Human Papillomavirus Type 6 and 11 Genetic Variants Found in 71 Oral and Anogenital Epithelial Samples from Australia

Abstract

Genetic variation of 49 human papillomavirus (HPV) 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP) (n = 17), genital warts (n = 43), anal cancer (n = 6) and cervical neoplasia cells (n = 5), was determined by sequencing the long control region (LCR) and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65%) clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04). This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02). Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these HPV types.

Human papillomavirus infection in oral fluids of HIV-1-positive men:prevalence and risk factors

“…Regarding the low-risk groups, HPV-6 and 11 are the most prevalent26. In our study, HPV-6 was found in 20% of the samples.…”

Human papillomavirus (HPV) genotypes in an Australian sample of anal cancers

“…Some of the samples in which only HPV 6 or 11 were detected have been further investigated using laser capture micro dissection and have been confirmed to only contain these “low‐risk” types . Furthermore, a recent detailed evaluation of the HPV genotypes in these samples failed to detect any unusual genomic variants . Clearly the role of HPV 6 and 11 in the etiology of anal cancer warrants further investigations …”

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

“…uman papillomavirus 11 (HPV11), which belongs to species 10 of the Alphapapillomavirus genus (Alpha-PV), is etiologically associated with approximately 20% of anogenital warts and 30 to 40% of laryngeal papillomas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). HPV11 is generally considered a low-risk HPV type due to its rare presence in HPVrelated cancers in humans, especially cervical cancer (9).…”

“…On the basis of the analysis of 32 complete HPV11 genomes originating mainly from Slovenia, HPV11 genomic variants were classified into two sublineages: sublineage A1 (previously termed the "prototypic variant") and sublineage A2 (previously termed the "nonprototypic variant"). Three additional HPV11 genomic diversity studies that focused on samples from the head and neck and the anogenital regions and that described the variability of the HPV11 genome from ethnogeographically closed cohorts and/or focused on individual complete or partial HPV11 genomic regions have recently been published (7,27,28). Several HPV11 genomic variants with highly similar nucleotide profiles were identified in these studies.…”

“…Several HPV11 genomic variants with highly similar nucleotide profiles were identified in these studies. Apart from the observation that isolates from sublineage A2 prevail globally (7,28), no other ethnogeographical or clinical associations with HPV11 variants have been described to date (7,24,25,27,28).…”