Oral Cancer diagnosis: biopsy and histology still best method

herpetic ulcer on tongue

The incidence and mortality rates for oral cancer are increasing and it represents an important global health problem. Many oral cancers are preceded by potentially malignant disorders (PMD) e.g erythroplakia, non-homogeneous leukoplakia, erosive lichen planus and oral submucous fibrosis. Early detection of PMD can reduce malignant transformation rate and improve survival from oral cancer.

The aim of this review was to estimate the diagnostic accuracy of tests for the detection of oral cancer and PMD of the lip and oral cavity, in people presenting with clinically evident lesions.


Searches were conducted in the Cochrane Oral Health Group’s Trials Register, Cochrane Register of Diagnostic Test Accuracy Studies, Medline, Embase, and MEDION. Searches were not limited by language or publication status.

Cross-sectional diagnostic test accuracy studies (or consecutive series) and randomised studies of diagnostic test accuracy that reported the diagnostic test accuracy of the following index tests when used as an adjunct to conventional oral examination in detecting PMD or oral squamous cell carcinoma of the lip or oral cavity: vital staining, oral cytology, light-based detection and oral spectroscopy, blood or saliva analysis (which test for the presence of biomarkers in blood or saliva) were considered. Scalpel, punch or fine needle aspiration biopsy with histological diagnosis was the reference test.

Two reviewers independently selected studies, extracted data and assessed methodological quality using a modified QUADAS-2 approach. Meta-analysis was used to combine the results of studies for each index test using the bivariate approach to estimate the expected values of sensitivity and specificity.


  • 41 studies, recruiting 4002 patients were included.
  • No single study could be classified as being at low risk of bias across all domains.
  • 14 studies evaluated vital staining,
  • 13 studies oral cytology,
  • 13 studies light-based detection or oral spectroscopy
  • Six studies assessed two combined index tests.
  • There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis.
No. of studies in meta-analysis Sensitivity(95%CI) Specificity(95%CI)
Vital staining 14 0.84 (0.74 to 0.90) 0.70 (0.59 to 0.79)
Cytology 12 0.91 (0.81 to 0.96) 0.91 (0.81 to 0.95)
light-based detection 11 0.91 (0.77 to 0.97) 0.58 (0.22 to 0.87)


The authors concluded:

The overall quality of the included studies was poor. None of the adjunctive tests can be recommended as a replacement for the currently used standard of a scalpel biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation.


This Cochrane review was able to identify a large number of studies relating to adjunctive tests (vital staining, cytology, and light-based detection) for the identification of oral cancer. However as the authors highlight the quality of the included studies in poor. It is also important to note that the included studies were all caries out in a secondary care environment, usually specialist clinics that would see a larger pool of patients with PMD or oral cancers. As these adjunctive tests have been marketed in primary care great care should be taken when considering the relevance of these results for primary care patients. Indeed in the discussions the authors state:

The utility of vital staining should be confined for use by expert clinicians to facilitate biopsy site selection in heterogeneous PMDs, or as a surveillance tool.


Macey R, Walsh T, Brocklehurst P, Kerr AR, Liu JLY, Lingen MW, Ogden GR, Warnakulasuriya S, Scully C. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No.: CD010276. DOI: 10.1002/14651858.CD010276.pub2.

Cochrane Oral Health Group – Testing for oral cancer

Cochrane Resources on Mouth Cancer

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