Classification schemes for lesions of the oral cavity typically have used the clinical appearance of lesions to determine which are premalignant. (1) Leukoplakia and erythroplakia are two clinical lesions widely considered to be premalignant. However, using clinical features to classify lesions is difficult because they vary in appearance and are likely to be interpreted subjectively by the clinician. A histopathologic diagnosis is generally more indicative of premalignant change than clinically apparent alterations.

A State of the Science

Clinical Lesions Associated with Premalignancy


The term leukoplakia is sometimes used inappropriately to indicate a premalignant condition. In fact, the term describes a white plaque that does not rub off and cannot be clinically identified as another entity. Most cases of leukoplakia are a hyperkeratotic response to an irritant and are asymptomatic,
but about 20% of leukoplakic lesions show evidence of dysplasia or carcinoma at first clinical recognition.(1) However, some anatomic sites (floor of mouth and ventral tongue) have rates of dysplasia or carcinoma as high as 45%. There is no reliable correlation between clinical appearance and the histopathologic presence of dysplastic changes except that the possibility of epithelial
dysplasia increases in leukoplakic lesions with interspersed red areas. In one large study, (2) lesions with an erythroplakic component had a 23.4% malignant transformation rate, compared with a 6.5% rate for lesions that were homogeneous. The term erythroleukoplakia has been used to describe
leukoplakias with a red component.


An erythroplakia is a red lesion that cannot be classified as another entity. Far less common than leukoplakia, erythroplakia has a much greater probability (91%) of showing signs of dysplasia or malignancy at the time of diagnosis.(3) Such lesions have a flat, macular, velvety appearance and may be speckled with white spots representing foci of keratosis.

Lichen planus

The premalignant or malignant potential of lichen planus is in dispute. Some believe that the occasional epithelial dysplasia or carcinoma found in patients with this relatively common lesion may be either coincidental or evidence that the initial diagnosis of lichen planus was erroneous.(4) It is frequently difficult to differentiate lichen planus from epithelial dysplasia; one study found that 24% of oral lichen planus cases had 5 of the 12 World Health Organization (WHO) diagnostic criteria for epithelial dysplasia, and only 6% had no histologic features suggestive of that disorder. (5) However, Oral Cancer Background Papers as many reports on lichen planus patients followed over time indicate a higher than expected rate of malignant transformation,(6) it is prudent practice to biopsy the lesion at the initial visit to confirm the diagnosis and to monitor it thereafter for clinical changes suggesting a premalignant or malignant change.

Other Lesions

Premalignant changes arising in other oral lesions are uncommon. White lesions such as linea alba, leukoedema, and frictional keratosis are common in the oral cavity but have no propensity for malignant transformation. The health professional can usually identify them by patient history and clinical xamination.

Clinical Features of Oral Premalignancy

A diagnostic biopsy should be considered for any mucosal lesion that persists for more than 14 days after obvious irritants are removed; simply noting the clinical appearance or presentation of a lesion is not enough to determine premalignant changes. The following overview describes clinical features generally but is insufficient to identify premalignancy in a specific patient.

Anatomic Location

Studies relating premalignant tissue changes to anatomic sites have produced varying results. One study found that 21.8% of oral epithelial dysplasias occurred on the buccal mucosa, 13.7% on the palate, and 12.3% on the floor of the mouth. (7) A study of leukoplakia by Shafer and Waldron8 found that the mandibular mucosa and sulcus were involved in 25.2% of their cases and on the buccal mucosa in 21.9%. Because many oral premalignancies present as leukoplakias, the similar findings are not unexpected. Interestingly, the distribution of locations is much different from that of squamous cell carcinomas of the oral cavity, for which the tongue, oropharynx, lip, and floor of mouth are the most common sites.(9) Perhaps there is a subset of epithelial dysplasias, such as those that occur on the buccal mucosa, that have a lower rate of malignant transformation than those found at other sites.


The mean age at diagnosis of oral premalignancy is 50-69; less than 5% of diagnoses are in patients under 30 years of age.7,10,11 Thus, the aging process itself is the greatest risk factor for premalignant and malignant changes.


Studies have shown that epithelial dysplasia has a predilection for males, but the decrease in the (7,10,11) male:female ratio for oral squamous cell carcinoma suggests the picture may be changing. This may be due to increased use of tobacco and alcohol among women (Chapter 1” target=”_self”>see Chapter I).

Clinical Appearance

Although most premalignant lesions are white (leukoplakia), they vary considerably in their initial presentation. These lesions are usually asymptomatic; the development of pain or soreness may be
associated with a malignant change.

Probability of Malignant Change

About 5-18% of epithelial dysplasias become malignant. (7,11,1, 2) Although expecting a greater probability of malignant change for dysplasias with a greater histologic degree of epithelial dysplasia seems intuitive, that relationship is hard to prove because only a few cases of epithelial dysplasia have
been diagnosed but not excised, then monitored to see whether malignant change occurred. A greater risk of malignant change in an epithelial dysplasia has been associated with the following factors: (1) erythroplakia within a leukoplakia, (2) a proliferative verrucous appearance, (3) location at a high-risk
anatomic site such as the tongue or floor of mouth, (4) the presence of multiple lesions, and, paradoxically, (5) a history of not smoking cigarettes. (2)

Transition Time from Epithelial Dysplasia to Malignancy

Although most oral carcinomas have adjacent areas of epithelial dysplasia, some carcinomas may not evolve from epithelium with top-to-bottom dysplastic changes but rather arise from basilar keratinocytes. Silverman and colleagues2 monitored 257 patients with oral leukoplakia; (22) had a diagnosis of epithelial dysplasia, the remaining 235, hyperkeratosis. Eight of the 22 (36.4%) with
epithelial dysplasia developed carcinoma. Of the 107 patients with a homogeneous leukoplakic lesion and a diagnosis of hyperkeratosis, (7) (6.5%) developed carcinoma. However, (30) (23.4%) of the 128 patients with erythroplakic lesions and a diagnosis of hyperkeratosis were eventually diagnosed with carcinoma. The time from initial diagnosis of either epithelial dysplasia or hyperkeratosis to carcinoma ranged from 6 months to 39 years. In another study, reported by Lumerman and colleagues,(11, 7) (15.9%) of 44 patients with oral epithelial dysplasia identified in a biopsy service
developed carcinoma; mean time from biopsy to cancer diagnosis was 33.6 months. Epithelial dysplasia has been more extensively studied in association with the uterine cervix than with the oral cavity. Based on clinical reviews, approximately 12% of cervical epithelial dysplasias progress to carcinoma in