What are the most accurate tests for finding cancer of the mouth or lips (oral cancer) and conditions that may lead to oral cancer?

Review question

The current method of diagnosing cancer of the mouth or lips involves the surgical removal of a piece of affected tissue that is sent to a laboratory for histological examination using a microscope (scalpel biopsy). This is painful for patients and involves a delay. The aim of this review was to find out the accuracy of three alternative diagnostic tests that are less invasive and provide more timely results.

Background

Oral cancer (OSCC - oral squamous cell carcinoma) often occurs after a condition called PMD (potentially malignant disorder), which can sometimes progress to cancer. If conditions such as oral cancer or PMD are identified early enough, outcomes for patients can be improved.

Study characteristics

The search on which the evidence is based was carried out on 30 April 2013. Forty-one studies involving 4002 participants, published between 1980 and 2012, were included. Each participant underwent one of three diagnostic tests for oral cancer and PMD as well as the standard method of diagnosis by surgical biopsy. By comparing results, the researchers were able to evaluate the accuracy of each test as compared to surgical biopsy.

Three tests (index tests) were evaluated.

1. Vital stain – a liquid that can be used as a mouthrinse or applied straight on to a suspected area of the mouth. It is thought that any area that is coloured blue after rinsing with water has a high chance of being oral cancer or PMD.

2. Oral cytology – instead of using a scalpel to cut away a piece of the suspected area, a brush is used to remove cells that are sent to a laboratory for examination under a microscope.

3. Light-based detection – a special light shone in the mouth that is believed to make cancerous areas appear different to healthy areas.

There were no eligible studies that looked at the accuracy of tests of blood or saliva.

Key Results

The proportion of people with OSCC or PMD identified through surgical biopsy varied in the included studies. We used the middle value for the included studies to illustrate the implications of the different tests. A false negative result means that people that truly have oral cancer or PMD will be diagnosed as free from the condition, possibly to be correctly diagnosed at a later date when the condition will be more difficult to treat successfully. A false positive result would mean that people who did not truly have PMD or oral cancer would be diagnosed as having it and therefore unnecessarily undergo invasive treatment.

If vital staining was used to identify OSCC or PMD in a sample of 1000 people (of whom 500 truly have OSCC or PMD), then the condition would go undetected in 80 people (false negative result) and 150 people without the condition would be told they have the condition (false positive result). If cytology was used, the condition would go undetected in 45 people and 45 people without the condition would be told they have the condition. If a light-based detection method was used, the condition would go undetected in 45 people and 210 people without the condition would told they have the condition.

Therefore, in terms of correctly classifying people, cytology was the most accurate of the three tests.

Quality of the evidence

There were shortcomings in many of the studies that put them at high risk of bias and so the key results should be interpreted with caution. The main concern was the ways in which people were selected to take part in the studies. When patients at particularly high or low risk of oral cancer are selected to participate then this can influence the results of the study. Additionally, there were studies where the results from the standard method of diagnosis ('index test') were not reported and the reasons for this were not explained.

Conclusion

None of the tests evaluated in this review that were additional to a visual examination can be recommended as a replacement for the currently used standard of a scalpel biopsy and histological assessment.

Authors' conclusions: 

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.

Read the full abstract...
Background: 

Oral squamous cell carcinoma is the most common form of malignancy of the lip and oral cavity, often being proceeded by potentially malignant disorders (PMD). Early detection can reduce the malignant transformation of PMD and can improve the survival rate for oral cancer. The current standard of scalpel biopsy with histology is painful for patients and involves a delay whilst histology is completed; other tests are available that are unobtrusive and provide immediate results.

Objectives: 

Primary objective: To estimate the diagnostic accuracy of index tests for the detection of oral cancer and PMD of the lip and oral cavity, in people presenting with clinically evident lesions.

Secondary objective: To estimate the relative accuracy of the different index tests.

Search strategy: 

The electronic databases were searched on 30 April 2013. We searched MEDLINE (OVID) (1946 to April 2013) and four other electronic databases (the Cochrane Diagnostic Test Accuracy Studies Register, the Cochrane Oral Health Group's Trials Register, EMBASE (OVID) and MEDION (Ovid)). There were no restrictions on language in the searches of the electronic databases. We conducted citation searches and screened reference lists of included studies for additional references.

Selection criteria: 

We selected studies 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).

Data collection and analysis: 

Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction and quality assessment were carried out by at least two authors, independently and in duplicate. Studies were assessed for methodological quality using QUADAS-2. 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.

Main results: 

We included 41 studies, recruiting 4002 participants, in this review. These studies evaluated the diagnostic accuracy of conventional oral examination with: vital staining (14 studies), oral cytology (13 studies), light-based detection or oral spectroscopy (13 studies). Six studies assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis.

The summary estimates for vital staining obtained from the meta-analysis were sensitivity of 0.84 (95% CI 0.74 to 0.90) with specificity of 0.70 (0.59 to 0.79), with 14 studies were included in the meta-analysis. For cytology, sensitivity was 0.91 (0.81 to 0.96) and specificity was 0.91 (0.81 to 0.95) with 12 studies included in the meta-analysis. For light-based detection, sensitivity was 0.91 (0.77 to 0.97) and specificity was 0.58 (0.22 to 0.87) with 11 studies included in the meta-analysis. The relative test accuracy was assessed by adding covariates to the bivariate analysis, no difference in model fit was observed.

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