NPC Detection & Diagnosis

How is nasopharyngeal cancer detected and diagnosed?

Why is Nasopharyngeal Carcinoma difficult to diagnose?

NPC develops silently. Few symptoms are present during the early and intermediate stages. The nasopharynx is located deep behind the nose, inside the head (at the center of the skull). Visual examination via routine check-up is difficult. Special equipment and techniques are needed to detect changes in this 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 is subjective. Unless the cancer is large enough, it may be missed. Sometimes, the procedure is uncomfortable and may require local anesthetic using an endoscope.

Fiber-optic nasopharyngoscopy is the current standard of practice for detection of NPC. It is often done by an Ear, Nose, and Throat (ENT) Specialist. However, a significant number of early NPC cases remain clinically inconspicuous. Some are hidden under the lining of the nasopharynx mucosal surface and evade detection even by experienced ENT specialists. Historically, most NPC becomes clinically evident during the advanced stage. Less than half of those diagnosed at this stage survive.

Why early detection matters

The prognosis for NPC depends significantly on the extent of disease at diagnosis.

Patients diagnosed in the early stages have excellent long-term survival rates and prognosis. Unfortunately, less than 20% of patients are diagnosed during the more treatable stages.

The ten-year survival rates for tumor stages I, II, III and IV are estimated at 90%, 70%, 50% and 40% respectively, indicating better outcomes through early diagnosis and treatment.

Existing methods of detection

There are currently six options for detecting NPSC

Trans-oral mirror examination

This is the routine, visual examination of the nasopharyngeal space by a family physician or ENT surgeon. However, this method is inaccurate and difficult to perform due to frequent patient gag reflex. Compliance rate is low and false negative rates are high.

EBV Serology

This laboratory test relies on the detection of antibodies against EBV in the blood. It has a high false positive rate because over 90% of people have past exposure to EBV infections and subsequently develop positive serology. Even a common cold can affect the result. In addition, patients with positive serology may already be at an advanced stage of NPC. Therefore, serology is not useful for early-stage detection.

Circulating EBV DNA in plasma (Plasma DNA)

This method tests the amount of circulating EBV DNA in the blood. Rapid growth of tumor cells releases EBV DNA into the bloodstream. In addition, DNA is also released from dead tumor cells.

Circulating DNA has a short half-life. It is quickly removed by the liver. For circulating EBV DNA to be detectable, a significant tumor load needs to be present.

This method has higher sensitivity and specificity than EBV serology. However, the value of plasma EBV DNA in the screening and detection of early NPC is unknown. It is currently useful for monitoring treatment response.

Nasoendoscopy

This is the current gold standard used by ENT surgeons for identifying NPC. Local anesthetic is sometimes needed to minimize discomfort.

Nasoendoscopy relies on the subjective assessment and experience of the physician. Because a significant proportion of NPC can be underneath the deeper mucosal surface and not visible by endoscopy, false negative rates are as high as 40%. Small early-stage cancer may also be missed. There is also a minor risk of contamination and cross-infection from insufficient sterilization of the endoscope.

Biopsy

A surgeon inserts an endoscope into the patient’s nose, passes it through to the nasopharynx, and uses forceps to obtain samples for microscopic examination by a pathologist. This method is the gold standard for confirming the disease. While it is the most accurate, it is highly subjective. Surgeons can miss a small area of cancer and biopsy a negative site. Alternatively, the biopsy may not be deep enough, leading to a false negative.

A random, multiple-site, deep biopsy is recommended to avoid missed diagnosis. The nasopharynx is divided into 9 quadrants and samples are collected in all quadrants to minimize the risk of missing cancerous growths.

The NP Screen Advantage

NP Screen detects Epstein-Barr virus DNA, which is consistently present in all NPC cells. It is therefore a very sensitive and specific method for detecting NPC, even in the early stages.

A clinician takes a swab of the nasopharynx through the patient’s mouth. The sample is subsequently analyzed for the presence of EBV DNA. The advantages of this method include:

PATIENT CONVENIENCE AND SAFETY: the test can be done without sedation, pain or discomfort in an outpatient setting

ACCURACY: NP Screen can detect miniscule, potentially early-stage cancer, as well as cancer hidden underneath the mucosal surface, which may be missed by endoscopy.

DETECTION OF EARLY RECURRENCE: Clinical studies also suggest that this method may detect early local recurrence after radiotherapy, so further treatment can be initiated early.