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| Open AccessSingle cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer
The role of keratinocyte subpopulations in the different phases of the viral cycle during HPV16 infection remains to be characterised. Here, single cell RNA sequencing of HPV16 infected and uninfected organoids identifies 12 distinct keratinocyte populations including an HPV-reprogrammed keratinocyte subpopulation that is linked to cancer.
- Mary C. Bedard
- , Tafadzwa Chihanga
- & Susanne I. Wells
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| Open AccessA multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma
Patients with recurrent or metastatic cervical cancer have limited therapeutic options. Here the authors report efficacy and safety of camrelizumab (anti-PD-1 antibody) in combination with famitinib (anti-angiogenic agent) in pre-treated recurrent or metastatic squamous cervical cancer.
- Lingfang Xia
- , Qi Zhou
- & Xiaohua Wu
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| Open AccessHuman papillomavirus integration perspective in small cell cervical carcinoma
Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, the authors report human papillomavirus features and genomic landscape in SCCC via high-throughput sequencing methods and identify MYC, SOX, NR4A, ANKRD and CEA family genes as HPV-integrated hotspots.
- Xiaoli Wang
- , Wenlong Jia
- & Shuang Li
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| Open AccessIntegrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance
Human papillomavirus (HPV) is a known cause of cervical cancer. Here, the authors perform a multi-omic analysis using published cervical squamous cell carcinoma cohorts from the USA, Europe, and SubSaharan Africa and identify two cervical squamous cell carcinoma subtypes that display prognostic differences.
- Ankur Chakravarthy
- , Ian Reddin
- & Tim R. Fenton
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| Open AccessLong-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer
The molecular mechanisms underlying cervical carcinogenesis following integration of HPV DNA into the human genome remain elusive. Here, the authors perform long-read sequencing in 16 HPV16-positive cervical tumors and identify distinct integration types, structural variations and potential driver genes.
- Liyuan Zhou
- , Qiongzi Qiu
- & Yan Lu
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| Open AccessThe vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions
Persistent infection with human papillomavirus can lead to cervical intraepithelial neoplasia (CIN). Here, the authors profile the vaginal microbiota in a cohort of non-pregnant young women diagnosed with CIN2 and find that absence of Lactobacillusspp. and presence of a diverse population of strict anaerobes associates with a decreased regression of untreated CIN2 lesions.
- Anita Mitra
- , David A. MacIntyre
- & Maria Kyrgiou
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| Open AccessMutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance
The APOBEC mutational signature is prevalent in different tumour types. Here, using HPV16- positive cervical samples, the authors show that the signature is more prevalent in the viral genome of benign or clearing HPV16 infections compared to the viral genomes of the more advanced precancerous lesions or cervical cancer.
- Bin Zhu
- , Yanzi Xiao
- & Lisa Mirabello
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| Open AccessNuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth
High-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and current evidences link E7 to HPV-associated carcinogenesis. Here the authors propose a model in which the infection of epithelial cells with high risk HPV results in a burst of reactive oxygen species, translocation of LDHA to the nucleus and activation of a gene profile that supports the growth of cervical cancer.
- Yuan Liu
- , Ji-Zheng Guo
- & Qun-Ying Lei
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Article
| Open AccessPI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis
Mutations and post-translational modifications of the PI3K/AKT pathway inhibitor PTEN are a feature of many cancers, but these have not been associated with cervical cancer. Here, the authors identify a PI3K/AKT-mediated ubiquitination degradation pathway of PTEN that occurs in patients with cervical cancer.
- Min-Sik Lee
- , Man-Hyung Jeong
- & Jaewhan Song
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Article
| Open AccessNF-κB-induced KIAA1199 promotes survival through EGFR signalling
The cross-talk between constitutively active EGFR- and NF-κB-dependent pathways in cancer is poorly understood. Here, the authors identify KIAA1199 as a BCL3 and NF-κB-regulated protein that is expressed in cervical lesions and promotes tumorigenesis through Plexin A2 binding and regulation of EGFR stability.
- Kateryna Shostak
- , Xin Zhang
- & Alain Chariot
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Article
| Open AccessClearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients
While several human papilloma virus (HPV) vaccines exist, a highly effective vaccine that mediates regression of HPV-induced tumours is lacking. Here the authors show that a therapeutic DNA vaccine-induced HPV-specific polyfunctional CD8 T cell in 7 out of 9 patients who all exhibited complete regression of lesions and viral clearance.
- Tae Jin Kim
- , Hyun-Tak Jin
- & Young Chul Sung
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Gene network reconstruction reveals cell cycle and antiviral genes as major drivers of cervical cancer
As cervical tumours become more invasive, levels of episomal human papillomavirus paradoxically tend to decrease. Here the authors identify a network of antiviral and cell cycle genes that is amplified by chromosomal aberrations and promotes cervical tumour progression.
- Karina L. Mine
- , Natalia Shulzhenko
- & Andrey Morgun