Proliferative Verrucous Leukoplakia Research Articles

Eradication of proliferative verrucous leukoplakia with toll-like receptor 7 agonist (topical imiquimod): a case report

Proliferative verrucous leukoplakia (PVL) is an aggressive and distinct type of oral precancerous lesion characterized by warty surfaced white plaque diffusely involving oral mucosa. Surgical excision is the treatment of choice. However, PVL has persistent and recurrent growth patterns, requiring multiple surgical procedures. Surgical intervention is especially challenging if PVL extends between teeth limiting access. These interproximally located lesions have a high propensity to undergo malignant transformation. We report a case of a 53-year-old man with recurrent PVL diffusely covering the maxillary and mandibular gingiva. Despite complete surgical excisions, PVL recurred, and a focal area in the interproximal mandibular gingiva progressed to invasive squamous cell carcinoma requiring marginal resection. The remaining PVL areas were treated with topical imiquimod (toll-like receptor 7 agonist) for six months, resulting in complete clinical and histological resolution. Topical agents can cover a larger surface area and penetrate in between interproximal areas. Importantly, it allows for maximal local exposure with minimal systemic toxicity, essential for long-term treatment and prophylactic use of the agent to prevent relapse.

A review of proliferative verrucous leukoplakia

Proliferative verrucous leukoplakia (PVL) is a rare, but relentless, form of leukoplakia, with a high recurrence rate and a tendency to become malignant, either as an oral squamous cell carcinoma (OSCC) or verrucous carcinoma (VC). Its aetiology is mainly unknown, and there is uncertainty around its management owing to its resistance to most treatments with a high rate of recurrence. CPD/Clinical Relevance: Understanding PVL is key to making prompt diagnosis and referral for improved outcome of treatment due to its high malignancy transformation rate.

Gingival Proliferative Verrucous Leukoplakia and Cancer: A Systematic Review With Meta-Analysis.

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.

Management of Oral Leukoplakia – A Systematic Umbrella Review of Global Evidence

Objective: To summarize the global evidence related to various interventions for treating Oral Leukoplakia. Introduction: Oral leukoplakia is a common oral potentially malignant lesion that precedes the development of oral cancer. The main aim of any treatment is to prevent the malignant transformation. This umbrella review updates the global evidence of different medicinal treatment available for Oral Leukoplakia. Methods: The databases searched were Cochrane database of systematic reviews, JBI Evidence Synthesis, MEDLINE, Web of Science, Scopus. The key terms used were leukoplakia, oral leukoplakias, Proliferative verrucous leukoplakia, interventions, management, chemoprevention, laser, photodynamic, topical agents. JBI Sumari software was used to screen and appraise the articles along with data extraction and data synthesis. Results: A total of 670 citations were identified through the electronic search. Out of which 61 systematic reviews were recognized. Following removal of duplicates, 47 records were retrieved. The full texts of 13 papers were retrieved for further examination with 9 systematic reviews meeting the inclusion criteria and therefore included in this umbrella review. Study overlap calculation was conducted and pooled results showed that the treatments available for oral leukoplakia has little effect on clinical response and malignant transformation rate. Conclusions: Currently we do not have evidence of a treatment that is preventing oral leukoplakia from converting to oral cancer. Treatments such as vitamin A and beta carotene may be effective in reducing clinical size of oral lesions. More long-term studies are required for surgical management, lasers and photodynamic therapy.

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

BackgroundThe 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 methodsOral 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.ResultsOur 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.ConclusionsDifferent disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

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.

Interpretation of "Proliferative verrucous leukoplakia: an expert consensus guideline for stadardized assessment and reporting"

Proliferative verrucous leukoplakia (PVL) is a special oral leukoplakia, which has the characteristics of high recurrence and canceration rate. In 2021, the American Society of Oral and Maxillofacial Pathology and the North American Association of head and neck Pathologists published "Proliferative verrucous leukoplakia: an expert consensus guideline for standardized assessment and reporting", and divided PVL into four categories: ①Corrugated ortho(para)hyperkeratotic lesion, not reactive; ②Bulky hyperkeratotic epithelial proliferation, not reactive; ③Squamous cell carcinoma, or suspicious for squamous cell carcinoma; and ④Does not fit any above category. This paper intends to interpret the new classifications of PVL in the guidelines in order to provide guidance for clinical diagnosis and treatment.

Epidemiological Trends and Clinicopathological Characteristics of Oral Leukoplakia: A Retrospective Analysis From a Single Institution in Chennai, Tamil Nadu, India.

Background India has a high prevalence of oral potentially malignant disorders and malignant transformation. Cases of oral leukoplakia are not commonly encountered, and only a small cohort of patients undergo biopsies for the same. This study aims to assess the various etiological factors causing leukoplakia, the clinical features, histopathological findings, and treatment received by the patients who were histopathologically diagnosed with oral leukoplakia. Methodology Oral leukoplakia cases were included in this study from total biopsy samples received in the oral pathology department. Details were collected from the Dental Information Archival Software of our institution. The period analyzed was from January 1, 2021, to December31, 2023. Relevant clinical and histopathological details were retrieved and tabulated. Statistical analysis (chi-square test) was used to assess the association between the clinicopathological parameters using SPSS software version 21.0 (IBM Corp., Armonk, NY, USA) with a significance level set at a p-value <0.05. Results A total of 76 oral leukoplakia cases were retrieved from 2,600 biopsy samples. The prevalence of oral leukoplakia was 3.1% to 3.4% for the three years. Leukoplakia was commonly observed in those aged 51 to 60 years (33%). Overall, 21% of the patients with leukoplakia showed severe epithelial dysplasia, 22% showed mild epithelial dysplasia, and 39% showed moderate epithelial dysplasia. Moreover, 30% of the patients presented with leukoplakia and oral submucous fibrosis and showed varying degrees of epithelial dysplasia. Finally, 45% of the patients were managed conservatively using pharmacotherapy. Conclusions Severe epithelial dysplasia was commonly associated with oral leukoplakia. Oral submucous fibrosis was also found to be associated with leukoplakia and showed epithelial dysplasia. None of our proliferative verrucous leukoplakia cases showed any association with oral submucous fibrosis. Surgical management was the preferred treatment.

Genome-wide characterization of the mutational landscape of proliferative verrucous leukoplakia

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

370 Point-of-Service Salivary Microbiome Analysis in the Prevention and Detection of Oral Premalignant Lesions

OBJECTIVES/GOALS: Our aim is to establish soluble salivary biomarkers indicative of increased risk of oral premalignancy to be used in a point-of-service technology. Our goal is to non-invasively assess risk level for premalignancy by characterizing a molecular signature pattern that can be applied to such a diagnostic tool at routine dental or medical visits. METHODS/STUDY POPULATION: Adult patients 18 years of age and older who are non-smokers and patients of the University of Maryland School of Dentistry Oral Medicine Clinic and have been diagnosed with oral premalignancy (proliferative verrucous leukoplakia) are eligible. Exclusion criteria include history of immunosuppression or immune compromise; use of antifungal, antibiotic, and/or antiviral medications within the past three months; and gross dental disease. Serial unstimulated saliva samples will be collected at baseline or diagnosis of oral premalignancy, 6 months and 12 months. Solubility testing will be completed to determine whether malignant markers such as EGFR/mTOR/PI3K/p53 are soluble in saliva, and patient samples will be analyzed by ELISA and compared to appropriate controls. RESULTS/ANTICIPATED RESULTS: We anticipate demonstrating increased activity of molecular pathways known to be involved in malignant transformation, such as EGFR/mTOR/PI3K/p53, or increased burden of select microbial pathogens to be associated with increased risk of oral premalignancy in the form of proliferative verrucous leukoplakia. Preliminary sensitivity and specificity testing of the identified markers will provide additional insight to the utility of a diagnostic tool with salivary specimen. Therefore, the microbiome and/or molecular profile proposed from these results will serve as a translational application to development of future point-of-service test devices to be used in the prevention and detection of oral premalignant lesions. DISCUSSION/SIGNIFICANCE: Oral cancer is the sixth most common cancer worldwide, and presents challenges in its diagnosis and clinical management. Later diagnosis is associated with poorer patient outcomes—therefore, a molecular and microbiome profile that may be used in a noninvasive diagnostic test technology would prove beneficial to providers and patients.

Spectrum of white lesions in the oral cavity- A review

The white lesions occurring in the oral cavity consist of 5% of the oral pathoses but some of these like leukoplakia, lichen planus, proliferative verrucous leukoplakia, etc have a high potential of malignant transformation up to 0.5-100%. As they are visualized as shades of white, they are of diagnostic challenge. Some of the lesions are also associated with other skin lesions viz. lichen planus, pemphigus, etc. The etiology, pathogenesis, and mode of treatment varies with the different type of lesions. This spectrum consists of lesions from harmless reactive lesions to dysplastic and malignant entities. The white appearance of these lesions is may be because of hyperkeratosis, acanthosis, intracellular/intercellular edema, necrosis of the epithelial cell or increased fibrosis. They are seen as patches, papules, or plaques unilaterally or bilaterally in the oral cavity involving buccal mucosa, tongue, palate, labial mucosa, gingiva etc. While there are a few clinical and histological elements that assist in the identification of this wide range of white lesions to arrive at an accurate diagnosis, further lending a hand in providing appropriate treatment for the same.

Global gene expression profile of proliferative verrucous leukoplakia and its underlying biological disease mechanisms

BackgroundProliferative verrucous leukoplakia (PVL) is a rare and enigmatic oral potentially malignant disorder which almost invariably results in oral squamous cell carcinoma (OSCC). The aims of this project were to use transcriptome profiling to characterise PVL gene expression patterns for biomarker identification and gain insight into the molecular aetiopathogenesis of PVL. MethodsForty-three oral cavity mucosal biopsies from 32 patients with oral lesions clinically compatible with either PVL or non-PVL conventional oral leukoplakia (OLK) underwent transcriptome profiling by RNA sequencing. Data was analysed by hierarchical clustering, differential gene expression, functional enrichment and network analysis, sparse partial least squares discriminant analysis sPLS-DA, and immune cell phenotypic estimation. ResultsWe found 464 genes significantly differentially expressed at least 2-fold between PVL and non-PVL OLK (193 up and 271 down). HOX genes, including HOXA1 and HOXB7, keratin-associated proteins (KRTAPs) and olfactory receptor G proteins (OR) were significantly upregulated in PVL. Other upregulated genes in PVL included FOS, WNT16 and IFNA1. Pathway analysis showed that there was a significant downregulation of connective tissue signalling in PVL. Classifying multivariate models based upon 22 genes discriminated PVL from non-PVL OLK. Bioinformatic profiling showed that immune cell profiles in PVL and OLK were similar except that fibroblast markers were reduced in PVL. ConclusionThese results demonstrate that PVL and conventional OLK are molecularly distinct with upregulation of many cancer-associated genes. They provide insight into the pathogenesis of PVL and show that biomarker based molecular diagnostics is feasible to discriminate and inform diagnosis and management.

Proliferative verrucous leukoplakia: a general dental practitioner-focused clinical review

Proliferative verrucous leukoplakia (PVL) is a distinct type of oral leukoplakia which has the potential to enlarge or develop into new areas of leukoplakia coupled with areas of a warty surface texture. PVL is usually diagnosed from the fifth decade onwards and is more common in female patients. The most frequent sites involved tend to be gingivae, followed by buccal mucosa and lateral border of tongue. It is one of the oral potentially malignant conditions with a high risk of malignant transformation. It is important for general dental practitioners (GDPs) to identify such lesions to facilitate referral for further investigation and diagnosis. Management is challenging with long-term monitoring and surgical excision when appropriate; however, PVL tends to recur following surgical excision. This article provides an up-to-date review tailored for GDPs on the present knowledge of PVL and illustrates the management challenges with clinical cases.

Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis.

Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oral potentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinical practice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF to outline the clinical behavior and challenges in the management of this high-risk group in clinical practice. We retrospectively analyzed cases of six Indian patients (four with OSF) managed over a period of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, medical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits, the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or when surgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twice daily was initiated. All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesions were either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional or systemic metastasis. Despite thorough interventions, the patients died of, or with the disease. The occurrence of two or more oral potentially malignant disorders poses challenges in patient management and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to assess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.

Clinicopathological Features of a Lower Lip Verruciform Xanthoma: A Rare Case Report

Verruciform Xanthoma (VX) is an uncommon, benign, asymptomatic lesion of the oral cavity. The incidence rate of VX is 0.025%, with the most common location reported to be the gingival margin, followed by the tongue, hard palate, buccal and labial mucosa. It may also present on the skin and genitals. VX can manifest as a solitary or multiple lesion with well-defined margins. It appears as a papule or plaque with verrucous or papillary growth, exhibiting variable colours ranging from reddish-pink and yellow to grey. While the lesion typically appears verruciform, it may also have a polypoid, papillomatous, or sessile nature. In the present case report, the authors present a 45-year-old male patient with a history of tobacco use, who exhibited a reddish-pink papillomatous growth on his labial mucosa for a duration of three months. The growth was surgically excised, and histopathological evaluation confirmed the characteristic features of VX. The lesion healed without complications, and no recurrence was observed. Clinically, VX may be mistaken for various malignant or premalignant lesions such as papilloma, verrucous carcinoma, or proliferative verrucous leukoplakia. Therefore, it is crucial to differentiate VX from these conditions to avoid inappropriate intervention. Histopathological evaluation is necessary for the definitive diagnosis of the lesion, which reveals the pathognomonic presence of foamy histiocytes within the elongated dermal papillae. The present case report highlighted the diverse clinical features of VX and discusses its histological findings along with the differential diagnosis.

Enigmatic Cer Enigmatic Cervicofacial Actinomy vicofacial Actinomycosis P cosis Post Radiother ost Radiotherapy - A Case Report

Although thought to be uncommon, it is believed that cervicofacial actinomycosis is underreported due to frequent misdiagnosis. It has been called the “most misdiagnosed disease by experienced clinicians”. A wide range of dental procedures or trauma, including tooth eruption, may precipitate actinomycosis by enabling microorganisms to penetrate the deeper tissue layers via an entry point. This infective disease is significant due to its potentially aggressive and locally destructive nature. This case describes a patient diagnosed with cervicofacial actinomycosis. Her history prior to this was significant for proliferative verrucous leukoplakia, and T4aN0M0 (AJCC 7th Edition) squamous cell carcinoma of the right hard palate for which she received surgery and post-operative radiotherapy. The mechanism of actinomycotic infection, its presentation, differential diagnosis, and management is discussed, with review of the relevant literature. This case highlights an unusual case of cervicofacial actinomycosis and demonstrates the complexities in reaching a definitive diagnosis in cases of osteomyelitis and osteoradionecrosis with significant bacterial burden.

The Follow-Up Necessity in Human Papilloma Virus-Positive vs. Human Papilloma Virus-Negative Oral Mucosal Lesions: A Retrospective Study.

Human papilloma virus (HPV) is known as the main cause of cervical cancer. Data also indicate its role in head-neck cancer, especially oropharyngeal cancer. The correlation between high-risk HPV and oral cancer is still controversial. HPV-related lesions of the oral cavity are frequent and, in most cases, benign. The primary aim of this study was to establish if there is a different follow-up necessity between HPV-positive compared to HPV-negative oral lesions. The secondary aim was to evaluate the recurrence of HPV-related lesions. All patients who underwent a surgical procedure of oral biopsy between 2018 and 2022, with ulterior histopathological examination and HPV typing, were examined. A total of 230 patients were included: 75 received traumatic fibroma as diagnosis, 131 HPV-related lesions, 9 proliferative verrucous leukoplakia, and 15 leukoplakia. The frequency and period of follow-up varied in relation to HPV positivity and diagnosis. This study confirms what has already been reported by other authors regarding the absence of recommendations of follow-up necessity in patients with oral mucosal lesions. However, the data demonstrate that there was a statistically significant difference in the sample analyzed regarding the follow-up of HPV-positive vs. HPV-negative patients. It also confirms the low recurrence frequency of HPV-related oral lesions.

Nivolumab for Patients With High-Risk Oral Leukoplakia

Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy. To determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL. This nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia). Patients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit. The primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response. A total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss. This immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study. ClinicalTrials.gov Identifier: NCT03692325.

Proliferative Verrucous Leukoplakia: An Update

Objectives: Proliferative verrucous leukoplakia was first described by Hansen et al. in 1985. It is a rare form of oral leukoplakia with a high risk of malignant transformation. A review of the scientific literature indicates that there is no consensus on the management and follow-up of proliferative verrucous leukoplakia. This article aims to provide an update on the epidemiological, clinical, histological and immunohistochemical, diagnostic, treatment and follow-up data on the disease. Materials and Methods: We performed a narrative review by searching the Pubmed and Google Scholar databases using keywords. Results: 93 out of 446 selected articles were selected for analysis. The majority of affected patients are women. The lesions are multifocal and usually occur on the gingiva and alveolar mucosa. The aetiology is idiopathic. The diagnosis is retrospective and based on the history of the disease. Apart from mapping the lesions using repeated biopsies to detect a malignant area progression, there is no recommended treatment to cure the disease. Conclusion: The current understanding of this entity is based on the analysis of retrospective studies with weak scientific evidence. Expert recommendations regarding follow-up and management would facilitate better control of recurrence and malignant transformation rates.

Research progress in the diagnosis and management of proliferative verrucous leukoplakia

Proliferative verrucous leukoplakia (PVL) is one of the oral potentially malignant disorders (OPMD) with the highest malignant potential. PVL tends to be easily misdiagnosed owing to the resemblance in clinical manifestations between PVL and other diseases such as oral leukoplakia or oral lichen planus. PVL is considered as a special type of oral leukoplakia by some scholars, which is characterized by its tendency of recurrence and metastasis, along with its high risk of malignant transformation. So far, the accurate clinic diagnosis and management of PVL are still intractable due to the lack of definite histopathological definition, unified diagnostic criteria and effective treatment modalities. This review aims to provide the clinical practitioners with a series of advices on the clinical diagnosis and management of PVL by systematically reviewing the diagnostic logistics, therapeutic strategies, malignant transformation detection based on tremendous relevant data and evidence-based medicine.