The role of integration in oncogenic progression of HPV-associated cancers

McBride, Alison A.; Warburton, Alix

doi:10.1371/journal.ppat.1006211

Cited by 300 publications

(289 citation statements)

References 36 publications

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“…From this time on, HPV E6 and E7 expression is rising. Thus, in high‐grade lesions and cancer, the expression of E6 and E7 is no longer attenuated, which makes them ideal targets for immunotherapy . These low levels of viral protein expression can hinder detection of infected cells by local APCs and in turn the induction of a potent adaptive immune response directed against HPV‐infected cells.…”

Section: Gene Expressionmentioning

confidence: 99%

Immune evasion mechanisms of human papillomavirus: An update

Steinbach

Riemer

2017

Intl Journal of Cancer

108

107

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Human papillomavirus (HPV) is the most frequently sexually transmitted agent in the world. It can cause cervical and other anogenital malignancies, and oropharyngeal cancer. HPV has the unique ability to persist in the host's epithelium for a long time-longer than most viruses do-which is necessary to complete its replication cycle. To this end, HPV has developed a variety of immune evasion mechanisms, which unfortunately also favor the progression of the disease from infection to chronic dysplasia and eventually to cancer. This article summarizes the current knowledge about HPV immune evasion strategies. A special emphasis lies in HPV-mediated changes of the antigen processing machinery, which is generating epitopes for T cells and contributes to the detectability of infected cells.

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Section: Gene Expressionmentioning

confidence: 99%

Immune evasion mechanisms of human papillomavirus: An update

Steinbach

Riemer

2017

Intl Journal of Cancer

108

107

View full text Add to dashboard Cite

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“…HPVs persistent infection is the causative cause of cervical cancer . Some of the hrHPV persistent infection will be followed by viral DNA integration with human genome, resulting in over expression of two viral oncogene E6 and E7 . These oncoproteins bind to the tumor suppressor genes p53 and the retinoblastoma protein (pRB), destroy their function, leading to dysplasia and invasive cancer .…”

Section: Discussionmentioning

confidence: 99%

REBACIN® as a noninvasive clinical intervention for high‐risk human papillomavirus persistent infection

Yang

Duan

et al. 2019

Intl Journal of Cancer

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The development of highly sensitive HPV‐genotyping tests has opened the possibility of treating HPV‐infected women before high‐grade lesions appear. The lack of efficient intervention for persistent high‐risk HPV infection necessitates the need for development of novel therapeutic strategy. Here we demonstrate that REBACIN®, a proprietary antiviral biologics, has shown potent efficacy in the clearance of persistent HPV infections. Two independent parallel clinical studies were investigated, which a total of 199 patients were enrolled and randomly divided into a REBACIN®‐test group and a control group without treatment. The viral clearance rates for the REBACIN® groups were 61.5% (24/39) and 62.5% (35/56), respectively, for the two independent parallel studies. In contrast, the nontreatment groups showed self‐clearance rates at 20.0% (8/40) and 12.5% (8/64). We further found that REBACIN® was able to significantly repress the expression of HPV E6 and E7 oncogenes in TC‐1 and Hela cells. The two viral genes are well known for the development of high‐grade premalignancy lesion and cervical cancer. In a mouse model, REBACIN® was indicated to notably suppress E6/E7‐induced tumor growth, suggesting E6 and E7 oncogenes as a potential target of REBACIN®. Taken together, our studies shed light into the development of a novel noninvasive therapeutic intervention for clearance of persistent HPV infection with significant efficacy.

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“…We expect the correlation observed here to hold in a ground-truth scenario, such as in HPV-infected human epithelial tissue, because keratin expression patterns in human cells (reviewed in Moll et al 2008) are the same as those observed in our mouse model. One potential complication is the polycistronic nature of HPV mRNAs; RNAs encoding HPV genes are spliced to contain segments spanning multiple genes, resulting in different transcript variants that can encode different genes (McBride and Warburton, 2017). The spliced viral transcripts are generated with either the 'early' or 'late' polyadenylation sites following E5 and L1 respectively, a limitation that will be encountered by the 10X Chromium 3' system, but one that would be overcome with full length scRNA-seq.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis

Lukowski

Tuong

Nöske

et al. 2018

Journal of Investigative Dermatology

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Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA-sequencing (scRNA-seq) may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted scRNA-seq on keratinocytes from a mouse transgenic for the E7 gene of HPV16, and showed sensitive and specific detection of HPV16-E7 mRNA, predominantly in basal keratinocytes. We showed that increased E7 mRNA copy number per cell was associated with increased expression of E7 induced genes. This technique enhances detection of active viral transcription in solid tissue and may clarify possible linkage of HPV infection to development of squamous cell carcinoma.

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The role of integration in oncogenic progression of HPV-associated cancers

Cited by 300 publications

References 36 publications

Immune evasion mechanisms of human papillomavirus: An update

Immune evasion mechanisms of human papillomavirus: An update

REBACIN® as a noninvasive clinical intervention for high‐risk human papillomavirus persistent infection

Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis

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