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Oral Premalignancy

Premalignant lesions and conditions

Premalignant condition: a systemic condition that increases the changes of malignant change.

Premalignant lesion: localised areas more likely to undergo malignant change

Premalignant lesion

  • Leukoplakia
  • Erythroplakia
  • Sublingual keratosis
  • Chronic hyperplastic candidal leukoplakia
  • Actinic chelitis

Premalignant conditions

  • Pipe smokers' keratosis
  • Oral submucosa fibrosis
  • Lupus erythematous
  • Lichen planus
  • Dyskeratosis congenital
  • Tylosis
  • Sideropenic dysphagia

It is beyond the scope of this article to describe in detail all premalignant oral lesions and conditions. Therefore only leukoplakia has been considered in detail. 


Definition: a predominantly white lesion of the oral mucosa that can not be classified as any other lesion; associated with no other cause than tobacco.

Diagnosis: Leukoplakia is a clinical diagnosisand has no histological connotations. Clinical diagnosis is made by exclusion of all other causes.


White lesions such as leukoplakia appear white due to heaping of keratin that appears white when wet. Changes with the potential for malignancy occur in leukoplakia. Certain changes are indicators of an increased risk of malignancy.

  • Abnormal keratosis: Orthokeratosis or parakeratosis
  • Alteration in epithelial thickness: hyperplastic or atrophic
  • Epithelial dysplasia
  • Chronic inflammatory cell infiltration in the lamina propria
  • Melanin pigment accounts for the grey colouration of some leukoplakias
  • Cellular atypia


Incidence: 1-10% depending on the part of the world and cultural smoking habits.  Men and women are equally affected. Increasingly, younger people are being affected.

Presentation: the floor of the mouth and the buccal mucosa are the most common sites. Lesions affecting the floor of the mouth or the ventral of the tongue have an increased risk of malignant change.

Clinical features:

  • Size varies
  • Homogenous white plaque-like lesions or non-homogenous white and red lesion. Non-homogenous lesions may be speckled, ulcerated or have a heaped surface.
  • Smooth or wrinkled surface: Verrucous leukoplakia  has a warty appearance.
Leukoplakia on the buccal mucosa Erythroplakia: early carcinoma


Definition: red, velvety plaques that cannot be clinically or pathologically classified as any other condition. 

Presentation:  plaques can be homogenous or associated with white areas of leukoplakia (erythroplakia/speckled leukoplakia). Transformation from leukoplakia to erythroplakia is a sinister sign.

Histologically: carcinoma in situ or invasive carcinoma

Aetiology of Leukoplakia/erythroplakia

The exact aetiologyis unknown. However, several predisposing factors have been identified.

Tobacco: prevalence increases with the amount of tobacco use.  In cigarette smokers, diffuse lesions occur on the cheeks, lips and tongue.

Smokeless tobacco and snuff dipping are associated with oral keratosis. Smokeless tobacco is banned in the UK.

The use of paan containing Areca nut is associated with lesions on the buccal sulcus in Asia. 

Tobacco-associated keratosis can regress on cessation of the habit.

 Alcohol: synergistic effects of alcohol and tobacco increase the risk of malignancy

Viruses:  Human papilloma virus types 6, 16 and 18.

Epithelial atrophy:  conditions that predispose to atrophy may increase the risk of leukoplakia e.g.

  • Iron deficiency: Patterson Kelly/ Plummer-Vinson syndrome
  • Submucosa fibrosis
  • Tertiary syphilis

Tumour suppressor genes: TSG regulate cell proliferation.  Mutation of gene P53 results in inactivation of the suppressor activity and uncontrolled cell proliferation resulting in dysplasia and leukoplakia.

Candidal leukoplakia

Candida: the cause or effect role of candida is unclear. Candida has been identified in the premalignant lesion chronic hyperplastic candidosis and has been shown to thrive in tissues of altered morphology. Candida albicans can induce epithelial proliferation and can produce nitrosamines which might be carcinogenic. The plaques cannot be wiped off but may be removed by firm scraping. It is distinguishable from other leukoplakias only by biopsy.

Candidal leukoplakia


The rate of malignant transformation is highly variable. The floor of the mouth, ventral of the tongue and the lingual aspect of the lower alveolar mucosa are most likely to undergo malignant transformation. Lesions showing dysplasia are high risk for malignant transformation. Non-homogeneous, erythroplakia and candidal-associated leukoplakia are the highest risk. However, even dysplastic lesions can regress reflecting the unpredictability of leukoplakia.  

Histological indications of dysplasia:

Speckled leukoplakia and erythroplakia are the most likely to show dysplasia.

  • Increased and abnormal mitosis
  • Basal cell hyperplasia
  • Drop-shaped rete pegs
  • Loss of basal cell orientation
  • Increase in the nuclear to cytoplasm ratio
  • Nuclear hyperchromatism
  • Prominent and enlarged nuclei
  • Irregular epithelium stratification and disturbed maturation
  • Nuclear and cellular pleomorphism
  • Abnormal keratosis
  • Loss of intercellular adhesion

If a lesion is clinically unchanged following 3 months, the patient should be kept under 6 month review then a re-biopsy should be carried out after 3 years.  

 Clinical features indicating malignant transformation of leukoplakia or erythroplakia:

  • Fixation
  • Induration
  • Ulceration
  • Lymphadenopathy
  • Bone destruction

Size is irrelevant to the risk of malignant change. Non-smokers have the highest risk of malignant transformation.

Management of leukoplakia

  • Stop smoking habit
  • Reduction of alcohol
  • Treat any underlying haematinic deficiency
  • Re-biopsy after 3 months
  • Topical bleomycin is an anti-cancer drug that can be applied topically but is restricted to specialist use
  • Retinoids


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  • Lamey PJ & Lewis MAO.1997. A clinical guide to oral medicine. 2nd Ed. London; British Dental association
  • Scully C & Porter S. 1999: Orofacial Disease Update for the dental clinical team: 3. White lesions. Dental Update
  • Warnakulasuriya S. 2009. Causes of oral cancer an appraisal of controversies. British Dental Journal.207:471-475

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