Global genomic diversity of human papillomavirus 6 based on 724 isolates and 190 complete genome sequences

Mateja M. Jelen, Zigui Chen, Boštjan J. Kocjan, Felicity J. Burt, Paul K.S. Chan, Diego Chouhy, Catharina E. Combrinck, François Coutlée, Christine Estrade, Alex Ferenczy, Alison Fiander, Eduardo L. Franco, Suzanne M. Garland, Adriana A. Giri, Joaquín Víctor González, Arndt Gröning, Kerstin Heidrich, Sam Hibbitts, Lea Hošnjak, Tommy N. TommyKarina Marinic, Toshihiko Matsukura, Anna Neumann, Anja Oštrbenk, Maria Alejandra Picconi, Harriet Richardson, Martin Sagadin, Roland Sahli, Riaz Y. Seedat, Katja Seme, Alberto Severini, Jessica L. Sinchi, Jana Smahelova, Sepehr N. Tabrizi, Ruth Tachezy, Sarah Tohme, Virgilijus Uloza, Astra Vitkauskiene, Yong Wee Wong, Snježana Židovec Lepej, Robert D. Burk, Mario Poljak

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution.

Original languageEnglish (US)
Pages (from-to)7307-7316
Number of pages10
JournalJournal of virology
Issue number13
StatePublished - 2014

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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