What do systematic reviews say?

Systemic beta carotene or carotenoids (incl. lycopene) vs placebo or no treatment

Systemic beta carotene or carotenoids (incl. lycopene) may leads to lower improvement of histological features (not improved) compared with placebo or no treatment (low certainty).

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  5 months (treatment lasted 3 months)
  RR 0.24 [0.12, 0.46]
  1 study · 58 participants
  Low

Bowman-Birk inhibitor vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  SoF 6, Histological changes: 'Not measured'. Effects text: data on histological changes from Armstrong 2013 were not available for analysis, but study authors reported no statistically significant differences in…
  1 study
  GRADE not reported

Systemic beta carotene or carotenoids (incl. lycopene) vs placebo or no treatment

It is very uncertain whether systemic beta carotene or carotenoids (incl. lycopene) changes oral cancer development compared with placebo or no treatment (very low certainty).

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  24 months
  RR 0.71 [0.24, 2.09]
  2 studies · 132 participants
  Very low

Herbal extracts (tea components; Chinese herbal mixture; freeze-dried black raspberry gel) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  SoF 4 (Herbal extracts vs placebo), Cancer development: SoF cell 'Not measured'. Effects text: cancer development was among the outcomes in Tsao 2009 (green tea extract) but it was not possible to analyse the data…
  1 study
  GRADE not reported

Vitamin A or retinoids (systemic or topical; incl. 13-cis-retinoic acid, acitretin) vs placebo or no treatment

Vitamin A or retinoids (systemic or topical; incl. 13-cis-retinoic… probably leads to lower improvement of histological features (not improved) compared with placebo or no treatment (moderate certainty).

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  3 months
  RR 0.43 [0.24, 0.76]
  1 study · 41 participants
  Moderate

Systemic beta carotene or carotenoids (incl. lycopene) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  5 to 12 months
  SoF 2, Safety of the intervention at 5 to 12 months: 'Systemic beta carotene did not cause any adverse effects in 1 study supplementing 10 mg/d (Nagao), and caused adverse effects of varying severity in 9% of…
  3 studies
  GRADE not reported

Bowman-Birk inhibitor vs placebo or no treatment

Bowman-Birk inhibitor showed no clear difference in clinical resolution (oral lesion not completely resolved) compared with placebo or no treatment (low certainty).

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  6 months
  RR 1.00 [0.91, 1.09]
  1 study · 21 participants
  Low

NSAIDs (ketorolac oral rinse; systemic celecoxib) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  SoF 3 (NSAIDs vs placebo), Cancer development: SoF cell 'Not measured'. Effects text: cancer development was among outcomes in Papadimitrakopoulou 2008 (celecoxib) but did not occur in either arm, probably because of…
  1 study
  GRADE not reported

Bowman-Birk inhibitor vs placebo or no treatment

The review found no eligible studies for this question.

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  SoF 6 (Bowman-Birk inhibitor vs placebo), Cancer development: 'Not measured'. Effects text: 'Cancer development was not among the outcomes of the study testing the Bowman-Birk inhibitor (Armstrong 2013).'
  0 studies
  No studies found

Herbal extracts (tea components; Chinese herbal mixture; freeze-dried black raspberry gel) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  3 months
  SoF 4, Histological changes (not improved) at 3 months: '2 studies (green tea extract capsules and freeze-dried raspberry gel) did not find evidence of benefit.' No GRADE. Effects text: Mallery raspberry RR 0.97…
  2 studies
  GRADE not reported

Surgical removal of the lesion (surgical excision, laser surgery, cryotherapy) vs Placebo or no treatment

The review found no eligible studies for this question.

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  'We did not identify any RCTs that compared surgical treatments with placebo or no treatment.' Three surgical RCTs were found (Chee 2013, Lopez-Jornet 2013, Schwarz 2005) but all excluded because they did not include a…
  Studies not reported
  No studies found

Topical bleomycin vs placebo or no treatment

It is very uncertain whether topical bleomycin changes improvement of histological features (not improved) compared with placebo or no treatment (very low certainty).

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  3 months
  RR 0.49 [0.22, 1.10]
  1 study · 21 participants
  Very low

Herbal extracts (tea components; Chinese herbal mixture; freeze-dried black raspberry gel) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  up to 3 months
  SoF 4, Safety of the intervention up to 3 months: '3 studies measured adverse effects: green tea extract capsules caused high frequency (93%) of adverse effects of varying severity in 1 study; the mixed tea study did…
  3 studies
  GRADE not reported

Removal of predisposing habits (e.g. tobacco/alcohol cessation) vs Placebo or no treatment

The review found no eligible studies for this question.

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes
  '...nor did we identify any RCTs of risk factor cessation.' Removal of predisposing habits (e.g. smoking cessation) was a planned intervention; no eligible RCT found.
  Studies not reported
  No studies found

Vitamin A or retinoids (systemic or topical; incl. 13-cis-retinoic acid, acitretin) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  4 to 12 months
  SoF 1, Safety of the intervention at 4 to 12 months: '3 studies (1 each evaluating topical acitretin, topical 13-cis-retinoic acid, 200,000 IU per week of vitamin A) found no adverse effects. Systemic 13-cis-retinoic…
  4 studies
  GRADE not reported

Bowman-Birk inhibitor vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  up to 6 months
  SoF 6, Safety of the intervention up to 6 months: 'Trial authors reported that there were no significant adverse effects. 33 participants in the intervention group reported 75 adverse effects. 25 participants in the…
  1 study
  GRADE not reported

Systemic beta carotene or carotenoids (incl. lycopene) vs placebo or no treatment

• Interventions for treating oral leukoplakia to prevent oral cancer 2016 · Cochrane All outcomes

  5 to 12 months
  SoF 2, Clinical resolution (not completely resolved) at 5 to 12 months: 'The 3 studies could not be combined in meta-analysis. 2 found benefit for systemic beta carotene, and 1 did not.' No GRADE rating. Effects text…
  3 studies
  GRADE not reported

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone (radiotherapy or chemoradiotherapy)

Non-specific immunotherapy (recombinant interleukin-2 or BCG cell… showed no clear difference in adverse effects compared with standard therapy alone; GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Moderate to severe chills (BCG-CWP, all grades)
  RR 11.00 [0.67, 179.29]
  1 study · 24 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Nausea/vomiting (rIL-2, grades >=3)
  RR 3.40 [0.15, 77.34]
  1 study · 30 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Stomatitis (rIL-2, all grades)
  RR 1.47 [0.75, 2.90]
  1 study · 30 participants
  GRADE not reported

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus… led to higher adverse effects compared with standard therapy alone (radiotherapy or chemoradiotherapy); GRADE not reported.

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Skin toxicity (lapatinib, all grades)
  RR 2.02 [1.23, 3.32]
  1 study · 67 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gastrointestinal complaints (gefitinib, all grades)
  RR 1.04 [0.98, 1.11]
  1 study · 226 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  40 to 60 months · Gastrointestinal complaints (lapatinib, all grades)
  RR 15.53 [2.18, 110.55]
  1 study · 67 participants
  GRADE not reported

EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)

• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Mucositis (all grades)
  Mucositis all grades: not estimable due to high heterogeneity (P=0.0009; I2=86%) between subgroups (cetuximab; nimotuzumab) and within cetuximab (I2=93%); 1417 participants, 3 studies. Table 3, row 1.6 (Ang 2014;…
  3 studies · 1417 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Skin toxicity/acneiform rash (cetuximab, all grades)
  RR 6.56 [5.35, 8.03]
  2 studies · 1311 participants
  GRADE not reported
• Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy 2015 · Cochrane All outcomes

  24 to 70 months · Xerostomia (grades >=3)
  RR 1.36 [0.80, 2.31]
  2 studies · 1311 participants
  GRADE not reported