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. 2022 Oct 14:12:941676.
doi: 10.3389/fonc.2022.941676. eCollection 2022.

Prognostic role of HPV integration status and molecular profile in advanced anal carcinoma: An ancillary study to the epitopes-HPV02 trial

Alice Debernardi  1 , Aurélia Meurisse  2   3 , Jean-Luc Prétet  1   4 , David Guenat  1   5 , Franck Monnien  6 , Laurie Spehner  3   7 , Angélique Vienot  3   7 , Patrick Roncarati  8 , Thierry André  9 , Laurent Abramowitz  10   11 , Chloé Molimard  12 , Christiane Mougin  3   4 , Michael Herfs  8 , Stefano Kim  3   13   14 , Christophe Borg  3   5   13
Affiliations

Prognostic role of HPV integration status and molecular profile in advanced anal carcinoma: An ancillary study to the epitopes-HPV02 trial

Alice Debernardi et al. Front Oncol. .

Abstract

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.

Keywords: HPV integration; NGS - next generation sequencing; SCCA; Somatic mutation analysis; TERT promoter mutation.

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Conflict of interest statement

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. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier diagrams representing (A) PFS and (B) OS according to the integration of HPV genome. Blue line symbolizes integrated/mixed forms, black line episomal forms.
Figure 2
Figure 2
TERT promoter mutation distribution in human SCCA from the HPV02 and EDITH V cohorts (444 samples). (A) Wild-type (WT) TERT promoter prevalence versus C228T, C228A and C250T mutations. (B) Distribution of HPV status according to TERT promoter mutations.
Figure 3
Figure 3
Heatmap of gene alteration frequency clustered by PFS (whether it reaches 12 months or not). The type of alterations is described in the heatmap legend, with the list of genes on the right, and PFS of patients is found at the bottom of the heatmap.
Figure 4
Figure 4
OS in presence of PIK3CA alteration. Blue line symbolizes no alteration, black line symbolizes the presence of a mutation and/or amplification.
See this image and copyright information in PMC

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