Cancer

💡Epidemiology

• Oral cancer accounts for approximately 3–5% of malignancies worldwide.
• Squamous cell carcinoma (SCC) accounts for approximately 90% of oral malignancies.
• Oral cancer is the sixth most common cancer worldwide particularly prevalent in regions where tobacco and areca nut use are common.
• Male-to-female ratio: approximately 2:1, although the difference is narrowing.
• Peak age: 40–70 years; HPV-associated disease may affect younger patients.
• In India, oral cancer may account for up to 30% of cancers in some populations with high gutka and betel-quid use.

💡Risk Factors

Tobacco — strongest risk factor

• Smoking: cigarettes, bidis, cigars and pipes; risk increases with cumulative exposure.
• Smokeless tobacco: gutka, khaini, snuff and chewing tobacco.
• Reverse smoking: particularly associated with palatal cancer in some South Asian populations
• Tobacco contains numerous carcinogens, including polycyclic aromatic hydrocarbons, nitrosamines and benzopyrene.

Alcohol

• Independent risk factor, associated with approximately 2–3 times increased risk.
• Tobacco and alcohol act synergistically, with a combined risk reported at approximately 15–30 times.
• Alcohol acts as a solvent, increasing mucosal permeability to carcinogens.
• Acetaldehyde, an alcohol metabolite, is directly carcinogenic.

Betel quid (paan) / areca nut

• Major risk factor in South Asia and the Indian subcontinent.
• May contain areca nut, lime, tobacco and other ingredients.
• Associated with leukoplakia, oral submucous fibrosis (OSMF) and oral cancer.
• Gutka is particularly carcinogenic because of the combination of areca nut, tobacco and lime.
• Areca nut itself is carcinogenic, even without tobacco.

💡HPV (Human Papillomavirus)

• High-risk types: HPV-16 and HPV-18.
• More important in oropharyngeal cancer, especially tonsillar and base-of-tongue SCC, than in conventional oral cavity SCC.
• HPV-positive oropharyngeal SCC generally has a better prognosis than HPV-negative disease.

Other risk factors

Clinical pearl: Tobacco plus alcohol produces a synergistic increase in risk. Areca nut is carcinogenic even without tobacco. HPV-positive oropharyngeal SCC generally has a better prognosis than HPV-negative disease.

💡Oral Squamous Cell Carcinoma (OSCC)

Any suspicious oral ulcer persisting for more than 3 weeks requires biopsy to exclude malignancy

Common sites

1. Lateral border of tongue — most common intraoral site
2. Floor of mouth.
3. Lower lip, particularly the vermilion border.
4. Retromolar trigone/posterior mandibular gingiva.
5. Buccal mucosa, particularly in betel-quid users.
6. Hard palate and upper gingiva.

Clinical presentation

Early signs

• Non-healing ulcer persisting more than 3 weeks.
• White patch (leukoplakia) or red patch (erythroplakia).
• Painless lump or mucosal thickening.
• Numbness or paraesthesia of the lip, chin or tongue.

Advanced signs

• Indurated ulcer with rolled or everted margins.
• Fixation to underlying tissues.
• Bleeding, pain, dysphagia or odynophagia.
• Trismus due to invasion of pterygoid or other masticatory muscles.
• Cervical lymphadenopathy, classically hard, fixed and non-tender.
• Weight loss and cachexia.

Histopathology

Invasion pattern

• Cohesive tumour fronts generally have a more favourable pattern.
• Infiltrative cords and individual tumour cells are associated with more aggressive behaviour.

💡TNM Staging

T classification: Primary tumour size and depth of invasion

Depth of invasion (DOI)

• DOI is measured from the basement membrane of adjacent normal mucosa to the deepest point of tumour invasion.
• DOI is different from tumour thickness.

Exam pearl: DOI greater than 10 mm automatically places an oral cavity tumour in T3, unless a higher T category applies.

N classification: Regional lymph nodes

ENE = extranodal extension, where tumour extends beyond the lymph node capsule.

M classification: Distant metastasis

N classification — general regional lymph node

M classification

Histopathological grade

Residual tumour after surgery

💡TNM stage grouping: general snapshot

💡Spread of Oral Cancer

Local spread

• Direct invasion of adjacent muscle, bone, nerve and skin.
• Perineural spread may occur along the inferior alveolar nerve, causing numbness of the chin or lower lip.
• Mandibular invasion is particularly relevant in floor-of-mouth and gingival SCC.

Lymphatic spread

• Level I–II nodes are commonly involved first.
• Tongue lesions drain to submandibular and upper deep cervical nodes.
• Floor-of-mouth lesions commonly drain to submandibular nodes.
• Lip lesions commonly drain to submental and submandibular nodes.
• Midline lesions of the tongue or floor of mouth may spread bilaterally.

Haematogenous spread

• Usually a late manifestation.
• Most common distant metastatic site: lung.
• Other sites: liver and bone.
• Chest X-ray or CT can be used to assess pulmonary metastasis.

💡Verrucous Carcinoma

Definition and behaviour

• Well-differentiated variant of SCC.
• Low-grade malignancy.
• Strongly associated with smokeless tobacco.

Clinical features

• Large, exophytic, cauliflower-like or warty white mass.
• Common sites: buccal mucosa and gingiva, especially at the tobacco-placement site.
• Locally aggressive but rarely metastasizes.
• Tumour pushes adjacent tissues rather than infiltrating them.

Histopathology

• Well-differentiated squamous epithelium.
• Minimal cytological atypia.
• Marked hyperkeratosis.
• Broad, bulbous rete ridges with a pushing invasion pattern.
• Church-spire keratosis may be seen.

Treatment

• Surgical excision with wide margins.
• Radiotherapy has historically been controversial because of concerns about anaplastic transformation; more recent evidence suggests this is uncommon.

Prognosis

• Excellent
• Recurrence can occur if margins are inadequate.

💡Investigations and Diagnosis

Biopsy

• Incisional biopsy from the most suspicious area.
• Include the lesion edge and adjacent normal tissue.
• In mixed lesions, target the red or indurated area.
• Avoid sampling only the necrotic centre because this may be nondiagnostic.

Imaging

Tumour markers

• SCC antigen: not routinely used.
• p53 expression: may have prognostic relevance.
• Ki-67 proliferation index: may provide prognostic information.
• p16 immunohistochemistry: surrogate marker for HPV-associated oropharyngeal SCC.

💡Management

Surgery

Primary treatment for most resectable oral cavity SCC, particularly stages I–IVA when surgery is appropriate.

• Wide local excision with adequate margins.
• Histological margin assessment is essential.
• The clinical margin target of at least 1–1.5 cm to account for tissue shrinkage; final adequacy is determined histologically.

Mandibulectomy

Maxillectomy

• Used for selected palatal or maxillary tumours involving the maxilla.

Neck dissection

Indications include clinically involved nodes or elective treatment in selected high-risk primary sites.

Reconstruction

Free-flap reconstruction may be needed after extensive resection.

Radiotherapy

Adjuvant postoperative radiotherapy

• Advanced-stage disease.
• Positive or close margins, depending on final pathology.
• Perineural invasion.
• Nodal disease and other adverse pathological features.

Definitive radiotherapy

• Selected unresectable tumours.
• Patients unsuitable for surgery.

Side effects

• Mucositis.
• Xerostomia.
• Osteoradionecrosis (ORN).
• Radiation caries.
• Trismus.
• Taste loss.

Chemotherapy

Chemotherapy alone is generally not curative for localized oral cavity SCC.

Targeted therapy and immunotherapy

Clinical pearl: Surgery is the primary treatment for most resectable oral SCC. Adjuvant treatment is determined by final stage and histopathological risk factors.