Oral Cancer

Diagnosis

How do we recognise oral cancer?

Early diagnosis of oral cancer lies mainly in the hands of primary dental care professionals. However, patients with oral cancer symptoms may present to a medical practitioner and family physicians should therefore be aware of the anatomy, including normal structures of the oral cavity and abnormal signs that indicate cancer.

Let us now consider:

  1. How to examine thoroughly the oral soft tissues

  2. The role of those working in primary care

  3. Using detecting systems to aid early detection

  4. Undertaking a biopsy to confirm diagnosis

Thorough Systematic Examination of All Oral Soft Tissues

A thorough systematic examination is mandatory every time a dentist sees one of his or her patients. This shall include palpation of the neck and visual examination of the mouth mucosa.  A routine which is comprehensive, effective and should not take more than three minutes to perform, is illustrated here (Figures 30-39).

Screening of the oral mucosa is most effective if a systematic examination procedure is followed. The system described here is quick and easy to use. It minimises the risk of missing any particular area of oral mucosa that could harbour an asymptomatic risk lesion.

When perfected, the time taken for a routine mucosal examination is less than three minutes.

Two mouth mirrors are preferable when retracting the tissues. A piece of gauze is used to retract the tongue. This visual inspection should be supplemented by palpation with a gloved finger of any suspicious area.

The examination should commence with a general appraisal of the well-being of the patient on entering the surgery. If the patient is wearing dentures request that these be removed and placed in a small bowl.

Observe the face for asymmetry, swellings, skin blemishes, moles and pigmentation.

Palpate lymph nodes of face and neck (Figure 30).

Examine the vermilion border of the lips and corners of the mouth, note any change in colour and texture (Figure 31).

Examine the labial mucosa and sulcus with the mouth half open (Figures 32a and 32b).

With the mouth open wide, retract the cheek on one side and examine the colour and texture of the buccal mucosa (Figures 33a and 33b). Repeat this sequence for the other side of the mouth.

Then, with the mouth half open, observe the maxillary and mandibular sulci (Figures 34a and 34b). Repeat this sequence for the other side of the mouth.

Inspect the tongue at rest and protruded (Figure 35). Note any aberrations in colour, texture, distribution of papillae, symmetry or mobility.

To facilitate inspection of the lateral borders, hold the tip of the tongue with a gauze square and move it to one side, whilst also retracting the cheek to the opposite side (Figures 36a and 36b). Repeat for the other side of the tongue.

Examine the floor of the mouth and ventral surface of the tongue with the tip of the tongue raised to the palate (Figure 37).

Depress the tongue and inspect the hard and soft palate (Figure 38).

Request the patient to say “Ah” and examine the pillars of the fauces, tonsils, uvula and oropharynx (Figure 39).

Finally, palpate any abnormal areas noted in your visual inspection.

If any oral mucosal disorder is found during the visual screening examination, it is essential that the examination is extended to include palpation of the area of concern.

On palpation, if the practitioner feels an abnormal hardening of tissue this is referred to as “induration”. This is a cardinal sign of malignancy. Along with visual features noted (a lump, an ulcer or redness) presence of induration points towards reasonable suspicion that the area concerned needs further urgent investigation. Where there is a suspicion of malignancy, the regional lymph nodes must be palpated.

The findings should be noted in the clinical notes  and the area of suspicion marked on a mouth map.

Upon  clinical examination, the clinician should request an urgent hospital appointment for any patient who presents with a lesion which is suspected of malignancy, or having noted an enlargement or hardness of regional lymph nodes.

Fig30

Figure 30. Examination should include palpitation of the lymph nodes

Fig31

Figure 31. Examine the lips and corners of the mouth, noting any changes

Fig32a

Figure 32a. Examine the upper and lower labial mucosa; note the use of two mirrors

Fig32b

Figure 32b. Examine the upper and lower labial mucosa; note the use of two mirrors

Fig33a

Figure 33a. Examine the buccal mucosa; note the use of two mouth mirrors

Fig33b

Figure 33b. Examine the buccal mucosa; note the use of two mouth mirrors

Fig34a

Figure 34a. Examine the maxillary and mandibular sulci; note the use of two mouth mirrors

Fig34b

Figure 34b. Examine the maxillary and mandibular sulci; note the use of two mouth mirrors

Fig35a

Figure 35. Examine the tongue; note the use of gauze to help examine the lateral borders

Fig35b

Figure 36a. Examine the tongue; note the use of gauze to help examine the lateral borders

Fig35c

Figure 36b. Examine the tongue; note the use of gauze to help examine the lateral borders

Fig37

Figure 37. Examine the floor of the mouth and ventral surface of the tongue

Fig38

Figure 38. Inspect the hard and soft palate

Fig39

Figure 39. Inspect the pillars of the faces, tonsils, uvula and oropharynx

Guidelines for referral are given in the referral guide. A referral form for oral mucosal lesions may be downloaded from the resources section of this website. This may be printed and used as a referral pro-forma.

Carrying out a biopsy is a skillful procedure.  If the dentist is experienced in undertaking a biopsy this may be done in the dental practice.  While in some European countries, this is standard practice, in the UK a dentist would refer the patient to a specialist.

Early Detection: Primary Care Roles

As seen in previous sections, the prevention and early diagnosis of oral cancer lies mainly in the hands of primary dental care professionals:

  • Dentists are important in early detection through opportunistic screening and planned invitational screening of populations at high risk.

  • Physicians can attempt a targeted approach on high risk subjects (smokers and heavy alcohol drinkers, see causes), directing them for regular check-ups by a local dental practitioner.

  • Dental hygienists should bring to the attention of the supervising dentists any suspicious lesions they might notice during hygiene visits.

  • Receptionists in dental practices can help allay the fears of those seeking opinions and encourage them to attend the dentist.

  • Pharmacists should encourage people requesting over-the-counter medications for a mouth ulcer that persists for longer than 2 weeks to immediately ask their general practitioner or dentist for an opinion.

Using Detecting Systems to Aid Early Diagnosis

Thorough visual and digital examination of all the oral soft tissues, along with the careful examination of the head and neck for enlarged cervical lymph nodes, followed by biopsy of suspicious areas, remains the mainstay of diagnosis.

Adjuncts to conventional methods of visual detection include:

  • Toluidine blue test

  • Brush biopsy

  • Autofluorescence

  • Chemiluminescence

How useful is toluidine blue?

Figure 40. A distinctive lesion in an area of atrophic mucosa

Figure 40. A distinctive lesion in an area of atrophic mucosa

Figure 41. Dye taken up by the area, which on biopsy showed epithelial dysplasia

Figure 41. Dye taken up by the area, which on biopsy showed epithelial dysplasia

The use of toluidine blue dye as a mouthwash or topical application has been tried as an aid to the diagnosis of oral cancer and potentially malignant lesions. It certainly has a place, with appropriate training, in screening high-risk subjects and in helping to define the site for biopsy.

Figure 40 shows an area of altered mucosa with a speckled leukoplakia (erythroplakia). Figure 41 shows that the mucosa took up the dye which proved, on biopsy, to show epithelial dysplasia. This indicated an increased risk of progressing to malignancy if untreated.

The FDI Commission, through its report after Project on Oral Cancer, has agreed a statement on the use of toluidine blue, supporting its use in appropriately experienced hands, and urging further research on its clinical utility in primary care settings.

FDI Statement – Toluidine Blue Mouthwash

1% Toluidine Blue Mouthwash is being promoted as an adjunct to oral cancer diagnosis – for use on high-risk individuals and explicitly not as a tool for population screening.

The sensitivity and specificity of toluidine blue as a test for early detection of oral cancer is adequate. However, the sensitivity and specificity are given for both overtly malignant lesions and potentially malignant lesions (particularly severe epithelial dysplasia) under the umbrella oral cancer. Although 100% of cancers may stain, most studies show that only 50% to 70% of dysplasias are detected by this technique.

The use of toluidine blue in expert and experienced hands is recommended in clinical practice:

  1. In the monitoring of suspicious lesions over time

  2. In the follow-up of patients already treated for upper aero-digestive tract cancer

  3. In helping to determine an optimal site for biopsy when a suspicious lesion or condition is present; and

  4. Intra-operatively during surgery of upper aero-digestive tract malignancy

For further research in primary care:

  • In screening for oral mucosal malignancy and potentially malignant lesions in high risk individuals and population groups

For clinicians in primary care settings, specific training is required for correct application of the test and correct interpretation of the results. Toluidine blue shall not be considered a replacement for a detailed visual and digital examination. It is an extra tool for the identification of patients who should be referred to specialists or centres experienced in the diagnosis and treatment of oral cancer and potentially malignant lesions or conditions.

Brush Biopsy

Figure 42. Brush biopsy sample

Figure 42. Brush biopsy sample

Figure 43. Brush biopsy analysis

Figure 43. Brush biopsy analysis

A transepithelial biopsy obtained using a Cytospin brush (Figures 42 & 43) has been advocated for reporting on cellular atypia by computer assisted diagnosis.

A few false negative cases have been reported probably due to sampling errors.

Brush biopsy samples transported in a liquid medium could also be used for ploidy analysis.

Autofluoresence

The presence of cellular alterations will change the concentrations of fluorophores, which affect the scattering and absorption of light in the tissue, thereby resulting in change in colour that can be observed visually. The potential application of fluorescence visualisation as an adjunctive tool in identifying high-risk lesions has recently been investigated by us at King’s College London (Awan et al., 2011).

Figure 44. A suspect area on the right soft palate. The toluidine blue stain is equivocal.

Figure 44. A suspect area on the right soft palate. The toluidine blue stain is equivocal.

Figure 45. The same area examined with fluorescence visualisation that showed a positive area. Biopsy revealed severe dysplasia.

Figure 45. The same area examined with fluorescence visualisation that showed a positive area. Biopsy revealed severe dysplasia.

Visually Enhanced Lesion Scope (VELscope) is a hand held device that is based on the direct visualization of tissue fluorescence and the changes in fluorescence that occurs when abnormalities are present. The VELscope hand-piece emits a safe blue light into the oral cavity, which excites the tissue from the surface of the epithelium through to the basement membrane and into the stroma beneath, causing it to fluoresce. The clinician is then able to immediately view the different fluorescence responses and the manufacturer claims that this tool helps to differentiate between normal and abnormal tissue. Typically, healthy tissue appears as a bright apple-green glow while suspicious regions are identified by a loss of fluorescence, which thus appear dark.

Figure 45 shows loss of fluorescence in a suspect area when an exciting light wave is applied using a fluoroscope. The same area stained with toluidine blue produced an equivocal result.

Figure 44 and 45 Copyright 2002-2003 Oral Health Study, Oral Oncology/Dentistry, BCCA

Chemiluminescence

Chemiluminescence was developed for use in detecting abnormal growths on the uterine cervix. The technique has been adapted for use in the oral cavity with the development of two hand held devices, namely ViziLiteTM & MicroLux/DLTM system. These devices function under the assumption that mucosal tissue undergoing abnormal metabolic or structural changes have different absorbance and reflectance profiles when exposed to various forms of light sources – as a result enhancing the identification of oral mucosal abnormalities.

Figure 46. An area of keratosis observed with ViziLite following an acetic acid rinse. Under ViziLite the area appears bright and sharp demarcating the white plaque and making it more visible.

Figure 46. An area of keratosis observed with ViziLite following an acetic acid rinse. Under ViziLite the area appears bright and sharp demarcating the white plaque and making it more visible.

The ViziLite & MicroLux/DLTM systems involve an oral rinse with 1% acetic acid solution for 1 minute to help remove surface debris and slightly desiccate the oral mucosa. This is followed by direct visual examination of the oral cavity using the chemiluminescent blue-white light stick with an average wavelength of 490 to 510 nm. Normal cells absorb the illumination and appear lightly bluish, whereas abnormal cells within a white patch reflects the illumination and appear “aceto-white” with brighter, sharper, more distinct margins (Figure 48). The technique gives more reliable results, when used to investigate “white lesions” compared to “red plaques”.

Combined devices

ViziLite Plus consists of the ViziLite used as an adjunct with chemiluminescent blue-white light as described above and a swab with Toluidine blue. The advantage of the combined system is that the practitioner can apply the dye to ViziLite-identified oral lesions to assist with further evaluation and tissue sampling.

Identafi® uses multi-spectral fluorescence and reflectance technology providing a tool that emits white, violet, and green-amber wavelengths of light to excite oral tissue. First, white light is used for tissue visualization. Then, violet light is used to enhance the fluorescence of normal tissue allowing for stronger contrast relative to abnormal tissue. Finally, green-amber light is used to evaluate vascularity. This is a new tool and more research is needed on its utility in primary care. However, the multi functional elements are attractive.

Biopsy

A diagnostic biopsy is indicated for any mucosal lesion suspected of cancer, particularly for any ulcer or growth that persists for more than 3 weeks following the elimination of local factors. An inadequately performed biopsy may complicate patient care and result in delay in the care pathway.

Several biopsy techniques are available; the choice of biopsy is based on the size and location of the mass and the experience of the surgeon. Incisional biopsy is preferred and excisional biopsy is indicated only for small, superficial masses (<1 cm in greatest dimension), in which the probability of malignancy is low. During biopsy a generous wedge of tissue is removed, with minimal manipulation of tissue. Several important technical factors must be considered while performing an incisional biopsy. The incision should be oriented along the long axis, avoiding necrotic or grossly ulcerated areas and should include deeper tissue preferably including muscle. It is important that an incisional biopsy is of sufficient size and depth to include part of the advancing front of the tumour. Ideally, the deep front should be included, but if not, as in large tumours, the peripheral (lateral) front is often sufficiently representative to allow provisional assessment.

A biopsy of a carcinoma enables histologic grading based on tumour differentiation, an important prognostic factor in squamous cell carcinoma and if deep enough in assessing infiltrative margins.

A biopsy of a white or red patch enables the pathologist to exclude an early malignancy, and if dysplasia is present to grade the dysplasia.

This is the end of the Diagnosis module, please select the next module to continue through the guide.

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