Research Papers:

Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a non-endemic area

Salvatore Alfieri _, Nicola Alessandro Iacovelli, Sara Marceglia, Irene Lasorsa, Carlo Resteghini, Francesca Taverna, Arabella Mazzocchi, Ester Orlandi, Marco Guzzo, Roberto Bianchi, Diana Fanti, Laura Pala, Sara Racca, Roee Dvir, Pasquale Quattrone, Annunziata Gloghini, Chiara Costanza Volpi, Roberta Granata, Cristiana Bergamini, Laura Locati, Lisa Licitra and Paolo Bossi

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Oncotarget. 2017; 8:47780-47789. https://doi.org/10.18632/oncotarget.17822

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Salvatore Alfieri1, Nicola Alessandro Iacovelli2, Sara Marceglia3, Irene Lasorsa3, Carlo Resteghini1, Francesca Taverna4, Arabella Mazzocchi4, Ester Orlandi2, Marco Guzzo5, Roberto Bianchi5, Diana Fanti6, Laura Pala7, Sara Racca8, Roee Dvir8, Pasquale Quattrone9, Annunziata Gloghini9, Chiara Costanza Volpi9, Roberta Granata1, Cristiana Bergamini1, Laura Locati1, Lisa Licitra1,10 and Paolo Bossi1

1Department of Medical Oncology 3, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

2Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

3Department of Engineering and Architecture, University of Trieste, Trieste, Italy

4Laboratory of Immunohematology & Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

5Department of Head and Neck Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

6Laboratory of Clinical Chemistry and Microbiology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

7Department of Medical Oncology of Melanoma and Sarcoma, Istituto Europeo di Oncologia, Milan, Italy

8Laboratory of Clinical Microbiology & Virology, San Raffaele IRCCS Hospital, Milan, Italy

9Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

10Department of Medical Oncology 3, University of Milan, Milan, Italy

Correspondence to:

Salvatore Alfieri, email: salvatore.alfieri@istitutotumori.mi.it

Keywords: nasopharyngeal cancer, Epstein-Barr virus, prognosis, head and neck cancer, non endemic

Received: February 06, 2017     Accepted: April 12, 2017     Published: May 11, 2017


The prognostic value of pre-treatment Epstein-Barr Virus (EBV) DNA viral load for non-endemic, locally-advanced, EBV-related nasopharyngeal cancer (NPC) patients is yet to be defined. All patients with EBV encoded RNA (EBER)-positive NPC treated at our Institution from 2005 to 2014 with chemotherapy (CT) concurrent with radiation (RT) +/- induction chemotherapy (ICT) were retrospectively reviewed. Pre-treatment baseline plasma EBV DNA (b-EBV DNA) viral load was detected and quantified by PCR. Median b-EBV DNA value was correlated to potential influencing factors by univariate analysis. Significant variables were then extrapolated and included in a multivariate linear regression model. The same variables, including b-EBV DNA, were correlated with Disease Free Survival (DFS) and Overall Survival (OS) by univariate and multivariate analysis.

A total of 130 locally-advanced EBER positive NPC patients were evaluated. Overall, b-EBV DNA was detected in 103 patients (79.2%). Median viral load was 554 copies/mL (range 50–151075), and was positively correlated with T stage (p=0.002), N3a-b vs N0-1-2 stage (p=0.048), type of treatment (ICT followed by CTRT, p=0.006) and locoregional and/or distant disease recurrence (p=0.034). In the overall population, DFS and OS were significantly longer in patients with pre-treatment negative EBV DNA than in positive subjects at the multivariate analysis.

Negative b-EBV DNA can be considered as prognostic biomarker of longer DFS and OS in NPC in non-endemic areas. This finding needs confirmation in larger prospective series, with standardized and inter-laboratory harmonized method of plasma EBV DNA quantification.

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