Oral squamous cell carcinoma (OSCC)

Etiology of oral cancer

1. Familial/hereditary/genetic factors

2. Occupation: Exposure to nitrosamines, polycyclic aromatic hydrocarbons, oncogenic viruses

3. Solar irradiation: UVB exposure – angular cheilitis, lip cancer

4. Atmospheric pollution: Benzene trichloroethylene in traffic emissions

5. Immunosuppression

6. Tobacco consumption (toxins): Aromatic hydrocarbons eg. Benzene, tobacco specific nitrosamines

7. Alcohol consumption:

  • Increase permeability of oral mucosa to other carcinogens especially tobacco
  • Poor oral hygiene – intraoral metabolism of alcohol to acetaldehyde by bacterial alcohol dehydrogenases
  • Damage liver – decrease detoxification of carcinogens
  • Secondary nutritional deficiency eg. B12

8. Other culture specific habits: Toombak, betel plant, areca nut

9. Virus: EBV, HPV 2, 6, 16, 18, 57 (deactivate p53 by E6 proteins)

10. Diet: Lack of antioxidants and vitamin A, C, E

11. Poor oral hygiene: Chronic irritation

12. Autoimmune: Oral lichen planus

13. Infections: Syphilis, chronic candidiasis

Pathogenesis of oral cancer – Multistep hypothesis

Accumulation of a series of genetic changes that lead to:

  • Loss of cell growth control
  • Increased cell motility
  • Induction of neo-angiogenesis

Mutations of specific oncogenes and tumor suppressor genes – leads to selective growth advantage – enhances clonal expansion of malignant cells

1. Change in expression of tumor suppressor gene – p53

  • 50% of OSCC
  • p53 is a key regulator of G1-S cell cycle checkpoint
  • Dysfunction of it’s encoded proteins – uncontrolled proliferation of cells

2. Dysregulation of it’s other cell cycle proteins

  • Cyclin D1
  • MDM2
  • p16ink4a
  • p27Kip1

3. Overexpression of anti-apoptotic proteins – evade apoptosis

  • Bcl-2
  • Bcl-x
  • Bid
  • Bax

4. Maintenance of telomere length – Increased replicative life span of neoplastic clones

5. Other oncogenes

  • Growth factors – FGF
  • Growth factor receptors – ErbB1 and ErbB2 
  • Signal transducing proteins – Ras
  • Nuclear regulatory proteins – Myc
  • Overexpression of angiogenic proteins – angiogenesis:
    • VEGF
    • FGF
    • IL-8

6. Invasiveness

  • Cadherins
  • Catenin
  • Matrix metalloproteinases

7. Non antigenicity

  • HLA proteins
  • TGF-β  immune suppressors
  • FasL (for T cells)

Clinical presentation of orofacial tumors

Tumor morphology:

  • Papillary
  • Ulcerative
  • Deeply infiltrative

Common symptoms:

  1. Progressive swelling/enlargement, cortical expansion, asymmetry
  2. Sudden tooth mobility/migration of teeth without apparent cause
  3. Persistent/referred pain
  4. Paresthesia/dysesthesia of tongue or lips
  5. Soft tissue ulceration – non healing, persistent (>14 days), indurated, necrotic base, rolled margin
  6. Lymphadenopathy – rare in pediatrics
  7. Red/White lesions – precursors
  8. Induration of tongue – fixed to underlying tissues
  9. Airway obstruction – respiratory distress
  10. Dysphagia
  11. Chronic ear ache
  12. Trismus
  13. Alteration/blurring of vision
  14. Unusual oral bleeding
  15. Dysphonia – prolonged vocal hoarseness

Lymph node levels:

Lymph node levels

Level I: Submental, submandibular

Level II: Cranial jugular (deep cervical) nodes – Skull base to hyoid

Level III: Medial jugular (deep cervical) nodes – Hyoid to cricoid

Level: IV: Caudal jugular (deep cervical) nodes – Cricoid to clavicle

Level V:

  • Supraclavicular nodes (posterior triangle)
  • Dorsal cervical (superficial cervical) nodes along accessory nerve

Level VI: Prelaryngeal and paratracheal nodes

Other nodes:

  • Parotid nodes
  • Occipital nodes
  • Buccal nodes
  • Retroauricular nodes
  • Retropharyngeal nodes


Systemic investigations:

  1. Chest xray
  2. Full blood screen
  3. Blood group and cross match
  4. Clotting assays
  5. U&E
  6. LFT
  7. Blood gases
  8. ECG

Primary site:

  1. Clinical examination
  2. OPG
  3. Lesional biopsy
  4. Nodal biopsy
  5. Endoscopy – Nasal, esophageal, bronchial
  6. MRI and CT scan
  7. Diagnosis and treatment of any dental problem

TNM classification of lip and oral cavity carcinomas

  • Assessed by CT, MRI and palpating
T = Primary tumorN = Regional lymph nodesM = Metastases
TX: Cannot be assessedNX: Cannot be assessedMX: Cannot be assessed
T0: No evidenceN0: No regional lymph node metastasesM0: No distant metastases
Tis: Carcinoma in situN1: Metastasis to 1 ipsilateral lymph node, ≤ 3cm in diameterM1: Distant metastasis present
T1: ≤ 2cm in diameterN2: Metastasis of > 3cm, ≤ 6cm in diameter
T2: > 2cm, ≤ 4cm in diameterN2a: Single ipsilateral lymph node
T3: > 4cm in diameterN2b: Multiple ipsilateral lymph node
T4: Invades into adjacent structuresN2c: Bilateral/contralateral lymph node
N3: Metastases to lymph node > 6cm in diameter
TNM Classification
StageTNM groups
0Tis, N0, M0
IT1, N0, M0
IIT2, N0, M0
IIIT3, N0, M0
T1/T2/T3, N1, M0
IVaT4, N0/N1, M0
Any T, N2, M0
IVbAny T, N3, M0
IVcAny T, any N, M1
Oral cancer staging

Mode of management:

  • Stage 0, I, II – Surgery (wide excision)
  • Stage III, IV – Surgery to also include neck dissection (selective, modified, radical) + adjuvant therapy (chemo and radiotherapy)

Oral squamous cell carcinoma

  • Malignant epithelial neoplasm
  • Non healing ulcer
  • Exhibits squamous differentiation – characterized by:
  • Consists of solid sheets, cords, islands or individual malignant cells

Modes of spread:

  • Lymphatic
  • Intravascular
  • Local soft tissue infiltration
  • Bone infiltration
  • Perineural spread


  • Keratin pearls
  • Epithelial dysplasia, characterized by:
    • Cellular pleomorphism
    • Hyperchromatic nuclei
    • Abnormal mitosis
    • Individual cell keratinization
    • Loss of cohesion
  • Malignant epithelium invades CT and underlying muscles

Premalignant lesions:

Management: Surgery, chemotherapy, radiotherapy

Broder’s system

Histological grades of oral cancer:

GradeDifferentiationResemblance to original stratified squamous epitheliumIntercellular bridgesKeratinizationMitotic figuresAtypical mitosisMultinucleated cellsCellular and nuclear pleomorphism
IWell differentiatedCloselyPresent and of varying proportionsPresentFewRareRareMinimal
IIModerately differentiatedIntermediateLess conspicuousLess MoreSeenSeenMore
IIIPoorly differentiatedSlightExtremely scarceRarely presentFrequent activityFrequentFrequentMore and obvious
Broder’s system – histological grades
  • Low grade: Well and moderately differentiated tumors
  • High grade: Poorly/undifferentiated tumors


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