Nasal pharyngeal carcinoma (NPC) is a form of nose cancer situated at the back of the nasal airway.
The Globocan project in 2012 reported that NPC is the third most frequent cancer among males in Malaysia and the fifth overall commonest cancer for both genders in Malaysia.
Males outnumber females by two to one, and the cancer has a bimodal age distribution, first peaking at adolescence, and then at the fifth to sixth decade of life.
It is common among Asians, especially those of Chinese descent.
How does it occur?
The human nose starts with the nostrils, the openings that can be seen from the outside. As we travel further inside to the back of the nose, we reach the nasopharynx, which connects to the back of the mouth and throat below.
The epithelial cells in the nasopharynx contribute to the formation of NPC.
Like all cancers, the cause of NPC is often multifactorial, i.e. a combination of factors contributing to cell abnormality and formation of cancer cells.
For simplicity’s sake , the causes of NPC can be classified into the following, though it is not an exhaustive list:
• Genetics – As mentioned above, NPC is common among the Chinese, even after migration to other nations.
It is common among first-degree relatives of affected patients, and among those with A2 HLA genetic haptotypes.
Research is still ongoing, especially in Asia, to identify the genes involved in NPC.
• Viral – Recent literature suggests that the Epstein Bar virus (EBV) has a contributory role in NPC.
University Kebangsaan Malaysia Medical Centre (UKMMC) Ear, Nose and Throat (ENT) Department head and consultant head and neck surgeon Associate Professor Dr Mohd Razif Mohamad Yunus says that a large number of the world’s population are EBV positive and asymptomatic.
Not all people with EBV develop NPC, but a large population of patients with NPC are positive for EBV.
There are still a small population of NPC positive patients with no evidence of EBV infection, although this is rare.
This is supported by a 2004 New England Journal of Medicine article based on research conducted in Taiwan, which revealed that EBV DNA was detected in the blood of 94 out of 99 patients with NPC.
There was no EBV DNA detected in all 40 patients with no NPC used as controls and patients cured of NPC.
• Environmental – Air pollution, smoking, incense and wood burning contribute indirectly to NPC.
Many studies have associated a link between cigarette smoking to NPC, but no reliable study has distinguished the difference in effect (if any) of pipe smoking, cigars, and lately, electronic cigarettes (vaping), in comparison to cigarette smoking in NPC.
Salted fish also contains nitrosamines that have been shown to have a link to NPC occurrence.
How does it present?
NPC may present with different symptoms.
Some may have a one-sided neck swelling as the only sign or symptom. Many will dismiss it and only seek medical attention when the swelling does not shrink, even with first-line antibiotic therapy.
The neck swelling is the spread of the tumour to the surrounding neck lymph nodes, drain lymph from the nose.
Others may have nasal symptoms such as bleeding (can be one sided or both) and nose blockage (if the mass has grown to a sufficiently large enough size to partially obstruct the nasal airways).
Ear pain and buzzing are also possible as NPC often develops in the area where the tympanic tube that equilibrates air in our ears opens up at the back of the nose.
Fast-growing tumours may invade the base of the skull towards the brain, resulting in an intracranial extension. In such cases, the patient may suffer from headaches and some may even have a clear discharge from their nostrils.
This occurs when the tumour has breached the outer layer covering the brain known as the dura, and eventually results in the leakage of clear fluid surrounding the brain known as cerebrospinal fluid (CSF), into the nose or ears.
These aggressive tumours may also compress the nerves in the brain and result in weakness of eye movement, as well as loss of hearing and smell.
UKMMC senior consultant ENT surgeon Prof Datuk Dr Balwant Singh Gendeh says these varied and unspecific symptoms often contribute to a delay in diagnosis in such patients, as they can be misleading.
If the patient’s neck swelling does not resolve with first and second line antimicrobials for a presumed lymph node infection, medical practitioners should have a strong suspicion of malignancy (either NPC or lymphoma) or chronic infection such as tuberculosis.
At this juncture, if symptoms and patient history is suggestive of NPC, a referral to an ENT specialist should be made.
Before that, the medical practitioner may request blood tests to check the blood count.
The ENT specialist will perform a thorough head and neck examination followed by nasal endoscopy, which is simply a visual examination of the back of the nose looking for the source of bleeding or any suspicious mass.
If there is a mass, a small tissue sample will be obtained and sent to the lab for microscopic examination and confirmation of diagnosis. This can be done in a controlled setting in the outpatient clinic or in the operation theatre if there is a tendency of uncontrolled bleeding.
An EBV DNA test or blood test can also be carried out.
Patients with neck swellings will be subjected to fine needle aspiration of the neck swelling. It is a straightforward outpatient procedure whereby a small needle is introduced into the neck swelling to obtain cellular samples for confirmation of diagnosis under the microscope.
If diagnosis is confirmed, the patient will be subjected to imaging tests – either a contrasted computed tomography (CT scan) or magnetic resonance imaging (MRI) of the head and neck to properly determine the spread of the cancer.
The ENT specialist may also request for a chest radiograph (x-ray) and abdominal ultrasound to rule out any spread of the disease.
These imaging tests will contribute to the staging of the disease and ultimately help direct treatment options.
A baseline hearing assessment can be done for hearing loss secondary to treatment and assessing the presence of concurrent ear infection.
Yes, there are treatment options for NPC.
Radiotherapy and chemotherapy are the treatment of choice in NPC. Radiotherapy alone may be used for early stage I and II diseases, while combined chemo-radiotherapy (CCRT) is often used for stage III and IV disease.
UKMMC consultant ENT surgeon Assoc Prof Dr Salina Husain notes that radiotherapy may cause damage to surrounding structures or structures in between the beam and the tumour.
This may result in scarring of surrounding tissue and patients may also experience trismus, which is difficulty in opening the jaw fully.
However, she adds that the benefit of CCRT often outweighs the risk in terms of survival, while side effects can be managed with lifestyle measures.
Technologies such as three-dimensional conformal radiotherapy and intensity modulated radiotherapy (IMRT) offer a higher dose and more focused delivery of radio-waves to the tumour in order to minimise damage to surrounding structures of the head and neck.
This is preferred in recurrent disease and is only available in select healthcare centres in Malaysia.
A referral to the dental surgeon will be required for a dental assessment as some patients may require extraction of teeth prior to CCRT and the management of good oral hygiene during treatment.
Chemotherapy can be given together or after radiotherapy treatment.
Chemotherapy plays an important role in improving local control of the disease and treating distant spread of the cancer.
Surgery is only indicated if there is disease spread to the neck, or in the case of recurrent or persistent NPC, in the nose.
Assoc Prof Mohd Razif says, “The ENT surgeon may have to perform a neck dissection to identify and remove swellings in the form of affected lymph nodes in the neck on either one or both sides of the neck.
“This is done if there is no spread of the NPC to other body sites and when there is a hope for cure.”
Surgery to remove the back of the nose or nasopharyngectomy will be performed if there is recurrence or persistent NPC after CCRT.
Prof Gendeh says, “Recent advances favours a minimally-invasive approach to a nasopharyngectomy by using endoscopic surgery that may allow access to the base of skull for better clearance of tumour in tertiary referral centres.
“If the centre lacks the facilities for a minimally-invasive approach, then the traditional open nasopharyngectomy may be perform- ed.”
He adds: “Ultimately, the decision for surgery should take into account the extent of tumour spread, tumour aggression, disease control, chances for cure and the patient’s wishes and expectations.”
Brachytherapy is a form of sealed radiation from a substance placed next to the affected area.
Gold grains or iodine seeds have been used to deliver high doses of radiation to the NPC site with less radiation to the surrounding structures.
Such stereostatic treatment has shown promising results in initial trials, but studies on larger population and long term effects are still ongoing.
The role of screening and surveillance
The early detection of NPC allows for early diagnosis and treatment.
The golden rule that prevention is better than cure still holds true.
However, there is a conundrum as screening tests should be proven to reduce morbidity and mortality, besides being socially and ethically acceptable.
A screening review conducted by the Health Ministry in 2011 in its Health Technology Assessment Report involved a systematic review and randomised control trial for testing the effectiveness and cost efficiency of screening for NPC among children and adults.
It involved four population-based studies from China, and among its findings was that there is insufficient evidence to recommend a population-based NPC screening programme as a public health policy in Malaysia as yet.
This is in line with Singapore’s policy that does not recommend mass screening of the general population with EBV blood tests in its 2010 Clinical Practice Guidelines.
“As a general guidance, individuals with first-degree relatives diagnosed with NPC should regularly visit their ENT doctor for a surveillance endoscopy to allow for early detection of the disease.
“However, this is merely precautionary and there has yet to be a guideline in Malaysia for the surveillance of NPC,” adds Assoc Prof Mohd Razif.
Several Asian countries recommend screening for all high risk family members aged over 30.
The journey of a patient with NPC will involve the family physician, ENT specialist, radiologist, oncologist, dental surgeon and occupational therapist, as well as the support of their loved ones.
One might lose the scent of a rose with NPC, but with early detection and newer treatment modalities, one might not lose the sight of the beauty of a rose.
Dr Hardip Singh Gendeh is a medical officer at the UKMMC Department of Otorhinolaryngology – Head & Neck Surgery in Kuala Lumpur. For further information, e-mail email@example.com. The information provided is for educational and communication purposes only and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.