Elevated HPV16 E1 Expression Is Associated with Cervical Cancer Progression

Baedyananda, Fern; Chaiwongkot, Arkom; Bhattarakosol, Parvapan

doi:10.1159/000487048

Cited by 17 publications

(25 citation statements)

References 35 publications

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“…Among the processes associated with the development of cancer induced by HPV, viral persistence represents a leading key event at the beginning of this process 42 . Recently it was determined that E1 is expressed throughout the different stages of cervical cancer 43 . The authors analyzed the levels of HPV16 E1 mRNA in biopsies with different lesion degrees (CIN) as well as in cervical cancer, observing an increased expression of E1 as long as the lesion advances.…”

Section: Discussionmentioning

confidence: 99%

The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

Castro-Muñoz

Manzo-Merino

Muñoz-Bello

et al. 2019

Sci Rep

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The Human Papillomavirus (HPV) E1 protein is the only viral protein with enzymatic activity. The main known function of this protein is the regulation of the viral DNA replication. Nevertheless, it has been demonstrated that the ablation of HPV18 E1 mRNA in HeLa cells promotes a deregulation of several genes, particularly those involved in host defense mechanisms against viral infections; however, the specific contribution of E1 protein in HPV-independent context has not been studied. The aim of this work was to determine the effect of the HPV E1 protein in the regulation of cellular gene expression profiles evaluated through RNA-seq. We found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNβ1 and IFNλ1 and Interferon-stimulated gene (ISG), which are important components involved in the antiviral immune response. Together, our results indicate that HR-(High-Risk) and LR-(Low-Risk) HPV E1 proteins play an important role in inhibiting the anti-viral immune response.

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Section: Discussionmentioning

confidence: 99%

The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

Castro-Muñoz

Manzo-Merino

Muñoz-Bello

et al. 2019

Sci Rep

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“…According to previous research considered E6 and E7 proteins are targets for immunotherapy against tumors induced by HPV [ 17 ], but the immune response to HPV E1 antigen protein was not reported. Another study also showed the E1 expression can be detected at various stages of CC development where the level was associated with CC prognosis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Human papilloma virus E1-specific T cell immune response is associated with the prognosis of cervical cancer patients with squamous cell carcinoma

Fan

et al. 2018

Infect Agents Cancer

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BackgroundCervical cancer is attributable to human papilloma virus (HPV) infection in the majority cases. E1, an HPV derived-protein, plays an important role in the initiation and development of cervical cancer. Our study aims to investigate the HPV E1-specific T cell response in patients with cervical squamous cell carcinoma (CSCC).MethodsA total of 66 CSCC patients with FIGO stage IIB-IIIB and 60 healthy controls were enrolled. Enzyme-Linked ImmunoSpot (ELISPOT) assays was used to measure the HPV E1-specific T cell response in the peripheral blood of these patients before treatment. The patients were treated with chemotherapy and/or radiotherapy and followed up clinically for three years. The relationship between the T cell response, various clinical characteristics and the prognosis were studied with univariate analysis, multivariate analysis and survival curve analysis.ResultsThe frequency of HPV E1-specific T cell response in peripheral blood of cervical cancer patients was 59.09%, with mean response intensity 24.56 SFC/106 PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls(p < 0.001; p = 0.009). The intensity of HPV E1-specific T cell responses were higher in the stage IIB patients and patients with no pelvic lymph node metastasis (p = 0.038; p = 0.044). Univariate analysis showed that HPV E1 specific T cell response was associated with progression-free survival (PFS) and overall survival (OS) (PFS: p = 0.021; OS: p = 0.004). Multivariate analysis showed that HPV E1-specific T cell response was an independent prognostic factor influencing PFS and OS among all the factors included in our study (PFS: HR = 7.252, 95%CI = 1.690–31.126, p = 0.008; OS: HR = 7.499, 95%CI = 1.661–33.856, p = 0.009). The survival curves showed that the rate of PFS and OS in patients with HPV E1 specific T cell response was significantly higher than those who did not response.ConclusionsOur study demonstrated that the level of HPV E1-specific T cell response was correlated with the survival of advanced patients with CSCC. Patients who displayed no HPV E1-specific T cell response were more likely to be those with poor prognosis.

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“…Some studies reported hypomethylation of HPV16 early promoter in cervical carcinoma or so-called progressive hypomethylation [23, 24]. Other studies reported hypermethylation of early promoter in cervical carcinoma or progressive hypermethylation [21, 25, 26, 30, 44]. The physical state and copy number of integrated HPV16 genomes were the main reasons of these methylation differences as shown in CaSki and SiHa cells.…”

Section: Discussionmentioning

confidence: 99%

“…The methylation pattern in early promoter especially HPV16 E2BS has been widely studied in cervical cells and the methylation patterns were reported either progressive hypomethylation [23, 24] and progressive hypermethylation [21, 25, 26]. One study showed that high methylation of E2BS was correlated with episomal form in high grade cervical lesions, cervical carcinoma and multiple copies of integrated HPV genome [27].…”

Section: Introductionmentioning

confidence: 99%

Potential biomarker of human papillomavirus 16 L1 methylation for prediction of anal intraepithelial neoplasia in men who have sex with men (MSM)

Chaiwongkot

Bhattarakosol

Phanuphak

et al. 2021

Preprint

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Quantitative measurement of human papillomavirus (HPV) 16 early promoter and L1 genes methylation were analyzed in anal cells collected from men who have sex with men (MSM) to determine the potential biomarker for screening of HPV related anal cancer. The methylation patterns of the HPV16 genes including early promoter (CpG 31, 37, 43, 52 and 58) and L1 gene (CpG 5600, 5606, 5609, 5615, 7136 and 7145) were analyzed in 178 anal samples with histology diagnosed as normal, anal intraepithelial neoplasia (AIN) 1, AIN2 and AIN3 by pyrosequencing assay. Low methylation levels of early promoter (<10%) and L1 genes (<20%) were found in all detected normal anal cells, while medium to high methylation (>20-60%) in early promoter was found 1.5% (1/67) and 5% (2/40) in AIN1 and AIN2-3 samples, respectively. Interestingly, slightly increased L1 gene methylation level (>20-60%) especially at HPV16 5’L1 regions CpGs 5600 and 5609 from normal to AIN3 were demonstrated. Moreover, negative correlation between high HPV16 L1 gene methylation at CpGs 5600, 5609, 5615 and 7145 and low percentage of CD4+ was found in AIN3 HIV positive cases. When compared methylation status of AIN2-3 to those of the normal/AIN1 lesion, the results indicated potential of using HPV16 L1 gene methylation as a biomarker for HPV related cancer screening.

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Elevated HPV16 E1 Expression Is Associated with Cervical Cancer Progression

Cited by 17 publications

References 35 publications

The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

Human papilloma virus E1-specific T cell immune response is associated with the prognosis of cervical cancer patients with squamous cell carcinoma

Potential biomarker of human papillomavirus 16 L1 methylation for prediction of anal intraepithelial neoplasia in men who have sex with men (MSM)

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