Department of Coloproctology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
Department of Coloproctology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
Clin Oncol (R Coll Radiol). 2019 Dec;31(12):e1-e13. doi: 10.1016/j.clon.2019.06.013. Epub 2019 Jul 10.
Recent studies suggest that the treatment response and survival from head and neck tumours can be stratified according to biomarker status, particularly human papillomavirus (HPV) status and p16 expression, but the evidence for predictive biomarkers in anal squamous cell carcinoma (ASCC) remains limited. The aim of this study was to determine which biomarkers were associated with locoregional recurrence (LRR), overall survival and disease-free survival (DFS) in ASCC. A systematic search was undertaken of the MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science databases using validated terms for ASCC, biomarkers and prognosis. Biomarkers were included in the meta-analysis if they were reported by at least four studies and provided sufficient data to permit the calculation of survival effect estimates. HPV status, p16, p53 and epidermal growth factor receptor (EGFR) met the inclusion criteria for meta-analysis and were reported by 17 retrospective cohort studies describing 1635 patients. When compared with HPV-negative tumours, HPV-positive tumours were associated with reduced LRR (pooled hazard ratio = 0.27 [95% confidence interval 0.16-0.48]; P < 0.001), improved overall survival (hazard ratio =0.26 [0.12-0.59]; P = 0.001) and DFS (hazard ratio = 0.33 [0.16-0.70]; P = 0.003). Likewise, p16-positive tumours were associated with reduced LRR (hazard ratio = 0.26 [0.13-0.52]; P < 0.001), improved overall survival (hazard ratio = 0.44 [0.24-0.81]; P = 0.009) and DFS (hazard ratio = 0.44 [0.23-0.83]; P = 0.012) when compared with p16-negative tumours. HPV-positive/p16-positive tumours had improved overall survival when compared with HPV-negative/p16-negative tumours (hazard ratio = 0.27 [0.15-0.48], P < 0.001), but not HPV-negative/p16-positive tumours (hazard ratio = 0.64 [0.21-1.90]; P = 0.421). p53 mutation was associated with worse DFS (hazard ratio = 1.63 [1.33-2.01]; P = 0.003). There was no association between EGFR status and any survival outcome. HPV status, p16 and p53 expression are of prognostic utility in ASCC. Future studies should prospectively validate these findings with a view to conducting subsequent randomised controlled trials where patients are stratified according to biomarker status and randomised to different treatment regimens.
最近的研究表明，头颈部肿瘤的治疗反应和生存可以根据生物标志物状态进行分层，尤其是人乳头瘤病毒（HPV）状态和 p16 表达，但在肛门鳞状细胞癌（ASCC）中预测生物标志物的证据仍然有限。本研究旨在确定哪些生物标志物与 ASCC 的局部区域复发（LRR）、总生存和无病生存（DFS）相关。使用经过验证的 ASCC、生物标志物和预后术语，对 MEDLINE、Embase、Cochrane 图书馆、CINAHL 和 Web of Science 数据库进行了系统搜索。如果生物标志物至少被四项研究报告，并提供了足够的数据来计算生存效应估计，则将其纳入荟萃分析。HPV 状态、p16、p53 和表皮生长因子受体（EGFR）符合荟萃分析的纳入标准，有 17 项回顾性队列研究描述了 1635 名患者。与 HPV 阴性肿瘤相比，HPV 阳性肿瘤的 LRR 降低（合并危险比为 0.27 [95%置信区间 0.16-0.48]；P < 0.001），总生存率提高（危险比=0.26 [0.12-0.59]；P = 0.001）和 DFS（危险比=0.33 [0.16-0.70]；P = 0.003）。同样，与 p16 阴性肿瘤相比，p16 阳性肿瘤的 LRR 降低（危险比=0.26 [0.13-0.52]；P < 0.001），总生存率提高（危险比=0.44 [0.24-0.81]；P = 0.009）和 DFS（危险比=0.44 [0.23-0.83]；P = 0.012）。与 HPV 阴性/p16 阴性肿瘤相比，HPV 阳性/p16 阳性肿瘤的总生存率提高（危险比=0.27 [0.15-0.48]，P < 0.001），而 HPV 阴性/p16 阳性肿瘤则不然（危险比=0.64 [0.21-1.90]；P = 0.421）。p53 突变与较差的 DFS 相关（危险比=1.63 [1.33-2.01]；P = 0.003）。EGFR 状态与任何生存结果均无关。HPV 状态、p16 和 p53 表达在 ASCC 中有预后作用。未来的研究应前瞻性地验证这些发现，以便进行随后的随机对照试验，根据生物标志物状态对患者进行分层，并随机分配到不同的治疗方案。
