title: Human papillomavirus (HPV) genotype 18 variants in patients with clinical manifestations of HPV related infections in Bilbao, Spain.
abstract: BACKGROUND
  Human papillomavirus (HPV) variants differ in their biological and chemical properties, and therefore, may present differences in pathogenicity. Most authors classified variants based on the phylogenetic analysis of L1 region. Nevertheless, recombination in HPV samples is becoming a usual finding and thus, characterizing genetic variability in other regions should be essential.
  
  
  OBJECTIVE
  We aimed to characterize the genetic variability of HPV 18 in 5 genomic regions: E6, E7, E4, L1 and the Upstream Regulatory Region (URR), working with both single infection and multiple HPV infection samples. Furthermore, we aimed to assess the prevalence of HPV 18 variants in our region and look for possible existence of recombination as well as analyze the relationship between these variants and the type of lesion.
  
  
  METHODS
  From 2007 to 2010, Clinical Microbiology and Infection Control Department analyzed 44 samples which were positive for HPV 18. Genetic variability was determined in PCR products and variants were assigned to European, Asian-amerindian or African lineage. Recombination and association of variants with different types of lesion was studied.
  
  
  RESULTS
  Genetic analysis of the regions revealed a total of 56 nucleotide variations. European, African and Asian-amerindian variants were found in 25/44 (56.8%), 10/44 (22.7%) and 5/44 (11.4%) samples, respectively. We detected the presence of recombinant variants in 2/44 (4.5%) cases. Samples taken from high-grade squamous intraepithelial lesions (H-SIL) only presented variants with specific-african substitutions.
  
  
  CONCLUSIONS
  Multiple HPV infection, non-european HPV variants prevalence and existence of recombination are considered risk factors for HPV persistence and progression of intraepithelial abnormalities, and therefore, should be taken into consideration in order to help to design and optimize diagnostics protocols as well as improve epidemiologic studies.Our study is one of the few studies in Spain which analyses the genetic variability of HPV18 and we showed the importance of characterizing more than one genomic region in order to detect recombination and classify HPV variants properly.
authors.affiliation: Immunology, Microbiology and Parasitology Department, University of Basque Country, Leioa, 48940, Spain.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Arroyo
authors.forename: Miren
authors.initials: M
authors.lastname: Basaras
authors.forename: Elixabete
authors.initials: E
authors.lastname: Arrese
authors.forename: Silvia
authors.initials: S
authors.lastname: Hernáez
authors.forename: Daniel
authors.initials: D
authors.lastname: Andía
authors.forename: Valentín
authors.initials: V
authors.lastname: Esteban
authors.forename: Koldo
authors.initials: K
authors.lastname: Garcia-Etxebarria
authors.forename: Begoña M
authors.initials: BM
authors.lastname: Jugo
authors.forename: Ramón
authors.initials: R
authors.lastname: Cisterna
mesh_terms: D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology; D014764:Viral Proteins / Q000235:genetics
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins