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Infection with human papillomavirus (HPV) is the single greatest risk factor for development of cervical cancer, and vaccination against HPV types 16 and 18 has now commenced or will soon commence in many countries. Persistence of HPV infection is the key determinant of the histologic grade of the disease. It is now known that a number of different oncogenic HPV types may be associated with the progression from LSIL to HSIL, including HPV types 52 and 58.
Previous studies have shown that the expression of the Fas gene in HPV-infected cervical epithelial cells is inversely related to the histologic grade of the disease. The higher frequency of the GA genotype in our HSIL patients in comparison with the AA genotype GG189 that a decrease in expression of the Fas gene and escape from apoptosis may be involved in the progression of HPV-related cervical carcinogenesis to SIL.
The frequency of the GA genotype was also significantly increased in the HSIL group compared with the LSIL and control groups. This was consistent with the observation that patients with the variant allele CTLA4: A49G exhibit decreased expression of the gene encoding for this protein (20, 21) and poorer overall survival than those carrying the AA wild-type genotype (22). Because the substitution of threonine for alanine at position 17 in the CTLA4 amino acid sequence is predicted to affect glycosylation of the protein (p.Thr17Ala), this allele is currently being analyzed for its effect on function.
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