Test and Diagnosis
Why is NPC difficult to detect?
NPC develops silently. Few, if any symptoms are noticed during the early and intermediate stages of the disease. The nasopharynx is located deep behind the nose inside the head (at the center of the skull) and is not easily visualized during routine clinical examination by family physicians. Special techniques are needed to screen this area. Doctors use an indirect mirror or direct nasopharyngoscopy instruments to examine the nasopharynx. These instruments allow the doctor to look inside the nasopharynx for abnormal growths, asymmetries, bleeding, or other signs of disease.
Detection or screening of NPC using these techniques are either inaccurate or very complex, requiring the use of local or sometimes general anesthetic for better patient’s comfort and safety. Fibre-optic nasopharyngoscopy Nasopharyngeal Endoscopy (nasoendoscopy) is often done by an Ear, Nose and Throat (ENT) Specialist. However, a significant number of early NPC cases remain hidden under the lining of the nasopharynx and evade detection even by the most experienced ENT specialist. Historically, most NPC becomes clinically evident during the advanced stage and less than half of those diagnosed survive.
Early Detection can Save Lives!
The prognosis for NPC is significantly dependent upon the extent of disease at diagnosis. Patients with early disease have excellent long term survival rates and prognosis. Today, there are less than 10% of patients diagnosed during the early, more treatable, stages of the disease. The survival rate for early diagnosis can exceed 90%. Unfortunately, there currently exists no accepted or widely promoted population based screening programs for early detection of NPC. The ten year survival rates for tumor stages I, II, III and IV are estimated to be 90%, 70%, 50% and 40% respectively, indicating better outcomes through early diagnosis and treatment.
Existing Methods for Detection
There are currently six known medical techniques that can detect NPC:
- Trans-oral mirror examination – This is the routine and traditional examination of the nasopharyngeal space by an ENT specialist/Otolaryngologist. However, this method is highly inaccurate and difficult to perform due to frequent patients gag reflex. The compliance rate is low and false negative rates are unacceptable.
- EBV Serology – This method is a blood laboratory test that also has a high rate of false positive results. Over 90% of the general population have past exposure to EBV infections and subsequently developed positive serology. Even a common cold that happened a few months ago can affect the result. In addition, patients with positive serology may already be in an advanced large tumor stage and may not benefit in detecting early stage disease.
- Circulating EBV DNA in plasma (Plasma DNA) – This method involves testing the amount of circulating plasma EBV DNA in the blood. The presence of the viral DNA in the blood is due to rapid tumor cell growth and release of DNA into the blood. Some of the DNA comes from dead tumor cells. Circulating DNA has a short half-life (10 to 15 min) which is removed by the liver. In order for the circulating EBV DNA to be detected, a significant tumor load needs to be present. This method has been shown to be better than the serology method with higher sensitivity and specificity in detecting NPC. At the present time, the value of plasma EBV DNA in screening for early NPC is not known.
- Nasoendoscopy – This is the current gold standard of identifying NPC. Local anesthetic is sometime applied to the nasal passage for fibre-optic nasopharyngoscopy by an Ear, Nose and Throat (ENT) Specialist/Otolaryngologist. However, a significant proportion of NPC patients are clinically inconspicuous (sub-mucosal disease). False negative rates can be as high as 30% to 40%. There is also a risk of contamination and cross-infection due to insufficient sterilization of the endoscope.
- Biopsy – A surgeon inserts an endoscope into the patient’s nose, passes it through to the nasopharynx to view the area and then uses a cutting tool to cut out tissue samples for subsequent examination under a microscope by a pathologist. This method is the ‘gold standard’ for detection, but it is still very subjective, since the sample area is approximate.
Human inspection of the samples through a microscope is only 80+% effective (from meta-analysis studies).
Sample collection is extremely important. If a tumor is prominently visible, then there is no issue about where to sample. However, if there is just a suspicion of NPC, or even a non-visible sub-mucosal tumor, then there is a high chance of missing the actual tumor when sampling.
Current practice is to perform a blind biopsy where the nasopharynx is divided into 9 quadrants and samples are collected in all quadrants to minimize the risk of missing cancerous growths. Yet still, sub-mucosal tumor identification depends on whether or not the biopsy sample was collected deep enough or not.
- NP Screen™ – A clinician takes a simple swab through the patient’s mouth, obtaining a cell sample, which is then analyzed for the presence of the Epstein Barr virus in the DNA of the cells. This screening test has a number of significant advantages, including: ease for the patient, ability to detect very tiny (early stage) tumours, as well as recurrent growths, extreme specificity and ability to detect sub-mucosal tumours which grow just underneath the surface and may be missed by both nasoendoscopic examination and biopsy.
Current screening methods and their estimated values for early detection are provided below:
|Sensitivity||Specificity||Value for Early Detection||Invasive Index (1-10)|