Detection
Screening
Medical history sheets which include lifestyle questions and soft tissue assessment charts can save a lot of time for dentists. Mouth maps will help with soft tissue monitoring. It will also help to flag up patients who are ‘at risk’ as shown on their records.
  • History and physical examination. Includes risk factor analysis and exposure to carcinogens.
  • Head and neck examination: Direct visualization, mirror examination, manual palpation and toluidine blue staining.
  • Laboratory tests: CBC liver function.
  • Radiology: CT or MRI of head and neck, chest X-ray, dental films, bone scan when indicated.
  • Pathology: Incisional biopsy, excisional biopsy, fine needle aspiration biopsy, molecular markers, flow cytometry.
  • Panendoscopy: T- stage schematic tumour map, evaluate for second malignancies.
  • Pre-therapy consultation with: Radiation oncology, medical oncology, head and neck surgery, reconstructive surgery, dental oncology, speech pathology and psychosocial service.
  • Multidisciplinary Tumour Board: Finalize staging and formulate treatment plan.

Screening is the process by which practitioner evaluates an asymptomatic patient to determine if he or she is likely or unlikely to have a potentially malignant or malignant lesion. This can be done by a conventional oral examination.

Conventional/Routine Oral Examination
To ensure completeness, a soft tissue examination needs to follow a pattern. Work out a logical sequence and then stick to it. Since your first step will be a general appraisal of the patient’s well-being, it could make sense to start with soft tissues, before moving on to examination of the teeth and gums. But this is a personal choice - carry out the examination in an order that you are comfortable with and that you find easy to explain to the patient. Use gloved fingers or preferably, two mouth mirrors to retract the tissues. The visual inspection should be supplemented by palpation of any suspicious area and the submandibular and cervical lymph nodes.
Any intraoral prostheses (dentures or partial dentures) are removed before starting the inspection. The extraoral and perioral tissues are examined first, followed by the intraoral tissues.
I. The Extra Oral Examination
  • Face: The extra-oral assessment includes an examination of the face, head and neck. The face, ears and neck are observed, noting any asymmetry or changes on the skin such as crusts,fissuring, growths and/or colour change. The regional lymph node areas are bilaterally palpated to detect any enlarged nodes and if detected, their mobility and consistency are checked. A recommended order of examination includes the preauricular, submandibular, anterior cervical or auricular and posterior cervical regions.
II. Perioral and Intraoral Soft Tissue Examination: The perioral and intra-oral examination procedure follows a seven-step systematic assessment of the lips; labial mucosa and sulcus; commissures, buccal mucosa and sulcus,gingiva and alveolar ridge, tongue, floor of the mouth and hard and soft palate.
  • Lips: Observe the lips with the patient's mouth both closed and open. Note the colour, texture and any surface abnormalities of the upper and lower vermilion borders.
  • Labial Mucosa: With the patient's mouth partially open, visually examine the labial mucosa and sulcus of the maxillary vestibule and frenum and the mandibular vestibule. Observe the colour, texture, and any swelling or other abnormalities of the vestibular mucosa and gingiva.
  • Buccal Mucosa: Retract the buccal mucosa. Examine first the right then the left buccal mucosa extending from the labial commissure and back to the anterior tonsillar pillar. Note any change in pigmentation, colour, texture, mobility and other abnormalities of the mucosa, making sure that the commissures are examined carefully and are not covered by the retractors during the retraction of the cheek.
  • Gingiva: First, examine the buccal and labial aspects of the gingiva and alveolar ridges (processes) by starting with the right maxillary posterior gingiva and alveolar ridge and then move around the arch to the left posterior area. Drop to the left mandibular posterior gingiva and alveolar ridge and move around the arch to the right posterior area. Second, examine the palatal and lingual aspects as had been done on the facial side, from right to left on the palatal (maxilla) and left to right on the lingual (mandible).
  • Tongue: With the patient's tongue at rest and mouth partially open, inspect the dorsum of the tongue for any swelling, ulceration, coating or variation in size, colour or texture. Also note any change in the pattern of the papillae covering the surface of the tongue and examine the tip of the tongue. The patient should then protrude the tongue and the examiner should note any abnormality of mobility or positioning.

    With the aid of mouth mirrors, inspect the right and left lateral margins of the tongue. Grasping the tip of the tongue with a piece of gauze will assist full protrusion and will aid examination of the more posterior aspects of the tongue's lateral borders. Then examine the ventral surface. Palpate the tongue to detect growths.

  • Floor: With the tongue still elevated, inspect the floor of the mouth for changes in colour, texture, swellings or other surface abnormalities.
  • Palate: With the mouth wide open and the patient's head tilted back, gently depress the base of the tongue with a mouth mirror. First inspect the hard and then the soft palate. Examine all soft palate and oropharyngeal tissues. Bimanually palpate the floor of the mouth for any abnormalities. All mucosal or facial tissues that seem to be abnormal should be palpated.
Early stage lesions often are asymptometric and may mimic other conditions, whereas others may not be readily evident in routine examination. Malignent and benign lesions may not be clinically distinguishable, the dentist cannot predict the biological relevance of lesions on the basis of physical features alone. The following screening aids assist dentist with the detection of early cancerous changes or for the assessment of the biological relevance of mucosal lesion.
1. Toluidine blue stain
Toluidine blue (also known as tolonium chloride) is a vital dye that may stain nucleic acids and abnormal tissues. It has been used for decades as an aid to the identification of mucosal abnormalities of the cervix as well as in the oral cavity. It has been valued by surgeons as a useful way of demarcating the extent of a lesion prior to excision. Toluidine blue has been used for several decades as a means of identifying clinically occult lesions in patients whose oral mucosa may otherwise be normal – that is, as a screening test or adjunct.
  • The topical application of toluidine blue to a suspicious area helps identify the presence of dysplastic or carcinomatous lesions. But to verify the premalignant status of an oral lesion a biopsy is required.
  • It may be that toluidine blue selectively stains for acidic tissue components and thus binds more readily to DNA, which is increased in neoplastic cells.
  • Toluidine blue has been recommended for use as a mouthwash or for direct application on suspicious lesions; its value comes from its simplicity, low cost, noninvasiveness and accuracy.
  • Clinicians can use toluidine blue to help select an appropriate biopsy site within a large lesion or monitor high-risk patients who have been previously diagnosed with a premalignant or malignant lesion.
  • Toluidine blue is an adjunct to biopsy, not a replacement for it.
2. Brush biopsy
The Brush Biopsy (CDx Laboratories, Suffren, NY) was introduced as a potential oral cancer case-finding device in 1999. It was designed for clinical lesions that would otherwise not be subjected to biopsy because the level of suspicion for carcinoma, based upon clinical features, was low. When an abnormal result is reported (atypical or positive), the clinician must follow-up with a scalpel biopsy of the lesion, as the use of brush cytology does not provide a definitive diagnosis.
3. Exfoliative cytology
A procedure to collect cells from the lip or oral cavity. A piece of cotton, a brush or a small wooden stick is used to gently scrape cells from the lips, tongue, mouth or throat. The cells are viewed under a microscope to find out if they are abnormal.
4. Chemiluminescence (reflective tissue fluorescence)
Chemiluminescence has been used for many years as an adjunct in the examination of the cervical mucosa for “acetowhite” premalignant and malignant lesions. Recently, this technology 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 percent acetic acid solution followed by direct visual examination of the oral cavity using a blue-white light source. ViziLite Plus uses a disposable chemiluminescent light packet, while the MicroLux unit offers a reusable, battery- powered light source. The 1 percent acetic acid wash is used to help remove surface debris and may increase the visibility of epithelial cell nuclei, possibly as a result of mild cellular dehydration. Under blue-white illumination, normal epithelium appears lightly bluish while abnormal epithelium appears distinctly white (acetowhite). ViziLite Plus also provides a tolonium chloride solution (TBlue), which is intended to aid in the marking of an acetowhite lesion for subsequent biopsy once the light source is removed.
5. Velscope
The Velcope is a portable device that allows for direct visualization of the oral cavity and is being marketed for use in oral cancer screening. Under intense blue excitation light (400 to 460 nm) provided by the unit, normal oral mucosa emits a pale green autofluorescence when viewed through the selective (narrow- band) filter incorporated within the instrument handpiece. Proper filtration is critical, as the intensity of the reflected blue-white light makes it otherwise impossible to visualize the narrow autofluorescent signal. In contrast, abnormal or suspicious tissue exhibits decreased levels of normal autofluorescence and appears dark by comparison to the surrounding healthy tissue.

Early-stage oral cancer can be cured, but most oral cancers generally spread to lymph nodes or other areas by the time they are found.

Top
Diagnosis
Early diagnosis is very important for prompt treatment and better prognosis of oral cancer.

Diagnostic aids for oral cancer:

  1. Imaging
    • Radiography
    • MRI
    • CT Scan
    • Ultrasound
  2. Histopathologic Diagnosis
    • Brush Biopsy
    • Scalpel Biopsy
      • Excisional biopsy
      • Incisional biopsy
      • Needle biopsy
      • Punch biopsy
    • Exfoliative cytology
  3. Biomarkers/Tumor Markers
I] Imaging of the Oral Cavity
Unlike many other malignancies, oral cancer can usually be seen with the naked eye. But as some cancers are located internally in the body, it makes their detection difficult. Different kinds of scanning options, determining the presence of tumours or growths detect malignancy, are necessary.

Imaging for oral cancer include:

  1. Radiographs
  2. MRI and CT Scans
  3. PET
  4. Ultrasounds
1. Radiographs: The dentist will take X- rays of the mouth and teeth to try and determine if anything irregular is visible on these photos and check for symptoms. Oral cancer tumors develop fairly quickly and can possibly grow, for example into the jaw bone. X- rays will help a doctor to find the growth. After that the best method of oral cancer treatment can be picked.
X-rays, can assist in determining the potential growth of a tumor into bone. Images of the chest and lungs can show whether cancer has spread to these areas.
2. MRI and CT Scans: A diagnostic imaging evaluation consisting of either computer tomography (CT) scanning or magnetic resonance imaging (MRI) to assesses the extent of local and regional tumor spread, the depth of invasion and the extent of lymphadenopathy. CT scan is superior in detecting early bone invasion and lymph node metastasis. MRI assesses the extent of soft tissue involvement and for providing a three-dimensional display of the tumor. MRI is also the preferred technique for imaging carcinoma of the nasopharynx or lesions involving paranasal sinuses or the skull base.
The diagnostic imaging often detects subsurface masses and intra-osseous definite lesion. Although imaging of pathologic lesions does not produce a diagnosis, it frequently helps to define the extent of the tumor. Both CT and MRI have its limitations as well as advantages. This fact frequently makes them complementary rather than competitive in studies.
3. PET [Positron Emission Tomography]: PET or Positron Emission Tomography, lets doctors display the body's actual metabolism. Since cells use a simple sugar- glucose, as a source of energy, PET can track down how much glucose is being metabolized in different areas of the body. Cancer cells divide rapidly, they break down glucose much faster than normal cells. The increased activity will show up on a PET scan to indicate both primary and metastatic tumors.
4. Ultrasound: Ultrasound is a diagnostic technique which uses high-frequency sound waves to create an image of the internal organs. Although less frequently used for oral cancer detection, ultrasonography is another way to produce pictures of an area in the body. This method involves high- frequency sound waves (ultrasound) bouncing off organs and tissues. The pattern of echoes produced by these waves creates a picture called a sonogram.
II] Biopsy
All cases of cancer must be diagnosed by removing a sample of tissue from the patient and sending it to a pathologist for examination. This procedure is called a biopsy, a Greek-derived word that may be loosely translated as "view of the living." Any organ in the body can be biopsied using a variety of techniques. The most common types include: (a) Excisional biopsy, where only a sample of tissue is removed; (b) Incisional biopsy, where an entire lump or suspicious area is removed and (c) Needle biopsy, where a sample of tissue or fluid is removed with a needle. The procedure is called a core biopsy when a wide needle is used and when a thin needle is used, the procedure is called a fine-needle aspiration biopsy.
Types of biopsy
a) Excisional biopsy: Here, a whole organ or a whole lump is removed (excised). This type of biopsy is less common now, since the development of fine needle aspiration. But, some types of tumours (such as lymphoma, a cancer of the lymphocyte blood cells) have to be examined whole to allow an accurate diagnosis. So, enlarged lymph nodes are good candidates for excisional biopsies. Some surgeons prefer excisional biopsies of most breast lumps to ensure diagnostic accuracy. Some organs, such as the spleen, are dangerous to cut into without removing the whole organ, so excisional biopsies are preferred for these.
b) Incisional biopsy: Only a portion of the lump is removed surgically in this case. This type of biopsy is most commonly used for tumours of the soft tissues (muscle, fat, connective tissue) to distinguish benign conditions from malignant soft tissue tumours, called sarcomas.
c) Needle biopsy: Fine Needle Aspiration Biopsy (FNA biopsy) is an extremely simple technique. A needle no wider than that typically used to give routine injections (about 22-gauge) is inserted into a lump (tumours) and a few tens to thousands of cells are drawn up (aspirated) into a syringe. These are smeared on a slide, stained and examined under a microscope by the pathologist, who can render a diagnosis in a few minutes. The procedure is called core biopsy when a wide needle is used.Tumours of deep, hard-to-get-to structures (pancreas, lung and liver) are especially good candidates for FNA. Otherwise, the only other way to sample them is with major surgery. Such FNA procedures are typically done by a radiologist under guidance by ultrasound or computed tomography (CT scan) and require not even local anasthesia. Thyroid lumps for one, are also excellent candidates for FNA.
d) Punch biopsy: The punch biopsy technique is typically used to sample skin tissues and small masses. After a local anesthetic is injected, a biopsy punch, which is basically a small (3 or 4 mm in diameter) version of a cookie cutter, is used to carve out a cylindrical piece of skin. The portion is typically closed with a suture and heals with minimal scarring.
e) Brush biopsy: Please refer "screening" for details.
III] Cytology
Under certain conditions, exfoliative cytology (cell scrapings) serves as an adjunct to clinical diagnosis, as it enables more extensive screening and provides microscopic material if there is a delay in or contraindication to biopsy. However, cytologic smears are used infrequently and patients are not treated on the basis of cytologic findings alone. Smears are most helpful in differentiating inflammatory conditions, especially candidiasis, from dysplastic or neoplastic surface lesions. In addition, cytology may be helpful in detecting field change in oral cancer, especially if this method is used in conjunction with vital staining. Cytology may also be helpful when ulcerations following radiation are suspicious and biopsy is delayed.
IV] Biomarkers/Tumourmarkers
This remains the most acceptable method for the definitive diagnosis. But it is invasive and cannot be used in high risk surgical patients. Studies have proved that any surgical invasiveness for oral cancer, including incisional biopsy, causes dissemination of cancer cells into circulation, resulting in increase risk of metastasis. There in lies the importance of tumor markers in the early detection of cancer since biochemical studies of serum is a non- invasive procedure, rapid and easy to perform.
Tumour markers are biological products synthesized or released by cancer cells or produced by host cells under the influence of tumour cells. An ideal tumour marker should differentiate cancer not only from healthy state (control) but also from benign/non-malignant and precancerous lesions and conditions.
A major goal in oral pathology has been the search for such markers of potential malignancy. There is a need to identify those potentially malignant lesions that will truly progress to malignancy from the majority that will not.
a) Carbohydrates: Cell surface carbohydrates, recently, have attracted much interest because essentially all human cancer show changes in the synthesis of many of these structures. In a recent study of the occurrence of a carbohydrate, blood group antigen H, there was a loss of expression of H antigen on cells at both invasive margins of the tumors with the presence of metastasis and with poor prognosis.
b) Histocompatibility antigens: A small molecular protein, beta 2 microglobulin which is a component of histocompatibility antigens has been seen to be elevated in patients with oral squamous cell carcinoma, oral keratosis and dysplasia.
c) Other squamous cell antigen: The detection of Ca-1-antibody and Ca antigen, a glycoprotein with high carbohydrate content on cell membranes of a variety of malignant cells, seemed to be a breakthrough for the immunohistochemical detection of cancer.
d) Growth factors and receptors: Epidermal growth factors (EGF), a polypeptide is found in small amount in oral mucosa, mainly in the lamina propria close to the epithelium. Increased amounts of EGF at this site are seen in dysplastic and malignant oral epithelial lesions. Two forms of transforming growth factors (TGF) are not expressed in normal epithelium but are expressed in oral squamous cell carcinoma.
e) Intracellular markers: Cytokeratins can be used as epithelial differentiation markers in oral malignant lesions and epithelial tumours has rapidly become a diagnostic routine method. Involucrin a precursor of the envelop protein present in the stratum corneum is useful as a specific marker for squamous differentiation e.g. in spindle cell carcinoma. The increased concentration of microfilament action in cells during locomotion and in invasive malignant cells has been known for sometime and could be demonstrated by immunohistochemistry and by electron microscopy. Using commercial antibodies, the occurrence of carcinoembryonic antigen (CEA) has been demonstrated. e.g. tumors of the salivary glands and the oral cavity.
f) Nuclear analysis: The number of mitotic figures as well as the expression of proliferation- associated antigens like the Ki-67 antigen or the S- phase correlated antigen proliferating cell nuclear antigen (PCNA) are increased indicating of high cell turnover in oral dysplasia.
g) Silver binding nuclear organizer regions: Silver binding nuclear organizer regions (AgNORs) are loops of ribosomal DNA that can transcribe for ribosomal RNA. In a cancer cell chromosome disarray with multiple nucleoli appears to result in an increase in AgNORs and higher AgNORs count indicates poor prognosis for oral cancer.
h) Oncogenes: In the deregulation and differentiation of cell growth that can lead to cancer, genetic disorders are observed. Oncogenes may well play a role in carcinogenesis and there have now been several studies of them in oral cancers.
i) Tumour suppressor genes: Oncosuppressor gene p53 appear to be one of the commonest genetic changes in human cancer. Mutations can result in increased expression of p53 and this now has been demonstrated in head, neck and oral carcinomas as well as in premalignant lesions. There is also a clear correlation reported between p53 expression and heavy smoking and alcohol consumption.
j) Arachidonic acid products: Lipoxygenase metabolites including prostaglandin E2, 5, 12 and 15 hydroxyeicosatetraenoic acids and leukotriene B4 are increased in oral squamous cell carcinoma.
k) Enzymes: Gamma glutamyl transpeptidase (GGT) is a membrane associated enzyme involved in transport of aminoacids. GGT is expressed in dysplasias and carcinomas of the oral, pharyngeal and laryngeal mucosa. High activity of lactate dehydrogenase and changes in isoenzyme pattern have been demonstrated in oral carcinoma cells but not in adjacent normal oral epithelium. In oral squamous cell carcinoma, guanidinobenzoatase can be demonstrated in area of invasion and it has therefore been advocated as a marker of tumor cells.
Most of these cell products are glycoprotein in nature. The cell surface membrane is chiefly composed of glycoproteins and lipids. Any intracellular change may lead to alteration in the surface membranes constituents, releasing certain molecules in the blood of such patients.
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