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:

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

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

Investigations

Systemic investigations:

Chest xray
Full blood screen
Blood group and cross match
Clotting assays
U&E
LFT
Blood gases
ECG

Primary site:

Clinical examination
OPG
Lesional biopsy
Nodal biopsy
Endoscopy – Nasal, esophageal, bronchial
MRI and CT scan
Diagnosis and treatment of any dental problem

TNM classification of lip and oral cavity carcinomas

Assessed by CT, MRI and palpating

T = Primary tumor	N = Regional lymph nodes	M = Metastases
TX: Cannot be assessed	NX: Cannot be assessed	MX: Cannot be assessed
T0: No evidence	N0: No regional lymph node metastases	M0: No distant metastases
Tis: Carcinoma in situ	N1: Metastasis to 1 ipsilateral lymph node, ≤ 3cm in diameter	M1: Distant metastasis present
T1: ≤ 2cm in diameter	N2: Metastasis of > 3cm, ≤ 6cm in diameter
T2: > 2cm, ≤ 4cm in diameter	N2a: Single ipsilateral lymph node
T3: > 4cm in diameter	N2b: Multiple ipsilateral lymph node
T4: Invades into adjacent structures	N2c: Bilateral/contralateral lymph node
	N3: Metastases to lymph node > 6cm in diameter

TNM Classification

Stage	TNM groups
0	Tis, N0, M0
I	T1, N0, M0
II	T2, N0, M0
III	T3, N0, M0 T1/T2/T3, N1, M0
IVa	T4, N0/N1, M0 Any T, N2, M0
IVb	Any T, N3, M0
IVc	Any 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)