Centre for Virus Research, Institute of Infection Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Sussex Cancer Centre, Brighton, UK.
J Clin Virol. 2020 Aug;129:104505. doi: 10.1016/j.jcv.2020.104505. Epub 2020 Jun 20.
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.
尽管 HPV 阳性口咽癌（OPC）患者的预后优于 HPV 阴性患者，但仍有一部分 HPV 阳性患者预后较差。因此，需要有生物标志物来对不同患者的结局进行分层。我们的目的是分析 HPV 阳性 OPC 患者的病毒载量（VL），这些患者有可用的临床结局数据。
在一组先前通过常规 PCR 检测为 HPV 阳性的患者中，使用 ddPCR 检测 HPV16 L1 和 E6 基因来确定 VL。如果 HPV16 L1 或 E6 基因的检测值分别超过 5.57 拷贝或 8.68 拷贝，则将 VL 归类为“中/高”。采用 Cox 比例风险模型对 VL 与总生存和死亡/疾病进展风险的相关性进行调整，调整因素包括性别、年龄、贫困程度、吸烟、饮酒和分期。
L1 VL 范围为 0.0014-304 个细胞/基因拷贝，平均值为 30.9；E6 VL 范围为 0.0012-356 个细胞/基因拷贝，平均值为 37.9。单因素分析显示，VL 中/高的患者死亡风险较低；L1 有显著差异（p=0.02），但 E6 无显著差异（p=0.67）。大多数样本中 E6 与 L1 的比值偏离 n=1，但对临床结局没有影响。
HPV 病毒载量可能有助于进一步分层 HPV 阳性 OPC 患者的临床结局。
