Abstract
Simple SummaryProliferative verrucous leukoplakia (PVL) was recognized in 2005 by the World Health Organization as a rare subtype of true oral leukoplakia, with unknown etiology. Since its first description in 1985, several diagnostic criteria have been proposed over the years. The aim of this systematic review is to investigate the percentage of patients diagnosed with proliferative verrucous leukoplakia who progressed to oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC).Aim: The aim of the present systematic review was to investigate the risk of malignant transformation of proliferative verrucous leukoplakia (PVL). Materials and Methods: the search was carried out using a combination of terms (leukoplakia OR leucoplakia) AND (multifocal OR proliferative) on the following databases: PubMed, Scopus, Web of Science (WOS Core Collection), Cochrane Library, selecting only articles published since 1985 and in the English language. Demographic, disease-related, and follow-up data extracted from the studies included in the qualitative synthesis were combined. Weighted means ± standard deviations were calculated for continuous variables, while categorical variables were reported as frequencies and percentages. Dichotomous outcomes were expressed as odd ratios (ORs) with 95% confidence intervals (CIs). Odd ratios for individual studies were combined using a random-effects meta-analysis, conducted using Review Manager 5.4 Software (Cochrane Community, Oxford, England). Results: twenty-two articles were included, with a total of 699 PVL patients, undergoing a mean follow-up of 7.2 years. Sixty-six percent of patients were females, with a mean age of 70.2 years, and 33.3% were males, with a mean age of 59.6 years. Most patients were non-smokers and non-alcohol users, and the gingiva/alveolar ridge mucosa was the most involved anatomical site by both PVL appearance and malignant transformation. A total of 320 PVL patients developed oral verrucous carcinoma (OVC) or conventional oral squamous cell carcinoma (OSCC) because of malignant transformation of PVL lesions (45.8%). A statistically significant 3.8-fold higher risk of progression to conventional OSCC was found compared to OVC in PVL patients, with women being 1.7 times more likely to develop oral cancer than men, as a consequence of PVL progression. Moreover, a statistically significant higher likelihood of developing conventional OSCC in female PVL patients than in males was found. In 46.5% of patients with PVL malignant transformation, multiple carcinomas, in different oral sites, occurred during follow-up. Conclusions: PVL is an aggressive lesion, which, in a high percentage of cases (almost 50%), undergoes malignant transformation, mainly toward OSCC. The female gender is most affected, especially in the elderly, with a negative history for alcohol and tobacco consumption.
Highlights
Weighted means ± standard deviations were calculated for continuous variables, while categorical variables were reported as frequencies and percentages
Dichotomous outcomes were expressed as odd ratios (ORs) with 95% confidence intervals (CIs)
One of them [12] referred to the same patient group reported by another [11], but provided data related to the development of multiple carcinomas (Table 1)
Summary
Proliferative verrucous leukoplakia (PVL) was recognized in 2005 by the World Health Organization (WHO) as a rare subtype of true oral leukoplakia, with unknown etiology, which mainly affects women in old age, often with a clinical history that does not include tobacco or alcohol consumption, with high risk of malignant transformation and diagnosis, usually retrospective, based on the association of clinical and histopathological aspects [1].The expression “proliferative verrucous leukoplakia” was firstly introduced in literature in 1985 by Hansen et al to define a lesion characterized mainly by multifocal presentation, exophytic and verruciform appearance, resistance to all therapeutic approaches, both surgical and non-surgical, high tendency to malignant transformation and progressive histological changes, evidenced in sequential biopsies, with evolution from simple hyperkeratosis, to lesions with increasing degrees of dysplasia, oral verrucous carcinoma (OVC), and conventional oral squamous cell carcinoma (OSCC) [2].Several diagnostic criteria for PVL have been proposed over the years to help clinicians in diagnosis. Proliferative verrucous leukoplakia (PVL) was recognized in 2005 by the World Health Organization (WHO) as a rare subtype of true oral leukoplakia, with unknown etiology, which mainly affects women in old age, often with a clinical history that does not include tobacco or alcohol consumption, with high risk of malignant transformation and diagnosis, usually retrospective, based on the association of clinical and histopathological aspects [1]. The expression “proliferative verrucous leukoplakia” was firstly introduced in literature in 1985 by Hansen et al to define a lesion characterized mainly by multifocal presentation, exophytic and verruciform appearance, resistance to all therapeutic approaches, both surgical and non-surgical, high tendency to malignant transformation and progressive histological changes, evidenced in sequential biopsies, with evolution from simple hyperkeratosis, to lesions with increasing degrees of dysplasia, oral verrucous carcinoma (OVC), and conventional oral squamous cell carcinoma (OSCC) [2]. (3) Lesions that progress/expand and/or develop multifocality over time. (4) Histopathology, which, in absence of dysplasia or carcinoma, still shows hyperkeratosis, parakeratosis, atrophy, or acanthosis with minimal or absent cytological atypia, with or without the presence of a lymphocytic band, or verrucous hyperplasia.
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