Debernardi Alice, Meurisse Aurélia, Prétet Jean-Luc, Guenat David, Monnien Franck, Spehner Laurie, Vienot Angélique, Roncarati Patrick, André Thierry, Abramowitz Laurent, Molimard Chloé, Mougin Christiane, Herfs Michael, Kim Stefano, Borg Christophe
EA3181, University of Bourgogne Franche-Comté, LabEx LipSTIC ANR-11-LABX-0021, Besançon, France.
Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.
Front Oncol. 2022 Oct 14;12:941676. doi: 10.3389/fonc.2022.941676. eCollection 2022.
Squamous Cell Carcinoma of the Anal canal (SCCA) is a rare disease associated with a Human Papillomavirus (HPV) infection in most cases, predominantly the HPV16 genotype. About 15% of SCCA are diagnosed in metastatic stage and some will relapse after initial chemoradiotherapy (CRT). Treatment of patients by Docetaxel, Cisplatin and 5-fluorouracil (DCF) has been recently shown to improve their complete remission and progression-free survival. The aim of this retrospective study was to explore the impact of HPV infection, HPV DNA integration, TERT promoter mutational status and somatic mutations of oncogenes on both progression-free (PFS) and overall survivals (OS) of patients treated by DCF. Samples obtained from 49 patients included in the Epitopes-HPV02 clinical trial, diagnosed with metastatic or non-resectable local recurrent SCCA treated by DCF, were used for analyses. Median PFS and OS were not associated with HPV status. Patients with episomal HPV had an improved PFS compared with SCCA patients with integrated HPV genome (p=0.07). promoter mutations were rarely observed and did not specifically distribute in a subset of SCCA and did not impact DCF efficacy. Among the 42 genes investigated, few gene alterations were observed, and were in majority amplifications (68.4%), but none were significantly correlated to PFS. As no biomarker is significantly associated with patients' survival, it prompts us to include every patient failing CRT or with metastatic disease in DCF strategy.
肛管鳞状细胞癌（SCCA）是一种罕见疾病，在大多数情况下与人类乳头瘤病毒（HPV）感染相关，主要是HPV16基因型。约15%的SCCA在转移阶段被诊断出来，一些患者在初始放化疗（CRT）后会复发。最近研究表明，多西他赛、顺铂和5-氟尿嘧啶（DCF）联合治疗可提高患者的完全缓解率和无进展生存期。这项回顾性研究的目的是探讨HPV感染、HPV DNA整合、TERT启动子突变状态和癌基因的体细胞突变对接受DCF治疗患者的无进展生存期（PFS）和总生存期（OS）的影响。从Epitopes-HPV02临床试验纳入的49例患者中获取样本，这些患者被诊断为转移性或不可切除的局部复发性SCCA并接受DCF治疗，用于分析。PFS和OS的中位数与HPV状态无关。与HPV基因组整合的SCCA患者相比，游离型HPV患者的PFS有所改善（p = 0.07）。启动子突变很少见，未在特定的SCCA亚组中分布，也不影响DCF疗效。在所研究的42个基因中，很少观察到基因改变，且大多为扩增（68.4%），但均与PFS无显著相关性。由于没有生物标志物与患者生存显著相关，这促使我们将每例CRT失败或患有转移性疾病的患者纳入DCF治疗策略。
