What do systematic reviews say?

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

Visual screening (oral visual inspection) by trained health workers vs No screening

Visual screening (oral visual inspection) by trained health workers showed no clear difference in oral cancer incidence compared with no screening; GRADE not reported.

• Screening programmes for the early detection and prevention of oral cancer 2013 · Cochrane All outcomes

  15-year follow-up
  RR 1.14 [0.91, 1.44]
  1 study · 191873 participants
  GRADE not reported
• Screening programmes for the early detection and prevention of oral cancer 2013 · Cochrane All outcomes

  15-year follow-up · High-risk individuals (tobacco and/or alcohol users)
  RR 0.97 [0.79, 1.19]
  1 study
  GRADE not reported

Visual screening (oral visual inspection) by trained health workers vs No screening

Visual screening (oral visual inspection) by trained health workers showed no clear difference in oral cancer mortality (disease-specific) compared with no screening (low certainty).

• Screening programmes for the early detection and prevention of oral cancer 2013 · Cochrane All outcomes

  15-year follow-up
  RR 0.88 [0.69, 1.12]
  1 study · 191873 participants
  Low
• Screening programmes for the early detection and prevention of oral cancer 2013 · Cochrane All outcomes

  15-year follow-up · High-risk individuals (tobacco and/or alcohol users)
  RR 0.76 [0.60, 0.97]
  1 study
  GRADE not reported

Visual examination (VE) vs Reference standard: examination and clinical evaluation by a physician/clinician with specialist knowledge or training (long-term follow-up accepted for those screened negative)

• Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy… 2021 · Cochrane All outcomes
  Summary of findings 1 (no pooled analysis): for the 7 low-prevalence studies specificity ranged from 0.94 (95% CI 0.88 to 0.97) to 0.99 (95% CI 0.98 to 1.00); for the 3 higher-prevalence studies specificity ranged from…
  10 studies · 25568 participants
  Low

Visual examination (VE) vs Reference standard: examination and clinical evaluation by a physician/clinician with specialist knowledge or training (long-term follow-up accepted for those screened negative)

• Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy… 2021 · Cochrane All outcomes
  Summary of findings 1 (no pooled analysis): for the 7 studies with low prevalence (<=10%) sensitivity ranged from 0.50 (95% CI 0.07 to 0.93) to 0.99 (95% CI 0.97 to 1.00); for the 3 higher-prevalence studies…
  10 studies · 25568 participants
  Low

Remote screening of the oral cavity (mobile application/telemedicine) vs Reference standard: examination and clinical evaluation by a physician/clinician with specialist knowledge or training (long-term follow-up accepted for those screened negative)

• Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy… 2021 · Cochrane All outcomes
  Summary of findings 4 (no pooled analysis): specificity 0.99 (95% CI 0.99 to 1.00), 1.00 (95% CI 0.91 to 1.00), and 0.72 (95% CI 0.63 to 0.80) across the 3 studies. Certainty VERY LOW.
  3 studies · 3600 participants
  Very low

Remote screening of the oral cavity (mobile application/telemedicine) vs Reference standard: examination and clinical evaluation by a physician/clinician with specialist knowledge or training (long-term follow-up accepted for those screened negative)

• Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy… 2021 · Cochrane All outcomes
  Summary of findings 4 (no pooled analysis): sensitivity 0.85 (95% CI 0.81 to 0.88), 0.82 (95% CI 0.57 to 0.96), and 0.94 (95% CI 0.70 to 1.00) across the 3 studies. Prevalence 12.2% to 30.9%. Certainty VERY LOW.
  3 studies · 3600 participants
  Very low

Periodontitis vs Individuals without periodontal disease (by LOA)

Periodontitis is associated with roughly a threefold higher odds of oral cancer (pooled OR 2.94, 95% CI 2.13-4.07; low certainty of evidence), though heterogeneity is moderate (I2=52.4%).

• Periodontitis and the risk of oral cancer: a meta-analysis of case-control studies. 2024 All outcomes

  Not specified · Case-control studies conducted in Asia (n=6), Europe (n=5), USA (n=2) and other countries (n=3) · Overall (random-effects pooled estimate)
  OR 2.94 [2.13, 4.07]
  8 studies · 6927 participants
  Low

Higher number of lost teeth (per one additional lost tooth) vs One fewer missing tooth

The number of missing teeth (per tooth) was not significantly associated with oral cancer (OR 0.96, 95% CI 0.92-1.01); ungraded.

• Periodontitis and the risk of oral cancer: a meta-analysis of case-control studies. 2024 All outcomes

  Not specified · Case-control studies conducted in Asia (n=6), Europe (n=5), USA (n=2) and other countries (n=3) · Missing teeth (per tooth)
  OR 0.96 [0.92, 1.01]
  2 studies
  GRADE not reported

Missing teeth / tooth loss vs Fewer or no missing teeth

Pooling across all missing-teeth measures, the overall association with oral cancer was not statistically significant (OR 1.20, 95% CI 0.97-1.48; high heterogeneity, I2=82.8%); ungraded.

• Periodontitis and the risk of oral cancer: a meta-analysis of case-control studies. 2024 All outcomes

  Not specified · Case-control studies conducted in Asia (n=6), Europe (n=5), USA (n=2) and other countries (n=3) · Overall (all missing-teeth measures pooled)
  OR 1.20 [0.97, 1.48]
  6 studies
  GRADE not reported

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

It is very uncertain whether vitamin A or retinoids (systemic or topical; incl. 13-cis-retinoic… 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 (treatment lasted 12 months)
  RR 0.11 [0.01, 2.05]
  1 study · 85 participants
  Very low

Topical bleomycin vs placebo or no treatment

It is very uncertain whether topical bleomycin 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

  up to 7 years
  RR 3.00 [0.32, 27.83]
  1 study · 20 participants
  Very low

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

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

More than 15 missing teeth vs 15 or fewer missing teeth

More than 15 missing teeth was associated with higher odds of oral cancer.

• Periodontitis and the risk of oral cancer: a meta-analysis of case-control studies. 2024 All outcomes

  Missing teeth >15
  OR 1.91 [1.01, 3.62]
  5 studies
  GRADE not reported

Intervention not reported

The intervention led to higher oral cancer (OC); GRADE not reported.

• Periodontitis and the risk of oral cancer: a meta-analysis of case-control studies. 2024 All outcomes

  Sensitivity analysis: excluding Moraes et al. [34]
  OR 2.63 [1.92, 3.62]
  7 studies
  GRADE not reported

Mouth self-examination (MSE) vs Reference standard: examination and clinical evaluation by a physician/clinician with specialist knowledge or training (long-term follow-up accepted for those screened negative)

• Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy… 2021 · Cochrane All outcomes
  Summary of findings 2 (no pooled analysis): specificity 1.00 (95% CI 1.00 to 1.00), 0.95 (95% CI 0.88 to 0.99), 0.44 (95% CI 0.20 to 0.70), and 0.54 (95% CI 0.37 to 0.69) across the 4 studies. Certainty VERY LOW.
  4 studies · 35059 participants
  Very low

Mouth self-examination (MSE) vs Reference standard: examination and clinical evaluation by a physician/clinician with specialist knowledge or training (long-term follow-up accepted for those screened negative)

• Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy… 2021 · Cochrane All outcomes
  Summary of findings 2 (no pooled analysis): sensitivity 0.18 (95% CI 0.13 to 0.24), 0.09 (95% CI 0.04 to 0.15), 0.43 (95% CI 0.24 to 0.63), and 0.33 (95% CI 0.10 to 0.65) across the 4 studies. Prevalence 0.6% to 63.6%.…
  4 studies · 35059 participants
  Very low