Nasopharyngeal Cancer

What is Nasopharyngeal Cancer?

Nasopharyngeal cancer is a disease in which malignant (cancerous) cells form in the tissues of the nasopharynx. The nasopharynx is located behind the nose and just above the throat. It serves as a passageway for air travelling from the nose to the throat and the rest of the respiratory tract (breathing system). The nasopharynx is also connected to the ear via the Eustachian tubes which open into the middle ear.

Nasopharyngeal cancer is often difficult to detect and is diagnosed late for several reasons:

• The nasopharynx is not readily visible and small abnormalities may be easily missed.
• The symptoms of nasopharyngeal cancer, when present, can be vague and similar to other more common conditions.

Types of Nasopharyngeal Cancers

Most nasopharyngeal cancers start in the cells that line the nasopharynx (known as epithelial cells). They can be grouped according to how the cancer cells look under the microscope^1,2:

• Keratinising squamous cell carcinoma: The cancer cells in this type of nasopharyngeal cancer are covered with keratin (similar to the protein in hair and nails). This is the most common type in countries where nasopharyngeal cancer is rare.

• Non-keratinising differentiated squamous cell carcinoma: The cancer cells are not covered with keratin and look more like normal cells under the microscope. It is often seen with a common virus, known as the Epstein-Barr virus (EBV).

• Non-keratinising undifferentiated squamous cell carcinoma: The cancer cells look very different from healthy cells under a microscope and are called poorly differentiated or undifferentiated cells. This is the most common type seen in regions where nasopharyngeal cancer is more common and is often associated with EBV. Poorly differentiated or undifferentiated cancer cells tend to grow and spread more quickly.

• Basaloid squamous cell carcinoma: This is a rare and very aggressive form of nasopharyngeal cancer.

Cancer can also sometimes start in other cells in the nasopharynx such as in lymph nodes (lymphoma), soft tissue (sarcoma) and pigment-producing cells (melanoma). They are rare and account for less than 10% of cancers in the nasopharynx².

How Common is Nasopharyngeal Cancer?

Nasopharyngeal cancer is relatively uncommon worldwide, accounting for less than 1% of all cancers diagnosed. However, more than 80% of cases and deaths from nasopharyngeal cancer are reported in Asia, making it a significant health challenge in this part of the world³. In Singapore, nasopharyngeal cancer is the third most common cancer diagnosed in men aged between 30 to 49 years⁴.

The good news is that over the past fifty years, the incidence rate (number of cases per 100,000 population) of nasopharyngeal cancer cases has been steadily declining. This is thought to be related to a decreased intake of salted fish and preserved food, a reduction in tobacco smoking and the implementation of Epstein-Barr virus (EBV) screening for early detection in countries such as China where there is a high rate of EBV and nasopharyngeal cancer⁵.

What causes Nasopharyngeal Cancer?

Nasopharyngeal cancer begins when something triggers the cells that line the surface of the nasopharynx to develop mutations (changes) in their DNA that cause them to grow abnormally and develop into a tumour that can grow to invade nearby structures and spread to other parts of the body. The exact trigger for the mutation is not fully understood yet.

Nasopharyngeal Cancer Risk Factors

There are certain risk factors that increase the chance of DNA damage in cells that may lead to nasopharyngeal cancer. Such risk factors include ^6,7,8:

• Sex: Nasopharyngeal cancer is two to three times more common in men than it is in women.

• Race: Nasopharyngeal cancer is more commonly seen in parts of China, Southeast Asia, and northern Africa. In Singapore, people of Chinese ethnicity account for about 90% of nasopharyngeal cancer cases diagnosed⁹.

• Age: In areas where nasopharyngeal cancer is not common, it is more likely to be diagnosed in people who are aged over 50 years. However, in high-risk areas, younger people are more likely to be affected.

• Salt-cured foods: Chemicals (such as nitrosamine, which is a carcinogen/cancer-causing substance) released when cooking and consuming salt-cured foods, such as salted fish and meats as well as preserved vegetables, may enter the nasal passage, increasing the risk of nasopharyngeal cancer. Someone who consumes Chinese-style salted fish daily has up to twenty times higher chance of getting nasopharyngeal cancer compared to someone who rarely eats them⁵. Being exposed to these chemicals at an early age may increase the risk even higher. In contrast, diets high in nuts, legumes, fruits, and vegetables and low in dairy products and meat may help lower the risk of nasopharyngeal cancer¹⁰.

• Epstein-Barr virus (EBV): This common virus usually causes a mild flu-like illness and infectious mononucleosis or glandular fever. EBV can remain in a dormant (inactive) state in blood cells after the initial infection. In some people, the EBV infection subsequently triggers the development of nasopharyngeal cancer, although it is not fully understood how and why. It is possible that a person’s genes or smoking may affect how the body responds to the virus. EBV is found in up to 85% of nasopharyngeal cancers⁵.

• Human papillomavirus (HPV): Infection with certain types of HPV may increase the risk of nasopharyngeal cancer.

• Alcohol and tobacco: Heavy alcohol intake and tobacco use can raise your risk of developing nasopharyngeal cancer, particularly for keratinising squamous cell carcinoma¹¹.

• Family history: Having one or more family members with nasopharyngeal cancer increases your risk of the disease. It is not clear if this is due to inherited genes, shared environmental factors (such as the same diet or living spaces), or possibly a combination of these¹⁰.

Having one or more of these risk factors does not automatically mean that you will get nasopharyngeal cancer. Many people with risk factors never develop nasopharyngeal cancer, whilst some with no known risk factors do.

What are the Signs and Symptoms of Nasopharyngeal Cancer?

This cancer has few or no symptoms in the early stages, which makes early detection difficult. When they do occur, signs and symptoms of nasopharyngeal cancer may include^6,7:

• A painless lump in your neck caused by swollen lymph node(s)
• Blood-tinged saliva
• Nose bleeds or blood-stained discharge
• Congestion or stuffiness in your nose
• Ringing in your ears
• Pain or pulsing in your ears
• Hearing loss
• Frequent ear infections
• Sore throat
• Headaches
• Blurred or double vision
• Facial numbness or weakness

Many of these symptoms are more likely to be caused by common ailments such as a viral infection. However, if you have any of these symptoms, especially if they persist for more than two weeks or get worse, you should see a doctor to have it checked out and treated if needed.

If you have symptoms or signs that suggest nasopharyngeal cancer, your doctor will investigate further to determine if you have cancer. Nasopharyngeal cancer may be detected through the following procedures and tests^6,7,12:

• Clinical history and examination: Your doctor will ask about symptoms, risk factors and family history as well as perform a physical examination including feeling your neck for any enlarged lymph nodes. A bedside neurological examination of the cranial nerves (nerves in your head and neck) may also be done, including testing of your hearing and vision.

• Blood tests: Blood tests to check your overall health including your blood count, kidney, liver and thyroid function will be done. Epstein-Barr virus (EBV) DNA test is a blood test to check for EBV DNA markers that are found in the blood of people who have been infected with EBV. Doctors may repeat this test during and after treatment to understand how the cancer is responding and what your prognosis (outcome) may be.

• Nasoendoscopy (Nasendoscopy or nasopharyngoscopy): During this procedure, the doctor puts an endoscope (a long flexible tube with a camera and light at the end) through the nose into the back of the throat to visualise the nasopharynx and look for abnormalities. A biopsy (tissue sample) may be taken using instruments inserted through the endoscope if any abnormal areas are seen.

• Biopsy sample testing: Samples of cancer cells obtained through biopsy is tested in the laboratory to provide further information on the type of nasopharyngeal cancer it is. In addition, biomarker testing may be done to look for specific genes, proteins and other substances (called biomarkers or tumour markers) that the cancer cells might have. The presence of biomarkers can guide cancer treatment selection

Depending on your signs and symptoms, you may also be referred for¹²:

• A baseline hearing test by an audiologist.
• A complete assessment of your eyes and vision by an ophthalmologist (eye doctor).
• A full dental and oral hygiene evaluation by a dentist.
• A swallowing assessment by a speech therapist.

How is Nasopharyngeal Cancer Assessed?

After nasopharyngeal cancer has been diagnosed, your doctor will determine the extent (stage) of the disease. Staging, usually done with CT scans, PET-CT scans or MRI, is carried out to find out whether the cancer has spread, and if so, to what parts of the body. Nasopharyngeal cancer spreads most often to nearby lymph nodes, bones, lungs and liver. The majority of nasopharyngeal cancers are diagnosed after they have already spread beyond the nasopharynx.

Doctors describe nasopharyngeal cancer stages as^1,13:

• Stage 0: Cancer only affects the top layer of cells inside your nasopharynx.
• Stage I: Cancer has grown into the oropharynx (back of your throat) or nasal cavity (space inside your nose).
• Stage II: Cancer has spread to one or more lymph nodes on one side of your neck or behind your throat on one or both sides.
• Stage III: Cancer has spread to surrounding tissues and lymph nodes on both sides of your neck.
• Stage IV: Cancer has spread to your skull, eye, cranial nerves, salivary glands or lower part of your throat. It may have spread to more distant areas of your body like your lungs or liver.

The lower the stage at diagnosis, the higher the chance of successful treatment and long-term survival.

Nasopharyngeal Cancer Treatment Options

When considering your treatment plan your doctor will take into account the following factors⁷:

• The stage of your cancer when it is discovered.
• The size, type and location of the tumour.
• The level of EBV DNA in your blood.
• Your age and overall health.
• Your preferences.

The first goal of nasopharyngeal cancer treatment is to get rid of the cancer. When that is unachievable, the focus may be on stabilising the cancer to prevent its progression for as long as possible and improving quality of life. Nasopharyngeal cancer can be treated with the following methods, often used in combination^6,14,15,16:

• Radiation therapy (Radiotherapy): Radiation therapy is the use of powerful, high-energy beams to kill cancer cells or keep them from growing. Radiation therapy is usually given to treat both the main nasopharyngeal tumour as well as nearby lymph nodes in the neck. For small, early-stage nasopharyngeal cancers, radiation therapy may be the only treatment required. In other situations, it may be combined with chemotherapy. Nasopharyngeal cancer radiation therapy treatments may involve:

  • External beam radiation (Radiation that comes from outside of your body): External beam radiation uses a machine outside the body that delivers radiation towards the cancer. This is the most common form of radiation therapy used in the treatment of nasopharyngeal cancers. Intensity-modulated radiation therapy (IMRT) and stereotactic radiotherapy are newer ways of delivering external radiation to the cancer with less damage to healthy tissue.

  • Proton beam radiation: Proton beam radiation therapy is a new form of high-energy, external radiation therapy that uses streams of protons (tiny particles with a positive charge) instead of x-rays to kill cancer cells. Protons cause little damage to tissues that they pass through and release their energy mainly at the target area. This means that proton beam radiation can deliver more radiation to the cancer with lower dose radiation and less damage to nearby healthy tissues.

  Radiation therapy to the head and neck area, especially when combined with chemotherapy, can often cause severe sores to develop in the throat and mouth which may make it difficult to eat or drink. Your doctor may recommend inserting a feeding tube into your stomach to deliver food and water to maintain your calorie and nutritional intake until your mouth and throat recover.

  Recent advances in radiation therapy technology, together with enhanced shielding techniques to protect healthy tissues, have led to a significant improvement in the precision of radiation delivery. This means that nerves, organs and tissues in the face, eyes and brain are more likely to be spared, improving the outcomes following treatment.

• Chemotherapy: Chemotherapy is the use of drugs to kill cancer cells or stop them from dividing. The drugs enter the bloodstream and can affect cancer cells all over the body. Chemotherapy is used in the treatment of nasopharyngeal cancers that have spread beyond the nasopharynx or that have recurred. Chemoradiation is chemotherapy given at the same time as radiation. The combination has been shown to be more effective than either treatment alone and is helpful for people whose cancers are locally advanced. However, this combined approach can be hard to tolerate, especially for people in poor health. Further chemotherapy either before or after radiation may be needed for some patients.

• Surgery: Surgery is not often used as a treatment for nasopharyngeal cancers as the area is difficult to access and is in close proximity to important nerves and blood. It is usually reserved for cases where a small cancer recurs at the nasopharynx or in the lymph nodes of the neck after initial treatment. Surgery may be performed either through open surgery or endoscopic (keyhole) surgery through the nose.

• Targeted therapy: Targeted therapies are drugs that block the growth of cancer by interfering with specific molecules present in cancer cells that are involved in tumour expansion and spread. Some targeted therapies only work in people whose cancer cells have certain genetic mutations. Monoclonal antibodies are a form of treatment that target specific proteins on nasopharyngeal cancer cells, such as EGFR which is a protein found on the surface of the cancer cells that help them grow and divide. By blocking EGFR, the drug helps to slow or stop cancer growth. It may be used along with chemotherapy in cases where the cancer has spread, recurred, or continued to grow after initial treatment¹⁷.

• Immunotherapy: Immunotherapy uses the body's natural defences to fight cancer by enhancing the immune system's ability to attack cancer cells. In recent years, immunotherapy drugs such as PD-1 inhibitors that target a protein on T cells to boost the immune system have been approved to treat advanced nasopharyngeal cancers that cannot be treated with radiation or have recurred or progressed after initial treatment¹⁸.

Nasopharyngeal Cancer Survival Rate

Compared to many other cancers, nasopharyngeal cancer has a relatively good outlook. The earlier it is detected, the higher the chance of cure. Around 25% of cases are diagnosed at Stage I or II, which has a 5-year survival rate of 93% and 87% respectively. This means that 9 out of 10 people with Stage I and II nasopharyngeal cancer are alive five years after their diagnosis. A further 25% of cases are diagnosed at Stage III, which still carries a good prognosis (outcome) with a survival rate of just over 80%. The remaining 50% of patients, however, are diagnosed with advanced (Stage IV) nasopharyngeal cancer and the prognosis for this group is less favourable, with a survival rate of 64%.⁹

It is worth noting that survival rates are grouped based on stage (how far the cancer has spread), but other factors such as your age, overall health and how well the cancer responds to treatment can also affect your prognosis (outcome). Even taking these things into account, the prognosis your doctor gives you will be an estimate based on the statistics we have of people who have had the same diagnosis. Your journey may still differ from another person’s in a similar situation.

Nasopharyngeal Cancer Screening

Screening refers to looking for cancer before a person has any symptoms. There is currently no recommended routine screening for nasopharyngeal cancer for the general population. It is therefore important, especially if you have one or more risk factors (see Nasopharyngeal Cancer Risk Factors above) to be vigilant and see your doctor for prompt investigation if you have any symptoms.

People at high risk of getting nasopharyngeal cancer, in particular those with a family history of the cancer should be closely monitored, usually with regular nasoendoscopy and blood test to detect the Epstein-Barr virus. This may detect nasopharyngeal cancer at an early stage when the cancer is localised and more likely to be cured with radiation therapy.

Nasopharyngeal Cancer Prevention

While there is no guaranteed way to prevent nasopharyngeal cancer, there are some measures you can take to reduce your risk¹⁴:

• Avoid or quit smoking: Smoking increases your risk of nasopharyngeal cancer and many other types of cancers. Quitting smoking can be very hard, so ask your health care provider for help. These might include support groups, medicines and nicotine replacement therapy.

• Limit or avoid alcohol consumption: Drink alcohol in moderation, if at all. For healthy adults, that means up to one drink a day for women of all ages and men older than 65 years, and up to two drinks a day for men aged 65 and younger.

• Eat a healthy, balanced diet: A diet with less fat, sugar, red meat and processed foods, and more fresh fruits, vegetables, nuts and whole grains can help to reduce the risk of many diseases and cancers including nasopharyngeal cancer. Limit the intake of salt-cured and preserved foods that contain nitrosamine, a known cancer-causing substance (carcinogen).

• Stay active and exercise regularly: Exercise improves your overall health and wellbeing. Try to exercise most days of the week. If you are new to exercise, start slow with a gentle activity such as a walk around the park, and work your way up gradually.

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