Oral Proliferative Verrucous Leukoplakia: Progression to Malignancy and Clinical Implications. Systematic Review and Meta-Analysis

Abstract

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.