Oral cancer

Oral cancer is an umbrella term for cancers that arise within the mouth and throat (oral cavity) and a subcategory of head & neck cancers. They can arise through various genetic factors because cancer is fundamentally ‘a genetic disease’. These cancers typically start in areas such as lips, tongue, gums, lining of the cheeks, floor of the mouth, hard and soft palate, tonsils, and throat. They can spread to other tissues. This is especially dangerous when cancer spreads (metastasis); it can be life-threatening because 90% of cancer-related deaths are from metastasis of other organs.¹ Therefore, oral cancer is a serious condition that requires prompt medical attention.

Treatment options for oral cancer are surgery, chemotherapy, radiotherapy, and immunotherapy, and the type of treatment usually depends on the stage of the oral cancer. The most common type of oral cancer is oral squamous cell carcinoma, which accounts for 9 out of 10 cases.²

Prevalence 

In the UK, oral cancer is the sixth most common cancer globally.  In 2020, there were 3777,13 new cases of oral cancer globally, resulting in 177,757 deaths.³ Oral cancer is most prevalent in developing countries such as Southeast Asia and the Asia-Pacific region.⁴ The incidence rates are 2 to 3 times higher in males than females. The average age of diagnosis for oral cancer is between 50 and 69 years.⁶ Alarmingly,  the Global Cancer Observatory (GCO)predicts that the incidence of oral squamous cell carcinoma alone will rise by 40% by 2040.⁷

Signs and symptoms of oral cancer

• A sore, irritation, or thickness in your mouth or throat
• A white or red patch inside your mouth
• Vocal changes partially, your voice sounds rough, raspy strained, or breathy
• Difficulty chewing, swallowing, or speaking

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Importance of genetics in oral cancer

Genetic factors play a crucial role in oral cancer. These alterations disrupt essential cellular processes. One well-studied genetic factor is the TP53 gene, which is mutated in 40-70% of all oral cancers.⁸ TP53 acts as the ‘guardian of the genome’, repairing damaged DNA. However, loss-of-function mutations in TP53 can promote cancerous cell growth.”

Important genetic markers 

Other than TP53, additional generic markers play a crucial role in oral cancers. One such marker is CDKN2A, which acts as a stop signal in cell division, preventing rapid cell growth. Alterations in CDKN2A disrupt cellular processes, leading to uncontrolled tumour cell proliferation.⁹ HRas, another commonly mutated gene in oral cancer, functions as a prominent oncogene.¹⁰ These genetic markers are essential for understanding oral cancer.  

Tumor suppressor genes like CDKN2A and TP53, act as brakes, preventing cells from dividing uncontrollably. In contrast, oncogenes, such as HRAs, accelerate cancer cell growth. Advances in genetic research have paved the way for personalized medicine and novel genetic markers in oral cancer detection and treatment.

Family history and inherited disorders

A positive family history of cancer in one or more siblings is an additional risk factor for oral cancer.¹¹ Therefore, individuals with a history of oral cancer could benefit from screening and lifestyle modifications such as avoiding tobacco, avoiding prolonged exposure to UV rays,  avoiding alcohol, and maintaining good oral hygiene (regular dental care, brushing, and flossing). 

Furthermore, genetic counselling can be effective in circumstances where oral cancer is present within family history for screening, surveillance, and preventive measures. This could be especially effective as 66.70% of oral cancers are detected at an advanced stage of disease, with a 5-year survival rate of less than 50%.¹² Finding the cancer at an early stage is the key to ‘curing’ the cancer, patients detected with early cancer have much higher survival rates compared to those diagnosed at a later stage. 

Disorders like Fanconi anaemia (a rare genetic disorder that causes gradual bone marrow failure) are characterized by light or dark skin patches or abnormal thumbs. Secondly, dyskeratosis is congenital (another inherited disorder that causes bone marrow failure) which is characterized by abnormal nails, skin colour changes on the neck and chest, and white patches in the mouth. Patients diagnosed with these inherited disorders have a significantly higher risk of developing oral cancer.¹³ This shows the importance of genetics in an individual's susceptibility to oral cancer.

Lifestyle and environmental factors

Although the article has heavily focused on genetics, this is just a fraction of oral cancer. This is because most cases of oral cancer are not inherited! Furthermore, environmental factors such as tobacco use, alcohol consumption, poor oral hygiene, poor diet that lacks fruit and vegetables, mouthwashes with high alcohol content, and HPV infection also play a significant role in oral cancer development.¹⁴ One study showed that people who drank heavily and smoked had a 300 times higher risk of oral cancer than people who neither drank nor smoked.¹⁵ Therefore, public health initiatives have aimed at raising awareness through regular dental checks, tobacco cessation, and HPV vaccinations.

Summary

To conclude, oral cancer is a multifaceted disease influenced by a variety of genetic and environmental factors. Genetic predispositions and mutations, which can be inherited or sporadic contribute to oral cancer, but environmental factors and lifestyle factors also play a massive role in the development of oral cancer. It’s estimated about 75% of oral cancers are related to lifestyle and could have been prevented.¹⁶ 

The article has focused a lot on oral cancer and its potential causes through inherited genetic disorders, sporadic genetic mutations, and environmental factors. However, it's essential to highlight the need for early detection of oral cancer as the majority of them are diagnosed at a late stage. The survival rates are approximately 80-90% when detected at the earliest stage.¹⁶ Therefore, all should follow key self-examination tips, such as checking for unusual lumps. Any persistent symptoms, such as those mentioned in this article, should be immediately reported to your doctor.

FAQs

How can I prevent oral cancer?  

Eat a healthy diet, practice good oral hygiene (regular visits to the dentist), cessation tobacco smoking and chewing, avoid drinking more than 14 units a week, avoid prolonged sun exposure, and if in the sun, use SPF lip balm, wear hats, and undergo regular screening tests by a healthcare professional, especially if oral cancer runs in your family.

What role does genetics play in oral cancer?

Genetics can make an individual more susceptible to oral cancer. For example, mutations in the TP53 and CDN2A genes can disrupt cellular processes and promote tumorigenesis (this is a process that involves the transformation of normal cells into cancer cells). These mutations are commonly found in oral cancer. 

Can genetic testing help identify individuals at risk of oral cancer?

Genetic testing can help identify individuals with inherited genetic variations associated with an increased risk of developing oral cancer. However, this is not typically used as a standalone tool for oral cancer screening, and screening comes with its drawbacks.