Nasopharyngeal Carcinoma
EBV is a necessary cause of undifferentiated NPC, with tumors displaying an EBV latency program characterized by the expression of EBNA1 and at least 1 of the latent membrane proteins (latent membrane proteins 1–2). In multiple case-control studies conducted in previous decades, associations between the presence of elevated anti-EBV antibody titers and NPC were found. More recent evidence from prospective studies in populations at high risk of undifferentiated NPC has confirmed these earlier observations and demonstrated that high antibody titers, particularly IgA antibodies directed against EBV structural proteins, precede the development of NPC. Taiwanese men who tested positive for VCA IgA antibodies had a higher risk of developing NPC than did men who tested negative for VCA IgA (hazard ratio = 22.0, 95% confidence interval (CI): 7.3, 66.9), even 5 or more years after antibodies were measured (hazard ratio = 13.9, 95% CI: 3.1, 61.7).
In a longitudinal study from China, Ji et al. described a characteristic window approximately 3 years before NPC diagnosis during which VCA IgA antibodies are elevated in the majority of individuals who develop the disease. Additional recent work in a high-risk region of China has provided a strong addition to the connection between prediagnostic EBV serological markers and NPC by describing a dose-dependent relationship, linking higher VCA IgA titers to elevated risk of NPC, and reporting higher disease risk in individuals with increasing versus stable VCA IgA titers over time (hazard ratio = 12.4, 95% CI: 5.4, 28.5).
Furthermore, in a prospective study of members of high-risk Taiwanese multiplex families, which are defined as families with at least 2 first- or second-degree relatives who have been diagnosed with NPC, Yu et al. observed elevated levels of both VCA IgA and IgA antibodies against the nonstructural EBNA1 protein before NPC diagnosis. Individuals who were positive for EBNA1 IgA at baseline experienced higher rates of NPC over follow-up (median, 6.5 years) than did persons who tested negative for EBNA1 IgA (relative risk = 6.6, 95% CI: 1.5, 61).