Interventions for treating oral leukoplakia

 

Abstract

Background

Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation.

Objectives

To assess effectiveness, safety and acceptability of treatments for leukoplakia.

Search methods

The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register (to April 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (from 1966 to December 2005), and EMBASE (from 1980 to December 2005). Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED).

Selection criteria

Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects.

Data collection and analysis

Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed by two review authors, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating risk ratio. When valid and relevant data were collected, a meta-analysis of the data was undertaken.

Main results

The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT with a no treatment/placebo arm. Twenty-five eligible RCTs of non-surgical interventions were identified: 11 were excluded for different reasons, five were ongoing studies, leaving nine studies to be included in the review (501 patients). Two studies resulted at low risk of bias, six at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs, two studies investigated beta carotene or carotenoids, the other drugs tested were bleomycin (one study), mixed tea (one study) and ketorolac (one study). One study tested two treatments. Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene, lycopene and vitamin A or retinoids, was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups.

Authors' conclusions

To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.

 

Plain language summary

Interventions for treating oral leukoplakia

No evidence from trials to show how to prevent leukoplakia in the mouth becoming malignant.
Oral leukoplakia is a thickened white patch formed in the mouth lining that cannot be rubbed off. Leukoplakia is a lesion that sometimes becomes cancerous (a tumour that invades and destroys tissue, then spreads to other areas). Preventing this change is critical as survival rates of more than 5 years after diagnosis with oral cancer is low. Drugs, surgery and other therapies have been tried. The review of trials compared several drugs such as bleomycin, vitamin A and beta carotene supplements and mixed tea. There was no evidence found to show the effects of these treatments. More research is needed.

 

摘要

背景

評估口腔白斑病之治療

口腔白斑病是一種相對上較為常見的口腔病灶，其中有少數但顯著比例的病例會轉變成癌症。因為多數之白班是沒有症狀的，故治療的首要目標應為預防此種惡性轉變。

目標

評估各種白斑治療方式之效度，安全性與接受度。

搜尋策略

我們在下列的資料庫中搜尋相關的試驗: Cochrane Oral Health Group's Trials Register (至2006年4月), CENTRAL (TheCochrane Library 2006年 第1期), MEDLINE (自1966年至2005年12月), and EMBASE (自 1980年至2005年12月。)主要之口腔醫學期刊則以人工搜尋。亦檢查採納之研究及文獻回顧中之參考文獻。口腔醫學專家則以European mailing list (EURORALMED)取得聯繫。

選擇標準

採納收錄診斷為口腔白斑病之病人的隨機對照試驗(randomised controlled trials；RCTs)。任何手術或給藥 (局部或全身性) 的治療方式皆被採納。首要考量之臨床結果為白斑之惡性轉變。其餘考量之臨床結果為: 臨床病灶消解，組織學轉變及不良副作用之頻率。

資料收集與分析

我們以特定之資料回收格式搜集資料。由組織病理學判讀確認之白斑惡性轉變為主要考量之臨床結果。次要考量之臨床結果有臨床病灶消解及上皮細胞異生嚴重度之改變。已收錄研究之信度由兩位審查委員評估。評估標準為分組隱匿(allocation concealment)，盲度(Blindness)及參與者喪失(loss of participants)。資料以計算風險比例(risk ratio)來分析。當收集到可信(valid)且相關(relevant)的資料時， 就會進行統合分析(metaanalysis)

主要結論

手術治療，包括雷射治療及冷凍治療的可能效果，從未以具有未治療/安慰劑群組的隨機對照試驗研究過。我們找到25篇符合的非手術治療之隨機對照試驗， 其中11篇因不同原因而被排除，另外5篇則是正在進行的研究，所以只有9篇研究收錄在本篇回顧中(共501位病人)。其中兩篇具有低度偏差風險(risk of bias)，6篇有中度偏差風險且有1篇具高度偏差風險。5篇隨機對照試驗研究Vitamin A 及retinoids， 2篇研究beta carotene 或carotenoids,其他被測試的藥有bleomycin (1篇)， 綜合茶(1篇)及ketorolac (1篇)。有1篇研究測試兩種治療方式。 惡性轉變僅在2篇研究中被記載:沒有任何一種被測試之治療方式優於安慰劑。與安慰劑或不接受治療相比，以beta carotene, lycopene 及 vitamin A 或 retinoids治療， 皆有顯著之臨床病灶消解率。 在報告中，高復發率為一常見之現象。嚴重度不一的副作用也常被報導；然而，各式的治療方式都被病人廣泛接受，因為治療組跟控制組的退出率(dropout rate)類似。

作者結論

迄今仍無證據顯示具有有效防範白班惡性轉變的治療。治療可能對病灶消解有效，但常見復發及不良副作用。

翻譯人

本摘要由臺灣大學附設醫院王逸平翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

並無由試驗而來的證據顯示如何防止口內白斑病惡性轉變。 口腔白斑病是一形成在口腔內襯之刮不掉的白色增厚區塊。白斑為一有時會轉換成癌(侵犯並破壞組織的腫瘤，之後亦會擴散至其他區域)之病灶。 因為口腔癌診斷後之5年以上存活率很低，故預防惡性轉變十分重要。 藥物，手術及他種治療皆被嘗試過。本篇試驗回顧比較了多種藥物，如bleomycin, vitamin A 及 beta carotene supplements 和綜合茶，並無證據顯示這些治療具有效果，必須要更多的研究。