HPV integration; NGS - next generation sequencing; SCCA; Somatic mutation analysis; TERT promoter mutation; Oncology; Cancer Research
Abstract :
[en] 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). TERT 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.
Disciplines :
Oncology
Author, co-author :
Debernardi, Alice; EA3181, University of Bourgogne Franche-Comté, LabEx LipSTIC ANR-11-LABX-0021, Besançon, France
Meurisse, Aurélia; Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France ; INSERM, EFS BFC, UMR1098 RIGHT, University of Bourgogne Franche-Comté, Besançon, France
Prétet, Jean-Luc; EA3181, University of Bourgogne Franche-Comté, LabEx LipSTIC ANR-11-LABX-0021, Besançon, France ; Papillomavirus National Reference Center, University Hospital, Besançon, France
Guenat, David; EA3181, University of Bourgogne Franche-Comté, LabEx LipSTIC ANR-11-LABX-0021, Besançon, France ; Molecular Biology and Microbiology Department, Anamed SA Laboratory, Lausanne, Switzerland
Monnien, Franck; Department of Pathology, University Hospital of Besançon, Besançon, France
Spehner, Laurie; INSERM, EFS BFC, UMR1098 RIGHT, University of Bourgogne Franche-Comté, Besançon, France ; Department of Medical Oncology, University Hospital of Besançon, Besançon, France
Vienot, Angélique; INSERM, EFS BFC, UMR1098 RIGHT, University of Bourgogne Franche-Comté, Besançon, France ; Department of Medical Oncology, University Hospital of Besançon, Besançon, France
RONCARATI, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
André, Thierry; Department of Medical Oncology, University Hospital Saint Antoine, Paris, France
Abramowitz, Laurent; Division of Gastroenterology and Hepatology and Proctology, University Hospital Bichat, Paris, France ; Ramsay GDS, Blomet Clinic, Paris, France
Molimard, Chloé; Department of Anatomopathology, University Hospital of Besançon, Besançon, France
Mougin, Christiane; INSERM, EFS BFC, UMR1098 RIGHT, University of Bourgogne Franche-Comté, Besançon, France ; Papillomavirus National Reference Center, University Hospital, Besançon, France
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Kim, Stefano; INSERM, EFS BFC, UMR1098 RIGHT, University of Bourgogne Franche-Comté, Besançon, France ; Clinical investigation center, CIC-1403 University Hospital of Besançon, Besançon, France ; Department of Medical Oncology, Sanatorio Allende, Cordoba, Argentina
Borg, Christophe; INSERM, EFS BFC, UMR1098 RIGHT, University of Bourgogne Franche-Comté, Besançon, France ; Molecular Biology and Microbiology Department, Anamed SA Laboratory, Lausanne, Switzerland ; Clinical investigation center, CIC-1403 University Hospital of Besançon, Besançon, France
Part of this work was funded by the Région Franche-Comté and the Belgian Fund for Scientific Research (FNRS; MIS F.4520.20).CB has received a research grant from companies Bayer and Roche, and was an advisory board member of Bayer, MSD and Pierre Fabre companies. None of them had a role in the study design, analysis, or interpretation of the results.
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