Longitudinal follow-up of HPV16 sequence after cervical infection: low intra-host variation and no correlation with clinical evolution.

Fiche publication


Date publication

juillet 2022

Journal

Journal of medical virology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr PRETET Jean-Luc, Pr RAMANAH Rajeev, Pr HOCQUET Didier


Tous les auteurs :
Debernardi A, Valot B, Almarcha J, Guenat D, Hocquet D, Algros MP, Riethmuller D, Ramanah R, Mougin C, Prétet JL, Lepiller Q

Résumé

Human papillomavirus (HPV) 16 exhibits different variants that may differ in their carcinogenic risk. In order to identify some high-risk variants, we sequenced and compared HPV16 whole genomes obtained from a longitudinal cohort of 34 HPV16-infected women who had either spontaneously cleared their infection (clearance group or "C"), or developed cervical high-grade lesions following a viral persistence (group persistence or "P"). Phylogenetic analysis of paired samples obtained at the beginning (C0 or P0) and at the end (C2 or P2) of the follow-up (median intervals between C0-C2 and between P0-P2 were 16 and 36.5 months, respectively) revealed a low genetic variability within the host compared to the genetic inter-host diversity. By comparing our HPV16 sequences to a reference sequence, we observed 301 different substitutions, more often transitions (60.9%) than transversions (39.1%), that occurred throughout the viral genome, but with a low frequency in E6 and E7 oncogenes (10 and 9 substitutions), suggesting a high conservation of these genes. Deletions and insertions were mostly observed in intergenic regions of the virus. The only significant substitution found between the subgroups C2 and P2 was observed in the L2 gene (L330F), with an unclear biological relevance. Our results suggest a low longitudinal intra-host evolution of HPV16 sequences and no correlation between genetic variations and clinical evolution. This article is protected by copyright. All rights reserved.

Mots clés

HPV16, Next Generation Sequencing, cervical cancer, variants

Référence

J Med Virol. 2022 07 7;: