Differential distribution of sequence variations in HPV-16 E6

Objective. The E6 regions of the oncogenic human papillomaviruses (HPVs) ar e important in carcinogenesis and immune recognition. We examined the E6 DN A sequence from HPV-16 associated cervical cancers to determine the frequen cy and degree of variation from the consensus sequence in selected populati ons. Methods. Samples positive for HPV-16 were analyzed using polymerase chain r eaction followed by automated DNA sequencing: 62 from U.S. women, 20 each f rom Italian and Indian women, and 21 from Thai women. Results. Of 151 codons, 18 contained 24 base substitutions, reflecting the overall conserved nature of this region. The HPV-16 E6 region from U.S, wom en showed considerably more sequence variation than that from European and Asian women. Five patterns common to U.S. and European and Asian samples ac counted for 78% of all tumor-associated viruses. The E6 regions known to be involved in p53 binding and degradation are involved with a surprising deg ree of sequence variation, whereas the carboxy end of the molecule is highl y conserved. Conclusions. The area of greatest sequence variation includes a proposed hu man leukocyte antigen interaction site. A novel large deletion in one sampl e results in loss of all functional regions of E6. These findings were anal yzed for possible significance with regard to immune selection and function al importance of the carboxy end of the E6 protein. (C) 2000 Academic Press .