title: Genetic Diversity in the Major Capsid L1 Protein of HPV-16 and HPV-18 in the Netherlands.
abstract: OBJECTIVE
  Intratypic molecular variants of human papillomavirus (HPV) type-16 and -18 exist. In the Netherlands, a bivalent vaccine, composed of recombinant L1 proteins from HPV-16 and -18, is used to prevent cervical cancer since 2009. Long-term vaccination could lead to changes in HPV-16 and -18 virus population, thereby hampering vaccination strategies. We determined the genetic diversity of the L1 gene in HPV-16 and -18 viral strains circulating in the Netherlands at the start of vaccination in order to understand the baseline genetic diversity in the Dutch population.
  
  
  METHODS
  DNA sequences of the L1 gene were determined in HPV-16 (n = 241) and HPV-18 (n = 108) positive anogenital samples collected in 2009 and 2011 among Dutch 16- to 24-year old female and male attendees of the sexually transmitted infection (STI) clinics. Phylogenetic analysis was performed and sequences were compared to reference sequences HPV-16 (AF536179) and HPV-18 (X05015) using BioNumerics 7.1.
  
  
  RESULTS
  For HPV-16, ninety-five single nucleotide polymorphism (SNPs) were identified, twenty-seven (28%) were non-synonymous variations. For HPV-18, seventy-one SNPs were identified, twenty-nine (41%) were non-synonymous. The majority of the non-silent variations were located in sequences encoding alpha helix, beta sheet or surface loops, in particular in the immunodominant FG loop, and may influence the protein secondary structure and immune recognition.
  
  
  CONCLUSIONS
  This study provides unique pre-vaccination/baseline data on the genetic L1 diversity of HPV-16 and -18 viruses circulating in the Netherlands among adolescents and young adults.
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: King
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Sonsma
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Henrike J
authors.initials: HJ
authors.lastname: Vriend
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Julius Centre for Primary Care and Public Health, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Marianne A B
authors.initials: MA
authors.lastname: van der Sande
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mariet C
authors.initials: MC
authors.lastname: Feltkamp
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Boot
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Marion P G
authors.initials: MP
authors.lastname: Koopmans
mesh_terms: D000293:Adolescent; D000328:Adult; D002213:Capsid / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D008297:Male; D009426:Netherlands; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000821:virology; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral