What is oral leukoplakia?
Oral leukoplakia is the most common premalignant or potentially malignant disorder of the oral mucosa.
It is defined as a white patch or plaque of the oral mucosa that cannot be characterised clinically or pathologically as any other disease.
Oral leukoplakia is a clinical diagnosis of exclusion. Diseases to be excluded include nicotine stomatitis, candidiasis, lichen planus, frictional keratoses, habitual cheek or lip biting, lupus erythematosus, etc.
Who does it affect?
Oral leukoplakia may affect about 0.5% of the world population, although it is likely to vary with gender, geography and ethnicity.
There is a strong association with tobacco smoking (six times more common in smokers than non-smokers) and alcohol intake (independent of drinking pattern or beverage type). It is also associated with betel quid chewing and oral submucous fibrosis.
It usually appears in adult life with prevalence increasing with increasing age:
- found in less than 1% of men under 30 years of age
- 8% of men over 70 years of age
- 2% of women over 70 years of age
- rare before age 30, peaks after 50 years
- mainly affects middle aged to elderly men
- non-smokers are likely to present at an older age.
Clinical features of oral leukoplakia
An early lesion is a slightly elevated grey-white plaque either well defined or which blends in gradually with surrounding mucosa. It can be a localised solitary lesion or multifocal and diffuse.
Two clinical forms are recognised.
1. Homogeneous – refers to homogeneous uniform colour AND texture
- uniform white colour
- uniform flat, thin appearance
The surface may become leathery – smooth, wrinkled, corrugated or with shallow cracks. This form is usually asymptomatic.
2. Non-homogeneous – refers to irregularity of either the colour OR the texture
- predominantly white or white-red (erythroleukoplakia)
- irregular texture which can be flat, nodular, exophytic, warty
Variants of the non-homogeneous form have been described including nodular, verrucous (including proliferative verrucous) and speckled. This form may be associated with mild discomfort or localized pain.
The most common site affected is the inside cheeks (buccal mucosa) and then in decreasing order of frequency:
- gums (alveolar mucosa)
- lower lip
- floor of mouth (under tongue)
- sides or undersurface of tongue (lateral or ventral tongue)
- soft palate
Association with squamous cell carcinoma (SCC)
A large proportion of oral cancers are associated with preceding longstanding oral leukoplakia and possibly 1% of oral leukoplakias overall become cancer. This figure is higher for the non-homogeneous form, especially the proliferative verrucous variant, which nearly always becomes cancerous.
There may be no change in appearance or symptoms in the early stages of cancer development. Classic changes of cancer are ulceration, induration/hardness, bleeding and tumour outgrowth.
Factors reported as associated with increased risk of SCC development:
- Dysplasia (atypical changes) on histology is regarded as the most important factor. However it is important to note that dysplastic lesions can resolve spontaneously and nondysplastic lesions may develop into cancer.
- Site – floor of mouth under the tongue and the sides/undersurface of tongue
- Clinical type – speckled non-homogeneous, especially proliferative verrucous leukoplakia
- Female sex
- If the leukoplakia is NOT associated with tobacco use.
- Long duration of disorder
- Large lesion size
- Presence of Candida albicans – but this is most commonly found in lesions at the angles of the mouth or top surface of tongue, which are rare sites for cancer development.
No molecular tumour markers have yet been found that can be used to predict cancer development in an individual or lesion. The role of human papillomaviruses (wart virus) has not yet been determined.
How is the diagnosis made?
- Biopsy of clinically suspected oral leukoplakia is mandatory to: exclude recognised diseases, and to assess for the absence or presence and grade of dysplasia.
- It is appropriate to wait 2 weeks after first presentation to assess clinical response to initial treatment, e.g. for candida, change in tooth brushing habit, cessation of smoking, etc
- The biopsy may be incisional or excisional, single or multiple and may be done under local or general anaesthetic depending on site, number of biopsies required and type of biopsy.
- Biopsies should be taken from either a symptomatic area, or if asymptomatic then from red or indurated areas.
- The presence of dysplasia, carcinoma-in-situ and invasive carcinoma cannot always be predicted clinically.
The histopathology of oral leukoplakia is not diagnostic. Epithelial changes range from atrophy (thinned) to hyperplasia (thickened) and it may show hyperkeratosis. Dysplasia (atypical changes) may be mild, moderate, severe, carcinoma in situ or invasive carcinoma. The pathology report must comment on the absence or presence of dysplasia, and the severity.
Treatment of oral leukoplakia
It is not known if early active treatment prevents the possible development of squamous cell carcinoma and there is a high recurrence rate after treatment.
- Avoid aggravating habits eg quit smoking, and
- Surgical excision, or
- CO2 laser – excision or vaporisation.
- Possible other options – retinoids (acitretin or isotretinoin), photodynamic therapy.
Lifelong follow-up is recommended whether or not the disorder has been treated:
- 3-12 monthly clinical checks
- Biopsy of suspicious changes
Oral mucosal examination must include the floor of mouth and sides of tongue using gauze to hold tip of the tongue and pull upwards and side to side. Most oral SCC develop in the sides & undersurface of the tongue, floor of mouth and back to the soft palate and tonsillar area.
- Dermatology. Ed. Bolognia, J et al. 2nd edition 2007. Mosby.
- van der Waal, Isaäc . Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classiﬁcation and present concepts of management. Oral Oncology 45 (2009) 317–323. Medline.
On DermNet NZ:
- Leukoplakia, Oral – Medscape Reference
- Patient information: Leukoplakia (The Basics) – UpToDate (for subscribers)
Books about skin diseases:
See the DermNet NZ bookstore