Preventing oral cancer by treating oral leukoplakia: limited evidence

shutterstock_163829423Oral leukoplakia is a white patch formed in the mouth lining that cannot be rubbed off. It often does not hurt and may go unnoticed for years. People with leukoplakia develop oral cancer more often than people without it. Preventing this is critical; rates of oral cancer survival longer than five years after diagnosis are low. Drugs, surgery and other therapies have been tried for treatment of oral leukoplakia. Medical and complementary treatments can be locally applied (i.e. directly onto the white patch) or systemic (affecting the whole body, e.g. taken as a pill).

What was the research?

A systematic review of the evidence to evaluate whether people affected by oral leukoplakia can benefit from surgical, medical or complementary treatments, either local or systemic. In particular, this review was conducted to find out which, if any, treatment is able to prevent people with leukoplakia of the mouth from getting oral cancer. This review updates the previous review published in 2006.

Who conducted the research?

The research was conducted by a team led by Giovanni Lodi, from Università degli Studi di Milano, on behalf of Cochrane Oral Health. Roberto Franchini, Saman Warnakulasuriya, Elena Maria Varoni, Andrea Sardella, Alexander R Kerr, Antonio Carrassi, LCI MacDonald and Helen V Worthington were also on the team.

What evidence was included in the review?

The evidence on which this review is based is up-to-date as of May 2016. 14 randomised controlled trials (RCTs) of medical and complementary treatments were found, which involved 909 participants in total. Treatments included herbal extracts, anti-inflammatory drugs, vitamin A, beta carotene supplements and others. Surgical treatment has not been compared with placebo or no treatment in an RCT.

What did the evidence say?

Cancer development was measured in studies of three treatments: systemic vitamin A, systemic beta carotene and topical bleomycin. None of these treatments showed effectiveness in preventing cancer development, as measured up to two years for vitamin A and beta carotene, and seven years for bleomycin.

Some individual studies of vitamin A and beta carotene suggested that these treatments may be effective for improving or healing oral lesions. However, some studies observed a high rate of relapse in participants whose lesions were initially resolved by treatment.

Most treatments caused side effects of differing severity in a high proportion of participants.

It seems likely that the treatments were well accepted by participants because drop-out rates were similar between treatment and control groups.

How good was the evidence?

The available evidence is very limited. Most interventions were assessed by only one small study. Most studies had problems in the way they were conducted, making their results unreliable. The quality of evidence for the outcome of cancer development was judged to be very low.

What are the implications for dentists and the general public?

No randomised controlled trials (RCTs) on surgical treatment for people who have oral leukoplakia have included placebo and active treatment arms. Nor have RCTs examined risk factor cessation (e.g. smoking). Therefore, the effectiveness of these interventions cannot be reliably assessed. None of the medical and complementary treatments studied (vitamin A, beta carotene, bleomycin) has been shown to be effective in preventing cancer onset in people with leukoplakia, and, despite the findings of some studies that vitamin A or beta carotene may be effective in reducing or even resolving oral leukoplakia in the short term, the risk of subsequent relapse seems high.

What should researchers look at in the future?

Although surgery remains the treatment option favoured by most clinicians, the effectiveness of surgery compared with no treatment (“wait and see”) has not been assessed in RCTs for prevention of cancer development in people with leukoplakia. Research is needed to assess surgical treatment of patients with leukoplakia and to evaluate effects of risk factor cessation in people with leukoplakia. Larger, better conducted trials of longer duration are required to properly evaluate the effects of any treatment on malignant transformation rates, which should be considered the primary outcome when effectiveness of treatments for leukoplakia is tested.

Author conclusions

Larger, better studies of longer duration are required. As well as further studies of drug treatment and alternative treatments like vitamins, studies are needed to evaluate the effectiveness and safety of surgery, and of stopping risk factor habits such as smoking.


Lodi G, Franchini R, Warnakulasuriya S, Varoni EM, Sardella A, Kerr AR, Carrassi A, MacDonald LCI, Worthington HV. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database of Systematic Reviews 2016 , Issue 7 . Art. No.: CD001829. DOI: 10.1002/14651858.CD001829.pub4

This blog post is based on the review’s plain language summary and was compiled at the Cochrane Oral Health Editorial Base by Anne Littlewood0024 Oral leukoplakia blogshot

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  1. Pingback: Oral leukoplakia: very limited evidence for treatments - National Elf Service

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