Human Papillomavirus Type 16 E1 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 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.

Association of Human Papillomavirus Type 16 Long Control Region Variations with Cervical Cancer in a Han Chinese Population

“…Our previous study also showed that the HPV16 variants and the variations in theE1, E2, E6 and E7 genes were associated with cervical cancer in the Chinese Han population [26][27][28].Thus, in the current study, we investigated the distribution of LCR variation in the HPV16-positive asymptomatic individuals and HPV16-positive cervical cancer patients and found an association between the LCR variations and cervical cancer in a Han Chinese population.…”

Sequence variation analysis of the E1 and E2 genes of human papillomavirus type 16 in cervical lesions in women from the south of Poland

“…It is one of the key proteins in the process of replication of a viral genome -it has an ATP helicase activity (McBride & Warburton, 2017). The influence of the E1 protein mutations on oncogenesis has been studied by several authors and their results clearly show a correlation of some mutations of this protein with the occurrence of HSIL and cervical cancers (Sabol et al, 2012;Tsakogiannis et al, 2014;Yao et al, 2019). The relationship with the process of cervical oncogenesis was found in the case of following mutations: T933A, T1014G, A1668G, G2073A, G2160A, T2169C, T2189C, T2232C, G2337A, A2453T, C2454T, A2547G, A2587T and G2650A.…”

“…Presence of specific mutations in genes encoding E1, E2 and E6 proteins is also associated with an increased oncogenic potential of the virus (Bae et al, 2009;Hu et al, 2001Kahla et al, 2014Szostek et al, 2017;Tsakogiannis et al, 2014, Yao et al, 2019. Many publications show that the distribution of different variants of HPV16 mutations in the world population is not identical, some variants are characteristic of the European population, others are typical for Asian population and yet they are different from the African one (Burk et al, 2009).…”

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

“…In particular, the nucleotide variations T933A and T1014G were observed only in the A4 sub-lineage, the nucleotide variation A2547G was detected only in the A1-A3 sub-lineages, whereas the sequence changes G2160A and T2232C were detected in all members of the A lineage (Ref. 89). In contrast, these changes were not noticed in Greek patients.…”