BACKGROUND

Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008.

OBJECTIVES

To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis.

SEARCH METHODS

We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022.

SELECTION CRITERIA

We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies.

DATA COLLECTION AND ANALYSIS

We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5.

ADVERSE EFFECTS

Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome.

MAIN RESULTS

We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular.

AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.