Technologies Enable Early and Accurate Oral Cancer Detection

Dr. Camile Farah
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Traditional methods of visualization and detection of oral potentially malignant lesions (OPML) and oral squamous cell carcinoma (OSCC) involve a conventional oral examination (COE) with digital palpation. Currently, COE is the accepted method to assess the clinical characteristics of OPML under normal clinical light without the use of stains, light filters, or magnification. However, evidence indicates that COE is a poor discriminator of oral mucosal lesions.

Many optical adjuncts have been developed to assist the clinician to better visualize and detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. Characteristics that should be noted include changes in color, texture, and ulceration and the presence of a persistent swelling. Studies have shown that an annual oral examination carried out by a primary care dentist can detect mucosal abnormalities that are unknown to the patient.

Devices utilizing the principles of tissue reflectance, tissue auto-fluorescence, or reflectance spectroscopy have been commercialized as adjunctive aids to COE for the detection of OPML and OSCC, although these devices are equally helpful in determining the nature of other benign mucosal pathology such as oral lichen planus, pigmented lesions, and vascular lesions once the clinician fully understands the basic principles of their use.

Although a common feature of these devices is their ease of use, a common unappreciated problem with them is the skill required on behalf of the clinician to interpret their findings, particularly for those devices utilizing fluorescence or spectroscopy approaches.

Reflectance

Oral mucosal examination has traditionally been undertaken under incandescent yellow light of often inadequate intensity, mounted on an extension arm attached to a dental chair. Anyone who has used a white LED headlight would confirm that the traditional manner of oral examination is ineffective for proper visualization of oral mucosal surfaces and mucosal pathology.

The best way to currently undertake a comprehensive head and neck examination is with the use of white LED light, preferably with some form of magnification (typically up to 2.5) with the use of loupes. This enhances both illumination and magnification, resulting in a superior oral examination and an increased opportunity to visualize and detect lesions, improving the net gains from the examination as well as patient care several-fold.

A good example of this combination is Orascoptic’s HiRes 2 (2.5x) loupes and Discovery headlight. This combination is closely comparable to more advanced and expensive imaging modalities used by otolaryngologists and head and neck surgeons in tertiary care facilities. Another device that also enhances oral mucosal surfaces is AdDent’s battery operated intraoral LED Microlux DL trans-illuminator with diffused light attachment.

Fluorescence

Next-level optical adjuncts take advantage of the oral mucosa’s fluorescent characteristics and how they change under different pathological conditions. Devices such as LEDDental’s VELscope, DentalEZ’s Identafi, Forward Science’s OralID, and AdDent’s Bio/Screen all operate by emitting violet or blue excitation light at 405 to 450 nm.

In the case of VELscope, OralID, and Bio/Screen, which emit blue light, normal oral mucosa is associated with a pale green fluorescence when viewed through a filter, whereas abnormal tissue is associated with loss of auto-fluorescence, also known as fluorescence visualisation loss, and appears dark. In the case of Identafi, which emits violet (405 nm) light, normal oral mucosa appears blue when viewed through a filter whereas abnormal tissue presents with a dark purple hue.

Auto-fluorescence is a phenomenon whereby an extrinsic light source is used to excite endogenous fluorophores such as certain amino acids, metabolic products, and structural proteins. The fluorophores absorb photons from the exogenous light source and emit lower-energy photons that present clinically as fluorescence. Each fluorophore is associated with specific excitation and emission wavelengths.

Assessment of oral mucosal pathology utilizing fluorescence-based optical adjuncts should always occur after a white light examination, as undertaking an auto-fluorescence examination without first noting any soft tissue changes with white light will result in a significant number of false positives and undue referral for biopsy of tissues. In fact, a specific decision-making protocol should be adopted to avoid false positive findings and to enhance the utility of these devices in general dental practice.

It should be remembered that vascular, haemorrhagic, and pigmented lesions in addition to areas of exogenous staining such as amalgam tattoos will all lose auto-fluorescence. Applying pressure to the lesion, known as diascopy, can help determine if the lesion is vascular or inflammatory, as both these lesion types will blanch under pressure, whereas haemorrhagic lesions such as petechia or purpura and foreign bodies such as amalgam will not.

Spectroscopy

Lastly, devices that utilize reflectance spectroscopy such as the Identafi and Narrow Band Imaging (NBI) from Olympus Medical Systems can enhance the underlying vasculature in the mucosa and provide additional information regarding the vascular or inflammatory nature of the lesion in question. For example, NBI is an endoscopic optical imaging enhancement technology that improves the contrast of the mucosal surface texture and mucosal and submucosal vasculature.

Utilizing the principle that different wavelengths of light will penetrate at different depths, the technology filters white light to emit a pair of 30-nm narrow bands of blue and green light simultaneously. The blue light centred at 415 nm corresponds to the main peak absorption spectrum of haemoglobin and penetrates the superficial mucosal layer, whereas blood vessels in the deeper mucosal and submucosal layers are visible due to the deeper penetration of the green light centred at 540 nm. NBI is restricted to specialist and tertiary referral centers primarily due to the level of training required, high cost, large size, and limited portable capacity of the NBI equipment.

In contrast, Identafi is the only handheld intra-oral commercially available device that can provide additional information garnered from reflectance spectroscopy utilizing a green-amber light at 545 nm. Identafi is a multispectral screening device that incorporates 3 different lights that are designed to be used in a sequential manner to facilitate intraoral examination.

In addition to an LED white light, Identafi includes violet and green-amber lights to induce direct tissue fluorescence and tissue reflectance, respectively. By integrating tissue fluorescence and tissue reflectance into one tool, Identafi aims to be an easy-to-use device maximizing the advantages of both white light examination and tissue fluorescence.

When using this device, it is essential that the clinician follow the manufacturer’s light sequence of white, violet, and green-amber to avoid false positive findings and to sequentially add clinical value to the oral examination by assessing color, texture, and ulceration under white light, loss of autoflorescence and diascopy under blue/violet light, and then the vascular and inflammatory nature of the lesion under green-amber light.

By doing this, clinicians will either include or exclude various abnormalities or pathologies in their differential diagnosis list and then consider the findings of all the lights collectively. Clinicians should remember to always interpret the clinical and optical findings as a whole and not in isolation.

Optical adjuncts are effective in assisting with the detection of oral mucosal abnormalities, though further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions.

Camile Farah is professor of oral oncology, head of the School of Dentistry, and director of the Oral Health Centre of WA at the University of Western Australia. He is a registered specialist in both oral medicine and oral pathology with subspecialty training in oral oncology, and he is director of the Australian Centre for Oral Oncology Research & Education, where he undertakes clinical and translational research into head and neck cancer early detection, molecular diagnostics, and imaging. He has written 125 peer reviewed publications including 10 book chapters and has attracted approximately $5 million in competitive research funding. His research interests in oral oncology span optical imaging systems (optical fluorescence imaging and narrow-band imaging), molecular genomics (next-generation sequencing), and clinical trials in early cancer detection and surgical margin delineation. He can be reached at camile.farah@uwa.edu.au.

Disclosure

Professor Farah has undertaken research on Vizilite, Microlux, VELScope, Identafi, Orascoptic, Narrow Band Imaging, and Bio/Screen but has no personal or commercial relationships with the products, their manufacturers, or their distributors that may bias the opinion provided in this article.

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