Elsevier

Oral Oncology

Volume 44, Issue 1, January 2008, Pages 10-22
Oral Oncology

Review
Critical evaluation of diagnostic aids for the detection of oral cancer

https://doi.org/10.1016/j.oraloncology.2007.06.011Get rights and content

Summary

Historically, the screening of patients for signs of oral cancer and precancerous lesions has relied upon the conventional oral examination. A variety of commercial diagnostic aids and adjunctive techniques are available to potentially assist in the screening of healthy patients for evidence of otherwise occult cancerous change or to assess the biologic potential of clinically abnormal mucosal lesions. This manuscript systematically and critically examines the literature associated with current oral cancer screening and case-finding aids or adjuncts such as toluidine blue, brush cytology, tissue reflectance and autofluorescence. The characteristics of an ideal screening test are outlined and the authors pose several questions for clinicians and scientists to consider in the evaluation of current and future studies of oral cancer detection and diagnosis. Although the increased public awareness of oral cancer made possible by the marketing of recently-introduced screening adjuncts is commendable, the tantalizing implication that such technologies may improve detection of oral cancers and precancers beyond conventional oral examination alone has yet to be rigorously confirmed.

Introduction

Oral cancer is traditionally defined as squamous cell carcinoma of the lip, oral cavity and oropharynx. At current rates, approximately 30,000 cases in the United States and more than 400,000 cases worldwide will be diagnosed in 2007, making it the sixth most common malignancy in the world.1, 2 Despite numerous advances in treatment, the 5-year survival has remained approximately 50% for the last 50 years.3 This poor prognosis is likely due to several factors. First, oral cancer is frequently associated with the development of multiple primary tumors. The rate of second primary tumors in these patients, 3–7% per year, is higher than for any other malignancy.4 This characteristic led Slaughter to propose that multiple individual primary tumors develop independently in the upper aerodigestive tract as a result of chronic exposure of the lining mucosal epithelium to carcinogens, a theory known as “field cancerization”.5 Although this theory is not accepted by all authorities, oral cancer patients who live five years after their initial primary disease is diagnosed and treated have up to a 35% chance of developing at least one new primary tumor during that time. To underscore the significance of this complication, the most common cause of treatment failure and death in oral cancer patients is their second primary tumor.6 Second, poor survival among oral cancer patients can also be attributed to the advanced extent of the disease at the time of diagnosis, with over 60% of patients presenting in stages III and IV. Such dismal statistics seem perverse since the disease primarily arises in the surface oral epithelium that is readily accessible to direct visual and tactile examination. The conclusion that at least some lesions are ignored or missed by patients, health care professionals or both is inescapable. In part, this may be due to an incomplete understanding or awareness that even small asymptomatic lesions can have significant malignant potential.

One approach to this problem would be to improve the ability of oral health care professionals to detect relevant potentially malignant lesions or cancerous lesions at their earliest or most incipient stage. Such a goal could be achieved by increasing public awareness about the importance of regular oral screening or case finding examinations to identify small, otherwise asymptomatic cancers and precancers (secondary prevention). Another strategy would be the development and use of diagnostic aids that could help the general dentist or dental specialist more readily identify or assess persistent oral lesions of uncertain biologic significance. This paper will examine the role of screening examinations in oral cancer and evaluate the literature regarding currently available diagnostic tests or techniques that are purported to aid in the detection and diagnosis of cancerous and precancerous lesions.

Section snippets

Screening

Screening for disease has a precise definition and implies an ongoing, structured health care intervention designed to detect disease at an asymptomatic stage when its natural course can be readily interrupted if not cured. It has been defined as: ‘the application of a test or tests to people who are apparently free from the disease in question in order to sort out those who probably have the disease from those who probably do not’.7 The important factor is that screening involves checking for

Criteria for screening and for screening tests

Because of the cost implications and the potential for over-diagnosis (false positive result), strict criteria are needed to evaluate screening programs and to determine their appropriateness. In the UK for example, the National Screening Committee lists 22 criteria that should be met before a screening program is introduced.8 These were originally taken from the work of Wilson and Jungner,7 and are summarized in Table 1. Since oral cancer meets at least three of these criteria, screening

Current oral cancer screening or case-finding tests

Among the screening tests or diagnostic aids now available for oral cancer, some have been used and studied for many years while others have recently become commercially available (Table 4). Screening or case-finding tests should always be evaluated with respect to their sensitivity, specificity and predictive values (Fig. 1). Such analysis requires that the test outcome from a sample of subjects be compared to the results of an appropriate gold standard on the same population. The gold

Tissue reflectance (ViziLite Plus, MicroLux DL)

Tissue reflectance has been used for many years as an adjunct in the examination of the cervical mucosa for “acetowhite” premalignant and malignant lesions. Recently, this form of tissue reflectance-based examination has been adapted for use in the oral cavity and is currently marketed under the names ViziLite Plus and MicroLux DL. These products are intended to enhance the identification of oral mucosal abnormalities. With both systems, the patient must first rinse with a 1% acetic acid

Summary

Screening and early detection in populations at risk have been proposed to decrease both the morbidity and mortality associated with oral cancer.17, 18 However, the visual detection of premalignant oral lesions has remained problematic throughout the world. This is in stark contrast to skin lesions such as melanoma, where visual screening has been shown to have sensitivity and specificity rates of 93 and 98%.15, 16 One explanation for this discrepancy is that early lesions of oral cancer and

Conflict of interest statement

None declared.

Acknowledgement

This work was supported in part by the NIH grant DE015830 (MWL).

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