General practitioners are crucial to screening and early detection of nasopharyngeal cancer, and can also play a key role throughout the patient journey. The SingHealth Duke-NUS Head & Neck Centre shares more.
Not only are primary care physicians crucial to screening and early detection of nasopharyngeal cancer, they can also play a key role throughout the patient journey – by helping their patients manage the side effects and comorbidities during treatment, as well as survivorship care to optimise outcomes.
Nasopharyngeal cancer (NPC), commonly known
as nose cancer, is a disease of particular interest to
Singapore due to its high incidence and tendency
to afflict people who are still in the economically
NPC arises from the epithelium of the nasopharynx
(also known as posterior nasal space). This small
cuboidal space is located behind the nasal cavity
and above the oropharynx. It has connections to the
middle ear via the Eustachian tubes on both sides of
the lateral walls.
According to data from GLOBOCAN 2020, more than
130,000 new cases of NPC are diagnosed worldwide
annually with the majority of cases occurring in South-East Asia, China and Northern Africa. Men are three
times more commonly affected than women.
Although data from the Singapore Cancer Registry
shows that the incidence of NPC has been gradually
declining since the 1970s, the incidence of NPC in
Singapore remains one of the highest in the world with
8.9 per 100,000 males affected per year.
While the reasons for this decline are unclear, it is
believed that lifestyle changes due to rapid economic
development are contributory. Most of the cases occur
in the Chinese race, with peak incidence at the age of 50-59 years.
Interaction of several factors increases the risk of NPC.
- Epstein-Barr virus (EBV) infection
- Environmental factors (frequent consumption of
salted and preserved foods, such as salted fish
and vegetables, which are high in nitrosamines –
carcinogenic compounds linked to NPC)
- Genetic predisposition – Patients with a family
history of NPC, especially in first degree relatives,
have an increased risk of developing NPC
SYMPTOMS AND SIGNS
In the early stage, patients with NPC may have
little or no symptoms. Some patients may present
with unilateral blocked ears that come and go, self-resolving
blood-stained sputum and small neck
nodes which are often attributed to upper respiratory
This makes diagnosis of NPC in the early stage
challenging. As a result, about three-quarters of patients with NPC have stage III or IV disease by the
time they are finally diagnosed.
In general, it may be prudent to refer the patient to
the otolaryngologist for an opinion if patients have
persistent symptoms that last more than a month or
are recurrent. Common symptoms and signs of NPC
are listed in Table 1 below.
- Blood-stained sputum / nasal discharge
- Blocked ears (especially unilateral)
- Nasal blockage
- Ear discharge
- Neck mass (especially if recurrent)
- Diplopia (due to sixth cranial nerve involvement)
- Headaches (due to base of skull involvement)
- Facial numbness (due to fifth cranial nerve
- Symptoms of metastatic disease
- Weight loss / loss of appetite
- Bony or back pain
- Abdominal symptoms related to liver metastasis (e.g., pain, jaundice)
- Without a nasoendoscope, it may be
difficult to visualise the primary tumour in
the nasopharynx, particularly if the tumour
is small (Figure 1)
- Rarely, large nasopharynx tumours can
be visible from the nostril or oropharynx
- Otitis media with effusion (especially if
unilateral) (Figure 2)
- Neck nodes
- Cranial neuropathies (III, IV, V, VI)
- Signs of metastatic disease
- Bony tenderness
- Pleural effusion
Figure 1 Tumour in
the post-nasal space
extending into the
fossa of Rosenmüller
and abutting the
posterior cushion of the Eustachian tube
Figure 2 Otitis
media with effusion
obstruction of the
opening in the
Photographs courtesy of Dr Constance Teo
The use of EBV serology (EBV VCA-IgA and EBV EAIgA)
and plasma EBV DNA has been proposed as a
screening test for NPC. However, there is no good
evidence to date that routine mass screening (even
in highly endemic populations) could improve the
outcome of NPC in the general population.
In Singapore, the Report of the Screening Test Review
Committee (2019) recommends the use of EBV
serology in combination with nasopharyngoscopy
for screening only in high-risk individuals (i.e.,
individuals with a first degree relative [e.g., parent or
sibling] with NPC).
INVESTIGATIONS AND STAGING FOR NPC
Several investigations are routinely performed
to determine the stage of disease and fitness for
treatment. These include:
Biopsy of the nasopharyngeal mass seen on
nasoendoscope is essential for the diagnosis
of NPC. Undifferentiated carcinoma is the most
common subtype seen in Singapore, and other
less common histologies include keratinising
squamous cell carcinoma and non-keratinising
Full blood count and tests for renal function and
Hepatitis B screening is done for all patients due
to endemicity, so that patients can be started on
anti-viral treatment to prevent hepatitis B flare
Plasma EBV DNA is a blood test that measures
the viral load of EBV. This has been shown to be
a predictive marker (i.e., patients with persistent
EBV DNA detectable in the blood at the end of
treatment have a poorer prognosis compared to
patients with undetectable EBV DNA).
MRI of nasopharynx and neck to determine local
and nodal extent of disease
FDG PET-CT has the highest sensitivity and
specificity in excluding distal metastasis. Alternatively,
CT chest abdomen and bone scan may
be used if cost is a consideration.
Baseline audiometry is performed as patients may
develop hearing loss due to effects of treatment.
Once the scans are performed, the oncologist will
‘stage’ the disease. The staging system currently used
is from the 8th edition of the American Joint Committee
on Cancer (AJCC) staging system which uses a
predefined combination of size and extent of the
tumour, lymph nodes and presence of metastasis to
determine the stage.
Stage distribution in 2017 from our cancer registry are
- Stage I: 7.3%
- Stage II: 17.5%
- Stage III: 25.2%
- Stage IV: 50%
It is important to note that stage IV is divided into two
- Patients with stage IVA are those with locally
advanced disease, but no spread to other parts of
the body (i.e., still considered curable)
- Patients with stage IVB are those in which there is
evidence of metastasis beyond the head and neck
region (i.e., generally considered incurable)
The main treatment for NPC is radiotherapy,
also known as radiation therapy. Radiotherapy
uses powerful and targeted X-ray beams to cure
cancer by causing double-strand DNA breaks
in cancer cells. Typically, the treatment covers
the nasopharynx (where the primary tumour
sits) and the neck node regions (even if none
are seen on scans due to high incidence of
Patients undergoing radiation usually go for once-a-day treatment (approximately 20 minutes every
weekday, with weekend breaks to recover from
side effects) over seven weeks (typically 33 to
Current evidence suggests that the addition of
chemotherapy to radiation has a significant survival
benefit for patients with stage III and IVA NPC, and
some patients with stage II NPC.
Patients derive the most benefit when chemotherapy
is given concurrently with radiation, but further
chemotherapy either before or after radiation may
be needed for some patients. The two commonly
used chemotherapy agents in NPC are cisplatin and
In patients with metastatic NPC, chemotherapy plays
an important role to help palliate symptoms by
controlling the growth of the cancer.
Surgery is not a common treatment for NPC and is
usually reserved for cases where the cancer recurs
after initial treatment. In cases where there is a small
cancer recurrence at the nasopharynx or in the lymph
nodes of the neck, surgery may be considered to treat
the recurrence. This may be performed either through
open surgery or endoscopic (keyhole) surgery through the nose.
The GP’s Role in NPC Patient Care
MANAGING SIDE EFFECTS OF TREATMENT
Most patients undergoing treatment will experience some side effects. Radiation side effects are divided into
acute effects (i.e., side effects that occur during radiation treatment) and late effects (i.e., side effects that
manifest many months to years after completion of radiation).
The oncologist will monitor patients closely during treatment to manage side effects, but patients may
still present to primary care if their symptoms are not better, especially if after-hours. Common side effects
of radiotherapy and chemotherapy are listed in Table 2 below.
- Skin reactions – dermatitis and
- Sore mouth/throat as a result of
mucositis – usually managed with
analgesia and topical medications
such as triamcinolone
- Dysphagia from mucositis leading
to weight loss – Encourage soft blended food, analgesia before
meals and nutritional milk replacements. Nasogastric tube may be needed if weight loss
- Hoarseness of voice
- Earaches or difficulty hearing
- Permanent xerostomia
- Dental decay due to
- Voice changes
- Dysphagia, with some patients needing tube feeding due to persistent aspiration pneumonia
- Vision changes / blindness
- Radiation myelopathy (very rare)
- Carotid stenosis
- Secondary malignancies
- Loss of appetite
- Nausea and vomiting
- Thinning or loss of hair
- Peripheral neuropathy
- Ototoxicity leading to hearing loss and tinnitus
- Liver dysfunction
- Cytopaenia (anaemia, neutropaenia and thrombocytopaenia)
- Sepsis (including neutropaenic sepsis)
WHAT GPs CAN LOOK OUT FOR IN NPC PATIENTS
There are a few considerations that a primary care physician should look out for, when a patient on
active NPC treatment presents to the clinic (Table 3).
Patients with dysphagia/mucositis may have reduced food intake. This may cause
hypoglycaemia that requires temporary adjustment in oral diabetic medications / insulin.
Patients with diabetes are also prone to diabetic ketoacidosis if they develop sepsis.
Poor fluid intake can lead to dehydration. Anti-hypertensives may exacerbate
hypotension caused by dehydration, and may have to be stopped temporarily.
Patients on treatment may develop febrile neutropaenia. This is a medical emergency
and patients should be referred to the accident and emergency department.
Patients on chemotherapy are given antiemetics. Despite this, some patients continue to
have nausea and vomiting. Patients should be referred back to the hospital if there are
signs of dehydration.
Pain (from mucositis)
Patients may consult their primary care physician due to uncontrolled pain. In general,
nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided due to the small risk of
nephrotoxicity, especially when patients are on cisplatin chemotherapy and may be
PROGNOSIS OF NPC
The prognosis of NPC is generally very good. The
reported five-year survival rates are:
- Stage I disease – 93%
- Stage II disease – 87%
- Stage III disease – 81%
- Stage IVA disease – 65%
- Stage IVB disease – 63%
FOLLOW-UP AND SURVIVORSHIP CARE
The oncologist will follow up with patients at regular
intervals for a minimum of five years. During the
consultations, patients are assessed for evidence
of recurrence using clinical examinations and
investigations. Long-term side effects, if any, are
monitored and managed.
Primary care physicians play an important role in
survivorship care. Some common issues that primary
care physicians should pay attention to are listed in
Patients who undergo radiation to the head and neck region have a slightly elevated risk of carotid artery stenosis, leading to strokes. Hence, optimal control of cardiovascular
risk such as diabetic control, blood pressure control, lipid levels control and smoking
cessation is important to minimise the risk of stroke.
Patients with NPC may develop xerostomia after treatment. This leads to early dental
decay. In general, extractions are not recommended, and patients should be advised to
see their dentist every six months.
About 5% of patients may develop chronic swallowing problems. Some of them may
present with recurrent chest infections due to aspiration pneumonia. Patients with this
symptom need to be referred back to the hospital for assessment by a speech therapist.
Hypothyroidism is a known long-term complication of radiation to the neck. The primary
care physician may be asked to co-manage this with the oncologist.
NPC is not uncommon in Singapore. Primary care physicians play an important role in early detection of the
cancer, managing comorbidities during treatment as well as looking after patients after the end of their treatment.
Singapore Cancer Registry 50th Anniversary Monograph (1968 – 2017). Accessed from: https://nrdo.gov.sg/publications/cancer
GLOBOCAN 2020 Nasopharyngeal Cancer Fact Sheet. Accessed from: https://gco.iarc.fr/today/data/factsheets/cancers/4-Nasopharynx-factsheet.pdf
Report of the Screening Test Review Committee (2019). Accessed from: https://www.ams.edu.sg/view-pdf.aspx?file=media%5c4817_fi_59.pdf&ofile=STRC+Report+March+2019.pdf
Dr Soong Yoke Lim is a Senior Consultant Radiation Oncologist and Deputy Chair at
the National Cancer Centre Singapore (NCCS). He sub-specialises in the radiotherapy
management of patients with gynaecological and head and neck cancers. Dr Soong
has an interest in cancer survivorship and is the medical advisor for the Nasopharyngeal Cancer Support Group at NCCS.
GPs can call the SingHealth Duke-NUS Head & Neck Centre for appointments at the following hotlines:
Singapore General Hospital: 6326 6060
Changi General Hospital: 6788 3003
Sengkang General Hospital: 6930 6000
KK Women’s and Children’s Hospital: 6692 2984
National Cancer Centre Singapore: 6436 8288
National Dental Centre Singapore: 6324 8798