Alice-Andrée Mariaggi1,2, Hélène Péré3, Marine Perrier1,2, Benoit Visseaux1,2, Gilles Collin1,2, David Veyer3, Quentin Le Hingrat1,2, Valentine Marie Ferré1,2, Véronique Joly1,4, Anne Couvelard5, Margot Bucau5, Carine Davitian6, Diane Descamps1,2, Laurent Abramowitz7, Charlotte Charpentier1,2. 1. Infection, Antimicrobials, Modelling, Evolution (IAME), Unité Mixte de Recherche 1137, Institut national de la santé et de la recherche médicale, Université Paris Diderot, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. 2. Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France. 3. Laboratoire de Virologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. 4. Service de Maladies Infectieuses et tropicales, Hôpital Bichat, AP-HP, Paris, France. 5. Bichat Hospital, Department of Pathology, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 6. Service de gynécologie-obstétrique, Paris, France. 7. Service de Gastroentérologie et Proctologie, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.
Abstract
Background: The aim of this study was to investigate the presence of minority variants (MVs) in high-risk human papillomavirus (HPV) types (HPV-16, -52, and -58) from cervical and anal smears. Methods: Whole HPV genome ultra-deep sequencing (UDS) was performed on cervical and anal smears collected during patient follow-up. Bioinformatics analyses were performed using Bowtie2 (Geneious). Results: We assessed 55 HPV-16-positive, 20 HPV-52-positive, and 17 HPV-58-positive samples, with significant differences in patient characteristics for the 2 anatomic sites. HPV-16 MVs were detected in 20 samples (36%), with no difference between cervical and anal samples. We did not find an association between the presence of MVs and cytovirological parameters. Seven HPV-16 genomes (13%) were apolipoprotein B messenger RNA editing, catalytic polypeptide-like 3 (APOBEC) edited. Among the cervical HPV-16-positive samples, most MVs (55%) resulted from APOBEC-related mutations. MVs were detected in 10 HPV-52-positive (50%) and 12 HPV-58-positive (71%) samples, with no difference between cervical and anal samples. No APOBEC-related mutations were found on HPV-58 or HPV-52 genomes. Conclusions: Overall, high-risk HPV MVs were found in about half of all cases in both anal and cervical samples. Interestingly, we reported for the first time a differential impact of APOBEC3 mutagenic activity depending on high-risk HPV type.
Background: The aim of this study was to investigate the presence of minority variants (MVs) in high-risk human papillomavirus (HPV) types (HPV-16, -52, and -58) from cervical and anal smears. Methods: Whole HPV genome ultra-deep sequencing (UDS) was performed on cervical and anal smears collected during patient follow-up. Bioinformatics analyses were performed using Bowtie2 (Geneious). Results: We assessed 55 HPV-16-positive, 20 HPV-52-positive, and 17 HPV-58-positive samples, with significant differences in patient characteristics for the 2 anatomic sites. HPV-16 MVs were detected in 20 samples (36%), with no difference between cervical and anal samples. We did not find an association between the presence of MVs and cytovirological parameters. Seven HPV-16 genomes (13%) were apolipoprotein B messenger RNA editing, catalytic polypeptide-like 3 (APOBEC) edited. Among the cervical HPV-16-positive samples, most MVs (55%) resulted from APOBEC-related mutations. MVs were detected in 10 HPV-52-positive (50%) and 12 HPV-58-positive (71%) samples, with no difference between cervical and anal samples. No APOBEC-related mutations were found on HPV-58 or HPV-52 genomes. Conclusions: Overall, high-risk HPV MVs were found in about half of all cases in both anal and cervical samples. Interestingly, we reported for the first time a differential impact of APOBEC3 mutagenic activity depending on high-risk HPV type.