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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cervix Uteri / virology
  • DNA, Viral / genetics
  • Female
  • Genetic Variation
  • Genome, Viral / genetics*
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Longitudinal Studies
  • Mutation
  • Netherlands / epidemiology
  • Papillomavirus Infections / virology*
  • Retrospective Studies
  • Viral Load
  • Young Adult


  • DNA, Viral