title: Analysis of human papillomavirus type 16 E6 variants in relation to p53 codon 72 polymorphism genotypes in cervical carcinogenesis.
abstract: This study aimed to assess the role of specific human papillomavirus type 16 (HPV-16) variants, in combination with p53 codon 72 polymorphism genotypes, in cervical carcinogenesis. An initial sequence analysis of HPV-16 long control, E6 and E7 regions of 53 well-defined cervical samples containing HPV-16 revealed that a T to G transition at nucleotide position 350 within the E6 open reading frame was the most common variation, the frequency of which seemed to decrease with increasing severity of the lesion. Therefore, a total of 246 cervical samples of residents of The Netherlands was specifically analysed for HPV-16 350G/T variants and/or p53 codon 72 genotypes. These comprised HPV-negative normal cervical scrapes (n=40), normal cervical scrapes containing HPV-16 (n=46), scrapes containing HPV-16 from women with abnormal cervical cytology participating in a non-intervention follow-up study without (n=38) and with (n=51) a histologically proven cervical intraepithelial neoplasia (CIN) III lesion at the end of the study, and cervical squamous cell carcinomas (n=71). Neither specific HPV-16 350G/T variants nor specific p53 genotypes were associated with a higher risk of developing CIN III or cervical cancer. However, HPV-16 350T variants were significantly over-represented in p53 Arg homozygous women with cervical cancer. This suggests that, in p53 Arg/Arg women, infection with HPV-16 350T variants confers a higher risk of cervical cancer.
authors.affiliation: Department of Pathology, University Hospital Vrije Universiteit, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Duin
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: M T
authors.initials: MT
authors.lastname: Vossen
authors.forename: E
authors.initials: E
authors.lastname: Klaassen
authors.forename: F
authors.initials: F
authors.lastname: Voorhorst
authors.forename: R H
authors.initials: RH
authors.lastname: Verheijen
authors.forename: T J
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000209:etiology / Q000235:genetics; D003062:Codon / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016158:Genes, p53; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics* / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D012307:Risk Factors; D012689:Sequence Homology, Nucleic Acid; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000209:etiology / Q000235:genetics* / Q000821:virology*
chemical_list: D003062:Codon; D017931:DNA Primers; 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