Mutation Detection of E6 and LCR Genes from HPV 16 Associated with Carcinogenesis

Mosmann, Jessica Paola; Monetti, Marina; Frutos, María Celia; Kiguen, Ana Ximena; Venezuela, Raúl Fernando; Cuffini, Cecilia

doi:10.7314/apjcp.2015.16.3.1151

Cited by 19 publications

(13 citation statements)

References 33 publications

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“…However, a larger female cohort is needed to test this hypothesis. All the mutations in the E6 and LCR sequences found in our study, such as the amino-acid substitutions Q14D, C51F, D64E and H78Y, which reduce intracellular binding to E6AP and degradation of the cellular tumor antigen p53, have already been described [16, 35–37]. Moreover, the nucleotide variations observed in the LCR sequence are known binding sites for various transcription factors, such as YY1, AP1, Oct-1 [38].…”

Section: Discussionmentioning

confidence: 54%

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) in Libreville, Gabon

Moussavou-Boundzanga

Koumakpayi

Nkili-Meyong

et al. 2016

Infect Agents Cancer

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BackgroundThe human papillomavirus (HPV) is the causative agent of cervical cancer, which is the leading cancer-related cause of death for women in Sub-Saharan Africa. In 2013, the Gabonese Ministry of Health and the Sylvia Bongo Ondimba Foundation implemented cervical cancer screening programs based on the detection of cancerous lesions by visual inspection with acetic acid and/or Lugol’s iodine (VIA/VILI). This pilot study was set up to determine the HPV profile and analyze the nucleotide sequence variation of HPV16 circulating in patients with cervical abnormalities detected by VIA/VILI testing.MethodsThe cervical abnormalities observed upon VIA/VILI were confirmed by liquid-based cytology for all tested women. Nested PCR using the MY09/11 and GP5+/6+ primer sets was used to detect HPVs present in the extracted DNA. HPV genotypes were determined after sequencing of amplicons based on a high-throughput sequencing approach. For isolates of the HPV16 genotype, the E6 gene and the long control region (LCR) were directly sequenced using Sanger method.ResultsThe study included 87 women who showed a positive VIA/VILI result. Cervical abnormalities were found in 40.23 % of women and 40 % were classified as high-grade lesions. The HPV detection rate was 82.9 % among women with abnormal cytology. Among all the identified high-risk HPV genotypes, HPV16, 18 and 33 were the most frequent. Multiple HPV infections were observed in 42.31 % of HPV-infected women. Analysis of the HPV16 sequence variation in the E6 gene and in the LCR showed that 85.3 and 14.7 % belonged to the African and European lineages, respectively. Among the African branch variants, Af2 was the most frequently identified in this study.ConclusionThis study offers the first report of the HPV detection rate and molecular epidemiology among Gabonese women with a positive result in a VIA/VILI screening test. Moreover, data on the HPV16 sequence variation confirm the predominance of African variants in high-grade lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-016-0098-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 54%

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) in Libreville, Gabon

Moussavou-Boundzanga

Koumakpayi

Nkili-Meyong

et al. 2016

Infect Agents Cancer

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“…Finally, a score based on SNP data was implemented in order to infer viral variants within HPV types. Briefly, SNPs detected in the E6/E7 region of the HR types and associated to each variant were extracted from previous reports [ 9 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Then, all the nucleotide positions reported to harbor an SNP were searched in the sequenced samples and, for each SNP, one point was rewarded to all the variants compatible with it.…”

Section: Methodsmentioning

confidence: 99%

Characterization of Intra-Type Variants of Oncogenic Human Papillomaviruses by Next-Generation Deep Sequencing of the E6/E7 Region

Lavezzo

Masi

Toppo

et al. 2016

Viruses

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Different human papillomavirus (HPV) types are characterized by differences in tissue tropism and ability to promote cell proliferation and transformation. In addition, clinical and experimental studies have shown that some genetic variants/lineages of high-risk HPV (HR-HPV) types are characterized by increased oncogenic activity and probability to induce cancer. In this study, we designed and validated a new method based on multiplex PCR-deep sequencing of the E6/E7 region of HR-HPV types to characterize HPV intra-type variants in clinical specimens. Validation experiments demonstrated that this method allowed reliable identification of the different lineages of oncogenic HPV types. Advantages of this method over other published methods were represented by its ability to detect variants of all HR-HPV types in a single reaction, to detect variants of HR-HPV types in clinical specimens with multiple infections, and, being based on sequencing of the full E6/E7 region, to detect amino acid changes in these oncogenes potentially associated with increased transforming activity.

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“…The LCR region contains the early promoter and various transcriptional regulatory sites for both viral and cellular proteins [ 4 – 6 ], such as E2, YY1, Oct-1, NF1, transcriptional enhancer factor-1 (TEF-1), and others. Based principally on the LCR sequences, several studies from the United States, Germany, and Europe have suggested that certain LCR variants of HPV-16 may play an important role in viral persistence and the development of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Genetic variability and functional implication of the long control region in HPV-16 variants in Southwest China

Chen

et al. 2017

PLoS ONE

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HPV-16 long control region (LCR) has been shown to be the most variable region of the HPV-16 genome and may play important roles in viral persistence and the development of cervical cancer. This study aimed to assess the risk of HPV-16 LCR variants for cervical cancer in women of Southwest China. 2146 cervical scrapings of volunteer outpatients and 74 cervical cancer tissues were screened.14 entire HPV-16 LCRs from asymptomatic carriers and 34 entire HPV-16 LCRs from cervical cancer patients were successfully amplified and sequenced to align to others described. 58 different point mutations were detected in 54 nucleotide sites of HPV-16 LCR. G7193T and G7521A variants, accounting for 100% of the infections, were predicted to locate at the binding site for FOXA1 and SOX9, respectively. A7730C variant which showed a high mutation frequency in cervical cancer was predicted to be a binding site for the cellular transcription factor PHOX2A. In addition, phylogenetic analysis displayed a high prevalence of A lineage in HPV-16 LCR in this Southwest China population. This study may help understanding of the intrinsic geographical relatedness and the correlations between LCR mutations and the development of carcinogenic lesions in Southwest China population. And it provides useful data for the further study of the biological function of HPV-16 LCR variants.

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Mutation Detection of E6 and LCR Genes from HPV 16 Associated with Carcinogenesis

Cited by 19 publications

References 33 publications

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) in Libreville, Gabon

Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) in Libreville, Gabon

Characterization of Intra-Type Variants of Oncogenic Human Papillomaviruses by Next-Generation Deep Sequencing of the E6/E7 Region

Genetic variability and functional implication of the long control region in HPV-16 variants in Southwest China

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