Familial Nasopharyngeal Carcinoma 6

Screening and Early Diagnosis of Nasopharyngeal Carcinoma 61Fig. 5.2. Endoscopic view of an insignificant tumor in thenasopharynx. Arrows indicate the areas of hypervascularitywith mild touch bleeding. Biopsy from the hypervascularareas confirmed the diagnosis of NPCapplied to the hypervascular areas. If there is anytouch bleeding of these lesions, biopsies should betaken to rule out the possibility of NPC.The diagnosis of NPC depends on the histologicalexamination of tissue biopsies. Although endoscopicexamination enables the clinicians to have directvisualization of the nasopharynx, and allows tissuebiopsy for pathological diagnosis, this invasive procedureis not ideal for mass screening. In patientswith relevant symptoms but without significanttumors in the nasopharynx, it is also difficult for theclinicians to decide which patient should receivebiopsy. Efforts have been taken in the past decades todevelop cheap, fast, and reliable methods to assistclinical decision making, and to facilitate massscreening in the community. Implementation of EBVDNA in nasal swab as a tumor marker for NPC is animportant example.5.5.3Nasopharyngeal Swab for EBV DNA in theScreening of NPCThe EBV DNA can be identified in the nasopharyngealswabs of NPC patients. Sheen et al. (1998) investigatedthe presence of EBV DNA (Bam HI-W) byPCR and gel electrophoresis in 133 different tissuesfrom nasopharynx, nose, and sinus and found thatEBV DNA was present in 91% (85/93) of NPC tissuesand in 25% (10/40) of nonNPC tissues. Nasopharyngealswabs were subsequently performed in 55cases to check the presence of EBV DNA and to investigatethe feasibility of using such approach in thescreening of NPC patients. Anti-EBV VCA IgA andIgG serostatus were tested for comparison. EBV DNAwas present in 87% (26/30) of NPC patients and 42%(8/19) of nonNPC controls. Its sensitivity (87%) andspecificity (58%) were similar to those of anti-EBVseromarkers (88% and 44%). Lin et al. (2001) used amodified nasopharyngeal swab method to check thepresence of EBV DNA (LMP1) in NPC patients byPCR and gel electrophoresis. There were 95% (36/38)of the NPC swab samples and none of 28 controlsamples positive for EBV DNA, showing a sensitivityof 95% and a specificity of 100%. Using nasopharyngealswabs, NPC was diagnosed with a sensitivity of87% and a specificity of 98% by detection of LMP1(Hao et al. 2003). The combination of EBV LMP1 andEBNA could detect NPC with a sensitivity of 91% anda specificity of 98% (Hao et al. 2004). The combinationof VCA-BALF4 and EBNA1 was found to have asensitivity of 90% and a specificity of 93% (Hu et al.2007).The EBV DNA seems to be a good tumor markerfor the diagnosis of NPC. For the benefit of furtherdevelopment in this field, the standardization ofspecimen collection, sample preparation protocol,target DNA region (EBNA-1 or Bam HI-W or LMP-1),and assay methodology (PCR and gel electrophoresisor real-time quantitative PCR) is necessary.Furthermore, a well-designed large-scale epidemiologicstudy is needed to confirm the reliability andfeasibility of EBV DNA in the screening and diagnosisof NPC.5.6SummaryNasopharyngeal carcinoma (NPC) is a commonlydiagnosed head and neck malignancy in SoutheastAsia, and is associated with a number of potentialcausative factors. The EBV seromarkers and EBVDNA have been demonstrated to be associated withthe presence of the malignancy.NPC in its early stages are highly curable withradiation therapy, thus early diagnosis of the diseaseis critical for the malignancy. As individuals with afamily history of NPC are at higher risk for the