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J Clin Virol. 2019 Oct;119:24-30. doi: 10.1016/j.jcv.2019.08.003. Epub 2019 Aug 12.

HPV16 whole genome minority variants in persistent infections from young Dutch women.

Author information

1
Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway; Department of Research, Cancer Registry of Norway, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
2
National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Research, Diagnostics and Screening, Bilthoven, the Netherlands; Vrije Universiteit-University Medical Center (VUmc), Department of Pathology, Amsterdam, the Netherlands.
3
Department of Research, Cancer Registry of Norway, Oslo, Norway.
4
Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway; Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
5
National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Research, Diagnostics and Screening, Bilthoven, the Netherlands. Electronic address: audrey.king@rivm.nl.
6
Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo, Norway. Electronic address: olam@oslomet.no.

Abstract

BACKGROUND:

Chronic infections by one of the oncogenic human papillomaviruses (HPVs) are responsible for near 5% of the global cancer burden and HPV16 is the type most often found in cancers. HPV genomes display unexpected levels of variation when deep-sequenced. Minor nucleotide variations (MNVs) may reveal HPV genomic instability and HPV-related carcinogenic transformation of host cells.

OBJECTIVES:

The objective of this study was to investigate HPV16 genome variation at the minor variant level on persisting HPV16 cervical infections from a population of young Dutch women.

STUDY DESIGN:

15 HPV16 infections were sequenced using a whole-HPV genome deep sequencing protocol (TaME-seq). One infection was followed over a three-year period, eight were followed over a two-year period, three were followed over a one-year period and three infections had a single sampling point.

RESULTS AND CONCLUSIONS:

Using a 1% variant frequency cutoff, we find on average 48 MNVs per HPV16 genome and 1717 MNVs in total when sequencing coverage was >100 × . We find the transition mutation T > C to be the most common, in contrast to other studies detecting APOBEC-related C > T mutation profiles in pre-cancerous and cancer samples. Our results suggest that the relative mutagenic footprint of HPV16 genomes may differ between the infections in this study and transforming lesions. In addition, we identify a number of MNVs that have previously been associated with higher incidence of high-grade lesions (CIN3+) in a population study. These findings may provide a starting point for future studies exploring causality between emerging HPV minor genomic variants and cancer development.

KEYWORDS:

Genome variation; Human papillomavirus; Mutational signature; Persistent infection

PMID:
31446251
DOI:
10.1016/j.jcv.2019.08.003
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