Human Papillomavirus Type 16 E1 Mutations Associated with Cervical Cancer in a Han Chinese Population
2019
: Human papillomavirus type 16 (HPV16) is a high-risk HPV type and a potent carcinogen. HPV E1 is one of the most highly conserved proteins and it plays a central role in initiating HPV DNA replication. In current study, we enrolled 161 HPV16-positive cervical cancer patients (case group) and 171 HPV16-positive asymptomatic individuals (control group) in a study to analyse the association between HPV16 E1 genetic mutations and cervical cancer. The samples of case group were cervical cancer tissues and the samples of control group were cervical exfoliated cells. Three variants (A4, A1-A3 and D3) were found in the case group, 68.3% of the HPV16 E1 sequences belonged to the A4 (As) sub-lineage, 29.2% belonged to the A1-A3 (EUR) sub-lineage, and 2.5% belonged to the D3 (AA1) sub-lineage. Two variants (A4 and A1-A3) occurred in the control group. The A4 (As) sub-lineage was predominant in this group as well (66.1%), followed by the A1-A3 (EUR) sub-lineage (33.9%), but the D3 (AA1) sub-lineage was not found in the control group. The distribution of the HPV16 variants between the case and control groups was significantly different (P<0.05). When the distribution of the HPV16 E1 gene mutations was compared, the distribution of twenty-seven mutations was significantly different between the case and control groups (P<0.05), and twenty-two mutations occurred only in the D3 (AA1) sub-lineage, two were found only in the A4 (As) sub-lineage, one was found in the A1-A3 (EUR) sub-lineage, two was found in both the A4 (As) and A1-A3 (EUR) sub-lineages. In the sub-lineage analysis, the differences in the T933A (A23A), T1014G (D50E) and G2160A (R432R) mutations were statistically significant between the case and control groups for the A4 (As) sub-lineage (P<0.05), and the differences in the T2232C (F456F), G2337A (M491I) and A2547G (P561P) mutations were statistically significant between the case and control groups for the A1-A3 (EUR) sub-lineage (P<0.05). In the current study, we describe specific mutations in the HPV16 E1 gene associated with cervical cancer, and our study will provide a good reference for further functional studies of the relationship between cervical cancer carcinogenesis and HPV genes.
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