Clinicians have a key role in the detection and prevention of oral cancer and its precursory lesions, which often manifest in the buccal mucosa. These lesions are the buccal expression of a dermatological or systemic disease1 that is collectively diagnosed by qualified healthcare professionals. The medical anamnesis and the examination performed by the clinician will be confirmed by a pathologist's subsequent evaluation and biopsy of the lesion. The personal and family medical history of the patient provide critical information on the nature of the infection and its treatment. To detect the patient at risk, several factors (eg, use of tobacco and/or alcohol, genetics, diet, and immunology) must be evaluated. It is also essential to determine if the patient has prior cancers or untreated oral lesions.
Suspect lesions and differential diagnosis are confirmed by a clinical examination that should include the neck, face, epidermis, and hair. Intraoral examination of the dentition, buccal mucosa, and hygiene should be performed with adequate light that allows the aspect and color of each structure to be assessed. This examination can provide the essential elements of the diagnosis: the characteristics of the primary lesion, its topography, and its progressive aspect. The primitive elementary lesion is the morphologic expression of a lesion process. Understanding the etiological pathogenecity mechanism is important, as it allows the lesions to be connected to a known group. Any discomfort or pain in masticating, swallowing, breathing, or speaking is an indication that a specialist should be consulted. Mucosal ulcers greater than 1 cm in size should also be regarded with great suspicion.
Potential Malignant Lesions
Several potential malignant lesions frequent the oral mucosa and must be continuously monitored to permit proper management. Leukoplakia presents as a white patch that cannot be removed by rubbing and cannot be characterized clinically or histologically. Associated with carcinogens such as tobacco, these lesions are generally regarded as precancerous. When formed on the floor of the mouth or on the tongue, hyperkeratosis is considered to be a high-risk lesion. Verrucous leukoplakia is a white lesion with a warty, hyperplastic surface. Nodular leukoplakia, a white lesion with a granular surface, is associated with candida albicans. Speckled leukoplakia is a red and white plane with irregular surface texture. Erythroplakia appears as a red, velvety irregular lesion, and is commonly located on the buccal mucosa and soft palate. Erythroplakia has a greater malignant potential than leukoplakia and exhibits histological changes that range from mild dysplasia to invasive squamous cell carcinoma.
Some conditions can assume a potentially malignant role: Patterson-Killy Syndrome combines the iron deficiency of anemia with dysphagia and glossitis. Erosive lichen planus is an atrophic erosion or superficial ulceration of the oral mucosa that has white papules, keratotic striae, and the characteristic reticular form of lichen planus. These erosive lesions must be treated as potential malignant lesions. Oral submucosal fibrosis is a loss of elasticity of the mucosa with fibrous bands that restrict the opening of the mouth. In this condition, the tongue has a lack of mobility, and a burning sensation may be present in the mouth or throat. Discoid lupus erythema may or may not be associated with lesions that appear as atrophic erosions surrounded by a white keratic halo. A keratic plaque of tertiary syphilis, appearing on the dorsum of the tongue, can occasionally be associated with the development of oral cancer. Actinic keratosis is characterized by an erosion of the lower lip with white or brown crusting of the vermilion border, and may also be a precancerous indication.
Primitive elementary lesions on the inferior lip are related to tabagism and exposure to the sun. They cause epidermoid carcinoma, are very well differentiated, and are preceded by leukoplakia or chronic cheilitis. These tumors tend to spread on the lip and to infiltrate the lip toward the orbicular muscle, and can have an ulcerated appearance that conceals a nodular infiltration. Consequently, a careful examination of all the ganglionic regions (ie, submental, submandibular, and jugulocarotid) must be performed.
Elementary lesions can also be observed on the tongue and floor of the mouth and on the thin mucosa that covers a complex muscular system, and can potentially extend to the periodontium and the mandible. Asymptomatic over time and limited to the irregular erythema zone of deep leukoplakia, lingual cancers are often revealed by a glossodynia. Although examination via palpation is difficult due to the pain and nauseal reflex, it is necessary to detect ulcerations with irregular edges on the side of the tongue, in the lingual sillon, or on the floor of the mouth. Since 30% of patients present with adenopathy, the ganglionic regions should also be palpated.
Inferior gum cancer presents in the mucoperiosteum, the mandibular alveolar crest, and in the vestibule and the floor of the mouth. The intimate connection with the mandibular bone of the tissues in this area results in lesions that require surgery (eg, gingivomandibulectomy). Superior gum and palatal arch cancer are related to the roof of the oral cavity, the mucoperiosteum covering the superior lateral alveolar crest, and the central palatal arch. The evolution of the lesions occurs rapidly through bone structures. Retromolar cancer afflicts the narrow mucosa between the posterior extent of the superior and inferior alveolar crest. Cancer of the salivary glands comprises various lesions, and may be the cause of submucosal tumefaction, pain, reduced mobility, and neurological difficulties.
The oropharynx is a complex region with a dense lymphatic network that contains frequent metastasizing adenopathies. Lateral dysphagia is one common symptom and is associated with difficult lingual protraction, hypersalivation, dysphonia, and trismus. Cancer of the hypopharynx quickly metastasizes and affects the piriform sinus, the posterior wall of the hypopharynx, and the retrocricoarytenoid area. The symptoms of this condition are dysphagia, dysphonia, otalgia, and adenopathy. Larynx cancer is frequently connected with tabagism and is presented on the glottis (vocal cords), the laryngeal aspect of the epiglottis, the ventricular strips, and ventricles. Nasosinal cancers occur with less frequency and damage the osteocartilaginous skeleton and mucosal covering. Nasopharynx cancer is of unknown epidemiology and is associated with the Epstein-Barr virus.
A malignant tumor in an adolescent significantly differs from that in an adult. Malignant lesions rapidly develop in adolescent patients and are highly resistant to treatment. These tumors are lymphoblastic in nature (Burkitt's lymphoma) and must be carefully managed.
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Cancer can only be histologically diagnosed. The treatment of this condition is formulated and initiated only after the histological study has been verified by biopsy, which is a microscopic examination used to confirm or establish this diagnosis. While a direct biopsy can be performed if the tumor is superficial, it may also require limited exploration. This microscopic examination should be completed prior to the initiation of medical treatment or a surgical excision of a large lesion. Once the tissue sample has been attached, histological examination can be performed by experienced histologists.
In order to facilitate cytodiagnosis, it is important to obtain tissue samples from palpable tumors. To preserve the structures, the cytodiagnosis requires technical proficiency and proper instrumentation. Although leukemia can be diagnosed by cytology, this examination must be considered as complementary only. While radiographic examinations are used only for orientation during the diagnostic phase, they are important in subsequent monitoring of the cancer's evolution. Echography, computed tomography, and nuclear magnetic resonance can indicate the necessity of surgical exploration. Isotopic examinations also have a modest role in the diagnosis of cancer.
Tolonium Chloride as a Diagnostic Adjunct
The application of tolonium chloride (toluidine blue) has been described as useful for the identification of malignancy in squamous mucosa. According to several investigations, this solution can be used by clinicians as an adjunct to conventional examination of patients for the detection of oral cancer.2,3 Tolonium chloride is thiazine that is generally in 3-Amino-7-dimethylamino-2-methylphenazothionium chloride compound. Since the DNA of the cell nucleus and the RNA of the cell cytoplasm attach to tolonium chloride, it is often used as a stain for nucleic acids.
For years, it has been hypothesized that lesions in the oral cavity and of the oropharynx could be stained with tolonium chloride to differentiate between tumor cells, normal mucosa, and leukoplakia. Initial reports, however, indicated a high percentage of false-positive results with inflammatory lesions. In an attempt to decrease false-positive results and expand its diagnostic applications, the staining protocol has undergone several revisions in the past decades. Although this procedure continues to be refined, the Mashberg protocol--which features a 10- to 14-day waiting period prior to staining--can often identify asymptomatic lesions that had been previously undetected.4
Although stain interpretation of early mucosal cancer is more objective than assessment of clinical indications, this interpretation must be performed by an experienced clinician. Normal tissue does not absorb stain, but small areas of intense stain can be observed by mechanically restaining. Lesions with limited dysplasia or atypia do not stain consistently, and the correlation with pathologic diagnosis in these cases is tenuous. The classic asymptomatic erythroplastic carcinoma associated with alcohol consumption and cigarette smoking generally stains as a stippled or patchy dark blue. Since keratin does not allow stain penetration, necrotic portions and submucosal extensions of larger asymptomatic carcinomas do not stain. While minute carcinoma stain, they cannot be microscopically confirmed.
The efficacy of tolonium chloride in assessing margin status following resection of squamous cell carcinomas has been confirmed for the upper aerodigestive tract,5 and its use for in situ and invasive carcinomas has drawn similar conclusions.6 The use of the test is recommended for monitoring suspicious lesions, screening for malignant lesions in high risk individuals, the follow-up of patients already treated for cancer, and for the determination of an optimal site for biopsy. Toluidine blue should not be considered as a replacement for a detailed visual and digital examination, but as a supplemental tool for the identification of patients who should be referred to specialists or centers experienced in the diagnosis and treatment of oral cancer.
When treatment is necessary, the dental professional can perform an evaluation of the hard and soft tissue prior to its initiation and address any potential situations (eg, extractions, infections) that may pose future difficulties.
Surgery has always been the first modality offered for the treatment of cancer, although it is generally regarded as a radical action. The surgery can have an immediate effect in the histological diagnosis and evaluation of the cancer. The objective of this treatment is the excision of all cancer tissue to partially or completely access the organ and ganglionic territory. Due to the extensive and preliminary nature of the surgical exercise, it is often utilized to initiate other therapeutic methods (eg, radiotherapy and chemotherapy).
Cancer is also treated with radiotherapy, which utilizes varying levels of radiation to ionize the tissues through which they pass. The therapeutic utilization of the ionizing radiation occurs through cell destruction, which eliminates not only tumor cells but also healthy cells. To ensure that the healthy cells are repaired faster than the cancer cells, the radiation must be carefully administered in staggered and split doses that are regulated with a computer.
Transcutaneous radiotherapy transmits radiation to the patient in a dose that is homogeneously distributed throughout the tumor. In curietherapy, radioactive sources are placed in direct contact with the tumor, and the dose is inhomogeneously distributed. In the use of metabolic radiotherapy, isotopes are preferentially fixed on the tissues that require destruction.
The chemotherapeutic treatment of cancer has benefited from developments in the fields of biochemistry and molecular and cellular biology that have formed the basis of medical oncology. In this process, cytotoxic drugs are injected into an organism to affect the DNA of the cells transported by the blood. Since tumor cells can develop a resistance to treatment, the intravenous or oral dose of the chemotherapy must be precise to be efficient.
As with radiotherapy, it is critical to administer chemotherapy at periodic intervals that allow normal cells to regenerate. The efficacy of this treatment is improved when the cytotoxic drugs are utilized in combination rather than succession. Since chemotherapy has a toxic effect on normal and tumor cells, an understanding of the action mechanism and the chemicals' specific toxicity may prevent side effects.
Immunotherapy collectively refers to the modification of the hosts' biological response. Molecules are secreted by specific cells that interact with intermediate receptors and affect the immune system. Lymphokines, colony-stimulating factors, and cytokines are the cells principally responsible for this treatment.
Oral Complications: Cytotoxic Effect and Pain
Numerous complications arise from the use of chemotherapy and radiotherapy, and they must be considered prior to the initiation of treatment. Cancer treatments are described as stomatotoxic due to their effects on the oral tissues. Chemotherapy may compromise the function of bone marrow by suppressing the formation of white blood cells, red blood cells, and platelets. Due to the irradiation of the healthy tissues, oral mucositis and pain may limit the patient's speech, oral hygiene, function, and consumption of medication. Mucositis can also be a dose-limiting factor that decreases the efficacy of conditioning chemotherapy.7
Since it may yield infectious and hemorrhagic complications, many hematologists feel that toothbrushing is dangerous. More serious complications appear 12 to 18 months following irradiation and are related to the dose and volume of the radiation. Viral, bacterial, and fungal infections can result in myelodestruction, xerostomia, and damage of the oral mucosa caused by the chemotherapy or radiotherapy. Rampant dental decay and demineralization result from disruption in the quantity and quality of saliva.
Functional disabilities can be attributed to mucositis, dry mouth, trismus, and infection, and are connected to taste alterations and nutritional compromise. Abnormal dental development can occur in children following high doses of radiotherapy and chemotherapy. Neurotoxicity, with deep, burning pain and bleeding, is an additional complication of chemotherapy. Radiation caries, rampant dental decay, trismus, tissue fibrosis, and osteoradionecrosis can be caused by high doses of radiation therapy.
Oral care during and following therapy must be collectively established by the oncological and dental professionals to minimize the risk of complications and maximize the efficacy of subsequent care. In order to ensure proper hydration of the oral cavity, the clinician may prescribe the use of various materials (eg, oral lubricants, sugarless gum, salivary stimulants). The use of supplemental fluoride mouth rinses and gels has also been recommended. Although topical anesthetics and systemic analgesics will be prescribed to address postoperative infections, sensitivity, and pain, it may prove beneficial for patients to avoid toothbrushing in bleeding regions altogether.
The clinician has a critical role in the early detection of oral cancer. By documenting the patient's medical history and performing a comprehensive clinical examination, the dental professional can identify high risk patients and potentially detect asymptomatic oral cancer. This preliminary clinical diagnosis is critical to the measurement of tumor volume, risk of metastasis, and prognosis of recovery. Since the available methods of treating cancer are invasive in nature, advanced detection of malignant lesions limits the necessity for these procedures and increases the survival rate of patients.
* Private practice, Paris, France.
- Rouëssé J, Turpin F. Oncologie: Abreges. Paris, France: Masson: 1998.
- Mashberg A. Reevaluation of toluidine blue application as a diagnostic adjunct in the detection of asymptomatic oral squamous carcinoma: A continuing prospective study of oral cancer III. Cancer 1980;46(4):758-763.
- Mashberg A. Tolonium (toluidine blue) rinse - A screening method for recognition of squamous carcinoma. Continuing study of oral cancer IV. J Am Med Assoc 1981;245(23):2408-2410.
- Warnakulasuriya KA, Johnson NW. Sensitivity and specificity of OraScan toluidine blue mouthrinse in the detection of oral cancer and precancer. J Oral Pathol Med 1996;25(3):97-103.
- Portugal LG, Wilson KM, Biddinger PW, Gluckman JL. The role of toluidine blue in assessing margin status after resection of squamous cell carcinomas of the upper aerodigestive tract. Arch Otolaryngol Head Neck Surg 1996;122(5):517-519.
- Epstein JB, Oakley C, Millner A, et al. The utility of toluidine blue application as a diagnostic aid in patients previously treated for upper oropharyngeal carcinoma. Oral Surg Oral Med Oral Path 1997;83(5):537-547.
- Borowski B, Benhamou E, Pico JL, et al. Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: A randomised controlled trial comparing two protocols of dental care. Eur J Cancer B Oral Oncol 1994;30B(2):93-97.