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The Physiologic Reservoir of Epstein-Barr Virus Does Not Map to Upper Aerodigestive Tissues

Authors

  • Per Gunnar Liavaag MD,

    1. Department of Otolaryngology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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  • Roy K. Cheung MSc,

    1. Departments of Paediatrics and Immunology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
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  • Jeroen D.F. Kerrebijn MD,

    1. Department of Otolaryngology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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  • Jeremy L. Freeman MD,

    1. Department of Otolaryngology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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  • Jonathan C. Irish MD,

    1. Department of Otolaryngology, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada.
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  • Hans-Michael Dosch MD

    Corresponding author
    1. Departments of Paediatrics and Immunology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
    • Hans-Michael Dosch, MD, Departments of Paediatrics and Immunology, University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto Ontario Canada, M5G 1X8;
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  • Supported by the the Medical Research Council of Canada and the Saul A. Silverman Family Foundation, and Temmy Latner/Dynacare, Toronto, Canada.

Abstract

The human Epstein-Barr herpesvirus (EBV) has distinct oncogenic potential, but with over 90% of the adult world population infected, malignancy is a rare outcome of carrier status. However, EBV's association with over half of Hodgkin's and non-Hodgkin's lymphomas as well as several solid tumors, notably nasopharyngeal carcinoma, makes EBV-linked malignancies one of the largest single cancer entities. EBV is a B-lymphotropic virus, well controlled by surveillant T cells in immunocompetent hosts. To determine the presence and site of principal virus reservoirs is a likely prerequisite for understanding the etiology of EBV-associated tumors. Its near 100% association with nasopharyngeal carcinoma led to postulates that the upper aerodigestive tract tissue may be common sites of persistent latent or low-grade replicating infection. Using a protocol designed to avoid viral crosscontamination, the authors employed polymerase chain reaction to detect genomic EBV DNA sequences in 231 biopsies from different mucosal sites in the upper aerodigestive tract, as well as from salivary gland tissue and neck nodes in individuals not suspected to have EBV-related malignancy. Only two samples, one from oral cavity mucosa and one from parotid gland tissue, were positive for EBV. The observation that oropharyngeal tissue is not the principal EBV reservoir has mechanistic implications for the development of EBV-positive tumors in that locale.

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