Epstein-Barr virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country

Simon, Julia, Schroeder, Lea, Ingarfield, Kate ORCID: https://orcid.org/0000-0002-6910-0267, Diehl, Stefan, Werner, Jill, Brenner, Nicole, Liu, Zhiwei, Pawlita, Michael, Pring, Miranda, Butt, Julia, Ness, Andy and Waterboer, Tim 2020. Epstein-Barr virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country. International Journal of Cancer 147 (2) , pp. 461-471. 10.1002/ijc.33006

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Abstract

Epstein-Barr virus (EBV) causes nasopharyngeal carcinoma (NPC) in endemic regions, where almost every tumor is EBV-positive. In Western populations, NPC is rare, and human papillomavirus infection (HPV) has been suggested as another viral cause. We validated multiplex serology with molecular tumor markers, to define EBV-positive, HPV-positive and EBV-/HPV-negative NPCs in the United Kingdom, and analyzed survival differences between those groups. Sera from NPC cases (n = 98) and age- and sex-matched controls (n = 142) from the Head and Neck 5000 clinical cohort study were analyzed. IgA and IgG serum antibodies against 13 EBV antigens were measured and compared with EBER in situ hybridization (EBER-ISH) data of 41 NPC tumors (29 EBER-ISH positive, 12 negative). IgG antibodies to EBV LF2 correctly diagnosed EBV-positive NPCs in 28 of 29 cases, while all EBER-ISH negative NPCs were seronegative to LF2 IgG (specificity = 100%, sensitivity = 97%). HPV early antigen serology was compared to HPV molecular markers (p16 expression, HPV DNA and RNA) available for 41 NPCs (13 positive, 28 negative). Serology matched molecular HPV markers in all but one case (specificity = 100%, sensitivity = 92%). EBV and HPV infections were mutually exclusive. Overall, 67% of the analyzed NPCs were defined as EBV-positive, 18% as HPV-positive and 14% as EBV/HPV-negative. There was no statistical evidence of a difference in survival between the three groups. These data provide evidence that both, EBV-positive and HPV-positive NPCs are present in a low incidence country, and that EBV and HPV serum antibodies correlate with the viral status of the tumor.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License
Publisher:	Wiley
ISSN:	0020-7136
Funders:	National Institute for Health Research (NIHR) and Cancer Research UK, and also University Hospitals Bristol Research Capability Funding
Date of First Compliant Deposit:	27 April 2022
Date of Acceptance:	20 March 2020
Last Modified:	09 May 2023 12:08
URI:	https://orca.cardiff.ac.uk/id/eprint/149403

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