Treatment options for oral leukoplakia
Näytönastekatsaukset
26.5.2026
Level of evidence: B
Treatment options for oral leukoplakia probably cannot permanently remove leukoplakia or prevent its malignant transformation.
The evidence is obtained from observational and RCT studies on oral leukoplakia patients. Studies have high risk of bias due to methodological concerns (e.g. small studies, no control groups), and results are inconcistent and imprecise. None of the tested interventions (scalpel or laser excision, vitamin C or A, beta carotene, curcumin or topical bleomycin) seem to be effective in preventing long-term recurrence or malignant transformation (MT) of oral leukoplakia (OL).
| Reference | Study type | Population | Exposure | Outcomes | Risk of bias «Additional comments»2 |
|---|---|---|---|---|---|
| «de Pauli Paglioni M, Migliorati CA, Schausltz Pereira Faustino I, ym. Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis.»1 | SR/MA | 36 studies, 5.051 patients with OL, 17 countries | CO2 laser, diode laser, Er:YAG laser, Nd:YAG laser | Rates of recurrence and malignant transformation of OL lesions | Moderate |
| «Li Y, Wang B, Zheng S, ym. Photodynamic therapy in the treatment of oral leukoplakia: A systematic review. Photodiagnosis Photodyn Ther 2019;25():17-22 »2 | SR | 16 articles, 352 patients with OL | PDT with photosensitizer: aminolevulinic acid, Photofrin, methylene blue, and chlorine-e6 and laser wavelength, duration of irradiation, and power density were 420–660 nm, 60–1000 s, and 100–150 mW/cm2, respectively | Management of OL (response to treatment and recurrence) | High |
| «Dong Y, Chen Y, Tao Y, ym. Malignant transformation of oral leukoplakia treated with carbon dioxide laser: a meta-analysis. Lasers Med Sci 2019;34(1):209-221 »3 | MA | 24 articles, 1546 patients with 1864 OL lesions | Carbon dioxide laser | Rate of malignant transformation | High |
| «Lodolo M, Valor J, Villa A. Randomized Controlled Trials for Oral Leukoplakia. Oral Dis 2025;31(11):3034-3038 »4 | SR (All RCTs on OL) | 7 RCT:s / patients with OL Intervention n=443 Control/other intervention n=440 | Topical Moringa oleifera, curcumin, beta-carotene with vitamin C, scalpel excision, carbon dioxide and diode laser ablation, and photodynamic therapy | Lesion size or short-term recurrence, long-term recurrence or malignant transformation | High |
| «Lodi G, Franchini R, Warnakulasuriya S, ym. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database Syst Rev 2016;7(7):CD001829 »5 | SR (Cochrane) | 14 articles/ 909 patients | Surgical or medical (local or systemic) treatment of OL or removal of risk factors | Malignant transformation | Moderate |
OL=oral leukoplakia; PDT=photodynamic therapy; RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis
| Reference | Comments |
|---|---|
| «de Pauli Paglioni M, Migliorati CA, Schausltz Pereira Faustino I, ym. Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis.»1 | Three studies were graded as having a low risk of bias, 25 studies were considered to have a moderate risk, and eight studies were classified having a high risk of bias. Intervention compared to another intervention, no control groups included in the studies. |
| «Li Y, Wang B, Zheng S, ym. Photodynamic therapy in the treatment of oral leukoplakia: A systematic review. Photodiagnosis Photodyn Ther 2019;25():17-22 »2 | In all included studies, parameters of PDT had no unified standard. However, due to low-quality clinic test and potential publication bias, the extant evidence is not enough to make a definite conclusion. No control groups included |
| «Dong Y, Chen Y, Tao Y, ym. Malignant transformation of oral leukoplakia treated with carbon dioxide laser: a meta-analysis. Lasers Med Sci 2019;34(1):209-221 »3 | The included literature had a large heterogeneity owing to the differences among study design, study purpose, study subjects, outcome measures, follow-up time, etc. Therefore, the results of this study should be contemplated with caution. No control groups included. |
| «Lodolo M, Valor J, Villa A. Randomized Controlled Trials for Oral Leukoplakia. Oral Dis 2025;31(11):3034-3038 »4 | Data remain limited, and further rigorously designed, large randomized controlled trials are needed to guide potential new management approaches for oral leukoplakia. Included RCT:s with control/comparison groups. |
| «Lodi G, Franchini R, Warnakulasuriya S, ym. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database Syst Rev 2016;7(7):CD001829 »5 | The selected studies had varying degrees of methodological weaknesses. Included RCT:s which compared any treatment to placebo or no treatment. |
PDT= photodynamic therapy
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Relative effect (95% CI) | |
|---|---|---|---|---|
| Level of evidence: very low The quality of evidence is downgraded due to study limitations and inconsistency. | ||||
| «de Pauli Paglioni M, Migliorati CA, Schausltz Pereira Faustino I, ym. Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis.»1 | 36/5.051 | Recurrence rate (pooled proportion, PP) 16.5% (95% CI 11.2-22.5%) of lesions treated with laser. | ||
| «Li Y, Wang B, Zheng S, ym. Photodynamic therapy in the treatment of oral leukoplakia: A systematic review. Photodiagnosis Photodyn Ther 2019;25():17-22 »2 | 16/352 | 1-119 mo | The rate of complete response 32.9%. Partial response 43.2%. The sum was 76.1 %. The recurrence rate of OL was 0–60%. | |
| «Lodolo M, Valor J, Villa A. Randomized Controlled Trials for Oral Leukoplakia. Oral Dis 2025;31(11):3034-3038 »4 | 7/426 | Vitamin C, beta carotene or curcumin showed no statistically significant effect. One study showed higher recurrence on scalpel excision group compared to usual care 23.6% vs. 4.0%; p < 0.001 One study showed recurrence in 25.9% of patients in the laser group and 15.3% in the scalpel group. | ||
| «Lodi G, Franchini R, Warnakulasuriya S, ym. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database Syst Rev 2016;7(7):CD001829 »5 | 14/909 | The appearance and size of the lesions can be reduced with some medications, but relapse occurs significantly. In addition, treatments cause side effects. | ||
OL=oral leukoplakia; PDT= photodynamic therapy; mo=months
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Relative effect (95% CI) |
|---|---|---|---|
| Level of evidence: very low The quality of evidence is downgraded due to study limitations, inconsistency, and imprecision. | |||
| «de Pauli Paglioni M, Migliorati CA, Schausltz Pereira Faustino I, ym. Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis.»1 | 36/5.051 | Malignant transformation rate of OL lesions treated with lasers PP 5.2% (95% CI 2.4 - 9%) | |
| «Dong Y, Chen Y, Tao Y, ym. Malignant transformation of oral leukoplakia treated with carbon dioxide laser: a meta-analysis. Lasers Med Sci 2019;34(1):209-221 »3 | 24/1546 patients, 1864 lesions | Malignant transformation rate of OL treated with CO2 laser PP 4.50% under the random effect model [95% CI 3.05–6.59%]. | |
| «Lodolo M, Valor J, Villa A. Randomized Controlled Trials for Oral Leukoplakia. Oral Dis 2025;31(11):3034-3038 »4 | 7/426 | One study showed no difference in malignant transformation rate between surgical excision group and usual care. One study (including also dysplastic OL) showed higher malignant transformation rate in “wait-and see” group (malignant transformation n=7) compared to scalpel or laser excision group (malignant transformation n=1). | |
| «Lodi G, Franchini R, Warnakulasuriya S, ym. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database Syst Rev 2016;7(7):CD001829 »5 | 1 RCT, 85 patients 2 RCT, 132 patients 1 RCT, 20 patients | 24 mo 24 mo Up to 7 y | Vitamin A: RR 0.11 (0.01 to 2.05) Beta carotene: RR 0.73 (0.24 to 2.20) Topical bleomycin: RR 3.00 (0.32 to 27.83) There is no effective treatment to prevent OL from becoming malignant. |
OL=oral leukoplakia; PDT= photodynamic therapy; mo=months; y=years
References
- de Pauli Paglioni M, Migliorati CA, Schausltz Pereira Faustino I, ym. Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis. Oral Oncol 2020;109():104850 «PMID: 32540612»PubMed
- Li Y, Wang B, Zheng S, ym. Photodynamic therapy in the treatment of oral leukoplakia: A systematic review. Photodiagnosis Photodyn Ther 2019;25():17-22 «PMID: 30391342»PubMed
- Dong Y, Chen Y, Tao Y, ym. Malignant transformation of oral leukoplakia treated with carbon dioxide laser: a meta-analysis. Lasers Med Sci 2019;34(1):209-221 «PMID: 30443884»PubMed
- Lodolo M, Valor J, Villa A. Randomized Controlled Trials for Oral Leukoplakia. Oral Dis 2025;31(11):3034-3038 «PMID: 40457716»PubMed
- Lodi G, Franchini R, Warnakulasuriya S, ym. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database Syst Rev 2016;7(7):CD001829 «PMID: 27471845»PubMed