title: Intratypic variants of human papillomavirus type 16 and risk of cervical neoplasia in Taiwan.
abstract: The associations between variants of human papillomavirus (HPV) 16 and risk of cervical neoplasia have been reported, but nucleotide variations of HPV 16 in Asian populations and their association with cervical neoplasia have not been evaluated extensively. During 1991-1992, 11,923 women from seven townships in Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped using EasyChip HPV blot. Nucleotide variations in the long control region (LCR), E6, and E7 genes were determined using DNA sequencing for 170 HPV 16-positive cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV 16 in Taiwan, and was also associated with increased prevalence of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age-adjusted odds ratio (exact confidence limits) of 10.70 (1.62-451.05; P = 0.0049) compared to the HPV 16 European variant. Similar significant associations with cervical intraepithelial neoplasia grade 3 or worse were also observed for distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G. These results demonstrate that non-European variants (non-E) of HPV 16, predominantly Asian variants, are associated with increased risk for severe cervical neoplasia, compared with European variants. Molecular mechanisms accounting for varied cervical neoplasia risk among different HPV 16 variants warrant further investigation.
authors.affiliation: Graduate Institute of Epidemiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Chang
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Chen
authors.forename: Mei-Hung
authors.initials: MH
authors.lastname: Pan
authors.forename: Bor-Heng
authors.initials: BH
authors.lastname: Lee
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chou
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Yu-Juen
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liaw
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D052162:Human papillomavirus 16 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology*; D017354:Point Mutation; D012097:Repressor Proteins / Q000235:genetics; D018570:Risk Assessment; D017422:Sequence Analysis, DNA; D013624:Taiwan / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: HPV 16; Taiwan; cervical neoplasia; prevalence; variants