title: Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters.
abstract: Infection with human papillomavirus type 16 (HPV-16) confers a high risk for the development of cervical neoplasia. Variants of this virus may interact differentially with host genetic factors, possibly altering the disease course. Thus, HPV-16 E6 variants may differ in their ability to degrade p53 whereas the polymorphic p53 alleles may provide more or less susceptible substrates for the viral oncogene product. Also, E6 variants may differ in immunogenicity by generating different peptides for presentation by polymorphic HLA molecules to specific T cells. This study examines HPV-16 E6 sequence variation in cervical carcinomas from the UK and its relationship to polymorphism of HLA and p53 and to clinical parameters. Sequence analysis of the HPV-16 E6 ORF from 77 tumour biopsies detected the viral prototype sequence in 38% of cases. The most common variation detected was a T to G transition at base pair 350, resulting in an amino acid change from a leucine to a valine. Overall, the frequencies of 350T and 350G sequences were similar (49. 4% and 50.6% respectively). Other mutations of lower frequencies were detected together with and independently of 350G. HPV-16 E6 sequence variation at base pair 350 did not correlate with HLA genotype or clinical outcome. There was no difference in the distribution of p53 proline and arginine alleles between HPV-16-positive cervical carcinoma patients and local controls, and no influence on clinical outcome; however, there was a trend for an increased frequency of p53 arginine homozygotes among the 350T carcinoma patients.
authors.affiliation: Departments of Immunology1 and Cancer Genetics2, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Claire S
authors.initials: CS
authors.lastname: Brady
authors.affiliation: Departments of Immunology1 and Cancer Genetics2, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Duggan-Keen
authors.affiliation: Transplantation Laboratory, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK3.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Davidson
authors.affiliation: Departments of Immunology1 and Cancer Genetics2, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Varley
authors.affiliation: Departments of Immunology1 and Cancer Genetics2, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Stern
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D016158:Genes, p53; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins