Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours

Stevenson, A., Wakeham, K., Pan, J., Kavanagh, K., Millan, D., Bell, S., McLellan, D., Graham, S.V. and Cuschieri, K. (2020) Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours. Journal of Clinical Virology, 129, 104505. (doi: 10.1016/j.jcv.2020.104505) (PMID:32604039)

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Abstract

Background: Although HPV-positive oropharyngeal cancer (OPC) patients have improved prognosis compared to HPV negative patients; there remains an HPV-positive group who have poor outcomes. Biomarkers to stratify discrete patient outcomes are thus desirable. Our objective was to analyse viral load (VL) by droplet digital PCR (ddPCR), in HPV-positive patients with OPC on whom clinical outcome data were available. Methods: In a cohort of patients that had previously tested HPV positive via conventional PCR, VL was determined using ddPCR assays for HPV16 L1 and E6 genes. VL was classed as “medium/high” if more than 5.57 copies or 8.68 copies of the HPV 16 L1 or E6 gene were detected respectively. Effect of VL on overall survival and hazard of death & disease progression was performed with adjustments made for sex, age, deprivation, smoking, alcohol consumption and stage. Results: L1 VL ranged from 0.0014–304 gene copies per cell with a mean of 30.9; comparatively E6 VL ranged from 0.0012–356 copies per cell with a mean of 37.9. Univariate analysis showed those with a medium/high VL had a lower hazard of death; this was significant for L1 (p = 0.02) but not for E6 (p = 0.67). The ratio of E6 to L1 deviated from n = 1 in most samples but had no influence on clinical outcomes. Conclusions: HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cuschieri, Dr Kate and Stevenson, Mr Andrew and Bell, Dr Sarah and Wakeham, Dr Katie and Millan, Dr David and McLellan, Dr Douglas
Authors: Stevenson, A., Wakeham, K., Pan, J., Kavanagh, K., Millan, D., Bell, S., McLellan, D., Graham, S.V., and Cuschieri, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Virology
Publisher:Elsevier
ISSN:1386-6532
ISSN (Online):1873-5967
Published Online:20 June 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Journal of Clinical Virology 129: 104505
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9III-MRC-GU CVR Support Services