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Oral Cavity Cancer

Disease Details

Family Health Simplified

Description
Oral cavity cancer is a type of cancer that forms in the tissues of the mouth or throat, including the lips, tongue, cheeks, floor of the mouth, hard and soft palates, sinuses, and pharynx (throat).
Type
Oral cavity cancer is a type of head and neck cancer that includes cancers of the lips, tongue, cheeks, floor of the mouth, hard and soft palate, sinuses, and throat. The primary type of genetic transmission for oral cavity cancer is not typically hereditary. Instead, it is usually caused by somatic mutations that occur due to environmental factors such as tobacco use, alcohol consumption, human papillomavirus (HPV) infection, and exposure to certain chemicals.
Signs And Symptoms
The signs and symptoms of oral cancer depend on the location of the tumor but are generally thin, irregular, white patches in the mouth. They can also be a mix of red and white patches (mixed red and white patches are much more likely to be cancerous when biopsied). The classic warning sign is a persistent rough patch with ulceration, and a raised border that is minimally painful. On the lip, the ulcer is more commonly crusting and dry, and in the pharynx it is more commonly a mass. It can also be associated with a white patch, loose teeth, bleeding gums, persistent ear ache, a feeling of numbness in the lip and chin, or swelling.When the cancer extends to the throat, there can also be difficulty swallowing (usually a base of tongue HPV16+ cancer) or a visibly enlarged tonsil unilaterally, also from the same etiology, painful swallowing, and an altered voice. Typically, the lesions have very little pain until they become larger and then are associated with a burning sensation. As the lesion spreads to the lymph nodes of the neck, a painless, hard mass will develop. If it spreads elsewhere in the body, general aches can develop, most often due to bone metastasis.
Prognosis
Survival rates for oral cancer depend on the precise site and the stage of the cancer at diagnosis. Overall, 2011 data from the SEER database shows that survival is around 57% at five years when all stages of initial diagnosis, all genders, all ethnicities, all age groups, and all treatment modalities are considered. Survival rates for stage 1 cancers are approximately 90%, hence the emphasis on early detection to increase survival outcome for people. Similar survival rates are reported from other countries, such as Germany.
Onset
Oral cavity cancer, also known as mouth cancer, can vary in its onset, but it often begins as a small, persistent sore or lump in the mouth. It may go unnoticed initially due to nonspecific symptoms or lack of pain. Key risk factors include tobacco use, heavy alcohol consumption, and human papillomavirus (HPV) infection, which can contribute to earlier onset. Generally, it is more frequently diagnosed in individuals over the age of 40.
Prevalence
The prevalence of oral cavity cancer varies by region and population, but it generally represents a significant portion of head and neck cancers. The condition is more common in men than in women and is often linked to risk factors such as tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Specific rates can differ widely, with higher incidences reported in areas with prevalent tobacco and betel quid use, such as parts of South and Southeast Asia.
Epidemiology
Globally, it newly occurred in about 355,000 people and resulted in 177,000 deaths in 2018. Of these 355,000, about 246,000 are males and 108,000 are females.In 2013, oral cancer resulted in 135,000 deaths, up from 84,000 deaths in 1990. Oral cancer occurs more often in people from lower and middle income countries.
Intractability
Oral cavity cancer is not necessarily intractable, but its treatability depends on various factors, including the stage at diagnosis, the specific location within the oral cavity, the type of cancer, and the patient's overall health. Early-stage oral cavity cancers are often more treatable with a combination of surgery, radiation therapy, and possibly chemotherapy. However, advanced stages can be more challenging to treat and may require more aggressive and complex treatment approaches. Early detection and prompt treatment are crucial for improving outcomes.
Disease Severity
Oral cavity cancer refers to malignant growths in the mouth and can vary significantly in severity. The disease is typically staged from I to IV, with higher numbers indicating more advanced disease:

- **Stage I**: Small, localized tumors that have not spread to lymph nodes or other tissues.
- **Stage II**: Larger tumors still contained within the mouth, but may start affecting nearby tissues.
- **Stage III**: Even larger tumors that may have spread to one lymph node but not to distant sites.
- **Stage IV**: Advanced disease with large tumors that have spread to multiple lymph nodes, surrounding tissues, or distant parts of the body.

Severity impacts prognosis and treatment options, with early stages generally having a better outlook.
Healthcare Professionals
Disease Ontology ID - DOID:8618
Pathophysiology
Oral squamous cell carcinoma is the end product of an unregulated proliferation of mucous basal cells. A single precursor cell is transformed into a clone consisting of many daughter cells with an accumulation of altered genes called oncogenes. What characterizes a malignant tumor over a benign one is its ability to metastasize. This ability is independent of the size or grade of the tumor (often seemingly slow growing cancers like the adenoid cystic carcinoma can metastasis widely). It is not just rapid growth that characterizes a cancer, but their ability to secrete enzymes, angiogeneic factors, invasion factors, growth factors and many other factors that allow it to spread.
Carrier Status
Oral cavity cancer is not typically associated with a "carrier status" concept, as it is generally not a hereditary disease passed down through carrier genes. Instead, risk factors include tobacco use, excessive alcohol consumption, human papillomavirus (HPV) infection, and prolonged sun exposure to the lips. Genetic predispositions to certain cancers may exist, but they do not involve classic carrier states like some inherited genetic conditions.
Mechanism
Oral cavity cancer, commonly referred to as oral cancer, primarily develops from squamous cells lining the oral cavity. The mechanisms and molecular pathways involved are multi-faceted.

### Mechanism:
- **Carcinogenesis Initiation**: Begins with genetic mutations in squamous cells due to carcinogen exposure, such as tobacco, alcohol, betel nut, or HPV infection.
- **Progression**: These mutations disrupt normal cellular regulatory mechanisms, leading to uncontrolled cell growth and division.
- **Metastasis**: Cancer cells invade surrounding tissues and spread to distant organs through the lymphatic system and bloodstream.

### Molecular Mechanisms:
1. **TP53 Mutations**: TP53 is a tumor suppressor gene. Mutations in TP53 can inhibit its role in DNA repair and apoptosis, allowing damaged cells to proliferate.
2. **Oncogenes Activation**:
- **Cyclin D1 (CCND1)**: Overexpression can drive the cell cycle progression and proliferation.
- **EGFR**: Overexpression or mutations can lead to enhanced cellular proliferation and survival.
3. **Loss of Heterozygosity (LOH)**: Common in chromosomal regions containing tumor suppressor genes such as 3p, 9p, and 17p.
4. **Epigenetic Changes**:
- **DNA Methylation**: Promoter hypermethylation of tumor suppressor genes (e.g., p16INK4a) can silence their expression, contributing to oncogenesis.
- **Histone Modifications**: Altered methylation and acetylation patterns can affect chromatin structure and gene expression.
5. **Human Papillomavirus (HPV)**: HPV-positive oral cancers involve viral oncoproteins E6 and E7, which inactivate tumor suppressor proteins p53 and Rb, respectively.
6. **Inflammatory Pathways**: Chronic inflammation and oxidative stress can lead to DNA damage and mutation accumulation, fostering a tumorigenic environment.

Understanding these mechanisms provides insights for targeted therapies and preventive measures in managing oral cavity cancer.
Treatment
Oral cavity cancer treatment typically involves a combination of the following approaches:

1. **Surgery**: Removal of the tumor and possibly some surrounding tissue. In advanced cases, part of the jawbone or tongue may also be removed.

2. **Radiation Therapy**: High-energy beams, such as X-rays or protons, are used to kill cancer cells. This may be employed after surgery to eliminate any remaining cancer cells.

3. **Chemotherapy**: The use of drugs to kill cancer cells. This is often combined with radiation therapy for advanced stages of oral cavity cancer.

4. **Targeted Therapy**: Drugs or other substances specifically target cancer cells with less harm to normal cells. This is often used in cases where cancers have specific genetic mutations.

5. **Immunotherapy**: Uses the body's immune system to fight the cancer. This is an emerging treatment option for certain types of oral cavity cancer.

6. **Reconstructive Surgery**: Follow-up surgeries to reconstruct parts of the mouth or face affected by cancerous tissue removal.

Each treatment plan is customized based on the patient's specific condition, including the cancer’s stage and location, as well as the patient’s overall health.
Compassionate Use Treatment
Compassionate use treatment for oral cavity cancer generally refers to the use of investigational drugs or therapies that have not yet been approved by regulatory authorities but are made available to patients with serious or life-threatening conditions when no other treatments are available. This often requires special approval and is handled on a case-by-case basis.

Off-label or experimental treatments for oral cavity cancer may include:

1. **Immunotherapy**: Checkpoint inhibitors such as pembrolizumab or nivolumab are sometimes used off-label for oral cavity cancer. These drugs, approved for other cancers, can help boost the body's immune response against cancer cells.

2. **Targeted Therapy**: Drugs that target specific genetic mutations or pathways in cancer cells can be used off-label. Examples include cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).

3. **Clinical Trials**: Participating in clinical trials gives patients access to new and experimental treatments that are being tested for efficacy and safety. These can include new chemotherapy agents, novel radiotherapy techniques, or combination treatments.

4. **Gene Therapy**: Experimental approaches involving gene therapy to target cancer cells more precisely are under investigation but are not yet standard practice.

5. **Photodynamic Therapy**: This involves using light-sensitive medication and a light source to destroy cancer cells, and it may be considered in experimental contexts for oral cavity cancer.

Patients considering these options should discuss them thoroughly with their healthcare provider to understand the potential benefits and risks.
Lifestyle Recommendations
For oral cavity cancer, lifestyle recommendations include:

1. **Avoid Tobacco**: Refrain from smoking and using smokeless tobacco products, as they contribute significantly to the risk.
2. **Limit Alcohol**: Reduce or avoid alcohol consumption, particularly heavy drinking, which is a significant risk factor.
3. **Healthy Diet**: Maintain a balanced diet rich in fruits and vegetables to support overall health and potentially reduce cancer risk.
4. **Oral Hygiene**: Practice good oral hygiene and have regular dental check-ups to identify any early signs of trouble.
5. **Sun Protection**: Use lip balm with SPF to protect against sun exposure, which can increase the risk of lip cancer.
6. **HPV Vaccination**: Consider getting the HPV vaccine, as human papillomavirus is linked to some types of oral cancers.
7. **Avoid Betel Quid**: Refrain from chewing betel quid, nuts, and similar substances known to cause oral cancer.
8. **Physical Activity**: Engage in regular physical activity to maintain overall health and well-being.

These recommendations can help reduce the risk of developing oral cavity cancer and promote overall health.
Medication
Medication for oral cavity cancer primarily involves chemotherapy drugs, which may be used alone or in combination with other treatments such as surgery or radiation therapy. Commonly used chemotherapy drugs include cisplatin, 5-fluorouracil (5-FU), and docetaxel. Targeted therapies like cetuximab, which targets the epidermal growth factor receptor (EGFR), may also be used. Treatment plans are individualized based on the stage of the cancer and the patient’s overall health. Always consult with a healthcare professional for the most appropriate treatment options.
Repurposable Drugs
Several repurposable drugs have shown promise in treating oral cavity cancer. These include:

1. Metformin: Originally used for diabetes, metformin has demonstrated anti-tumor effects in various cancers including oral cavity cancer by inhibiting cancer cell proliferation.
2. Sildenafil: Commonly used for erectile dysfunction, sildenafil has been found to potentially enhance the effects of chemotherapy and radiotherapy in cancer treatment.
3. Celecoxib: An anti-inflammatory drug, celecoxib has been studied for its ability to inhibit cancer cell growth and induce apoptosis in oral cancer cells.
4. Aspirin: This anti-inflammatory medication has been associated with reduced cancer risk and has potential as an adjuvant therapy in oral cancer.

Nan (not applicable or not available) generally means that no specific information is provided or needed about this parameter in the context of repurposable drugs for oral cavity cancer.
Metabolites
Oral cavity cancer involves a range of metabolic changes and altered metabolite levels. Some notable metabolites that have been studied in the context of oral cavity cancer include:

1. **Lactic acid**: Elevated levels due to increased glycolysis in cancerous cells (Warburg effect).
2. **Glutamine**: Utilized at higher rates as a carbon and nitrogen source for cancer cell growth.
3. **Reactive oxygen species (ROS)**: Increased levels, which can lead to DNA damage and further cancer progression.
4. **Amino acids**: Altered profiles, including increased serine, glycine, and alanine, associated with cancer metabolism.
5. **Lipids**: Changes in lipid metabolism, often evident in different lipid species and their derivatives.

These metabolic alterations can be used as potential biomarkers for diagnosis or targets for therapy.
Nutraceuticals
Nutraceuticals may play a supportive role in the management of oral cavity cancer by potentially enhancing overall health, improving immune function, and reducing side effects from conventional treatments. However, their therapeutic efficacy and safety should be discussed with healthcare providers.

Nanotechnology, on the other hand, is showing promise in oral cavity cancer through enhanced drug delivery systems that target cancer cells more precisely, reduce side effects, and improve the effectiveness of chemotherapeutic agents. Researchers are exploring nanoparticle-based therapies and diagnostic tools for early detection and more effective treatment outcomes.
Peptides
Peptides and nanoparticles (nan) are being explored for their potential in the treatment and detection of oral cavity cancer. Peptides can serve as therapeutic agents due to their ability to target specific tumor markers, enhancing the precision and efficacy of treatments. Nanoparticles can be used for targeted drug delivery, increasing the concentration of the therapeutic agent at the tumor site while minimizing side effects. Researchers are investigating these technologies to improve outcomes and reduce toxicity in patients with oral cavity cancer.