Cervical lesions ave associated with human papillomavirus type 16 intratypic variants that have high transcriptional activity and increased usage of common mammalian codons

Human papillomavirus type 16 (HPV-16) is a major cause of cervical neoplasi a, but only a minority of HPV-16 infections result in cancer. Whether parti cular HPV-16 variants are associated with cervical disease has not yet been clearly established. An investigation of whether cervical neoplasia is ass ociated with infection with HPV-16 intratypic variants was undertaken by us ing RFLP analyses in a study of 100 HPV-16 DNA-positive women with or witho ut neoplasia. RFLP variant 2 was positively associated [odds ratio (OR) = 2 .57] and variant 5 was negatively associated with disease (OR = 0.2). Varia nt 1, which resembles the reference isolate of HPV-16, was found at a simil ar prevalence among those with and without neoplasia, Variants 1 and 2 were also more likely to be associated with detectable viral mRNA than variant 5 (respectively P = 0.03 and P = 0.00). When HPV-16 E5 ORFs in 50 clones fr om 36 clinical samples were sequenced, 19 variant HPV-16 E5 DNA sequences w ere identified. Twelve of these DNA sequences encoded variant E5 amino acid sequences, 10 of which were novel. Whilst the associations between HPV-16 E5 RFLP variants and neoplasia could not be attributed to differences in am ino acid sequences, correlation was observed in codon usage. DNA sequences of RFLP variant 2 (associated with greatest OR for neoplasia) had a signifi cantly greater usage of common mammalian codons compared with RFLP pattern 1 variants.