Scottish HPV Reference Laboratory, NHS Lothian, Edinburgh, UK.
School of Medicine, University of St Andrews, St Andrews, UK.
Cancer Med. 2022 Nov;11(22):4193-4203. doi: 10.1002/cam4.4771. Epub 2022 Jul 4.
The incidence of anal cancer is increasing globally. Evidence-based improvement in early detection and management of this morbid cancer is thus required. In other cancers associated with Human Papillomavirus (HPV), viral status and dynamics, including viral load (VL) has been shown to influence clinical outcome. Our aim was to determine the influence of HPV status and HPV16 VL on the clinical outcomes of anal cancer patients.
A total of 185 anal cancer lesions were genotyped for HPV. Of the HPV16 positive component, VL was determined using a digital droplet PCR assay. The association of qualitative HPV status and VL (low (<12.3), medium (12.3-57) and high (>57 copies/cell)) on overall survival and hazard of death was assessed.
Of the 185 cases, 164 (88.6%) samples were HPV positive. HPV16 was detected in 154/185 samples (83.2%). HPV positive status was associated with improved overall survival in the univariate analysis [hazard ratio (HR) of 0.44, 0.23-0.82, p = 0.01]. When adjusted by age, sex, stage and response to treatment, the association of positive HPV status with improved survival remained (HR 0.24 [0.11-0.55] p < 0.001). High VL was associated with improved overall survival in the univariate analysis with a HR of 0.28 (0.11-0.71, p = 0.007). When adjusted only by age and sex, high VL was associated with better overall survival (HR 0.27, 0.11-0.68 p = 0.006).
HPV status appears to be independently associated with improved outcomes in anal cancer patients. Moreover, HPV viral load quantification may be informative for further risk stratification and warrants further investigation.
全球范围内肛门癌的发病率正在上升。因此，需要有循证医学证据来改善这种恶性肿瘤的早期检测和管理。在其他与人类乳头瘤病毒（HPV）相关的癌症中，病毒状态和动态，包括病毒载量（VL），已被证明会影响临床结局。我们的目的是确定 HPV 状态和 HPV16VL 对肛门癌患者临床结局的影响。
总共对 185 个肛门癌病变进行了 HPV 基因分型。对于 HPV16 阳性成分，使用数字液滴 PCR 检测法测定 VL。评估定性 HPV 状态和 VL（低（<12.3）、中（12.3-57）和高（>57 拷贝/细胞））对总生存率和死亡风险的关联。
在 185 例病例中，有 164 例（88.6%）样本 HPV 阳性。在 185 个样本中检测到 154 个 HPV16（83.2%）。在单因素分析中，HPV 阳性状态与总体生存率的提高相关[风险比（HR）为 0.44，0.23-0.82，p=0.01]。当通过年龄、性别、分期和治疗反应进行调整时，HPV 阳性状态与生存改善的相关性仍然存在（HR 0.24 [0.11-0.55]，p<0.001）。高 VL 在单因素分析中与总体生存率的提高相关，HR 为 0.28（0.11-0.71，p=0.007）。仅通过年龄和性别调整时，高 VL 与总体生存率的提高相关（HR 0.27，0.11-0.68，p=0.006）。
HPV 状态似乎与肛门癌患者的治疗结局改善独立相关。此外，HPV 病毒载量定量分析可能有助于进一步进行风险分层，值得进一步研究。
