Human Papillomavirus Type 16 <i>E1</i> Mutations Associated with Cervical Cancer in a Han Chinese Population

Abstract

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 <i>E1</i> 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 <i>E1</i> 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 (<i>P</i><0.05). When the distribution of the HPV16 <i>E1</i> gene mutations was compared, the distribution of twenty-seven mutations was significantly different between the case and control groups (<i>P</i><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 (<i>P</i><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 (<i>P</i><0.05). In the current study, we describe specific mutations in the HPV16 <i>E1</i> 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.