Defining the Clinical Utility of EBV Antibody Screening to Identify Individuals Susceptible to Nasopharyngeal Carcinoma (NPC) Within High-Risk, Multiplex NPC Families

The purpose of this proposed study is to evaluate the clinical utility of serum EBV antibody testing for the identification of individuals at increased risk of nasopharyngeal carcinoma (NPC) within high-risk, NPC multiplex families.

2,394 unaffected individuals from Taiwanese families, in which two or more relatives have been diagnosed with NPC, have been identified and sampled as part of an ongoing collaboration to identify genetic factors linked to NPC development. Serum from these individuals has been tested for three anti-EBV antibodies (VCA IgA, EBNA1 IgA, and anti-DNase) known to be associated with elevated risk of prevalent and incident NPC in general population studies. Results from testing of our study population indicate that apparently healthy individuals from high-risk multiplex families have a near 3-fold elevation in their EBV antibody prevalence when compared to the EBV antibody prevalence observed in the general community for these same EBV markers. However, the clinical implications of this apparent elevation in EBV antibody reactivity are not yet understood.

Therefore, we propose to evaluate whether individuals within our previously conducted high-risk family study with elevations in EBV antibody levels are at increased risk of incident NPC. Individual markers (VCA IgA, EBNIA1 IgA and anti-DNase antibodies) and combinations of markers will be evaluated to determine their performance as screening tests for NPC risk in high-risk multiplex families.

To achieve this goal, we propose to invite the 2,394 unaffected individuals from our multiplex family study, defined as those families with greater than or equal to 2 NPC. As a result of our recruitment efforts, we expect approximately 1,600 subjects to participate in an ear, nose, and throat (ENT) examination by an expert otolaryngologist to determine whether any of these individuals has occult or symptomatic NPC. We will correlate the three EBV antibody screening tests performed at the time of initial recruitment into our family study with NPC detection in the period between initial recruitment into the family study and the present study (median time between original EBV antibody testing and clinical evaluation = 5.5 years; range = less than 1 year - 10 years).

In addition to histopathological specimens collected for NPC diagnosis, participants in this study will be asked to agree to a brief risk factor questionnaire and to donate blood, saliva, a nasopharyngeal swab, nasopharyngeal tissue, and urine for future studies.

No accepted clinical management protocol exists for screening unaffected members from families at high-risk of NPC development. Results from this study have the potential to significantly impact the clinical management and follow-up of individuals with a family history of NPC.