Identification of novel E6-E7 sequence variants of human papillomavirus 16

Tsakogiannis, D.; Kyriakopoulou, Zaharoula; Amoutzias, Grigoris D.; Ruether, I. G. A.; Dimitriou, Tilemachos G.; Panotopoulou, Efstathia; Markoulatos, Panayotis

doi:10.1007/s00705-012-1555-9

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…In 2014, Tsakogiannis et al . reported that the A1668G (A268A), G2073A (K403K), T2169C (D435D), T2189C (I442T), A2453T (N530I), C2454T (N530N), A2587T (R575W) and G2650A (E596K) mutations of HPV16 E1 were identified only in high-grade dysplasia cases in a Greek population 18. In the current study, we also found that A1668G (A268A) and G2650A (E596K) occurred only in the case group, and this finding suggested these two mutations may play key roles in the carcinogenesis of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported that the distribution of HPV16 variants is different in different regions and ethnicities 18-21. For example, the A1-A3 (European, EUR) is the predominant variant in the Greek population 18-20, but the A4 (Asian, As) is the predominant variant in the Han Chinese population 21. Thus, in the present study, we aimed to identify HPV16 E1 mutations in HPV16-positive asymptomatic individuals and HPV16-positive cervical cancer patients and then to evaluate the association of HPV16 E1 mutations with cervical cancer in a Han Chinese population.…”

Section: Introductionmentioning

confidence: 99%

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Human Papillomavirus Type 16 E1 Mutations Associated with Cervical Cancer in a Han Chinese Population

et al. 2019

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Papillomavirus Type 16 E1 Mutations Associated with Cervical Cancer in a Han Chinese Population

et al. 2019

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“…On the other hand, the E7 variants have been studied to a lesser extent than the E6 variants. Some studies have reported, based on the conserved regions (CR) 1, CR2, and CR3 of E7, 4 variants in the CR1 domain [94,95], 5 in CR2 [94,[96][97][98][99], and 14 in CR3 [94,95,[100][101][102][103]. The most frequent variant, up to 70% in the Asian population, is the E7-G647 variant located in the CR2 domain [88,94].…”

Section: Variants Of Hpv 16mentioning

confidence: 99%

Metabolic Reprogramming in Cancer: Role of HPV 16 Variants

et al. 2021

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Metabolic reprogramming is considered one of the hallmarks in cancer and is characterized by increased glycolysis and lactate production, even in the presence of oxygen, which leads the cancer cells to a process called “aerobic glycolysis” or “Warburg effect”. The E6 and E7 oncoproteins of human papillomavirus 16 (HPV 16) favor the Warburg effect through their interaction with a molecule that regulates cellular metabolism, such as p53, retinoblastoma protein (pRb), c-Myc, and hypoxia inducible factor 1α (HIF-1α). Besides, the impact of the E6 and E7 variants of HPV 16 on metabolic reprogramming through proteins such as HIF-1α may be related to their oncogenicity by favoring cellular metabolism modifications to satisfy the energy demands necessary for viral persistence and cancer development. This review will discuss the role of HPV 16 E6 and E7 variants in metabolic reprogramming and their contribution to developing and preserving the malignant phenotype of cancers associated with HPV 16 infection.

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“…The HPVs that infect the mucosal epithelium are classified into the genus Alphapapillomaviruses (alpha-HPVs), and according to their tumourigenic capacity they are subdivided into high-risk (HR-HPV) and low-risk (LR-HPV) genotypes ( Refs 2,3,12). In particular, 15 HPV genotypes have been characterised as high-risk (HPV16, 18,31,33,35,39,45,51,52,56,58,59, 68, 73 and 82) (Ref. 14).…”

Section: Introductionmentioning

confidence: 99%

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

Bletsa¹,

Zagouri

Amoutzias

et al. 2021

Expert Rev. Mol. Med.

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Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6 : Q14H, H78Y, L83V, Ε7 : N29S, S63F, E2 : H35Q, P219S, T310K, E5 : I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

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Identification of novel E6-E7 sequence variants of human papillomavirus 16

Cited by 9 publications

References 38 publications

Human Papillomavirus Type 16 E1 Mutations Associated with Cervical Cancer in a Han Chinese Population

Human Papillomavirus Type 16 E1 Mutations Associated with Cervical Cancer in a Han Chinese Population

Metabolic Reprogramming in Cancer: Role of HPV 16 Variants

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

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