Abstract
Background: The most commonly found human papillomavirus (HPV) types in cervical cancer are HPV16 and HPV18. Genome variants of these types have been associated with differential carcinogenic potential. To date, only a handful of studies have described HPV18 whole genome sequencing results. Here we describe HPV18 variant diversity and conservation of persistent infections in a longitudinal retrospective cohort study. Methods: Cervical self-samples were obtained annually over four years and genotyped on the SPF10-DEIA-LiPA25 platform. Clearing and persistent HPV18 positive infections were selected, amplified in two overlapping fragments, and sequenced using 32 sequence primers. Results: Complete viral genomes were obtained from 25 participants with persistent and 26 participants with clearing HPV18 infections, resulting in 52 unique HPV18 genomes. Sublineage A3 was predominant in this population. The consensus viral genome was completely conserved over time in persistent infections, with one exception, where different HPV18 variants were identified in follow-up samples. Conclusions: This study identified a diverse set of HPV18 variants. In persistent infections, the consensus viral genome is conserved. The identification of only one HPV18 infection with different major variants in follow-up implies that this is a potentially rare event. This dataset adds 52 HPV18 genome variants to Genbank, more than doubling the currently available HPV18 information resource, and all but one variant are unique additions.
Highlights
Persistent high-risk human papillomavirus (HPV) infection is the prime cause for cervical cancer [1]
Complete HPV18 genomes were obtained from 26 participants with clearing infections and 25 participants with persistent infections (Figure 1)
We describe the remarkably large diversity of HPV18 variants circulating in a Dutch cohort study based on whole genome sequencing data
Summary
Persistent high-risk (hr) human papillomavirus (HPV) infection is the prime cause for cervical cancer [1]. 13 HPV types are considered to be high-risk based on criteria defined by the International Agency for Research on Cancer [2], with different carcinogenic risk for each hrHPV type. Individual HPV types are considered to show >90% sequence homology. All sequences belonging to the same HPV type are considered variants [4]. The most commonly found human papillomavirus (HPV) types in cervical cancer are HPV16 and HPV18. Genome variants of these types have been associated with differential carcinogenic potential. We describe HPV18 variant diversity and conservation of persistent infections in a longitudinal retrospective cohort study.
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