Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma (NPC) is a malignant tumour in the nasopharynx. It is the most common head and neck cancer in Hong Kong. Due to its prevalence in Southern China, it is also known as “Canton tumour”. There are around 772 new cases of NPC in 2021 in Hong Kong. The incidence rate is around 3 times higher for men (male and female ratio is 2.6: 1), whereas the peak incidence age is around 50 to 60.

The nasopharynx lies at the centre of the head. It is posterior to the nasal cavity and paranasal sinuses, and is connected to the pharynx underneath. NPC can spread to the Eustachian tube, which connects the nasopharynx to the middle ear, and nearby nerves. Furthermore, it has a strong lymphatic link, so it is common to spread to neck lymph nodes.

If discovered at an early stage, the cure rate is high. For stage I disease, the cure rate is about 90%.

There are four major known risk factors for NPC:

• Heredity: the most significant risk factor. First degree relatives (including parents, siblings and children) of an NPC patient have a higher risk of developing NPC than others.
• EB Virus (Epstein-Barr Virus) infection: the virus has been linked to an increased risk of developing NPC in persons who have the specific genetic make-up. The blood serum of most NPC patients contains one or more antibodies directed against the virus.
• Diet: NPC has a high incidence rate in Southern China, which may be related to the predilection for pickled vegetables and salted fish. Pickled food contains a large amount of chemicals, which may be detrimental to health upon accumulation inside the body. Animal experiments also showed that excessive intake of salted fish might induce nasal cancers. 
• Smoking: smokers have a higher risk of developing NPC than non-smokers

The nasopharynx is a non-exposed organ. In the early stage of NPC, there may be no obvious symptoms. However, when the tumour grows and spreads to other tissues, the following symptoms may appear:

• Stuffiness, nose bleeding or haemoptysis (blood-stained sputum)
• Post-nasal drip: mucus from the nose drips down the back of the throat
• Hearing loss, tinnitus (ringing in the ear) or discharge from the ear canal: the Eustachian tube is blocked by the tumour
• Swollen neck lymph nodes
• Headache (sustained migraine: a severe recurring throbbing headache), facial paralysis, double vision: when the tumour cells invade the cranium and surrounding nerves
• Hoarse voice, dysphagia (difficulty in swallowing)
• Weight loss, emaciation (becomes abnormally thin or weak)

Symptoms of the nose may not directly suggest NPC. You may observe if the symptoms persist for more than two weeks. However, if hearing loss, tinnitus or neck lymph node swelling is observed, you should consult an otolaryngologist (ear-nose-and-throat doctor) for checking as soon as possible. 

There are a number of diagnostic tests for nasopharyngeal carcinoma, including blood tests and imaging scans. The tests you take will depend on the type and stage of cancer.

The check-ups include:

• Blood check: to measure the blood serum concentration of antibodies directed against EB Virus
• Endoscopy: to check for any visible tumours or abnormalities in the nasopharynx
• Biopsy: the most used diagnostic method for cancer. When a suspected tumour is observed in the nasopharynx via endoscopy, a small piece of tumour tissue will be removed for further examination.

Once the patient is confirmed to have NPC, further tests may include the following:

• MRI Scan: a magnetic field is used to produce images of a cross-section of the interior of the body
• CT Scan: a number of detailed pictures are taken inside the body from different angles to create a 3D image. The scan helps locate the tumour and shows whether it has spread to other body parts.
• PET Scan: cancer cells are more metabolically active than normal cells. Therefore, they show up brighter in the picture. The scan helps determine the extent of the tumour.
• Chest X-ray: radiation is used to produce images of the inside of the chest
• EB Virus Test: a blood test to check for antibodies and DNA markers of the virus, which is used to determine the appropriate treatment method.
• Hearing Test: the doctor will check if the patient can hear sounds of different frequencies to determine if the hearing is affected by the cancer

According to the World Health Organization (WHO), NPC is classified into 3 subtypes:

• Keratinizing squamous cell carcinoma
• Non-keratinizing carcinoma: including non-keratinizing undifferentiated carcinoma and non-keratinizing differentiated carcinoma
• Basaloid squamous cell carcinoma

Non-keratinizing undifferentiated carcinoma is the most common type in Southeast Asia.

Stage I

• The tumor is confined to the nasopharynx or has extended to the oropharynx and/or nasal cavity without parapharyngeal extension

Stage II

• The tumor has extended beyond the nasopharynx to parapharyngeal space with or without spreading to the lymph nodes on one side of the neck/ behind the throat

Stage III

• The tumour has spread to bilateral cervical lymph nodes, or the tumor has invaded the skull base.

Stage IVA

• The tumor has extended up to reach part of the brain or down to the lower part of the throat. The tumor may also have extensive lymph node involvement (size over 6cm or to the lowest part of the neck)

Stage IVB

• The tumor spreads to distant sites, such as the liver, bones, and lungs

The recommended treatment options depend on the stage of the disease and your general fitness. Radiotherapy is the main treatment for NPC. You might have radiotherapy alone or with chemotherapy (called chemoradiotherapy).

Surgery is usually only used if cancer comes back after the original treatment (recurrence).

Overview according to cancer stage:

Stage I – II

Radiotherapy is the main choice of treatment. Radiotherapy will cover the nearby lymph nodes even though they are not involved. This is preventive (prophylactic) radiation because some patients may have cancer cells in these lymph nodes that cannot be detected. Selected patients with Stage II NPC may have chemoradiotherapy.

Stage III – IVA

Patients with higher stages of NPC usually receive induction chemotherapy followed by chemoradiotherapy to the nasopharynx and the neck lymph nodes.

Radiotherapy

Radiotherapy is the mainstay of treatment for NPC. External beam radiotherapy uses high energy radiation beams to destroy cancer cells. The delivery of external beam radiotherapy is usually by intensity-modulated radiotherapy (IMRT) or tomotherapy. This treatment allows highly precise radiation beams to be concentrated at the tumor. This could effectively kill tumor cells and, at the same time, reduce radiation damage to the surrounding normal tissues.

Figure: Intensity-modulated radiotherapy for NPC

Procedure:

• Before starting radiotherapy, the patient will have a thorough examination by a dentist to check for dental and oral health. Since radiotherapy can cause tooth decay, damaged teeth may need to be removed before radiotherapy.
• The treatment team will arrange a planning session. The patient will have a mould (shell) of the head and neck that keep the patient very still during each treatment session. The radiation therapist may also make marks on the mould. They will use these marks to line up the radiotherapy machine for each treatment. The patient will then have a planning CT together with the mould.
• The radiotherapy team will then use the information from the CT scan and decide on the radiotherapy plan. Beam information from the planning CT will be sent to the machine for treatment delivery. 
• Treatment will be carried out on a daily basis (from Monday to Friday) for six to seven weeks. Each treatment will last for 15 to 20 minutes.

Figure: moulding before planning CT for fixing the body

Side effects:

• Tiredness and weakness
• Redness and irritation of the skin in the treatment area
• Sore mouth and throat
• Difficulty in chewing and swallowing
• Dry mouth
• Change of taste and loss of appetite
• Hearing impairment or loss
• Hypothyroidism
• Swelling in the neck or face (lymphedema)

Chemotherapy

Patients with higher stages will receive chemotherapy. Chemotherapy will be given either together with radiotherapy (chemoradiotherapy) or on its own (before or after chemoradiotherapy).

For chemoradiotherapy, patients will receive chemotherapy and radiotherapy together. Chemotherapy drugs make cancer cells more sensitive to radiotherapy. Chemotherapy is usually given intravenously through a tube placed into a vein. The drugs that are commonly used together with radiotherapy are cisplatin or carboplatin. They are usually given weekly or every 3 weeks.

For patients with Stage III to Stage IVA NPC, chemotherapy may be given before (induction chemotherapy) or after (adjuvant chemotherapy) chemoradiotherapy. The extra chemotherapy aims to control the disease and reduce the risk of recurrence. The chemotherapy may include a single drug or a combination of drugs. Examples include:

• Cisplatin and Gemcitabine
• Cisplatin and 5-FU
• Cisplatin and Capecitabine
• Cisplatin and Docetaxel +/- 5-FU
• Capecitabine 

Side effects:

• Fatigue
• Increased risk of infection
• Nausea and vomiting
• Loss of appetite
• Weight loss
• Sore mouth and dry mouth
• Change of taste
• Diarrhea or constipation
• Bleeding and bruising easily
• Hair loss

How do nasopharyngeal carcinoma patients take care of themselves? 

Patients need to be aware of many issues before and after radiotherapy and during recovery. More understanding can help patients face the illness positively.

Regular follow-up and examination

• After radiotherapy, patients may have complications such as otitis externa (inflammation of the external ear), dermatitis (inflammation of the skin) or malfunctioned organs etc. Regular follow-up ensures appropriate treatment.
• Regular follow-up and examination (including fiberoptic nasopharyngoscopy, EBV DNA, MRI, etc) may also allow early detection and treatment of recurrence or metastasis, which allows early treatment

Prevention of decayed teeth and mouth infection

• Radiotherapy will reduce the secretion of the salivary glands, so patients may have higher chances of tooth decay. Therefore, they should:
• Consume less sweet food and drinks, brush their teeth immediately after meals, and visit dentists regularly for checkups.
• Keep the mouth moist: patients may wipe their mouth with clean gauze moistened with salt water before they sleep.
• Stop smoking and drinking alcohol to prevent exacerbation of dry mouth.

Mouth exercises

• Radiotherapy may cause lockjaw. Patients should do mouth exercises every day to enhance the flexibility of their mouths.

Diet

• Patients should consume a high protein and high caloric diet to help speed up recovery.
• Avoid foods that are deep fried, spicy, or dry and hard
• Drink nutritious supplements to increase energy intake.

Skincare

• The skin and lips within the radiotherapy treatment area may be burnt. Patients should:
• Avoid using soap, medicated cleanser and skin lotion. Use mild skin lotion instead
• Avoid direct sunlight and UV light.

Around 15% of patients will have recurrent of the disease after radical treatment. Moreover, around 20% of the patients with NPC have distant metastasis to start with. Treatment options are mainly palliative chemotherapy with or without consolidation radiotherapy. The efficacy of chemotherapy on NPC is high, and it can improve survival. The use of immunotherapy (immune-checkpoint inhibitors, e.g. pembrolizumab, nivolumab, camrelizumab, toripalimab, tislelizumab) together with chemotherapy may improve the treatment outcome. However, some of these agents are not currently licensed in Hong Kong. 

Chemotherapy commonly used in metastatic NPC includes cisplatin, carboplatin, gemcitabine, taxane (paclitaxel or docetaxel), 5-FU, capecitabine, irinotecan, cyclophosphamide, etc.

• Those with family members having NPC should go for screening: NPC has been confirmed to have a strong tendency of familial aggregation. Epidemiological studies have shown that siblings or close relatives with NPC are four to eight times more likely to develop NPC than those with no family history. Therefore, it is recommended that anyone with a family history of nasopharyngeal cancer should visit an ENT doctor regularly for examination and screening as detecting and treating cancer at an early stage can improve the chance of cure.
• Screening with serum EBV antibody: Epstein-Barr virus (EBV) is highly associated with NPC. Screening with serum EBV antibody or serum EBV DNA together with fibreoptic endoscopy can detect around 50% of patients with Stage I NPC. 
• Avoid consumption of salted fish or other preserved food.
• Eat more fruits and vegetables to have a balanced diet.

Smart Patient Website - Nasopharyngeal Carcinoma

The Hong Kong Anti-Cancer Society--Nasopharyngeal Carcinoma

HK Cancer Fund--Hong Kong Nasopharyngeal Cancer Support 

HK Cancer Fund -- Cancer Booklets 

Special thanks to Mr. Kenneth Leung (Class M25), Ms. Hilary Chiu (Class M27), medical students of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Prof. NG Wai Tong, Department of Clinical Oncology, the University of Hong Kong, for authoring and editing this article.

Last updated on 18th Dec, 2023.