Leukoplakia is a general term that describes the abnormal thickening of membranes and the formation of painless white or gray patches on the mucous membranes in the mouth (such as the tongue, checks and gums). These patches are often benign, but leukoplakia can also be present as a precursor to more serious conditions, such as oral cancer. Although leukoplakia is often a benign condition, it should still be medically evaluated, as it can become malignant in a small number of cases.   

Leukoplakia refers to thick, white plaques or patches in the mouth that can’t be scraped off and do not match the description of any known disease. It typically results from chronic irritation of the oral tissues. Leukoplakia is referred to as a precancerous lesion, meaning it carries some risk of developing into oral cancer over time—especially when the underlying cause is unknown or untreated. Oral cancers may also develop near leukoplakia patches. Patches with both white and red areas, called speckled leukoplakia, are at an increased risk of becoming cancerous. 

You should see your dentist or doctor for any change in your mouth that does not resolve in a reasonable time—more so if there is a white or red patch that is persistently there.

Leukoplakia affects people mostly after the mid-adult years and is more common in men than women. Regular dental check-ups and good oral hygiene can aid in the early detection of leukoplakia and ultimately lower the risk of recurrence and/or complications.

While it is not always possible to determine the exact cause of leukoplakia, there are multiple well-established contributing risk factors. Most of these causative factors have to do with chronic irritation or repeated trauma to the mucous membranes of the mouth.

1. Tobacco (Smoker’s Keratosis): Tobacco use, whether through smoking cigarettes or cigars, or by using smokeless tobacco (chew or snuff), is the most common risk factor for leukoplakia. Chronic exposure to tobacco irritants will thicken the oral mucosa, eventually causing the epithelium to aberrantly keratinize and develop white patches. Smokers have an estimated six times greater likelihood of developing leukoplakia compared to non-smokers.
2. Alcohol: Heavy drinking, especially when combined with tobacco use, will also increase the risk of leukoplakia. Alcohol acts as a chemical irritant, and also increases the mucosal absorption of carcinogenic agents found in tobacco, creating a compounded risk.
3. Chronic Mechanical Irritation: Continual irritation may overwhelm the normal reparative mechanisms of the oral cavity and cause aberrant cell change or leukoplakia. Some common associated agents are:
   • Rough edges of broken or decaying teeth
   • Ill-fitting dentures/ dental appliances
   • Sharp crowns/ restorations
   • Chronic habitual biting of the cheek or tongue

     These factors repeatedly traumatize the mucous membranes, triggering abnormal thickening as a defense mechanism.

4. Human Papillomavirus (HPV): Some specific strains of human papillomavirus have been recognized as a risk factor for leukoplakia and oral cancers such as HPV-16. HPV-related leukoplakia is very concerning due to the chance for malignant change.
5. Poor Oral Hygiene: Failure to maintain oral hygiene or adequate dental hygiene including chronic poor oral hygiene may lead to chronic inflammation/infection in the mouth and could contribute to the production of leukoplakia. Bacterial plaque and calculus provide a chronic irritant.
6. Nutritional Deficiencies: Deficiency of vitamins and nutrients necessary for maintaining health, primarily:
   • Vitamin A (important for epithelial health)
   • B-complex vitamins (specifically B12 and folate)
   • Iron (important for understanding the mucosal healing process)
   • May impair the renewal of oral tissues thereby lending to increase the chance of leukoplakia.
7. Genetic Mutations: Genetic mutations can contribute to leukoplakia and allow cells of the mucous membranes to be hyperproliferative resulting in thin, whitish patches. These mutations occur spontaneously but can also arise from long-standing exposures to the environment (tobacco).
8. Compromised Immune System: Patients with immunosuppression are at greater risk of developing leukoplakia. This would include persons living with HIV/AIDS or patients who have undergone bone marrow transplants or organ transplants and require immunosuppressive therapy. A compromised immune system permits opportunistic infections and viral triggers to persist and damage oral tissues.

Leukoplakia will often develop quietly, with no pain or discomfort, and the symptoms don’t always scream “leukoplakia.” When it comes to oral lesions like leukoplakia, you may see one or more of the following presenting symptoms: 

• White or Gray Patches: The most notable sign of leukoplakia is a flat or slightly elevated white or gray patch in the mouth. The patches may occur on the: 
  • Inner cheeks (buccal mucosa) 
  • Gums 
  • Floor of mouth 
  • Under or top of tongue 

• Thickened or Hard Place: The patches will often feel hardened or rough to touch. Depending on how they develop, the surface may be smooth, or it may be wrinkled, or a combination. The surface of the location can change slowly over a matter of weeks to months. 
• Cannot Be Removed: The most significant diagnostic hallmark is that these patches cannot be wiped or scraped off like oral thrush (a fungal infection). 
• Occasional Sensitivity or Pain: While many individuals with leukoplakia don’t have any pain and/or simply ignore the overgrowth, some people report sensitivity or mild pain when they eat spicy or acidic foods, or they felt pain caused by touch, heat, and/or other irritation.
• Red Areas (Erythroplakia): Occasionally, the leukoplakia patches are accompanied by red areas—called erythroleukoplakia. The erythroplakia areas are more likely to contain dysplastic or malignant cells.
• Leukoplakia at Non-Oral Sites: Leukoplakia can also appear at sites outside the oral cavity—most commonly, the genitalia. In menopausal women, some women may experience leukoplakia in the vulvar area or, sometimes, intermediate to the vagina.

Leukoplakia can appear in different forms:

1. Homogenous: Flat, white, and uniformly discolored patches; low to no surface risk of cancer.
2. Non-homogenous: Mixed white with red, cobbled or thickened patches; high risk of cancer.
3. Hairy Leukoplakia: Fuzzy white patches on the sides of the tongue commonly seen in the HIV/AIDS population.
4. Proliferative Verrucous Leukoplakia (PVL): Rare, but slow spreading that often recurs and will likely become cancerous.

If you or your dentist observe suspicious white patches in your mouth that do not heal within a 2-week timeframe, you should have them examined by a healthcare provider. Diagnosing leukoplakia typically consists of a few steps: 

1. Clinical Exam: A thorough examination of the intraoral cavity is done to assist in the assessment of the size, shape, texture, and location of the lesion. Furthermore, the clinician may inquire about tobacco/alcohol use, oral hygiene practices, and a history of chronic irritation. 

2. Rule Out Other Conditions: There are a wide variety of conditions that look similar to leukoplakia, such as oral candidiasis (thrush), lichen planus, lupus, and frictional keratosis. These need to be ruled out before a definitive diagnosis can be made. 

3. Tissue Biopsy: Biopsy is still the most reliable way to diagnose leukoplakia. A small piece of tissue from the lesion is taken and analyzed under a microscope. There are two common types: 

• Oral Brush Biopsy: In this test, cells are scraped from the surface of the patch using a small, spinning brush. However, this method does not guarantee a definitive diagnosis every time. 
• Excisional Biopsy: In this case, a small piece of the patch (or sometimes the whole thing) is surgically removed for examination. An excisional biopsy usually provides a definitive diagnosis.

4. Adjuvant Tests: In some circumstances, there are additional modalities that can be utilized to evaluate or monitor suspicious lesions. These include toluidine blue stain, fluorescence imaging, and brushing advanced biopsy techniques as needed, particularly when assessing potentially malignant sites.

The primary aim of treatment is to remove the source of irritation, if indicated debride patchy lesions, and monitor the potential for malignant transformation. Treatment options will vary depending on the severity and type of the lesion.

1. Lifestyle Changes: In many patients, removal of the underlying cause can effect resolution:  
   • Stop smoking and tobacco use: This is the most critical step.
   • Limit or preferably eliminate alcohol consumption: Important if using large amounts of alcohol.
   • Improve oral hygiene: Brush and floss your teeth regularly and see your dentist for routine cleanings.
   • Correct dental problems: Remove or replace poorly fitting dentures or dental restorations.
2. Watch and Wait: If the lesion is small, non-dysplastic, and asymptomatic, your doctor may recommend monitoring the lesion over time and documenting any changes with regular follow up and clinical photographs.
3. Medical Therapies: There is not a specific medication known to cure leukoplakia but other therapies can help reduce size and/or discomfort associated with lesions:
   • Topical retinoid (vitamin A derivatives)  
   • Topical corticosteroids or antivirals (in the case of oral hairy leukoplakia) 
   • Antioxidant supplements (beta-carotene or vitamin E)    
   • Antifungals if a Candida infection is also diagnosed.
4. Surgical Removal: Surgery may be recommended when:
   • The lesion is dysplastic (a precancerous lesion)
   • The lesion has mixed red and white areas (erythroleukoplakia) surgical procedures include:
     • Excision using a scalpel
     • Laser surgery (CO₂ laser, diode laser)
     • Cryotherapy (freezing the lesion)
5. Photodynamic Therapy: This is utilization of light-activated drugs to destroy abnormal cells, which may be used with high-risk lesions.
6. Electrocauterization: Electrocauterization uses an electrically heated needle or other device to burn and remove the patches.

Follow-Up Care: Long-term follow-up is crucial for all patients and particularly those with dysplastic lesions and all risk factors persisted. In fact, leukoplakia can return if the underlying causes are not managed even if treatment has been completed.

Leukoplakia is more than just a patch or plaque, in white, red, or gray, in the mouth—it can represent a clinical sign of other health issues and may even be a precursor to oral cancer. Even if it looks harmless at first, leukoplakia can develop into malignancy, so early detection and treatment are important.

If you use tobacco or drink alcoholic beverages, you can decrease your risk of leukoplakia by practicing good oral hygiene and by continuing to see your dentist regularly. If you notice any unexplained patches or plaques that are white or grey that last longer than 2 weeks, you should not ignore these lesions. If you ask your healthcare provider to evaluate these lesions quickly you may identify, and treat, early and avoid malignancy.

If you make some lifestyle adjustments, are monitored by a healthcare system, and have good support, the majority of leukoplakia cases can be safely treated and will resolve.

• American Cancer Society. (2022). Leukoplakia
• Mayo Clinic. (2023). Leukoplakia. Mayo Foundation for Medical Education and Research. 
• MedlinePlus. (2022). Leukoplakia. U.S. National Library of Medicine. 
• National Institute of Dental and Craniofacial Research. (n.d.). Oral cancer. National Institutes of Health.