Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Leeds Institute of Medical Research, University of Leeds, Leeds Cancer Centre, Leeds, UK.
Clin Oncol (R Coll Radiol). 2021 Oct;33(10):638-649. doi: 10.1016/j.clon.2021.04.015. Epub 2021 May 21.
Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores.
Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan-Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression.
Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36-4.63) for p16 negative versus p16 positive, 2.17 (1.34-3.5) for T3/4 versus T1/2, 2.42 (1.52-3.8) for males versus females and 3.30 (1.52-7.14) for TIL1 versus TIL3 (all P < 0.05).
We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282).
分析鳞状细胞癌（ASCC）与人乳头瘤病毒密切相关。标准治疗方法是采用统一剂量的化疗和放疗，不进行治疗分层。p16INK4A（p16）的免疫组织化学染色（p16）是人乳头瘤病毒的替代物，对预后有预测作用。我们在该研究中联合了临床病理因素，包括肿瘤浸润淋巴细胞（TIL）评分。
我们使用了一个独立的、多中心的 257 例接受化疗和放疗的 ASCC 患者队列，对治疗前的活检标本进行了 p16 和 TIL 的染色和评分。根据分期、p16 和 TIL 评分绘制了生存（无病生存[DFS]、总生存和癌症特异性生存）的 Kaplan-Meier 曲线，并通过对数秩检验分析了预后的影响。使用 Cox 回归进行了多变量分析。
分期、性别、p16 和 TIL 是独立的预后因素。p16 阴性与阳性相比，死亡（总生存）的风险比（HR）为 2.51（95%置信区间 1.36-4.63），T3/4 期与 T1/2 期相比为 2.17（1.34-3.5），男性与女性相比为 2.42（1.52-3.8），TIL1 与 TIL3 相比为 3.30（1.52-7.14）（均 P < 0.05）。
我们已经对 ASCC 的预后因素进行了细化。p16 除了根据分期进行分层外，在早期疾病的 DFS 和局部晚期癌症的总生存/DFS 方面也具有分层作用。我们的数据支持宿主免疫反应在介导结局方面的作用。这些因素将在 PLATO（ISRCTN88455282）中进行前瞻性评估。
