title: Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women.
abstract: BACKGROUND
  Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role.
  
  
  METHODS
  HPV16-positive women with normal cytology in a large Danish cohort were reassessed for HPV16 status at 2 years and followed-up for cervical intraepithelial neoplasia 3 or worse (CIN3+) over 11 years through linkage with a national pathology database. Relative risks for clearance, persistence, and progression were compared with different HPV16 variant lineages based upon E6 gene sequencing.
  
  
  RESULTS
  Sixty-two (23.7%) of 261 HPV16 infections were persistent at 2 years, and 32 (51.6%) persistent infections progressed to CIN3+. The majority of baseline infections belonged to the European lineage (97.3%), with EUR-350T and EUR-350G accounting for 61.3% and 36.0% of infections, respectively. At two years, the proportion of HPV16 infections that persisted was significantly higher for EUR-350T (28.2%) than EUR-350G (15.9%) variants (odds ratio = 2.06, 95% CI, 1.04-4.25). This increased risk for persistence was consistent both in the absence (OR = 2.16, 95% CI, 0.84-6.26) or presence (OR = 1.89, 95% CI, 0.76-5.15) of progression to CIN3+. Among persistent HPV16 infections, there was no significant difference in risk of progression to CIN3+ between EUR-350T and EUR-350G sub-lineages, which were both associated with a substantial absolute risk (>50%) of CIN3+.
  
  
  CONCLUSIONS
  Significant differences in risk for persistence exist between the HPV16 variants that predominate in Europe.
  
  
  CONCLUSIONS
  Understanding the genetic basis of HPV16 persistence and carcinogenicity may help unravel important interactions between HPV16 and the host immune system.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.forename: Iris
authors.initials: I
authors.lastname: Cornet
authors.forename: Gary M
authors.initials: GM
authors.lastname: Clifford
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.forename: Christian
authors.initials: C
authors.lastname: Munk
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D003718:Denmark; D018450:Disease Progression; D005260:Female; D005828:Genetics, Population; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000821:virology*
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins