Authors
Victor Malassigné, Julien Puech, Sandrine Imbeaud, Anne Auperin, Caroline Even, Dac Hung Nguyen, Maxime Wack, Bastien Rance, Léa Benyakar, Léa Picavet, Victor Euzen, Laurent Bélec, Narjis Boukli, Benjamin Morin, Imane Doghman, Emmanuelle Fabiano, Sarah Kreps, Anne-Laure Gaultier, Laure Monard, Michael Chevrot, Mélodie Bonvalet, Jessica Zucman-Rossi, Cécile Badoual, Aurélien Marabelle, Pierre Blanchard, Haitham Mirghani, Hélène Péré, David Veyer
Published in
Clinical cancer research : an official journal of the American Association for Cancer Research. Jul 15, 2026. Epub Jul 15, 2026.
Abstract
A subset of patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma develops disease recurrence despite generally favorable outcomes. Reliable biomarkers for risk stratification remain lacking. We investigated whether comprehensive viral genomic profiling refines prognostic classification.
Tumor samples from 100 patients with p16-positive and human papillomavirus DNA-positive oropharyngeal squamous cell carcinoma enrolled in two independent cohorts were analyzed using targeted viral capture sequencing. Viral genotype, sublineage, single-nucleotide variation, viral-host integration sites, viral structural variants, clonality, and viral copy number were characterized. Associations with cumulative incidence of progression, progression-free survival and overall survival were assessed at 60 months.
Human papillomavirus 16 was detected in 94 tumors, of which 83 belonged to the HPV16_A1 sublineage. Within this sublineage, 20 tumors harbored strictly episomal viral genomes, whereas 63 exhibited integration and/or viral structural variants. No progression events occurred in the strictly episomal HPV16_A1 subgroup, while 12 occurred among tumors HPV16_A1 with integration and/or structural variant. At 60 months, no progression events were observed in strictly episomal HPV16_A1 tumors, compared with a 23.1% cumulative incidence of progression in HPV16_A1 tumors with integration and/or structural variant. Previously reported high-risk single-nucleotide variants and a novel upstream regulatory region variant were associated with worse progression-free survival. Integration sites were enriched in open chromatin and promoter regions and clustered within viral E2 and E4 genes.
Within human papillomavirus 16 A1 tumors, viral genomic architecture defines clinically distinct subgroups. Strictly episomal (WT) genomes identify a low-risk population, whereas integration and structural variants characterize higher-risk disease.
PMID:
42456052
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.
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