Patterns of cellular and HPV 16 methylation as biomarkers for cervical neoplasia

Patel, Divya; Rozek, Laura S.; Colacino, Justin A.; Zomeren-Dohm, Adrienne Van; Ruffin, Mack T.; Unger, Elizabeth R.; Dolinoy, Dana C.; Swan, David C.; Onyekwuluje, Juanita; DeGraffinreid, Cecilia R.; Paskett, Electra D.

doi:10.1016/j.jviromet.2012.05.022

Cited by 22 publications

(20 citation statements)

References 45 publications

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“…As for precancerous lesions, we found a low methylation frequency (2%) of the five target CpGs, and normal samples harbored only unmethylated CpGs. Several studies also reported a very low methylation frequency in cervical dysplasia (28,30,32,33,36). This contrasts with the work of Mazumder and collaborators (31), who describe methylated CpG in 50% of LSIL-HSIL.…”

Section: Hpv16 E2bs Hrm-pcr Is a Reliable Methods For Methylation Assementioning

confidence: 80%

“…Some studies reported decreased E2BS methylation during lesion progression (30)(31)(32) or a trend of a lower risk of incident precancerous and cancerous lesions for patients with high E2BS methylation (33,34). On the contrary, methylation of the five CpGs located in the E2BS1 and E2BS2 and Sp1-binding site (Sp1BS) has frequently been associated with cervical cancer (28,29,(35)(36)(37)(38), and a gradual increase in methylation during lesion progression toward cancer has been reported in some studies (29,36,37,39).…”

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confidence: 99%

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Methylation of Human Papillomavirus Type 16 CpG Sites at E2-Binding Site 1 (E2BS1), E2BS2, and the Sp1-Binding Site in Cervical Cancer Samples as Determined by High-Resolution Melting Analysis–PCR

et al. 2013

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Certain Alphapapillomavirus species classified as high-risk human papillomaviruses (HR-HPVs) have been recognized as the etiologic factors of invasive cervical carcinoma worldwide (1, 2). HR-HPV infections are frequent in young women but they are generally transient, with an estimated mean duration of incident infection of 16 months (3). Only persistent HR-HPV infections are associated with an increased risk of developing high-grade cervical lesions or cancer of the cervix (4-6). Persistent HR-HPV infections may be associated with microscopic abnormalities called low-grade squamous intraepithelial lesions (LSIL). These LSIL present a high rate of regression following HPV clearance but may progress toward high-grade squamous intraepithelial lesions (HSIL) if HR-HPV infection persists. Upon diagnosis, HSIL are treated mostly by excisional procedures to avoid the risk of progression toward invasive cancer (for a review, see reference 7).Among the HR-HPV types, HPV16 exhibits the highest persistence rate (8). Moreover, HPV16 is associated with an increased risk of developing precancerous and cancerous lesions (9) and is considered the most carcinogenic PV in humans (10). This is probably why HPV16 prevalence increases with the severity of cervical lesions (11), reaching 61% in invasive cervical carcinoma worldwide (12).HPV-associated carcinogenesis requires the continuous overexpression of the two main viral oncoproteins E7 and E6, which interact with many cellular proteins leading to the induction and the maintenance of a transformed phenotype in infected cells (for a review, see reference 13). E7 and E6 expression is regulated by the viral E2 protein through the early promoter (named p97 for HPV16) located in the long control region (LCR) of the PV genome. This promoter harbors four specific E2-binding sites (E2BSs) sharing the consensus sequence 5=-ACCG(N) 4 15). The three sites proximal to the TATA box have been shown to be involved in E2-mediated repression of the promoter activity, and E2BS1 and E2BS2 are probably the main sites to achieve this effect (for a review, see reference 16). From a mechanistic point of view, the binding of E2 to E2BS1 and E2BS2 induces a displacement of transcription activators, such as specificity protein 1 (Sp1) and TATA binding protein (TBP), from their binding sites, leading to a repression of E7 and E6 expression from the early promoter (17, 18). HR-HPV DNA integration has been described as a key step in the carcinogenesis process, since it generally results in the disruption of the E2 open reading frame (ORF) (19,20).Epigenetic alterations, and particularly aberrant DNA methylation, are frequently associated with tumor progression. Methylation of DNA mainly occurs on cytosines located in CpG dinucle-

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Section: Hpv16 E2bs Hrm-pcr Is a Reliable Methods For Methylation Assementioning

confidence: 80%

mentioning

confidence: 99%

Methylation of Human Papillomavirus Type 16 CpG Sites at E2-Binding Site 1 (E2BS1), E2BS2, and the Sp1-Binding Site in Cervical Cancer Samples as Determined by High-Resolution Melting Analysis–PCR

et al. 2013

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“…The methylation level in cervical cancer correlates with HPV16 infection in cervical cells (Patel et al, 2012), and HPV16 virus integration is related to the development of cervical carcinogenesis (Mazumder et al, 2011). In our previous study, the HPV-positive rate reached up to 73.56% in cervical intraepithelial neoplasias and cervical cancer; a study examining the cervical cancer spectrum in Xinjiang Uyghur women demonstrated that HPV16 accounted for the highest proportion in Uyghur cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of P16 gene CpG methylation in Uyghur patients with cervical squamous cell carcinoma and its relationship with HPV16 infection

Cheng¹,

Yuan²,

Li³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The methylation of CpG sites in the promoter region of the P16 gene in Uyghur patients with cervical squamous cell carcinoma (CSCC) was quantitatively analyzed and its relationship with human papillomavirus 16 (HPV16) infection was explored. Cervical samples were collected from 20 Uyghur patients with CSCC and 20 Uyghur controls. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was applied to detect methylation of CpG sites in the promoter region of the P16 gene; polymerase chain reaction was performed to assess HPV16 infection in the 2 groups. Among the 16 CpG sites in the P16 gene promoter region, the methylation level of the CpG1-2 and CpG 6 sites, as well as the HPV16 infection rate, was higher in the CSCC group than in the control group (P < 0.05). There was no significant correlation between P16 CpG methylation and HPV16 infection in Uyghur patients with CSCC. The P16 gene 7429 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (3): 7428-7436 (2014) Relationship of P16 gene CpG methylation and HPV16 infection CpG1-2 and CpG 6 hypermethylation and HPV16 infection, which are independent of each other, play an important role in cervical squamous cell carcinogenesis in Uyghur patients.

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“…These tests can be based on the detection of specific types of oncogenic HPV that identify women at a higher cancer risk (e.g., HPV genotypes 16 and 18) (37). However, many other molecular mechanisms associated with HPV infection are necessary for cervical cancer development, such as chromosomal abnormalities, expression of oncogenes, epigenetic regulation (hyper methylation), and apoptotic markers, which cover a large number of potential biomarkers (38–40). Molecular tests have been lately under intensive study as a potential alternative and triage tests for cervical cancer screening.…”

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confidence: 99%

Disparity in rates of HPV infection and cervical cancer in underserved US populations

et al. 2017

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There is a higher rate of HPV infection and cervical cancer incidence and mortality in underserved US population who reside in Appalachian mountain region compared to Northern Plains. Social and behavioral factors such as smoking and alcohol consumption are for such a high incidence. However, by and large, the reasons for these discrepancies lie in the reluctance of the underserved population to adopt preventive measures such as prophylactic Human papilloma virus (HPV) vaccines and Pap smear screening that have significantly reduced the incidence and mortality rate of cervical cancer in Caucasian women. Thus, it is clear that drastic change in social behavior and implementation of preventive measures is required to effectively reduce the incidence and mortality from cervical cancer in this underserved population.

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Patterns of cellular and HPV 16 methylation as biomarkers for cervical neoplasia

Cited by 22 publications

References 45 publications

Methylation of Human Papillomavirus Type 16 CpG Sites at E2-Binding Site 1 (E2BS1), E2BS2, and the Sp1-Binding Site in Cervical Cancer Samples as Determined by High-Resolution Melting Analysis–PCR

Methylation of Human Papillomavirus Type 16 CpG Sites at E2-Binding Site 1 (E2BS1), E2BS2, and the Sp1-Binding Site in Cervical Cancer Samples as Determined by High-Resolution Melting Analysis–PCR

Quantitative analysis of P16 gene CpG methylation in Uyghur patients with cervical squamous cell carcinoma and its relationship with HPV16 infection

Disparity in rates of HPV infection and cervical cancer in underserved US populations

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