Abstract: Background and purpose: The incidence of cervical cancer is rather high in Xinjiang, which is closely associated with the infection of human papilloma virus type 16 (HPV-16). The purpose of this study was to analyze the variants and function of HPV-16 upstream regulatory region (URR) in the tissues of cervical cancer biopsies from Xinjiang. Methods: The DNAs were extracted from the tissues of cervical epithelial atypical hyperplasia (CIN) and cervical cancer biopsies. HPV-16 URR segments were amplified by PCR. Based on the sequence analysis of the URR, the representative URR variants were selected and cloned into pGL3-Basic. The recombinant plasmids were transfected into Vero cell lines respetively. Luciferase activity of transfected cells was detected 48 h after transfection. Results: Fifty-five HPV-16 URR DNA fragments were obtained through PCR, and 44 mutations were found from the URR fragments. 4 of these mutations, including nt7192(G→T) , nt7433(- →T), nt7435 (C→G) and nt7863 (A→-) occurred in all sequences. The mutation at nt7520 (G→A) occurred in 54 URR sequences, and the 39 other mutations were present in different samples. Based on the location and frequency of the mutations in the URR fragments, 9 URR variants were selected and cloned into pGL3-Basic. Then the luciferase activity of the cells transfected with pGL3- URR plasmids was detected respectively. Promoter activity of URR mutants from cervical cancer are significantly higher than that of URR mutants from CIN (P<0.01). Promoter activity of URR fragments from some cervical cancer was significantly higher than that of the URR fragments from SiHa and Caski cells. Conclusion: Multiple mutations occurred in HPV-16 URR of cervical cancer patients from Xinjiang. The promoter activity and carcinogenicity of some URR mutants have been enhanced.

Key words: Human papillomavirus type 16, Upstream regulatory region, Mutation, Promoter