Introduction

Definition and Overview

Oral cancer includes any cancer originating in the mouth or the back of the throat.¹ Mouth cancer can affect the lips, inside of the cheeks, gums or tongue.² In a process called metastasis, abnormal cells in these regions grow and divide uncontrollably and can spread to other healthy tissues and organs in your body.³ 

Prevalence and risk factors

Cancer is a highly prevalent disease with approximately 1 in 2 individuals being diagnosed in their lifetime.⁴ In the United States (US), oral cancer accounts for 3% of all cancers diagnosed yearly.¹ Research indicates that 20% of oral cancer patients experience recurrence with 76% diagnosed within the first 2 years.⁵ Age and gender play a major role in this cancer type, predominantly affecting individuals over 40, with men being twice as likely to be diagnosed as women.¹

Cancer is associated with worry, anxiety and uncertainty. Raising awareness of cancer subtypes and the role of preventative health can help mitigate these feelings and decrease the likelihood of recurrent diagnosis. 

This article will delve into the following key points:

• What is oral cancer recurrence?
• What are the risk factors associated with this cancer type?
• What are the signs and symptoms?
• How is oral cancer diagnosed?
• What are the treatment options?
• How to manage complications and side effects
• What are the prevention strategies?
• What support and resources are available?

Understanding oral cancer recurrence

Definition of recurrence

Cancer recurrence refers to the return of cancer after treatment.⁶ The initial treatment method may not have completely removed or destroyed all the cancer cells.⁶ Although this news can be concerning and shocking, understanding the risk factors, types of recurrence, and alternative treatment options is beneficial for individuals who receive this diagnosis. 

Types of recurrence

• Local recurrence: the cancer growth is in its original place, or is very close to the initial cancer diagnosis⁶ 
• Regional recurrence: the cancer and resulting tumour development is in the surrounding tissues or lymph nodes near the initial cancer⁶
• Distant recurrence: the cancer has spread from the original place of diagnosis to organs and tissues in distant areas of the body. This is referred to as metastatic cancer⁶

Risk factors for oral cancer recurrence

Initial stage and grade of cancer

Confirmation of oral cancer recurrence involves a health assessment referred to as restaging.⁶ A healthcare professional (HCP) will perform similar tests that were used to diagnose the original oral cancer to confirm the type of recurrence and how far the cancer has spread.⁶ If the cancer has returned, the letter ‘r’ will be assigned to the cancer stage.⁶

Mouth cancer has 4 stages according to its severity and spread.⁷ The initial stages are listed below. For more information on the final stages (3 and 4) please refer to this link.

• Stage 0: Also referred to as carcinoma in situ (CIS) or pre-cancer. This is a very early stage where the cancer cells are contained within the mouth lining and have not yet invaded other parts of the body
• Stage 1: Earliest stage of invasive cancer where the growth is 2cm or smaller or 5mm deep or less. Nearby tissues, lymph nodes and organs are cancer-free
• Stage 2: Either the cancer is 2cm and deeper than 5mm (but no more than 10mm) or larger than 2cm (but no larger than 4cm) and 10mm deep or less. Metastasis has not occurred at this stage

Grades of mouth cancer are important to establish what the cancer cells look like compared to healthy cells.⁷ This can help your doctor decide the best course of treatment.

• Grade 1 (low grade): the cancer cells do not look different to normal mouth cells
• Grade 2 (intermediate): the cancer cells look slightly different
• Grade 3 (high grade): the cancer cells look very abnormal

In some cases, it may be difficult to determine the grade, in which case the cancer will be graded ‘Gx’.⁷

Margins of the original surgery

If the cancer is aggressive, invading local tissues and spreading to distant parts of the body (distant metastasis), the original surgery may have failed to eliminate all cancer cells, resulting in recurrence.⁸ Increasing the margin of the tumour resection site in oral cancer patients at stage 3 or 4 could decrease the risk of recurrence.⁸ 

HPV status

Human papillomavirus (HPV) infection is strongly associated with a higher risk of oral cancer.⁹ There are over 100 types of HPV which infect the skin or cells lining the body cavities usually during sexual activity.⁹ The main type found in oral cancer is HPV 16, which is responsible for 25% of diagnoses in the UK.⁹ Patients infected with HPV show a higher stage of oral cancer compared to those that test negative.¹⁰ 

Tobacco and alcohol use

Smoking is linked with an increased risk of developing oral cancer with 25% of cases in the UK associated with the use of cigars, cigarettes and pipes.⁹ Those exposed to second-hand smoke should also be cautious as this can increase the risk of oral cancer. Drinking alcohol is also associated with a higher cancer risk as it causes 35% of mouth and oropharyngeal cancers in the UK.⁹ 

Genetic and molecular markers

The genome (complete set of genes) plays a major role in determining the likelihood of disease, its onset, and response to treatment. Mutations in genes responsible for maintaining cell growth can increase cancer risk by disrupting key biological processes. Genetic markers that regulate cell death and proliferation are linked to an increased risk of oral cancer recurrence.¹¹ 

Symptoms and signs of recurrence

If you experience any of the following symptoms for more than 2 weeks, please seek advice from a HCP.¹

• Changes in speech, swallowing or breathing
• Difficulty moving your jaw or tongue
• Persistent pain (e.g. sore throat or ear pain)
• New lumps, discolouration, irritation or swellings (e.g., mouth, lips, neck or throat)
• Bleeding in the mouth
• Numbness in your mouth or other areas
• Unexplained weight loss

Diagnosing oral cancer recurrence

Physical examination

Early detection is essential to ensure rapid diagnosis and treatment. Regular dental check-ups play a major role in detecting oral cancer through physical examination.¹ Dentists can check your neck, lips, mouth and back of the throat and refer you to a specialist if signs of cancer are observed. Additional imaging tests can confirm a cancer diagnosis and enable the appropriate staging of the disease.¹² 

Imaging tests

A range of imaging techniques can be used to diagnose oral cancer. The most common tests are positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT). Imaging is crucial to determine the staging of the tumour and the presence of metastases in local or distal areas. Test results are vital to facilitate treatment planning such as the scope of surgical resection.¹²

Biopsy procedures

Examination of a tissue sample using a biopsy can aid in diagnosis. This method is reliable and involves removing a section of soft tissue from the mouth or lymph nodes via surgery. Different tissue biopsy procedures include surgical, punch, lymph node and needle aspiration. Techniques such as immunofluorescent staining or DNA sequencing are then applied to the sample to confirm the presence of cancer cells.¹³

Treatment options for recurrent oral cancer

Oral cancer recurrence may require a combination of treatments depending on the stage and grade upon diagnosis.¹ This type of cancer is associated with a poorer prognosis compared to other sites in head and neck cancer. Managing recurrent oral cancer can be difficult due to previous heavy surgery treatment.¹⁴

Surgical intervention

Salvage surgery

Salvage surgery (or ‘rescue’) refers to surgery after failure of the initial treatment.¹⁵ This term is associated with the best survival rate compared to other standard treatments.¹⁴ It involves resection and removal of the tumour. However, inadequate margins at the tumour site can cause local or distal relapse. Trials investigating the combination of surgical salvage with immunotherapy in patients with oral cancer recurrence may shed light on improving survival rates and preserving organ function.¹⁴

Radiation therapy

Reirradiation

Certain tumours are unresectable using salvage surgery, especially at later stages when the cancer is more advanced. Radiation therapy offers an alternative treatment for oral cancer recurrence that is precise and can improve patient outcomes. Managing reirradiation presents a challenge if the patient has been previously exposed to high doses of radiation therapy during initial treatment.¹⁶ 

Chemotherapy

Chemotherapy usually involves delivering intravenous anti-cancer drugs into your bloodstream to destroy cancer cells. Chemotherapy is administered in cycles every 3-4 weeks.¹⁷ This can be combined with radiotherapy or pre- and post-surgery to improve patient outcomes.

Recurrent oral cancer may have spread throughout the body, which is usually treated with chemotherapy by itself or alongside radiotherapy. If cancer has metastasised at advanced stages, chemotherapy can also be combined with targeted or immunotherapy.¹⁷ Patients not eligible for salvage surgery or irradiation usually receive chemotherapy, however this is linked with poor prognosis.¹⁸

Targeted therapy and immunotherapy

Targeted therapy is a newer form of cancer treatment that utilises cancer-cell-specific drugs to attack and destroy targets to limit cancer progression.¹ This is advantageous compared to other treatments as healthy cells are not also destroyed in the process. Current clinical trials using targeted therapy may improve patient survival rates with advanced oral cancer.¹⁸

Immunotherapy stimulates specific elements in the immune system to enable the body to fight the immune-suppressing signals released by the cancer cells.¹⁹ There are 2 types of immunotherapy:¹⁹

• Active immunotherapy: immune cells from the tumour or blood are taken from the patient, cultured in a laboratory and returned to the body to directly attack the cancer cells
• Passive immunotherapy: involves enhancing the immune response through drugs that target cell surface receptors (CSRs) to enable antibody-dependent cell-specific immunity 

Palliative care

Palliative care refers to improving the quality of life for those with a life-threatening illness. Carers, social workers and psychologists can aid patients with severely advanced oral cancer to provide comfort and relieve suffering. This holistic approach supports the physical, psychological, spiritual and social needs of both the patient and their family. A multi-disciplinary team can help to assess and manage any pain that a patient is experiencing.²⁰

Managing complications and side effects

Complications from treatment can be short-term or long-lasting impeding patient recovery. Oncologists and dentists collaborate to ensure the patient has access to other HCPs if required including dietitians, speech therapists and social workers.²¹

Addressing treatment-related complications

Chemotherapy and radiotherapy prevent new cell growth, which can limit the rate at which tissue in the oral cavity can repair itself. Treatment-related complications can be due to direct damage of tissue, bone and salivary glands severely impacting quality of life. The mouth’s natural balance of healthy bacteria (microbiome) can be disrupted in anti-cancer treatment causing tooth decay, mouth sores and infections. A common side-effect of chemotherapy and radiotherapy is malnutrition due to the patient’s inability to eat.²¹ 

Managing pain and discomfort

The most common symptoms of oral cancer treatment include:²¹

• Infection
• Salivary gland function
• Changes in taste
• Oral mucositis (inflammation of mucous membranes)
• Pain

Regular dental checkups are crucial to prevent or reduce oral complications.²¹ 

Nutritional support

The risk of malnutrition is high in regards to chemotherapy or radiotherapy due to side effects such as nausea, vomiting, mouth sores and dry mouth.²¹ Consuming chopped or blended food, eating between meals to increase calorie intake, and taking vitamin and mineral supplements can be extremely beneficial for patients recovering from oral cancer. Nutritional support can aid your body during cancer treatment, fight infection, and help rebuild healthy tissue once treatment is finished.²¹ 

Speech therapy

Oral cancer can result in complications affecting the mouth and throat, such as dry mouth (xerostomia), which occurs when damage to the salivary glands reduces saliva production.²¹ Saliva is vital for swallowing, taste and speech.²¹ Speech and swallowing therapists can help improve time to recovery and assist in palliative care.

Prevention and monitoring

Lifestyle modifications

Key factors such as weight, diet and physical activity have been demonstrated to play a significant role in cancer prevention, prognosis, quality of life and recurrences.²² Maintaining a healthy lifestyle is essential for patients post-cancer treatment to assist with the healing process. Tracking elements such as alcohol consumption, tobacco use and level of exercise can provide insight into modifications that should be applied to relieve stress and improve recovery. Awareness of health specifications such as UK alcohol guidelines - a maximum of 14 units per week for men and women - is crucial to reduce the risk of a second cancer.⁹

Regular follow-up and monitoring

Patients who have been treated for oral cancer recurrence must have regular check-ups from HCPs such as oncologists and dentists. Follow-up appointments ensure the site of the cancer is monitored for any abnormal changes that may be a sign of recurrence. The rate of oral cancer recurrence varies from 18-76% post-standard treatment, highlighting the importance of routine examination.¹⁸ 

Support and resources

Support groups and community resources

Patients diagnosed with oral cancer recurrence can seek advice from their team of healthcare specialists on local support groups and charities.²³ These services can be beneficial in combating the overwhelming emotions associated with a recurrent cancer diagnosis.

• Mouth Cancer Foundation (support for head and neck cancers)
• Macmillan (online support, funding, research)
• Cancer Research UK (funding cancer research)
• Marie Curie (expert hospice care, support over the phone)

Palliative and end-of-life care options

Cancer charities such as Marie Curie provide companion volunteers to help patients feeling isolated attend appointments, hospice care to support patients with end-of-life options and free information for emotional assistance.²⁴ If you are concerned about a friend or family member and need support or access to resources to cope with a cancer diagnosis please seek advice from a healthcare provider.

FAQs

What is oral cancer recurrence?

Oral cancer recurrence is the return of cancer in the mouth, lips, back of the throat or lymph nodes in the neck after the initial treatment failed to destroy all the cancer cells. The recurrence may be local, regional or distant (metastasis).

How common is recurrence in oral cancer patients?

Recurrence after initial curative treatment can be found in 20% of oral cancer cases, with 76% occurring within the first 2 years.

Are there specific risk factors for oral cancer recurrence?

Yes, risk factors associated with oral cancer recurrence include tobacco and alcohol use, margins of the original surgery, HPV status and genetics such as a family history of head and neck cancer. 

How is oral cancer recurrence diagnosed?

Diagnosis of oral cancer involves a combination of physical examination, imaging tests and biopsy procedures. Regular dental check-ups are crucial for early detection. 

What treatment options are available for recurrent oral cancer?

Post-diagnosis of oral cancer stage and grade, a treatment plan can be established by a team of HCPs. This may include salvage surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy and palliative care. 

Can oral cancer recur after complete remission?

Yes, oral cancer may recur months or years after complete remission, underlining the importance of regular follow-ups.

What role does genetics play in oral cancer recurrence?

Genetics can influence an individual's susceptibility to oral cancer and the likelihood of recurrence. However, this is an ongoing area of research. 

How does treatment for recurrent oral cancer differ from treatment for the initial diagnosis?

If the oral cancer has returned, the treatment may be more aggressive than at the initial diagnosis and involve different methods to help combat the cancer’s behaviour and previous treatment outcomes.

What is the latest research on preventing and treating oral cancer recurrence?

Ongoing research focuses on targeted therapy and immunotherapies to improve patient outcomes and quality of life. Identifying and understanding genetic and molecular markers may lead to improved treatment and prevention strategies. 

Summary

Importance of awareness and regular check-ups

Oral cancer recurrence can severely impact a patient's emotional, physical and psychological well-being. Understanding the risk factors associated with cancer recurrence can aid in reducing a recovering patient's worry, fear and anxiety. Support services and charities play a significant role in funding research and improving palliative care to fight cancer and relieve suffering. Raising awareness of the prevalence of oral cancer recurrence will encourage patients in remission to ensure they have regular check-ups with the appropriate HCPs. Follow-up care is vital to monitor the patient for signs of recurrence. Early detection is crucial to improve patient outcomes by establishing a rapid and effective treatment plan, especially when previous treatment methods have failed to destroy all cancer cells.

Future directions in research and treatment

Future research into targeted therapy and immunotherapy will pave the way for more successful treatment and improved quality of life for patients diagnosed with oral cancer recurrence. Preventing cancer relies on a thorough understanding of the causes and the role of nutrition in maintaining your health. Making adjustments to key lifestyle factors such as diet, weight, and physical activity can alleviate stress, support overall well-being, and reduce the risk of disease.