Different DNA methylation pattern of HPV16, HPV18 and HPV51 genomes in asymptomatic HPV infection as compared to cervical neoplasia

Simanaviciene, Vaida; Popendikyte, Violeta; Gudlevičienė, Živilė; Žvirblienė, Aurelija

doi:10.1016/j.virol.2015.06.008

Cited by 15 publications

(15 citation statements)

References 37 publications

(59 reference statements)

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“…Moreover, they showed that the viral URR becomes hypo-methylated upon squamous cell differentiation in cells capable of replicating the viral genomes and producing progeny viral particles. These data were corroborated by further studies showing that in cells capable of producing papillomavirus particles, the URR tends to become hypomethylated in more differentiated cells [6]. However, the E2BSs and in particular the SP1 binding site seem to be highly methylated in the very superficial cell layers consistent with the downregulation of the early genes and the activation of the late genes due to the SP1 site methylation in these fully differentiated cells (early late shift) [7].…”

Section: Dna Methylation Of Viral Genomes In the Pv Life Cyclementioning

confidence: 59%

Role of DNA methylation in HPV associated lesions

Doeberitz

Prigge

2019

Papillomavirus Research

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sss Papillomavirus replication is tightly linked to squamous epithelial differentiation which in turn is governed to a large extent by epigenetic remodeling of genomes within the differentiating squamous epithelial cells. Over the past years it became evident that epigenetic and in particular differential methylation events substantially contribute to the regulation of the papillomavirus life cycle. Moreover, there is now good evidence that the initial trigger for HPV-mediated transformation of squamous epithelial cells is mediated by methylation of distinct CpG dinucleotides within E2-binding sites of the papillomavirus upstream regulatory region (URR). These findings have important implications for novel diagnostic markers but also for novel and indeed targeted therapy strategies for HPV linked neoplastic lesions.

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Section: Dna Methylation Of Viral Genomes In the Pv Life Cyclementioning

confidence: 59%

Role of DNA methylation in HPV associated lesions

Doeberitz

Prigge

2019

Papillomavirus Research

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“…The literature search yielded 572 potentially eligible studies; 44 studies [6], [7], [8], [9],[21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60] and 8819 women were included in the analysis (supplementary table 1, supplementary figure 1).…”

Section: Resultsmentioning

confidence: 99%

The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis

et al. 2019

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BackgroundMethylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN).MethodsWe performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates.Findings44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8–92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0–74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5–16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5–8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse (pooled sensitivity 77% (95%CI:63–87), specificity 64% (95%CI:55–71), area under the curve (0·73 (95%CI:0·69–0·77)).InterpretationHigher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing.FundingNIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020

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“…The L1 and L2 regions of other types of HPVs are methylated in cervical cancer/CIN. Aberrant methylation of CpG sites in the L1 and L2 regions of HPV18 and other high-risk HPV types including HPV31, HPV33, HPV45, HPV52, HPV51, and HPV58 relates with the progression from early-stage CINs and may be considered as a biomarker of the progression of cervical neoplasia [ 57 , 58 ]. Another research shows that the methylation of L1 in HPV16, HPV18, and HPV52 does not only play an important role in cervical cancer alone.…”

Section: Dna Methylation In Cervical Cancer and Cinmentioning

confidence: 99%

The Progress of Methylation Regulation in Gene Expression of Cervical Cancer

Feng

Dong

Chang

et al. 2018

International Journal of Genomics

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Cervical cancer is one of the most common gynecological tumors in females, which is closely related to high-rate HPV infection. Methylation alteration is a type of epigenetic decoration that regulates the expression of genes without changing the DNA sequence, and it is essential for the progression of cervical cancer in pathogenesis while reflecting the prognosis and therapeutic sensitivity in clinical practice. Hydroxymethylation has been discovered in recent years, thus making 5-hmC, the more stable marker, attract more attention in the field of methylation research. As markers of methylation, 5-hmC and 5-mC together with 5-foC and 5-caC draw the outline of the reversible cycle, and 6-mA takes part in the methylation of RNA, especially mRNA. Furthermore, methylation modification participates in ncRNA regulation and histone decoration. In this review, we focus on recent advances in the understanding of methylation regulation in the process of cervical cancer, as well as HPV and CIN, to identify the significant impact on the prospect of overcoming cervical cancer.

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Different DNA methylation pattern of HPV16, HPV18 and HPV51 genomes in asymptomatic HPV infection as compared to cervical neoplasia

Cited by 15 publications

References 37 publications

Role of DNA methylation in HPV associated lesions

Role of DNA methylation in HPV associated lesions

The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis

The Progress of Methylation Regulation in Gene Expression of Cervical Cancer

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