Elsevier

Oral Oncology

Volume 42, Issue 5, May 2006, Pages 461-474
Oral Oncology

Long-term treatment outcome of oral premalignant lesions

https://doi.org/10.1016/j.oraloncology.2005.08.011Get rights and content

Summary

The purpose of the present retrospective study was to learn the long-term outcome of oral premalignant lesions, leukoplakia and erythroplakia, with or without surgical intervention and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery. A total of 269 lesions in 236 patients were included. Ninety-four lesions were surgically removed, 39 lesions (41%) being homogenous and 46 (49%) non-homogenous leukoplakias whereas nine (5%) were erythroplakias. Seventy-three percent of the lesions were associated with tobacco habits. The mean size of the lesions was 486 mm2, and 71% of the lesions showed a degree of epithelial dysplasia. After excision the defects were closed primarily by transposition of mucosal flaps or they were covered by free mucosal or skin grafts. A few defects were left for secondary healing. After surgical treatment the patients were followed (mean 6.8 yrs, range 1.5–18.6 yrs), and new biopsies taken in case of recurrences. One hundred and seventy five lesions had no surgical intervention, 149 lesions (85%) being homogenous and 20 (11%) non-homogenous leukoplakias, and 6 (3%) erythroplakias. Eighty-one percent of the lesions were associated with smoking. The mean size of the lesions was 503 mm2 and 21 of the lesions (12%) exhibited epithelial dysplasia. Sixty-five lesions were not biopsied. These patients were also followed (mean 5.5 yrs, range 1.1–20.2 yrs), and biopsies taken in case of changes indicative of malignant development. All patients were encouraged to quit smoking and candidal infections were treated. The possible role of different variables for malignant development was estimated by means of logistic regression analysis. Following surgical treatment 11 lesions (12%) developed carcinoma after a mean follow-up period of 7.5 yrs. Non-homogenous leukoplakia accounted for the highest frequency of malignant development, i.e. 20%, whereas 3% of the homogenous leukoplakias developed carcinomas. Surgically treated lesions with slight, moderate, severe and no epithelial dysplasia developed carcinoma with similar frequencies, i.e. 9–11%. Without surgical intervention 16% of the 175 lesions disappeared whereas seven lesions (4%) developed carcinoma after a mean observation period of 6.6 yrs. The highest frequency of malignant development (15%) was seen for non-homogenous leukoplakias, this figure being 3% for homogenous leukoplakias. Fourteen percent of lesions with slight epithelial dysplasia developed malignancy and 2% of lesions with no dysplasia showed malignant transformation. Logistic regression analysis showed a seven times increased risk (OR = 7.0) of non-homogenous leukoplakia for malignant development as compared with homogenous leukoplakia and a 5.4 times increased risk for malignant development for lesions with a size exceeding 200 mm2. No other examined variables including presence of any degree of epithelial dysplasia, site, demarcation, smoking and surgical intervention were statistically significant factors for malignant development.

Introduction

The main purpose of identifying oral premalignant lesions is to prevent malignant transformation by initiating adequate intervention. It is widely approved that the oral premalignant lesions, leukoplakia and erythroplakia, show a significant tendency to malignant transformation. For the most common lesion, leukoplakia, the malignant transformation rate has been reported from 0.13% to 17.5%.1 Various treatment modalities for oral leukoplakia have been reported, but there is currently no consensus on the most appropriate treatment.2, 3

The treatment modalities include change of lifestyle factors such as tobacco and alcohol intake,4, 5 medication with retinoids or antimycotics,6, 7, 8 surgical excision,9, 10, 11, 12 cryosurgery,12, 13, 14, 15, 16 laser evaporation17, 18, 19 or laser excision.18, 20, 21, 22 The outcome of these interventions appears to vary, and long-term follow-up studies are few. After surgical intervention, recurrencies and cancer development in areas of excised lesions have been reported in as much as 10–20% and 3–9%, respectively,10, 23, 24 but no randomized clinical trials have been reported so far.25

Moreover, a number of paradigms about premalignant lesions, including factors significant for malignant development, have not been convincingly approved. These factors include clinical type,4, 26, 27, 28, 29, 30, 31, 32 demarcation, size,33, 34 site,27, 35, 36 presence and grade of epithelial dysplasia,4, 11, 27, 37, 38, 39, 40 and smoking.41 Some of the factors have even been questioned in the past. This applies to site, 31 smoking,4, 31, 42, 43 and epithelial dysplasia. 4, 30, 31, 38, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50, 51

To challenge the above paradigms the hypothesis behind the present study was that the outcome after follow-up of oral premalignant lesions is independent of clinical type, demarcation, size, site, histopathology, smoking and surgery.

Therefore, the aim of the present study was to learn the long-term outcome of oral premalignant lesions, including leukoplakia and erythroplakia, after surgical intervention and after follow-up without surgery and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery.

Section snippets

Lesions

In this retrospective study, a total of 269 lesions comprising 188 (70%) homogenous, 66 (25%) non-homogenous leukoplakias, and 15 (6%) erythroplakias in a total of 236 patients (132 women and 104 men; mean age: 60.8 yrs, range 23–92 yrs), referred between 1977 and 1997, were included. The clinical diagnosis of the lesions was based on the criteria provided by Axéll et al.,52 adjusted to the most recent definition,53 adopted by WHO,54 and histopathological diagnosis of epithelial dysplasia was

Lesions with surgical intervention

The outcome of surgical treatment of the various types of lesions is presented in Figures 5A–C, 6A and B, 7A and 8A. Out of the 94 surgically treated lesions approximately two thirds had a successful treatment outcome characterized by normal mucosa or skin graft (Fig. 8A). The successful outcome was equally distributed among homogenous and non-homogenous leukoplakias, with erythroplakia showing slightly less.

Recurrences occurred in 12 cases (13%) (eight non-homogenous and two homogenous

Discussion

The present study includes two groups of patients with premalignant lesions. One group had surgical intervention whereas the other group had no surgical treatment. The study is not a randomized clinical trial and the two groups under investigation are not directly comparable, because the composition of lesions in the groups is different. Surgically treated lesions comprised 49% non-homogenous leukoplakias in contrast to 12% non-homogenous leukoplakias in the group of non-surgically treated

Acknowledgements

We are most grateful for the contribution of the late Professor J.J. Pindborg and to associate Professor F. Praetorius by making the histopathologic diagnosis of several of the biopsies included in the present study.

References (59)

  • P.J. Gooris et al.

    Carbon dioxide laser evaporation of leukoplakia of the lower lip: a retrospective evaluation

    Oral Oncol

    (1999)
  • J.W. Frame

    Removal of oral soft tissue pathology with the CO2 laser

    J Oral Maxillofac Surg

    (1985)
  • H.H. Horch et al.

    CO2 laser surgery of oral premalignant lesions

    Int J Oral Maxillofac Surg

    (1986)
  • P.J. Thomson et al.

    Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management

    Int J Oral Maxillofac Surg

    (2002)
  • F. Chiesa et al.

    Risk of preneoplastic and neoplastic events in operated oral leukoplakias

    Eur J Cancer B Oral Oncol

    (1993)
  • J.J. Pindborg et al.

    Studies in oral leukoplakia: a preliminary report on the period pervalence of malignant transformation in leukoplakia based on a follow-up study of 248 patients

    J Am Dent Assoc

    (1968)
  • J. Banoczy

    Follow-up studies in oral leukoplakia

    J Maxillofac Surg

    (1977)
  • K.P. Schepman et al.

    Malignant transformation of oral leukoplakia: a follow-up study of a hospital-based population of 166 patients with oral leukoplakia from The Netherlands

    Oral Oncol

    (1998)
  • I. van der Waal et al.

    Oral leukoplakia: a proposal for uniform reporting

    Oral Oncol

    (2002)
  • J.J. Pindborg et al.

    A follow-up study of sixty-one oral dysplastic precancerous lesions in Indian villagers

    Oral Surg Oral Med Oral Pathol

    (1977)
  • J. Sudbo et al.

    Abnormal DNA content predicts the occurrence of carcinomas in non-dysplastic oral white patches

    Oral Oncol

    (2001)
  • D.G. Macdonald et al.

    Oral epithelial atypia in denture induced hyperplasia, lichen planus and squamous cell papilloma

    Int J Oral Surg

    (1975)
  • H.H. Mincer et al.

    Observations on the clinical characteristics of oral lesions showing histologic epithelial dysplasia

    Oral Surg Oral Med Oral Pathol

    (1972)
  • L.M. Abbey et al.

    Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (1995)
  • G.L. Hays et al.

    Co-carcinogenesis and field cancerization: oral lesions offer first signs

    J Am Dent Assoc

    (1995)
  • J. Reibel

    Prognosis of oral pre-malignant lesions: significance of clinical, histopathological, and molecular biological characteristics

    Crit Rev Oral Biol Med

    (2003)
  • S. Silverman et al.

    Oral leukoplakia and malignant transformation. A follow-up study of 257 patients

    Cancer

    (1984)
  • P.C. Gupta et al.

    Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10-yr follow-up study of 12,212 users

    Oral Dis

    (1995)
  • S. Boisnic et al.

    Topical tretinoin in the treatment of lichen planus and leukoplakia of the mouth mucosa. A clinical evaluation

    Ann Dermatol Venereol

    (1994)
  • Cited by (0)

    View full text