In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.

Bernal Institute University of Limerick V94 T9PX Limerick Ireland

Cancer Pathology Department South Egypt Cancer Institute Assiut University Assiut 71526 Egypt

Cancer Research UK Clinical Trials Unit Institute of Cancer and Genomic Sciences College of Medicine and Dental Sciences University of Birmingham Edgbaston Birmingham B15 2TT UK

Department of Clinical and Molecular Pathology Institute of Molecular and Translational Medicine Palacky University 77900 Olomouc Czech Republic

Department of Histopathology Sheffield Teaching Hospitals Sheffield S10 2JF UK

Department of Histopathology Wye Valley NHS Trust Hereford HR1 2ER UK

Department of Pediatrics Faculty of Medicine and Dentistry Palacky University 77900 Olomouc Czech Republic

Department of Public Health and Epidemiology University of Birmingham Birmingham B15 2TT UK

Institute of Immunology and Immunotherapy University of Birmingham Edgbaston Birmingham B15 2TT UK

Medical School Queen's Medical Centre Nottingham NG7 2UH UK

School of Medicine University of Limerick V94 T9PX Limerick Ireland

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