title: Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18.
abstract: BACKGROUND
  Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated.
  
  
  METHODS
  Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages.
  
  
  RESULTS
  Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants.
  
  
  CONCLUSIONS
  The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN.
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle, Washington 98103, USA. longfu@u.washington.edu
authors.forename: Long Fu
authors.initials: LF
authors.lastname: Xi
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Denise A
authors.initials: DA
authors.lastname: Galloway
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Winer
authors.forename: Jesse
authors.initials: J
authors.lastname: Ho
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000821:virology*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*