Ubiquitous Distribution of Epstein–Barr Virus and the Highly Uneven Distribution of Nasopharyngeal Carcinoma

Correspondence To the Editor: Nasopharyngeal carcinoma (NPC) is a type of cancer that is rare in western countries, but common in the Middle East, Southeast Asia, and Africa. Epstein–Barr virus (EBV) infection of nasopharyngeal epithelial cells, including interactions involving its putative cofactors, is commonly considered critical in NPC development. We propose that if this hypothesis is true, either the geographic distribution of EBV infections, or the associated cofactors, should mirror that of NPC. That is, for at least one of these factors, their prevalence should be significantly higher in the Middle East, Southeast Asia, and Africa than in western countries. However, this is not the case. Rather, EBV is a ubiquitous human herpes virus; more than 90% of adults, worldwide, have evidence of infection. Furthermore, EBV's cofactors have not been shown to parallel the geographic distribution of NPC. A virus is usually regarded as being oncogenic if it is able to induce the malignant transformation of cells. An EBV infection of healthy human nasopharyngeal epithelial cells is rare. Although such infections do occur, infection of these healthy cells primarily results in the lysis of the infected cells. In contrast, EBV is commonly found in the nasopharyngeal epithelial tissue of patients with NPC. These observations indicate that nasopharyngeal epithelial cells may be more prone to EBV infection after the onset of malignancies. Thus, EBV infections may play a role in late NPC events. Studies have shown that blood from NPC patients contains high densities of EBV or high titers of EBV antibodies; blood from healthy individuals shows low levels. [5] However, these studies were unable to determine whether the high EBV levels or EBV antibody titers occur before or after the onset of carcinogenesis. Thus, these data are amenable to two possible interpretations. First, EBV infection may be a risk factor for the transformation of healthy cells into NPC‑positive cells. Second, the immune system may have been impaired, leading to the development of NPC and allowing an increase in the number of EBV. In the latter case, EBV infection is unlikely to be a risk factor for the development of NPC but occurs concurrently with NPC. EBV can infect B‑cells and is associated with immune disorders that impair the body's immune system function. In this regard, EBV infection may present a general risk for the development of various diseases, including NPC. Indeed, research has shown that EBV infection is associated with …