Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters

Infection with human papillomavirus type 16 (HPV-16) confers a high risk fo r the development of cervical neoplasia. Variants of this virus may interac t differentially with host genetic factors, possibly altering the disease c ourse. Thus, HPV-16 E6 variants may differ in their ability to degrade p53 whereas the polymorphic p53 alleles may provide more or less susceptible su bstrates for the viral oncogene product. Also, E6 variants may differ in im munogenicity by generating different peptides for presentation by polymorph ic HLA molecules to specific T cells. This study examines HPV-16 E6 sequenc e variation in cervical carcinomas from the UK and its relationship to poly morphism of HLA and p53 and to clinical parameters. Sequence analysis of th e HPV-16 E6 ORF from 77 tumour biopsies detected the viral prototype sequen ce in 38% of cases. The most common variation detected was a T to G transit ion 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 de tected together with and independently of 350G. HPV-16 E6 sequence variatio n 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 al leles between HPV-16-positive cervical carcinoma patients and local control s, and no influence on clinical outcome; however, there was a trend for an increased frequency of p53 arginine homozygotes among the 350T carcinoma pa tients.