Oral leukoplakia is a common premalignant condition most commonly identified in the smoking patient population. Once oral leukoplakia is diagnosed, the fundamental goal is to minimize progression towards invasive carcinoma through the use of various treatment methods such as traditional scalpel excision, cryotherapy, and carbon dioxide (CO2) laser therapy.

Epidemiology and Pathogenesis of Oral Leukoplakia

Leukoplakia is defined as a white, painless, plaque most commonly occurring on the buccal mucosa, lateral tongue, or floor of the mouth.1 Leukoplakia is considered one of the most common oral potentially malignant disorders (OPMDs) with an estimated worldwide prevalence of 1.5% to 2.6%.1 This premalignant condition, which can lead to oral cancer, particularly squamous cell carcinoma, presents with various transformation rates ranging from 0.1% to 17.5%.2 Due to variability in transformation to malignancy, identification, treatment, and monitoring is imperative.

The etiology of oral leukoplakia is multifactorial and many cases are considered idiopathic; however, several strong risk factors are associated with this condition, the most common being chronic exposure to all forms of tobacco products, which cause mucosal irritation over time.1,2 Prolonged use of tobacco products is attributed to the conversion of normal cells to hyperplasia, dysplasia, and eventually carcinoma in situ or invasive carcinoma. It is reported that leukoplakia is 6 times more common in smokers than nonsmokers.1

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Oral leukoplakia is most commonly seen in men aged 40 years and older, particularly after years of chronic tobacco use.1,2 Other common contributory risk factors include: alcohol use, betel nut use, genetics, poor oral hygiene, human papillomavirus (HPV), Epstein-Barr virus, and chronic candidiasis.1-6

Clinical Presentation

Because oral leukoplakia is a painless and generally asymptomatic condition, it often goes unnoticed unless careful inspection is taken by both patient and primary care provider. Upon inspection of the tongue, buccal mucosa, and floor of the mouth, a white patch will be seen that can vary in appearance. Leukoplakia presents in 3 different forms:

  • Homogenous: typically presents as a white, thin plaque that is even in color and smooth or wrinkled in appearance and consistent throughout; this form has a lower risk for malignancy1,2
  • Nonhomogenous: presents as a white lesion that is typically irregularly shaped with inconsistencies throughout and may show erythema; this form has a higher risk for malignancy1,2
  • Proliferative verrucous: presents as a white, hyperkeratotic, wart-like lesion. This form is aggressive, associated with HPV and EBV, and has a high malignancy rate.6

Diagnosis of Oral Leukoplakia

The differential diagnosis should include oral candidiasis, oral lichen planus, oral erythroplakia, oral hairy leukoplakia, or nicotine stomatitis in smokers.2,6,11 Scraping the lesion is important during the initial workup. In oral leukoplakia, the lesion will remain intact, while in oral candidiasis the plaque will be removed upon scraping and will bleed.2,11 A potassium hydroxide smear should be performed to identify Candida albicans as the causative agent. HIV testing may also be considered if suspicious of hairy leukoplakia or oral candidiasis without any known risk factors such as recent use of antibiotics, inhaled corticosteroids without use of a spacer, or chemotherapy.12 Other tests to consider for the workup of a white oral lesion may include hepatitis C antigen and antibody, which are linked to oral lichen planus and dermal lesions on the body.13 Lastly, because HPV is a risk factor for leukoplakia cases, clinicians should consider HPV testing.

Once other causes of white plaques have been ruled out through noninvasive testing, biopsy can be performed for a definitive diagnosis.2 Biopsy options include incisional and punch biopsy, which are performed to examine for histologic changes to the cells in the lesion. An excisional biopsy, which includes removal of the whole lesion, may be considered as well if the plaque is small in size. For larger lesions, an incisional biopsy is used and includes adjacent healthy tissue. Common histologic changes that are associated with oral leukoplakia seen on biopsy include loss of polarity of basal cells, nuclear hyperchromatism, nuclear pleomorphism, keratinization of cells, loss of intercellular adherence, increased nuclear-cytoplasmic ratio, and irregular epithelial stratification.2,7  A biopsy can also determine if the white lesion is benign, dysplastic, or has transformed to in situ or invasive carcinoma. The histologic results and lesion staging also play a key role in assessing which treatment options are most appropriate for the patient.

Although brush biopsy, in which a brush is swept along the lesion to collect cells, may be performed before surgical biopsy, evidence of the accuracy of this technique is mixed.2,8-10

Treatment Options for Oral Leukoplakia

As a premalignant condition with a high likelihood of progression to squamous cell carcinoma, immediate treatment of oral leukoplakia is encouraged. The main goal of treatment is to prevent further dysplasia and excision of moderate to severe dysplasia or carcinoma. A key aspect of management is removal of the primary source of irritation.2 This most commonly involves tobacco cessation as well as avoiding alcohol to help prevent further dysplastic changes to the tissue.