EBV is the principal etiological agent of infectious mononucleosis (IM) and is associated with several human cancers. There are at least 125,000 new cases of IM reported in the United States each year, and ~200,000 new cases of EBV-associated malignances are reported each year worldwide (). Although effective vaccines are licensed for prevention of infection with hepatitis B virus and selected subtypes of human papillomaviruses (HPVs), which cause hepatocellular carcinoma and cervical carcinoma, respectively, a vaccine for EBV remains unavailable.
Table 1 EBV by the numbers. Estimated new cases of EBV-associated cancers worldwide per year (9, 10).
EBV infects more than 90% of the human population and is associated with a diverse array of diseases (2
). Most infections occur during early childhood and are asymptomatic or cause nonspecific symptoms. However, in highly developed countries up to 50% of adolescents and young adults have not yet been infected, and nearly 50% of these susceptible individuals may develop IM if infected with EBV. IM presents with fever, swollen lymph nodes, sore throat, severe fatigue, and immune dysfunction. Although most persons with IM resolve their symptoms within 2 to 4 weeks, up to 10% can have fatigue that persists for 6 months or longer. Approximately 1% of persons have complications such as liver (hepatitis), brain (neurological), or blood (hematological) disease. IM is the major infectious cause of time lost for military recruits.
EBV is associated with a wide range of cancers that vary in incidence in different parts of the world. In the United States, Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma are the most common EBV-positive malignancies. In Southern China, the rate of EBV-associated nasopharyngeal carcinoma is 50 per 100,000 in men over the age of 50 years. EBV-positive Burkitt lymphoma is the most common childhood tumor in equatorial Africa and New Guinea. Gastric carcinomas are prevalent in Eastern Asia, Eastern Europe, and South America, with nearly 1 million new cases each year worldwide, and although only ~9% are EBV-positive, this cancer is the most common EBV-associated malignancy worldwide. Chemotherapy is effective for many EBV-associated malignancies, but up to 50% of survivors of all forms of Hodgkin lymphoma die from chemotherapy-associated complications, secondary malignancies, or disease relapse.
EBV-associated lymphomas occur in 1 to 20% of bone marrow and organ transplant recipients, depending on the type of transplant and the method of immunosuppression used, and is the second most common malignancy, after skin cancer, in organ transplant recipients. In persons infected with the human immunodeficiency virus (HIV), ~90% of Hodgkin and immunoblastic lymphomas and 50% of Burkitt lymphomas are EBV-positive. Although improved therapy for HIV has increased survival and reduced the prevalence of some tumor types in HIV-infected patients, the rates of EBV-positive Burkitt and Hodgkin lymphomas have not declined in this patient group and in the case of Hodgkin lymphoma, may actually be increasing. Other malignancies associated with EBV include certain non-Hodgkin lymphomas, T cell lymphomas, and smooth-muscle tumors.
Taken together, these epidemiological data show that prevention of these diseases through EBV vaccination would have a substantial public health and economic impact.