title: Lineages of oncogenic human papillomavirus types other than type 16 and 18 and risk for cervical intraepithelial neoplasia.
abstract: BACKGROUND
  Data on clinical outcomes of infection with variants of oncogenic human papillomavirus (HPV) types other than HPV16 and HPV18 are rare. We investigated intratypic variations in non-HPV16/18 oncogenic types and their corresponding relationships with cervical intraepithelial neoplasia grades 2-3 (CIN2/3).
  
  
  METHODS
  Study subjects were women who were positive for one or more of 11 non-HPV16/18 oncogenic types. Subjects were followed every six months for two years for detection of HPV and cervical lesions. Variant lineages were defined by sequencing the 3' part of the long control region and the entire E6/E7 region of HPV genome. Lineage-associated risk of CIN2/3 was assessed using logistic regression with generalized estimating equations.
  
  
  RESULTS
  A total of 4591 type-specific HPV infections among 2667 women were included in the analysis. The increase in risk of CIN2/3 was statistically significant for women with HPV31 A or B compared with C variants, HPV33 A1 compared with B variants, HPV45 A3 or B2 compared with B1 variants, HPV56 B compared with A2 variants, and HPV58 A1 or A3 compared with C variants. For these five types, the adjusted odds ratio associated with CIN2/3 was 2.0 (95% confidence interval [CI] = 1.5 to 2.6) for infections with single-type high-risk (HR) variants, 1.7 (95% CI = 1.0 to 2.7) for infections with two or more types but only one HR variant, and 5.3 (95% CI = 3.1 to 8.4) for infections with HR variants of two or more types as compared with those with single-type non-HR variants. The likelihood of CIN2/3 was similar for women with HPV16 infection and for those with HPV58 A1 variant infection.
  
  
  CONCLUSIONS
  These findings suggest that for a given HPV type, intratypic nucleotide changes may alter phenotypic traits that affect the probability of neoplasia.
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD. longfu@u.washington.edu.
authors.forename: Long Fu
authors.initials: LF
authors.lastname: Xi
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: James P
authors.initials: JP
authors.lastname: Hughes
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Winer
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Constance
authors.initials: C
authors.lastname: Mao
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hulbert
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Shu-Kuang
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
mesh_terms: D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics* / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications*; D018570:Risk Assessment; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000821:virology*
chemical_list: D004279:DNA, Viral