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 most family physicians. Special equipment and techniques are needed to examinethis area.
Doctors use an indirect mirror or nasopharyngoscope to examine the nasopharynx. These instruments allow the doctor to look directly at the nasopharynx for evidence of abnormal growths, asymmetries, bleeding, or other signs of disease.
Detection or screening of NPC using these techniques are subjective; experience dependent, and therefore may not be very accurate, unless the cancer is obvious or large enough to be seen by visualization. In some cases, it can be uncomfortable and may require the use of local anesthetic using endoscope to examine.
Fibre-optic nasopharyngoscopy is the current standard of practice (and the most commonly used) for detection of NPC, and is often done by an Ear, Nose and Throat (ENT) Specialist. However, a significant number of early NPC cases remain clinically inconspicuous. Some are simply hidden under the lining of the nasopharynx mucosal surface and evade visual 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 20% 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 visual examination of the nasopharyngeal space by family physicians or ENT surgeons. 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 laboratory test that relies on detection of antibody against EBV in the blood. This test has a high false positive rate due to the fact that 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 NPC stage with a large tumor and therefore, serology is not useful for early stage detection.
- Circulating EBV DNA in plasma (Plasma DNA) – This method involves testing the amount of circulating EBV DNA in the blood. Viral DNA in the blood come from rapid tumor cell growth and release of DNA into the blood. Some of the DNA are also released from dead tumor cells. Circulating DNA has a short half-life which is removed by the liverquickly. For the circulating EBV DNA to be detectable, 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 and detection for early NPC is not known. It has been shown to be useful to monitor treatment response.
- Nasoendoscopy – This is the method used by ENT surgeons and is the current gold standard of identifying NPC. Local anesthetic is sometime needed to minimize discomfort. This method relies on subjective assessment as well as experience of the physician. Since a significant proportion of NPC can be underneath the deeper mucosal surface and not visible by endoscopy (so called submucosal disease), false negative rates can be as high as 30% to 40%. Small early stage cancer may also be missed by this method. There is also a small 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 forceps device to obtain samples for subsequent examination under a microscope by a pathologist. This method is the ‘gold standard’ for confirming the disease. While this method is the most accurate to confirm the diagnosis, it is still highly subjective. Surgeons can miss a small area of cancer and biopsy a negative site. Similarly, the tumor may be very small or submucosal and the surgeon may not biopsy deep enough to obtain the sample, leading to a false negative result.A random multiple sites blind deep biopsy (the nasopharynx is divided into 9 quadrants and samples are collected in all quadrants to minimize the risk of missing cancerous growths) is done in some situations to avoid missing small or deep-seated NPC.
- NP Screen™ – This method detect Epstein Barr Virus DNA which has been shown to be consistently present in all NPC cancer cells even in early stage, rendering it a very sensitive and specific method to detect NPC.
A clinician takes a simple swab of the Nasopharynx, through the patient’s mouth in an outpatient clinic. The cellular sample is then analyzed in the laboratory for the presence of the EBV DNA. This detection method has a number of significant advantages, including: ease for the patient (can be done simply in an outpatient clinic without pain); ability to detect very tiny cancer (ie, potentially early stage detection) as well as those hidden underneath the mucosal surface not visible by endoscopy. Clinical studies also suggest that this method may detect early local recurrence after radiotherapy, so that further treatment can be initiated early.
Current detection methods and their estimated values for early detection are provided below:
|Sensitivity||Specificity||Value for Early Detection||Invasive Index
(1 least Invasive -10 Most Invasive)
|EBV Serology||80%-90%||50%-80%||20%*||10 (Blood samples with needle)|
|Plasma DNA||80%-95%||87%-95%||Unknown (Likely Low*)||10 (Blood samples with needle)|
Depending on the physician