Abstract
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.
Highlights
The incidence of oropharyngeal cancer (OPC) has increased dramatically over the last two decades including in the United Kingdom [1,2]
While the extent of HPV driven OPC varies, data converge on the fact that HPV positive status is independently associated with better clinical outcomes [4,5]
This has led to a recent change in tumour classification which incorporates HPV status and trials to determine the efficacy of de-escalated therapy in HPV positive OPC patients [6,7]
Summary
The incidence of oropharyngeal cancer (OPC) has increased dramatically over the last two decades including in the United Kingdom [1,2]. While the extent of HPV driven OPC varies, data converge on the fact that HPV positive (versus negative) status is independently associated with better clinical outcomes [4,5]. This has led to a recent change in tumour classification which incorporates HPV status and trials to determine the efficacy of de-escalated therapy in HPV positive OPC patients [6,7]. 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). Conclusions: HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients
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