Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions.

BACKGROUND: Squamous cell carcinoma is the most common form of malignancy of the oral cavity, and is often proceeded by oral potentially malignant disorders (OPMD). Early detection of oral cavity squamous cell carcinoma (oral cancer) can improve survival rates. The current diagnostic standard of surgical biopsy with histology is painful for patients and involves a delay in order to process the tissue and render a histological diagnosis; other diagnostic tests are available that are less invasive and some are able to provide immediate results. This is an update of a Cochrane Review first published in 2015. OBJECTIVES: Primary objective: to estimate the diagnostic accuracy of index tests for the detection of oral cancer and OPMD, in people presenting with clinically evident suspicious and innocuous lesions. SECONDARY OBJECTIVE: to estimate the relative accuracy of the different index tests. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were also searched for ongoing trials to 20 October 2020. No restrictions were placed on the language or date of publication when searching 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 OPMD or oral cavity squamous cell carcinoma: vital staining (a dye to stain oral mucosa tissues), 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 the Quality Assessment of Diagnostic Accuracy Studies 2 (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: This update included 63 studies (79 datasets) published between 1980 and 2020 evaluating 7942 lesions for the quantitative meta-analysis. These studies evaluated the diagnostic accuracy of conventional oral examination with: vital staining (22 datasets), oral cytology (24 datasets), light-based detection or oral spectroscopy (24 datasets). Nine datasets assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis. Two studies were classed as being at low risk of bias across all domains, and 33 studies were at low concern for applicability across the three domains, where patient selection, the index test, and the reference standard used were generalisable across the population attending secondary care. The summary estimates obtained from the meta-analysis were: - vital staining: sensitivity 0.86 (95% confidence interval (CI) 0.79 to 0.90) specificity 0.68 (95% CI 0.58 to 0.77), 20 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; - oral cytology: sensitivity 0.90 (95% CI 0.82 to 0.94) specificity 0.94 (95% CI 0.88 to 0.97), 20 studies, sensitivity moderate-certainty evidence, specificity moderate-certainty evidence; - light-based: sensitivity 0.87 (95% CI 0.78 to 0.93) specificity 0.50 (95% CI 0.32 to 0.68), 23 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; and - combined tests: sensitivity 0.78 (95% CI 0.45 to 0.94) specificity 0.71 (95% CI 0.53 to 0.84), 9 studies, sensitivity very low-certainty evidence, specificity very low-certainty evidence. AUTHORS' CONCLUSIONS: At present none of the adjunctive tests can be recommended as a replacement for the currently used standard of a surgical biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for oral cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation. Potentially eligible studies of blood and salivary biomarkers were excluded from the review as they were of a case-control design and therefore ineligible. In the absence of substantial improvement in the tests evaluated in this updated review, further research into biomarkers may be warranted.

Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy adults.

BACKGROUND: The early detection of oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD), followed by appropriate treatment, may improve survival and reduce the risk for malignant transformation respectively. This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To estimate the diagnostic test accuracy of conventional oral examination, vital rinsing, light-based detection, mouth self-examination, remote screening, and biomarkers, used singly or in combination, for the early detection of OPMD or OSCC in apparently healthy adults. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 October 2020), MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching 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 test accuracy of any of the aforementioned tests in detecting OPMD or OSCC during a screening procedure. Diagnosis of OPMD or OSCC was provided by specialist clinicians or pathologists, or alternatively through follow-up. 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 the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We reported the sensitivity and specificity of the included studies. We provided judgement of the certainty of the evidence using a GRADE assessment. MAIN RESULTS: We included 18 studies, recruiting 72,202 participants, published between 1986 and 2019. These studies evaluated the diagnostic test accuracy of conventional oral examination (10 studies, none new to this update), mouth self-examination (four studies, two new to this update), and remote screening (three studies, all new to this update). One randomised controlled trial of test accuracy directly evaluated conventional oral examination plus vital rinsing versus conventional oral examination alone. There were no eligible studies evaluating light-based detection or blood or salivary sample analysis (which tests for the presence of biomarkers for OPMD and OSCC). Only one study of conventional oral examination was judged as at overall low risk of bias and overall low concern regarding applicability. Given the clinical heterogeneity of the included studies in terms of the participants recruited, setting, prevalence of the target condition, the application of the index test and reference standard, and the flow and timing of the process, the data could not be pooled within the broader categories of index test. For conventional oral examination (10 studies, 25,568 participants), prevalence in the test accuracy sample ranged from 1% to 51%. For the seven studies with prevalence of 10% or lower, a prevalence more comparable to the general population, the sensitivity estimates were variable, and ranged from 0.50 (95% confidence interval (CI) 0.07 to 0.93) to 0.99 (95% CI 0.97 to 1.00); the specificity estimates were more consistent and ranged from 0.94 (95% CI 0.88 to 0.97) to 0.99 (95% CI 0.98 to 1.00). We judged the overall certainty of the evidence to be low, and downgraded for inconsistency and indirectness. Evidence for mouth self-examination and remote screening was more limited. We judged the overall certainty of the evidence for these index tests to be very low, and downgraded for imprecision, inconsistency, and indirectness. We judged the evidence for vital rinsing (toluidine blue) as an adjunct to conventional oral examination compared to conventional oral examination to be moderate, and downgraded for indirectness as the trial was undertaken in a high-risk population. AUTHORS' CONCLUSIONS: There is a lack of high-certainty evidence to support the use of screening programmes for oral cavity cancer and OPMD in the general population. Frontline screeners such as general dentists, dental hygienists, other allied professionals, and community healthcare workers should remain vigilant for signs of OPMD and OSCC.

Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions.

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. 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 METHODS: 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. 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.

Oral cancer awareness among undergraduate dental students in Iran.

The aim of this study was to assess undergraduate dental students' knowledge about prevention and detection of oral cancer in Tehran University of Medical Sciences (TUMS). A validated questionnaire which tested oral cancer awareness and procedure was given to 3rd to 6th year students of the dental faculty of TUMS. A total of 165 students participated in this survey. As expected, students of the final years showed greater knowledge of risk factors and clinical features of the disease. This study highlights for consideration regarding improvement to undergraduate dental education.

Oral cancer awareness of undergraduate medical and dental students.

BACKGROUND: The incidence of oral cancer is increasing in the United Kingdom. Early detection of oral cancers makes them more amenable to treatment and allows the greatest chance of cure. Delay in presentation and/or referral has a significant effect on the associated morbidity and mortality. Lack of general medical practitioner and general dental practitioner oral cancer knowledge has been shown to contribute to delays in referral and treatment. The aim of this study was to investigate the oral cancer awareness of future general medical and general dental practitioners by assessing undergraduate medical and dental students' knowledge of prevention and early detection of oral cancer. METHOD: Questionnaires were delivered to undergraduate medical and dental students at the University of Dundee, assessing oral examination habits, delivery of advice on oral cancer risk factors, knowledge of oral cancer risk factors and clinical appearance, preferred point of referral and requests for further information. RESULTS: Undergraduate medical students were less likely to examine patients' oral mucosa routinely and less likely to advise patients about risk factors for oral cancer. Medical students identified fewer oral cancer risk factors. In particular alcohol use was identified poorly. Medical students also identified fewer oral changes associated with oral cancer. Erythroplakia and erythroleukoplakia were identified poorly. Medical students felt less well informed regarding oral cancer. 86% and 92% of undergraduate medical and dental students respectively requested further information about oral cancer. CONCLUSION: This study highlights the need for improved education of undergraduate medical and dental students regarding oral cancer.

Alcohol and oral cancer.

Alcohol, particularly when associated with tobacco use, has been recognized as an important risk factor for mouth cancer for almost 50 years. Together, they are associated with approximately 75% of upper aerodigestive tract cancers. However, intake of alcohol remains high in many countries. The rising incidence of oral cancer has prompted a revaluation of the role of alcohol (both alone and in partnership with other etiologic agents). In this article, the potential role of alcohol in the development of oral cancer is reviewed. In particular, the effect of alcohol on cellular structure and function is considered by reference to histologic and exfoliative cytologic studies of the oral epithelia. Alcohol may influence the proliferative cells by both intracellular (e.g., endocytosis) and intercellular (permeability) pathways. The carcinogenic exposure of the proliferating stem cells in the basal layer may be regulated through these pathways. Individual variation might help explain why oral cancer arises in some, but not in most, people who smoke and consume excess alcohol. Despite this finding, alcohol is strongly associated with the development of oral cancer and other upper aerodigestive tract cancers. Efforts to reduce this burden on the individual and society must be directed toward patient and professional education and research regarding (genetic) susceptibility.