title: Optimal Management of Proliferative Verrucous Leukoplakia: A Systematic Review of the Literature.
abstract: OBJECTIVE
  Proliferative verrucous leukoplakia (PVL) is a rare and recalcitrant form of leukoplakia. The purpose of this review is to further characterize the risk factors, clinical course, and optimal treatment for this highly aggressive, premalignant lesion.
  
  
  METHODS
  Twenty-six articles on PVL with a total of 329 PVL cases.
  
  
  METHODS
  A systematic review of the literature using Ovid, PubMed, Cochrane Database, and gray literature was conducted of all PVL cases reported between 1985 and 2014. Inclusion criteria required reporting of patient follow-up and recurrence rates. Data were analyzed using descriptive statistics. Student t test and Fisher exact test were used to identify factors associated with malignant transformation.
  
  
  RESULTS
  The mean patient age was 63.9 years. Most patients were female (66.9%) and nontobacco users (65.22%). Mean follow-up was 7.4 years, with an average of 9.0 biopsies per patient during this period. Proliferative verrucous leukoplakia exhibited histopathologic features along a progressive spectrum, evolving from leukoplakia to verrucous hyperplasia and ultimately invasive carcinoma. Surgery was the most common treatment implemented, but recurrence rates among 222 patients reached 71.2%. Subgroup analysis of 277 patients identified a 63.9% malignant transformation rate, and 39.6% of patients died of their disease. Age, sex, and tobacco use were not identified as risk factors associated with progression to cancer.
  
  
  CONCLUSIONS
  Proliferative verrucous leukoplakia is a rare form of leukoplakia with a high rate of malignant transformation. It necessitates high clinical suspicion, to include a lifetime of close follow-up and repeat biopsies by a health care provider well versed in oral carcinoma.
authors.affiliation: Department of Otolaryngology, Mike O'Callaghan Federal Medical Center, Nellis AFB, Nevada, USA.
authors.forename: Wesley M
authors.initials: WM
authors.lastname: Abadie
authors.affiliation: Division of Otolaryngology, University of Alabama-Birmingham, Birmingham, Alabama, USA epartington@uabmc.edu.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Partington
authors.affiliation: Division of Oral and Maxillofacial Pathology, University of Kentucky School of Dentistry, Lexington, Kentucky, USA.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Fowler
authors.affiliation: Division of Otolaryngology, University of Alabama-Birmingham, Birmingham, Alabama, USA.
authors.forename: Cecelia E
authors.initials: CE
authors.lastname: Schmalbach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D005260:Female; D006801:Humans; D007971:Leukoplakia / Q000473:pathology / Q000601:surgery*; D007972:Leukoplakia, Oral / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology
keywords: leukoplakia; oral cancer; oral cavity; squamous cell carcinoma