UNLABELLED: Human papillomavirus 11 (HPV11) is an etiological agent of anogenital warts and laryngeal papillomas and is included in the 4-valent and 9-valent prophylactic HPV vaccines. We established the largest collection of globally circulating HPV11 isolates to date and examined the genomic diversity of 433 isolates and 78 complete genomes (CGs) from six continents. The genomic variation within the 2,800-bp E5a-E5b-L1-upstream regulatory region was initially studied in 181/207 (87.4%) HPV11 isolates collected for this study. Of these, the CGs of 30 HPV11 variants containing unique single nucleotide polymorphisms (SNPs), indels (insertions or deletions), or amino acid changes were fully sequenced. A maximum likelihood tree based on the global alignment of 78 HPV11 CGs (30 CGs from our study and 48 CGs from GenBank) revealed two HPV11 lineages (lineages A and B) and four sublineages (sublineages A1, A2, A3, and A4). HPV11 (sub)lineage-specific SNPs within the CG were identified, as well as the 208-bp representative region for CG-based phylogenetic clustering within the partial E2 open reading frame and noncoding region 2. Globally, sublineage A2 was the most prevalent, followed by sublineages A1, A3, and A4 and lineage B. IMPORTANCE: This collaborative international study defined the global heterogeneity of HPV11 and established the largest collection of globally circulating HPV11 genomic variants to date. Thirty novel complete HPV11 genomes were determined and submitted to the available sequence repositories. Global phylogenetic analysis revealed two HPV11 variant lineages and four sublineages. The HPV11 (sub)lineage-specific SNPs and the representative region identified within the partial genomic region E2/noncoding region 2 (NCR2) will enable the simpler identification and comparison of HPV11 variants worldwide. This study provides an important knowledge base for HPV11 for future studies in HPV epidemiology, evolution, pathogenicity, prevention, and molecular assay development.

Department of Experimental Virology National Reference Laboratory for Papillomaviruses Institute of Hematology and Blood Transfusion Prague Czech Republic

Department of Health Social Hygiene Service Centre for Health Protection Hong Kong Special Administrative Region China

Department of Medical Microbiology and Virology Faculty of Health Sciences University of the Free State Bloemfontein South Africa

Department of Microbiology and Infectious Diseases The Royal Women's Hospital Parkville Victoria Australia

Department of Microbiology Faculty of Medicine The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong Special Administrative Region China

Department of Molecular Diagnostics University Hospital for Infectious Diseases Dr Fran Mihaljević Zagreb Croatia

Department of Obstetrics and Gynaecology Cardiff University School of Medicine Institute of Cancer and Genetics Cardiff United Kingdom

Department of Obstetrics and Gynaecology University of Melbourne Melbourne Victoria Australia

Department of Otolaryngology Lithuanian University of Health Sciences Medical Academy Kaunas Lithuania

Department of Otorhinolaryngology Faculty of Health Sciences University of the Free State Bloemfontein South Africa

Departments of Pediatrics Microbiology and Immunology Epidemiology and Population Health Obstetrics and Gynecology and Women's Health Albert Einstein College of Medicine New York New York USA

Dermatology Research Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong Special Administrative Region China

DNA Laboratories Sdn Bhd UKM MTDC Technology Centre Universiti Kebangsaan Malaysia Bangi Malaysia

Histocompatibility and Molecular Genetics Laboratory Dr Julio C Perrando Hospital Resistencia Chaco Argentina

Human Virology Group National Council of Scientific and Technical Research Institute of Molecular and Cell Biology of Rosario Rosario Argentina

Institute of Microbiology and Immunology Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Institute of Microbiology Lausanne University Hospital and University of Lausanne Lausanne Switzerland

Institute of Pathology Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH Hannover Germany

Momate Memorial Laboratory Tokyo Japan

Murdoch Childrens Research Institute Parkville Victoria Australia

Oncogenic Viruses Service National Institute of Infectious Diseases ANLIS Dr Carlos G Malbrán Buenos Aires Argentina

Viral Exanthemata and STD Section National Microbiology Laboratory Public Health Agency of Canada Winnipeg Manitoba Canada

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