Photodynamic Therapy For Oral Cancer

Introduction

Photodynamic therapy also known as PDT is a treatment method, is a cutting-edge treatment whereby a drug is activated by light to eradicate cancer cells. This drug, known as a photosensitiser, is designed to specifically target cancer cells when exposed to a certain type of light.¹ Recently, PDT has been adapted to treat oral cancers, and cancers in the mouth. This is an extremely important development as oral cancers are often caught at later stages, when the disease has progressed and may be difficult to treat. 

This article aims to address the use of photodynamic therapy to treat oral cancer. 

Overview of oral cancer

Oral cancers commonly occur in areas such as the lip, tongue and other areas of the mouth and account for 48% of head and neck cancer cases.² The most common type is oral squamous cell carcinomas abbreviated to OSCCs. OSCCs account for 90% of oral cancers.¹ 

Oral cancers arise from mutations in the cells in the lining of the mouth. These mutations arise from a mixture of environmental factors known as carcinogens as well as genetic factors. Over time, this causes the cells to grow abnormally leading to the formation of a tumour. 

The most common environmental risk factors are:

• Excessive alcohol consumption
• Tobacco consumption
• Betel nut chewing
• Poor nutrition such as a lack of fruit and vegetable consumption. 
• The presence of human papillomavirus (HPV)^1,2 

In the beginning stages of formation, oral cancers can present as a white or red patch on the mouth. As it progresses it may form an ulcerated surface that does not go away after 3 weeks or so⁶. Depending on the location in the mouth there can also be pain or bleeding.

Other symptoms include: 

• A persistent sore throat
• A lump in the neck 
• Finding it hard to chew, swallow, speak or move your jaw
• Swelling on your jaw⁴ 

Oral cancers are frequently diagnosed via biopsy where a tissue sample is taken to be analysed in the lab. The cancer can then be diagnosed according to what stage it has been caught at ranging from stage I-IV. A cancer in stage I-II is classified as an early-stage cancer, while cancers in stages III-IV are classified as late-stage cancers.⁵

Routine treatment for oral cancers is surgical intervention which is followed by chemotherapy or radiotherapy depending on the stage of cancer. If the cancer is in a more advanced stage (stages III-IV) then a combination of these treatments may be used or immunotherapy may also be introduced into the treatment regime^6,7 

Basics of photodynamic therapy

Photodynamic therapy (PDT) has gained more and more traction as a therapy for cancer in recent years as it is a non-invasive way to tackle cancer. PDT has been successfully used in cases relating to dermatology, gynaecology and urology alongside cancer.⁷ As mentioned previously a drug is administered known as a photosensitizer which can be administered either intravenously or topically e.g. as a cream. 

The way PDT works is the photosensitizer accumulates in a specific area which is known as the ‘drug-light interval’. Therefore after exposure to a certain wavelength of light, the light is converted into molecular oxygen to generate a reactive oxygen species. These products destroy the cancer cells.^7,8 The use of photosensitizers can also initiate your immune system to fight against the tumour cells.⁹ 

Currently, photosensitizers known as porphyrins and chlorine are used as they are able to penetrate the tissue effectively. Additionally, a photosensitizer known as methylene blue is commonly used in tumours which require deeper penetration due to its location or thickness.¹³ However, there are more and more ongoing developments to make photosensitizers more selective and applicable to a range of cases.  

Application of PDT in oral cancer

Photodynamic therapy for use in oral cancer has been applied to manage cancers in the early stage as well as superficial oral cancers (cancers that are on the surface).¹⁰ Additionally, PDT can be used to treat precancerous lesions, helping to prevent the development of invasive cancer.¹¹ By targeting these lesions early, PDT reduces the risk of them progressing into more advanced stages, which would require more aggressive treatments like surgery or radiation. This approach is particularly beneficial for high-risk patients, such as smokers or individuals with HPV, who are more likely to develop oral cancers.

Advantages

Treating early-stage and superficial cancers has been seen to show promising results due to its non-invasive nature thus allowing there to be less side effects.¹⁰ This is especially helpful for elderly patients, who may not tolerate more aggressive treatments well. For many, PDT means a quicker recovery time and less damage to healthy tissue. 

Another advantage of using PDT is that, contrary to conventional therapies like surgery and radiation where there may be tissue damage, PDT is highly selective. This therefore means that healthy tissues are preserved thus maintaining their function. This is highly important in oral cancers as essential functions such as speech and swallowing can be maintained.¹⁰ 

Alongside this, PDT can be safely repeated with reduced toxicity, making it a potentially safer option for multiple treatments. This is particularly beneficial for patients who may need ongoing therapy, as traditional treatments like chemotherapy or radiation often cause cumulative side effects with repeated use. By contrast, PDT’s lower toxicity allows for more frequent or extended use without damaging healthy tissue, reducing the overall strain on the body. This makes PDT especially promising for managing recurrent or persistent oral cancers, where maintaining quality of life is a priority.¹⁰

Limitations

Although the use of PDT is novel, it does come with some limitations. For example, the effectiveness of the treatment may differ depending on the tumour's characteristics such as the size of the tumour, how close the tumour is to the vital structures as well as how thick the tumour is.¹⁰ Due to the use of light, some patients may develop a sensitivity to light, leading to side effects such as blistering and oedema. However, this can be minimised by avoiding direct sunlight and covering the affected area.¹⁰

One is the lack of depth that the light used in activating the photosensitizer may not actually penetrate that deep. This therefore means that the potential of the therapy is currently limited to early-stage cancers.¹²

Future use 

Despite this, using PDT in combination with known therapies such as chemotherapy or immunotherapy has been researched and provides backing for the future of PDT therapy. Research shows that when used in combination, there is a synergistic effect.^10,12 This means that the results when used together are much more effective than when used individually. You can think of it as the therapies lending a helping hand to each other so that the cancer is eradicated much more effectively. 

On the other hand, advancements in applying PDT to more complex tumours are also being actively researched. One upcoming approach is through the use of nanoparticles which can help improve the precision and effectiveness of PDT. Nanoparticles can be made to specifically target cancer cells therefore leading to an increase in the selectivity of the treatment whilst minimising damage to surrounding healthy tissues. 

Additionally, nanoparticles can be designed to help carry the photosensitizer deeper into the tissue, addressing one of the key limitations of traditional PDT, which struggles with limited light penetration. By enhancing the delivery of photosensitizers and improving light absorption, nanoparticles allow PDT to be more effective in treating larger and more complex tumours, which were previously difficult to reach with this therapy alone.¹² 

Summary

To summarise, photodynamic therapy (PDT) represents a promising, non-invasive treatment option for oral cancer, particularly in its early stages and for superficial tumours. By using light to activate a drug that targets and destroys cancer cells, PDT offers a more selective and tissue-preserving alternative to traditional treatments like surgery or radiation. This helps maintain critical functions such as speech and swallowing, which are essential for a good quality of life.

While PDT is not without limitations, such as restricted light penetration and photosensitivity, ongoing advancements, such as the use of nanoparticles, are expanding their potential for treating more complex tumours. Additionally, combining PDT with other therapies like chemotherapy or immunotherapy has shown synergistic effects, increasing its effectiveness. As research continues to improve its precision and reduce side effects, PDT holds great promise for becoming a more widespread and versatile treatment for oral cancers.

FAQs

What is oral cancer? 

Oral cancer falls under the category of head and neck cancers however oral cancers mainly develop in the mouth and the back of the throat. Common areas include the tongue, the gums and the throat. 

What is a reactive oxygen species? 

A reactive oxygen species can be described as a molecule that contains oxygen that will be reactive with other molecules in cells due to its instability. 

What is photodynamic therapy? 

Photodynamic therapy is a non-invasive form of treatment that uses light and a drug, known as a photosensitizer to tackle diseases such as cancer. 

What is a photosensitizer?  

A photosensitizer is a special type of drug that becomes active when exposed to a specific type of light. When exposed to a certain light its products become reactive which allows it to trigger an immune response and kill certain cells such as cancer cells.