Speaker
Description
Human papillomaviruses (HPVs) are common sexually transmitted viruses. Most infections they cause clear naturally within a few months or years, but can become chronic and can cause many ano-genital cancers, especially cervical cancers. Although safe and effective vaccines are available, the genetic bases of persistence and pathogenicity remain poorly understood. Some HPV genotypes, such as HPV16, are strikingly more virulent because their prevalence is over-represented in high-grade lesions and cancers. Within genotypes, some variants also appear to be more virulence (e.g. HPV16A compared to HPV16B, C, or D). The variability within variants is debated but recent evidence from HPV16 suggests that specific genetic motifs may be associated with cancers. An open question is whether these are present upon infection or acquired during intra-host evolution. HPVs being double-stranded DNA viruses, their evolution is expected to be slow and their within-host evolution has rarely been studied, although some studies suggest that it could be less negligible than might be suggested by the high genetic stability of HPVs at the population level. To explore HPV genetic variability and evolution, as well as potential transmission bottlenecks, we analyse longitudinal data from the PAPCLEAR cohort, which followed HPV genital infections in 189 young women for an average duration of 290 days. Metagenomic sequencing was conducted on 658 vaginal swabs, and 88 cervical smears were specifically amplified for HPV prior to sequencing using a capture protocol. We analyse the HPV reads detected by both methods to identify changes in substitution frequency over time, global genetic diversity, and evolutionary rates. These are analysed in the light of covariates such as HPV genotype, vaginal microbiota composition, or vaccination status. Overall, this represents one of the first studies to analyse the within-host evolution of HPV genotypes other than HPV16 in young women.
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