Leukoplakia, Oral

BASICS

DESCRIPTION

  • Leukoplakia is defined by the World Health Organization (WHO) as “a white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer.”
  • Characterized by asymptomatic, well-demarcated white plaques that cannot be wiped away, this condition requires a biopsy for histopathologic evaluation to assess for premalignant or malignant changes, or to rule out other differential diagnoses.
  • System(s) affected: gastrointestinal (GI)

EPIDEMIOLOGY

Most common in individuals who use tobacco (smoking and especially smokeless), heavy alcohol use, and areca nuts (Asian populations).

Incidence

250,000 annual cases worldwide

Prevalence

  • Age of onset is >40 years old with peak in the 60s.
  • Males are 3 times more likely to be affected than females.
  • Smokers are 6 times more likely to be affected than nonsmokers.
  • Higher prevalence in Asian and Oceanic populations.

Geriatric Considerations
Malignant transformation to carcinoma is more common in older patients.

ETIOLOGY AND PATHOPHYSIOLOGY

Hyperkeratosis or dyskeratosis of the oral squamous epithelium; tissue cell exposure to carcinogens spurs adaptive changes including hyperplasia. Continued irritant exposure can lead to cellular degeneration of the epithelium and eventually apoptosis or malignant transformation.

  • Tobacco use in any form
  • Alcohol consumption
  • Dental restorations/prosthetic appliances/periodontitis
  • Candida albicans infection
  • Human papillomavirus, types 16 and 18
  • Vitamin and combined micronutrient deficiencies
  • Syphilis
  • Chronic trauma or irritation
  • Epstein-Barr virus (oral hairy leukoplakia)
  • Areca/betel nut (Asian populations)
  • Mouthwash/toothpaste containing the herbal root extract sanguinaria
  • Hormonal disturbances/estrogen therapy
  • Ultraviolet exposure

Genetics

  • Dyskeratosis congenital and epidermolysis bullosa increase the likelihood of oral malignancy.
  • p53 overexpression; PTEN allelic loss correlates with leukoplakia and particularly squamous cell carcinoma.
  • Changes in expression of p53, FGFR1, p16INK4a, and 3p, 9p, and 17 (especially TP53) gene mutations can have greater cancer risk. Decreased expression of E-cadherin, hMLH1, and CD1a.
  • Biomarkers: IL-6, IL-8, and TNF-α have been detected in leukoplakia, and there is new research showing possible use of Hsp27 and PTHRP/PTHLH as biomarkers.

RISK FACTORS

  • 70–90% of oral leukoplakia is related to tobacco, particularly smokeless tobacco or areca/betel nut use.
  • Alcohol increases risk 1.5-fold.
  • Repeated or chronic mechanical trauma from dental appliances or cheek biting
  • Chemical irritation to oral regions
  • Diabetes
  • Risk factors for malignant transformation of leukoplakia:
    • Female
    • Long duration of leukoplakia
    • Nonsmoker (idiopathic leukoplakia)
    • Located on tongue or floor of mouth
    • Size >200 mm2
    • Nonhomogenous type
    • Presence of epithelial dysplasia
    • Presence of C. albicans
    • Possible shift of oral microbiome in those with malignant transformation.

GENERAL PREVENTION

  • Avoid tobacco of any kind, alcohol, habitual cheek biting, tongue chewing, areca/betel nut chewing/ingestion.
  • Use well-fitting dental equipment.
  • Regular dental check-ups to avoid bad restorations
  • Diet rich in fresh fruits and vegetables may help to prevent cancer.
  • HPV vaccination may be preventive.

COMMONLY ASSOCIATED CONDITIONS

  • Oral hairy leukoplakia; Epstein-Barr virus-induced lesion that occurs primarily in HIV patients
  • Erythroplakia in association with leukoplakia, “speckled leukoplakia,” or erythroleukoplakia is a marker for underlying dysplasia.

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