Proliferative leukoplakia: Proposed new clinical diagnostic criteria

Villa, Alessandro; Menon, RS; Kerr, A. Ross; Alves, Fábio Abreu; Guollo, André; Ojeda, David; Woo, Sook Bin

doi:10.1111/odi.12830

Cited by 83 publications

(143 citation statements)

References 40 publications

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“…The malignant transformation of PL has been reported in different oral locations, but some authors have described a strong predilection for gingival occurrence . We have found that the most frequent locations of OSCC developed from PL are the gingiva and palate, and the least common locations are the tongue and floor of the mouth …”

Section: Introductionmentioning

confidence: 58%

“…Villa et al . also presented modified criteria, proposing four requirements related to the characteristics of PL lesions, the multifocal tendency, progression over time, and histopathological features.…”

Section: Discussionmentioning

confidence: 99%

“…According to other authors PL can be located anywhere in the mouth, but many authors cite the gingiva as the most common location (Table ) …”

Section: Discussionmentioning

confidence: 99%

“…Villa et al . reported that the gingiva was the most common location of PL, with gingival/alveolar mucosal lesions found in 33 of 42 (78.5%) patients.…”

Section: Discussionmentioning

confidence: 99%

“…The inclusion criteria, recently reported by Villa et al., were presence of smooth, fissured, verrucous, or erythematous white/keratotic lesions, with or without ulceration; presence of multifocal non‐contiguous lesions, a single large (>4.0 cm) lesion involving one site, or a single large (>3 cm) lesion involving contiguous sites; lesion progression, enlargement, or development of multifocality over time; histopathological findings of obvious dysplasia or carcinoma; hyperkeratosis, parakeratosis, atrophy, or acanthosis with minimal to no cytological atypia, with or without a lymphocytic band; and VH, not supporting a diagnosis of frictional or reactive keratosis.…”

Section: Methodsmentioning

confidence: 99%

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Oral cancer on the gingiva in patients with proliferative leukoplakia: A study of 30 cases

Bagán

Murillo-Cortés

Leopoldo-Rodado

et al. 2019

Journal of Periodontology

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Background Proliferative verrucous leukoplakia, recently coined as proliferative leukoplakia (PL), is associated with a strong tendency to recur after treatment and an elevated rate of malignant transformation. We compared the clinical characteristics of patients with gingival PL with and without progression to oral squamous cell carcinoma. Methods The patients were divided into two groups: group 1 included 33 patients with gingival PL that did not progress to cancer, and group 2 included 30 patients with PL who developed malignant transformation during follow‐up. We compared age, sex, tobacco habit, clinical characteristics of gingival PL lesions, and location, tumor‐node‐metastasis (TNM) stage, and clinical characteristics of gingival malignancy between groups. Results Female sex was predominant in the group with gingival cancer, and simultaneous involvement of the buccal mucosa, tongue, and palate was more common in this group than in the group without cancer. PL lesions were also largest in the group of patients with cancer. Most gingival cancer occurred in areas with teeth and took the form of oral ulceration. TNM stage I was most common. Conclusions The simultaneous presence of lesions on the buccal mucosa, grade of lesion extension, and presence of ulcerative lesion were significantly associated with gingival cancer in patients with PL.

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Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

“…According to other authors PL can be located anywhere in the mouth, but many authors cite the gingiva as the most common location (Table ) …”

Section: Discussionmentioning

confidence: 99%

“…Villa et al . reported that the gingiva was the most common location of PL, with gingival/alveolar mucosal lesions found in 33 of 42 (78.5%) patients.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Oral cancer on the gingiva in patients with proliferative leukoplakia: A study of 30 cases

Bagán

Murillo-Cortés

Leopoldo-Rodado

et al. 2019

Journal of Periodontology

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Nivolumab for Patients With High-Risk Oral Leukoplakia

Hanna,

Villa,

Nandi

et al. 2024

JAMA Oncol

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ImportanceProliferative 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.ObjectiveTo determine the safety and clinical activity of anti–programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL.Design, Setting, and ParticipantsThis 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).InterventionPatients 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.Main Outcomes and MeasuresThe primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: &gt;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.ResultsA 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 (&gt;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.Conclusions and RelevanceThis 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.Trial RegistrationClinicalTrials.gov Identifier: NCT03692325

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Oncological Outcomes of Patients With Oral Potentially Malignant Disorders

Villa,

Lodolo,

2024

JAMA Otolaryngol Head Neck Surg

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ImportanceUnderstanding the clinical course and malignant transformation rate of oral potentially malignant disorders (OPMDs)—including oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus—is crucial for early detection and improved survival rates in patients with oral cancer.ObjectiveTo evaluate the progression of oral cancer from OPMDs using a large US electronic medical database.Design, Setting, and ParticipantsThis retrospective cohort study used data from the University of California, San Francisco’s PatientExploreR database between January 1973 and March 2024. Patients with oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes and keywords. Demographics, tobacco and alcohol use, HIV status, and other known risk factors for oral cancer were recorded to identify factors associated with malignant transformation. Logistic regression and descriptive analyses were used.ExposureDiagnosis of oral leukoplakia, oral erythroplakia, oral submucous fibrosis, or oral lichen planus.Main Outcomes and MeasuresIncidence of oral cancer, malignant transformation rate, median time to progression, and associations between demographics and risk factors and the development of oral cancer.ResultsAmong 4 225 251 individuals in the database, 4371 were diagnosed with oral cancer (median [IQR] age, 63 [53-71] years; 2610 [59.9%] male; 0.1% of the cohort), and 110 (2.5%) had a preceding OPMD. Oral leukoplakia was found in 1124 patients, with 94 (8.4%) undergoing malignant transformation (median [IQR] time to progression, 25 [7-129] months). HIV-positive patients with oral leukoplakia were more likely to develop oral cancer (odds ratio, 3.80; 95% CI, 1.35-10.70). Of 22 patients with oral erythroplakia, 11 (50.0%) developed oral cancer (median [IQR] time to progression, 3.7 [0.2-334] months). Those who smoked tobacco with oral erythroplakia showed a higher malignant transformation rate (odds ratio, 3.75; 95% CI, 0.54-26.05). Of the 78 patients with oral submucous fibrosis, 4 (5.1%) underwent malignant transformation (median [IQR] time to progression, 36 [36-48] months). Only 1 patient with oral lichen planus developed oral cancer after 5 years.Conclusions and RelevanceThis cohort study showed that OPMDs have notable but varying propensities to progress to oral cancer. Early detection and monitoring of OPMDs are crucial for improving patient outcomes. However, the risk, etiopathogenesis, and clinical presentation vary for each OPMD and should, therefore, be considered distinct diseases.

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Proliferative leukoplakia: Proposed new clinical diagnostic criteria

Cited by 83 publications

References 40 publications

Oral cancer on the gingiva in patients with proliferative leukoplakia: A study of 30 cases

Oral cancer on the gingiva in patients with proliferative leukoplakia: A study of 30 cases

Nivolumab for Patients With High-Risk Oral Leukoplakia

Oncological Outcomes of Patients With Oral Potentially Malignant Disorders

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