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.
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, 119, 24-30. https://doi.org/10.1016/j.jcv.2019.08.003