High Whole-Genome Sequence Diversity of Human Papillomavirus Type 18 Isolates

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.

HPV16 and HPV18 type-specific APOBEC3 and integration profiles in different diagnostic categories of cervical samples

“…Recent HPV deep sequencing studies, exploring HPV genomic variation with various PCR-based NGS approaches and different variant calling thresholds, show slightly divergent numbers of MNVs [10,18,30]. We found a total of 3747 MNVs in the 131 samples, being in line with studies reporting a high number of HPV variation at the population level [20,42,43], within infected hosts [10,11,30]. A recent study on HPV16 genome stability analysed possible HPV16 sublineage co-infections and observed 20-38 variants in each sample [44], corresponding to the mean numbers of MNVs in this study.…”

Lineage analysis of human papillomavirus type 18 based on E6 region in cervical samples of Iranian women

“…Regarding different sublineages among studied subjects, we found no significant difference between groups (Table 2). Although few studies have shown an association between distinctive variant and histopathology, 30,31 most studies failed to find any associations 14,26,32,33 . A recent study in Japan has been revealed that almost a uniform distribution of distinctive variants of HPV 18 was observed in this population as the sublineage A1 was dominant in both case and control groups 34 .…”

“…Sublineages A3 and A4 are prevalent in almost all parts of the world particularly in Europe although A5 have the highest prevalence in Northern Africa. It has also been shown that sublineages B1‐3 and C are common in Sub‐Saharan Africa 7,12‐14,24‐27 …”

Abundance of HPV L1 Intra-Genotype Variants With Capsid Epitopic Modifications Found Within Low- and High-Grade Pap Smears With Potential Implications for Vaccinology

“…Recently, whole-genome Sanger and deep sequencing studies have shown a surprisingly high level of intra-host diversity of HPV-16, -18, -52, and -58 (van der Weele et al, 2017, 2018; Hirose et al, 2018). Extensive intra-host HPV L1 sequence variability in 35 HPV genotypes was also discovered in samples from Zimbabwean women by deep sequencing (Dube Mandishora et al, 2018).…”