Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours.
Droplet digital PCR
HPV
Oropharyngeal cancer
Viral load
Journal
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
ISSN: 1873-5967
Titre abrégé: J Clin Virol
Pays: Netherlands
ID NLM: 9815671
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
05
03
2020
revised:
03
06
2020
accepted:
08
06
2020
pubmed:
1
7
2020
medline:
21
8
2021
entrez:
1
7
2020
Statut:
ppublish
Résumé
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. 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. 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. HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients.
Sections du résumé
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.
Identifiants
pubmed: 32604039
pii: S1386-6532(20)30247-X
doi: 10.1016/j.jcv.2020.104505
pii:
doi:
Substances chimiques
Oncogene Proteins, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104505Subventions
Organisme : Medical Research Council
ID : MC_PC_13063
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/9
Pays : United Kingdom
Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest No other authors report a conflict of interest in relation to this work.