Oral Cancer Treatment Options

Introduction

Oral cancer includes various types of malignancies in and around the mouth. Most of these (>90%) are squamous cell carcinomas, a cancer that begins in squamous cells - thin, flat cells found in the tissue that forms the surface of the skin. It can be divided into different types based on site, aetiology and prognosis. There are also cancers in the oropharynx - the middle part of the throat, which have different characteristics and are associated with infection by human papillomavirus (HPV).¹

Oral cancer is the 7th in terms of frequency and 9th in terms of cancer-related deaths, with hundreds of thousands of new cases and deaths annually. Therefore, it's crucial to detect oral cancer early and get treatment.^1,2

Causes and risk factors

Oral cancer is a multifactorial condition and the risk factors include:³

• Tobacco and alcohol - smoking and drinking alcohol are the main things that increase the chances of getting oral cancer. Cigarettes have lots of chemicals that can harm your mouth and body, and nicotine byproducts have carcinogenic properties. Drinking alcohol by itself doesn't cause cancer, but when drinking and smoking together make the risk much higher
• Chronic inflammation - when your mouth gets swollen and irritated, it can lead to cancer because of certain inflammatory molecules in your body
• Ultraviolet (UV) radiation - harmful exposure to UV rays is associated with lip cancer
• Human papillomavirus (HPV) - this virus is often spread through sexual activity and is a big cause of oropharynx cancer
• Candida infections - have been found more in people with oral cancer. It's also linked to white patches in the mouth that could become cancerous
• Immunosuppression - people who have had organ transplants or bone marrow transplants are more likely to get oral cancer because their immune systems are weaker
• Genetic predisposition - your genes also play a part in whether you might get oral cancer, especially if you smoke or drink. But it's hard to say for sure if it's just genetics because tobacco and alcohol also play a big role

Diagnosis

Early detection of cancers is very important because it enhances the chances of a successful treatment. When cancer is found early, it's easier and cheaper to treat. Since dentists are usually the first to check your mouth, they can spot any signs of oral cancer early. There are different ways to detect oral cancer, for example:^3,4

• Looking for visible signs, such as lesions in the mouth
• Using biomarkers found in saliva, that is, molecules that indicate a normal or abnormal biological process, condition, or response to treatment. These biomarkers can indicate if someone might have cancer even before any visible signs show up
• Staining can also help identify pre-cancerous or cancerous lesions in the mouth
• Biopsies and examination of the tissue by a pathologist are the best way to confirm if someone has oral cancer
• Newer methods, like brush biopsy and micro biopsy, are less invasive and can help monitor suspicious lesions over time

Which visible signs are suspicious? Common signs of oral cancer include the following:⁴

• Long-lasting sores or pain in the mouth
• Changes in how the inside of the mouth looks or feels in one area
• Changes in how the inside of the mouth feels in one area
• Long-lasting white, red, or mixed patches in the mouth
• Raised areas or plaques in the mouth
• Long-lasting lumps or growths in the mouth
• Bleeding in one area of the mouth

Some conditions in the mouth could lead to cancer if you don’t treat them early. They are known as potentially malignant oral epithelial lesions. These include things like leukoplakia, erythroplakia, and lichen planus. However, most of these lesions don't turn into cancer.⁴

Treatment options

Up to now, surgery, radiation, and chemotherapy have been the main treatments for managing cancer, either used alone or together. However new targeted drugs under development are showing potential to enhance results for cancer patients.⁵

Surgery

The main goal of surgery is to remove the tumour completely, prevent it from spreading, and minimise damage to surrounding tissues while keeping in mind the patient's quality of life. Surgeons have a tough job because they need to find the right balance. Cancer treatment follows the 4R principle:⁵

• Resection (removing the tumour completely)
• Reconstruction (fixing the area where the tumour was to help it heal and work properly)
• Rehabilitation (helping the patient recover and feel normal again)
• Recall (making sure the cancer doesn't come back)

The challenges in surgery are making sure every bit of the tumour is removed and avoiding damage to nearby structures like the jaw.⁵

There are also modern treatments like laser therapy and robotic surgery. The choice of treatment depends on factors like where the cancer is, how big it is, and the patient's overall health. Some oral cancers have a better outlook than others, and the size and location of the tumour affect treatment choices. Other factors that affect treatment choices include the patient's age, overall health, and lifestyle habits like smoking and drinking. Although age alone isn't a barrier to surgery, older patients with other health problems might face more risks. Previous treatments in the same area also influence what treatment is chosen.⁵

Radiotherapy 

Also known as radiation therapy, is a treatment that targets and kills cancer cells in a specific area. It works by damaging the DNA of cancer cells, preventing them from repairing themselves and causing them to die. Traditional radiotherapy uses high-energy photons to kill cancer cells, but it can also damage healthy cells like hair, salivary glands, and the lining of the mouth.⁵

Radiotherapy isn't usually the first treatment choice, but it's often recommended as the main treatment for patients with small tumours or those who can't have surgery. It's also used before surgery to shrink the tumour, after surgery to kill any remaining cancer cells and prevent cancer from coming back, or if cancer has spread outside its original area. One big advantage of radiotherapy over surgery is that it helps preserve the normal anatomy and function of the mouth, which is important for quality of life.⁵

There are two main types of radiotherapy used for oral cancer: external beam radiation therapy, where radiation is delivered from a machine outside the body and requires regular hospital visits for several weeks, and brachytherapy, where a radioactive source is placed directly into the tissue. Some people may undergo both types of radiotherapy.⁵ 

Chemotherapy 

Chemotherapy is a treatment that works by disrupting the synthesis and replication of DNA in cancer cells, leading to their death. When cancer is in advanced stages, radiotherapy alone may not be very effective, so chemotherapy is often used as part of the treatment plan.⁵ 

There are different types of chemotherapy given at different times during treatment:⁵ 

• Induction or neoadjuvant chemotherapy is given before the main treatment
• Concomitant or concurrent chemotherapy is given during the main treatment like radiotherapy or surgery
• Adjuvant chemotherapy is given afterwards to prevent a recurrence of the disease

However, chemotherapy can have side effects like nausea, vomiting, mouth ulcers, hair loss, and suppression of the bone marrow, which can weaken the immune system. Despite these side effects, chemotherapy can improve overall survival rates in patients with oral and throat cancers, especially when used in combination with other treatments like radiotherapy and surgery.⁵ 

In some cases, chemotherapy may be used as palliative care to relieve symptoms and improve quality of life, especially when cancer has recurred or spread to other parts of the body. Nonetheless, it's important to weigh the potential benefits and risks of chemotherapy with the patient's medical team to determine the best course of action.⁵

Targeted biological therapy

At the moment, several targeted drugs are being developed. These drugs target specific molecules involved in cancer growth and immune evasion - a strategy used by tumours to evade your immune response and maximise their probability to continue growing.⁵ 

Small molecule tyrosine kinase inhibitors

These medications belong to a category known as targeted therapy. They work by blocking tyrosine kinase enzymes, molecules that help manage how cells work, including their growth and how often they divide. Small molecule tyrosine kinase inhibitors are often used alongside chemotherapy and radiation therapy to treat advanced cancer. However, we still need more evidence to know how well they work for newly diagnosed cases of head and neck cancer.⁵

There are also new methods to make radiation therapy more effective, called molecular targeted radiosensitisers. These methods aim to make cancer cells more sensitive to radiation, so the treatment works better. These methods, along with advanced types of radiation therapy like intensity-modulated radiotherapy and image-guided radiotherapy, offer better control of tumours with fewer side effects.⁵

Immunotherapy 

Immunotherapy is a new way to treat oral cancer. Normally, cancer cells can hide from the body's defences and immunotherapy works by either targeting the cancer cells directly or by boosting the body's immune system to fight the cancer better.⁵

There are different types of immunotherapy for cancer treatment:⁵ 

• Monoclonal antibodies are medicines that target specific molecules in cancer cells. It can also target proteins in the body to help cancer cells avoid being attacked by the immune system, helping it to fight the cancer better
• Cancer vaccines aim to train the immune system to recognise and attack cancer cells
• Non-specific immunotherapies: include molecules that stimulate the immune system to fight cancer

Immunotherapy works differently from traditional chemotherapy and may take longer to show results. It can also cause side effects like skin rashes or problems with the thyroid or adrenal glands. There are different ways to give immunotherapy: directly into the tumour or throughout the body. It can be expensive and challenging to decide which patients will benefit from it and which medicine to use and researchers are still studying how well immunotherapy works compared to other treatments and what side effects it might have.⁵

The importance of multidisciplinary management

Treating cancer should involve a team of different health professionals like:⁵

• Surgeons
• Oncologists
• Radiologists
• Dental surgeons
• Nutritionists
• Specialists in rehabilitation and reconstruction 

This helps to take care of both the mouth and overall health, improving the quality of life for cancer patients. It's also important to keep a close eye on patients to catch any signs of cancer coming back or new tumours forming.⁵

Each patient needs a unique treatment plan depending on the type and stage of cancer, whether it has spread, the person's age, and overall health. Early-stage cancers are usually treated with just one method like surgery or radiation, while more advanced cases need a combination of treatments. Patients with advanced cancer may need extensive surgery that can change how their face looks. They might also need facial prostheses (artificial facial parts) to help with speaking, eating, making saliva, and dealing with the emotional impact.⁵

Treating cancer has gotten better with new treatments, but it's also important to focus on keeping people cancer-free and improving their quality of life.⁵

Summary

Oral cancer involves different types of cancers in and around the mouth that can be divided into different types based on site, aetiology and prognosis. It's important to catch oral cancer early, as it's the 7^th most frequent cancer and the 9^th leading cause of cancer-related deaths globally.^1,2

Several factors can increase the risk of oral cancer, including tobacco and alcohol use, chronic inflammation, exposure to UV radiation, human papillomavirus (HPV) infection, candida infections, immunosuppression, and genetic predisposition.³

Detecting oral cancer early is crucial for successful treatment. Dentists can often spot signs of oral cancer during routine check-ups. Diagnosis methods include looking for visible signs, using saliva biomarkers, staining, and biopsies.^3,4

Treatment options for oral cancer include surgery, radiotherapy, chemotherapy, and targeted biological therapy. Surgery aims to remove the tumour while preserving as much tissue as possible. Radiotherapy kills cancer cells with high-energy radiation, while chemotherapy disrupts their DNA synthesis. Targeted biological therapy focuses on specific molecules involved in cancer growth and immune evasion.⁵

Managing oral cancer requires a multidisciplinary approach involving several healthcare specialists. Besides, each patient needs a tailored treatment plan based on their cancer type, stage, and overall health. Early-stage cancers may be treated with surgery or radiotherapy, while advanced cases may require a combination of treatments. Overall, the goal of the treatment is to improve survival rates and quality of life for oral cancer patients.⁵