Discuss pathogenesis of oral cancer. Briefly describe the malignant lesions that are likely to affect the oral cavity.

Pathogenesis of Oral Cancer

The development of oral cancer is a multi-step process, often described as a sequence of genetic and epigenetic alterations leading to uncontrolled cell growth and invasion. This process, known as carcinogenesis, typically unfolds over years or decades.

1. Initiation

Initiation involves exposure to carcinogenic agents that cause genetic damage. Common initiators include:

• Tobacco: Contains numerous carcinogens, inducing DNA mutations.
• Alcohol: Acts as a solvent, enhancing the penetration of carcinogens and causing oxidative stress.
• Human Papillomavirus (HPV): Specifically HPV-16, integrates into the host genome, expressing oncoproteins E6 and E7 that disrupt cell cycle control.
• Betel Quid & Areca Nut: Contains arecoline, a stimulant, and other compounds with carcinogenic potential.

These agents cause mutations in key genes involved in cell growth regulation, such as TP53 (tumor suppressor gene), RB1 (retinoblastoma gene), and PIK3CA (involved in the PI3K/AKT signaling pathway).

2. Promotion

Promotion involves the selective growth advantage of initiated cells. This stage is often reversible in the early phases. Chronic inflammation and repeated exposure to promoting agents contribute to clonal expansion of pre-cancerous cells.

• Chronic irritation: From ill-fitting dentures, sharp teeth, or galvanic currents.
• Immunosuppression: Weakens the immune system's ability to eliminate abnormal cells.

3. Progression

Progression is characterized by irreversible genetic changes, leading to increased aggressiveness, invasion, and metastasis. This stage involves:

• Accumulation of mutations: Further genetic alterations in oncogenes and tumor suppressor genes.
• Angiogenesis: Formation of new blood vessels to supply the growing tumor.
• Invasion and Metastasis: Cancer cells break through the basement membrane and invade surrounding tissues, eventually spreading to distant sites.

Epigenetic modifications, such as DNA methylation and histone modification, also play a crucial role in regulating gene expression during progression.

Malignant Lesions of the Oral Cavity

Several malignant lesions can affect the oral cavity, with varying frequencies and prognoses.

1. Squamous Cell Carcinoma (SCC)

SCC accounts for over 90% of oral cancers. It typically presents as a non-healing ulcer, a white or red patch (leukoplakia or erythroplakia), or a mass. Common sites include the tongue, floor of the mouth, and buccal mucosa.

2. Verrucous Carcinoma

A low-grade SCC variant characterized by a warty appearance. It grows slowly and rarely metastasizes but can be locally destructive.

3. Adenoid Cystic Carcinoma

A relatively rare malignancy arising from minor salivary glands. It is known for its perineural invasion, leading to pain and nerve dysfunction.

4. Mucoepidermoid Carcinoma

Another salivary gland malignancy, often occurring in the palate. It has a variable prognosis depending on the grade and stage.

5. Ameloblastoma

A benign odontogenic tumor, but can be locally aggressive and difficult to eradicate. It arises from the dental lamina and typically presents as a slow-growing swelling.

6. Sarcomas

Rarely, sarcomas (e.g., fibrosarcoma, osteosarcoma) can occur in the oral cavity, often associated with previous radiation therapy.

Lesion	Frequency (%)	Common Site	Key Features
Squamous Cell Carcinoma	>90	Tongue, Floor of Mouth, Buccal Mucosa	Non-healing ulcer, Leukoplakia, Erythroplakia
Verrucous Carcinoma	<5	Gingiva, Palate	Warty appearance, Slow growth
Adenoid Cystic Carcinoma	<1	Palate, Minor Salivary Glands	Perineural invasion, Pain