Early diagnosis

The quality of life during and after cancer treatment has steadily improved but survival rates from OSCC have barely increased. The stage at which mouth cancer is diagnosed has a significant effect on overall survival. Early diagnosis reduces mortality and also minimises:

? Morbidity

? Disfigurement

? Poor quality of life

? Treatment duration

? Costs

However, most cancers are found at a late stage, when larger than 2cm. Indeed, about 60 per cent of patients with OSCC present with  uch late stage (stages III and IV) disease. Referral delays are associated with a three-fold increase in mortality. Delays in  iagnosis can lead to patients having more advanced stages of cancer, especially when delay is more than a month.

The  stage at which cancer is diagnosed has significant effect on overall survival and quality of life thus while localised cancer  confined to primary site) and small tumours (stage I: <2cm), have="" ~90="" per="" cent="" two-year="" survival="" rate,="" most="" cancers="" are="" found="" at="" a="" late="" stage,="" larger="" than="" 2cm="" (stages="" iii="" and="" iv)="" disease="" –="" when="" survival="" is="" about="" one="" half="" as="" good.="" late="" stage="" diagnosis="" is="" mainly="" because="" of="" a="" lack="" of="" patient="" awareness="" related="" to="" socio-economic="" status/education="" or="" cognitive="" function,="" not="" because="" oscc="" is="" hard="" to="" discover.="" opportunistic="" screenings="" would="" yield="" earlier="" discovery="" by="" healthcare="">

Early diagnosis is thus the most important factor for improving patient survival, since rates as high  as 80-90 per cent may be achievable. Early diagnosis also minimises the extent of treatment required.

 

 

 

Genetic changes in the upper aerodigestive tract mucosae are found in about 20 per cent, especially in those who use tobacco. Second primary tumours (SPTs) may occur or develop, especially in the lungs.

 

A conventional oral examination (COE) with white light (‘incandescent light’) (visual and palpation examination) still constitutes the gold standard for the diagnosis of oral precancer and cancer. There is no doubt that education improves the diagnostic skills and that experience counts. The main challenges are in prognosticating in potentially malignant lesions, and in deciding what to do about early lesions. A biopsy is mandatory to confirm any diagnosis of cancer. Informed consent is mandatory for biopsy as for all operative procedures, particularly noting the likelihood of post-operative discomfort, the possibility of bleeding or bruising, and any possible less-transient adverse effects such as post-operative reduction or loss of sensation. Care must be taken not to produce undue anxiety.

Biopsy is generally best performed by a specialist. Some specialists take several biopsies, and some advise that the biopsy should be done by the surgeon. Importantly there is a need to identify the site in the lesion most at risk: a non-representative biopsy may delay diagnosis. If adequate specimens and clinical data are provided by the clinician, the pathologist can perform optimally. However, even then, the best pathologists can still err, and it is important to repeat or challenge negative results if clinically suspicious of malignancy. In any potentially malignant lesion there might be a range of cells present of different malignant potential, including some that cross the epithelial basement membrane – defining the lesion as cancer.

The histopathological interpretation of a biopsy from such a lesion could thus vary from benign to malignant, depending on the site biopsied, the histopathologists acumen, and other factors. Total reliance on a biopsy result therefore, could be fraught. Indeed, more than 25 years ago, one study showed that oral leukoplakias which were non-dysplastic upon incisional biopsy, proved in around 10 per cent of cases to contain cancers on excision of the leukoplakias. Similar findings have been reported by other investigators.

As a general rule, the biopsy should include lesional and normal tissue. Perhaps the most difficult and important consideration is which part of the lesion should be included in the biopsy specimen. Any red area should ideally be included in the specimen and, in some potentially malignant lesions where no obvious site can be chosen, vital staining with ‘toluidine blue’ may first be indicated. Suspect areas absorb the dye preferentially and stain a deep blue.

Another consideration is whether to use a scalpel or a biopsy punch. When a scalpel is used, a specimen of elliptical shape is usually taken, most commonly from an edge of the lesion, and suturing is usually needed. The punch has the advantage that the incision is more controlled, an adequate specimen is still obtained (typically 4mm or 6mm diameter) and suturing may not be required.

Complete the histopathology request form with the:

? patient’s details (full name, hospital or clinic number, date of birth, and so on),

? date, clinic location and requesting clinician’s name,

? site of biopsy (diagrams can be useful),

? clinical résumé photographs may help),

? provisional diagnosis and dates and numbers of all previous biopsies.

The biopsy specimen container must be labeled clearly with the:

? patient’s details as above,

? date and time of the procedure, and

? specimen site.

 

A range of diagnostic aids is appearing on the market, or in the scientific literature, and this includes:

? Vital (toluidine blue) staining

? Exfoliative cytology/brush biopsy

? Autofluorescence spectroscopy/imaging

? Chemiluminescent illumination

? Narrow band imaging

? Confocal microscopy

Analysis of the evidence of adequacy of diagnostic aids has shown that there is insufficient evidence that:

? commercial devices based on autofluorescence enhance visual detection beyond a conventional visual and tactile examination,

? commercial devices based on tissue reflectance enhance visual detection beyond a conventional visual and tactile examination,

? can assess the validity of transepithelial cytology of seemingly innocuous mucosal lesions.

 

Vital staining using the dye toluidine (tolonium) blue has been available for at least 50 years but is insufficiently specific or sensitive- a problem faced by virtually all such ‘aids’. Toluidine blue staining in future may be combined with LOH studies, discussed previously, which have shown:

? Low risk - heterozygosity for chromosome 9p

? Intermediate risk - LOH for 9p alone or LOH 9p plus either LOH for 17p or LOH for 4q

? High risk - LOH for 9p, 17p, and 4q

 

This technique of transepithelial cytology is also insufficiently specific or sensitive but in future may be used with modern techniques such as DNA Image Cytometry (DNAICM), DNA analysis (aneuploidy), MALDI-ToF MS (Matrix-Assisted Laser Desorption/Ionisation Time of Flight Mass Spectrometry) or Peptidome profiling.

 

Autofluorescence spectroscopy/ imaging is available as:

? DentLight Oral Examination (DOE)

? Sapphire plus

? VELscope

Early studies suggest promise in this area.

 

Meantime, conventional oral examination (COE) plus biopsy, despite limitations, remains the gold standard. Therefore, to increase the chance of early diagnosis, it is important for yearly examinations to be carried out by a clinical dental professional. The patient should be aware of what is normal for them, keep an eye out for any changes, and seek advice from a dentist or clinical dental professional or GP if they suspect anything out of the ordinary. Failure to diagnose oral cancer is the second highest cause of dental malpractice in USA, with awards upwards of $1m.

References available on request.