Revisiting Papillomavirus Taxonomy: A Proposal for Updating the Current Classification in Line with Evolutionary Evidence

Abstract

Papillomaviruses infect a wide array of animal hosts and are responsible for roughly 5% of all human cancers. Comparative genomics between different virus types belonging to specific taxonomic groupings (e.g., species, and genera) has the potential to illuminate physiological differences between viruses with different biological outcomes. Likewise, extrapolation of features between related viruses can be very powerful but requires a solid foundation supporting the evolutionary relationships between viruses. The current papillomavirus classification system is based on pairwise sequence identity. However, with the advent of metagenomics as facilitated by high-throughput sequencing and molecular tools of enriching circular DNA molecules using rolling circle amplification, there has been a dramatic increase in the described diversity of this viral family. Not surprisingly, this resulted in a dramatic increase in absolute number of viral types (i.e., sequences sharing <90% L1 gene pairwise identity). Many of these novel viruses are the sole member of a novel species within a novel genus (i.e., singletons), highlighting that we have only scratched the surface of papillomavirus diversity. I will discuss how this increase in observed sequence diversity complicates papillomavirus classification. I will propose a potential solution to these issues by explicitly basing the species and genera classification on the evolutionary history of these viruses based on the core viral proteins (E1, E2, and L1) of papillomaviruses. This strategy means that it is possible that a virus identified as the closest neighbor based on the E1, E2, L1 phylogenetic tree, is not the closest neighbor based on L1 nucleotide identity. In this case, I propose that a virus would be considered a novel type if it shares less than 90% identity with its closest neighbors in the E1, E2, L1 phylogenetic tree.

High-risk human papillomaviruses l1 gene isolates identified in Western Kazakhstan

“…According to the nomenclature of HPV established by the International Committee on Taxonomy of Virus (ICTV), each HPV type can be differentiated into phylogenetic lineages in terms of geographic distribution, pathogenicity, regulation of transcription, and immunological response [18,19,20]. The HPV16 type has accordingly been divided into four phylogenetic lineages: A, B, C, and D. The lineage D consists of the three sub-lineages: D1, D2, and D3, that include Asian-American and North American sequences.…”

Counteracting HPV Cervical and Anal Infection through Dietary Supplementation of EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid: Clinical Case Reports

“…Human papilloma virus (HPV) is one of the most common sexually transmitted infections (STIs) around the world [ 1 ]. The HPV family includes over 100 types of viruses, and 40 of them may infect the genital tract [ 2 ]. According to their oncogenic potential, all the papillomaviruses are classified as low-risk (LR), which usually lead to benign lesions (such as warts, condylomas and recurrent respiratory papillomatosis) or precancerous lesions, and high-risk (HR), which are highly associated with cancers of the lower genital tract, anus and oropharynx both in men and women [ 3 ].…”

Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status

“…Over 450 HPV genomes have been sequenced and categorized into five genera [ 20 , 21 ]. The extensively studied alpha-papillomavirus (αHPV) species primarily target the mucosal epithelia of the anogenital and oral regions and can be categorized as high-risk (HR) or low-risk (LR), depending on their tumorigenic potential [ 22 , 23 , 24 ]. HR HPVs are associated with nearly 100% of cervical cancer cases, of which, the most notable are HPV16 and HPV18, which alone are responsible for approximately 70% of those cases.…”