Phylogenetic incongruence among oncogenic genital alpha human papillomaviruses

J Virol. 2005 Dec;79(24):15503-10. doi: 10.1128/JVI.79.24.15503-15510.2005.


The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whole-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the LILD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncogenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incongruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophyletic across all genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Viruses / genetics
  • Female
  • Genome, Viral
  • Humans
  • Oncogene Proteins, Viral / genetics*
  • Papillomaviridae / classification*
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Phylogeny
  • Tumor Virus Infections / immunology*
  • Uterine Cervical Neoplasms / virology


  • Oncogene Proteins, Viral