 studies reveal that high expression of podoplanin carries a pooled hazard ratio (HR) of 3.72 (95% CI, 2.40–5.76; p < 0.00001) for MD without statistical heterogeneity (I2 = 0%, p = 0.53). Conclusion: The results of this SRMA support the role of podoplanin immunohistochemical expression as a potential predictive biomarker to assess the risk of malignancy development in oral leukoplakia. [ABSTRACT FROM AUTHOR]

Objective: Proliferative verrucous leukoplakia (PVL) is characterized by a spectrum of clinicopathological features and a high risk of malignant transformation. In this study, we aimed to delineate the dynamic changes in molecular signature during PVL progression and identify the potential cell subtypes that play a key role in the premalignant evolution of PVL. Methods: We performed single‐cell RNA sequencing on three biopsy samples from a large PVL lesion. These samples exhibited a histopathological continuum of PVL progression. Results: By analyzing the transcriptome profiles of 27,611 cells from these samples, we identified ten major cell lineages and revealed that cellular remodeling occurred during the progression of PVL lesions, including epithelial, stromal, and immune cells. Epithelial cells are shifted to tumorigenic states and secretory patterns at the premalignant stage. Immune cells showed growing immunosuppressive phenotypes during PVL progression. Remarkably, two novel cell subtypes INSR+ endothelial cells and ASPN+ fibroblasts, were discovered and may play vital roles in microenvironment remodeling, such as angiogenesis and stromal fibrosis, which are closely involved in malignant transformation. Conclusion: Our work is the first to depict the cellular landscape of PVL and speculate that disease progression may be driven by functional remodeling of multiple cell subtypes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relation between the expression of PD‐1, PD‐L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD‐1 and PD‐L1 on immune microenvironment in the progression of oral carcinogenesis. Methods: We evaluated the expression of PD‐1/PD‐L1 and composition of CD3+, CD8+and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. Results: IHC staining demonstrated that the expression of PD‐1 was significantly increased in the high‐grade OLK group than in the low‐grade OLK group, while PD‐L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high‐grade OLK group than in the low‐grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high‐grade OLK group. PD‐1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD‐1‐expression group showed a better malignant‐free survival than high PD‐1 expression group in the OLK (p < 0.05). Conclusion: The PD‐1/PD‐L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation. [ABSTRACT FROM AUTHOR]

Objective: Snail family transcriptional repressor 2 (SNAI2) is a key regulator of partial epithelial‐mesenchymal transition (p‐EMT) and is associated with tumorigenesis. Whether SNAI2 promotes oral leukoplakia (OLK) malignant transformation by modulating p‐EMT is unclear. Materials and Methods: This study utilized two clinical datasets (GSE26549 and GSE85195) from the Gene Expression Omnibus database, cytological experiments, and a 4‐nitroquinoline 1‐oxide‐induced mice model to explore the role of SNAI2 in OLK malignant transformation. Results: The clinical cohort found SNAI2, as a risk factor (HR = 2.50, 95% CI: 1.08–5.79, p = 0.033), could promote OLK malignant transformation (p = 0.012). Cytological experiments indicated that SNAI2 overexpression promoted DOK cell proliferation, invasion, migration, and increase the protein expression of p‐EMT relative signatures, whereas SNAI2 silencing has opposite effects. Furthermore, the mice model and clinical datasets demonstrated the expression of SNAI2 and p‐EMT relative signatures were increased with OLK malignant transformation. And SNAI2 was strongly correlated with p‐EMT. Besides, co‐expressed genes of SNAI2 were also enriched in p‐EMT relative biological processes and signaling pathways. Conclusions: p‐EMT plays a significant role in promoting the OLK malignant transformation. As an important regulator of p‐EMT, SNAI2 could be a target to block the OLK malignant transformation. [ABSTRACT FROM AUTHOR]

The management of oral potentially malignant disorders (OPMD) including oral leukoplakia (OL) is not currently structured according to agreed guidelines. The current report presents survey data gathered from Oral Medicine Practitioners (OMPs) in Europe and Australia and is aimed to investigate attitudes and practice in the diagnosis, risk stratification and treatment of OL. In the presence of a clinical provisional diagnosis of OL, respondents reported always undertaking biopsy in 83% of cases, with most OMPs also relying on diagnostic adjuncts. The potential for malignant transformation is almost invariably assessed through epithelial dysplasia status, with other biomarkers described in the literature used less often. Active treatment of OL was considered mandatory by 20% of OMPs, while others reserve treatment for selected cases only. OMPs are mostly driven to active treatment by lesion‐related features which are frequently jointly considered including lesion site, clinical appearance and dysplasia status. Inconsistent assessment was observed regarding mild dysplasia, lesion size, presence of unavoidable trauma, exposure to tobacco and patient age. Frequently observed geographical variations were seldom statistically significant. In agreement with previous surveys, a lack of consensus around the management of OL was observed, supporting claims from learned academies and societies for treatment guidelines aiming to reduce inter‐practitioner variability. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OL) is an unfavorable oral disease often resistant to therapy. To this end, cold physical plasma technology was explored as a novel therapeutic agent in an experimental setup. Methods: Biopsies with a diameter of 3 mm were obtained from non‐diseased and OL tissues. Subsequently, cold atmospheric pressure plasma (CAP) exposure was performed ex vivo in the laboratory. After 20 h of incubation, biopsies were cryo‐conserved, and tissue sections were quantified for lymphocyte infiltrates, discriminating between naïve and memory cytotoxic and T‐helper cells. In addition, the secretion pattern related to inflammation was investigated in the tissue culture supernatants by quantifying 10 chemokines and cytokines. Results: In CAP‐treated OL tissue, significantly decreased overall lymphocyte numbers were observed. In addition, reduced levels were observed when discriminating for the T‐cell subpopulations but did not reach statistical significance. Moreover, CAP treatment significantly reduced levels of C‐X‐C motif chemokine 10 (CXCL10) and granulocyte‐macrophage colony‐stimulating factor in the OL biopsies' supernatants. In idiopathically inflamed tissues, ex vivo CAP exposure reduced T‐cells and CXCL10 as well but also led to markedly increased interleukin‐1β secretion. Conclusion: Our findings suggest CAP to have immuno‐modulatory properties, which could be of therapeutic significance in the therapy of OL. Future studies should investigate the efficacy of CAP therapy in vivo in a larger cohort. [ABSTRACT FROM AUTHOR]

Objective: Oral leukoplakia is the most common oral potentially malignant disorder. Malignant transformation of oral leukoplakia occurs at an annual rate of 1%–7%. WHO‐defined classic epithelial dysplasia is an important predictor of malignant transformation of oral leukoplakia, but we have previously shown in a proof of concept study that prediction improves by incorporation of an architectural pattern of dysplasia, also coined as differentiated dysplasia. We aimed to analyze this finding in a larger cohort of patients. Method: For this retrospective study 176 oral leukoplakia patients were included. Biopsies for all patients were assessed for the presence of dysplasia and analyzed for cytokeratin 13 and 17 expression. Moreover, the inter‐observer agreement for the diagnosis of differentiated dysplasia was determined. Results: In total, 33 of 176 patients developed oral squamous cell carcinoma during follow‐up. Presence of classic epithelial dysplasia increased cancer risk two‐fold (HR = 2.18, p = 0.026). Lesions without classic epithelial dysplasia could be further risk‐stratified by the presence of differentiated dysplasia (HR = 7.36, p < 0.001). Combined classic epithelial and differentiated dysplasia imparted a seven‐fold increased risk of malignant transformation (7.34, p = 0.001). Inter‐observer agreement for the diagnosis of dysplasia, including differentiated dysplasia, was moderate (κ = 0.56, p < 0.001). Discussion: This study emphasizes the importance of the recognition of the architectural pattern of differentiated dysplasia as a separate entity for risk prediction of malignant transformation of oral leukoplakia. Presence of any pattern of dysplasia results in accurate prediction of malignant transformation risk of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Recent new terminologies have been proposed for lesions in the sphere of oral lichen planus (OLP) that theoretically present unique aetiological, clinical, prognostic or management characteristics different from those of the so‐called typical forms of OLP. We aimed to critically analyse what concepts and terminologies related to OLP should we accept based on the available evidence. A review of the literature was carried out in order to critically analyse the concepts and terminologies related to OLP. New concepts and terminologies include oral lichenoid lesions; contact lichenoid reactions, drug lichenoid reactions or those in the context of graft‐versus‐host disease; chronic ulcerative stomatitis; lichen planus pemphigoid; and some lesions that are difficult to categorise, such as OLP with features of proliferative verrucous leukoplakia and lichenoid lesions of the upper labial mucosa. A multidisciplinary, multicontinent working group has recently published a guideline with recommendations for modifying definitions and terminologies associated with a disease, among which a reasoned, evidence‐based justification for the proposed change is considered essential. An in‐depth analysis of the newly proposed terms for OLP‐related lesions shows that many of them are not justified. In this paper, we set out our position on the basis of the existing evidence on the appropriateness of the use of these new terms. [ABSTRACT FROM AUTHOR]

Objectives: The main purpose of this study was to assess the response of oral leukoplakia to CO2 laser vaporization treatment, as well as determining possible factors that may affect recurrence of lesions. Materials and methods: A retrospective study was conducted, in which the medical records of patients who had been clinically and histologically diagnosed with oral leukoplakia and treated with CO2 laser between 1996 and 2019 at the Oral Medicine Teaching Unit of the Faculty of Dentistry of the University of Santiago de Compostela were reviewed. Results: Fifty‐eight patients were included: 36 female and 22 male subjects, with a mean age of 63.7 years old (SD ±13.1). The average follow‐up time was 57.5 months (SD ±57.9). A relapse rate of 52.6% was determined. Of all the studied variables, the margin was the only one for which a statistically significant association with recurrence of lesions was demonstrated (p < 0.05). Conclusion: The vaporization of lesions using CO2 laser with a safety margin of at least 3 mm from the clinical limits of OL is a key factor in preventing recurrence. [ABSTRACT FROM AUTHOR]

Objectives: A classification and staging system for oral leukoplakia (OL) was introduced to promote uniform reporting. In this system, size and the histopathologic diagnosis are assessed and combined in a staging system. The various stages could be predictive for malignant transformation of OL. Differentiated dysplasia (DD) was recently recognized as an important architectural pattern of dysplasia and is highly associated with malignant transformation (MT) of OL. In the present study, DD was incorporated in the OL‐system. The aim of the present study was to test the adapted system on a cohort of patients with OL. Patient and methods: The group consisted of 140 patients. The size, absence or presence and degree of classic dysplasia (CD) and DD were incorporated into the OL‐system. Results: In 31/140 patients, MT occurred. Size was not statistically significant with MT (p = 0.422). The presence of dysplasia was predictive for MT (p = 0.003), whereby severe CD and DD were highly statistically significant for MT (p = 0.008). Stage IV was statistically significant for MT (p = 0.011). Conclusions: The present study emphasizes the value of the slightly modified OL‐system with incorporation of DD in uniform reporting of OL and the value in predicting MT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This meta‐analysis aimed to assess the rate of malignant transformation (MT) of oral leukoplakia (OL) and to study potential risk factors for the MT of OL into oral squamous cell carcinoma (OSCC). Method: We performed a bibliographic search on nine electronic databases, including PubMed, MEDLINE, and Wanfang Data, for data on the MT rate of OL. Possible risk factors were calculated using Comprehensive Meta‐Analysis and Open Meta [Analyst] software. Results: The pooled proportion of OL MT for the total population described in the 26 selected studies was 7.20% (95% confidence interval: 5.40–9.10%). Nonhomogeneous type lesions, higher grades of dysplasia, the location of the lesion (tongue and multifocal), and female sex had significant effects on the MT of OL. Conclusion: OL tended to develop into OSCC (7.2%), and those with significant MT risk factors should be subjected to regular follow‐up and observation. However, we require large‐scale prospective studies to validate these results, together with unified clinicopathological diagnostic criteria, standardized risk factor recording/assessment methods, and long‐term follow‐up guidelines. [ABSTRACT FROM AUTHOR]

The article "Authors' Reply: Oral Leukoplakia Treated With Laser and Scalpel: Interim Trial Results of Recurrence and Malignancy" discusses the challenges and considerations in treating oral leukoplakia with laser and scalpel methods. The authors address concerns about the discrepancy in the number of patients with oral epithelial dysplasia (OED) between the treatment groups and emphasize the importance of prompt and effective treatment regardless of dysplasia grades. They also highlight the significance of lesion size, location, and the need for comprehensive randomized clinical trials to improve management strategies for oral leukoplakia. The study aims to provide a detailed analysis to enhance the evidence base for treatment decisions and outcomes. [Extracted from the article]

Background: Oral leukoplakia concomitant with oral submucous fibrosis is a high‐risk oral potentially malignant disorder, but little is known about its immune microenvironment. Methods: Thirty samples of oral leukoplakia concomitant with oral submucous fibrosis, 30 oral leukoplakia samples, and 30 oral submucous fibrosis samples were collected from two hospitals. Immunohistochemistry was performed to analyze expression of T cell biomarkers [CD3, CD4, CD8, and Forkhead box P3 (Foxp3)], a B cell biomarker (CD20), macrophage biomarkers (CD68 and CD163), an immune inhibitory receptor ligand (PD‐L1), and Ki‐67. Results: The numbers of CD3+ (p < 0.001), CD4+ (p = 0.018), and CD8+ (p = 0.031) cells in oral leukoplakia concomitant with oral submucous fibrosis were less than those in oral leukoplakia. The number of CD4+ cells (p = 0.035) in oral leukoplakia concomitant with oral leukoplakia was higher than that in oral submucous fibrosis. More CD3+(p < 0.001), CD4+(p < 0.001), Foxp3+(p = 0.019), and CD163+(p = 0.029) cells were found in oral leukoplakia than in oral submucous fibrosis. Conclusion: Various levels of immune infiltration were observed among oral leukoplakia concomitant with oral submucous fibrosis, oral leukoplakia, and oral submucous fibrosis. Characterization of the immune microenvironment may contribute to personalized immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high‐risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. Methods: PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. Results: A total of seven saliva biomarkers were analyzed in this paper, including interleukin‐1alpha, interleukin‐6 (IL‐6), interleukin‐6‐8, tumor necrosis factor alpha (TNF‐α), copper, zinc, and lactate dehydrogenase. IL‐6 and TNF‐α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL‐6, TNF‐α, C‐reactive protein, total cholesterol, triglycerides, high‐density lipoproteins, low‐density lipoproteins, albumin, protein, β2‐microglobulin, fucose, lipid‐bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. Conclusion: IL‐6 and TNF‐α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration. [ABSTRACT FROM AUTHOR]

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

Objective: This study aimed to evaluate prognostic outcomes of PVL‐derived oral squamous cell carcinomas (P‐OSCC) based on recurrence, new primary tumour, metastasis and survival information. Study design: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P‐OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies. Results: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P‐OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years. Conclusion: Apparently, P‐OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P‐OSCC; therefore, specific studies must be performed to achieve a better comparison between P‐OSCC and conventional OSCC progression. [ABSTRACT FROM AUTHOR]

Objectives: To assess the clinicopathological characteristics of a cohort of patients with oral leukoplakia (OL) managed in a Romanian dental hospital and to evaluate the risk of malignant transformation (MT). Materials and methods: We conducted a hospital‐based retrospective study using the clinical charts of patients diagnosed with OL that had complete clinical and histopathological evaluation followed up for 1–16 years. Results: From 120 included patients, 68 (56.7%) were females, and 71 (59.2%) were current smokers. The homogeneous form was present in 60% of cases; the buccal mucosa was the most frequently involved site. MT was observed in 9 cases, which was more common in females and in those with dysplastic leukoplakia. A significant statistical association was found between MT and dysplasia grade (χ2 test: p = 0.007). MT occurred during a mean interval of time 75 months in both treated and non‐treated patients. Conclusions: In this leukoplakia cohort, most of the lesions encountered were in smokers, clinically homogeneous and 62.5% proved histologically benign. But despite the clinically benign appearance of leukoplakia, tissue diagnosis of some cases was carcinoma. The results of the current study advocate the necessity for biopsy even in apparently homogeneous, clinically benign lesions. The malignization rate was 7.5%; two‐thirds were nonhomogeneous lesions. [ABSTRACT FROM AUTHOR]

Background: Establishing the risk of malignant transformation (MT) in oral leukoplakia is usually based on grading oral epithelial dysplasia (OED) on biopsy tissue, for which two systems are proposed: a 3‐tier and a binary system. Only very few actuarial studies have tested the accuracy of such methods in predicting MT, especially for the binary system. This study aimed to assess the accuracy of the two grading systems in predicting MT in a cohort of oral leukoplakia (OL) from Brazil, with follow‐up data. Methods: The sample comprised 878 individuals diagnosed with OL from 2005 to 2018. Follow‐up data were obtained both locally and from the regional cancer registry. All lesions were graded using both the 3‐tier and the binary systems. Kaplan–Meier curves (Log‐rank Mantel‐Cox) were used to assess risk and kappa to assess interobserver agreement. Results: Thirty‐five individuals underwent MT (4%). Both systems demonstrated prognostic value, though the 3‐tier system proved superior, with OR 9.23 (3.42–23.69), PPV 0.152, NPV 0.98, compared to binary OR 3.49 (1.79–6.79), PPV 0.079, NPV 0.976. Interobserver agreement was also superior in the 3‐tier system (0.47, p < 0.05) compared to the binary system (0.139, p = 0.39). Combining the two systems enhanced prognostic values (OR 14.28, PPV 0.217, NPV 0.981). Conclusion: The 3‐tier system presented superior prognostic value to the binary system. Combining both systems to double‐grade intermediate lesions might enhance risk assessment. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)‐based histology image analyses could accelerate the discovery of better OC progression risk models. Methods: Our CNN‐based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could identify abnormal morphological features of the oral epithelium. By applying this model to OL slides, we hypothesized that the extent of OC‐like features identified in the OL epithelium would correlate with its progression risk. The OMRS model scored and categorized the OL cohort (n = 62) into high‐ and low‐risk groups. Results: OL patients classified as high‐risk (n = 31) were 3.98 (95% CI 1.36–11.7) times more likely to develop OC than low‐risk ones (n = 31). Time‐to‐progression significantly differed between high‐ and low‐risk groups (p = 0.003). The 5‐year OC development probability was 21.3% for low‐risk and 52.5% for high‐risk patients. The predictive power of the OMRS model was sustained even after adjustment for age, OL site, and OL dysplasia grading (HR = 4.52, 1.5–13.7). Conclusion: The ORMS model successfully identified OL patients with a high risk of OC development and can potentially benefit OC early diagnosis and prevention policies. [ABSTRACT FROM AUTHOR]

A personal narrative is presented which explores the authors experience of analyzing data collected as part of the San Francisco Men's Health Study (SFMHS).

Objectives: To identify possible associations between patients' demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at patients' first visit. Method: A total of 140 consecutive patients with OL at a single institute between 1997 and 2019. All biopsies were microscopically examined for classic dysplasia (CD) (WHO definition oral epithelial dysplasia) and differentiated dysplasia (DD) known from differentiated vulvar intraepithelial neoplasia. Clinical characteristics were correlated to histopathological diagnosis and odds ratios (OR) were calculated. Results: A total of 96 females and 44 males, mean age 58 years, were presented. OLs were found mainly on the tongue (41%) and floor of mouth (FOM) (18%). Homogeneous OLs (58%) were associated with smoking, FOM and size <2cm and non‐homogeneous OLs (42%) with non‐smokers. No dysplasia was present in 40% and any dysplasia (AD) in 60%. Tongue OLs were correlated with AD (OR:6.0) and CD (OR:5.7). FOM OLs were correlated with CD (OR:4.5). DD was correlated with non‐homogeneous OLs (OR:2.6). Conclusions: CD was most frequently observed in tongue and FOM OLs, while DD was associated with non‐homogeneous OLs. In this series of patients, there was no consistent reliable association between the clinical and histopathological features and clinical characteristics can therefore not substitute microscopic examination of biopsies. [ABSTRACT FROM AUTHOR]

Objective: To assess the oral shedding and viremia of Epstein–Barr virus (EBV) in HIV‐positive patients and their relationship with oral hairy leukoplakia (OHL). Methodology: A total of 94 HIV‐positive patients were included in the study, in which blood and saliva samples were collected for EBV quantification. Data on gender, age, time of HIV seropositivity, combined antiretroviral therapy (cART), CD4+ T‐cell counts, and HIV viral load were collected. OHL diagnosis was based on histopathological examination and EBV in situ hybridization. Results: The EBV load in the 94 HIV‐positive patients was higher in saliva than in blood (2.4 and 1.6, respectively), and there was a positive correlation between EBV oral shedding and viremia (p = 0.001). Twenty (21.27%) patients had OHL and also a higher EBV load in saliva (mean log10 = 3.11) compared to those who had no OHL (p = 0.045). Presence of OHL was only associated with age (p = 0.030). Conclusion: In HIV‐positive patients, the presence of OHL was associated with EBV oral shedding but not with viremia, regardless of the amount of circulating CD4+ T cells. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Oral leukoplakia (OL) being the most frequent potentially malignant disorder. Topics include histopathological grading of epithelial dysplasia recommended by the World Health Organization (WHO); and representing a novel therapeutic target or biomarker for diagnosis and prognosis aiding cancer treatment.

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

The article discusses the treatment of oral leukoplakia, a condition that can potentially lead to oral cancer. The authors evaluate the effectiveness of surgical treatment using a diode laser compared to traditional scalpel in a randomized controlled trial. They highlight the importance of considering factors such as the grade of dysplasia and lesion size when determining the appropriate treatment method. The study emphasizes the need for larger patient cohorts and further research to improve outcomes. [Extracted from the article]

Background: Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. Methods: Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridization in the tongue squamous cell carcinoma cases. Results: Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p = 0.016, HR: 7.3, 95% CI: 1.4–37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease‐free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p = 0.024; HR: 4.9, 95% CI: 1.2–19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n = 8) showed markedly impaired overall survival (p = 0.020; HR: 6.4, 95% CI: 1.3–31.1) and disease‐free survival (p = 0.001, HR: 13.0, 95% CI: 3.0–55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p = 0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease‐free survival. Conclusion: Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma. [ABSTRACT FROM AUTHOR]