HPV16 whole genome minority variants in persistent infections from young Dutch women
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 H... Mehr ...
Verfasser: | |
---|---|
Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2019 |
Reihe/Periodikum: | Lagström , S , van der Weele , P , Rounge , T B , Christiansen , I K , King , A J & Ambur , O H 2019 , ' HPV16 whole genome minority variants in persistent infections from young Dutch women ' , Journal of Clinical Virology , vol. 119 , pp. 24-30 . https://doi.org/10.1016/j.jcv.2019.08.003 |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-27076391 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://research.vumc.nl/en/publications/32ac6baa-de0b-4dab-891b-a5f65d75e77a |
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.