Cochrane · intervention · CD007156
Interventions for managing oral submucous fibrosis
Jones, A, Veale, B, Li, T, et al. · Cochrane Database of Systematic Reviews · 2024 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
78
current version
GRADE rated
49
No studies
7
Included studies
30
as reported
No studies 7 · 9%Ungraded 22 · 28.2%Very low 35 · 44.9%Low 10 · 12.8%Moderate 4 · 5.1%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF) | 2176 participants (8 to 400 per study); baseline characteristics such as age, sex and disease stage inconsistently reported; 27 trials in India, 2 in China, 1 in Nepal |
| Intervention | Systemic, intralesional or topical drugs, of any dosage, duration or delivery method; surgical procedures; and others such as physiotherapy, local heat therapy, jaw stretching exercises | Antioxidants (lycopene, curcumin, Oxitard, spirulina, Turmix, salvianolic acid) (n=14); intralesional corticosteroids (betamethasone, dexamethasone, triamcinolone, prednisolone, hydrocortisone); pentoxifylline (n=5); vasodilators (isoxsuprine, xanthinol nicotinate) (n=2); levamisole (n=1); surgery (buccal fat pad graft, nasolabial flap, abdominal dermal fat graft); physiotherapy/ultrasound (n=2); topical aloe vera (n=3) |
| Comparison | Placebo; no active treatment; each other | Placebo (13 trials vs placebo/non-active); no active treatment; active comparators (head-to-head, n=22 trials) |
| Outcomes | Primary: participant-reported resumption of normal eating, chewing and speech; change or improvement in maximal mouth opening (interincisal distance); improvement in range of jaw movement; change in severity of oral/mucosal burning pain/sensation; adverse effects. Secondary: quality of life; postoperative discomfort or pain; participant satisfaction; hospital admission; direct costs | Maximal mouth opening/interincisal distance (n=29); burning sensation VAS (n=14-15); adverse effects (n=15); participant-reported difficulty in speech/swallowing/mouth opening (proxy) (n=4) |
| Study designs | Only randomised controlled trials (RCTs) were considered for inclusion in this review | RCT (n=30) |
| Timing | Outcomes assessed at less than 3 months, 3 to 6 months, and more than 6 months | Treatment courses one week to 18 months; outcomes at <3 months, 3-6 months and >6 months |
Search date: 2022-09. Databases: Cochrane Oral Health's Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE Ovid; Embase Ovid; ClinicalTrials.gov; WHO International Clinical Trials Registry Platform
Questions and results
Show all 3 versionsAntioxidants (lycopene, curcumin, Oxitard) vs Placebo or no active treatment
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Intolerance to spicy food (participant-reported proxy) | OR 0.02 [0.00, 0.43] | 1 study · 100 participants | Ungraded |
Burning sensation (VAS 0-100) 3 to 6 months | MD -70.82 [-94.39, -47.25] | 2 studies · 500 participants | Moderate Downgraded: risk of bias |
Maximal mouth opening (interincisal distance) More than 6 months | MD -1.41 [-5.74, 2.92] | 1 study · 90 participants | Low Downgraded: imprecision |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD 8.83 [8.22, 9.45] | 3 studies · 620 participants | Moderate Downgraded: risk of bias |
Postoperative discomfort or pain | The trials did not measure postoperative discomfort or pain. | 0 studies | No studies |
Maximal mouth opening (interincisal distance) Less than 3 months | MD 3.11 [0.46, 5.77] | 2 studies · 520 participants | Low Downgraded: risk of bias, inconsistency |
Participant-reported resumption of normal eating, chewing and speech | SoF: participant-reported resumption of normal eating, chewing and speech - outcome not reported by included studies. | 0 studies | No studies |
Burning sensation (VAS 0-100) Less than 3 months | MD -30.92 [-31.57, -30.27] | 1 study · 400 participants | Moderate Downgraded: risk of bias |
Adverse effects | Adverse effects (any): 0 in placebo vs 2 minor (flatulence and bloating); 90 (1); no GRADE rating given. 0 (placebo) vs 2 (minor) - flatulence and bloating | 1 study · 90 participants | Ungraded |
Burning sensation (VAS 0-100) More than 6 months | MD -27.60 [-36.21, -18.99] | 1 study · 90 participants | Moderate Downgraded: imprecision |
Hospital admission (length of stay) | The trials did not measure hospital admission. | 0 studies | No studies |
Difficulty in speech (participant-reported proxy) | OR 0.51 [0.21, 1.22] | 1 study · 120 participants | Ungraded |
Participant satisfaction | The trials did not measure participant satisfaction. | 0 studies | No studies |
Improvement in range of jaw movement | The trials did not measure range of jaw movement. | 0 studies | No studies |
Quality of life | The trials did not measure quality of life. | 0 studies | No studies |
Difficulty in mouth opening (participant-reported proxy) | OR 0.00 [0.00, 0.02] | 1 study · 100 participants | Ungraded |
Difficulty in swallowing (participant-reported proxy) | OR 0.24 [0.10, 0.60] | 2 studies · 220 participants | Ungraded |
Direct costs | The trials did not measure costs. | 0 studies | No studies |
Lycopene plus intralesional betamethasone vs Placebo
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Severity of oral/mucosal burning pain/sensation | Kumar 2007 reported burning sensation using a non-validated scale; not included in quantitative analysis. | 1 study | Ungraded |
Maximal mouth opening (interincisal distance) | Kumar 2007 (3-arm: lycopene vs lycopene+intralesional betamethasone vs placebo): appeared to show increased interincisal distance in the two active groups, but limited withdrawal information/incomplete data meant… | 1 study | Ungraded |
Pentoxifylline vs Multivitamin
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) | Rajendran 2006 (pentoxifylline 14 vs multivitamins 15): reported increased interincisal distance in the pentoxifylline group but no baseline data, so change could not be determined; excluded from meta-analysis. | 1 study · 29 participants | Ungraded |
Severity of oral/mucosal burning pain/sensation | Rajendran 2006 concluded the intervention reduced pain, but pain intensity evaluations were inadequately defined and from interview data, making mean scores difficult to interpret. | 1 study · 29 participants | Ungraded |
Pentoxifylline vs Placebo or no active treatment
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Difficulty in speech (participant-reported proxy) | OR 0.20 [0.08, 0.48] | 1 study · 106 participants | Ungraded |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -0.15 [-5.04, 4.74] | 2 studies · 136 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Difficulty in swallowing (participant-reported proxy) | OR 0.42 [0.19, 0.92] | 1 study · 106 participants | Ungraded |
Maximal mouth opening (interincisal distance) Less than 3 months | MD 1.80 [1.02, 2.58] | 1 study · 106 participants | Low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) 3 to 6 months | MD -7.00 [-28.8, 42.8] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Intralesional dexamethasone injections vs Placebo injections
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -2.10 [-6.77, 2.57] | 1 study · 25 participants | Very low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) Less than 3 months | MD -1.80 [-6.30, 2.70] | 1 study · 25 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) Less than 3 months | MD -52.00 [-62.04, -41.96] | 1 study · 25 participants | Very low Downgraded: risk of bias, imprecision |
Adverse effects | Adverse effects (any): no adverse effects reported; 25 (1); no GRADE rating. | 1 study · 25 participants | Ungraded |
Burning sensation (VAS 0-100) 3 to 6 months | MD -46.00 [-53.44, -38.56] | 1 study · 25 participants | Very low Downgraded: risk of bias, imprecision |
Vasodilators (isoxsuprine, xanthinol nicotinate) vs Placebo or no active treatment
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects | Adverse effects (any): 0 placebo vs 14 minor (transient flushing and upper trunk warmness); 85 (2); no GRADE rating. 0 (placebo) vs 14 (minor) - transient flushing and upper trunk warmness | 2 studies · 85 participants | Ungraded |
Maximal mouth opening (interincisal distance) Less than 3 months | MD 2.51 [-0.99, 6.01] | 2 studies · 85 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) 3 to 6 months | MD -51.02 [-72.85, -29.20] | 2 studies · 85 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD 4.04 [-1.93, 10.02] | 2 studies · 85 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) Less than 3 months | MD -38.79 [-52.06, -25.53] | 2 studies · 85 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Hydrocortisone plus hyaluronidase (intralesional) vs Placebo or no active treatment
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -4.88 [-12.87, 3.11] | 1 study · 12 participants | Very low Downgraded: risk of bias, imprecision |
Physiotherapy (tongue-spatula jaw exercises) vs No active treatment
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) 3 to 6 months | MD 0.50 [-7.72, 8.72] | 1 study · 24 participants | Very low Downgraded: risk of bias, imprecision |
Intralesional steroid injections vs Alternative medicinal treatments
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -0.57 [-2.34, 1.19] | 3 studies · 98 participants | Low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) Less than 3 months | MD -0.64 [-2.16, 0.89] | 4 studies · 128 participants | Low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) Less than 3 months | MD -0.06 [-10.64, 10.52] | 2 studies · 58 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) 3 to 6 months | MD 8.61 [-4.52, 21.74] | 3 studies · 98 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Intralesional steroid injection plus adjunctive treatment vs Intralesional steroid injection alone
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD -0.03 [-2.48, 2.43] | 2 studies · 148 participants | Low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -0.85 [-3.31, 1.61] | 2 studies · 148 participants | Low Downgraded: risk of bias, imprecision |
Levamisole vs Antioxidant (Antoxid)
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD -1.00 [-7.18, 5.18] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) 3 to 6 months | MD -7.00 [-13.56, -0.44] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) Less than 3 months | MD -9.10 [-16.23, -1.97] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -1.00 [-7.18, 5.18] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Topical curcumin gel vs Topical aloe vera gel
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD -0.64 [-3.91, 2.63] | 1 study · 60 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) Less than 3 months | MD 16.00 [7.21, 24.79] | 1 study · 60 participants | Very low Downgraded: risk of bias, imprecision |
Spirulina vs Oxitard (antioxidant)
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD -2.60 [-3.82, -1.38] | 1 study · 50 participants | Low Downgraded: risk of bias, imprecision |
Oxitard (antioxidant) vs Aloe vera gel
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD 9.40 [8.52, 10.28] | 1 study · 120 participants | Low Downgraded: risk of bias, imprecision |
Difficulty in speech (participant-reported proxy) 3 to 6 months | OR 0.32 [0.14, 0.76] | 1 study · 120 participants | Ungraded |
Difficulty in swallowing (participant-reported proxy) 3 to 6 months | OR 0.17 [0.07, 0.44] | 1 study · 120 participants | Ungraded |
Pentoxifylline vs Spirulina
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Burning sensation (VAS 0-100) 3 to 6 months | MD 0.50 [-6.60, 7.60] | 1 study · 40 participants | Very low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -8.00 [-14.47, -1.53] | 1 study · 40 participants | Low Downgraded: risk of bias, imprecision |
Intralesional triamcinolone vs Intralesional salvianolic acid B
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) More than 6 months | MD -0.60 [-3.76, 2.56] | 1 study · 28 participants | Very low Downgraded: risk of bias, imprecision |
Intralesional triamcinolone vs Intralesional triamcinolone plus salvianolic acid B
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) More than 6 months | MD -2.38 [-5.64, 0.88] | 1 study · 28 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) Less than 3 months | MD -1.00 [-10.37, 8.37] | 1 study · 28 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) 3 to 6 months | MD -16.30 [-28.15, -4.45] | 1 study · 28 participants | Very low Downgraded: risk of bias, imprecision |
Buccal fat pad graft vs Extended nasolabial flap
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) More than 6 months | MD 6.50 [-10.72, 23.72] | 1 study · 8 participants | Very low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) Less than 3 months | MD -7.25 [-14.19, -0.31] | 1 study · 8 participants | Very low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD 6.00 [-11.36, 23.36] | 1 study · 8 participants | Very low Downgraded: risk of bias, imprecision |
Abdominal dermal fat graft vs Nasolabial flap
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects | Kania 2022 reported 3/30 serious adverse effects (graft failure) requiring prolonged hospital stay in the abdominal dermal fat graft group; no GRADE rating. | 1 study · 30 participants | Ungraded |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD -14.87 [-19.93, -9.81] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Maximal mouth opening (interincisal distance) Less than 3 months | MD -3.60 [-5.17, -2.03] | 1 study · 30 participants | Very low Downgraded: risk of bias, imprecision |
Buccal fat pad pedicle plus placental extract vs Buccal fat pad pedicle alone
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD 7.80 [4.90, 10.70] | 1 study · 10 participants | Very low Downgraded: risk of bias, imprecision |
Jaw opening exercises alone vs Ultrasound plus jaw opening exercises
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD -3.70 [-11.53, 4.13] | 1 study · 20 participants | Very low Downgraded: risk of bias, imprecision |
Tongue depressor stretches (physiotherapy) vs Intralesional steroid plus hyaluronidase injections
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) Less than 3 months | MD 5.38 [-2.24, 13.00] | 1 study · 20 participants | Very low Downgraded: risk of bias, imprecision |
Surgery plus Heister jaw opener vs Surgery plus wooden tongue depressors
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) More than 6 months | MD 0.60 [0.01, 1.19] | 1 study · 50 participants | Very low Downgraded: risk of bias, imprecision |
Burning sensation (VAS 0-100) | Vadepally 2019 measured burning sensation on a VAS but did not fully report results, stating there was no significant difference between the 2 groups (p=0.617). | 1 study · 50 participants | Ungraded |
Maximal mouth opening (interincisal distance) 3 to 6 months | MD 0.92 [0.28, 1.56] | 1 study · 50 participants | Very low Downgraded: risk of bias, imprecision |
Intralesional betamethasone vs Placebo
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) | Goel 2015 (3-arm: intralesional betamethasone vs lycopene vs placebo, 90 per arm): appeared to show increased interincisal distance in both intervention groups vs placebo, but only between-group differences with no… | 1 study · 180 participants | Ungraded |
Hydrocortisone plus hyaluronidase (intralesional) vs Triamcinolone plus hyaluronidase (intralesional)
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) | Singh 2010 (hydrocortisone+hyaluronidase 50 vs triamcinolone+hyaluronidase 50): mouth opening reported categorically (trismus) rather than as continuous data, precluding quantitative analysis; authors found no… | 1 study · 100 participants | Ungraded |
Antioxidant capsules vs Topical aloe vera gel
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Burning sensation (VAS 0-100) | Sudarshan 2012 reported a reduction in burning sensation but no baseline data, so change could not be determined. | 1 study · 20 participants | Ungraded |
Maximal mouth opening (interincisal distance) | Sudarshan 2012 (topical aloe vera 10 vs antioxidant capsules 10): reported improvement in interincisal distance but no baseline data, so change could not be determined; excluded from meta-analysis. | 1 study · 20 participants | Ungraded |
Spirulina vs Topical aloe vera gel
Population: People of any age with a confirmed diagnosis, by clinical examination and biopsy, of oral submucous fibrosis (OSF)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Maximal mouth opening (interincisal distance) | Patil 2015b (spirulina vs topical aloe vera gel): reported important outcomes but data not in a usable format; excluded from meta-analysis. | 1 study | Ungraded |