Oral Squamous Cell Carcinoma

Overview

Oral Squamous Cell Carcinoma (OSCC) is the malignant transformation of stratified squamous epithelium in the oral cavity. It occurs between the vermillion borders of the lips and the junction of the soft and hard palates.

It is the most common oral malignancy and accounts for nearly 90% of all oral cancers. The oral cavity is one of the 10 most common sites for cancer so this explains why it is prevalent. OSCC commonly affects the adult and elderly population with the male sex carrying much of the disease burden. Though this is changing as a rising number of young women are reporting cases of OSCC.

It typically presents with an ulcerated lesion with a necrotic centre and elevated borders.

• Common sites affected in OSCC
  • Lower lip
  • Lateral border of the tongue
  • Floor of the mouth
  • Soft palate
  • Buccal mucosa
  • Alveolar ridge

Etiology

A number of factors contribute to the development of OSCC. They are discussed below:

• Risk/predisposing factors for OSCC
  • Tobacco smoking – 75% of cases of OSCC have a history of tobacco use, as such, it is the major source of intra-oral carcinogens. Carcinogens in tobacco such as nitrosamine(nicotine) and and polycyclic aromatic hydrocarbons play a role in initiating carcinogenesis. Heavy tobacco smokers have a 20 fold increased risk of developing OSCC.
  • Alcohol consumption – this is the second major risk factor in the development of OSCC. Long-time alcohol consumption leads to chronic irritation and dehydration of the oral mucosa while exposing it to carcinogens such as ethanol and its metabolic product acetaldehyde. Associated with cancer of the floor of the mouth. Heavy alcohol consumption have a 5fold increased risk of developing OSCC.
  • Betel quid – certain populations(South East Asia) are known to chew betel quid and paan which are mixtures of tobacco and plant material.
  • Cannabis use
  • Infections – OSCC has been linked to HPV (particularly HPV16), Candida, EBV and Hepatits C infections
  • Nutritional deficiencies – diets rich in fruits and vegetables are recommended to prevent cancer. Diets deficient in this may predispose one to OSCC
  • Sunlight exposure – chronic ultraviolet radiation may lead to lip cancer
  • Oral health – poor dentition such as missing teeth may contribute to the development of OSCC. It may cause poor nutrition as well.
  • Overuse of mouthwash – chronic irritation of the oral mucosa may lead to OSCC
  • Inadequate immune response – immunosuppression due to drugs, infection and organ transplantation increases the risk of OSCC
  • Poor socioeconomic status – this increases the risk of having a poor diet and poor oral health.
  • Family history
  • Personal history of previous cancer
• Potentially malignant disorders that may lead to OSCC
  • Lichen planus
  • Submucous fibrosis
  • Dyskeratosis congenita
  • Discoid lupus erythematosus
  • Fanconi anemia
  • Plummer-Vinson syndrome

Pathophysiology

The development of OSCC is dependent on genetic aberrations that lead to uncontrolled cell proliferation. It involves susceptible genes and exposure to environmental carcinogens. Specifically affecting the Tumor Suppressing Genes (TSG) on chromosomes 3, 9, 11, 17. Particularly tumor suppressor p53 and p16 are inactivated. Leading to unregulated progression through the cell cycle and increased cell proliferation.

Oncogenes are also activated leading to continuous activation of the cell cycle leading to uncontrolled growth of cancer. Particularly the oncogene on chromosomes 11 and 17 are implicated.

Certain enzymes such as alcohol dehydrogenase break down pro-carcinogens such as alcohol into carcinogens such as acetaldehyde. People with alcohol dehydrogenase type 3 are predisposed to OSCC. Cytochrome P450 also metabolises pro-carcinogens to carcinogenic material.

Clinical presentation

• Patient History

History

It initially presents asymptomatically hence delaying diagnosis, and the presentation is variable depending on the stage. Pain may not be a feature in early disease. While taking the patient’s history look out for the following:

• Initially painless lump in the oral cavity that progresses to a painful lump.
• The lesion may erupt from normal mucosa but in some cases there may be premalignant lesions first such as erythroplakia which will present as red plaques, leukoplakia which is a white patch or a mixture of both.
  • Persistent mouth ulcers, white, red or speckles lesions, nodules to an ulcer with indurated rolled margins and a necrotic base
  • The ulcer is non-healing and fast-growing
  • It may be fixed to neighbouring structures and result in functional impairment
• A nonhealing extraction tooth socket
• An indurated lump
• A large exophytic lesion with a necrotic centre
• Difficulty chewing and/or swallowing
• Increased salivation
• A mass in the neck
• Persistent bad breath: due to debris and necrosis
• Bleeding from ulcer
• Cervical lymph node enlargement: initially mobile but becomes fixed due to extracapsular spread
• Cachexia: in advanced disease
  • Due to the production of TNF (Cachexin) and malnutrition due to feeding difficulties

Use the mnemonic RULE – Red Ulcerated Lump Extending over 3 weeks to remember which type of lesion you should be worried about being malignant. As such a biopsy needs to be done.

Physical examination

Conduct a thorough, systematic physical examination paying close attention to:

• The mouth, lips and the rest of the face
• Common areas to be affected such as the ventro-lateral tongue, floor of the mouth, buccal mucosa etc
• Presence of lesions: Erythroplakia(velvety red patches) and leukoplakia (white areas) which can be confused as candidiasis, ulcerated lesions with induration (late OSCC). Ensure to palpate every lesion and see if there is hardening or tenderness.
• Palpate the lymph nodes to check for metastasis.

Diagnosis

Diagnosis is confirmed histologically as such a tissue biopsy must be performed.

• Laboratory tests
  • Complete blood count
  • Liver function test – check for metastasis
  • Urea and electrolyte test – check kidney function
  • Calcium levels – raised levels are a poor prognostic factor
• Imaging studies
  • Photography – to record the progress of the lesion
  • Chest x ray – to rule out a primary cancer and metastasis
  • Endoscopy – to detect second primary tumour
  • CT scan head and neck – to map the tumour in 3D
  • Orthopantogram
• Histopathology and cytological tests
  • Incisional or brush biopsy
  • Fine needle aspiration biopsy

Staging

UICC and AJC classifications can be used. UICC (TNM) is more commonly used.

Treatment

Early diagnosis is key to a better prognosis. Treatment is a combination of radiotherapy, chemotherapy and surgery and is dependent on tumour, patient and technical factors.

• Stage I and stage II – Surgery and/or radiotherapy
• Stage III and stage IV – A combination of surgery, chemotherapy(Cisplatin based)and radiotherapy

Cervical lymph node involvement occurs in 80% of cases hence radical neck dissection is indicated.

Other therapies such as the use of gene therapy and monoclonal antibodies are being introduced specifically targeting:

• Epidermal Growth Factor Receptor (EGFR)
• COX-2
• Progesterone receptor

Patients should strive to maintain good oral hygiene to reduce liability to adverse effects of the treatment modalities.

• Advantages of radiotherapy
  • Normal anatomy and physiology are maintained
  • No general anesthesia is needed
• Disadvantages of radiotherapy
  • Adverse effects are common
  • Cure is uncommon; even more unlikely with a large tumor
  • General prognosis is worsened
• Complications of cancer therapy
  • Hyposalivation – salivary glands are damaged by radiation
  • Mucositis
  • Oral infections – microbial populations increase in the oral cavity increasing the risk of infection.
  • Loss of taste – xerostomia may contribute to this
  • Osteoradionecrosis – damage to bone cells causing bone thinning and reduced bone strength
• Differentials
  • Acitinic keratosis – occurs over the vermillion region of the lower lip
  • Lichen planus – bilaterally symmetrical lesions
  • Mucosal candidiasis
  • Traumatic lesion – would be associated with other injuries such as a broken tooth
  • Malignant sarcoma (soft – start as a swelling but overlying surface ulceration mimics OSCC
  • Lobular capillary hemangioma – more sharply demarcated and grows more rapidly
  • Amelonotic melanoma

Prognosis

Depends on tumour staging and location. The more advanced the lesion the poorer the prognosis. Lesions that are well differentiated, localised with no metastasis have a good prognosis.

OSCC affecting the floor of the mouth has the poorest prognosis while that affecting the lip has the best prognosis for the same reason. Early recognition is leads to lower tumour staging meaning there is a better chance of survival. One is more likely to seek medical attention earlier if a lesion occurs on their lip than if it is on the floor of the mouth.

• The survival rate
  • With at an early stage – 84%
  • With local metastasis – 65%
  • With distant metastasis – 39%