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Animal: DNA Viruses |
The Richard Dimbleby Laboratory of Cancer Virology1 and the Departments of Infection2, Obstetrics and Gynaecology3 and Public Health Medicine4, Guy’s, King’s College and St Thomas’ Medical and Dental Schools, King’s College London, St Thomas’ Campus, Lambeth Palace Road, London SE1 7EH, UK
Author for correspondence: John Cason. Fax +44 20 7922 8394. e-mail jwcason{at}AOL.com
Human papillomavirus type 16 (HPV-16) is a major cause of cervical neoplasia, but only a minority of HPV-16 infections result in cancer. Whether particular HPV-16 variants are associated with cervical disease has not yet been clearly established. An investigation of whether cervical neoplasia is associated with infection with HPV-16 intratypic variants was undertaken by using RFLP analyses in a study of 100 HPV-16 DNA-positive women with or without neoplasia. RFLP variant 2 was positively associated [odds ratio (OR)=2·57] and variant 5 was negatively associated with disease (OR=0·2). Variant 1, which resembles the reference isolate of HPV-16, was found at a similar 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 from 36 clinical samples were sequenced, 19 variant HPV-16 E5 DNA sequences were 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 amino acid sequences, correlation was observed in codon usage. DNA sequences of RFLP variant 2 (associated with greatest OR for neoplasia) had a significantly greater usage of common mammalian codons compared with RFLP pattern 1 variants.
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