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David Guenat, Véronique Dalstein, Frédéric Mauny, Maëlle Saunier, Jenny Briolat, Christine Clavel, Didier Riethmuller, Christiane Mougin, Jean-Luc Prétet
High risk HPV infection is the necessary cause for the development of precancerous and cancerous lesions of the cervix. Among HPV, HPV16 represents the most carcinogenic type. Since the determination of HPV16 DNA load could be clinically useful, we assessed quantitative real-time PCR targeting E6HPV16 and albumin genes on two different platforms. Series of SiHa cells diluted in PreservCyt were used to assess repeatability and reproducibility of two in-house real-time PCR techniques run in two different laboratories to determine HPV16 load...
October 18, 2018: Papillomavirus Research
Han Deng, Eric Hillpot, Sumona Mondal, Kamal K Khurana, Craig D Woodworth
A major risk factor for cervical cancer is persistent infection with high-risk human papillomaviruses (HPV) which can cause cervical intraepithelial neoplasia. Greater than 90% of cervical cancers develop in the transformation zone (TZ), a small region of metaplastic squamous epithelium at the squamocolumnar junction between endocervix and ectocervix. However, it is unclear why this region is highly susceptible to malignant progression. We hypothesized that cells from TZ were more susceptible to dysplastic differentiation, a precursor to cervical cancer...
October 18, 2018: Scientific Reports
Qian Wang, Xiaomeng Ma, Xiaosong Zhang, Jason J Ong, Jun Jing, Lei Zhang, Lin-Hong Wang
OBJECTIVE: Women living with HIV (WLHIV) face disproportionately higher risks of acquiring human papillomavirus (HPV) compared with HIV negative counterparts. We aimed to investigate the prevalence of HPV in WLHIV in Chinese hospital setting and identify associated factors to the progression of late-stage cervical intraepithelial neoplasia (CIN2+) in this population. METHOD: This retrospective study collected data from 183 WLHIV on antiretroviral treatment (ART), based on reproductive health questionnaires...
October 18, 2018: Sexually Transmitted Infections
Nasreen Bano, Manisha Yadav, Bhudev C Das
Aim: To investigate the role of a herbal antioxidative compound curcumin on cell proliferation, orosphere formation and miRNA-21 expression in HPV16+ve/-ve oral cancer stem cells. Materials and Methods: Oral cancer stem cells were isolated from HPV+ve/HPV-ve oral cancer cell lines by FACS and stemness markers. MTT, spheroid assay and qRT-PCR were employed to examine the effects of curcumin. Results: Curcumin treatment in micromolar concentration (0-50 μM) demonstrated significant differential inhibition in CSC proliferation, orosphere formation and miRNA-21 expression in a dose dependent manner, the effect being highly pronounced in HPV positive CSCs...
2018: Frontiers in Oncology
Pranvera Zejnullahu Raçi, Lea Hošnjak, Mario Poljak, Snježana Židovec Lepej, Adriana Vince
OBJECTIVES: Kosovo's current health care system does not support organized nationwide cervical cancer screening and human papillomavirus (HPV) vaccination programs. To date, no reliable data are available on cervical cancer incidence and mortality in Kosovo, or on high-risk HPV (HR-HPV) prevalence and HPV type distribution. Our aim is to determinate the pre-vaccination prevalence and distribution of HR-HPVs and to assesses the associations between sociodemographic characteristics and increased risk of HPV infection in women from Kosovo...
2018: Ginekologia Polska
Shuai Zhen, Jiaojiao Lu, Ling Hua, Yun-Hui Liu, Wei Chen, Xu Li
Targeted therapy results in objective responses in cervical cancer. However, the responses are short. In contrast, treatment with immune checkpoint inhibitors results in a lower responses rate, but the responses tend to be more durable. Based on these findings, we hypothesized that HPV16 E6/E7-targeted therapy may synergize with the PD-1 pathway blockade to enhance antitumor activity. To test the hypothesis, we described the effects of CRISPR/Cas9 which targeted to the HPV and PD1 in vitro and in vivo. Our data showed that gRNA/cas9 targeted HPV16 E6/E7 induced cervical cancer cell SiHa apoptosis, and suggested that overexpression of PD-L1, induced by HPV16 E6/E7, may be responsible for lymphocyte dysfunction...
October 10, 2018: Archives of Biochemistry and Biophysics
Vladimir Gilca, Chantal Sauvageau, Gitika Panicker, Gaston De Serres, Manale Ouakki, Elizabeth R Unger
BACKGROUND: Limited data is available on the use of different HPV vaccines in the same subjects. We evaluated the immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent (9vHPV) and one dose of bivalent vaccine (2vHPV) administered in different order versus two doses of 9vHPV vaccine. METHODS: 371 girls and boys aged 9-10 years were randomized (1:1) to receive (I) two doses of 9vHPV or (II) a mixed schedule of 2vHPV + 9vHPV or 9vHPV + 2vHPV with a 6 month interval...
October 9, 2018: Vaccine
Bernd Peter Kost, Susanne Beyer, Lennard Schröder, Junyan Zhou, Doris Mayr, Christina Kuhn, Sandra Schulze, Simone Hofmann, Sven Mahner, Udo Jeschke, Helene Heidegger
PURPOSE: Cervical cancer is one of the most frequent cancers in women worldwide. In most of all cases, a persistent HPV infection is the leading cause. HPV-specific sequences are able to bind glucocorticoid receptor (GR). Dexamethasone can increase the activity of early promoters in HPV16 and HPV18 interfering in transcription control of viral oncogenes. The aim of our study was to evaluate glucocorticoid receptor as transcriptional factor in its active form in the nucleus of in cervical cancer cells and to correlate the results with clinical patient specific parameters...
October 10, 2018: Archives of Gynecology and Obstetrics
Chengjun Wu, Kersti Nilsson, Yunji Zheng, Camilla Ekenstierna, Natsuki Sugiyama, Ola Forslund, Naoko Kajitani, Haoran Yu, Johan Wennerberg, Lars Ekblad, Stefan Schwartz
Here we show that treatment of the HPV16-positive tonsillar cancer cell line HN26 with DNA alkylating cancer drug melphalan induced p53 and activated apoptosis. Melphalan reduced the levels of RNA polymerase II and cellular transcription factor Sp1 that were associated with HPV16 DNA. The resulting inhibition of transcription caused a rapid loss of the HPV16 early mRNAs encoding E6 and E7 as a result of their inherent instability. As a consequence of HPV16 E6 and E7 down-regulation, the DNA damage inflicted on the cells by melphalan caused induction of p53 and activation of apoptosis in the HN26 cells...
October 10, 2018: International Journal of Cancer. Journal International du Cancer
D Tsakogiannis, G D Moschonas, M Daskou, Z Stylianidou, Z Kyriakopoulou, C Kottaridi, T G Dimitriou, C Gartzonika, P Markoulatos
PURPOSE: The tumour suppressor protein RB plays a decisive role in negative control of the cell cycle, inhibiting tumour development. The present analysis investigated the prevalence of the nucleotide polymorphism A153104G, which is located at intron 18 of the RB1 gene, and investigated the impact of the polymorphic variability in the exon 19 and its flanking intronic sequences on the severity of cervical disease in HPV16-positive Greek women. METHODOLOGY: The nucleotide polymorphism A153104G was detected by PCR-RFLP assay, while the amplicons were further subjected to cloning and sequencing...
October 10, 2018: Journal of Medical Microbiology
Terry R Medler, Dhaarini Murugan, Wesley Horton, Sushil Kumar, Tiziana Cotechini, Alexandra M Forsyth, Patrick Leyshock, Justin J Leitenberger, Molly Kulesz-Martin, Adam A Margolin, Zena Werb, Lisa M Coussens
Complement is a critical component of humoral immunity implicated in cancer development; however, its biological contributions to tumorigenesis remain poorly understood. Using the K14-HPV16 transgenic mouse model of squamous carcinogenesis, we report that urokinase (uPA)+ macrophages regulate C3-independent release of C5a during premalignant progression, which in turn regulates protumorigenic properties of C5aR1+ mast cells and macrophages, including suppression of CD8+ T cell cytotoxicity. Therapeutic inhibition of C5aR1 via the peptide antagonist PMX-53 improved efficacy of paclitaxel chemotherapy associated with increased presence and cytotoxic properties of CXCR3+ effector memory CD8+ T cells in carcinomas, dependent on both macrophage transcriptional programming and IFNγ...
October 8, 2018: Cancer Cell
Risa Kudo, Manako Yamaguchi, Masayuki Sekine, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Megumi Hara, Sharon J B Hanley, Takayuki Enomoto
Background: Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended for 5 years because of safety concerns. While no scientific evidence exists to substantiate these concerns, one reason given for not reinstating recommendations is the lack of reliable vaccine effectiveness (VE) data in a Japanese population. This study reports the VE of the bivalent HPV vaccine in Japanese women aged 20-22 years. Methods: During cervical screening between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and provided data about their sexual history...
October 9, 2018: Journal of Infectious Diseases
Jin Qiu, Shiwen Peng, Ying Ma, Andrew Yang, Emily Farmer, Max A Cheng, Richard B S Roden, T-C Wu, Yung-Nien Chang, Chien-Fu Hung
While both pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV recombinant vaccinia viral vector-based vaccines have elicited HPV-specific CD8+ T cell responses in HPV16/E7-expressing tumor models, and been used as prime-boost regimen to enhance HPV-specific immune responses in humans (NCT00788164), the optimal route of administration for TA-HPV remains unclear. In a preclinical model, we examined the immunogenicity of priming with intramuscular pNGVL4a-Sig/E7(detox)/HSP70 followed by TA-HPV boost through different administration routes...
October 5, 2018: Virology
Andrey Coatrini Soares, Juliana Coatrini Soares, Valquiria Cruz Rodrigues, Heveline Dal Magro Follmann, Lidia Maria Rebolho Batista Arantes, Ana Carolina Carvalho, Matias Eliseo Melendez, José Humberto Tavares Guerreiro Fregnani, Rui M Reis, Andre L Carvalho, Osvaldo Novais Oliveira
High-risk HPV infection, mainly with HPV16 type, has been increasingly considered as an important etiologic factor in head and neck cancers. Detection of HPV16 is therefore crucial for these types of cancer, but clinical tests are not performed routinely in public health systems owing to the high cost and limitations of existing tests. In this paper, we report on a potentially low cost genosensor capable of detecting low concentrations of HPV16 in buffer samples and distinguishing, with high accuracy, head and neck cancer cell lines according to their HPV16 status...
October 8, 2018: ACS Applied Materials & Interfaces
Stephanie van de Wall, Karl Ljungberg, Peng Peng Ip, Annemarie Boerma, Maria L Knudsen, Hans W Nijman, Peter Liljeström, Toos Daemen
Cervical cancer develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7. Our group pioneered a recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. The most striking benefit of this alphavirus vector-based vaccine platform is its high potency. DNA vaccines on the other hand, have a major advantage with respect to ease of production. In this study, the benefits associated with both SFV-based vaccines and DNA vaccines were combined with the development of a DNA-launched RNA replicon (DREP) vaccine targeting cervical cancer...
2018: Oncoimmunology
Cai Zhang, Xiaofen Huang, Siyi Chen, Yike Li, Yufang Li, Xin Wang, Jixian Tang, Lin Xia, Zhijie Lin, Wenxin Luo, Tingdong Li, Shaowei Li, Jun Zhang, Ningshao Xia, Qinjian Zhao
Human papillomavirus (HPV) type 16 is the most common type implicated as the etiological agent that causes cervical cancer. The marketed prophylactic vaccines against HPV infection are composed of virus-like particles (VLPs) assembled from the recombinant major capsid protein L1. Elicitation of functional and neutralizing antibodies by vaccination is the mode of action by which the vaccines prevent the viral infection. In this study, a panel of murine mAbs against HPV16 L1 were generated and comprehensively characterized with respect to their mapping to the epitope spectrum on the viral capsid...
October 1, 2018: Vaccine
Laura A Fast, Snježana Mikuličić, Anna Fritzen, Jonas Schwickert, Fatima Boukhallouk, Daniel Hochdorfer, Christian Sinzger, Henar Suarez, Peter N Monk, María Yáñez-Mó, Diana Lieber, Luise Florin
Tetraspanins are suggested to regulate the composition of cell membrane components and control intracellular transport, which leaves them vulnerable to utilization by pathogens such as human papillomaviruses (HPV) and cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection. In this study, by means of cellular depletion, the cluster of differentiation (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in HeLa cells by 50 to 80%. Moreover, we tested recombinant proteins or peptides of specific tetraspanin domains on their effect on the most oncogenic HPV type, HPV16, and HCMV...
October 2, 2018: International Journal of Molecular Sciences
Elgar S Quabius, Julius Loehr, Dirk Haaser, Veronika Günther, Nico Maass, Christoph Röcken, Micaela Mathiak, Ibrahim Alkatout, Markus Hoffmann
In HNSCC, protein- and mRNA-expression of the antileukoproteinase SLPI are significantly inverse correlated with HPV-infection suggesting that elevated expression of SLPI protects against HPV-infections. Moreover, SLPI-expression is up-regulated in HNSCC-patients reporting a smoking habit. Here, we investigate the described correlation in other HPV-driven cancers, namely vulvar squamous cell carcinoma (VSCC). FFPE samples of 99 VSCC were analyzed by PCR for HPV-DNA-expression and by RT-qPCR for SLPI-mRNA-expression...
September 26, 2018: Translational Oncology
Emmanuelle Jeannot, Alexandre Harlé, Allyson Holmes, Xavier Sastre-Garau
Anal carcinomas (AC) are associated with human papillomavirus (HPV) DNA sequences, but little is known about the physical state of the viral genome in carcinoma cells. To define the integration status and gene(s) targeted by viral insertions in AC, tumor DNAs extracted from 35 tumor specimen samples in patients with HPV16-associated invasive carcinoma were analyzed using the detection of integrated papillomavirus sequences-PCR approach. The genomic status at integration sites was assessed using comparative genomic hybridization-array assay and gene expression using reverse transcription quantitative PCR (RT-qPCR)...
September 27, 2018: Genes, Chromosomes & Cancer
Vladimir Gilca, Chantal Sauvageau, Gitika Panicker, Gaston De Serres, Manale Ouakki, Elizabeth R Unger
The objective of this study was to assess the persistence of antibodies after a single dose of quadrivalent HPV vaccine (4vHPV) and the effect of a dose of nonavalent HPV vaccine (9vHPV) given 3-8 years later. Such data might be of interest in the decision-making process regarding the 2-dose course completion in non-compliant vaccinees in jurisdictions which switched from 4vHPV to 9vHPV. Girls who previously received a single dose of 4vHPV were eligible to participate. Blood specimens were collected just before and one month post-9vHPV administration...
September 25, 2018: Human Vaccines & Immunotherapeutics
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