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Sample records for hpv cellular transactivator

  1. Hepatitis B virus DNA integration and transactivation of cellular genes

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    Vijay Kumar

    2007-02-01

    Full Text Available

    Chronic hepatitis B virus (HBV infection is etiologically related to human hepatocellular carcinoma (HCC. Most HCCs contain integrated HBV DNA in hepatocyte, suggesting that the integration may be involved in carcinogenesis. Available data on the integrants from human hepatocellular carcinomas seem to represent primary integrants as well as the products of secondary rearrangements. By means of structural analyses of the possible primary integrants, it has been observed that the replication intermediates of the viral genome are the preferred substrates for integration. The integrated HBV DNA and the target cellular DNA are invariably associated with deletions, possibly reflecting the substrate for, and the mechanism of, the integration reaction. The host DNA sequences as well as the target site of integration in chromosomes are selected randomly suggesting that HBV DNA integration should bring about random mutagenic effects. Analysis of the samples recovered from hepatocellular carcinomas show that the integrated HBV DNA can mediate secondary rearrangements of chromosomes, such as translocations, inversions, deletions and (possibly amplifications. The integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion. The integration has been shown in a number of cases to affect a variety of cancer-related genes and to exert insertional mutagenesis. However, in contrast to the woodchuck model, in which specific HBV-DNA integration is detectable in most cases, insertional activation or inactivation of cellular genes appears to be a rare event in man. The discovery of transactivating functions exerted by HBx and truncated HBs(urface proteins supports the notion that these could be relevant to hepatocarcinogenesis as these transactivator sequences have been found in a large number of HCC tumors or hepatoma-derived cell lines. The HBx

  2. Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity.

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    Maria V Chiantore

    Full Text Available Interferon (IFN-β inhibits cell proliferation and affects cell cycle in keratinocytes transformed by both mucosal high risk Human Papilloma Virus (HPV and cutaneous HPV E6 and E7 proteins. In particular, upon longer IFN-β treatments, cutaneous HPV38 expressing cells undergo senescence. IFN-β appears to induce senescence by upregulating the expression of the tumor suppressor PML, a well known IFN-induced gene. Indeed, experiments in gene silencing via specific siRNAs have shown that PML is essential in the execution of the senescence programme and that both p53 and p21 pathways are involved. IFN-β treatment leads to a modulation of p53 phosphorylation and acetylation status and a reduction in the expression of the p53 dominant negative ΔNp73. These effects allow the recovery of p53 transactivating activity of target genes involved in the control of cell proliferation. Taken together, these studies suggest that signaling through the IFN pathway might play an important role in cellular senescence. This additional understanding of IFN antitumor action and mechanisms influencing tumor responsiveness or resistance appears useful in aiding further promising development of biomolecular strategies in the IFN therapy of cancer.

  3. Controlling cellular P-TEFb activity by the HIV-1 transcriptional transactivator Tat.

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    Lisa Muniz

    Full Text Available The human immunodeficiency virus 1 (HIV-1 transcriptional transactivator (Tat is essential for synthesis of full-length transcripts from the integrated viral genome by RNA polymerase II (Pol II. Tat recruits the host positive transcription elongation factor b (P-TEFb to the HIV-1 promoter through binding to the transactivator RNA (TAR at the 5'-end of the nascent HIV transcript. P-TEFb is a general Pol II transcription factor; its cellular activity is controlled by the 7SK small nuclear RNA (snRNA and the HEXIM1 protein, which sequester P-TEFb into transcriptionally inactive 7SK/HEXIM/P-TEFb snRNP. Besides targeting P-TEFb to HIV transcription, Tat also increases the nuclear level of active P-TEFb through promoting its dissociation from the 7SK/HEXIM/P-TEFb RNP by an unclear mechanism. In this study, by using in vitro and in vivo RNA-protein binding assays, we demonstrate that HIV-1 Tat binds with high specificity and efficiency to an evolutionarily highly conserved stem-bulge-stem motif of the 5'-hairpin of human 7SK snRNA. The newly discovered Tat-binding motif of 7SK is structurally and functionally indistinguishable from the extensively characterized Tat-binding site of HIV TAR and importantly, it is imbedded in the HEXIM-binding elements of 7SK snRNA. We show that Tat efficiently replaces HEXIM1 on the 7SK snRNA in vivo and therefore, it promotes the disassembly of the 7SK/HEXIM/P-TEFb negative transcriptional regulatory snRNP to augment the nuclear level of active P-TEFb. This is the first demonstration that HIV-1 specifically targets an important cellular regulatory RNA, most probably to promote viral transcription and replication. Demonstration that the human 7SK snRNA carries a TAR RNA-like Tat-binding element that is essential for the normal transcriptional regulatory function of 7SK questions the viability of HIV therapeutic approaches based on small drugs blocking the Tat-binding site of HIV TAR.

  4. HPV

    Science.gov (United States)

    Human papillomaviruses (HPV) are a group of related viruses. They can cause warts on different parts of your body. There are ... cancer. There are two categories of sexually-transmitted HPV. Low-risk HPV can cause genital warts. High- ...

  5. Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

    International Nuclear Information System (INIS)

    Pinto, Ligia A.; Viscidi, Raphael; Harro, Clayton D.; Kemp, Troy J.; Garcia-Pineres, Alfonso J.; Trivett, Matthew; Demuth, Franklin; Lowy, Douglas R.; Schiller, John T.; Berzofsky, Jay A.; Hildesheim, Allan

    2006-01-01

    Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologous types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes

  6. Karyopherin β3: A new cellular target for the HPV-16 E5 oncoprotein

    International Nuclear Information System (INIS)

    Krawczyk, Ewa; Hanover, John A.; Schlegel, Richard; Suprynowicz, Frank A.

    2008-01-01

    Epidemiological and experimental studies have shown that high-risk human papillomaviruses (HPVs) are the causative agents of cervical cancer worldwide, and that HPV-16 is associated with more than half of these cases. In addition to the well-characterized E6 and E7 oncoproteins of HPV-16, recent evidence increasingly has implicated the HPV-16 E5 protein (16E5) as an important mediator of oncogenic transformation. Since 16E5 has no known intrinsic enzymatic activity, its effects on infected cells are most likely mediated by interactions with various cellular proteins and/or its documented association with lipid rafts. In the present study, we describe a new cellular target that binds to 16E5 in COS cells and in stable human ectocervical cell lines. This target is karyopherin β3, a member of the nuclear import receptor family with critical roles in the nuclear import of ribosomal proteins and in the secretory pathway

  7. HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression

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    Redmond, Catherine J.; Dooley, Katharine E.; Fu, Haiqing; Gillison, Maura L.; Akagi, Keiko; Symer, David E.; Aladjem, Mirit I.

    2018-01-01

    Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2, interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression. PMID:29364907

  8. Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus.

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    He, Zhiheng; Liu, Yunhua; Liang, Deguang; Wang, Zhuo; Robertson, Erle S; Lan, Ke

    2010-02-01

    Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jkappa, Ap-1, C/EBP-alpha, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jkappa has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.

  9. Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100

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    Matthew P Morrow

    2016-01-01

    Full Text Available We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFNγ production, tumor necrosis factor (TNFα production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth “booster” dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.

  10. Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes.

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    White, Elizabeth A; Walther, Johanna; Javanbakht, Hassan; Howley, Peter M

    2014-08-01

    The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly in patients with the genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two of the genus beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in squamous epithelial cells. This is in contrast to a well-characterized ability of the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have investigated the ability of genus beta E6 proteins from eight different HPV types to block the transactivation of p53 target genes following DNA damage. We find that the E6 proteins from diverse beta HPV species and types vary in their capacity to block the induction of MDM2, p21, and proapoptotic genes after genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at least some p53 target genes, although perhaps not by the same mechanism or to the same degree as the high-risk genus alpha HPV E6 proteins. This study addresses the ability of various human papillomavirus E6 proteins to block the activation of p53-responsive cellular genes following DNA damage in human keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high-risk, cancer-associated HPV types of genus alpha HPV have a well-established activity to target p53 degradation and thereby inhibit the response to DNA damage. In this study, we have investigated the ability of genus beta HPV E6 proteins from eight different HPV types to block the ability of p53 to transactivate downstream genes following DNA damage. We find that some, but not all, genus beta HPV E6 proteins can block the transactivation of some p53 target genes. This differential response to DNA damage furthers the understanding of cutaneous HPV biology and may help to explain the

  11. The synergistic transactivation of the hepatitis B viral (HBV) pregenomic promoter by the E6 protein of human papillomavirus type 16 (HPV-16 E6) with HBV X protein was mediated through the AP1 site of E element in the enhancer I (EnI) in human liver cell.

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    Lee, D H; Choi, B H; Rho, H M

    1999-11-01

    Infection by HBV of a cell already infected with other viral species or vice versa has been suggested as being involved in hepatocellular carcinoma. Using the CAT assay method, we investigated the interactive roles of HBx and potentially oncogenic and transactivating viral early proteins such as Ad5 E1A, HPV-16 E6, and SV40 T ag. In the presence of HBx, only HPV-16 E6 showed significant synergistic transactivation of EnI. We further investigated the function of the HPV-16 E6 using deletion, heterologous promoter, and mutation analyses on the EnI promoter. The results showed that the synergistic effect was mediated through the AP1 site of the E element in EnI by the direct activation of AP1 and support the idea that the infection by HBV of the cell with other viral species such as HPV-16 could increase the transcription activity of the HBV and other oncogenes containing an AP1 site in the promoter. Copyright 1999 Academic Press.

  12. Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions

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    Z.K. Tuong

    2018-06-01

    Full Text Available Currently available vaccines prevent HPV infection and development of HPV-associated malignancies, but do not cure existing HPV infections and dysplastic lesions. Persistence of infection(s in immunocompetent patients may reflect induction of local immunosuppressive mechanisms by HPV, providing a target for therapeutic intervention. We have proposed that a mouse, expressing HPV16 E7 oncoprotein under a Keratin 14 promoter (K14E7 mice, and which develops epithelial hyperplasia, may assist with understanding local immune suppression mechanisms that support persistence of HPV oncogene-induced epithelial hyperplasia. K14E7 skin grafts recruit immune cells from immunocompetent hosts, but consistently fail to be rejected. Here, we review the literature on HPV-associated local immunoregulation, and compare the findings with published observations on the K14E7 transgenic murine model, including comparison of the transcriptome of human HPV-infected pre-malignancies with that of murine K14E7 transgenic skin. We argue from the similarity of i the literature findings and ii the transcriptome profiles that murine K14E7 transgenic skin recapitulates the cellular and secreted protein profiles of high-grade HPV-associated lesions in human subjects. We propose that the K14E7 mouse may be an appropriate model to further study the immunoregulatory effects of HPV E7 expression, and can facilitate development and testing of therapeutic vaccines.

  13. Differential expression of cellular microRNAs in HPV 11, -16, and -45 transfected cells

    DEFF Research Database (Denmark)

    Dreher, Anita; Rossing, Maria; Kaczkowski, Bogumil

    2011-01-01

    Human papillomaviruses (HPVs) are highly prevalent giving rise to both benign and malignant lesions why they are classified as high- and low-risk viruses. In this study we selected one low-risk (HPV 11) and two high-risk (HPV 16 and -45) types for genomewide miRNA analysis to investigate possible...

  14. Genetically modified cellular vaccines for therapy of human papilloma virus type 16 (HPV 16)-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2008-01-01

    Roč. 8, č. 3 (2008), s. 180-186 ISSN 1568-0096 Grant - others:EU-FP6-NoE Clinigene(XE) 018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * genetically modified vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.316, year: 2008

  15. BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression

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    Shwu-Yuan Wu

    2016-08-01

    Full Text Available Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4, a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV to viral early gene and cellular matrix metalloproteinase-9 (MMP-9 promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.

  16. Transactivation of a cellular promoter by the NS1 protein of the parvovirus minute virus of mice through a putative hormone-responsive element.

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    Vanacker, J M; Corbau, R; Adelmant, G; Perros, M; Laudet, V; Rommelaere, J

    1996-01-01

    The promoter of the thyroid hormone receptor alpha gene (c-erbA-1) is activated by the nonstructural protein 1 (NS1) of parvovirus minute virus of mice (prototype strain [MVMp]) in ras-transformed FREJ4 cells that are permissive for lytic MVMp replication. This stimulation may be related to the sensitivity of host cells to MVMp, as it does not take place in parental FR3T3 cells, which are resistant to the parvovirus killing effect. The analysis of a series of deletion and point mutants of the c-erbA-1 promoter led to the identification of an upstream region that is necessary for NS1-driven transactivation. This sequence harbors a putative hormone-responsive element and is sufficient to render a minimal promoter NS1 inducible in FREJ4 but not in FR3T3 cells, and it is involved in distinct interactions with proteins from the respective cell lines. The NS1-responsive element of the c-erbA-1 promoter bears no homology with sequences that were previously reported to be necessary for NS1 DNA binding and transactivation. Altogether, our data point to a novel, cell-specific mechanism of promoter activation by NS1. PMID:8642664

  17. Multiple-integrations of HPV16 genome and altered transcription of viral oncogenes and cellular genes are associated with the development of cervical cancer.

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    Xulian Lu

    Full Text Available The constitutive expression of the high-risk HPV E6 and E7 viral oncogenes is the major cause of cervical cancer. To comprehensively explore the composition of HPV16 early transcripts and their genomic annotation, cervical squamous epithelial tissues from 40 HPV16-infected patients were collected for analysis of papillomavirus oncogene transcripts (APOT. We observed different transcription patterns of HPV16 oncogenes in progression of cervical lesions to cervical cancer and identified one novel transcript. Multiple-integration events in the tissues of cervical carcinoma (CxCa are significantly more often than those of low-grade squamous intraepithelial lesions (LSIL and high-grade squamous intraepithelial lesions (HSIL. Moreover, most cellular genes within or near these integration sites are cancer-associated genes. Taken together, this study suggests that the multiple-integrations of HPV genome during persistent viral infection, which thereby alters the expression patterns of viral oncogenes and integration-related cellular genes, play a crucial role in progression of cervical lesions to cervix cancer.

  18. NF-Y loss triggers p53 stabilization and apoptosis in HPV18-positive cells by affecting E6 transcription.

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    Benatti, Paolo; Basile, Valentina; Dolfini, Diletta; Belluti, Silvia; Tomei, Margherita; Imbriano, Carol

    2016-07-19

    The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonical motif within the URR and activates viral gene expression. In addition, NF-Y indirectly up-regulates HPV18 transcription through the transactivation of multiple cellular transcription factors. NF-YA depletion inhibits the expression of E6 and E7 genes and re-establishes functional p53. The activation of p53 target genes in turn leads to apoptotic cell death. Finally, we show that NF-YA loss sensitizes HPV18-positive cells toward the DNA damaging agent Doxorubicin, via p53-mediated transcriptional response.

  19. Genetically modified cellular vaccines against human papillomavirus type 16 (HPV16)-associated tumors: adjuvant treatment of minimal residual disease after surgery/chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Šímová, Jana

    2009-01-01

    Roč. 14, č. 1 (2009), s. 169-173 ISSN 1107-0625 R&D Projects: GA ČR GA301/06/0774; GA ČR GA301/07/1410 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : residual tumour disease * HPV16 * cellular vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.600, year: 2009

  20. Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer.

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    Mishra, Alok; Kumar, Rakesh; Tyagi, Abhishek; Kohaar, Indu; Hedau, Suresh; Bharti, Alok C; Sarker, Subhodeep; Dey, Dipankar; Saluja, Daman; Das, Bhudev

    2015-01-01

    In this study, we investigated the effects of the natural antioxidant curcumin on the HPV16-positive oral carcinoma cell line 93VU147T and demonstrated that curcumin is not only a potent inhibitor for the activity of host nuclear transcription factors AP-1 and NF-kB but it also selectively suppresses transcription of the HPV16/E6 oncogene during the carcinogenic process in oral cancer cells. This study suggests a therapeutic potential of curcumin for high-risk human papilloma virus (HPV)-infected oral cancers.

  1. A Simple and Robust Method for Semi-Quantitative Detection of Human Papillomavirus Nucleic Acids (HPV Helps Oncological Clinicians to Assess the Severeness of HPV Cellular Changing

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    Florian Heirler

    2011-01-01

    Full Text Available A simple and robust method for the detection of nucleic acids of human papilloma virus (HPV has been developed. The assay exploits the excellent sensitivity and specificity of “nested” polymerase chain reaction (nPCR that is designed in the original single tube configuration to effectively prevent the carry-over contamination. This approach theoretically covers the amplification of all cancer developing genotypes currently known. The nPCR, paired with very simple nucleic acids isolation steps, is a real alternative to the standard method. This manuscript shows its capacity for routine use under clinical conditions. It is shown that the strategy is at least as sensitive as the standard two tube nPCR and the data are acceptably reproducible.

  2. HPV Vaccine

    Science.gov (United States)

    ... Against HPV Print en español Vacuna contra el virus del papiloma humano (VPH) What Is HPV and Why Is It a Problem? Human papillomavirus (HPV) is one of the most common sexually transmitted diseases (STDs) . HPV is the virus that causes genital warts . Besides genital warts, an ...

  3. BS69 : A novel adenovirus E1A-associated protein that inhibits E1A transactivation

    NARCIS (Netherlands)

    Hateboer, G.; Gennissen, A.M.C.; Ramos, Y.F.M.; Kerkhoven, R.; Sonntag-Buck, V.; Stunnenberg, H.G.; Bernards, R.A.

    1995-01-01

    The adenovirus ElA gene products are nuclear phosphoproteins that can transactivate the other adenovirus early genes as well as several cellular genes, and can transform primary rodent cells in culture. Transformation and transactivation by ElA proteins is most likely to be mediated through

  4. The Paradigm of G Protein Receptor Transactivation: A Mechanistic Definition and Novel Example

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    Peter J. Little

    2011-01-01

    Full Text Available Seven transmembrane G protein—coupled receptors are among the most common in biology and they transduce cellular signals from a plethora of hormones. As well as their own well-characterized signaling pathways, they can also transactivate tyrosine kinase growth factor receptors to greatly expand their own cellular repertoire of responses. Recent data in vascular smooth muscle cells have expanded the breadth of transactivation to include serine/threonine kinase receptors, specifically the receptor for transforming growth factor beta (TGF-β. Stimulation with endothelin and thrombin leads to the rapid formation of C-terminal phosphorylated Smad2, which is the immediate product of activation of the TGF-β receptor. Additionally, it appears that no definition of transactivation based on mechanism is available, so we have provided a definition involving temporal aspects and the absence of de novo protein synthesis. The phenomenon of transactivation is an important biochemical mechanism and potential drug target in multiple diseases.

  5. Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR

    DEFF Research Database (Denmark)

    Dreher, Anita; Rossing, Maria; Kaczkowski, Bogumil

    2010-01-01

    Human papillomavirus type 11 (HPV-11) infects the genital and the respiratory tract leading to condylomas and respiratory papillomatosis. HPV infections are restricted to epithelial tissue and the progression through the virus lifecycle is tightly coordinated to the differentiation of the host ce...

  6. Genital Warts (HPV)

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    ... Videos for Educators Search English Español Genital Warts (HPV) KidsHealth / For Teens / Genital Warts (HPV) What's in ... HPV infection. How Do People Know They Have HPV? Most HPV infections have no signs or symptoms. ...

  7. Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.

    Science.gov (United States)

    Kehrmann, Angela; Truong, Ha; Repenning, Antje; Boger, Regina; Klein-Hitpass, Ludger; Pascheberg, Ulrich; Beckmann, Alf; Opalka, Bertram; Kleine-Lowinski, Kerstin

    2013-01-01

    The fusion between human tumorigenic cells and normal human diploid fibroblasts results in non-tumorigenic hybrid cells, suggesting a dominant role for tumor suppressor genes in the generated hybrid cells. After long-term cultivation in vitro, tumorigenic segregants may arise. The loss of tumor suppressor genes on chromosome 11q13 has been postulated to be involved in the induction of the tumorigenic phenotype of human papillomavirus (HPV)18-positive cervical carcinoma cells and their derived tumorigenic hybrid cells after subcutaneous injection in immunocompromised mice. The aim of this study was the identification of novel cellular genes that may contribute to the suppression of the tumorigenic phenotype of non-tumorigenic hybrid cells in vivo. We used cDNA microarray technology to identify differentially expressed cellular genes in tumorigenic HPV18-positive hybrid and parental HeLa cells compared to non-tumorigenic HPV18-positive hybrid cells. We detected several as yet unknown cellular genes that play a role in cell differentiation, cell cycle progression, cell-cell communication, metastasis formation, angiogenesis, antigen presentation, and immune response. Apart from the known differentially expressed genes on 11q13 (e.g., phosphofurin acidic cluster sorting protein 1 (PACS1) and FOS ligand 1 (FOSL1 or Fra-1)), we detected novel differentially expressed cellular genes located within the tumor suppressor gene region (e.g., EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) and leucine rich repeat containing 32 (LRRC32) (also known as glycoprotein-A repetitions predominant (GARP)) that may have potential tumor suppressor functions in this model system of non-tumorigenic and tumorigenic HeLa x fibroblast hybrid cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. HPV16-E2 induces prophase arrest and activates the cellular DNA damage response in vitro and in precursor lesions of cervical carcinoma.

    Science.gov (United States)

    Xue, Yuezhen; Toh, Shen Yon; He, Pingping; Lim, Thimothy; Lim, Diana; Pang, Chai Ling; Abastado, Jean-Pierre; Thierry, Françoise

    2015-10-27

    Cervical intraepithelial neoplasia (CIN) is caused by human papillomavirus (HPV) infection and is the precursor to cervical carcinoma. The completion of the HPV productive life cycle depends on the expression of viral proteins which further determines the severity of the cervical neoplasia. Initiation of the viral productive replication requires expression of the E2 viral protein that cooperates with the E1 viral DNA helicase. A decrease in the viral DNA replication ability and increase in the severity of cervical neoplasia is accompanied by simultaneous elevated expression of E6 and E7 oncoproteins. Here we reveal a novel and important role for the HPV16-E2 protein in controlling host cell cycle during malignant transformation. We showed that cells expressing HPV16-E2 in vitro are arrested in prophase alongside activation of a sustained DDR signal. We uncovered evidence that HPV16-E2 protein is present in vivo in cells that express both mitotic and DDR signals specifically in CIN3 lesions, immediate precursors of cancer, suggesting that E2 may be one of the drivers of genomic instability and carcinogenesis in vivo.

  9. Human Papillomavirus (HPV) Vaccine

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    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  10. Smoking and human papillomavirus (HPV) infection in the HPV in Men (HIM) study.

    Science.gov (United States)

    Schabath, Matthew B; Villa, Luisa L; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Quiterio, Manuel; Giuliano, Anna R

    2012-01-01

    The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01-1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05-1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05-1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11-1.92) was only evident among men reporting fewer lifetime sexual partners. These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection.

  11. Mutations that abrogate transactivational activity of the feline leukemia virus long terminal repeat do not affect virus replication

    International Nuclear Information System (INIS)

    Abujamra, Ana L.; Faller, Douglas V.; Ghosh, Sajal K.

    2003-01-01

    The U3 region of the LTR of oncogenic Moloney murine leukemia virus (Mo-MuLV) and feline leukemia viruses (FeLV) have been previously reported to activate expression of specific cellular genes in trans, such as MHC class I, collagenase IV, and MCP-1, in an integration-independent manner. It has been suggested that transactivation of these specific cellular genes by leukemia virus U3-LTR may contribute to the multistage process of leukemogenesis. The U3-LTR region, necessary for gene transactivational activity, also contains multiple transcription factor-binding sites that are essential for normal virus replication. To dissect the promoter activity and the gene transactivational activity of the U3-LTR, we conducted mutational analysis of the U3-LTR region of FeLV-A molecular clone 61E. We identified minimal nucleotide substitution mutants on the U3 LTR that did not disturb transcription factor-binding sites but abrogated its ability to transactivate the collagenase gene promoter. To determine if these mutations actually have altered any uncharacterized important transcription factor-binding site, we introduced these U3-LTR mutations into the full-length infectious molecular clone 61E. We demonstrate that the mutant virus was replication competent but could not transactivate cellular gene expression. These results thus suggest that the gene transactivational activity is a distinct property of the LTR and possibly not related to its promoter activity. The cellular gene transactivational activity-deficient mutant FeLV generated in this study may also serve as a valuable reagent for testing the biological significance of LTR-mediated cellular gene activation in the tumorigenesis caused by leukemia viruses

  12. The pathobiology and mechanisms of infection of HPV.

    Science.gov (United States)

    Wood, N H; Khammissa, R A G; Chikte, U M E; Meyerov, R; Lemmer, J; Feller, L

    2010-04-01

    There are more than 120 types of low-risk and high-risk human papillomaviruses, all of which are epitheliotropic. HPV infection may be latent, or active in a subclinical form or a symptomatic form, the latter manifesting as benign or malignant neoplasms. In basal cells with non-productive HPV infection some early HPV proteins are expressed independently of cell maturation: the productive cycle of HPV replication depends upon specific cellular factors of the maturation of the infected keratinocytes. In HPV-mediated oncogenesis, the combined pathobiological effects of E6 and E7 oncoproteins of high-risk HPV culminate in cellular genomic instability and transformation of persistently infected cells, that progress to the development of a malignant phenotype. In this article we provide insights into the stages of HPV infection, and into the viral genomic organization and replicative cycle.

  13. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Yoshimitsu, Makoto; Hachiman, Miho [Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ikeda, Masanori [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2015-12-15

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

  14. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

    International Nuclear Information System (INIS)

    Kusano, Shuichi; Yoshimitsu, Makoto; Hachiman, Miho; Ikeda, Masanori

    2015-01-01

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

  15. The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity

    International Nuclear Information System (INIS)

    Meissner, Torsten B.; Li, Amy; Liu, Yuen-Joyce; Gagnon, Etienne; Kobayashi, Koichi S.

    2012-01-01

    Highlights: ► NLRC5 requires an intact NLS for its function as MHC class I transactivator. ► Nuclear presence of NLRC5 is required for MHC class I induction. ► Nucleotide-binding controls nuclear import and transactivation activity of NLRC5. -- Abstract: Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a ‘master regulator’ of MHC class II genes, CIITA, has long been known, NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine.

  16. HPV: Molecular pathways and targets.

    Science.gov (United States)

    Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C

    2018-04-05

    Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction

  17. Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.

    Science.gov (United States)

    Suk, Hyung; Knipe, David M

    2015-06-01

    The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16-interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF-1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate-early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well-documented function in transactivation of IE gene expression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. HPV and Cancer

    Science.gov (United States)

    Human papillomaviruses (HPVs) are a group of more than 200 related viruses that can cause several cancers including cervical cancer, anal cancer, and oropharyngeal cancer. Learn more about how HPV is transmitted, the different types of HPV, HPV vaccines, and HPV treatment.

  19. Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

    International Nuclear Information System (INIS)

    Pei, Xin-Hong; Lv, Xin-Quan; Li, Hui-Xiang

    2014-01-01

    Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression

  20. Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context

    Energy Technology Data Exchange (ETDEWEB)

    Joslin, Elizabeth J.; Shankaran, Harish; Opresko, Lee K.; Bollinger, Nikki; Lauffenburger, Douglas A.; Wiley, H. S.

    2010-05-10

    Transactivation of the epidermal growth factor receptor (EGFR) has been proposed to be a mechanism by which a variety of cellular inputs can be integrated into a single signaling pathway, but the regulatory topology of this important system is unclear. To understand the transactivation circuit, we first created a “non-binding” reporter for ligand shedding. We then quantitatively defined how signals from multiple agonists were integrated both upstream and downstream of the EGFR into the extracellular signal regulated kinase (ERK) cascade in human mammary epithelial cells. We found that transactivation is mediated by a recursive autocrine circuit where ligand shedding drives EGFR-stimulated ERK that in turn drives further ligand shedding. The time from shedding to ERK activation is fast (<5 min) whereas the recursive feedback is slow (>15 min). Simulations showed that this delay in positive feedback greatly enhanced system stability and robustness. Our results indicate that the transactivation circuit is constructed so that the magnitude of ERK signaling is governed by the sum of multiple direct inputs, while recursive, autocrine ligand shedding controls signal duration.

  1. Interactions of Chromatin Context, Binding Site Sequence Content, and Sequence Evolution in Stress-Induced p53 Occupancy and Transactivation

    OpenAIRE

    Su, Dan; Wang, Xuting; Campbell, Michelle R.; Song, Lingyun; Safi, Alexias; Crawford, Gregory E.; Bell, Douglas A.

    2015-01-01

    Cellular stresses activate the tumor suppressor p53 protein leading to selective binding to DNA response elements (REs) and gene transactivation from a large pool of potential p53 REs (p53REs). To elucidate how p53RE sequences and local chromatin context interact to affect p53 binding and gene transactivation, we mapped genome-wide binding localizations of p53 and H3K4me3 in untreated and doxorubicin (DXR)-treated human lymphoblastoid cells. We examined the relationships among p53 occupancy, ...

  2. HPV and Men

    Science.gov (United States)

    ... Controls Cancel Submit Search the CDC Human Papillomavirus (HPV) Note: Javascript is disabled or is not supported ... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) HPV and Men - Fact Sheet Language: English (US) Español ( ...

  3. HPV (Human Papillomavirus)

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... Español In Chamorro In Urdu In Vietnamese HPV (human papillomavirus) is a sexually transmitted virus. It is ...

  4. Modulation of antigen presenting cell functions during chronic HPV infection

    Directory of Open Access Journals (Sweden)

    Abate Assefa Bashaw

    2017-12-01

    Full Text Available High-risk human papillomaviruses (HR-HPV infect basal keratinocytes, where in some individuals they evade host immune responses and persist. Persistent HR-HPV infection of the cervix causes precancerous neoplasia that can eventuate in cervical cancer. Dendritic cells (DCs are efficient in priming/cross-priming antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T cells. However, HR-HPV have adopted various immunosuppressive strategies, with modulation of DC function crucial to escape from the host adaptive immune response. HPV E6 and E7 oncoproteins alter recruitment and localization of epidermal DCs, while soluble regulatory factors derived from HPV-induced hyperplastic epithelium change DC development and influence initiation of specific cellular immune responses. This review focuses on current evidence for HR-HPV manipulation of antigen presentation in dendritic cells and escape from host immunity.

  5. HPV Vaccine and Pregnancy

    Science.gov (United States)

    ... and anus. If I have HPV, will that cause pregnancy problems? It is unclear. Even though HPV is ... HPV can be passed to a newborn during pregnancy or through the birth canal. Usually this causes no problems for the newborn. In rare cases, ...

  6. Prevalence and genotyping of HPV, by cervical brushing, in Irpinia area of Campania region

    Directory of Open Access Journals (Sweden)

    Pia Carmen Melillo

    2012-03-01

    Full Text Available Cervical cancer is due to persistent genital infection with Human Papillomavirus (HPV.The purpose of this study was to evaluate prevalence of HPV in Irpinia (Campania region, Italy, distribution of different viral genotypes, correlating cytological results and virological investigations. In the period 2006-2011, were made 1080 cervical samples of women aged 18-65 years for HPV identification and genotyping. Detection of the virus was performed by Multiplex-PCR System (Seegene,Arrow and typing with INNO-LiPA HPV Genotyping Extra test (Innogenetics. Out of the 1080 tested samples, 330 (30.6% samples were positive for HPV DNA. The most frequently occurring High Risk (HR-HPV genotype in single infections was HPV16 (16.6%, followed by HPV51 (10.7%, in multiple infections HPV16 (15.7% and 31 (14.6%. The prevalence of infection, correlated with age of patients studied, is greater in the group aged 26-30 years (42.5%. HR-HPV were detected in different percent in patients with Pap test scores: 22.5% in normal Pap smear (20% HPV16, 14.5% ASCUS (47.6% HPV16, 24% LSIL (20% HPV16, 79.3% HSIL (72.7% HPV16; 9.1% HPV18 detected only in this type of cellular alteration. The high prevalence of HR-HPV in patients with ASCUS or normal Pap test, suggesting the real advantage of HPV screening test, more sensitive in selecting the actual population at risk. Based on the findings of our epidemiological study, HR-HPV screening and HPV genotyping test should be strongly advised also to the vaccinated population for the high incidence of genotypes which are not included in vaccines (67%.

  7. Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39.

    OpenAIRE

    Longuet, M; Beaudenon, S; Orth, G

    1996-01-01

    The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low-grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and partially sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, clone...

  8. HPV-FASTER

    DEFF Research Database (Denmark)

    Bosch, F Xavier; Robles, Claudia; Díaz, Mireia

    2016-01-01

    protocol would represent an attractive approach for many health-care systems, in particular, countries in Central and Eastern Europe, Latin America, Asia, and some more-developed parts of Africa. The role of vaccination in women aged >30 years and the optimal number of HPV-screening tests required......Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. The effectiveness of these approaches is, however, suboptimal owing to limited implementation of screening programmes and restricted...... indications for HPV vaccination. Trials of HPV vaccination in women aged up to 55 years have shown almost 90% protection from cervical precancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programmes to women of up to 30 years of age (and to the 45-50-year...

  9. HPV Infection in Men

    Directory of Open Access Journals (Sweden)

    Joel M. Palefsky

    2007-01-01

    Full Text Available While much is known about the natural history of cervical human papillomavirus (HPV infection and its consequences, including cervical intraepithelial neoplasia and cervical cancer, relatively little is known about the natural history of anogenital HPV infection and diseases in men. In part this reflects difficulties in penile sampling and visual assessment of penile lesions. Anal HPV infection and disease also remain poorly understood. Although HPV is transmitted sexually and infects the genitals of both sexes, the cervix remains biologically more vulnerable to malignant transformation than does the penis or anus in men. An understanding of male HPV infection is therefore important in terms of reducing transmission of HPV to women and improving women's health. However, it is also important due to the burden of disease in men, who may develop both penile and anal cancer, particularly among HIV-positive men who have sex with men. Improved sampling techniques of the male genitalia and cohort studies in progress should provide important information on the natural history of anogenital HPV infection and disease in men, including risk factors for HPV acquisition and transmission. The impact of HPV vaccination in women on male anogenital HPV infection will also need to be assessed.

  10. A transgenic model of transactivation by the Tax protein of HTLV-I.

    Science.gov (United States)

    Bieberich, C J; King, C M; Tinkle, B T; Jay, G

    1993-09-01

    The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.

  11. HPV-specific immunotherapy: key role for immunomodulators.

    Science.gov (United States)

    Van de Wall, Stephanie; Nijman, Hans W; Daemen, Toos

    2014-02-01

    Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and 18-specific prophylactic vaccination, established HPV infections and associated neoplasia require therapeutic vaccines with the induction of cellular immunity. The sustained expression of early proteins E6 and E7 from major oncogenic HPV genotypes in cervical lesions are ideal targets for the design of immunotherapeutic strategies. These strategies, particularly subunit vaccines, may require additional help from immunomodulators to enhance HPV-specific cellular responses. This review discusses recent studies, published since 2008, relating to immunotherapeutic strategies against HPV that include immunomodulators. These immunomodulators fall within the category of toll-like receptor adjuvants for innate immune activation, adjuvants directly contributing to adaptive immunity, such as cytokines and costimulatory molecules, and those that target tumor-induced immunosuppressive mechanisms. Using a combination of these strategies with delivery-based approaches may be most beneficial for the success of therapeutic vaccines against HPV-induced neoplasia in the clinic.

  12. A central role for CK1 in catalysing phosphorylation of the P53 transactivation domain at serine 20 after HHV-6B viral infection

    DEFF Research Database (Denmark)

    Maclaine, NJ; Øster, Bodil; Bundgaard, Bettina

    2008-01-01

    The tumour suppressor protein p53 is activated by distinct cellular stresses including radiation, hypoxia, type-I interferon, and DNA/RNA virus infection. The transactivation domain of p53 contains a phosphorylation site at serine 20 (Ser20) whose modification stabilises the binding of the transc...... was not blocked by D4476. These data highlight a central role for CK1 as the Ser20-site kinase for p53 in DNA virus-infected cells, but also suggest that distinct stresses may selectively trigger different protein kinases to modify the transactivation domain of p53 at Ser20....

  13. Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma.

    Science.gov (United States)

    Gerle, Mirko; Medina, Tuula Peñate; Gülses, Aydin; Chu, Hanwen; Naujokat, Hendrik; Wiltfang, Jörg; Açil, Yahya

    2018-03-21

    Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, has been increasingly associated with head and neck squamous cell carcinoma. The treatment of HPV-positive squamous cell carcinoma has a better response to both radiotherapy and chemotherapy and presents a better prognosis for the patient. Defining the underlying mechanism of the difference might help in developing future treatment options and could be an important factor in personal therapy planning. Endogenously secreted acid sphingomyelinase (ASMase) levels in the cellular stress caused by irradiation and cisplatin were investigated. MTT assay was performed to evaluate the viability of the treated cells. Keratinocytes were used to evaluate the effects of radiation on normal tissues. Irradiation caused a dose-dependent increase in ASMase activity in both SCC9 HPV-negative, and UDSCC2 HPV-positive cells. ASMase activity in UDSCC2 cells was significantly higher than that in SCC9 cells. UDSCC cells were more sensitive to cisplatin treatment than SCC cells, and the dose-response in the activity was observed in long-time treatments when high doses of cisplatin were used. The results of the current study have clearly showed that HPV positivity should be considered as one of the determinative factors which should be considered when tumor treatments are planned. However, further studies are needed to determine the differences in cellular responses and pathways among HPV-negative and HPV-positive cells.

  14. The HPV Vaccination Crisis

    Science.gov (United States)

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  15. HPV DNA test

    Science.gov (United States)

    ... test; Cancer of cervix - HPV DNA test References Hacker NF. Cervical dysplasia and cancer. In: Hacker NF, Gambone JC, Hobel CJ, eds. Hacker and Moore's Essentials of Obstetrics and Gynecology . 6th ...

  16. Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells.

    Science.gov (United States)

    Kannappan, Ramaswamy; Mattapally, Saidulu; Wagle, Pooja A; Zhang, Jianyi

    2018-05-18

    The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells. Exposure to low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) measured by RAD50 and MRE11 expression, Checkpoint kinase 2 activation and γH2A.X recruitment at DNA strand breaks in both the cell groups indicating silencing p53-TAD do not affect DDR mechanism upstream of p53. Following removal of Doxo p53-WT hiPS cells underwent DNA repair, corrected their damaged DNA and restored DNA integrity. Conversely, p53-TAD KO hiPS cells did not undergo complete DNA repair and failed to restore DNA integrity. More importantly continuous culture of p53-TAD KO hiPS cells underwent G2/M cell cycle arrest and expressed cellular senescent marker p16 INK4a . Our data clearly shows that silencing transactivation domain of p53 did not affect DDR but affected the DNA repair process implying the crucial role of p53 transactivation domain in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent senescence.

  17. HPV16 RNA patterns defined by novel high-throughput RT-qPCR as triage marker in HPV-based cervical cancer precursor screening.

    Science.gov (United States)

    Höfler, Daniela; Böhmer, Gerd; von Wasielewski, Reinhard; Neumann, Heinrich; Halec, Gordana; Holzinger, Dana; Dondog, Bolormaa; Gissmann, Lutz; Pawlita, Michael; Schmitt, Markus

    2015-09-01

    Cervical cancer precursor screening by HPV testing has a low positive predictive value for advanced lesion. HPV16 RNA patterns characteristic for HPV16-transformed cells but based on laborious, cost-intensive singleplex NASBA reactions promised high value in triaging HPV16 DNA-positive women. We developed two high-throughput reverse transcriptase quantitative (RT-q) PCR assays for the HPV16 transcripts E6*I, E1^E4 and E1C and the cellular transcript ubiquitin C and analysed RNA of 158 singly HPV16 DNA-positive cervical cell samples archived in PreservCyt buffer for the presence of transformation-associated HPV16 RNA patterns, i.e., upregulation of E6*I relative to E1^E4 and/or presence of E1C. HPV16 RNA pattern analyses classified 85% of 58 samples diagnosed ≤CIN1 (no cytologically and histologically detectable cervical lesion or CIN grade 1) as negative and 90% of 59 samples diagnosed as ≥CIN3 (CIN grade 3 or invasive cancer) as positive. Among 41 CIN grade 2 samples representing an intermediate lesion group, 49% were HPV16 RNA patterns-positive. Interestingly, 3 of 4 HPV16 RNA patterns-positive lesions initially diagnosed as ≤CIN1 at follow-up 5-24 months later had progressed to ≥CIN2. We successfully developed and validated a second generation of HPV16 RNA patterns assay by rapid RT-qPCR as triage marker for HPV16 DNA-positive women offering clinical utility to distinguish between the need for immediate colposcopy and continued observation. Limited follow-up data suggests that HPV16 RNA patterns-positivity in ≤CIN1 lesions can predict disease progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. NLRC5: a newly discovered MHC class I transactivator (CITA)

    OpenAIRE

    Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.

    2011-01-01

    Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class II gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NLR protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as “CITA” (MHC class I transactivator)...

  19. Trans-activation function of a 3' truncated X gene-cell fusion product from integrated hepatitis B virus DNA in chronic hepatitis tissues

    International Nuclear Information System (INIS)

    Takada, Shinako; Koike, Katsuro

    1990-01-01

    To investigate the expression and transactivation function of the X gene in integrated hepatitis B virus (HBV) DNA from chronic hepatitis tissues, a series of transfectants containing cloned integrated HBV DNAs was made and analyzed for X mRNA expression and trans-activation activity by using a chloramphenicol acetyltransferase assay. Most of the integrated HBV DNAs expressed X mRNA and encoded a product with trans-activation activity in spite of the loss of the 3' end region of the X gene due to integration. From cDNA cloning and sequence analysis of X mRNA transcribed from native or integrated HBV DNA, the X protein was found to be translated from the X open reading frame without splicing. For integrated HBV DNA, transcription was extended to a cellular flanking DNA and an X gene-cell fusion transcript was terminated by using a cellular poly(A) signal. The amino acid sequence deduced from an X-cell fusion transcript indicated truncation of the carboxyl-terminal five amino acids, but the upstream region of seven amino acids conserved among hepadnaviruses was retained in the integrated HBV DNA, suggesting that this conserved region is essential for the transactivation function of the X protein. These findings support the following explanation for hepatocarcinogenesis by HBV DNA integration: the expression of a cellular oncogene(s) is transactivated at the time of chronic infection by the increasing amounts of the integrated HBV gene product(s), such as the X-cell fusion product

  20. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

    Directory of Open Access Journals (Sweden)

    Barry Peter A

    2009-05-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

  1. Reparative Spheroids in HPV-Associated Chronic Cervicitis

    Directory of Open Access Journals (Sweden)

    Gennadiy T. Sukhikh

    2013-09-01

    Full Text Available Background: Spheroid cell structures (SCS described in cell culture are used to study cell-cell and cell-matrix interactions. However, the role of the SCS in the repair process in vivo remains unexplored. The aim of the study was to examine the cellular composition of the spherical structures and their functional significance in the repair of the squamous epithelium in human papilloma virus-associated chronic cervicitis (HPV-CC. Methods and Results: The cytology and biopsy materials from 223 patients with HPV-CC were subjected to molecular testing for HPV DNA by Real-Time Polymerase Chain Reaction (Real-Time PCR with genotyping and chromogenic in situ hybridization (CISH, as well as immunocytological and immunohistochemical analyses of p16INK4A, Ki67, SMA, Vimentin, CD34, E-cadherin, Oct4, CD44, CKW markers. In the stem cell niche zone, these spheroid structures were discovered having proliferative activity and showing signs of producing stem cells involved in the repair of the cervical mucosa in HPV-CC. Conclusion: The persistence of the HPV in the stem cell niche zone cells in the cervix determines the chronization of inflammation in this area, with the ability to perform pathological repair. The immunophenotype of the spheroid cell structures in the HPV-CC includes cells with signs of stem cells (‘stemness’ and the mesenchymal-epithelial transition.

  2. HPV Infections in Adolescents

    Directory of Open Access Journals (Sweden)

    Anna-Barbara Moscicki

    2007-01-01

    Full Text Available Adolescents who are sexually active have the highest rates of prevalent and incident HPV infection rates with over 50–80% having infections within 2–3 years of initiating intercourse. These high rates reflect sexual behavior and biologic vulnerability. Most infections are transient in nature and cause no cytologic abnormality. However, a small number of adolescents will not clear the infection. Persistence of HPV is strongly linked to the development of high-grade squamous intra-epithelial lesions (HSIL and invasive cancer. The HSIL detected, however, does not appear to progress rapidly to invasive cancer. Understanding the natural history of HPV in adolescents has shed light into optional treatment strategies which include watchful observation of atypical squamous cells of undetermined significance (ASCUS and low grade (LSIL. The association between age of first intercourse and invasive cancer cannot be ignored. Consequently, initiating screening at appropriate times in this vulnerable group is essential. In addition, with the advent of the HPV vaccine, vaccination prior to the onset of sexual activity is critical since most infections occur within a short time frame post initiation.

  3. HPV Testing Among Providers

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Walter Kinney, a gynecologic oncologist with The Permanente Medical Group in Sacramento, California, talks about Pap and human papillomavirus (HPV) cotesting in women aged 30 and over.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  4. HPV Vaccine PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.)

  5. Comparison of Real-Time Multiplex Human Papillomavirus (HPV) PCR Assays with INNO-LiPA HPV Genotyping Extra Assay▿

    OpenAIRE

    Else, Elizabeth A.; Swoyer, Ryan; Zhang, Yuhua; Taddeo, Frank J.; Bryan, Janine T.; Lawson, John; Van Hyfte, Inez; Roberts, Christine C.

    2011-01-01

    Real-time type-specific multiplex human papillomavirus (HPV) PCR assays were developed to detect HPV DNA in samples collected for the efficacy determination of the quadrivalent HPV (type 6, 11, 16, and 18) L1 virus-like particle (VLP) vaccine (Gardasil). Additional multiplex (L1, E6, and E7 open reading frame [ORF]) or duplex (E6 and E7 ORF) HPV PCR assays were developed to detect high-risk HPV types, including HPV type 31 (HPV31), HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, and H...

  6. The epithelial-mesenchymal transition induced by keratinocyte growth conditions is overcome by E6 and E7 from HPV16, but not HPV8 and HPV38: Characterization of global transcription profiles

    International Nuclear Information System (INIS)

    Azzimonti, Barbara; Dell'Oste, Valentina; Borgogna, Cinzia; Mondini, Michele; Gugliesi, Francesca; De Andrea, Marco; Chiorino, Giovanna; Scatolini, Maria; Ghimenti, Chiara; Landolfo, Santo; Gariglio, Marisa

    2009-01-01

    The aim of this study was to evaluate the growth properties of primary human keratinocytes expressing E6 and E7 proteins, which are from either the β- or α-genotypes, under different culture conditions. We demonstrated that keratinocytes expressing E6 and E7, from both HPV8 and 38, irreversibly underwent the epithelial-mesenchymal transition (EMT) when grown on plastic with FAD medium (F12/DMEM/5%FBS). Expression of E6/E7 from HPV16 was capable of fully overcoming the FAD-induced EMT. Immortalization was only observed in HPV16-transduced cell lines, while the more proliferating phenotype of both KerHPV8 and 38 was mainly related to FAD-induced EMT. Microarray analysis of exponentially growing cells identified 146 cellular genes that were differentially regulated in HPV16 compared to HPV8- and 38-transduced cells. A large accumulation of transcripts associated with epidermal development and differentiation was observed in HPV16-transduced cells, whereas transcripts of genes involved in the extracellular matrix, multicellular organismal processes, and inflammatory response were affected in HPV8 and 38-transduced cells.

  7. HPV vaccines: a controversial issue?

    Science.gov (United States)

    Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  8. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  9. Cytological Evaluation and REBA HPV-ID HPV Testing of Newly Developed Liquid-Based Cytology, EASYPREP: Comparison with SurePath.

    Science.gov (United States)

    Lee, Youn Soo; Gong, Gyungyub; Sohn, Jin Hee; Ryu, Ki Sung; Lee, Jung Hun; Khang, Shin Kwang; Cho, Kyung-Ja; Kim, Yong-Man; Kang, Chang Suk

    2013-06-01

    The objective of this study was to evaluate a newly-developed EASYPREP liquid-based cytology method in cervicovaginal specimens and compare it with SurePath. Cervicovaginal specimens were prospectively collected from 1,000 patients with EASYPREP and SurePath. The specimens were first collected by brushing for SurePath and second for EASYPREP. The specimens of both methods were diagnosed according to the Bethesda System. Additionally, we performed to REBA HPV-ID genotyping and sequencing analysis for human papillomavirus (HPV) on 249 specimens. EASYPREP and SurePath showed even distribution of cells and were equal in cellularity and staining quality. The diagnostic agreement between the two methods was 96.5%. Based on the standard of SurePath, the sensitivity, specificity, positive predictive value, and negative predictive value of EASYPREP were 90.7%, 99.2%, 94.8%, and 98.5%, respectively. The positivity of REBA HPV-ID was 49.4% and 95.1% in normal and abnormal cytological samples, respectively. The result of REBA HPV-ID had high concordance with sequencing analysis. EASYPREP provided comparable results to SurePath in the diagnosis and staining quality of cytology examinations and in HPV testing with REBA HPV-ID. EASYPREP could be another LBC method choice for the cervicovaginal specimens. Additionally, REBA HPV-ID may be a useful method for HPV genotyping.

  10. BFV activates the NF-κB pathway through its transactivator (BTas) to enhance viral transcription

    International Nuclear Information System (INIS)

    Wang Jian; Tan Juan; Zhang Xihui; Guo Hongyan; Zhang Qicheng; Guo Tingting; Geng Yunqi; Qiao Wentao

    2010-01-01

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-κB (NF-κB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-κB pathway through the action of its transactivator, BTas. Both cellular IKKβ and IκBα also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-κB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKα and IKKβ), which may be responsible for regulation of IKK kinase activity and persistent NF-κB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-κB. Together, this study suggests that BFV activates the NF-κB pathway through BTas to enhance viral transcription.

  11. HPV Vaccine Information for Young Women

    Science.gov (United States)

    ... Transmitted Diseases (STDs) HPV Vaccine Information For Young Women Language: English Español (Spanish) Recommend on Facebook Tweet ... warts at any point in time. Which girls/women should receive HPV vaccination? HPV vaccination is recommended ...

  12. Preventing Cervical Cancer with HPV Vaccines

    Science.gov (United States)

    Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

  13. Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia

    NARCIS (Netherlands)

    van den Hende, Muriel; van Poelgeest, Mariëtte I. E.; van der Hulst, Jeanette M.; de Jong, Joan; Drijfhout, Jan W.; Fleuren, Gert Jan; Valentijn, A. Rob P. M.; Wafelman, Amon R.; Slappendel, Gijs M.; Melief, Cornelis J. M.; Offringa, Rienk; van der Burg, Sjoerd H.; Kenter, Gemma G.

    2008-01-01

    We have tested the safety and feasibility of a synthetic long peptide-based HPV16-specific skin test to detect cellular immune responses to HPV16 E2, E6 and E7 in vivo. Women with cervical neoplasia (n = 11) and healthy individuals (n = 19) were intradermally challenged with 8 different pools of

  14. Specificity of the Linear Array HPV Genotyping Test for detecting human papillomavirus genotype 52 (HPV-52)

    OpenAIRE

    Kocjan, Boštjan; Poljak, Mario; Oštrbenk, Anja

    2015-01-01

    Introduction: HPV-52 is one of the most frequent human papillomavirus (HPV) genotypes causing significant cervical pathology. The most widely used HPV genotyping assay, the Roche Linear Array HPV Genotyping Test (Linear Array), is unable to identify HPV- 52 status in samples containing HPV-33, HPV-35, and/or HPV-58. Methods: Linear Array HPV-52 analytical specificity was established by testing 100 specimens reactive with the Linear Array HPV- 33/35/52/58 cross-reactive probe, but not with the...

  15. Role of Human Papilloma Virus (HPV) in Common and Genital Warts and its Relation to P53 Expression

    International Nuclear Information System (INIS)

    Zekri, A.; Bahnassy, A.A.

    2006-01-01

    Background and Aim: Human papilloma viruses (HPVs) are small DNA tumor viruses that infect epithelial tissues and cause warts. One of the viral genes responsible for HPV's oncogenic activity is E6 which is known to inactivate the cellular p53 tumor suppressor gene. We aim to detect the presence of HPV infection and its different types in human warts, and to identify the relation between HPV and p53 expression in skin and genital lesions. Patients and Methods: We studied markers of HPV infection in overall of 30 patients (20 with common warts, and 10 with genital warts). Also, 30 normal skin samples were taken from each patient as a normal control. Detection of HPV was done using polymerase chain reaction (PCR), and HPV typing was performed using LiPA (Line immuno Probe Assay). In addition, all skin lesions were examined by immunohistochemistry for p53 expression. Results: In patients with common warts, HPV DNA was found in 4/20 (20%) of cases which was of HPV types 11, 31, 6, 33 (p=0.28). Also, P53 expression was found in 4/20 (20%) of cases (p=0.26). No single patient showed reactivity of both HPV and p53 expression. In patients with genital warts, however, HPV DNA was found in 6/10 (60%) of cases. Of these, 5 cases were positive for HPV type 6 and one case had HPV type 11. Three patients (30%) were positive for p53, and two of them (66%) were positive for both HPV and p53. In the normal skin control, 2/30 (6.6%) were positive for HPV DNA which were of types 5, and 31. Conclusions: We conclude that; (1) Prevalence rate of HPV infection in warts is higher than those of normal control group, and Egyptian patients with genital warts had higher prevalence rate of HPV than those with common warts, (2) In Egypt, HPV types 6, and 11 are the most prevalent genotypes associated with genital warts and HPV types 6, 11, 31, and 33 are associated with common warts, (3) There was no definite relation between p53 expression and HPV detection, (4) Also, there was no association

  16. HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

    Science.gov (United States)

    Castellsagué, Xavier; Alemany, Laia; Quer, Miquel; Halec, Gordana; Quirós, Beatriz; Tous, Sara; Clavero, Omar; Alòs, Llúcia; Biegner, Thorsten; Szafarowski, Tomasz; Alejo, Maria; Holzinger, Dana; Cadena, Enrique; Claros, Edith; Hall, Gillian; Laco, Jan; Poljak, Mario; Benevolo, Maria; Kasamatsu, Elena; Mehanna, Hisham; Ndiaye, Cathy; Guimerà, Núria; Lloveras, Belen; León, Xavier; Ruiz-Cabezas, Juan C; Alvarado-Cabrero, Isabel; Kang, Chang-Suk; Oh, Jin-Kyoung; Garcia-Rojo, Marcial; Iljazovic, Ermina; Ajayi, Oluseyi F; Duarte, Flora; Nessa, Ashrafun; Tinoco, Leopoldo; Duran-Padilla, Marco A; Pirog, Edyta C; Viarheichyk, Halina; Morales, Hesler; Costes, Valérie; Félix, Ana; Germar, Maria Julieta V; Mena, Marisa; Ruacan, Arzu; Jain, Asha; Mehrotra, Ravi; Goodman, Marc T; Lombardi, Luis Estuardo; Ferrera, Annabelle; Malami, Sani; Albanesi, Estela I; Dabed, Pablo; Molina, Carla; López-Revilla, Rubén; Mandys, Václav; González, Manuel E; Velasco, Julio; Bravo, Ignacio G; Quint, Wim; Pawlita, Michael; Muñoz, Nubia; de Sanjosé, Silvia; Xavier Bosch, F

    2016-06-01

    We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. HPV prevalence and HPV-related dysplasia in elderly women.

    Directory of Open Access Journals (Sweden)

    Ruth S Hermansson

    Full Text Available In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above.From September 2013 until June 2015, 1051 women aged 60-89 years (mean 68 years were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC, after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained.The prevalence of HPV was 4.1%, (95%CI 3.0-5.5, n = 43 at the first test, and at the second test 2.6% remained positive (95%CI 1.7-3.8, n = 27. The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27 (4 CIN 2-0.4%, 18 CIN 1-1.7%. HPV-related dysplasia was found in 2.1%, (95%CI 1.3-3.2, n = 22 of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected.A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity.

  18. HPV Carcinomas in Immunocompromised Patients

    Directory of Open Access Journals (Sweden)

    Nicole M. Reusser

    2015-01-01

    Full Text Available Human papillomavirus (HPV infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient.

  19. Characterization of two novel cutaneous human papillomaviruses, HPV93 and HPV96

    DEFF Research Database (Denmark)

    Vasiljevic, Natasa; Hazard, Kristina; Eliasson, Linda

    2007-01-01

    Two novel human papillomaviruses (HPVs), HPV93 and HPV96, with genomes of 7450 and 7438 bp, respectively, are described. The L1 open reading frame of HPV93 showed highest identity to HPV24 (79%) and that of HPV96 had highest identity to HPV92 (71%). Real-time PCR for HPV92, 93 and 96 on stripped ...... per 45 cells to one copy per 10,000 cells. The E7 proteins of HPV92, 93 and 96 were found to bind the retinoblastoma protein (pRb). These results suggest a possible role for these HPV types in skin carcinogenesis that deserves further study....

  20. HPV-16 L1 genes with inactivated negative RNA elements induce potent immune responses

    International Nuclear Information System (INIS)

    Rollman, Erik; Arnheim, Lisen; Collier, Brian; Oeberg, Daniel; Hall, Haakan; Klingstroem, Jonas; Dillner, Joakim; Pastrana, Diana V.; Buck, Chris B.; Hinkula, Jorma; Wahren, Britta; Schwartz, Stefan

    2004-01-01

    Introduction of point mutations in the 5' end of the human papillomavirus type 16 (HPV-16) L1 gene specifically inactivates negative regulatory RNA processing elements. DNA vaccination of C57Bl/6 mice with the mutated L1 gene resulted in improved immunogenicity for both neutralizing antibodies as well as for broad cellular immune responses. Previous reports on the activation of L1 by codon optimization may be explained by inactivation of the regulatory RNA elements. The modified HPV-16 L1 DNA that induced anti-HPV-16 immunity may be seen as a complementary approach to protein subunit immunization against papillomavirus

  1. HPV Infection: Immunological Aspects and Their Utility in Future Therapy

    Directory of Open Access Journals (Sweden)

    Efthimios Deligeoroglou

    2013-01-01

    Full Text Available High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (Th2 and T-regulatory cell phenotypes and reduces Th1 phenotype, leading to suppression of cellular immunity and lesion progression to cancer. Humoral response after natural infection is inefficient, and neutralizing antibodies are not adequate in many women. Utilizing this knowledge, new endeavors, such as therapeutic vaccination, aim to stimulate cellular immune response against the virus and alter the milieu of the lesion.

  2. Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism.

    Science.gov (United States)

    Fu, Maofu; Wang, Chenguang; Rao, Mahadev; Wu, Xiaofang; Bouras, Toula; Zhang, Xueping; Li, Zhiping; Jiao, Xuanmao; Yang, Jianguo; Li, Anping; Perkins, Neil D; Thimmapaya, Bayar; Kung, Andrew L; Munoz, Alberto; Giordano, Antonio; Lisanti, Michael P; Pestell, Richard G

    2005-08-19

    Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor gamma-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

  3. HPV Vaccine PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  4. HPV DNA methylation at the early promoter and E1/E2 integrity: A comparison between HPV16, HPV18 and HPV45 in cervical cancer.

    Science.gov (United States)

    Amaro-Filho, Sérgio Menezes; Pereira Chaves, Cláudia Bessa; Felix, Shayany Pinto; Basto, Diogo Lisbôa; de Almeida, Liz Maria; Moreira, Miguel Angelo Martins

    2018-04-09

    To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2. The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate. The 3'LCR of HPV16 showed a higher methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18 regions (4%, 5%. 6%, 9% and 5%) and HPV45 regions (7%, 7% and 5%). Presence of intact E1/E2 was associated with higher HPV16 and HPV18 methylation levels at all CpG sites (p < 0.05). Disruption of E1/E2 was more frequently found in HPV45 (97%) and HPV18 (84%) than in HPV16 DNA (30%). HPV16 disruption was more frequently found in E1 (48%) unlike HPV18, where it was found in E2 (61%). Concomitant disruption of E1/E2 was most frequent in HPV45 (72%). The findings showed a higher methylation associated with intact E1/E2 for HPV16 and HPV18. The closely phylogenetic related HPV18 and HPV45 share a similar methylation level and the frequency of viral genome disruption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  5. ATF3 inhibits PPARγ-stimulated transactivation in adipocyte cells

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Min-Kyung; Jung, Myeong Ho, E-mail: jung0603@pusan.ac.kr

    2015-01-02

    Highlights: • ATF3 inhibits PPARγ-stimulated transcriptional activation. • ATF3 interacts with PPARγ. • ATF3 suppresses p300-mediated transcriptional coactivation. • ATF3 decreases the binding of PPARγ and recruitment of p300 to PPRE. - Abstract: Previously, we reported that activating transcription factor 3 (ATF3) downregulates peroxisome proliferator activated receptor (PPARγ) gene expression and inhibits adipocyte differentiation in 3T3-L1 cells. Here, we investigated another role of ATF3 on the regulation of PPARγ activity. ATF3 inhibited PPARγ-stimulated transactivation of PPARγ responsive element (PPRE)-containing reporter or GAL4/PPARγ chimeric reporter. Thus, ATF3 effectively repressed rosiglitazone-stimulated expression of adipocyte fatty acid binding protein (aP2), PPARγ target gene, in 3T3-L1 cells. Coimmunoprecipitation and GST pulldown assay demonstrated that ATF3 interacted with PPARγ. Accordingly, ATF3 prevented PPARγ from binding to PPRE on the aP2 promoter. Furthermore, ATF3 suppressed p300-mediated transcriptional coactivation of PPRE-containing reporter. Chromatin immunoprecipitation assay showed that overexpression of ATF3 blocked both binding of PPARγ and recruitment of p300 to PPRE on aP2 promoter induced by rosiglitazone treatment in 3T3-L1 cells. Taken together, these results suggest that ATF3 interacts with PPARγ and represses PPARγ-mediated transactivation through suppression of p300-stimulated coactivation in 3T3-L1 cells, which may play a role in inhibition of adipocyte differentiation.

  6. Current Status of HPV Vaccines

    Science.gov (United States)

    Ma, Barbara; Roden, Richard; Wu, T.C.

    2010-01-01

    Cervical cancer is the second largest cause of cancer deaths in women worldwide, with ~500,000 diagnoses and 274,000 deaths annually. It remains a significant source of morbidity and mortality despite effective screening tools and treatments for its precursor high-grade cervical intraepithelial neoplasia (CIN). Increased understanding of cervical pathogenesis has led to the identification of human papillomavirus (HPV) as the etiological agent for cervical cancer and the development of preventive and therapeutic vaccines targeting HPV antigens for the control of cervical cancer. Herein, we discuss the current status of HPV vaccines. PMID:20677402

  7. Worldwide burden of cancer attributable to HPV by site, country and HPV type

    OpenAIRE

    de Martel, Catherine; Plummer, Martyn; Vignat, Jerome; Franceschi, Silvia

    2017-01-01

    HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV?attributable cancer burden can boost programs of HPV vaccination and HPV?based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age?standardized incidenc...

  8. Regulatory elements involved in tax-mediated transactivation of the HTLV-I LTR.

    Science.gov (United States)

    Seeler, J S; Muchardt, C; Podar, M; Gaynor, R B

    1993-10-01

    HTLV-I is the etiologic agent of adult T-cell leukemia. In this study, we investigated the regulatory elements and cellular transcription factors which function in modulating HTLV-I gene expression in response to the viral transactivator protein, tax. Transfection experiments into Jurkat cells of a variety of site-directed mutants in the HTLV-1 LTR indicated that each of the three motifs A, B, and C within the 21-bp repeats, the binding sites for the Ets family of proteins, and the TATA box all influenced the degree of tax-mediated activation. Tax is also able to activate gene expression of other viral and cellular promoters. Tax activation of the IL-2 receptor and the HIV-1 LTR is mediated through NF-kappa B motifs. Interestingly, sequences in the 21-bp repeat B and C motifs contain significant homology with NF-kappa B regulatory elements. We demonstrated that an NF-kappa B binding protein, PRDII-BF1, but not the rel protein, bound to the B and C motifs in the 21-bp repeat. PRDII-BF1 was also able to stimulate activation of HTLV-I gene expression by tax. The role of the Ets proteins on modulating tax activation was also studied. Ets 1 but not Ets 2 was capable of increasing the degree of tax activation of the HTLV-I LTR. These results suggest that tax activates gene expression by either direct or indirect interaction with several cellular transcription factors that bind to the HTLV-I LTR.

  9. Four regulatory elements in the human c-fos promoter mediate transactivation by HTLV-1 Tax protein.

    Science.gov (United States)

    Alexandre, C; Verrier, B

    1991-04-01

    Expression of the human c-fos proto-oncogene is activated in trans by the Tax protein encoded by human T-cell leukemia virus type-1 (HTLV-1). Indeed, we show here that a HeLa clone stably transfected by Tax expresses Fos at a high level. We also show that multiple elements of the human c-fos promoter, i.e. the v-sis conditioned medium inducible element (SIE), the dyad symmetry element (DSE) necessary for growth factor induction, the octanucleotide direct repeat element (DR), and the cyclic AMP response element (CRE) centred at -60, can all mediate Tax transactivation. In the DSE, the 10bp central core that binds the serum response factor (SRF) is, by itself, sufficient to mediate Tax transactivation. Moreover, a CRE-binding protein is involved in Tax activation through the CRE-60 element. Since Fos is a transregulator of cellular genes, our results suggest that the oncoprotein plays a crucial role in T-cell transformation by HTLV-1 in conjunction with other Tax-inducible genes.

  10. The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity.

    Science.gov (United States)

    Zhang, Yiguo; Hayes, John D

    2013-01-01

    The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression.

  11. HPV-Associated Cancers Statistics

    Science.gov (United States)

    ... What CDC Is Doing Related Links Stay Informed Statistics for Other Kinds of Cancer Breast Cervical Colorectal ( ... Vaginal and Vulvar Cancer Home HPV-Associated Cancer Statistics Language: English (US) Español (Spanish) Recommend on Facebook ...

  12. Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

    International Nuclear Information System (INIS)

    Arenz, Andrea; Ziemann, Frank; Wittig, Andrea; Preising, Stefanie; Engenhart-Cabillic, Rita; Mayer, Christina; Wagner, Steffen; Klussmann, Jens-Peter; Wittekindt, Claus; Dreffke, Kirstin

    2014-01-01

    Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair. (orig.) [de

  13. Perspectives for Preventive and Therapeutic HPV Vaccines

    Science.gov (United States)

    Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T-C

    2010-01-01

    Cervical cancer is the second most common cause of female cancer death worldwide. Persistent infection with `high risk' HPV genotypes is the major etiological factor in cervical cancer and thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The FDA has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions. PMID:20123582

  14. Predictors of Adults' Knowledge and Awareness of HPV, HPV-Associated Cancers, and the HPV Vaccine: Implications for Health Education.

    Science.gov (United States)

    McBride, Kimberly R; Singh, Shipra

    2018-02-01

    High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified sociodemographic characteristics associated with HPV knowledge at the population level. Data from adult men ( n = 1,197) and women ( n = 1,906) who participated in the National Cancer Institute's 2014 Health Information National Trends Survey were analyzed. Multivariable regression was used to identify predictors of four HPV knowledge categories: (1) general knowledge, (2) cervical cancer knowledge, (3) "other" cancer knowledge (i.e., anal, oral, penile), and (4) vaccine knowledge. Significant gender differences in awareness and knowledge of HPV and the HPV vaccine were revealed. Most participants (>70%) knew that HPV could cause cervical cancer, but fewer (14.9% to 31.5%) knew of the association between HPV and "other" cancers. Women were more likely to report that a health care provider recommended vaccination. Significant predictors of general HPV and HPV vaccine knowledge included gender, education, income, race, and other sociodemographic characteristics. Age and income predicted cervical cancer knowledge. Knowledge of "other" HPV-associated cancers was predicted by having a child under 18 years in the household and relationship status. HPV knowledge appears to be socially patterned. Low HPV knowledge among men and some racial minorities suggests a need for further intervention. Health education should emphasize risks of noncervical HPV-associated cancers. Patient-provider communication that includes education, counseling, and clear recommendations favoring vaccination may improve uptake.

  15. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  16. Human Papillomavirus 16 (HPV-16), HPV-18, and HPV-31 E6 Override the Normal Phosphoregulation of E6AP Enzymatic Activity.

    Science.gov (United States)

    Thatte, Jayashree; Banks, Lawrence

    2017-11-15

    The human papillomavirus (HPV) E6 oncoproteins recruit the cellular ubiquitin ligase E6AP/UBE3A to target cellular substrates for proteasome-mediated degradation, and one consequence of this activity is the E6 stimulation of E6AP autoubiquitination and degradation. Recent studies identified an autism-linked mutation within E6AP at T485, which was identified as a protein kinase A phosphoacceptor site and which could directly regulate E6AP ubiquitin ligase activity. In this study, we have analyzed how T485-mediated regulation of E6AP might affect E6 targeting of some of its known substrates. We show that modulation of T485 has no effect on the ability of E6 to direct either p53 or Dlg for degradation. Furthermore, T485 regulation has no effect on HPV-16 or HPV-31 E6-induced autodegradation of E6AP but does affect HPV-18 E6-induced autodegradation of E6AP. In cells derived from cervical cancers, we find low levels of both phosphorylated and nonphosphorylated E6AP in the nucleus. However, ablation of E6 results in a dramatic accumulation of phospho-E6AP in the cytoplasm, whereas nonphosphorylated E6AP accumulates primarily in the nucleus. Interestingly, E6AP phosphorylation at T485 confers association with 14-3-3 proteins, and this interaction seems to be important, in part, for the ability of E6 to recruit phospho-E6AP into the nucleus. These results demonstrate that HPV E6 overrides the normal phosphoregulation of E6AP, both in terms of its enzymatic activity and its subcellular distribution. IMPORTANCE Recent reports demonstrate the importance of phosphoregulation of E6AP for its normal enzymatic activity. Here, we show that HPV E6 is capable of overriding this regulation and can promote degradation of p53 and Dlg regardless of the phosphorylation status of E6AP. Furthermore, E6 interaction with E6AP also significantly alters how E6AP is subject to autodegradation and suggests that this is not a simple stimulation of an already-existing activity but rather a

  17. HPV infections among MSM in Shenzhen, China.

    Directory of Open Access Journals (Sweden)

    Dong-Yan Zhang

    Full Text Available BACKGROUND: An increasing incidence of anal cancer among men, especially men who have sex with men (MSM suggests a need to better understand anal human papillomavirus (HPV infection among this group. METHODS: A cross-sectional study was conducted among MSM in Shenzhen, China. Blood was collected for HIV serological testing and syphilis serological screening, and anal swabs were collected for HPV genotyping. Difference of HPV prevalence between HIV seropositive and HIV seronegative MSM was assessed by chi-square test. Factors associated with anal canal HPV infection were assessed by univariate and multivariate logistic regression. RESULTS: A total of 408 MSM were recruited. HIV and HPV prevalence were 6.9% and 36.4%, respectively. HPV was detected in the anal canal in 71.4% of the HIV-positive MSM and in 33.8% of the HIV-negative MSM (P<0.001. Oncogenic types were seen more often in anal specimens of HIV-positive MSM than in specimens of HIV-negative MSM (P = 0.001. The HPV genotypes detected most frequently were HPV06 (8.2%, HPV16 (7.2%, HPV11 (6.4%, HPV18 (4.7%, HPV58 (4.7%, and HPV52 (4.2%. CONCLUSIONS: In this study, HIV positive MSM had a higher burden of HPV infection, especially oncogenic HPV infection. HPV types 52 and 58 were as popular as those types designed for the currently available vaccine (HPV6, 11, 16, 18.

  18. Role of EGFR transactivation in preventing apoptosis in Pseudomonas aeruginosa-infected human corneal epithelial cells.

    Science.gov (United States)

    Zhang, Jing; Li, Hui; Wang, Jinzhao; Dong, Zheng; Mian, Shahzad; Yu, Fu-Shin X

    2004-08-01

    To determine the role of epidermal growth factor (EGF) receptor (EGFR)-mediated signaling pathways in preventing infection-induced apoptosis in human corneal epithelial cells (HCECs). Epithelial monolayers of a telomerase-immortalized HCEC line, HUCL, and primary culture of HCECs were infected with Pseudomonas aeruginosa in the presence of the EGFR inhibitor tyrphostin AG1478, the extracellular signal-regulated kinase (ERK) inhibitor U0126, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, the heparin-binding EGF-like growth factor (HB-EGF) antagonist CRM197, the HB-EGF neutralizing antibody, or the matrix metalloproteinase inhibitor GM6001. The activation of EGFR was analyzed by immunoprecipitation using EGFR antibodies, followed by Western blot analysis with phosphotyrosine antibody. Phosphorylation of ERK and Akt, a major substrate of PI3K, and generation of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) were determined by Western blot analysis. Apoptotic cells were characterized by positive staining of active caspase-3, loss of mitochondrial cytochrome c, and condensation of chromosomes. Apoptosis was also confirmed by measuring caspase-3 activity and assessing the generation of cleaved caspase-3 and PARP. P. aeruginosa infection of HUCL cells resulted in EGFR activation and EGFR-dependent ERK1/2 and PI3K phosphorylation. Inhibition of EGFR, ERK1/2, and PI3K activities with kinase-specific inhibitors (AG1478, U0126, and LY294002, respectively) resulted in an increase in the number of apoptotic cells, in elevated cellular caspase-3 activity, and/or in increased cleaved PARP in P. aeruginosa-infected HUCL cells or primary culture of HCECs. Blocking HB-EGF ectodomain shedding by inhibition of matrix metalloproteinase-mediated proteolysis, downregulation of HB-EGF, or neutralization of its activity retarded infection-induced EGFR transactivation and, as a consequence, increased infection-induced HUCL apoptosis. Bacterial infection of HCECs induces

  19. Role of EGFR Transactivation in Preventing Apoptosis in Pseudomonas aeruginosa–Infected Human Corneal Epithelial Cells

    Science.gov (United States)

    Zhang, Jing; Li, Hui; Wang, Jinzhao; Dong, Zheng; Mian, Shahzad; Yu, Fu-Shin X.

    2009-01-01

    PURPOSE To determine the role of epidermal growth factor (EGF) receptor (EGFR)–mediated signaling pathways in preventing infection-induced apoptosis in human corneal epithelial cells (HCECs). METHODS Epithelial monolayers of a telomerase-immortalized HCEC line, HUCL, and primary culture of HCECs were infected with Pseudomonas aeruginosa in the presence of the EGFR inhibitor tyrphostin AG1478, the extracellular signal-regulated kinase (ERK) inhibitor U0126, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, the heparin-binding EGF-like growth factor (HB-EGF) antagonist CRM197, the HB-EGF neutralizing antibody, or the matrix metalloproteinase inhibitor GM6001. The activation of EGFR was analyzed by immunoprecipitation using EGFR antibodies, followed by Western blot analysis with phosphotyrosine antibody. Phosphorylation of ERK and Akt, a major substrate of PI3K, and generation of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) were determined by Western blot analysis. Apoptotic cells were characterized by positive staining of active caspase-3, loss of mitochondrial cytochrome c, and condensation of chromosomes. Apoptosis was also confirmed by measuring caspase-3 activity and assessing the generation of cleaved caspase-3 and PARP. RESULTS P. aeruginosa infection of HUCL cells resulted in EGFR activation and EGFR-dependent ERK1/2 and PI3K phosphorylation. Inhibition of EGFR, ERK1/2, and PI3K activities with kinase-specific inhibitors (AG1478, U0126, and LY294002, respectively) resulted in an increase in the number of apoptotic cells, in elevated cellular caspase-3 activity, and/or in increased cleaved PARP in P. aeruginosa–infected HUCL cells or primary culture of HCECs. Blocking HB-EGF ectodomain shedding by inhibition of matrix metalloproteinase–mediated proteolysis, downregulation of HB-EGF, or neutralization of its activity retarded infection-induced EGFR transactivation and, as a consequence, increased infection-induced HUCL apoptosis

  20. Macrophage Transactivation for Chemokine Production Identified as a Negative Regulator of Granulomatous Inflammation Using Agent-Based Modeling

    Directory of Open Access Journals (Sweden)

    Daniel Moyo

    2018-03-01

    Full Text Available Cellular activation in trans by interferons, cytokines, and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and/or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling, and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation.

  1. Contribution to the investigation of the p53 in vivo and in vitro trans-activation activity

    International Nuclear Information System (INIS)

    Meiller, A.

    2004-03-01

    Among the body's defence mechanisms, the programmed cellular death or apoptosis is an important safeguard way which allows the body to get rid of the injured cells before they acquire steady genetic modifications leading to an anarchistic multiplication. As p53 tumor suppressor gene plays a predominant role within this process, this research report first presents the p53 protein, its structure, its activities as a transcription factor, its modifications and the implications on its functional activities, its biological activities, and describes the p53 intracellular rate regulation and the use of this protein in radiology, particularly in 'in vivo' investigations on irradiated mice. It also presents the p53 family. Then, the author reports experimental investigations on possible other genes which could be trans-activated by p53. A gene is identified as a new target gene. She also demonstrates a new p53 activation path induced by another member of the p53 family, the p73 alpha protein

  2. Pathogenic role of the eight probably/possibly carcinogenic HPV types 26, 53, 66, 67, 68, 70, 73 and 82 in cervical cancer.

    Science.gov (United States)

    Halec, Gordana; Alemany, Laia; Lloveras, Belen; Schmitt, Markus; Alejo, Maria; Bosch, Franz X; Tous, Sara; Klaustermeier, Jo Ellen; Guimerà, Nuria; Grabe, Niels; Lahrmann, Bernd; Gissmann, Lutz; Quint, Wim; Bosch, Francesc X; de Sanjose, Silvia; Pawlita, Michael

    2014-12-01

    Eight HPV types (HPV26, 53, 66, 67, 68, 70, 73 and 82) that are phylogenetically closely related to 12 WHO-defined high-risk (HR) HPV have been rarely but consistently identified as single HPV infections in about 3% of cervical cancer (CxCa) tissues. Due to lack of biological data, these types are referred to as probable/possible (p) HR-HPV. To analyse their biological activity in direct comparison to HR-HPV types, we selected 55 formalin-fixed, paraffin-embedded (FFPE) CxCa tissues harbouring single pHR-HPV infections (2-13 cases per type) and 266 tissues harbouring single HR-HPV (7-40 cases per type) from a worldwide, retrospective, cross-sectional study. Single HPV infection was verified by two genotyping methods. Presence of type-specific spliced E6*I mRNA transcripts and expression of cellular proteins indicative of HPV transformation were assessed in all cases. In 55 CxCa tissues with pHR-HPV, E6*I mRNA expression was 100%; high p16(INK4a) , 98%; low pRb, 96%; low CyD1, 93%; and low p53, 84%. Compared to HPV16 tissues as a reference, individual frequencies of these five markers did not differ significantly, either for any of the eight pHR-HPV and the 11 other HR types individually or for the groups of pHR and HR types without HPV16. We conclude that the eight pHR-HPV types, when present as a single infection in CxCa, are biologically active and affect the same cellular pathways as any of the fully recognized carcinogenic HR-HPV types. Therefore we have provided molecular evidence of carcinogenicity for types currently classified as probably/possibly carcinogenic. Although this evidence is crucial for HPV-type carcinogenicity classification, per se it is not sufficient for inclusion of these HPV types into population-wide primary and secondary prevention programmes. Such decisions have to include careful estimation of effectiveness and cost-benefit analyses. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons

  3. Burden of HPV-caused cancers in Denmark and the potential effect of HPV-vaccination

    DEFF Research Database (Denmark)

    Skorstengaard, Malene; Thamsborg, Lise Holst; Lynge, Elsebeth

    2017-01-01

    -caused cancers in women and men, and to evaluate the potential of HPV-vaccination in cancer control. Methods: Data were retrieved from the literature on population prevalence of high risk (HR) HPV, on HR HPV-prevalence and genotypes in HPV-related cancers, and on number of cytology samples in cervical screening...... were preventable with HPV vaccination. However, including screening prevented cervical cancers, the burden of cancers caused by HPV-infection would be 1300–2000 in women as compared to 234 in men. Conclusion: Taking screening prevented cervical cancers into account, the cancer control potential of HPV...

  4. One Family's Struggles with HPV (Human Papillomavirus)

    Medline Plus

    Full Text Available ... sq how to do kids infect kids links & resources M.O.V.E. parents for prevention ... go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV We provide ...

  5. One Family's Struggles with HPV (Human Papillomavirus)

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  6. HPV Vaccine Effective at Multiple Anatomic Sites

    Science.gov (United States)

    A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l

  7. Predictors of Adults' Knowledge and Awareness of HPV, HPV-Associated Cancers, and the HPV Vaccine: Implications for Health Education

    Science.gov (United States)

    McBride, Kimberly R.; Singh, Shipra

    2018-01-01

    High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified…

  8. The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines

    International Nuclear Information System (INIS)

    Güster, Julian David; Weissleder, Stephanie Valerie; Busch, Chia-Jung; Kriegs, Malte; Petersen, Cordula; Knecht, Rainald; Dikomey, Ekkehard; Rieckmann, Thorsten

    2014-01-01

    Background and purpose: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay. Results: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1. Conclusions: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity

  9. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  10. Prevalência dos HPV 16, 18, 45 e 31 em mulheres com lesão cervical Prevalence of HPV 16, 18, 45 and 31 in women with cervical lesions

    Directory of Open Access Journals (Sweden)

    Denise Rocha Pitta

    2010-07-01

    Full Text Available OBJETIVO: avaliar a prevalência dos HPV 16, 18, 31 e 45 em amostras de raspado cervical de mulheres com alterações celulares e/ou colposcopia sugestiva de lesão de alto grau ou lesão de baixo grau persistente submetidas à conização. MÉTODOS: Foram incluídas 120 mulheres. A análise histológica dos cones cervicais revelou 7 casos de cervicite, 22 de NIC1, 31 de NIC2, 54 de NIC3 e 6 carcinomas invasores. Foram analisadas as amostras de raspado cervical coletadas antes da conização para a presença do DNA-HPV por PCR com os primers de consenso, PGMY09/11. As amostras positivas para DNA de HPV foram testadas para presença do HPV16, 18, 31 e 45 utilizando-se primers tipo específico para esses HPV. RESULTADOS: O DNA-HPV foi detectado em 67,5% das mulheres. O HPV 16 (40% foi o tipo mais prevalente na maioria das lesões, seguido dos HPV 31 (13,3%, 45 (13,3% e 18 (4,1%. Infecções múltiplas ocorreram em 15% dos casos e as infecções por outros tipos de HPV foram detectadas em 14% da amostra. CONCLUSÕES: as infecções pelos HPV 16 e 18 nem sempre ocorrem de maneira solitária (infecção única, estando associadas a outros tipos de HPV em diversas ocasiões.PURPOSE: to determine the prevalence of HPV 16, 18, 31 and 45 in cervical screening samples of women with cellular changes and/or colposcopy suggestive of persistent high grade or low grade lesion who were submitted to conization. METHODS: a total of 120 women were included in the study. Histological analysis of the cervical cones revealed 7 cases of cervicitis, 22 of CIN1, 31 of CIN2, 54 of CIN3, and 6 invasive carcinomas. The cervical screening samples were analyzed before conization for the presence of HPV-DNA by PCR using the consensus primers PGMY09/11. HPV-DNA-positive samples were tested for the presence of HPV16, 18, 31 and 45 using type-specific primers for these HPV. RESULTS: HPV-DNA was detected in 67.5% of the studied women. HPV 16 (40% was the most prevalent type in

  11. Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients.

    Science.gov (United States)

    Carpén, Timo; Sjöblom, Anni; Lundberg, Marie; Haglund, Caj; Markkola, Antti; Syrjänen, Stina; Tarkkanen, Jussi; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri

    2018-05-01

    Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody. Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV-/p16- patients but also rather common among HPV+/p16+ patients. This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.

  12. HPV Vaccine Safety PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.)

  13. HPV Vaccine (:30) (No Tag)

    Centers for Disease Control (CDC) Podcasts

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.)

  14. The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.

    Directory of Open Access Journals (Sweden)

    Anders Friberg

    2015-05-01

    Full Text Available Epstein-Barr virus (EBV is a γ-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2 is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four β-strands and an α-helix which form a parallel dimer by interaction of two β-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the α-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics.

  15. Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis

    International Nuclear Information System (INIS)

    Lee, San San; Crabb, Simon J.; Janghra, Nari; Carlberg, Carsten; Williams, Ann C.; Cutress, Ramsey I.; Packham, Graham; Hague, Angela

    2007-01-01

    In oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-1S, enhanced VDR transactivation in response to 1α,25-dihydroxyvitamin D 3. BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified the nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1α,25-dihydroxyvitamin D 3 . By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis

  16. Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

    LENUS (Irish Health Repository)

    Keegan, Helen

    2012-02-01

    Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.

  17. Awareness and Knowledge About HPV and HPV Vaccine Among Romanian Women.

    Science.gov (United States)

    Grigore, Mihaela; Teleman, Sergiu Iuliu; Pristavu, Anda; Matei, Mioara

    2018-02-01

    Cervical cancer is one of the most prevalent gynecological malignancies worldwide. Romania has the highest incidence of this type of cancer in Europe. A successful prevention strategy has to consider the primary prevention measures (including health education on human papilloma virus (HPV) infection but also vaccination). The aim of this study was to assess the knowledge and attitudes of Romanian women about HPV and HPV vaccine. We conducted a cross-sectional study survey of 454 women using an anonymously completed questionnaire covering the awareness and knowledge of HPV infection and attitudes to vaccination. We also analyzed the discussions and conclusion from a focus group of healthcare professionals regarding (1) HPV and HPV awareness and attitude, and (2) suggestions for improving HPV vaccine knowledge and acceptance. 69.2% of women were aware about HPV but their knowledge was minimal and incomplete. While 62.3% had heard about HPV vaccine, only 50.7% had a positive attitude toward it. The main barriers to vaccination were the fear of side effects, the perception that is risky, and the financial concerns. Deficiencies in knowledge were noted for vaccine, genital warts, or risks factors for HPV infection like the early onset of sexual life. The information regarding HPV and vaccine is not always accurate and complete, and only 50.7% of women have a positive attitude toward the vaccine. More educational programs and clearer communication are needed to raise awareness and knowledge regarding HPV and HPV vaccine.

  18. Young adults awareness of HPV and vaccine acceptance after introduction of the HPV vaccine in the Dutch national vaccination program

    NARCIS (Netherlands)

    Schmeink, C.E.; Gosens, K.C.; Melchers, W.J.G.; Massuger, L.F.A.G.; Bekkers, R.L.M.

    2011-01-01

    PURPOSE: To investigate the effect of implementation of the HPV vaccine on HPV knowledge and HPV vaccine acceptance. METHODS: From June until December 2009 in Nijmegen, the Netherlands, 698 male and female students aged 18-25 years were recruited and interviewed about HPV, cervical carcinoma and HPV

  19. Deconstructing Human Papillomavirus (HPV) Knowledge: Objective and Perceived Knowledge in Males' Intentions to Receive the HPV Vaccine

    Science.gov (United States)

    Krawczyk, Andrea; Stephenson, Ellen; Perez, Samara; Lau, Elsa; Rosberger, Zeev

    2013-01-01

    Background: The human papillomavirus (HPV) vaccine was recently approved for men. To effectively tailor HPV education efforts toward men, it is important to understand what men know about HPV and how this knowledge relates to their decision to receive the vaccine. This study examines how objective HPV knowledge, objective HPV vaccine knowledge,…

  20. The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis.

    Science.gov (United States)

    Mirabello, Lisa; Clarke, Megan A; Nelson, Chase W; Dean, Michael; Wentzensen, Nicolas; Yeager, Meredith; Cullen, Michael; Boland, Joseph F; Schiffman, Mark; Burk, Robert D

    2018-02-13

    Of the ~60 human papillomavirus (HPV) genotypes that infect the cervicovaginal epithelium, only 12-13 "high-risk" types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral-host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.

  1. The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lisa Mirabello

    2018-02-01

    Full Text Available Of the ~60 human papillomavirus (HPV genotypes that infect the cervicovaginal epithelium, only 12–13 “high-risk” types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral–host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.

  2. Human papillomavirus (HPV) and HPV-associated tumour vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2006-01-01

    Roč. 52, 1-2 (2006), s. 45-46 ISSN 0015-5500 R&D Projects: GA MZd(CZ) NR7807; GA MZd(CZ) NR8004; GA ČR(CZ) GA301/04/0492; GA AV ČR(CZ) IAA500520605 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.387, year: 2006

  3. HPV and HPV vaccination: knowledge and consciousness of young women.

    Science.gov (United States)

    Coşar, E; Gencer, M; Hacivelioğlu, S O; Güngör, A C; Uysal, A

    2014-01-01

    The aim of the study was to explore the knowledge and the awareness of the young Turkish women regarding cervical cancer and human papilloma virus (HPV) vaccines. The authors analyze a probable relationship between the overall knowledge level and a few socio-demographic parameters. The authors interviewed with students from Canakkale 18 March University and young women that did not continue with school in the same city from January to September 2011. All the students answered the questionnaire voluntarily and independently. The participants had low level of knowledge about the risk factors for cervical cancer. Smoking is the major risk factor that was known by the participants (65%). Proportion of the participants that were aware of pap smear test and HPV were 65% and 17% respectively. A small proportion of young women had knowledge regarding protection from HPV. Educational stream, educational level, family income, and family size had significant association knowledge level (p level of knowledge so that general public can easily take preventative measures.

  4. HPV Infections Decrease in the U.S.

    Science.gov (United States)

    Infection with human papillomavirus (HPV) types targeted by the quadrivalent HPV vaccine has declined by nearly two-thirds among teenage girls since HPV vaccination was recommended in the United States.

  5. HPV (Human Papillomavirus) vaccine - what you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv.html . CDC review information for HPV (Human Papillomavirus) ...

  6. Differences in T-cell infiltrates and survival between HPV+ and HPV- oropharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    Matlung, Sanne Evelien; van Kempen, Pauline Maria Wilhelmina; Bovenschen, Niels; van Baarle, Debbie; Willems, Stefan Martin

    2016-01-01

    Recent studies have suggested that immune cells as part of tumor's microenvironment could partly explain the better outcome in HPV-associated oropharyngeal carcinoma. We performed a systematic review of the literature focused on differences in immune-infiltrate in HPV+ versus HPV- oropharyngeal

  7. Variables associated with human papillomavirus (HPV) vaccine acceptance by men.

    Science.gov (United States)

    Ferris, Daron G; Waller, Jennifer L; Miller, Jeremiah; Patel, Pratik; Price, George A; Jackson, Lanier; Wilson, Courtesia

    2009-01-01

    To determine correlates of human papillomavirus (HPV) vaccine acceptance for men. A convenience sample of men aged 18 to 45 years read a one-page information sheet about HPV and the HPV vaccine, then completed a 29-item questionnaire. chi(2) tests were used to determine whether differences in demographic, sexual, and vaccine-related variables existed between levels of wanting the HPV vaccine. Positive correlates of HPV vaccine acceptance included higher education (P acceptance of the HPV vaccine by men.

  8. Monitoring HPV-16 E7 phosphorylation events

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Marcela O.; Hošek, Tomáš; Calçada, Eduardo O.; Castiglia, Francesca [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Massimi, Paola; Banks, Lawrence [International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, Trieste (Italy); Felli, Isabella C., E-mail: felli@cerm.unifi.it [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Pierattelli, Roberta, E-mail: pierattelli@cerm.unifi.it [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy)

    2017-03-15

    HPV-16 E7 is one of the key proteins that, by interfering with the host metabolism through many protein-protein interactions, hijacks cell regulation and contributes to malignancy. Here we report the high resolution investigation of the CR3 region of HPV-16 E7, both as an isolated domain and in the full-length protein. This opens the way to the atomic level study of the many interactions in which HPV-16 E7 is involved. Along these lines we show here the effect of one of the key post-translational modifications of HPV-16 E7, the phosphorylation by casein kinase II.

  9. Impact of HPV in Oropharyngeal Cancer

    Directory of Open Access Journals (Sweden)

    Linda Marklund

    2011-01-01

    Full Text Available The incidence of oropharyngeal cancers has increased in the western world and Human Papilloma Virus (HPV has been recognised as a risk factor in the last decades. During the same period the prevalence of HPV in oropharyngeal tumours has increased and HPV has been suggested responsible for the increase. The HPV-positive tumours are today recognized as a distinct subset of head and neck cancers with its own clinopathological and risk profile and have a significantly improved prognosis regardless of treatment strategy. This review summarizes current knowledge regarding human papillomavirus biology, oncogenic mechanisms, risk factors, and impact of treatment.

  10. Dimerization of BTas is required for the transactivational activity of bovine foamy virus

    International Nuclear Information System (INIS)

    Tan Juan; Qiao Wentao; Xu Fengwen; Han Hongqi; Chen Qimin; Geng Yunqi

    2008-01-01

    The BTas protein of bovine foamy virus (BFV) is a 249-amino-acid nuclear regulatory protein which transactivates viral gene expression directed by the long terminal repeat promoter (LTR) and the internal promoter (IP). Here, we demonstrate the BTas protein forms a dimeric complex in mammalian cells by using mammalian two hybrid systems and cross-linking assay. Functional analyses with deletion mutants reveal that the region of 46-62aa is essential for dimer formation. Furthermore, our results show that deleting the dimerization region of BTas did not affect the localization of BTas, but that it did result in the loss of its transactivational activity on the LTR and IP. Furthermore, BTas (Δ46-62aa) retained binding ability to the LTR and IP similar to that of the wild-type BTas. These data suggest the dimerization region is necessary for the transactivational function of BTas and is crucial to the replication of BFV

  11. A Cross-Sectional Study to Assess HPV Knowledge and HPV Vaccine Acceptability in Mali

    Science.gov (United States)

    Poole, Danielle N.; Tracy, J. Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S.

    2013-01-01

    Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12–17 years and men and women aged ≥18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns. PMID:23431375

  12. A cross-sectional study to assess HPV knowledge and HPV vaccine acceptability in Mali.

    Directory of Open Access Journals (Sweden)

    Danielle N Poole

    Full Text Available Despite a high prevalence of oncogenic human papilloma virus (HPV infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12-17 years and men and women aged ≥ 18 years (N = 51 in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI, 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005, a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns.

  13. Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology.

    Science.gov (United States)

    Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang

    2016-02-02

    Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

  14. HPV testing and vaccination in Europe.

    LENUS (Irish Health Repository)

    Leeson, Simon C

    2014-01-01

    Current cytology-based screening has a moderate sensitivity to detect cervical intraepithelial neoplasia grade 3 (CIN 3) and cervical cancer even in those states providing rigorous quality control of their cervical screening programs. The impact of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the incorporation of HPV testing on the detection of CIN 3 and cancer is discussed. HPV testing used as a triage for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions, test of cure after treatment, and HPV-based primary screening may improve current cervical screening programs.HPV testing as a triage test for ASCUS seems to offer an improved sensitivity, with a similar specificity as compared to repeat cytology for diagnosing high-grade CIN and has been recommended throughout most EU states. HPV testing as a triage test for low-grade squamous intraepithelial lesions has a low specificity and is not recommended in most member states. HPV test of cure offers an improved sensitivity compared to cytology for women with persistent cervical precancer after treatment. HPV-based cervical cancer screening is more effective than screening with cytology. The effects of HPV-based screening depend on the organization of the program and on adherence to algorithms for screening triage. Otherwise, it is likely that HPV-based screening will increase the referral rate to colposcopy including more women with no detectable cervical lesion. HPV vaccination will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.

  15. Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes*

    Science.gov (United States)

    Villota, Claudio; Campos, América; Vidaurre, Soledad; Oliveira-Cruz, Luciana; Boccardo, Enrique; Burzio, Verónica A.; Varas, Manuel; Villegas, Jaime; Villa, Luisa L.; Valenzuela, Pablo D. T.; Socías, Miguel; Roberts, Sally; Burzio, Luis O.

    2012-01-01

    The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis. PMID:22539350

  16. Expression of mitochondrial non-coding RNAs (ncRNAs) is modulated by high risk human papillomavirus (HPV) oncogenes.

    Science.gov (United States)

    Villota, Claudio; Campos, América; Vidaurre, Soledad; Oliveira-Cruz, Luciana; Boccardo, Enrique; Burzio, Verónica A; Varas, Manuel; Villegas, Jaime; Villa, Luisa L; Valenzuela, Pablo D T; Socías, Miguel; Roberts, Sally; Burzio, Luis O

    2012-06-15

    The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.

  17. [Colorimetric detection of HPV6 and HPV16 by loop mediated isothermal amplification].

    Science.gov (United States)

    Lu, Chun-bin; Luo, Le; Yang, Meng-jie; Nie, Kai; Wang, Miao; Ma, Xue-Jun

    2011-01-01

    A simple, rapid and sensitive colorimetric loop mediated isothermal amplification (LAMP) method was established to detect HPV6 and HPV 16 respectively. The method employed a set of four specially designed primers that recognized six distinct sequences of HPV6-E6 or HPV16-E7 for amplification of nucleic acid under isothermal conditions at 63 degrees C for one hour. The amplification process of LAMP was monitored by the addition of HNB (hydroxy naphthol blue) dye prior to amplification. A positive reaction was indicated by a color change from violet to sky blue and confirmed by real-time turbidimeter and agarose electrophoresis. Thirteen cervical swab samples having single infection with 13 different HPV genotypes were examined to evaluate the specificity. A serial dilution of a cloned plasmid containing HPV-E6 or HPV-E7 gene was examined to evaluate the sensitivity. The results showed that no cross-reaction with other HPV genotypes was observed. The colorimetric LAMP assay could achieve a sensitivity of 1000 copies, 10-20 times lower than that of real-time PCR. The assay was further evaluated with 62 clinical specimens and consistent results were obtained compared with the detection using Kai Pu HPV Genotyping Kit. We concluded that this colorimetric LAMP assay had potential usefulness for the rapid screening of the HPV6 or HPV16 infection in the laboratories and hospitals of provincial and municipal region in China.

  18. 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.

    Science.gov (United States)

    Pitisuttithum, Punnee; Velicer, Christine; Luxembourg, Alain

    2015-01-01

    Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.

  19. Assessing HPV and Cervical Knowledge, Preference and HPV Status Among Urban American Indian Women.

    Science.gov (United States)

    Cina, Kristin R; Omidpanah, Adam A; Petereit, Daniel G

    2017-10-01

    To evaluate whether or not an educational intervention would lead to a change in knowledge and attitudes about human papillomavirus (HPV), HPV vaccines, and cervical cancer. The HPV status was also investigated for interested participants. We provided HPV and cervical cancer education to urban American Indian (AI) women 18 and older using a pre and post-knowledge exam to assess knowledge and attitudes. Women were also given the option to perform vaginal self-tests for high risk HPV (hrHPV) analysis immediately after the education. Ninety-six women participated in our educational sessions. Improvement in performance on a knowledge exam increased from 61.6 to 84.3 percent. Ninety-three women performed the vaginal self-test with 63.1 percent of women preferring vaginal self-testing over conventional screening methods. Thirty-five out of 91 women (38.5 percent) had hrHPV types with 12 of the 35 harboring multiple hrHPV types (13 percent overall). HPV and cervical cancer education was beneficial for urban AI women with the majority of women preferring vaginal self-testing. HPV self-testing may be a strategy to improve screening rates for cervical cancer. Urban AI women had high rates of hrHPV compared to rural AI populations as reported in previous studies.

  20. Parent HPV vaccine perspectives and the likelihood of HPV vaccination of adolescent males.

    Science.gov (United States)

    Clark, Sarah J; Cowan, Anne E; Filipp, Stephanie L; Fisher, Allison M; Stokley, Shannon

    2016-01-01

    In 2013, approximately one-third of US adolescent males age 13-17 y had received ≥1 doses of HPV vaccines and only 14% had received ≥3 doses. This study used a nationally representative, online survey to explore experiences and attitudes related to HPV vaccination among parents with adolescent sons. Analyses compared the perspective of parents who do not intend to initiate HPV vaccine for ≥1 adolescent son to that of parents who are likely to initiate or continue HPV vaccination. Of 809 parents of sons age 11-17 years, half were classified as Unlikely to Initiate HPV vaccination and 39% as Likely to Vaccinate. A higher proportion of the Likely to Vaccinate group felt their son's doctor was knowledgeable about HPV vaccine, did a good job explaining its purpose, and spent more time discussing HPV vaccine; in contrast, over half of the Unlikely to Initiate group had never discussed HPV vaccine with their child's doctor. The majority of parents in both groups showed favorable attitudes to adolescent vaccination in general, with lower levels of support for HPV vaccine-specific statements. Physician-parent communication around HPV vaccine for adolescent males should build on positive attitude toward vaccines in general, while addressing parents' HPV vaccine-specific concerns.

  1. Oral HPV infection and MHC class II deficiency (A study of two cases with atypical outcome

    Directory of Open Access Journals (Sweden)

    Guirat-Dhouib Naouel

    2012-04-01

    Full Text Available Abstract Background Major histocompatibility complex class II deficiency, also referred to as bare lymphocyte syndrome is a rare primary Immunodeficiency disorder characterized by a profondly deficient human leukocyte antigen class II expression and a lack of cellular and humoral immune responses to foreign antigens. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections. The infections begin in the first year of life and involve usually the respiratory system and the gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood. Bone marrow transplantation is the curative treatment. Case reports Here we report two cases with a late outcome MHC class II deficiency. They had a long term history of recurrent bronchopulmonary and gastrointestinal infections. Bone marrow transplantation could not be performed because no compatible donor had been identified. At the age of 12 years, they developed oral papillomatous lesions related to HPV (human papillomavirus. The diagnosis of HPV infection was done by histological examination. HPV typing performed on the tissue obtained at biopsy showed HPV type 6. The lesions were partially removed after two months of laser treatment. Conclusions Viral infections are common in patients with MHC class II and remain the main cause of death. Besides warts caused by HPV infection do not exhibit a propensity for malignant transformation; they can cause great psychosocial morbidity.

  2. Promoter trans-activation of protooncogenes c-fos and c-myc, but not c-Ha-ras, by products of adenovirus early region 1A

    International Nuclear Information System (INIS)

    Sassone-Corsi, P.; Borrelli, E.

    1987-01-01

    The E1A (early region 1A) oncogene products of adenovirus type 2 trans-activate the other early viral transcription units, as well as some cellular promoters. Using a short-term cotransfection assay in murine NIH 3T3 fibroblasts, we show that c-fos and c-myc promoter activities are stimulated by the E1A proteins, whereas c-Ha-ras transcription is not affected. The product of E1A 13S mRNA is responsible for the trans-activation, whereas the 12S mRNA product has no effect. Analysis of the c-fos promoter sequences required for the E1A stimulation shows that responsive sequences are located between positions -402 and -240 upstream of the transcription initiation site. This same region also contains the c-fos serum-responsive element. Furthermore, transcription of the endogenous c-fos gene in HeLa cells is increased after E1A transfection

  3. Incarcerated women's HPV awareness, beliefs, and experiences.

    Science.gov (United States)

    Pankey, Tyson; Ramaswamy, Megha

    2015-01-01

    The purpose of this paper is to explore incarcerated women's awareness, beliefs, and experiences with human papillomavirus (HPV) infection and vaccination. Researchers conducted focus groups with 45 incarcerated women in an urban Midwestern US jail to assess how women talked about their Papanicolaou (Pap) test screening and abnormal Pap test follow-up experiences. Some focus group questions specifically assessed individual awareness, beliefs, and experiences with HPV infection and vaccination. Based on these data, the authors described participants' awareness of HPV, as well as used open coding to ultimately extract themes related to beliefs and experiences with HPV infection and vaccine. While all 45 participants reported experiencing an abnormal Pap test event within the last five years, only two-thirds of participants (n=30) reported having heard of the HPV infection. Several themes emerged from the analysis of the data: the women's beliefs about cause and severity of HPV; frustration with age requirements of the vaccine; varied experiences with vaccinations for themselves and their children; the impact of media exposure on knowledge; and desire for more HPV infection and vaccine information. Incarcerated women's awareness and limited experiences with HPV infection and vaccination may be a barrier to adequate screening and cervical cancer prevention. This study has implications for the development of cervical health education for this high-risk group of women, who are four to five times as likely to have cervical cancer as non-incarcerated women.

  4. Is HPV vaccination in pregnancy safe?

    DEFF Research Database (Denmark)

    van Zwol, Ulla Bonde; Joergensen, J. S.; Lamont, R. F.

    2016-01-01

    the subject of HPV vaccine and pregnancy , the databases of PubMed and Embase were searched to find the relevant literature published in English within the last 10 y. Most of the evidence pertaining to fetal adverse events following HPV vaccination relates to spontaneous miscarriage. None of the relevant...

  5. HIV/AIDS, HPV and Anal Cancer

    Science.gov (United States)

    Wang, Chia-ching J.; Sparano, Joseph; Palefsky, Joel M.

    2016-01-01

    SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index. PMID:27889034

  6. Knowledge and Awareness of Cervical Cancer, Human Papillomavirus (HPV), and HPV Vaccine Among HPV-Infected Chinese Women.

    Science.gov (United States)

    Baloch, Zulqarnain; Yasmeen, Nafeesa; Li, Yuanyue; Zhang, Wenhui; Lu, Hongyu; Wu, Xiaomei; Xia, Xueshan; Yang, Shihua

    2017-09-04

    BACKGROUND It is important to understand the knowledge that various groups of a population have about cervical cancer and human papillomavirus (HPV) and their attitudes toward HPV vaccination, as it will ultimately influence their decision-making for or against the acceptability of vaccines and other preventive methods. This study was designed to determine the level of knowledge and awareness about cervical cancer, HPV, and the HPV vaccine among Chinese women in Yunnan province. MATERIAL AND METHODS A survey was conducted in Yunnan province by the Laboratory of Molecular Virology in collaboration with the Yunnan First People's Hospital in Feb 2015. A total of 388 women were recruited and asked to participate in a questionnaire-based interview that collected information related to their awareness and knowledge about: (1) cervical cancer, (2) HPV and HPV vaccine and willingness to have their children receive vaccination, and (3) demographic characteristics. RESULTS A total of 388 HPV-positive women were included; 300/388 (73.3%) were Han, and 88/388 (22.7%) were other ethnicities. Overall, 204/388 (52.6%) of the women were aware of cervical cancer, with a significant difference between Han women and women of other ethnic groups (168/388, 56.0% and 36/88, 40.9%; P=0.015). Overall, 26.5% of the women were aware of the role of HPV in cervical cancer; 29.0% of the Han women and 18.2% of women of other ethnic groups were aware of this role of HPV (P=0.05). The knowledge that HPV infection leads to cervical cancer was higher among Han women (29.0%) compared to women of other ethnicities (18.2%). Knowledge about the HPV vaccine was very low in all ethnic groups, but the Han women were more willing to allow their children to be vaccinated before they become sexually active. A similar difference has also been found in women from various regions. CONCLUSIONS Although level of awareness and knowledge about cervical cancer was moderate, knowledge and awareness of HPV and the HPV

  7. Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Arenz, Andrea; Ziemann, Frank; Wittig, Andrea; Preising, Stefanie; Engenhart-Cabillic, Rita [Philipps-University, Department of Radiotherapy and Radiooncology, BMFZ - Biomedical Research Center, Marburg (Germany); Mayer, Christina; Wagner, Steffen; Klussmann, Jens-Peter; Wittekindt, Claus [Justus Liebig University, Department of Otorhinolaryngology and Head and Neck Surgery, Giessen (Germany); Dreffke, Kirstin [Philipps-University, Institute for Radiobiology and Molecular Radiooncology, Marburg (Germany)

    2014-09-15

    Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair. (orig.) [German] Fuer Patienten mit HPV-assoziierten Kopf-Hals-Tumoren (HNSCC) ist im Vergleich zu Patienten mit nicht-HPV-assoziierten Tumoren ein besseres Ueberleben nach Radiotherapie gesichert. Ziel der Untersuchung war die Identifizierung von Unterschieden in der zellulaeren DNA-Schadensantwort von HPV-positiven und HPV-negativen Zelllinien, wodurch die bereits in Erprobung stehende Deeskalation einer Radiotherapie bei Patienten mit HPV-assoziierten HNSCC durch experimentelle Daten abgesichert werden koennte. Klonogenes Ueberleben, Induktion von Apoptose, DNA-Doppelstrang-Reparatur und Zellzyklusverhalten wurden in vier HPV-positiven (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) und vier HPV

  8. Primary Care Physicians' Perspectives About HPV Vaccine.

    Science.gov (United States)

    Allison, Mandy A; Hurley, Laura P; Markowitz, Lauri; Crane, Lori A; Brtnikova, Michaela; Beaty, Brenda L; Snow, Megan; Cory, Janine; Stokley, Shannon; Roark, Jill; Kempe, Allison

    2016-02-01

    Because physicians' practices could be modified to reduce missed opportunities for human papillomavirus (HPV) vaccination, our goal was to: (1) describe self-reported practices regarding recommending the HPV vaccine; (2) estimate the frequency of parental deferral of HPV vaccination; and (3)identify characteristics associated with not discussing it. A national survey among pediatricians and family physicians (FP) was conducted between October 2013 and January 2014. Using multivariable analysis, characteristics associated with not discussing HPV vaccination were examined. Response rates were 82% for pediatricians (364 of 442) and 56% for FP (218 of 387). For 11-12 year-old girls, 60% of pediatricians and 59% of FP strongly recommend HPV vaccine; for boys,52% and 41% ostrongly recommen. More than one-half reported ≥25% of parents deferred HPV vaccination. At the 11-12 year well visit, 84% of pediatricians and 75% of FP frequently/always discuss HPV vaccination. Compared with physicians who frequently/always discuss , those who occasionally/rarely discuss(18%) were more likely to be FP (adjusted odds ratio [aOR]: 2.0 [95% confidence interval (CI): 1.1-3.5), be male (aOR: 1.8 [95% CI: 1.1-3.1]), disagree that parents will accept HPV vaccine if discussed with other vaccines (aOR: 2.3 [95% CI: 1.3-4.2]), report that 25% to 49% (aOR: 2.8 [95% CI: 1.1-6.8]) or ≥50% (aOR: 7.8 [95% CI: 3.4-17.6]) of parents defer, and express concern about waning immunity (aOR: 3.4 [95% CI: 1.8-6.4]). Addressing physicians' perceptions about parental acceptance of HPV vaccine, the possible advantages of discussing HPV vaccination with other recommended vaccines, and concerns about waning immunity could lead to increased vaccination rates. Copyright © 2016 by the American Academy of Pediatrics.

  9. HPV genotype-specific concordance between EuroArray HPV, Anyplex II HPV28 and Linear Array HPV Genotyping test in Australian cervical samples

    Directory of Open Access Journals (Sweden)

    Alyssa M. Cornall

    2017-12-01

    Full Text Available Purpose: To compare human papillomavirus genotype-specific performance of two genotyping assays, Anyplex II HPV28 (Seegene and EuroArray HPV (EuroImmun, with Linear Array HPV (Roche. Methods: DNA extracted from clinican-collected cervical brush specimens in PreservCyt medium (Hologic, from 403 women undergoing management for detected cytological abnormalities, was tested on the three assays. Genotype-specific agreement were assessed by Cohen's kappa statistic and Fisher's z-test of significance between proportions. Results: Agreement between Linear Array and the other 2 assays was substantial to almost perfect (κ = 0.60 − 1.00 for most genotypes, and was almost perfect (κ = 0.81 – 0.98 for almost all high-risk genotypes. Linear Array overall detected most genotypes more frequently, however this was only statistically significant for HPV51 (EuroArray; p = 0.0497, HPV52 (Anyplex II; p = 0.039 and HPV61 (Anyplex II; p=0.047. EuroArray detected signficantly more HPV26 (p = 0.002 and Anyplex II detected more HPV42 (p = 0.035 than Linear Array. Each assay performed differently for HPV68 detection: EuroArray and LA were in moderate to substantial agreement with Anyplex II (κ = 0.46 and 0.62, respectively, but were in poor disagreement with each other (κ = −0.01. Conclusions: EuroArray and Anyplex II had similar sensitivity to Linear Array for most high-risk genotypes, with slightly lower sensitivity for HPV 51 or 52. Keywords: Human papillomavirus, Genotyping, Linear Array, Anyplex II, EuroArray, Cervix

  10. HPV genotype-specific concordance between EuroArray HPV, Anyplex II HPV28 and Linear Array HPV Genotyping test in Australian cervical samples.

    Science.gov (United States)

    Cornall, Alyssa M; Poljak, Marin; Garland, Suzanne M; Phillips, Samuel; Machalek, Dorothy A; Tan, Jeffrey H; Quinn, Michael A; Tabrizi, Sepehr N

    2017-12-01

    To compare human papillomavirus genotype-specific performance of two genotyping assays, Anyplex II HPV28 (Seegene) and EuroArray HPV (EuroImmun), with Linear Array HPV (Roche). DNA extracted from clinican-collected cervical brush specimens in PreservCyt medium (Hologic), from 403 women undergoing management for detected cytological abnormalities, was tested on the three assays. Genotype-specific agreement were assessed by Cohen's kappa statistic and Fisher's z-test of significance between proportions. Agreement between Linear Array and the other 2 assays was substantial to almost perfect (κ = 0.60 - 1.00) for most genotypes, and was almost perfect (κ = 0.81 - 0.98) for almost all high-risk genotypes. Linear Array overall detected most genotypes more frequently, however this was only statistically significant for HPV51 (EuroArray; p = 0.0497), HPV52 (Anyplex II; p = 0.039) and HPV61 (Anyplex II; p=0.047). EuroArray detected signficantly more HPV26 (p = 0.002) and Anyplex II detected more HPV42 (p = 0.035) than Linear Array. Each assay performed differently for HPV68 detection: EuroArray and LA were in moderate to substantial agreement with Anyplex II (κ = 0.46 and 0.62, respectively), but were in poor disagreement with each other (κ = -0.01). EuroArray and Anyplex II had similar sensitivity to Linear Array for most high-risk genotypes, with slightly lower sensitivity for HPV 51 or 52. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. HPV Vaccine Safety PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  12. HPV Vaccine (:30) (No Tag)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  13. [HPV immunization for the prevention of cervical cancer].

    Science.gov (United States)

    Mougin, Christiane; Bourgault-Villada, Isabelle; Coursaget, Pierre

    2009-12-01

    Human Papillomaviruses (HPV) infect epithelial cells of the skin and mucosae. Mucosal high-risk HPV types (mainly HPV 16 and 18) are involved in the development of cervical cancer, one of the most common cancers in young women. HPV infection is usually asymptomatic and clears spontaneously, but 10 - 15 % of high-risk HPV infections are persistent and increase the risk of precancerous and cancerous lesions of the cervix. Two HPV vaccines have been licensed to provide protection against cervical cancer. To report the different aspects of HPV infection in order to improve the understanding of the particular problems of HPV vaccination and to review the most recent findings related to HPV vaccines, particularly regarding the protective efficacy of vaccines and the roles of adjuvants and immune response in protection. Articles were selected from the PubMed database (National Library of Medicine- National Institute of Health) with the following Keywords "HPV", "Prevention", "HPV vaccines", "Immune response", "Antibody". Abstracts of oral presentations from international meetings were also selected for the more recent findings. a critical analysis of the majority of papers published was undertaken and relevant information summarized. Virus-like particle production by expressing the major protein of the HPV capsid was carried out in the early 90's, leading to the recent development of two HPV vaccines. These vaccines are now licensed in many countries and have been demonstrated to be highly immunogenic. In subjects that are non-infected at the time of vaccination, HPV vaccines are highly effective in preventing persistent HPV 16 - 18 infections (90 %) and precursors lesions of cervical cancer associated with these two HPV types (close to 100 %). Clinical trials have also confirmed that HPV vaccines are well tolerated by recipients. The present paper is a detailed review published in French on HPV vaccines, their efficacy in the prevention of HPV infections and unresolved

  14. Oncogenic and incidental HPV types associated with histologically ...

    African Journals Online (AJOL)

    Background. In Africa, data on the relationship between oncogenic human papillomavirus (HPV) types, immune status and cervical preinvasive lesions are lacking. Methods. We investigated low-risk (lrHPV) and high-risk (hrHPV) HPV types in a cohort of women with cervical intraepithelial neoplasia (CIN) II/III confirmed on ...

  15. Sensitivity and specificity of oral HPV detection for HPV-positive head and neck cancer.

    Science.gov (United States)

    Gipson, Brooke J; Robbins, Hilary A; Fakhry, Carole; D'Souza, Gypsyamber

    2018-02-01

    The incidence of HPV-related head and neck squamous cell carcinoma (HPV-HNSCC) is increasing. Oral samples are easy and non-invasive to collect, but the diagnostic accuracy of oral HPV detection methods for classifying HPV-positive HNSCC tumors has not been well explored. In a systematic review, we identified eight studies of HNSCC patients meeting our eligibility criteria of having: (1) HPV detection in oral rinse or oral swab samples, (2) tumor HPV or p16 testing, (3) a publication date within the last 10 years (January 2007-May 2017, as laboratory methods change), and (4) at least 15 HNSCC cases. Data were abstracted from each study and a meta-analysis performed to calculate sensitivity and specificity. Eight articles meeting inclusion criteria were identified. Among people diagnosed with HNSCC, oral HPV detection has good specificity (92%, 95% CI = 82-97%) and moderate sensitivity (72%, 95% CI = 45-89%) for HPV-positive HNSCC tumor. Results were similar when restricted to studies with only oropharyngeal cancer cases, with oral rinse samples, or testing for HPV16 DNA (instead of any oncogenic HPV) in the oral samples. Among those who already have HNSCC, oral HPV detection has few false-positives but may miss one-half to one-quarter of HPV-related cases (false-negatives). Given these findings in cancer patients, the utility of oral rinses and swabs as screening tests for HPV-HNSCC among healthy populations is probably limited. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The high-risk HPV E6 target scribble (hScrib is required for HPV E6 expression in cervical tumour-derived cell lines

    Directory of Open Access Journals (Sweden)

    Christian Kranjec

    2016-12-01

    Full Text Available The ability of high-risk HPV E6 oncoproteins to target cellular proteins which harbor PDZ domains is believed to play an important role in the virus life cycle and to influence the ability of these viruses to bring about malignant transformation. Whilst many of these PDZ proteins are potential tumour suppressors, involved in the control of cell polarity and cell-contact, recent studies suggest that mislocalisation or overexpression might result in the emergence of oncogenic functions. This has been shown most clearly for two E6 targets, hDlg and hScrib. In this study we show that hScrib plays such a role in HeLa cells, where its expression is required for maintaining high levels of HPV-18 E6 protein. Loss of hScrib has no effect on E6 stability but results in lower levels of E6 transcription and a reduced rate of E6 translation. We further show that, in the context of cervical tumour-derived cell lines, both hScrib and E6 cooperate in the activation of the S6 kinase signaling pathway, and thereby contribute towards maintaining high rates of protein translation. These results indicate that the residual hScrib that is present within HPV transformed cells is pro-oncogenic, and highlights the dual functions of E6 cell polarity targets. Keywords: HPV E6, hScrib, S6 kinase, Protein translation

  17. Cellular gravity

    NARCIS (Netherlands)

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  18. Cervical screening in HPV-vaccinated populations.

    Science.gov (United States)

    Canfell, K

    2018-06-01

    Cervical screening with cytology has been the basis for substantial reductions in cervical cancer incidence and mortality in most high-income countries over the last few decades. More recently, there have been two key, parallel developments which have prompted a major re-consideration of cervical screening. The first is the emergence of evidence on the improved sensitivity of human papillomavirus (HPV) DNA testing compared to cytology, and the second is the large-scale deployment of prophylactic vaccination against HPV. A key challenge to be overcome before HPV screening could be introduced into national cervical screening programs was the specificity of an infection, for detection of precancerous lesions. This has been done in three ways: (1) by considering the appropriate age for starting HPV screening (30 years in unvaccinated populations and 25 years in populations with mature vaccination programs and high vaccine uptake) and the appropriate screening interval; (2) via development of clinical HPV tests, which are (by design) not as sensitive to low viral loads; and (3) by introducing effective triaging for HPV-positive women, which further risk-stratifies women before referral for diagnostic evaluation. This review discusses these major developments and describes how the benefits of HPV screening are being optimized in both unvaccinated and vaccinated populations.

  19. Analysis of peripheral blood immune cells after prophylactic immunization with HPV-16/18 ASO4-adjuvanted vaccine

    Directory of Open Access Journals (Sweden)

    Iwona Hus

    2015-04-01

    Full Text Available Persistent infection with oncogenic types of human papillomavirus (HPV is a causal factor for more than 99% of cervical cancers. Recently, prophylactic vaccines have been developed to prevent infections with cancer-associated HPV types (HPV16 and HPV18. The aim of this study was to analyze the changes in the immune system that occur within four weeks of the first dose of HPV-16/18 ASO4-adjuvanted vaccine. Assessment of the percentages of selected cell populations in peripheral blood of 20 healthy volunteers vaccinated with Cervarix was performed using flow cytometry. The analysis revealed an increase in the proportion of activated B and CD4+ T helper cells and an absence of significant differences in cytotoxic CD8+ T lymphocytes, indicating activation of the humoral response after vaccination, without a significant effect on cellular response. There were no significant changes in the NK cell population, and there was a reduction of the percentage of NKT-like cells, which may result from expiry of the primary response at the time of analysis. The presented results are preliminary, and in the context of the increasing use of the anti-HPV vaccine, it would be worth continuing the study in larger groups of patients and at earlier and later time points in combination with the measurement of specific anti-HPV16 and -HPV18 antibody levels. Such an assessment could therefore contribute not only to better understanding of the exact mechanism of action of the vaccine, but also to defining the immunological parameters that determine its effectiveness.

  20. Parent HPV vaccine perspectives and the likelihood of HPV vaccination of adolescent males

    OpenAIRE

    Clark, Sarah J; Cowan, Anne E; Filipp, Stephanie L; Fisher, Allison M; Stokley, Shannon

    2015-01-01

    In 2013, approximately one-third of US adolescent males age 13–17 y had received ≥1 doses of HPV vaccines and only 14% had received ≥3 doses. This study used a nationally representative, online survey to explore experiences and attitudes related to HPV vaccination among parents with adolescent sons. Analyses compared the perspective of parents who do not intend to initiate HPV vaccine for ≥1 adolescent son to that of parents who are likely to initiate or continue HPV vaccination. Of 809 paren...

  1. HPV Vaccination: Preventing More with Less

    Science.gov (United States)

    Douglas Lowy is acting director of the National Cancer Institute and Chief of the intramural Laboratory of Cellular Oncology in the Center for Cancer Research at the NCI. He received his medical degree from New York University School of Medicine, and trained in internal medicine at Stanford University and dermatology at Yale University. His research includes papillomaviruses and the regulation of normal and neoplastic growth. The papillomavirus research is carried out in close collaboration with John Schiller, with whom he has co-authored more than 100 papers over the past 25 years. In the 1980s, he studied the genetic organization of papillomaviruses and identified the oncogenes encoded by the virus. More recently, he has worked on papillomavirus vaccines and the papillomavirus life cycle. Their laboratory was involved in the initial development, characterization, and clinical testing of the preventive virus-like particle-based HPV vaccines that have been approved by the US Food and Drug Administration and many other countries. It is for this body of work that Drs. Lowy and Schiller received the 2007 Federal Employee of the Year Award from the Partnership for Public Service, the 2007 Dorothy P. Landon-American Association for Cancer Research Prize for Translational Cancer Research, the Sabin Gold Medal in 2011, and the National Medal of Technology and Innovation from President Obama in 2014. Dr. Lowy also received the 2007 Medal of Honor for basic research from the American Cancer Society. He is listed by the Institute for Scientific Information as one of the most highly cited authors in microbiology, and is a member of the National Academy of Sciences and the Institute of Medicine of the NAS.

  2. Acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among men who have sex with men in Hong Kong.

    Directory of Open Access Journals (Sweden)

    Joseph T F Lau

    Full Text Available HPV vaccines are available to men but there are few studies investigating the acceptability of HPV vaccines among men who have sex with men (MSM, a high risk group. We assessed the intention to take up HPV vaccines among MSM in Hong Kong and the associated factors related to cognitions on HPV and HPV vaccines, basing on the Health Belief Model (n = 542. The acceptability of HPV vaccines was 20% (unconditional on efficacies and price, 29.2% (conditional on efficacies and market price, 51.7% (conditional on efficacies and discounted price and 79.1% (conditional on efficacies and free price. Adjusting for background variables, composite scores of perceived susceptibility, perceived severity, perceived barriers and cue to actions were significantly associated with acceptability of HPV vaccines conditional on specific efficacies and the market price. Acceptability of HPV vaccines was highly price sensitive. Future studies need to use conditional measures. Implementation and translational researches are warranted.

  3. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  4. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  5. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Science.gov (United States)

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  6. One Family's Struggles with HPV (Human Papillomavirus)

    Medline Plus

    Full Text Available ... news labs links & resources hpv overview why vaccinate posters buttons and banners videos someone you love flu ... such thing as stomach flu pregnancy and flu posters meningitis overview why vaccinate CDC and meningitis Stiletto ...

  7. One Family's Struggles with HPV (Human Papillomavirus)

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    Full Text Available ... getvaxed about GETVAXED print ads go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles ... free-of-charge. Branded videos contain the "PKIDs.ORG" end slate; unbranded videos are provided for organizations ...

  8. HPV and cancer of the oral cavity.

    Science.gov (United States)

    Hübbers, Christian U; Akgül, Baki

    2015-01-01

    Increased awareness of human papillomavirus (HPV) as an etiological cause of head and neck squamous cell carcinoma has increased the interest in analysis of distinct oral sub-sites. It is currently under debate, whether HPV plays a role in the development of squamous cell carcinoma of the oral cavity (OSCC). The weakness in most published studies is the lack of performing different HPV detection tests combined with analysis for biological activity of the virus. In addition, different sub-sites of the oral cavity had been combined to a single entity, which retrospectively leads to a highly heterogeneous basis of data. In this review we mainly discuss the unclear role of HPV in OSCC development.

  9. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Human papillomavirus (HPV) can cause serious health problems, including ... 6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov TOP

  10. Natural History of HPV and Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    Dr. Phil Castle, an intramural research scientist at the National Institutes of Health, talks about the natural history of human papillomavirus (HPV) infections, and cervical cancer and other anogenital cancers.

  11. One Family's Struggles with HPV (Human Papillomavirus)

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  12. One Family's Struggles with HPV (Human Papillomavirus)

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  13. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    International Nuclear Information System (INIS)

    Zacapala-Gómez, Ana Elvira; Del Moral-Hernández, Oscar; Villegas-Sepúlveda, Nicolás; Hidalgo-Miranda, Alfredo; Romero-Córdoba, Sandra Lorena

    2016-01-01

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  14. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    Energy Technology Data Exchange (ETDEWEB)

    Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com [Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Gro., México (Mexico); Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx [Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D.F., México (Mexico); Hidalgo-Miranda, Alfredo, E-mail: ahidalgo@inmegen.gob.mx [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); Romero-Córdoba, Sandra Lorena, E-mail: sromero_cordoba@hotmail.com [Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., México (Mexico); and others

    2016-01-15

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such as adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.

  15. Knowledge of HPV, Perception of Risk, and Intent to Obtain HPV Vaccination among Male University Students

    Science.gov (United States)

    Larsen, Dawn

    2014-01-01

    Human papillomavirus (HPV), the most common sexually transmitted virus in the world, is associated with almost all cases of cervical cancer. It is also related to vulvar, vaginal, penile, anal, and oropharyngeal cancer. HPV vaccination is recommended by the Centers for Disease Control and Prevention (CDC) for both boys and girls. Unfortunately,…

  16. No evidence for active human papillomavirus (HPV) in fields surrounding HPV-positive oropharyngeal tumors

    NARCIS (Netherlands)

    Rietbergen, M.M.; Braakhuis, B.J.M.; Moukhtari, N.; Bloemena, E.; Brink, A.; Sie, D.; Ylstra, B.; Baatenburg de Jong, R.J.; Snijders, P.J.F.; Brakenhoff, R.H.; Leemans, C.R.

    2014-01-01

    Background Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with HPV-negative OPSCCs. Important factors contributing to this better prognosis are relatively low numbers of local/regional recurrences (LRRs) and

  17. Papillomavirus E2 induces senescence in HPV-positive cells via pRB- and p21CIP-dependent pathways

    OpenAIRE

    Wells, Susanne I.; Francis, Delicia A.; Karpova, Alla Y.; Dowhanick, Jennifer J.; Benson, John D.; Howley, Peter M.

    2000-01-01

    A hallmark of human papillomavirus (HPV) associated carcinogenesis is the integration of the viral DNA into the cellular genome, usually accompanied by the loss of expression of the viral E2 gene. E2 binds to and represses the viral promoter directing expression of the E6 and E7 oncogenes. The re-introduction and expression of exogenous E2 in HPV-positive cancer cells results in cellular growth arrest, while growth in the context of exogenous E2 can be restored through the expression of exoge...

  18. Successes and Challenges of Vaccines to Prevent HPV-associated Cancers

    Science.gov (United States)

    Dr. John T. Schiller received his bachelor’s degree in Molecular Biology from the University of Wisconsin, Madison in 1975, and his master’s and PhD degrees in Microbiology from the University of Washington, Seattle, in 1978 and 1982, respectively. He is currently a NIH Distinguished Investigator and Section Chief in the Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD. In his 35 years at the NCI, Dr. Schiller has studied various aspects of papillomavirus molecular biology, immunology, and epidemiology The laboratory headed by Dr. Schiller and Dr. Lowy led in the discovery, characterization, and clinical testing of virus-like particle (VLP) vaccines to prevent the HPV infections that cause cervical and other cancers. They have facilitated technology transfer to potential HPV vaccine manufactures in developing countries and provided leadership in promoting global public health issues related to the implementation of HPV vaccination. They have received numerous awards for this work including the 2007 Sabin Gold Medal Award, the 2014 National Medal of Technology and Innovation, and the 2017 Lasker~DeBakey Clinical Medical Research Award. Dr. Schiller’s current interests include basic studies of papillomavirus virion assembly and infection, the development of 2 generation HPV vaccines, and vaccines and therapies for other infectious diseases and cancers.  

  19. HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Oscar Peralta-Zaragoza

    2013-01-01

    Full Text Available Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.

  20. The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation

    International Nuclear Information System (INIS)

    Stuqui, Bruna; Conceição, André Luis Giacometti; Termini, Lara; Sichero, Laura; Villa, Luisa Lina; Rahal, Paula; Calmon, Marília de Freitas

    2016-01-01

    High-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellular proteins, triggering cell transformation. One protein that is associated with pathological conditions and has a PDZ domain is the protease HTRA1 (high temperature requirement 1). This protein is poorly expressed in some cancers, suggesting a tumor suppressor role. The aim of this study was to evaluate the effect of HTRA1 overexpression in HPV16-positive (CasKi) and HPV-negative (C33) cervical cell lines. The cells were transfected with a vector containing the HTRA1 ORF or an empty vector. HTRA1 overexpression was confirmed by qRT-PCR. The cells were subjected to cell proliferation, colony formation, apoptosis and cell cycle assays. C33 cells expressing HTRA1 grew significantly fewer colonies and showed less proliferation than cells without HTRA1 expression. In contrast, in the CasKi cells overexpressing HTRA1, there was an increase in the cell growth rate and in the colonies density compared to cells expressing low levels of HTRA1. An apoptosis assay showed that HTRA1 does not interfere with the apoptosis rate in these cells. A cell cycle immunofluorescence assay revealed more CasKi cells overexpressing HTRA1 in the S phase and more C33 HTRA1-transfected cells in the G0/G1 phase, suggesting that HTRA1 plays different roles in the cell cycle progression of these cells. HTRA1 overexpression prevents cell proliferation in the HPV-negative cell line and increases cell proliferation in the HPV-positive cell line. Although the E6/HTRA1 interaction has already been described in the literature, more studies are required to confirm whether the present functional findings are a result of this interaction

  1. Worldwide burden of cancer attributable to HPV by site, country and HPV type

    Science.gov (United States)

    Plummer, Martyn; Vignat, Jerome; Franceschi, Silvia

    2017-01-01

    HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV‐attributable cancer burden can boost programs of HPV vaccination and HPV‐based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age‐standardized incidence rates of HPV‐attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from 20% in India and sub‐Saharan Africa. Cervix accounts for 83% of HPV‐attributable cancer, two‐thirds of which occur in less developed countries. Other HPV‐attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men) and 13,000 penis. In the head and neck, HPV‐attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV‐attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross‐protection emphasize the importance of the introduction of more affordable vaccines in less developed countries. PMID:28369882

  2. Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing.

    Science.gov (United States)

    Demarco, Maria; Carter-Pokras, Olivia; Hyun, Noorie; Castle, Philip E; He, Xin; Dallal, Cher M; Chen, Jie; Gage, Julia C; Befano, Brian; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy; Raine-Bennett, Tina R; Wentzensen, Nicolas; Schiffman, Mark

    2018-05-01

    As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity (Becton Dickinson Diagnostics, Sparks, MD), a nine-channel HPV test recently approved by the FDA, by assessing (i) the association of Onclarity types/channels with precancer/cancer; (ii) HPV type/channel agreement between the results of Onclarity and cobas (Roche Molecular Systems, Pleasanton, CA), another FDA-approved test; and (iii) Onclarity typing for all types/channels compared to typing results from a research assay (linear array [LA]; Roche). We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample ( n = 9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2; Qiagen, Germantown, MD). A subset had already been tested by cobas and LA ( n = 1,965). Cervical histopathology was ascertained from electronic health records. Hierarchical Onclarity channels showed a significant linear association with histological severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other 12 types as a pool (sample-weighted kappa value of 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and groups of types identified by LA (kappa values from 0.80 for HPV39/68/35 to 0.97 for HPV16). Onclarity typing results corresponded well to histopathology and to an already validated HPV DNA test and could provide additional clinical typing if such discrimination is determined to be clinically desirable. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  3. Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

    Science.gov (United States)

    Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

    2017-10-01

    The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. Comparison of the cobas Human Papillomavirus (HPV) Test with the Hybrid Capture 2 and Linear Array HPV DNA Tests

    Science.gov (United States)

    Sadorra, Mark; LaMere, Brandon J.; Kail, Randi; Aldrich, Carrie; Kinney, Walter; Fetterman, Barbara; Lorey, Thomas; Schiffman, Mark; Castle, Philip E.

    2012-01-01

    The cobas human papillomavirus (HPV) test (cobas) was recently approved by the U.S. Food and Drug Administration (FDA) and identifies HPV16 and HPV18 separately as well as detecting a pool of 11 HR-HPV genotypes (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68) and also HPV66. We compared cobas, Linear Array (LA), and Hybrid Capture 2 (HC2) assays for detection of carcinogenic HPV DNA, and cobas and LA for detection of HPV16 and HPV18 DNA, among the first 1,852 women enrolled in the HPV Persistence and Progression Cohort (PaP Cohort) study. Specimens were tested by all 3 assays 1 year after an HC2-positive result. In 1,824 specimens with cobas results, cobas had an 85.9% agreement with HC2 and 91.0% agreement with LA for carcinogenic HPV detection. When results between cobas and HC2 disagreed, cobas tended to call more women HPV positive (P < 0.01). Categorizing cobas and LA results hierarchically according to cancer risk (HPV16, HPV18, other carcinogenic HPV genotypes, or carcinogen negative), there was a 90% agreement for all categories of HPV (n = 1,824). We found good agreement between the two U.S. FDA-approved HPV tests, with discrepancies between the two assays due to specific characteristics of the individual assays. Additional studies are needed to compare HC2 and cobas for detecting and predicting CIN3 to understand the clinical implications of the discrepant test results between the two tests. PMID:22075592

  5. Moderate Awareness and Limited Knowledge Relating to Cervical Cancer, HPV, and the HPV Vaccine Among Hispanics/Latinos in Utah.

    Science.gov (United States)

    Bodson, Julia; Warner, Echo L; Kepka, Deanna

    2016-07-01

    We investigate the demographic factors associated with human papillomavirus (HPV) vaccine-related awareness and knowledge in an emerging (rather than established) Hispanic/Latino population. We surveyed 119 Spanish-speaking, mostly low-income and immigrant, Hispanic/Latino parents and guardians of adolescents 11 to 17 years old (i.e., eligible to receive the HPV vaccine) about their HPV vaccine-related awareness and knowledge. Data collection took place between August 2013 and October 2013 in Salt Lake City, Utah. Participants had moderately high awareness scores, with more than half the participants reporting having heard of cervical cancer (84.5%), HPV (76.4%), and the HPV vaccine (67.3%). HPV vaccine-related knowledge was low, with fewer than half the participants reporting they knew that most people are infected with HPV (32.7%), that HPV is asymptomatic among women (16.4%), that the HPV vaccine requires more than one dose (33.6%), and that the HPV vaccine is recommended for adolescent girls (47.3%) and boys (35.5%). Combined awareness and knowledge was significantly associated with educational attainment (p = .02) and country of origin (p = .03). Results demonstrate moderate to high HPV vaccine-related awareness and limited HPV vaccine-related knowledge among Hispanic/Latino parents living in Utah. These findings will inform educational interventions to improve the HPV vaccine-related awareness and knowledge in this vulnerable population. © 2016 Society for Public Health Education.

  6. Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study.

    Science.gov (United States)

    Pierce Campbell, Christine M; Viscidi, Raphael P; Torres, B Nelson; Lin, Hui-Yi; Fulp, William; Abrahamsen, Martha; Lazcano-Ponce, Eduardo; Villa, Luisa L; Kreimer, Aimée R; Giuliano, Anna R

    2016-07-01

    The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56-4.76). © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. HPV Prevention (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Human papillomavirus, or HPV, is a virus that can cause certain cancers and is the most commonly sexually transmitted infection in the U.S. In this podcast, Dr. Laura Viens discusses the importance of getting vaccinated against HPV.

  8. HPV Prevention (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Human papillomavirus, or HPV, is the most common sexually transmitted infection in the U.S. and is associated with almost 39,000 cancers each year. This podcast discusses the importance of getting the HPV vaccine.

  9. HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile.

    Science.gov (United States)

    Lagos, Marcela; Van De Wyngard, Vanessa; Poggi, Helena; Cook, Paz; Viviani, Paola; Barriga, María Isabel; Pruyas, Martha; Ferreccio, Catterina

    2015-01-01

    We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

  10. Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax.

    Science.gov (United States)

    Alefantis, Timothy; Barmak, Kate; Harhaj, Edward W; Grant, Christian; Wigdahl, Brian

    2003-06-13

    Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

  11. Towards the eradication of HPV infection through universal specific vaccination

    OpenAIRE

    Crosignani, Piergiorgio; De Stefani, Antonella; Fara, Gaetano Maria; Isidori, Andrea M; Lenzi, Andrea; Liverani, Carlo Antonio; Lombardi, Alberto; Mennini, Francesco Saverio; Palu?, Giorgio; Pecorelli, Sergio; Peracino, Andrea P; Signorelli, Carlo; Zuccotti, Gian Vincenzo

    2013-01-01

    Background The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm...

  12. Impact of HPV infection on oral squamous cell carcinoma.

    Science.gov (United States)

    Götz, Carolin; Drecoll, Enken; Straub, Melanie; Bissinger, Oliver; Wolff, Klaus-Dietrich; Kolk, Andreas

    2016-11-22

    Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5.94%) positive (+) cases by p16INK4a immunostaining. Only 4 (1.98%) of the p16INK4a+ cases were + for HPV using PCR. Our homogenous collective of OSCC allowed us to compare HPV+ and HPV negative (-) patients without creating bias for tumour localisation, age, gender or tumour stage. After testing OSCC samples for HPV positivity, we compared the results of two commonly used HPV detection methods, p16INK4a immunostaining and HPV DNA-related PCR, on 202 OSCC patients. HPV subtypes were determined with an HPV LCD Array Kit. Clinicopathological features of the patients were analysed, and the disease specific survival rates (DSS) for HPV+ and HPV- patients were obtained. p16INK4a immunostaining is a not a reliable HPV detection method for OSCC. Positive p16INK4a immunostaining did not agree with + results from PCR of HPV DNA. Furthermore, the influence of HPV-related oncogenic transformation in OSCC is overestimated. The significance of HPV infection remains clinically unclear, and its influence on survival rates is not relevant to OSCC cases.

  13. Is incidence of multiple HPV genotypes rising in genital infections?

    Directory of Open Access Journals (Sweden)

    Amir Sohrabi

    2017-11-01

    Full Text Available Frequency of cervical cancer related to Human Papilloma Virus (HPV has increased remarkably in less-developed countries. Hence, applying capable diagnostic methods is urgently needed, as is having a therapeutic strategy as an effective step for cervical cancer prevention. The aim of this study was to investigate the prevalence of various multi-type HPV infection patterns and their possible rising incidence in women with genital infections.This descriptive study was conducted on women who attended referral clinical laboratories in Tehran for genital infections from January 2012 until December 2013. A total of 1387 archival cervical scraping and lesion specimens were collected from referred women. HPV genotyping was performed using approved HPV commercial diagnostic technologies with either INNO-LiPA HPV or Geno Array Test kits.HPV was positive in 563 cases (40.59% with mean age of 32.35 ± 9.96. Single, multiple HPV genotypes and untypable cases were detected in 398 (70.69%, 160 (28.42% and 5 (0.89% cases, respectively. Multiple HPV infections were detected in 92 (57.5%, 42 (26.2%, 17 (10.6% and 9 (5.7% cases as two, three, four and five or more genotypes, respectively. The prevalence of 32 HPV genotypes was determined one by one. Seventeen HPV genotypes were identified in 95.78% of all positive infections. Five dominant genotypes, HPV6, 16, 53, 11 and 31, were identified in a total of 52.35%of the HPV positive cases.In the present study, we were able to evaluate the rate of multiple HPV types in genital infections. Nevertheless, it is necessary to evaluate the role of the dominant HPV low-risk types and the new probably high-risk genotypes, such as HPV53, in the increasing incidences of genital infections. Keywords: Multiple HPV Types, Incidence, Genital infection, Cervical cancer, Iran

  14. HPV Vaccine (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Nearly all sexually active men and women will get infected with the human papillomavirus, or HPV, at some point in their lives. HPV can lead to serious health problems later in life, including certain cancers in both men and women. Since 2006, a vaccine has been available that protects against the most frequent cancer-causing types of HPV. In this podcast, Shannon Stokley discusses the importance of getting the HPV vaccine.

  15. HPV genotypes in invasive cervical cancer in Danish women

    DEFF Research Database (Denmark)

    Kirschner, Benny; Junge, Jette; Holl, Katsiaryna

    2013-01-01

    Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer.......Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer....

  16. HPV test by Hybrid Capture II for the diagnosis of HR-HPV persistent infection.

    Science.gov (United States)

    Serour, Y; Bendahmane, M; Abbou Baker, F; Medles, M; Moueddene, B; Kraiba, R

    2017-11-01

    Persistent high-risk HPV (HR-HPV) infection is associated with a greater risk of cervical cancer. Statistical data on the prevalence of HR-HPV infections in the Algerian population is lacking. We conducted a prospective study of 300 women aged between 25 and 50 years, screened for cervical cancer from 2012 to 2015 in Sidi Bel Abbès, a western region of Algeria. We aimed to assess the reliability of the repeated use of the HC II test (three longitudinal HPV tests 9 months apart from each other) in diagnosing the persistence of HR-HPV infection. The prevalence of HR-HPV infection was 7.33% and infected women were aged 37.9±3years. For 90.9% of HR-HPV-positive patients, the infection persisted for a mean of 18.5months [95% CI: 16.9-22.1months]. Among these patients, 55.55% developed CIN1 and 11.11% developed CIN2. The sensitivity of the HC II test was 81.74% [95% CI: 71.3-89.6] and its positive predictive value associated with abnormal cervical biopsy was 27.49% [95% CI: 16.0-33.33]. Repeating the HC II test is a good predictor for identifying women at high risk of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Young multiethnic women's attitudes toward the HPV vaccine and HPV vaccination.

    Science.gov (United States)

    Wong, Li Ping

    2008-11-01

    To investigate the acceptability of the HPV vaccine among a multiethnic sample of young women in Malaysia. A qualitative study of 40 young women aged between 13 and 27 years recruited into 7 focus groups to discuss their knowledge of HPV infection, and their attitudes toward and acceptance of the HPV vaccine. The women were divided into Malay, Chinese, and Indian groups to allow for comparison among ethnicities. Poor knowledge about HPV did not influence the HPV vaccine's acceptability. Although participants were in favor of the vaccine, the majority preferred to delay vaccination because it is newly introduced, they did not perceive themselves to be at risk of HPV infection, or because of cost factors. Concerns were raised regarding the vaccine's safety, the potential to be perceived as promiscuous and sexually active, and whether the vaccine was halal. Promotion of the HPV vaccine should take account of social and cultural acceptability. The findings will help develop strategies for effective vaccination initiatives in a multiethnic and multireligious Asian society.

  18. Male Undergraduates' HPV Vaccination Behavior: Implications for Achieving HPV-Associated Cancer Equity.

    Science.gov (United States)

    Lee, Hee Yun; Lust, Katherine; Vang, Suzanne; Desai, Jay

    2018-06-01

    Despite the availability of the human papillomavirus (HPV) vaccine for males, uptake of the vaccine has been low, particularly among young adult males. This study aimed to investigate the levels of HPV vaccination and predictors of HPV vaccine completion in college men ages 18-26. We analyzed data from the 2015 College Student Health Survey, which was administered at 17 post-secondary institutions in Midwest areas. We included only responses from male participants who were ages 18-26 years old, resulting in a sample size of 2516. We used Andersen's Behavioral Model of Health Services Utilization to guide our study design. Multivariate logistic regression was used to examine predictors of HPV vaccine receipt. College-aged males in our sample had a HPV vaccine completion rate of 50.0%. Male students who were younger, had at least one parent who held a graduate degree, had initiated sex, and were enrolled at a private 4-year institution were more likely to have been vaccinated. These findings suggest that HPV vaccination in college-aged men are low. Efforts are needed to increase HPV vaccination in male students who are older, from lower socioeconomic statuses, have not initiated sex, and enrolled at public institutions. Findings also indicate important gender disparities in vaccine uptake that must be addressed in order to achieve optimal vaccine uptake in college-aged males.

  19. Influence of evidence type and narrative type on HPV risk perception and intention to obtain the HPV vaccine.

    Science.gov (United States)

    Nan, Xiaoli; Dahlstrom, Michael F; Richards, Adam; Rangarajan, Sarani

    2015-01-01

    This research examines the influence of evidence type (statistical, narrative, or hybrid) and narrative type (first-person or third-person) on risk perception about human papillomavirus (HPV) and behavioral intention to get the HPV vaccine. In total, 174 college students who had not received the HPV vaccine participated in a controlled experiment. Results show that the hybrid message containing both statistical and narrative descriptions of HPV resulted in greater perceived risk of getting HPV than either of the messages containing just one type of evidence--statistical or narrative. Moreover, the first-person narrative message led to greater risk perception about HPV than the third-person narrative message. Both evidence type and narrative type had an indirect effect on intention to get the HPV vaccine free of cost through HPV risk perception. Implications of the findings for vaccine risk communication are discussed.

  20. Human papillomavirus (HPV) vaccination of adolescents in the ...

    African Journals Online (AJOL)

    In SA, two vaccines (HPV quadrivalent (types 6, 11, 16, and 18) vaccine, recombinant (Gardasil) and HPV bivalent (types 16 and 18) vaccine, recombinant (Cervarix)) are currently registered for the prevention of HPV-related disease. In the past, there have been significant challenges to achieving high coverage and uptake ...

  1. HPV in minority populations : Epidemiology and vaccination acceptability

    NARCIS (Netherlands)

    Alberts, C.J.

    2017-01-01

    This dissertation describes the epidemiology of human papillomavirus (HPV) and the social-psychological aspects of HPV vaccination acceptability in two different minority populations. Both populations are at higher risk of developing HPV induced disease (notably cervical, penile, anal, and head and

  2. Understanding HPV Disease and Prevention: A Guide for School Nurses

    Science.gov (United States)

    Lockwood-Rayermann, Suzy; McIntyre, Susan J.

    2009-01-01

    Oncogenic human papillomavirus (HPV) causes 99.7% of all cervical cancers. HPV Types 16 and 18 are responsible for approximately 77% of cases, and peak prevalence occurs in females younger than 25 years of age. The recent implementation of HPV vaccination provides females with the opportunity to prevent infection. School nurses are advocates of…

  3. New Approaches to Immunotherapy for HPV Associated Cancers

    Directory of Open Access Journals (Sweden)

    Deepak Mittal

    2011-09-01

    Full Text Available Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18. Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials.

  4. Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

    Science.gov (United States)

    Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung

    2014-01-01

    Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an

  5. HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

    Science.gov (United States)

    DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

    2016-01-01

    The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL  CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions

  6. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  7. Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

    Directory of Open Access Journals (Sweden)

    Maria Grazia Romanelli

    2011-05-01

    Full Text Available Human T-lymphotropic viruses type 1 (HTLV-1 and type 2 (HTLV-2 present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

  8. Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types.

    Science.gov (United States)

    Kavanagh, K; Pollock, K G J; Potts, A; Love, J; Cuschieri, K; Cubie, H; Robertson, C; Donaghy, M

    2014-05-27

    In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12-13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12-13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%. To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV. From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated. This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake.

  9. The Role of Human Papillomavirus (HPV)-Related Stigma on HPV Vaccine Decision-Making among College Males

    Science.gov (United States)

    Jones, Georden; Perez, Samara; Huta, Veronika; Rosberger, Zeev; Lebel, Sophie

    2016-01-01

    Objective: The goals of the present study are (1) to identify sociodemographic and psychosocial predictors of human papillomavirus (HPV)-related stigma and (2) to examine the relationship between HPV-related stigma in predicting HPV vaccine decision-making among college males. Participants: Six hundred and eighty college males aged 18--26 from 3…

  10. The feminization of HPV: How science, politics, economics and gender norms shaped U.S. HPV vaccine implementation

    Directory of Open Access Journals (Sweden)

    Ellen M. Daley

    2017-06-01

    Full Text Available Human papillomavirus (HPV can cause a number of anogenital cancers (i.e., cervical, penile, anal, vaginal, vulvar and genital warts. A decade ago, the HPV vaccine was approved, and has been shown to be a public health achievement that can reduce the morbidity and mortality for HPV-associated diseases. Yet, the mistaken over-identification of HPV as a female-specific disease has resulted in the feminization of HPV and HPV vaccines. In this critical review, we trace the evolution of the intersection of science, politics, economics and gender norms during the original HPV vaccine approval, marketing era, and implementation. Given the focus on cervical cancer screening, women were identified as bearing the burden of HPV infection and its related illnesses, and the group responsible for prevention. We also describe the consequences of the feminization of HPV, which has resulted primarily in reduced protection from HPV-related illnesses for males. We propose a multilevel approach to normalizing HPV vaccines as an important aspect of overall health for both genders. This process must engage multiple stakeholders, including providers, parents, patients, professional organizations, public health agencies, policymakers, researchers, and community-based organizations. Keywords: HPV vaccination, Feminization, Critical review

  11. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Matthew H., E-mail: stenmark@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); McHugh, Jonathan B. [Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Walline, Heather M.; Komarck, Christine [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Worden, Francis P. [Department of Medical Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Mukherji, Suresh K. [Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Carey, Thomas E. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2014-03-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.

  12. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; McHugh, Jonathan B.; Schipper, Matthew; Walline, Heather M.; Komarck, Christine; Feng, Felix Y.; Worden, Francis P.; Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R.; Mukherji, Suresh K.; Eisbruch, Avraham; Carey, Thomas E.

    2014-01-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings

  13. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update.

    Science.gov (United States)

    Poljak, Mario; Kocjan, Boštjan J; Oštrbenk, Anja; Seme, Katja

    2016-03-01

    Commercial molecular tests for human papillomaviruses (HPV) are invaluable diagnostic tools in cervical carcinoma screening and management of women with cervical precancerous lesions as well as important research tools for epidemiological studies, vaccine development, and implementation and monitoring of vaccination programs. In this third inventory of commercial HPV tests, we identified 193 distinct commercial HPV tests and at least 127 test variants available on the market in 2015, which represents a 54% and 79% increase in the number of distinct HPV tests and variants, respectively, in comparison to our last inventory performed in 2012. Identified HPV tests were provisionally divided into eight main groups and several subgroups. Among the 193 commercial HPV tests, all but two target alpha-HPV types only. Although the number of commercial HPV tests with at least one published study in peer-reviewed literature has increased significantly in the last three years, several published performance evaluations are still not in line with agreed-upon standards in the HPV community. Manufacturers should invest greater effort into evaluating their products and publishing validation/evaluation results in peer-reviewed journals. To achieve this, more clinically oriented external quality-control panels and initiatives are required. For evaluating the analytical performance of the entire range of HPV tests currently on the market, more diverse and reliable external quality-control programs based on international standards for all important HPV types are indispensable. The performance of a wider range of HPV tests must be promptly evaluated on a variety of alternative clinical specimens. In addition, more complete HPV assays containing validated sample-extraction protocols and appropriate internal controls are urgently needed. Provision of a broader range of automated systems allowing large-scale HPV testing as well as the development of reliable, rapid, and affordable molecular

  14. Transactivation mediated by B-Myb is dependent on TAF(II)250.

    Science.gov (United States)

    Bartusel, Thorsten; Klempnauer, Karl-Heinz

    2003-05-15

    B-Myb is a highly conserved member of the Myb family of transcription factors, which has been implicated in cell cycle regulation. B-Myb is expressed in most proliferating cells and its activity is highly regulated around the G1/S-phase border of the cell cycle. It is generally assumed that B-Myb regulates the expression of genes that are crucial for cell proliferation; however, the identity of these genes, the molecular mechanisms by which B-Myb stimulates their expression and the involvement of other proteins have not been sufficiently clarified. We have employed the hamster cell line ts13 as a tool to demonstrate a functional link between B-Myb and the coactivator TAF(II)250, a key component of the transcriptional machinery which itself is essential for cell proliferation. ts13 cells express a point-mutated version of TAF(II)250 whose intrinsic histone acetyl transferase activity is temperature sensitive. Transactivation of Myb-responsive reporter genes by B-Myb is temperature-dependent in ts13 cells but not in ts13 cells, which have been rescued by transfection with an expression vector for wild-type TAF(II)250. Furthermore, B-Myb and TAF(II)250 can be coprecipitated, suggesting that both proteins are present in a complex. The formation of this complex is dependent on the DNA-binding domain of B-Myb and not on its transactivation domain. Taken together, these observations provide the first evidence that the coactivator TAF(II)250 is involved in the activation of Myb responsive promoters by B-Myb. The finding that B-Myb transactivation is dependent on a key coactivator involved in cell cycle control is consistent with and strengthens the idea that B-Myb plays a crucial role as a transcription factor in proliferating cells.

  15. Screening of the target genes trans-activated by HLA-HA8 in hepatocytes

    Directory of Open Access Journals (Sweden)

    Qi WANG

    2011-06-01

    Full Text Available Objective To clone and identify the target genes trans-activated by human minor histocompatibility antigen HLA-HA8 in hepatocytes with suppression subtractive hybridization(SSH and bioinfomatics technique.Methods mRNA was isolated from HepG2 cells transfected by pcDNA3.1(--HLA-HA8 and pcDNA3.1(- empty vector,and then used to synthesize the double-stranded cDNA(marked as Tester and Driver,respectively by reverse transcription.After being digested with restriction enzyme Rsa I,the tester cDNA was divided into two parts and ligated to the specific adaptor 1 and adaptor 2,respectively,and then hybridized with driver cDNA twice and underwent PCR twice.The production was subcloned into pEGM-Teasy plasmid vectors to set up the subtractive library.The library was then amplified by transfection into E.coli strain DH5α.The cDNA was sequenced and analyzed in GenBank with Blast search after PCR amplification.Results The subtractive library of genes trans-activated by HLA-HA8 was constructed successfully.The amplified library contained 101 positive clones.Colony PCR showed that all these clones contained 200-1000bp inserts.Twenty eight clones were selected randomly to analyze the sequences.The result of homologous analysis showed that altogether 16 coding sequences were gotten,of which 4 sequences were with unknown function.Conclusions The obtained sequences trans-activated by HLA-HA8 may code different proteins and play important roles in cell growth and metabolism,energy synthesis and metabolism,material transport and signal transduction.This finding will bring some new clues for the studies not only on the biological functions of HLA-HA8,but also on the HBV infection mechanism.

  16. A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results.

    Science.gov (United States)

    Schiffman, Mark; Vaughan, Laurence M; Raine-Bennett, Tina R; Castle, Philip E; Katki, Hormuzd A; Gage, Julia C; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas

    2015-09-01

    In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with HPV16, 7.4% for HPV18, 7.0% for HPV31, 7.1% for grouped HPV33/58, 4.3% for HPV52, 3.9% for HPV45, 2.7% for HPV51, 1.6% for HPV39/68/35, and 1.3% for HPV59/56/66. ASC-US linked to HPV16, HPV18, HPV31, or HPV33/58 warrants immediate colposcopy. Optimal management of women with HPV52 or HPV45 is uncertain. Risk of women with only HPV51, HPV39/68/35, or HPV59/56/66 might be low enough to recommend 1-year retesting permitting viral clearance. This strategy would defer colposcopy for 40% of women with HPV-positive ASC-US, half of whom would be cotest-negative at 1-year return. Approximately 10% of those with CIN3 diagnosable at enrollment would be delayed 1year instead. Cost-effectiveness analyses are needed. Published by Elsevier Inc.

  17. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  18. A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer

    OpenAIRE

    Metzger, Eric; Müller, Judith M.; Ferrari, Stefano; Buettner, Reinhard; Schüle, Roland

    2003-01-01

    In addition to the classical activation by ligands, nuclear receptor activity is also regulated by ligand-independent signalling. Here, we unravel a novel signal transduction pathway that links the RhoA effector protein kinase C-related kinase PRK1 to the transcriptional activation of the androgen receptor (AR). Stimulation of the PRK signalling cascade results in a ligand-dependent superactivation of AR. We show that AR and PRK1 interact both in vivo and in vitro. The transactivation unit 5 ...

  19. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  20. Acceptability of HPV vaccine implementation among parents in India.

    Science.gov (United States)

    Paul, Proma; Tanner, Amanda E; Gravitt, Patti E; Vijayaraghavan, K; Shah, Keerti V; Zimet, Gregory D; Study Group, Catch

    2014-01-01

    Due to high cervical cancer rates and limited research on human papillomavirus (HPV) vaccine acceptability in India, the research team examined parental attitudes toward HPV vaccines. Thirty-six interviews with parents were conducted to assess sexually transmitted infection (STI)-related knowledge and HPV-specific vaccine awareness and acceptability. Despite limited knowledge, parents had positive views toward HPV vaccines. Common barriers included concerns about side effects, vaccine cost, and missing work to receive the vaccine. Parents were strongly influenced by health care providers' recommendations. Our findings suggest that addressing parental concerns, health worker training and polices, and efforts to minimize cost will be central to successful HPV vaccine implementation.

  1. Significant difference in p53 and p21 protein immunoreactivity in HPV 16 positive and HPV negative breast carcinomas

    International Nuclear Information System (INIS)

    Hennig, E.M.; Norwegian Radium Hospital, Oslo; Kvinnsland, S.; Holm, R.; Nesland, J.M.

    1999-01-01

    Human papillomavirus (HPV) 16 has previously been found in 19/41 breast carcinomas (46%) in women with a history of HPV 16 positive CIN III lesions. There was no significant difference in distribution of histological subtypes, mean or median tumour diameter or number of regional lymph node metastases in the HPV positive and HPV negative breast carcinoma groups. P53, p21 and c-erbB-2 proteins were analyzed by immunohistochemistry in the HPV 16 positive and HPV negative breast carcinomas. There was a significant difference in p53 and p21 protein immunoreactivity between HPV 16 positive and HPV negative breast carcinomas (p=0.0091 and p=0.0040), with a significant less detectable p53 and p21 protein immunoreactivity in the HPV 16 positive cases. There was also a significant difference in the coexpression of p53/p21 between the HPV 16 positive and HPV 16 negative breast carcinomas (p=0.002). No significant difference in immunostaining for c-erbB-2 protein in the two groups was found (p=0.15), or for the coexpression of p53/c-erbB-2 (p=0.19). The significantly lower expression of p53 and p21 proteins in HPV 16 positive than in HPV 16 negative breast carcinomas supports the hypothesis of inactivation and degradation of wild-type p53 proteins by HPV 16 E6 and that p53 mutation is not necessary for transformation in the HPV 16 positive cases. (orig.)

  2. HPV primary cervical screening in England: Women's awareness and attitudes.

    Science.gov (United States)

    Patel, Hersha; Moss, Esther L; Sherman, Susan M

    2018-03-09

    Primary human papillomavirus (HPV) cervical screening is due to be implemented in England within the next 2 years; however, the acceptability of HPV testing as the primary screening test is unclear. This study explores women's awareness and attitudes toward HPV testing/screening. Qualitative interviews (semistructured and focus group) were conducted with 46 women (aged 25-65 years) from community and secondary care settings. Data were analyzed by using the inductive-framework method. Women were unaware that cervical screening currently includes HPV testing and lacked HPV-related knowledge. Emotions of shock, fear, and anxiety were reported upon receiving a positive HPV result. For women in long-term relationships, the realization that HPV is a sexually transmitted infection was seen as a barrier to primary HPV testing. Knowledge that HPV testing is a screening test to prevent cervical cancer did not change their attitudes. Women debated the need for continued screening following a negative result. Women feared judgment by the community if they participated with primary HPV screening because they were being tested for a sexually transmitted infection, with the possible attendant perception that they had adopted a high-risk lifestyle in comparison to nonattenders. The acceptability of HPV testing may be a limiting factor in encouraging participation with screening in the future. Copyright © 2018 John Wiley & Sons, Ltd.

  3. The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model

    OpenAIRE

    Chesson, Harrell W.; Markowitz, Lauri E.; Hariri, Susan; Ekwueme, Donatus U.; Saraiya, Mona

    2016-01-01

    Introduction: The objective of this study was to assess the incremental costs and benefits of the 9-valent HPV vaccine (9vHPV) compared with the quadrivalent HPV vaccine (4vHPV). Like 4vHPV, 9vHPV protects against HPV types 6, 11, 16, and 18. 9vHPV also protects against 5 additional HPV types 31, 33, 45, 52, and 58. Methods: We adapted a previously published model of the impact and cost-effectiveness of 4vHPV to include the 5 additional HPV types in 9vHPV. The vaccine strategies we examined w...

  4. HPV-testing versus HPV-cytology co-testing to predict the outcome after conization.

    Science.gov (United States)

    Bruhn, Laerke Valsøe; Andersen, Sisse Josephine; Hariri, Jalil

    2018-06-01

    The purpose of this study was to determine the feasibility of human Papillomavirus (HPV) testing alone as a prognostic tool to predict recurrent disease within a three-year follow-up period after treatment for cervical intraepithelial neoplasia (CIN)2 + . Retrospectively, 128 women with histologically verified CIN2 + who had a conization performed at Southern Jutland Hospital in Denmark between 1 January 2013 and 31 December 2013 were included. Histology, cytology and HPV test results were obtained for a three-year follow-up period. 4.7% (6/128) of the cases developed recurrent disease during follow-up. Of the cases without free margins, recurrent dysplasia was detected normal in 10.4% (5/48), whereas in the group with free margins it was 1.3% (1/80). The post-conization HPV test was negative in 67.2% (86/128) and Pap smear normal in 93.7% (120/128). Combining resection margins, cytology and HPV had sensitivity for prediction of recurrent dysplasia of 100%. Specificity was 45.8%, positive predictive value (PPV) 8.5% and negative predictive value (NPV) 100%. Using HPV test alone as a predictor of recurrent dysplasia gave a sensitivity of 83.3%, specificity 69.7%, PPV 11.9% and NPV 98.8%. Combining resection margin and HPV test had a sensitivity of 100%, specificity 45.9%, PPV 8.3% and NPV 100%. HPV test at six months control post-conization gave an NPV of 98.8% and can be used as a solitary test to identify women at risk for recurrent disease three years after treatment for precursor lesions. Using both resection margin and HPV test had a sensitivity of 100% and NPV 100%. Adding cytology did not increase the predictive value. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

  5. Young Hungarian Students’ Knowledge about HPV and Their Attitude Toward HPV Vaccination

    Directory of Open Access Journals (Sweden)

    Bettina Claudia Balla

    2016-12-01

    Full Text Available (1 Background: Hungarys’s estimated cervical cancer mortality was 6.9/100,000 in 2012, above the average of the EU27 countries (3.7/100,000 in the same year. Since 2014, the bivalent HPV vaccine has been offered to schoolgirls aged 12–13. (2 Methods: We conducted a cross-sectional study among 1022 high school seniors (492 girls, 530 boys in 19 randomly selected schools in Budapest. Our anonymous questionnaire contained 54 items: basic socio-demographic data, knowledge about HPV infection/cervical cancer and HPV vaccination. (3 Results: 54.9% knew that HPV caused cervical cancer, and 52.1% identified HPV as an STD. Knowledge of risk factors such as promiscuity (46.9% and early sexual activity (15.6% was low, but higher than that of further HPV-induced diseases: genital warts (in females 9.9%, in males 9%, anal cancer (in females 2.2%, in males 1.9%, penile cancer (9.4%, and vulvar cancer (7.8%. A percentage of 14.6% feared getting infected, and 35.7% supported compulsory HPV vaccination. A percentage of 51.2% would have their future children vaccinated—significantly more girls than boys. (4 Conclusion: Our results support the findings of previous studies about young adults’ HPV-related knowledge, which was poor, especially regarding pathologies in men. Despite the low level of awareness, the students’ attitude was mostly positive when asked about vaccinating their future children.

  6. Sequence imputation of HPV16 genomes for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Benjamin Smith

    Full Text Available Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity.A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica.HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution.Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable resource for future studies of HPV16

  7. One Family's Struggles with HPV (Human Papillomavirus)

    Medline Plus

    Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...

  8. Cancers Caused by HPV PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.)

  9. Cervical Cancer Screening with HPV Test

    Centers for Disease Control (CDC) Podcasts

    Dr. Stewart Massad, a professor in the Division of Gynecologic Oncology at Washington University in Saint Louis and a board member of the American Society for Colposcopy and Cervical Cancer Prevention (ASCCP), talks about cotesting with human papillomavirus (HPV) as part of a cervical cancer screening program.

  10. One Family's Struggles with HPV (Human Papillomavirus)

    Medline Plus

    Full Text Available ... immunizations about immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids ... abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus ...

  11. One Family's Struggles with HPV (Human Papillomavirus)

    Medline Plus

    Full Text Available ... and meningitis Stiletto and Extremus posters videos mono pertussis Silence the Sounds of Pertussis Acalla los Sonidos de la Tos Ferina AAP ... a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's ...

  12. HPV knowledge and factors associated with intention to use condoms for reducing HPV infection risk among adolescent women in Taiwan.

    Science.gov (United States)

    Tu, Yu-Ching; Wang, Hsiu-Hung; Lin, Yi-Jung; Chan, Te-Fu

    2015-01-01

    Human papillomavirus (HPV) is a frequent cause of sexually transmitted infection worldwide, and has a key role in the etiology of cervical cancer. Young people are the most vulnerable age group for acquiring HPV infection, but this particular age group in Taiwan knows little about it. This study investigated Taiwanese adolescent women's knowledge of HPV and factors associated with intention to use condoms for reducing HPV-related diseases among adolescent women. A descriptive cross-sectional design was used, and a convenience sample of 384 adolescent women aged 15 to 16 years in Southern Taiwan was recruited. Data were collected using a self-administered questionnaire and analyzed with descriptive statistics, t-test or ANOVA, and multiple regression analysis. Only 26.6% of the participants were aware of HPV. The percentage of correct answers for knowledge about HPV was 35.4%. Factors associated with intention to use condoms for HPV prevention were discussion of sexual issues, attitude, subjective norm, perceived behavioral control, and HPV knowledge. These variables accounted for 55.8% of the variance in scores for intention to use condoms for HPV prevention. These findings could be used in future HPV prevention education and campaigns. Future intervention programs might be particularly focused on insufficient HPV knowledge among adolescent females.

  13. Roscovitine strongly enhances the effect of olaparib on radiosensitivity for HPV neg. but not for HPV pos. HNSCC cell lines.

    Science.gov (United States)

    Ziemann, Frank; Seltzsam, Steve; Dreffke, Kristin; Preising, Stefanie; Arenz, Andrea; Subtil, Florentine S B; Rieckmann, Thorsten; Engenhart-Cabillic, Rita; Dikomey, Ekkehard; Wittig, Andrea

    2017-12-01

    At present, advanced stage human Papillomavirus (HPV) negative and positive head and neck squamous cell carcinoma (HNSCC) are treated by intense multimodal therapy that includes radiochemotherapy, which are associated with relevant side effects. Patients with HPV positive tumors possess a far better prognosis than those with HPV negative cancers. Therefore, new therapeutic strategies are needed to improve the outcome especially of the latter one as well as quality of life for all HNSCC patients. Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and 2. Surprisingly, all HPV positive cell lines were found to be defective in HR. In contrast, HPV negative strains demonstrated efficient HR, which was completely suppressed by roscovitine. In line with this, for HPV negative but not for HPV positive cell lines, treatment with roscovitine resulted in a pronounced enhancement of the radiation-induced G2 arrest as well as a significant increase in radiosensitivity. Due to a defect in HR, all HPV positive cell lines were efficiently radiosensitized by the PARP-1 inhibitor olaparib. In contrast, in HPV negative cell lines a significant radiosensitization by olaparib was only achieved when combined with roscovitine.

  14. Beliefs about cervical cancer and human papillomavirus (HPV) and acceptability of HPV vaccination among Chinese women in Hong Kong.

    Science.gov (United States)

    Lee, Peter W H; Kwan, Tracy T C; Tam, Kar Fai; Chan, Karen K L; Young, Phyllis M C; Lo, Sue S T; Cheung, Annie N Y; Ngan, Hextan Y S

    2007-01-01

    To assess the knowledge and beliefs on cervical cancer and HPV infection and to evaluate the acceptability of HPV vaccination among Chinese women. Seven focus groups were conducted with ethnic Chinese women aged 18-25 (n=20), 26-35 (n=13), and 36 and above (n=16) in a community women's health clinic in Hong Kong in 2006. The discussions were audio taped, transcribed and analyzed. Recurrent themes related to cervical cancer, HPV infection and vaccination were highlighted. Diverse conceptions on likely causes of cervical cancer were noted, covering biological, psychological, environmental, lifestyle and sexual factors. Most women had not heard of HPV and its mode of transmission. The participants had difficulties understanding and accepting the linkage between cervical cancer and the sexually transmitted HPV infection. HPV infection was seen as personally stigmatizing with significant adverse impact on self-esteem and significant relationships. Participants favored HPV vaccination both for themselves and their teenage daughters if authoritative endorsement was provided. Inadequate knowledge and misconceptions on cervical cancer and HPV were common. Most participants welcomed and favored having HPV vaccination. Apart from promoting HPV vaccination, cervical cancer prevention should also include strategies to promote knowledge and minimize the stigmatizing effect of a sexually transmitted HPV infection.

  15. NLRC5/MHC class I transactivator is a target for immune evasion in cancer.

    Science.gov (United States)

    Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A; Lizee, Gregory A; Kobayashi, Koichi S

    2016-05-24

    Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

  16. Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

    Science.gov (United States)

    Constantinidis, Theocharis; Constantinidis, Theodoros C.

    2015-01-01

    Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18

  17. HPV vaccination acceptability in young boys

    Directory of Open Access Journals (Sweden)

    Giancarlo Tisi

    2013-09-01

    Full Text Available PURPOSE: The aim of this study was to evaluate the comprehension and acceptance of HPV vaccination in parents of adolescent boys aged 11 to 15 years. METHODS: A cross-sectional survey was conducted by means of questionnaires sent directly to the homes of all families with young males aged between 11 and 15, residents of three municipalities of the Province of Brescia, Italy. The documentation also contained an informative leaflet summarizing the HPV-related disease characteristics, the burden of disease and the available strategies for prevention and treatment, illustrating the rationale of vaccination and describing the project and its phases. The questionnaire included questions on demographic data, acceptance and motivations for HPV vaccination. The collected data was analyzed using descriptive statistics. At the end of the study, parents who received the questionnaires were also offered the possibility of vaccinating their male sons for free. RESULTS: From a total of 1072 questionnaires sent, 161 where returned from the three selected municipalities (average response rate 15%; 97% of adolescent males involved in the study were Italian and 91% Catholic; 97% of parents declared themselves to be willing to vaccinate their sons: the principal motivation given (92% was prevention of the disease, cancerous or not, related to viral infection. Among the respondents not willing to vaccinate their sons, the motivation was lack of information about the vaccine and the disease. At the end of the study, around 71 boys were vaccinated. DISCUSSION: To our knowledge, this is the first survey in Italy exclusively conducted on parents of adolescent males about the acceptability and feasibility of vaccination against HPV: a very high percentage of respondents was favorable to accept the vaccination for their sons, the main motivation being the fact that parents considered protecting their sons from HPV-related diseases highly important. Of the 161 boys

  18. Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study.

    Science.gov (United States)

    Sichero, Laura; Pierce Campbell, Christine M; Ferreira, Silvaneide; Sobrinho, João S; Luiza Baggio, Maria; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L

    2013-09-01

    The HPV infection in men (HIM) study examines the natural history of genital HPV infection in men. Genotyping methods used in this study identify 37 α-HPV types; however, the viral type could not be identified in approximately 22% of male genital specimens that were HPV PCR positive. Our aim was to genotype HPV-unclassified specimens by sequencing PGMY09/11, GP5+/6+ or FAP59/64 PCR products. Using this approach we were able to detect 86 unique HPV types among 508 of 931 specimens analyzed. We report for the first time the presence of a broad range of α-, β- and γ-HPV at the male genitals. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPV-unvaccinated young Italian females with normal cytology.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Bianchi, Silvia; Frati, Elena Rosanna; Zotti, Carla Maria; Lai, Piero Luigi; Domnich, Alexander; Colzani, Daniela; Gasparini, Roberto; Tanzi, Elisabetta

    2015-01-01

    Infections caused by Chlamydia trachomatis (Ct) and human papillomavirus (HPV) are the two main sexually transmitted infections; however, epidemiological data on Ct prevalence and Ct/HPV co-infection in Italy are scant. This study aimed at estimating the prevalence of Ct infection and Ct/HPV co-infection in young HPV-unvaccinated females with normal cytology, and placed particular attention on the possible association between Ct-DNA positivity and different HPV infecting genotypes. Five hundred 66 healthy females aged 16-26 years without cervical lesions, previously assessed for HPV infection (HPV-DNA prevalence: 18.2%), were tested for Ct-DNA. The overall prevalence of Ct was 5.8% (95% CI: 4.2-8.1), while Ct/HPV co-infection was recorded in 2.7% (95% CI: 1.6-4.3) of subjects. Compared with HPV-DNA-negative females, HPV-DNA positive subjects had significantly (P < 0.001) higher odds of being infected with Ct (odds ratio of 4.20, 95% CI: 2.01-8.71). Both Ct and Ct/HPV infections were much more prevalent in under 18-year-olds than in older women. Subjects positive for single high-risk HPV genotypes and various multiple HPV infections had higher odds of being Ct-DNA positive. Our findings confirm that HPV and Ct infections are very common among asymptomatic young Italian females. This underlines the urgent need for nationwide Ct screening programs and reinforcement of sexual health education, which would be the most important public health strategies, since no Ct vaccines are currently available.

  20. Factors that Predict Parental Willingness to Have Their Children Vaccinated against HPV in a Country with Low HPV Vaccination Coverage.

    Science.gov (United States)

    Ganczak, Maria; Owsianka, Barbara; Korzeń, Marcin

    2018-03-31

    Background: Adolescent HPV (Human Papilloma Virus) vaccination is yet to be introduced as a mandatory program in Poland. Polish literature on factors associated with adolescent HPV vaccination is scant, despite the fact that uptake is one of the poorest in the European Union. Objectives: To assess HPV awareness and identify independent predictors for parental willingness to have their children vaccinated against HPV. Methods: All parents of first grade students from three selected high schools in Zgorzelec, Poland, who participated in parent-teacher meetings at the time the study was conducted, had their children unvaccinated regarding HPV, and who gave informed consent to participate were included. There were 600 first grade students; 9 were vaccinated against HPV. This left 591 parents who met the eligibility criteria; the response rate was 76.1%. Results: Awareness of HPV was reported by 55.3% of 450 parents (mean age 42 years, 70.9% females); 85.1% expressed their willingness to vaccinate their children against HPV; 31.3% identified HPV as a sexually transmitted pathogen, and 36.2% identified it as a risk factor of cervical cancer. Multivariable logistic regression analyses indicated that being employed (OR 2.09; 95% CI: 1.10-3.86), having positive attitudes toward vaccines (OR 3.02; 95% CI: 1.34-6.49), previous information about HPV (OR 2.02; 95% CI: 1.17-3.51), and concerns about the side effects of the HPV vaccine (OR 0.60; 95% CI: 0.35-0.99) were independent predictors of parents' willingness to vaccinate. Conclusions: Attitudes regarding their child being vaccinated against HPV were positive among Polish parents, even though awareness and knowledge of HPV in this group were low. Most of the significant factors that influenced their willingness were modifiable, such as being informed about HPV and having positive attitudes toward vaccines. Future interventions should focus specifically on vulnerable subgroups, such as unemployed parents.

  1. Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection.

    Science.gov (United States)

    Halfon, Philippe; Benmoura, Dominique; Agostini, Aubert; Khiri, Hacene; Penaranda, Guillaume; Martineau, Agnes; Blanc, Bernard

    2010-08-01

    Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in Abbott RT HR HPV assay is good and closely correlated with the two other assays. The automation and ability to identify type 16 and 18 make this a very attractive option for HPV testing in laboratories and potentially provides improved patient management. Copyright 2010. Published by Elsevier B.V.

  2. HPV detection in oral carcinomas Detecção do HPV em carcinomas orais

    Directory of Open Access Journals (Sweden)

    Aurora Karla de Lacerda Vidal

    2004-02-01

    Full Text Available The authors set out in this study to verify the presence of low- and high-risk DNA of human papillomavirus (HPV in oral cancer by means of the hybrid capture Digene® test (São Paulo-SP, Brazil in smears from exfoliative cytology and also to compare the findings with those of conventional light microscopy (hematoxylin-eosin (HE/Papanicolaou. Forty individuals gave their written informed consent to participate in the study and also had their clinical data analyzed. The 40 exfoliative cytology examinations performed to date produced the following results: 29 (72.5% negative for low- and high-risk HPV-DNA; nine (22.5% positive for low- and high-risk HPV-DNA; one (2.5% positive for low-risk HPV-DNA; and one (2.5% positive for high-risk HPV-DNA. There was agreement among the findings for the presence of DNA-HPV for both exfoliative cytology (smear to hybrid capture Digene® test and the cytological smear readings made by conventional light microscopy. It was therefore concluded that the HPV virus may be a cocarcinogen of the mouth cancer as it is in the cervix cancer.Os autores buscaram verificar, neste estudo, a presença do papilomavírus humano (HPV de baixo e de alto risco em carcinomas orais através do teste de captura híbrida Digene® (São Paulo-SP, Brasil em amostras colhidas pela citologia esfoliativa bucal e, ainda, avaliar comparativamente as referidas leituras com alterações celulares indicativas deste vírus obtidas com a interpretação citológica óptica convencional (hematoxilina-eosina (HE/Papanicolaou. Quarenta indivíduos concordaram, espontaneamente, através de assinatura do termo de consentimento livre e esclarecido, em participar da pesquisa, e seus dados clínicos foram analisados. Entre as 40 amostras provenientes da citologia esfoliativa 29 (72,5% mostraram-se negativas para presença de HPV-DNA de baixo e de alto risco; nove (22,5% foram positivas para o HPV-DNA de baixo e de alto risco; uma (2,5% foi positiva apenas

  3. Eurogin 2016 Roadmap: how HPV knowledge is changing screening practice.

    Science.gov (United States)

    Wentzensen, Nicolas; Arbyn, Marc; Berkhof, Johannes; Bower, Mark; Canfell, Karen; Einstein, Mark; Farley, Christopher; Monsonego, Joseph; Franceschi, Silvia

    2017-05-15

    Human papillomaviruses (HPVs) are the necessary cause of most cervical cancers, a large proportion of other anogenital cancers, and a subset of oropharyngeal cancers. The knowledge about HPV has led to development of novel HPV-based prevention strategies with important impact on clinical and public health practice. Two complementary reviews have been prepared following the 2015 Eurogin Conference to evaluate how knowledge about HPV is changing practice in HPV infection and disease control through vaccination and screening. This review focuses on screening for cervical and anal cancers in increasingly vaccinated populations. The introduction of HPV vaccines a decade ago has led to reductions in HPV infections and early cancer precursors in countries with wide vaccination coverage. Despite the high efficacy of HPV vaccines, cervical cancer screening will remain important for many decades. Many healthcare systems are considering switching to primary HPV screening, which has higher sensitivity for cervical precancers and allows extending screening intervals. We describe different approaches to implementing HPV-based screening efforts in different healthcare systems with a focus in high-income countries. While the population prevalence for other anogenital cancers is too low for population-based screening, anal cancer incidence is very high in HIV-infected men who have sex with men, warranting consideration of early detection approaches. We summarize the current evidence on HPV-based prevention of anal cancers and highlight important evidence gaps. © 2016 UICC.

  4. Surrogate for oropharyngeal cancer HPV status in cancer database studies.

    Science.gov (United States)

    Megwalu, Uchechukwu C; Chen, Michelle M; Ma, Yifei; Divi, Vasu

    2017-12-01

    The utility of cancer databases for oropharyngeal cancer studies is limited by lack of information on human papillomavirus (HPV) status. The purpose of this study was to develop a surrogate that can be used to adjust for the effect of HPV status on survival. The study cohort included 6419 patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012, identified in the National Cancer Database (NCDB). The HPV surrogate score was developed using a logistic regression model predicting HPV-positive status. The HPV surrogate score was predictive of HPV status (area under the curve [AUC] 0.73; accuracy of 70.4%). Similar to HPV-positive tumors, HPV surrogate positive tumors were associated with improved overall survival (OS; hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.59-0.91; P = .005), after adjusting for important covariates. The HPV surrogate score is useful for adjusting for the effect of HPV status on survival in studies utilizing cancer databases. © 2017 Wiley Periodicals, Inc.

  5. Parental acceptance of HPV vaccines in Chiang Mai, Thailand.

    Science.gov (United States)

    Juntasopeepun, Phanida; Thana, Kanjana

    2018-06-01

    To identify variables associated with the acceptance of HPV vaccination among Thai parents/primary caregivers. The present prospective cross-sectional study recruited the parents/caregivers of female adolescents aged 12-18 years from schools in Chiang Mai, Thailand, between January 1 and February 29, 2016. A four-part questionnaire was distributed to assess demographics, HPV vaccine acceptance, knowledge, and beliefs toward HPV and cervical cancer. Predictors of HPV vaccine acceptance were determined by logistic regression analysis. The study enrolled 331 parents; more than half (195 [61.1%]) had heard of HPV vaccines. Their knowledge related to HPV and cervical cancer was moderate. A majority of parents (266/313 [85.0%]) indicated they would accept HPV vaccination if the costs were subsidized by the government. Acceptance of HPV vaccines was associated with perceived benefits of HPV vaccination (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.18-1.88), perceived susceptibility to disease (OR 1.42; 95% CI 1.11-1.81), and household income (OR 1.35; 95% CI 1.02-1.78). Parental beliefs have an important role in their acceptance to vaccinate their daughters. These potentially modifiable beliefs offer strategies for future interventions designed to increase uptake for future HPV vaccination campaigns. © 2018 International Federation of Gynecology and Obstetrics.

  6. Human papilloma viruses and cervical tumours: mapping of integration sites and analysis of adjacent cellular sequences

    International Nuclear Information System (INIS)

    Klimov, Eugene; Vinokourova, Svetlana; Moisjak, Elena; Rakhmanaliev, Elian; Kobseva, Vera; Laimins, Laimonis; Kisseljov, Fjodor; Sulimova, Galina

    2002-01-01

    In cervical tumours the integration of human papilloma viruses (HPV) transcripts often results in the generation of transcripts that consist of hybrids of viral and cellular sequences. Mapping data using a variety of techniques has demonstrated that HPV integration occurred without obvious specificity into human genome. However, these techniques could not demonstrate whether integration resulted in the generation of transcripts encoding viral or viral-cellular sequences. The aim of this work was to map the integration sites of HPV DNA and to analyse the adjacent cellular sequences. Amplification of the INTs was done by the APOT technique. The APOT products were sequenced according to standard protocols. The analysis of the sequences was performed using BLASTN program and public databases. To localise the INTs PCR-based screening of GeneBridge4-RH-panel was used. Twelve cellular sequences adjacent to integrated HPV16 (INT markers) expressed in squamous cell cervical carcinomas were isolated. For 11 INT markers homologous human genomic sequences were readily identified and 9 of these showed significant homologies to known genes/ESTs. Using the known locations of homologous cDNAs and the RH-mapping techniques, mapping studies showed that the INTs are distributed among different human chromosomes for each tumour sample and are located in regions with the high levels of expression. Integration of HPV genomes occurs into the different human chromosomes but into regions that contain highly transcribed genes. One interpretation of these studies is that integration of HPV occurs into decondensed regions, which are more accessible for integration of foreign DNA

  7. Barriers and Facilitators of HPV Vaccination in the VFC Program.

    Science.gov (United States)

    Fleming, Wayne S; Sznajder, Kristin K; Nepps, Margaret; Boktor, Sameh W

    2018-06-01

    This study determined facilitators and barriers to human papillomavirus (HPV) vaccination perceived by providers of healthcare in the federally funded Pennsylvania Vaccines for Children (PA VFC) program. The cross-sectional study gathered descriptive data through a survey research design. Providers of healthcare were recruited through an email containing a link to an 18-question online survey. The survey was divided into four main sections which assessed the perceived facilitators and barriers to HPV vaccination of PA VFC program-eligibles. Survey respondents represented 65 of 66 Pennsylvania counties covered by the PA VFC Program. The study recruited 772 PA VFC participating healthcare facilities for a response rate of 52%. Ninety eight percent of the responding facilities reported that they offered the HPV vaccine. The most common barriers to vaccine administration were the parental belief that HPV vaccination is associated with sexual activity and parent/patient refusal of the HPV vaccination which together accounted for (44%) of responses. The majority of respondents (75.6%) indicated counseling parents and adolescents on the benefits of HPV vaccination was a very important factor in HPV vaccination uptake. Healthcare provider facility based training (32%) and web-based training for healthcare providers (22%) were the most recommended avenues for HPV training. The most common barrier to HPV vaccination was identified as the parental misconception that HPV vaccination is associated with sexual activity. Providers believed that the best way to increase HPV vaccination is through counseling parents and adolescents on the benefits of HPV vaccination and to correct misconceptions and change attitudes. Providers are desirous of receiving HPV web-based or workplace training.

  8. Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

    Science.gov (United States)

    Lim, Myong Cheol; Lee, Do-Hoon; Hwang, Sang-Hyun; Hwang, Na Rae; Lee, Bomyee; Shin, Hye Young; Jun, Jae Kwan; Yoo, Chong Woo; Lee, Dong Ock; Seo, Sang-Soo; Park, Sang-Yoon; Joo, Jungnam

    2017-05-01

    Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off C T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the C T threshold. Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off C T value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV

  9. Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T Cell Mediated Tumor Control in the Genital Tract

    Science.gov (United States)

    Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B.S.; Trimble, Cornelia L.; Hung, Chien-Fu; Wu, T-C

    2015-01-01

    Purpose Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Experimental Design Here we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than IM delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc). Results We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Conclusions Our results support future clinical translation using cervicovaginal TA-HPV vaccination. PMID:26420854

  10. Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development.

    Science.gov (United States)

    Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R

    2018-01-17

    When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights

  11. HPV-QUEST: A highly customized system for automated HPV sequence analysis capable of processing Next Generation sequencing data set.

    Science.gov (United States)

    Yin, Li; Yao, Jiqiang; Gardner, Brent P; Chang, Kaifen; Yu, Fahong; Goodenow, Maureen M

    2012-01-01

    Next Generation sequencing (NGS) applied to human papilloma viruses (HPV) can provide sensitive methods to investigate the molecular epidemiology of multiple type HPV infection. Currently a genotyping system with a comprehensive collection of updated HPV reference sequences and a capacity to handle NGS data sets is lacking. HPV-QUEST was developed as an automated and rapid HPV genotyping system. The web-based HPV-QUEST subtyping algorithm was developed using HTML, PHP, Perl scripting language, and MYSQL as the database backend. HPV-QUEST includes a database of annotated HPV reference sequences with updated nomenclature covering 5 genuses, 14 species and 150 mucosal and cutaneous types to genotype blasted query sequences. HPV-QUEST processes up to 10 megabases of sequences within 1 to 2 minutes. Results are reported in html, text and excel formats and display e-value, blast score, and local and coverage identities; provide genus, species, type, infection site and risk for the best matched reference HPV sequence; and produce results ready for additional analyses.

  12. Clinical and epidemiological correlations between the infection with HPV 16 and HPV 18 and female cervical lesions.

    Science.gov (United States)

    Stoian, M; Repanovici, R; Corniţescu, F

    1995-01-01

    A number of 66 specimens from female cervical lesions were examined for infection with human papillomavirus (HPV) types 6, 11, 16, and 18 by nucleic acid hybridization in dot-blot techniques and 35 sera were tested by the immunodot-blot technique, in order to detect the presence of anti E4 and E7 HPV protein antibodies. The findings were compared with the histologic diagnosis. Fifty-six per cent of specimens contained HPV DNA sequences. In 47% of specimens from cervical carcinoma, HPV 11 was detected in 4 cases, HPV 16 in 21 cases, and HPV 18 in 7 cases. Serum antibodies against HPV 16 E4 and HPV 16 E7 occurred in all the cases of uterine carcinoma, in 4 of 10 cases of CIN I-II, and in 3 of 5 sera obtained from apparently healthy women. The analysis of risk factors disclosed the early onset of sexual activity, a relatively high number of births and abortions before the age of 22 years, the use of oral oestroprogestative contraceptive agents, the presence in anamnesis of genital infections with bacterial flora--Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Mycoplasma, etc. Our results showed that HPV typing by nucleic acid hybridization was useful for differentiating low- from high-risk cervical lesions and also tried to elucidate the risk factors associated with HPV infections and progression to malignancy.

  13. Seroconversion following anal and genital HPV infection in men: The HIM study

    Directory of Open Access Journals (Sweden)

    Anna R. Giuliano

    2015-12-01

    Full Text Available Background: Protection from naturally acquired human papillomavirus (HPV antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Methods: Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Results: Seroconversion to ≥1 HPV type (6/11/16/18 in this sub-cohort (N=384 varied by anatomic site, with 6.3%, 18.9%, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%. Overall, seroconversion was highest following anal HPV 6 infection (69.2%. HPV persistence was the only factor found to influence seroconversion. Conclusions: Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease. Keywords: HPV, Men, Seroconversion, HPV antibodies, Human papillomavirus

  14. Relationship between Humoral Immune Responses against HPV16, HPV18, HPV31 and HPV45 in 12-15 Year Old Girls Receiving Cervarix® or Gardasil® Vaccine.

    Directory of Open Access Journals (Sweden)

    Anna Godi

    Full Text Available Human papillomavirus (HPV vaccines confer protection against the oncogenic genotypes HPV16 and HPV18 through the generation of type-specific neutralizing antibodies raised against virus-like particles (VLP representing these genotypes. The vaccines also confer a degree of cross-protection against HPV31 and HPV45, which are genetically-related to the vaccine types HPV16 and HPV18, respectively, although the mechanism is less certain. There are a number of humoral immune measures that have been examined in relation to the HPV vaccines, including VLP binding, pseudovirus neutralization and the enumeration of memory B cells. While the specificity of responses generated against the vaccine genotypes are fairly well studied, the relationship between these measures in relation to non-vaccine genotypes is less certain.We carried out a comparative study of these immune measures against vaccine and non-vaccine genotypes using samples collected from 12-15 year old girls following immunization with three doses of either Cervarix® or Gardasil® HPV vaccine.The relationship between neutralizing and binding antibody titers and HPV-specific memory B cell levels for the vaccine genotypes, HPV16 and HPV18, were very good. The proportion of responders approached 100% for both vaccines while the magnitude of these responses induced by Cervarix® were generally higher than those following Gardasil® immunization. A similar pattern was found for the non-vaccine genotype HPV31, albeit at a lower magnitude compared to its genetically-related vaccine genotype, HPV16. However, both the enumeration of memory B cells and VLP binding responses against HPV45 were poorly related to its neutralizing antibody responses. Purified IgG derived from memory B cells demonstrated specificities similar to those found in the serum, including the capacity to neutralize HPV pseudoviruses.These data suggest that pseudovirus neutralization should be used as the preferred humoral immune

  15. Prevalence of HPV 16 and 18 and attitudes toward HPV vaccination trials in patients with cervical cancer in Mali

    Science.gov (United States)

    Téguété, Ibrahima; Dolo, Amadou; Sangare, Kotou; Sissoko, Abdoulaye; Rochas, Mali; Beseme, Sarah; Tounkara, Karamoko; Yekta, Shahla; De Groot, Anne S.; Koita, Ousmane A.

    2017-01-01

    Background Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. Aim We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. Methods Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. Results HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. Conclusion This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali. PMID:28231334

  16. Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF).

    Science.gov (United States)

    Kubo, E; Fatma, N; Sharma, P; Shinohara, T; Chylack, L T; Akagi, Y; Singh, D P

    2002-07-26

    Human involucrin (hINV), first appears in the cytosol of keratinocytes and ultimately cross-linked to membrane proteins via transglutaminase and forms a protective barrier as an insoluble envelope beneath the plasma membrane. Although the function and evolution of involucrin is known, the regulation of its gene expression is not well understood. An analysis of the hINV gene sequence, upstream of the transcription start site (-534 to +1 nt) revealed the presence of potential sites for binding of lens epithelium-derived growth factor (LEDGF); stress response element (STRE; A/TGGGGA/T) and heat shock element (HSE; nGAAn). We reported earlier that LEDGF activates stress-associated genes by binding to these elements and elevates cellular resistance to various stresses. Here, gel-shift and super-shift assays confirm the binding of LEDGF to the DNA fragments containing HSEs and STREs that are present in the involucrin gene promoter. Furthermore, hINV promoter linked to CAT reporter gene, cotransfected in human corneal simian virus 40-transformed keratinocytes (HCK), was transactivated by LEDGF significantly. In contrast, the activity of hINV promoter bearing mutations at the WT1 (containing HSE and STRE), WT2 (containing STRE) and WT3 (containing STRE) binding sites was diminished. In addition, in HCK cell over-expressing LEDGF, the levels of hINV mRNA and hINV protein are increased by four to five-fold. LEDGF is inducible to oxidants. Cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate production of H(2)O(2), showed higher levels of LEDGF mRNA. Furthermore, our immunohistochemical studies revealed that hINV protein is found in the cytoplasm of HCK cells over-expressing LEDGF, but not detectable in the normal HCK cells or HCK cells transfected with vector. This regulation appears to be physiologically important, as over-expression of HCK with LEDGF increases the expression of the endogenous hINV gene and may provide new insight to understand

  17. HPV (Human Papillomavirus) Gardasil® Vaccine - what you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine - Gardasil® Vaccine Information Statement (VIS): www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv-gardasil.html . CDC review information for HPV Gardasil® ...

  18. HPV vaccine (Human Papillomavirus) Cervarix® - what you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC HPV (Human Papillomavirus) Cervarix® Vaccine Information Statement: www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv-cervarix.html . CDC review information for HPV Cervarix® ...

  19. Significance of molecular diagnostics in human papilloma virus (HPV determination

    Directory of Open Access Journals (Sweden)

    Kovačević G.

    2014-01-01

    Full Text Available HPV infection is considered to be the most important etiologic factor in cervical cancer development. In this retrospective study, which included the period from 2000 to 2012, the results of two molecular techniques used in the detection of HPV infection among women of the South Bačka District were analyzed. By using the technique of in situ hybridization and the rPCR method, the proportion of high-risk HPV among women with normal cytology was determined to be 19.8% and 32.7%, respectively, and among women with abnormal cytology 43.1% and 61%, respectively. Among the analyzed women, HPV type 16 was the most prevalent, followed by HPV types 31, 51 and 18. Application of molecular HPV diagnosis is valuable because it increases the sensitivity of the screening test, so that the application of both tests to detect cervical cancer is a true prevention of malignancy.

  20. Ethnic and Racial Disparities in HPV Vaccination Attitudes.

    Science.gov (United States)

    Otanez, Staci; Torr, Berna M

    2017-12-20

    There are substantial racial and ethnic disparities in the vaccination rate for human papillomavirus (HPV), which helps protect against cervical cancer. Using data from the 2007 Health Information National Trends Survey, we explore differences between Whites, Blacks, Hispanics, and Asians in attitudes toward vaccinating adolescent girls for HPV. We use logistic regression models to explore whether racial/ethnic differences in attitudes toward HPV vaccinations are explained by HPV knowledge, demographic and socioeconomic status, and/or general distrust of the healthcare system. We include interactions to explore whether the effects of HPV knowledge and doctor distrust vary by racial/ethnic group. We find that greater HPV knowledge increases general willingness to vaccinate for all groups except Blacks. Our findings point to a need for additional research and design of culturally appropriate interventions that address barriers to vaccination.

  1. Overview of Current Humman Papilloma Virus (HPV Vaccination

    Directory of Open Access Journals (Sweden)

    Cumhur Artuk

    2013-06-01

    Full Text Available Persistent viral infection with high-risk human papillomavirus (HPV genotypes causes virtually all cancer of the cervix. The same HPV genotypes (“types” also cause cases of anal cancer. Cervical cancer is the third most frequent cancer in women worldwide after breast and colorectal cancers. It ranks fourth of women’s cancers according to the mortality ratio. Two vaccines have been developed against HPV infection; one is a quadrivalent vaccine (Gardasil™ and the other is a bivalent vaccine (Cervarix™. This topic will cover issues related to HPV infections, routine HPV immunization recommendations, vaccination in special patient populations, the cost-effectiveness of HPV vaccination, and vaccine safety. [TAF Prev Med Bull 2013; 12(3.000: 327-334

  2. Development of a GAL4-VP16/UAS trans-activation system for tissue specific expression in Medicago truncatula.

    Directory of Open Access Journals (Sweden)

    Amélie Sevin-Pujol

    Full Text Available Promoters with tissue-specific activity are very useful to address cell-autonomous and non cell autonomous functions of candidate genes. Although this strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific regulation of root symbiotic interactions in legumes has only started recently. Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric transcription factor that can bind short upstream activation sequences (UAS is an efficient way to target and enhance the expression of any gene of interest. Here, we developed a collection of promoters with different root cell layers specific activities in Medicago truncatula and tested their abilities to drive the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation UAS: β-Glucuronidase (GUS reporter gene system. By developing a binary vector devoted to modular Golden Gate cloning together with a collection of adapted tissue specific promoters and coding sequences we could test the activity of four of these promoters in trans-activation GAL4/UAS systems and compare them to "classical" promoter GUS fusions. Roots showing high levels of tissue specific expression of the GUS activity could be obtained with this trans-activation system. We therefore provide the legume community with new tools for efficient modular Golden Gate cloning, tissue specific expression and a trans-activation system. This study provides the ground work for future development of stable transgenic lines in Medicago truncatula.

  3. 20180416 - Retrofitting an Estrogen Receptor Transactivation Assay with Metabolic Competence Using Alginate Immobilization of Metabolic Enzymes (AIME) (SETAC HTS)

    Science.gov (United States)

    The VM7Luc4E2 estrogen receptor (ER) transactivation assay is an OECD approved method (TG 457) for the detection of ER agonists and antagonists, and is also part of the Tox21 high-throughput screening (HTS) portfolio. Despite international acceptance as a screening assay, immorta...

  4. 20180312 - Retrofitting an Estrogen Receptor Transactivation Assay with Metabolic Competence Using Alginate Immobilization of Metabolic Enzymes (AIME) (SOT)

    Science.gov (United States)

    The VM7Luc4E2 estrogen receptor (ER) transactivation assay is an OECD approved method (TG 457) for the detection of ER agonists and antagonists, and is also part of the Tox21 high-throughput screening (HTS) portfolio. Despite its international acceptance as a screening assay, imm...

  5. Cellular dosimetry

    International Nuclear Information System (INIS)

    Humm, J.L.; Chin, L.M.

    1989-01-01

    Radiation dose is a useful predictive parameter for describing radiation toxicity in conventional radiotherapy. Traditionally, in vitro radiation biology dose-effect relations are expressed in the form of cell survival curves, a semilog plot of cell survival versus dose. However, the characteristic linear or linear quadratic survival curve shape, for high- and low-LET radiations respectively, is only strictly valid when the radiation dose is uniform across the entire target population. With an external beam of 60 Co gamma rays or x-rays, a uniform field may be readily achievable. When radionuclides are incorporated into a cell milieu, several new problems emerge which can result in a departure from uniformity in energy deposition throughout a cell population. This nonuniformity can have very important consequences for the shape of the survival curve. Cases in which perturbations of source uniformity may arise include: 1. Elemental sources may equilibrate in the cell medium with partition coefficients between the extracellular, cytosol, and nuclear compartments. The effect of preferential cell internalization or binding to cell membrane of some radionuclides can increase or decrease the slope of the survival curve. 2. Radionuclides bound to antibodies, hormones, metabolite precursors, etc., may result in a source localization pattern characteristic of the carrier agent, i.e., the sources may bind to cell surface receptors or antigens, be internalized, bind to secreted antigen concentrated around a fraction of the cell population, or become directly incorporated into the cell DNA. We propose to relate the distribution of energy deposition in cell nuclei to biological correlates of cellular inactivation. The probability of each cell's survival is weighted by its individual radiation burden, and the summation of these probabilities for the cell population can be used to predict the number or fraction of cell survivors

  6. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women

    DEFF Research Database (Denmark)

    Muñoz, Nubia; Kjaer, Susanne K; Sigurdsson, Kristján

    2010-01-01

    The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of...

  7. Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

    Science.gov (United States)

    Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

    2013-11-01

    In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral

  8. Factors Related To HPV Vaccine Practice Among Adult Women

    Directory of Open Access Journals (Sweden)

    Adelia Perwita Sari

    2014-09-01

    Full Text Available ABSTRACT Cervical cancer is one of most common diseases among women worldwide. Human papilloma virus (HPV is known as precursor of cervical cancer. Cervical cancer can be prevented effectively by practicing hpv vaccine. But the coverage of HPV vaccine is remain low. The objection of study was to analyze factors related to HPV vaccine pratice among adult women. This study used case control design with sample size 25 for each group. Sample case was women who took HPV vaccine in IBI Kota Kediri on 2013, while sample control was neighboor from the sample case who didn’t take HPV vaccine. The independent variabels were age, education level, marital status, income level, knowledge, family support, family history of cervical cancer and the dependent variable was HPV vaccine practice. Those variables was analyzed with chi square or Fisher’s exact with significancy level at 95%. The result showed that there were correlation between education level (p = 0.006; c = 0.346, knowledge (p = 0.001; c = 0.464, and family support (p = 0.000; c = 0.516 with HPV vaccination practice. While there were no correlation between age (p = 0.275, marital status (0.490 and income level (p = 0.098 and family history of cervical cancer (p = 1.000 with HPV vaccination practice. Based on data from this study can be concluded that family support and knowledge had average strenght correlation withHPV vaccine practice among adult women. So, the intervention should be focused in increasing knowledge among women and their family about the important of HPV vaccine as a cervical cancer prevention. Keywords: practice, preventive, HPV, vaccine, adult women

  9. Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China.

    Directory of Open Access Journals (Sweden)

    Yaofei Yue

    Full Text Available HPV account for most of the incidence of cervical cancer. Approximately 90% of anal cancers and a smaller subset (<50% of other cancers (oropharyngeal, penile, vaginal, vulvar are also attributed to HPV. The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers type restricted protection. The L2 protein is a promising candidate for a broadly protective HPV vaccine. In our previous study, we found the most prevalent high-risk HPV infectious serotypes were HPV-16 and HPV-58 among women of Southwest China. To explore gene polymorphisms and intratypic variations of HPV-16 and HPV-58 L1/L2 genes originating in Southwest China, HPV-16 (L1: n = 31, L2: n = 28 and HPV-58 (L1: n = 21, L2: n = 21 L1/L2 genes were sequenced and compared to others described and submitted to GenBank. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods (MEGA software, followed by an analysis of the diversity of secondary structure. Then selection pressures acting on the L1/L2 genes were estimated by PAML software. Twenty-nine single nucleotide changes were observed in HPV-16 L1 sequences with 16/29 non-synonymous mutations and 13/29 synonymous mutations (six in alpha helix and two in beta turns. Seventeen single nucleotide changes were observed in HPV-16 L2 sequences with 8/17 non-synonymous mutations (one in beta turn and 9/17 synonymous mutations. Twenty-four single nucleotide changes were observed in HPV-58 L1 sequences with 10/24 non-synonymous mutations and 14/24 synonymous mutations (eight in alpha helix and four in beta turn. Seven single nucleotide changes were observed in HPV-58 L2 sequences with 4/7 non-synonymous mutations and 3/7 synonymous mutations. The result of selective pressure analysis showed that most of these mutations were of positive selection. This study may help understand the intrinsic geographical relatedness and biological differences of HPV-16/HPV-58 and

  10. Characterization of two novel gammapapillomaviruses, HPV179 and HPV184, isolated from common warts of a renal-transplant recipient.

    Directory of Open Access Journals (Sweden)

    Lea Hošnjak

    Full Text Available Gammapapillomavirus (Gamma-PV is a diverse and rapidly expanding PV-genus, currently consisting of 76 fully characterized human papillomavirus (HPV types. In this study, DNA genomes of two novel HPV types, HPV179 and HPV184, obtained from two distinct facial verrucae vulgares specimens of a 64 year-old renal-transplant recipient, were fully cloned, sequenced and characterized. HPV179 and HPV184 genomes comprise 7,228-bp and 7,324-bp, respectively, and contain four early (E1, E2, E6 and E7 and two late genes (L1 and L2; the non-coding region is typically positioned between L1 and E6 genes. Phylogenetic analysis of the L1 nucleotide sequence placed both novel types within the Gamma-PV genus: HPV179 was classified as a novel member of species Gamma-15, additionally containing HPV135 and HPV146, while HPV184 was classified as a single member of a novel species Gamma-25. HPV179 and HPV184 type-specific quantitative real-time PCRs were further developed and used in combination with human beta-globin gene quantitative real-time PCR to determine the prevalence and viral load of the novel types in the patient's facial warts and several follow-up skin specimens, and in a representative collection, a total of 569 samples, of HPV-associated benign and malignant neoplasms, hair follicles and anal and oral mucosa specimens obtained from immunocompetent individuals. HPV179 and HPV184 viral loads in patients' facial warts were estimated to be 2,463 and 3,200 genome copies per single cell, respectively, suggesting their active role in the development of common warts in organ-transplant recipients. In addition, in this particular patient, both novel types had established a persistent infection of the skin for more than four years. Among immunocompetent individuals, HPV179 was further detected in low-copy numbers in a few skin specimens, indicating its cutaneous tissue tropism, while HPV184 was further detected in low-copy numbers in one mucosal and a few skin

  11. Diagnostic methods and techniques in cervical cancer prevention Part II: Molecular diagnostics of HPV infection

    Directory of Open Access Journals (Sweden)

    Adriana Vince,

    2010-02-01

    Full Text Available Clinical diagnostics of HPV infection is based on analytically andclinically validated assays for qualitative detection of HPV DNAfrom high risk genotypes. New generation of HPV DNA assayscombines qualitative detection of 12 high-risk HPV genotypeswith HPV-16 and HPV-18 genotyping. New generation of HPVmolecular assays designed to increase clinical specificity of moleculartesting is based on detection of mRNA for E6 and E7.

  12. A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine

    Directory of Open Access Journals (Sweden)

    Chen CY

    2017-06-01

    Full Text Available Chuanyu Chen, Peijun You Department of Anesthesiology, Shandong Jining No 1 People’s Hospital, Jining, Shandong, People’s Republic of China Purpose: Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC systems for the delivery of local anesthetic drug, ropivacaine (RVC. Methods: In this study, transcriptional transactivator peptide (TAT-decorated RVC-loaded NCs (TAT-RVC/NCs were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. Results: The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. Conclusion: These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia. Keywords: local anesthetic system, ropivacaine, transcriptional transactivator peptide, nanocarriers, skin delivery

  13. Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma: transactivation and phenotypic variability.

    Directory of Open Access Journals (Sweden)

    Cristina Medina-Trillo

    Full Text Available Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3% were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG or hypomorphic (p.I126S alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability.

  14. Hypo- and Hypermorphic FOXC1 Mutations in Dominant Glaucoma: Transactivation and Phenotypic Variability

    Science.gov (United States)

    Medina-Trillo, Cristina; Sánchez-Sánchez, Francisco; Aroca-Aguilar, José-Daniel; Ferre-Fernández, Jesús-José; Morales, Laura; Méndez-Hernández, Carmen-Dora; Blanco-Kelly, Fiona; Ayuso, Carmen; García-Feijoo, Julián; Escribano, Julio

    2015-01-01

    Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3%) were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG) or hypomorphic (p.I126S) alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG) and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability. PMID:25786029

  15. An Update on Cellular MicroRNA Expression in Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Emmett, Sarah; Whiteman, David C; Panizza, Benedict J; Antonsson, Annika

    2018-06-19

    Squamous cell carcinoma of mucosal sites in the head and neck (HNSCC) is the sixth most common cause of cancer worldwide, and despite advances in conventional management, it still has significant morbidity and mortality associated with both diagnosis and treatment. Advances in our understanding of the biological mechanisms underlying this disease have demonstrated a significant difference between human papillomavirus (HPV)-associated, HPV and tobacco associated, and HPV-negative disease. It remains important to further elucidate the biologic and genetic differences between HPV-associated and tobacco-associated disease, with the aim of earlier diagnosis through screening, and advances in management including the development of novel therapeutic agents. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression, and have effects on almost every cellular function, and have potentially important applications to diagnosis, management and prognosis in HNSCC. Establishing a cellular miRNA expression profile for HPV-associated disease may therefore have important implications for the screening and treatment of this disease. This review summarises the current findings regarding miRNA expression in mucosal HNSCC, and focuses particularly on miRNA expression in HPV-associated tumours. © 2018 S. Karger AG, Basel.

  16. HPV Vaccine Safety PSA (:30) (No Tag)

    Centers for Disease Control (CDC) Podcasts

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. No CDC tag at the end. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.)

  17. Cervical Cancer Screening with HPV Test

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Stewart Massad, a professor in the Division of Gynecologic Oncology at Washington University in Saint Louis and a board member of the American Society for Colposcopy and Cervical Cancer Prevention (ASCCP), talks about cotesting with human papillomavirus (HPV) as part of a cervical cancer screening program.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  18. Natural History of HPV and Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2009-10-12

    Dr. Phil Castle, an intramural research scientist at the National Institutes of Health, talks about the natural history of human papillomavirus (HPV) infections, and cervical cancer and other anogenital cancers.  Created: 10/12/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  19. Development of a Fish Cell Biosensor System for Genotoxicity Detection Based on DNA Damage-Induced Trans-Activation of p21 Gene Expression

    Directory of Open Access Journals (Sweden)

    Huarong Guo

    2012-09-01

    Full Text Available p21CIP1/WAF1 is a p53-target gene in response to cellular DNA damage. Here we report the development of a fish cell biosensor system for high throughput genotoxicity detection of new drugs, by stably integrating two reporter plasmids of pGL3-p21-luc (human p21 promoter linked to firefly luciferase and pRL-CMV-luc (CMV promoter linked to Renilla luciferase into marine flatfish flounder gill (FG cells, referred to as p21FGLuc. Initial validation of this genotoxicity biosensor system showed that p21FGLuc cells had a wild-type p53 signaling pathway and responded positively to the challenge of both directly acting genotoxic agents (bleomycin and mitomycin C and indirectly acting genotoxic agents (cyclophosphamide with metabolic activation, but negatively to cyclophosphamide without metabolic activation and the non-genotoxic agents ethanol and D-mannitol, thus confirming a high specificity and sensitivity, fast and stable response to genotoxic agents for this easily maintained fish cell biosensor system. This system was especially useful in the genotoxicity detection of Di(2-ethylhexyl phthalate (DEHP, a rodent carcinogen, but negatively reported in most non-mammalian in vitro mutation assays, by providing a strong indication of genotoxicity for DEHP. A limitation for this biosensor system was that it might give false positive results in response to sodium butyrate and any other agents, which can trans-activate the p21 gene in a p53-independent manner.

  20. Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).

    Science.gov (United States)

    Gachon, F; Thebault, S; Peleraux, A; Devaux, C; Mesnard, J M

    2000-05-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.

  1. [HPV (Human Papilloma Virus) implication in other cancers than gynaecological].

    Science.gov (United States)

    Badoual, C; Tartour, E; Roussel, H; Bats, A S; Pavie, J; Pernot, S; Weiss, L; Mohamed, A Si; Thariat, J; Hoffmann, C; Péré, H

    2015-08-01

    Worldwide, approximately 5 to 10% of the population is infected by a Human Papilloma Virus (HPV). Some of these viruses, with a high oncogenic risk (HPV HR), are responsible for about 5% of cancer. It is now accepted that almost all carcinomas of the cervix and the vulva are due to an HPV HR (HPV16 and 18) infection. However, these viruses are known to be involved in the carcinogenesis of many other cancers (head and neck [SCCHN], penis, anus). For head and neck cancer, HPV infection is considered as a good prognostic factor. The role of HPV HR in anal cancer is also extensively studied in high-risk patient's population. The role of HPV infection in the carcinogenesis of esophageal, bladder, lung, breast or skin cancers is still debated. Given the multiple possible locations of HPV HR infection, the question of optimizing the management of patients with a HPV+ cancer arises in the implementation of a comprehensive clinical and biological monitoring. It is the same in therapeutics with the existence of a preventive vaccination, for example. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  2. Assessing mandatory HPV vaccination: who should call the shots?

    Science.gov (United States)

    Javitt, Gail; Berkowitz, Deena; Gostin, Lawrence O

    2008-01-01

    In 2007, many legislatures considered, and two enacted, bills mandating HPV vaccination for young girls as a condition of school attendance. Such mandates raise significant legal, ethical, and social concerns. This paper argues that mandating HPV vaccination for minor females is premature since long-term safety and effectiveness of the vaccine has not been established, HPV does not pose imminent and significant risk of harm to others, a sex specific mandate raises constitutional concerns, and a mandate will burden financially existing government health programs and private physicians. Absent careful consideration and public conversation, HPV mandates may undermine coverage rates for other vaccines.

  3. Surveillance Imaging in HPV-related Oropharyngeal Cancer.

    Science.gov (United States)

    Su, William; Miles, Brett A; Posner, Marshall; Som, Peter; Kostakoglu, Lale; Gupta, Vishal; Bakst, Richard L

    2018-03-01

    Current guidelines derived from a pre-human papilloma virus (HPV) era in oropharyngeal cancer do not recommend routine surveillance imaging. We aimed to analyze the method of recurrence detection in HPV+ disease to determine a role for follow-up imaging. All HPV+ and HPV- oropharyngeal cancer patients treated at our institution from 2005-2016 with biopsy-proven recurrence were identified and their method of recurrence detection was analyzed. A total of 16 HPV+ oropharyngeal cancer patients were identified to have recurrence, 12 (75%) of which experienced distant recurrence and 13 (81.3%) were detected asymptomatically with imaging at a median time of 19.7 months after initial treatment and verifying no residual disease. Twelve (75%) detections were with PET-CT. While HPV- patients (17 patients) also have a high rate of asymptomatic detection (16 patients, 94.1%), their 3-year post-recurrence survival was significantly lower at 6.5% compared to 83.6% for the HPV+ group (pHPV+ patients, a large proportion of failures are asymptomatic distant metastases, which occur beyond 6 months following treatment completion, and are detected with whole body imaging alone. In light of long term post-recurrence survival observed, this preliminary data suggests that routine surveillance imaging should be further studied for HPV+ disease. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Immunogenicity of an HPV-16 L2 DNA vaccine

    Science.gov (United States)

    Hitzeroth, Inga I.; Passmore, Jo-Ann S.; Shephard, Enid; Stewart, Debbie; Müller, Martin; Williamson, Anna-Lise; Rybicki, Edward P.; Kast, W. Martin

    2009-01-01

    The ability to elicit cross-neutralizing antibodies makes human papillomavirus (HPV) L2 capsid protein a possible HPV vaccine. We examined and compared the humoral response of mice immunised with a HPV-16 L2 DNA vaccine or with HPV-16 L2 protein. The L2 DNA vaccine elicited a non-neutralising antibody response unlike the L2 protein. L2 DNA vaccination suppressed the growth of L2-expressing C3 tumor cells, which is a T cell mediated effect, demonstrating that the lack of non-neutralizing antibody induction by L2 DNA was not caused by lack of T cell immunogenicity of the construct. PMID:19559114

  5. HPV Vaccine (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2013-07-25

    Nearly all sexually active men and women will get infected with the human papillomavirus, or HPV, at some point in their lives. HPV can lead to serious health problems later in life, including certain cancers in both men and women. Since 2006, a vaccine has been available that protects against the most frequent cancer-causing types of HPV. In this podcast, Shannon Stokley discusses the importance of getting the HPV vaccine.  Created: 7/25/2013 by MMWR.   Date Released: 7/25/2013.

  6. Gavi HPV Programs: Application to Implementation

    Directory of Open Access Journals (Sweden)

    Celina M. Hanson

    2015-05-01

    Full Text Available Developing countries disproportionately suffer from the burden of cervical cancer yet lack the resources to establish systematic screening programs that have resulted in significant reductions in morbidity and mortality in developed countries. Human Papillomavirus (HPV vaccination provides an opportunity for primary prevention of cervical cancer in low-resource settings through vaccine provision by Gavi The Vaccine Alliance. In addition to the traditional national introduction, countries can apply for a demonstration program to help them make informed decisions for subsequent national introduction. This article summarizes information from approved Gavi HPV demonstration program proposals and preliminary implementation findings. After two rounds of applications, 23 countries have been approved targeting approximately 400,000 girls for vaccination. All countries are proposing primarily school-based strategies with mixed strategies to locate and vaccinate girls not enrolled in school. Experiences to date include: Reaching marginalized girls has been challenging; Strong coordination with the education sector is key and overall acceptance has been high. Initial coverage reports are encouraging but will have to be confirmed in population based coverage surveys that will take place later this year. Experiences from these countries are consistent with existing literature describing other HPV vaccine pilots in low-income settings.

  7. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  8. Large scale study of HPV genotypes in cervical cancer and different cytological cervical specimens in Thailand.

    Science.gov (United States)

    Chansaenroj, Jira; Junyangdikul, Pairoj; Chinchai, Teeraporn; Swangvaree, Sukumarn; Karalak, Anant; Gemma, Nobuhiro; Poovorawan, Yong

    2014-04-01

    Identification of high-risk HPV genotypes in patients is essential for vaccination and prevention programs while the geographic distribution of cervical cancer varies widely. HPV 16 is the major cause of cervical cancer followed by HPV 18, HPV 31, HPV 52, or HPV 58 depending on geographic area. In this study, the distribution of HPV genotypes in cervical specimens from women living in Thailand was analyzed by HPV testing with electrochemical DNA chip and PCR direct sequencing. The 716 specimens were grouped according to their cytological grades; 100 normal, 100 low-grade squamous intraepithelial lesions, 100 high grade squamous intraepithelial lesions, and 416 specimens of cervical cancer. The results showed that HPV 16, HPV 18, HPV 52, and HPV 58 are the most common HPV genotypes in Thailand, respectively. With respect to age, women below the age of 26 years were almost negative for high-risk HPV DNA exclusively. Conversely, high prevalence of high-risk HPV DNA and abnormal cytology were usually found in women between 26 and 45 years while cervical cancer was detected mainly in women above the age of 45 years. To increase protection efficiency, a vaccine including HPV 52 and HPV 58 should be offered to Asian women, and primary HPV screening should start at 26-30 years of age. © 2013 Wiley Periodicals, Inc.

  9. Human papilloma virus (HPV genotypes prevalence in a region of South Italy (Apulia

    Directory of Open Access Journals (Sweden)

    Maria Franca Coscia

    2015-09-01

    Full Text Available INTRODUCTION. Since human papillomavirus (HPV is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. AIM. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy. METHODS. HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR and low risk (LR. RESULTS. The most prevalent HPV genotypes were HPV 16 (35%, HPV 31 (16% HPV 6 (9%, HPV 58 and 66 (7%, followed by HPV 33 (6%, HPV 18 and 56 (4%, HPV 70 and 45 (3%, HPV 53 and 11 (2%. Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high-risk HPV genotypes were observed in 10% of specimens. CONCLUSIONS. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

  10. Human papilloma virus (HPV) genotypes prevalence in a region of South Italy (Apulia).

    Science.gov (United States)

    Coscia, Maria Franca; Monno, Rosa; Ballini, Andrea; Mirgaldi, Rosanna; Dipalma, Gianna; Pettini, Francesco; Cristallo, Vincenzo; Inchingolo, Francesco; Foti, Caterina; de Vito, Danila

    2015-01-01

    Since human papillomavirus (HPV) is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy). HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR) and low risk (LR). The most prevalent HPV genotypes were HPV 16 (35%), HPV 31 (16%) HPV 6 (9%), HPV 58 and 66 (7%), followed by HPV 33 (6%), HPV 18 and 56 (4%), HPV 70 and 45 (3%), HPV 53 and 11 (2%). Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high- risk HPV genotypes were observed in 10% of specimens. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

  11. Estimating HPV DNA Deposition Between Sexual Partners Using HPV Concordance, Y Chromosome DNA Detection, and Self-reported Sexual Behaviors.

    Science.gov (United States)

    Malagón, Talía; Burchell, Ann N; El-Zein, Mariam; Guénoun, Julie; Tellier, Pierre-Paul; Coutlée, François; Franco, Eduardo L

    2017-12-05

    Detection of human papillomavirus (HPV) DNA in genital samples may not always represent true infections but may be depositions from infected sexual partners. We examined whether sexual risk factors and a biomarker (Y chromosome DNA) were associated with genital HPV partner concordance and estimated the fraction of HPV detections potentially attributable to partner deposition. The HITCH study enrolled young women attending a university or college in Montréal, Canada, and their male partners, from 2005 to 2010. We tested baseline genital samples for Y chromosome DNA and HPV DNA using polymerase chain reaction. Type-specific HPV concordance was 42.4% in partnerships where at least one partner was HPV DNA positive. Y chromosome DNA predicted type-specific HPV concordance in univariate analyses, but in multivariable models the independent predictors of concordance were days since last vaginal sex (26.5% higher concordance 0-1 vs 8-14 days after last vaginal sex) and condom use (22.6% higher concordance in never vs always users). We estimated that 14.1% (95% confidence interval [CI], 6.3-21.9%) of HPV DNA detections in genital samples were attributable to vaginal sex in the past week. A substantial proportion of HPV DNA detections may be depositions due to recent unprotected vaginal sex. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Primary HPV testing recommendations of US providers, 2015.

    Science.gov (United States)

    Cooper, Crystale Purvis; Saraiya, Mona

    2017-12-01

    To investigate the HPV testing recommendations of US physicians who perform cervical cancer screening. Data from the 2015 DocStyles survey of U.S. health care providers were analyzed using multivariate logistic regression to identify provider characteristics associated with routine recommendation of primary HPV testing for average-risk, asymptomatic women ≥30years old. The analysis was limited to primary care physicians and obstetrician-gynecologists who performed cervical cancer screening (N=843). Primary HPV testing for average-risk, asymptomatic women ≥30years old was recommended by 40.8% of physicians who performed cervical cancer screening, and 90.1% of these providers recommended primary HPV testing for women of all ages. The screening intervals most commonly recommended for primary HPV testing with average-risk, asymptomatic women ≥30years old were every 3years (35.5%) and annually (30.2%). Physicians who reported that patient HPV vaccination status influenced their cervical cancer screening practices were almost four times more likely to recommend primary HPV testing for average-risk, asymptomatic women ≥30years old than other providers (Adj OR=3.96, 95% CI=2.82-5.57). Many US physicians recommended primary HPV testing for women of all ages, contrary to guidelines which limit this screening approach to women ≥25years old. The association between provider recommendation of primary HPV testing and patient HPV vaccination status may be due to anticipated reductions in the most oncogenic HPV types among vaccinated women. Published by Elsevier Inc.

  13. Changes in HPV Knowledge Among College Women from 2008 to 2015.

    Science.gov (United States)

    Thompson, Erika L; Vamos, Cheryl A; Griner, Stacey B; Daley, Ellen M

    2018-04-01

    The human papillomavirus (HPV) can cause anogenital cancers and genital warts; however, it can be prevented through the HPV vaccine, which has been available since 2006. While this vaccine is targeted toward 11-to-12-year-olds, 18-to-26-year-old young adult women are eligible for "catch-up" vaccination. Knowledge of HPV may impact HPV vaccine uptake among this population. The purpose of this study was to assess changes in HPV knowledge and HPV vaccine information sources among young adult college women over a 7-year period. Two independent samples (N = 223 for 2008; N = 323 for 2015) completed a 23-item knowledge scale and survey regarding HPV. Adjusted logistic regression models compared the odds of correctly answering each knowledge item between each time period. The study found that HPV knowledge increased significantly over time (p HPV transmission; there is a vaccine for women that prevents certain types of HPV; HPV can cause genital warts; HPV can be passed to a newborn at birth; and even if you do not see a wart, you can transmit HPV. Recent participants were also more likely to correctly report only women can get HPV as false. While improvements in HPV knowledge were found over time, misperceptions regarding outcomes associated with HPV persist. In order to promote HPV vaccination among this population, health literacy skills, in addition to knowledge, should be improved.

  14. Seroconversion Following Anal and Genital HPV Infection in Men: The HIM Study.

    Science.gov (United States)

    Giuliano, Anna R; Viscidi, Raphael; Torres, B Nelson; Ingles, Donna J; Sudenga, Staci L; Villa, Luisa L; Baggio, Maria Luiza; Abrahamsen, Martha; Quiterio, Manuel; Salmeron, Jorge; Lazcano-Ponce, Eduardo

    2015-12-01

    Protection from naturally acquired human papillomavirus (HPV) antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM) Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Seroconversion to ≥1 HPV type (6/11/16/18) in this sub-cohort (N=384) varied by anatomic site, with 6.3, 18.9, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%). Overall, seroconversion was highest following anal HPV 6 infection (69.2%). HPV persistence was the only factor found to influence seroconversion. Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease.

  15. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  16. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  17. Comparison of Abbott RealTime High-Risk HPV and Hybrid Capture 2 Assays for Detection of HPV Infection.

    Science.gov (United States)

    Ko, Kiwoong; Yu, Shinae; Lee, Eun Hee; Park, Hyosoon; Woo, Hee-Yeon; Kwon, Min-Jung

    2016-09-01

    Various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced recently, including the Abbott RealTime High-Risk HPV assay. We sought to compare the performance of Abbott PCR to Hybrid Capture 2 for the detection of HR HPV. A total of 941 cervical swab specimens were obtained. We submitted all specimens for HR HPV detection with HC2 and Abbott PCR, and then additionally analyzed discordant and concordant positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. HC2 detected one of 13 HR HPV types in 12.3% (116/941) of cases, while Abbott PCR detected one of 14 detectable HR HPV types in 12.9% (121/941) of cases. The overall agreement rate was 97.3% with a kappa coefficient of 0.879. Discordant results between these two assays were observed in 25 cases. HC2 showed a sensitivity of 90.0% and specificity of 95.9%, while Abbott PCR showed a sensitivity of 98.0% and specificity of 96.8% when using RFMP results as the gold standard. For HPV 16/18 detection, Abbott PCR showed 95.8%/88.9% sensitivity and 99.2%/99.8% specificity, respectively. The overall coinfection rate between HPV 16, 18 and non-16/18 was 9.9% (12/121) in Abbott PCR analysis. Considering its high agreement rate with HC2, higher sensitivity/specificity compared to HC2, and ability to differentiate HPV 16/18 from other HPV types, Abbott PCR could be a reliable laboratory testing method for the screening of HPV infections. © 2016 by the Association of Clinical Scientists, Inc.

  18. HPV Vaccination of College Males: Strategizing against HPV Infection in College Students

    Science.gov (United States)

    Cunningham-Erves, Jennifer; Talbott, Laura L.

    2015-01-01

    The disease burden of the Human Papillomavirus (HPV) among females and its associated sequelae have been widely studied by social and behavioral science researchers and medical professionals. Approved for administration to males as young as nine years old, the vaccination of males continues to spark much debate when older age groups are brought…

  19. HPV Vaccine: Access and Use in the U.S.

    Science.gov (United States)

    ... 25 Adolescent girls whose families live below the poverty line and girls living in urban areas were more likely to be HPV UTD compared to adolescent girls whose families live above the poverty line or live in rural areas. HPV vaccination ...

  20. Perceptions of HPV Vaccine amongst UK University Students

    Science.gov (United States)

    Martin, Ellen; Senior, Naomi; Abdullah, Ammar; Brown, Janine; Collings, Suzanne; Racktoo, Sophie; Walpole, Sarah; Zeiton, Moez; Heffernan, Catherine

    2011-01-01

    Purpose: The aim of this small-scale focus group study is to explore the impact the Human Papilloma Virus (HPV) vaccine has on attitudes towards HPV, cervical cancer and sexual risk taking amongst university students in the UK. Design/methodology/approach: Participants were recruited through advertisements placed on notice boards throughout the…

  1. HPV Prevention (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2016-07-07

    Human papillomavirus, or HPV, is the most common sexually transmitted infection in the U.S. and is associated with almost 39,000 cancers each year. This podcast discusses the importance of getting the HPV vaccine.  Created: 7/7/2016 by MMWR.   Date Released: 7/7/2016.

  2. HPV Prevention (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2016-07-07

    Human papillomavirus, or HPV, is a virus that can cause certain cancers and is the most commonly sexually transmitted infection in the U.S. In this podcast, Dr. Laura Viens discusses the importance of getting vaccinated against HPV.  Created: 7/7/2016 by MMWR.   Date Released: 7/7/2016.

  3. Men's perspectives on cancer prevention behaviors associated with HPV.

    Science.gov (United States)

    FitzGerald, Serena; Cornally, Nicola; Hegarty, Josephine

    2018-02-01

    The human papillomavirus (HPV) is associated with the diagnosis of anal, penile, and oropharyngeal cancers in men. Evidence indicates that correct condom use in addition to obtaining the HPV vaccine provides the greatest protection from HPV infections. To explore young men's beliefs and behavioral intention in relation to receiving the HPV vaccine and using a condom correctly and consistently for sexual contact. A cross-sectional study underpinned by the theory of planned behavior (TPB) was conducted with male participants (n = 359, 18-28 years) who completed an online survey. Descriptive, correlational, and hierarchical regression analyses were performed on both status variables and variables of the TPB. Subjective norms (β = 0.519, P HPV vaccine, while relationship status (β = -0.215, P HPV vaccine and 44% in intention to use a condom were explained by the TPB model. Results from this study will impact on future sexual health research, education programs, and interventions for both HPV preventative behaviors towards the elimination of HPV-related cancers in men. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Mothers' support for voluntary provision of HPV vaccine in schools.

    Science.gov (United States)

    Kadis, Jessica A; McRee, Annie-Laurie; Gottlieb, Sami L; Lee, Morgan R; Reiter, Paul L; Dittus, Patricia J; Brewer, Noel T

    2011-03-21

    HPV vaccination rates among adolescents in the United States lag behind some other developed countries, many of which routinely offer the vaccine in schools. We sought to assess mothers' willingness to have their adolescent daughters receive HPV vaccine at school. A national sample of mothers of adolescent females ages 11-14 completed our internet survey (response rate=66%). The final sample (n=496) excluded mothers who did not intend to have their daughters receive HPV vaccine in the next year. Overall, 67% of mothers who intended to vaccinate their daughters or had vaccinated their daughters reported being willing to have their daughters receive HPV vaccine at school. Mothers were more willing to allow their daughters to receive HPV vaccine in schools if they had not yet initiated the vaccine series for their daughters or resided in the Midwest or West (all pconcerns about voluntary school-based provision of HPV vaccine that mothers most frequently cited were that their daughters' doctors should keep track of her shots (64%) and that they wished to be present when their daughters were vaccinated (40%). Our study suggests that most mothers who support adolescent vaccination for HPV find school-based HPV vaccination an acceptable option. Ensuring communication of immunization records with doctors and allowing parents to be present during immunization may increase parental support. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Knowledge, practice and acceptability of HPV vaccine by mothers of ...

    African Journals Online (AJOL)

    Background: Human Papilloma Virus (HPV) is a sexually transmitted cause of carcinoma of the cervix. An important determinant of the success of a primary preventive strategy like HPV vaccination is the knowledge and willingness of parents to vaccinate adolescents before sexual debut. Materials and methods of study: A ...

  6. HPV Vaccine (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Since 2006, a vaccine has been available that protects against the most frequent cancer-causing types of HPV. This podcast discusses the importance of parents talking to their children’s health care providers about getting the HPV vaccine.

  7. Analyzing discussions on twitter: Case study on HPV vaccinations

    NARCIS (Netherlands)

    Kaptein, R.; Boertjes, E.; Langley, D.

    2014-01-01

    In this work we analyze the discussions on Twitter around the Human papillomavirus (HPV) vaccinations. We collect a dataset consisting of tweets related to the HPV vaccinations by searching for relevant keywords, by retrieving the conversations on Twitter, and by retrieving tweets from our user

  8. Cervical HPV prevalence and genotype distribution in immunosuppressed Danish women

    DEFF Research Database (Denmark)

    Roensbo, Mette T; Blaakær, Jan; Skov, Karin

    2018-01-01

    INTRODUCTION: Women receiving immunosuppressive treatment due to organ transplantation are at increased risk of Human papilloma virus (HPV)-related diseases, including cervical neoplasia. This pilot study aimed to describe the cervical HPV prevalence and genotype distribution in immunosuppressed...... in 2014 had three cervical cytologies performed; one before and two after transplantation. The samples were examined for cytological abnormalities and tested for HPV using Cobas(®) HPV Test and CLART(®) HPV2 Test. RESULTS: Of 94 eligible cases we included 60 RTR and BMTR. The overall prevalence of high......-risk HPV was 15.0 (95% CI; 7.1-26.6) and the prevalence was higher among BMTR (29.4, CI; 10.3-56.0) than in RTR (9.3%, CI; 2.6-22.1) although this was not statistically significant (p=0.10). The distribution of high-risk HPV was broad with HPV 45 as the most common genotype (3.3%). The prevalences of high...

  9. HPV Vaccine (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2013-07-25

    Since 2006, a vaccine has been available that protects against the most frequent cancer-causing types of HPV. This podcast discusses the importance of parents talking to their children’s health care providers about getting the HPV vaccine.  Created: 7/25/2013 by MMWR.   Date Released: 7/25/2013.

  10. HPV-Specific Immunotherapy : Key Role for Immunomodulators

    NARCIS (Netherlands)

    Van de Wall, Stephanie; Nijman, Hans W.; Daemen, Toos

    Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and

  11. Need for expanded HPV genotyping for cervical screening

    Directory of Open Access Journals (Sweden)

    Jack Cuzick

    2016-12-01

    Full Text Available The focus for HPV genotyping has largely been on types 16 and 18, based on their high prevalence in cervix cancer. However screening is focussed on the detection of high grade precursor lesions (CIN3 and CIN2, where other types have a greater role. While HPV16 retains its high predictive value in this context, HPV31 and especially HPV33 emerge as important types with higher positive predictive values (PPVs than HPV18. Additionally full typing indicates that types 39, 56, 59 and 68 have much lower PPVs than types 16, 18, 31, 33, 35, 45, 51, 52 and 58 and they should be considered as ‘intermediate risk’ types, whereas type 66 should not be treated as having an increased risk. Available data are summarized to support this view.

  12. Formative research to shape HPV vaccine introduction strategies in Peru.

    Science.gov (United States)

    Bartolini, Rosario M; Drake, Jennifer Kidwell; Creed-Kanashiro, Hilary M; Díaz-Otoya, Margarita M; Mosqueira-Lovón, Nelly Rocío; Penny, Mary E; Winkler, Jennifer L; LaMontagne, D Scott; Bingham, Allison

    2010-01-01

    To understand the sociocultural environment, health systems' capacities, and policy processes related to cervical cancer and HPV vaccines in order to inform HPV vaccine introduction. Mixed-method formative research using qualitative and quantitative data collection techniques. Participants included girls, parents, community leaders, health and education officials, and policymakers. Respondents, including policymakers, generally supported HPV vaccine introduction, due partly to appreciation for the benefits of vaccination and the desire to prevent cancer. Community-level concerns regarding safety and quality of services will need to be addressed. The immunization system in Peru is strong and has capacity for including the HPV vaccine. Formative research provides key insights to help shape an effective program for HPV vaccine introduction.

  13. Providers' perceptions of parental concerns about HPV vaccination.

    Science.gov (United States)

    Perkins, Rebecca B; Clark, Jack A

    2013-05-01

    Parental resistance is often posited to explain low rates of human papillomavirus (HPV) vaccine uptake. We sought to describe providers' perceptions of parents' attitudes towards HPV vaccination. Thirty-four providers from four federally qualified community health centers participated in semi-structured interviews related to their experiences discussing HPV vaccination with low-income and minority parents. Providers found that parents were eager to prevent cancer in their daughters. Safety concerns and feeling that vaccination was unnecessary for virgins were reasons for declining vaccination. Providers found that immigrants from low-resource settings were more receptive to HPV vaccination than White middle-class parents due both to personal experience with vaccine-preventable diseases and cervical cancer and more realistic impressions of their children's sexual activity. Immigrants from low-resource settings may be particularly receptive to HPV vaccination, while White middle-class parents may be more likely to defer vaccination due to concerns about safety or sexual issues.

  14. Safety profile of the 9-valent HPV vaccine

    DEFF Research Database (Denmark)

    Moreira, Edson D; Block, Stan L; Ferris, Daron G

    2016-01-01

    OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6....... More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive...... for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients...

  15. Human papillomavirus (HPV types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

    Directory of Open Access Journals (Sweden)

    Ferenczy Alex

    2010-11-01

    Full Text Available Abstract Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.

  16. AKT increases VEGF expression in tumor cells by transactivating the proximal VEGF promoter

    International Nuclear Information System (INIS)

    Pore, N.; Bernhard, E.J.; Shu, H.-K.; Li, B.; O'Rourke, D.M.; Maity, A.; Haas-Kogan, D.

    2003-01-01

    Vascular endothelial growth factor (VEGF) is overexpressed in many cancers including glioblastomas and may contribute to their growth. Epidermal growth factor receptor (EGFR) amplification and loss of PTEN, commonly found in glioblastomas leading to increase phosphatidylinositol-3-kinase (PI3K) activity and VEGF expression. In the current study we show that AKT, which is downstream of PI3K, regulates VEGF expression. U87MG human glioblastoma cells lack wildtype PTEN and express high levels of phosphorylated AKT. Over expression of AKT either by stable expression in immortalized human astrocytes or by transduction with adenovirus containing activated myristoylated AKT in SF188 glioblastoma cells increases VEGF expression. Moreover the elevation of angiogenesis by constitutively expressed AKT is further confirmed by in vivo matrigel plug assay in nude mice. The upregulation of VEGF by AKT is mediated through a region in the proximal promoter located between -88 and -70 (+1 is transcription start site). In transient transfection activity of a luciferase reporter containing the -88/+54 region of the VEGF promoter is increased by cotransfection with myristoylated AKT and downregulated by a dominant negative AKT expression vector. Mutation of the putative Sp1 binding sites located in the -88/-70 region we show that AKT acts through Sp1 to transactivate the VEGF promoter. Cotransfection of the VEGF promoter reporter with both Sp1 and myristoylated AKT expression vectors increases promoter activity to a greater extent than either Sp1 or Akt by itself. In vivo phosphate labeling of proteins reveals that AKT leads to increased Sp1 phosphorylation. Gel shift assays using a radio labeled probe corresponding to nucleotides -88 through -66 in the promoter show increased binding with nuclear extracts from cells transduced with adenovirus expressing myristoylated AKT. In conclusion, our results suggest that loss of PTEN leads to increased VEGF expression by increasing AKT

  17. Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors.

    Science.gov (United States)

    Lavania, Dhruv; Dhingra, Anuradha; Grover, Anil

    2018-06-01

    Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.

  18. Anti-inflammatory and PPAR transactivational effects of components from the stem bark of Ginkgo biloba.

    Science.gov (United States)

    Ngan, Nguyen Thi Thanh; Quang, Tran Hong; Tai, Bui Huu; Song, Seok Bean; Lee, Dongho; Kim, Young Ho

    2012-03-21

    Ginkgo biloba, which is considered a "living fossil", has been used for medicinal purposes for thousands of years. Currently, extracts of G. biloba are some of the most widely used herbal products and/or dietary supplements in the world. In this study, three new compounds, (2E,4E,1'R,3'S,5'R,8'S)-dihydrophaseic acid 3'-O-β-D-glucopyranoside (1), 7,8-dihydro-(R)-7-methoxyconiferyl alcohol (2), and (8S)-3-methoxy-8,4'-oxyneolignan-4,9,9'-triol 3'-O-β-D-glucopyranoside (3), and 13 known compounds (4-16) were isolated from the stem bark of G. biloba. Their structures were determined by extensive spectroscopic methods, including 1D and 2D NMR, MS, and circular dichroism spectra. Four of the compounds (1, 2, 7, and 10) inhibited TNFα-induced NF-κB transcriptional activity significantly in HepG2 cells in a dose-dependent manner, with IC₅₀ values ranging from 6.9 to 9.1 μM. Furthermore, the transcriptional inhibitory function of these compounds was confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells. Compounds 1-5, 7, 9, 10, and 12-14 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC₅₀ values ranging from 0.7 to 12.8 μM. Compounds 2, 3, and 12 exhibited dose-dependent PPARα transactivational activity, with EC₅₀ values of 7.0, 3.3, and 10.1 μM, respectively. Compounds 1-3 activated PPARγ transcriptional activity, with EC₅₀ values of 11.9, 11.0, and 15.3 μM, whereas compounds 1 and 3 promoted the transactivational activity of PPARβ(δ) with EC₅₀ values of 10.7 and 11.2 μM, respectively. These results provide a scientific support for the use of G. biloba stem bark for the prevention and treatment of inflammatory and metabolic diseases. Moreover, these data provide the rationale for further studies of the potential of G. biloba stem bark in functional foods.

  19. Parental decision making about the HPV vaccine.

    Science.gov (United States)

    Allen, Jennifer D; Othus, Megan K D; Shelton, Rachel C; Li, Yi; Norman, Nancy; Tom, Laura; del Carmen, Marcela G

    2010-09-01

    Prophylactic human papillomavirus (HPV) vaccines are available, but uptake is suboptimal. Information on factors influencing parental decisions regarding vaccination will facilitate the development of successful interventions. Parents of girls ages 9 to 17 years (n = 476; cooperation rate = 67%) from a panel of U.S. households completed online surveys between September 2007 and January 2008, documenting vaccine knowledge, attitudes, and intentions. Among those aware of the vaccine, 19% had already vaccinated their daughter(s), 34% intended to, 24% were undecided, and 24% had decided against vaccination. Awareness of HPV was high but knowledge levels were suboptimal (mean 72%, SEM 0.8%). Black and Hispanic parents were significantly less likely to be aware of the vaccine compared with White parents. In multivariate analyses, compared with parents who opposed vaccination, those who had already vaccinated their daughter(s) or who intended to do so had more positive attitudes, reported fewer barriers, and were more likely to perceive that family and friends would endorse vaccination. They also reported higher levels of trust in pharmaceutical companies that produce the vaccine. Despite limited knowledge, most parents had decided to vaccinate their daughter(s). Given evidence of diminished access to information among Black and Hispanic parents, programs should focus on reaching these groups. Interventions should address parental concerns about behavioral consequences, reduce structural barriers, and promote the perception that vaccination is endorsed by significant others. Moreover, interventions may need to address mistrust of pharmaceutical companies. IMPACT STATEMENT: This study documents factors associated with parental decisions about HPV vaccination for their daughter(s) and provides direction for intervention development. (c)2010 AACR.

  20. Oropharynx HPV status and its relation to HIV infection

    Directory of Open Access Journals (Sweden)

    Leonora Maciel de Souza Vianna

    2018-03-01

    Full Text Available Background The number of oropharyngeal lesions caused by HPV (Human papillomavirus has been increasing worldwide in the past years. In spite of the clinical relevance of HPV infection in the anogenital tract of HIV-positive patients, the relevance of oropharynx HPV infection in these patients is not clear. The aim of the present study was to detect HPV infection, and clinical and cytological changes in the oropharynx of HIV-positive patients. Methods Samples collected from the oropharynx of 100 HIV-positive patients were subjected to hybrid capture (HC, conventional and liquid-based cytology. Clinical data were also collected to investigate the relation with HPV status. Results High and low-risk types of HPV were present in 8% and 16.7% of the total sample. The mean ± sd (maximum-minimum of the relative ratio light unit (RLU/cutoff (CO was 2.94 ± 2.58 (1.09–7.87 and 1.61 ± 0.65 (1.07–2.8 for high- and low-risk-HPV, respectively. By cytology, dysplasia was not detected, but atypical squamous cells of undetermined significance (ASC-US were diagnosed in two samples. No clinical change, suggestive of dysplasia/cancer, was detected. Conclusion Our study was able to detect and characterize HPV infection by hybrid capture, which may represent a good tool for screening and follow-up of HPV in the studied population. The frequency and viral load of HPV were low. Neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive patients.

  1. HPV Vaccination: Attitude and Knowledge among German Gynecologists.

    Science.gov (United States)

    Kolben, T M; Dannecker, C; Baltateanu, K; Goess, C; Starrach, T; Semmlinger, A; Ditsch, N; Gallwas, J; Mahner, S; Friese, K; Kolben, T

    2016-10-01

    Purpose: In order to achieve a higher vaccination rate, education on HPV as well as options for prophylaxis performed by doctors is of great importance. One opportunity to increase the protection against HPV would be vaccinating boys. This study evaluated attitude and knowledge among German gynecologists regarding HPV vaccination, especially in boys. Material and Methods: A questionnaire with 42 questions about demographics, attitude and knowledge about HPV and HPV vaccination was sent to members of the German Society for Gynecology and Obstetrics (DGGG). Results: 998 out of 6567 addressed gynecologists participated. Knowledge about HPV, associated diseases and possible HPV vaccines was high among participants. The attitude towards vaccination in boys as well as girls was positive. Only 8.2 % refused to vaccinate their sons whereas 2.2 % refused to do this for their daughters. However, only few gynecologists vaccinated their daughters and sons against HPV. Main reason for girls was an age outside of vaccination guidelines; for boys it was the lack of cost coverage. Conclusion: The willingness of gynecologists to perform HPV vaccination in boys is as high as for girls. However, sons of gynecologists are only rarely vaccinated against HPV. Main reason is the lack of cost coverage. Vaccinating boys could decrease the disease burden in males, as well as protect women by interrupting ways of transmission. Since the main argument against vaccination of boys is only of financial nature, the necessity of a vaccination recommendation for boys needs to be re-evaluated taking into account the cost-reduced 2-dose vaccination scheme.

  2. Parents Who Decline HPV Vaccination: Who Later Accepts and Why?

    Science.gov (United States)

    Kornides, Melanie L; McRee, Annie-Laurie; Gilkey, Melissa B

    2018-03-01

    Parental declination contributes to low human papillomavirus (HPV) vaccination coverage among US adolescents, resulting in missed opportunities for cancer prevention. We sought to characterize parents' acceptance of HPV vaccination after declination ("secondary acceptance"). In September 2016, we conducted an online survey with a national sample of parents of children ages 11 to 17 years. For those who reported having ever declined HPV vaccination for their children (n = 494), our survey assessed whether they accepted the vaccine at a subsequent visit. We used multivariable logistic regression to assess correlates of secondary acceptance. Overall, 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months. In multivariable analyses, secondary acceptance was associated with receiving follow-up counseling about HPV vaccination from a health care provider (odds ratio, 2.16; 95% confidence interval, 1.42-3.28). However, only 53% of parents overall reported receiving such counseling. Secondary acceptance was also associated with receiving a higher quality HPV vaccine recommendation from a provider during the initial discussion and greater satisfaction with provider communication, as well as higher vaccination confidence. Among the reasons for secondary acceptance, parents most commonly reported the child getting older (45%), learning more about HPV vaccine (34%), and receiving a provider recommendation (33%). Our findings suggest secondary acceptance of HPV vaccination is common, with more than two-thirds of parents in this national sample accepting or intending to accept HPV vaccination after declination. Providers should seek to motivate secondary acceptance by delivering repeated, high-quality recommendations for HPV vaccination. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  3. Frequency of HPV in oral cavity squamous cell carcinoma.

    Science.gov (United States)

    de Abreu, Priscila Marinho; Có, Anna Clara Gregório; Azevedo, Pedro Leite; do Valle, Isabella Bittencourt; de Oliveira, Karine Gadioli; Gouvea, Sônia Alves; Cordeiro-Silva, Melissa Freitas; Louro, Iúri Drummond; de Podestá, José Roberto Vasconcelos; Lenzi, Jeferson; Sena, Agenor; Mendonça, Elismauro Francisco; von Zeidler, Sandra Lúcia Ventorin

    2018-03-27

    The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5 + /GP6 + as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro-Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

  4. HPV seroconversion following anal and penile HPV infection in HIV-negative and HIV-infected MSM

    NARCIS (Netherlands)

    Mooij, Sofie H.; Landén, Olivia; van der Klis, Fiona R. M.; van der Sande, Marianne A. B.; de Melker, Hester E.; Xiridou, Maria; van Eeden, Arne; Heijman, Titia; Speksnijder, Arjen G. C. L.; Snijders, Peter J. F.; Schim van der Loeff, Maarten F.

    2014-01-01

    We assessed human papillomavirus (HPV) seroconversion following anal and penile HPV infection in HIV-negative and HIV-infected men who have sex with men (MSM). MSM aged ≥18 years were recruited in Amsterdam, the Netherlands (2010-2011), and followed up semiannually. Antibodies against 7 high-risk

  5. HPV-related Multiphenotypic Sinonasal Carcinoma

    DEFF Research Database (Denmark)

    Bishop, Justin A; Andreasen, Simon; Hang, Jen-Fan

    2017-01-01

    . Immunohistochemistry for p16, c-kit, and myoepithelial cell markers (S100, actin, calponin, p63, and/or p40) was performed along with RNA in situ hybridization for HPV (type 33-specific as well as a high-risk cocktail). Fluorescence in situ hybridization studies for fusions of MYB, NFIB, and MYBL1 was performed...... gene fusions were positive. In the 38 cases with follow-up data, (mean follow-up, 42 mo) 14 recurred locally and 2 metastasized (lung, finger). There were no regional lymph node metastases, and no tumor-related deaths. HMSC is a distinct sinonasal neoplasm characterized by myoepithelial differentiation...

  6. HPV Vaccine Safety PSA (:30) (No Tag)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. No CDC tag at the end. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  7. Cancers Caused by HPV PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niños y las niñas de 11 a 12 años con la vacuna contra el VPH.).  Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD).   Date Released: 1/15/2014.

  8. Evaluation of HPV-16 and HPV-18 specific antibody measurements in saliva collected in oral rinses and merocel® sponges.

    Science.gov (United States)

    Parker, Katherine H; Kemp, Troy J; Pan, Yuanji; Yang, Zhen; Giuliano, Anna R; Pinto, Ligia A

    2018-05-03

    Current Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers. Serum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24-41) and 6 mid-adult aged males (ages 27-45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA). All vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV  0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum. This study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Factors that Predict Parental Willingness to Have Their Children Vaccinated against HPV in a Country with Low HPV Vaccination Coverage

    Directory of Open Access Journals (Sweden)

    Maria Ganczak

    2018-03-01

    Full Text Available Background: Adolescent HPV (Human Papilloma Virus vaccination is yet to be introduced as a mandatory program in Poland. Polish literature on factors associated with adolescent HPV vaccination is scant, despite the fact that uptake is one of the poorest in the European Union. Objectives: To assess HPV awareness and identify independent predictors for parental willingness to have their children vaccinated against HPV. Methods: All parents of first grade students from three selected high schools in Zgorzelec, Poland, who participated in parent–teacher meetings at the time the study was conducted, had their children unvaccinated regarding HPV, and who gave informed consent to participate were included. There were 600 first grade students; 9 were vaccinated against HPV. This left 591 parents who met the eligibility criteria; the response rate was 76.1%. Results: Awareness of HPV was reported by 55.3% of 450 parents (mean age 42 years, 70.9% females; 85.1% expressed their willingness to vaccinate their children against HPV; 31.3% identified HPV as a sexually transmitted pathogen, and 36.2% identified it as a risk factor of cervical cancer. Multivariable logistic regression analyses indicated that being employed (OR 2.09; 95% CI: 1.10–3.86, having positive attitudes toward vaccines (OR 3.02; 95% CI: 1.34–6.49, previous information about HPV (OR 2.02; 95% CI: 1.17–3.51, and concerns about the side effects of the HPV vaccine (OR 0.60; 95% CI: 0.35–0.99 were independent predictors of parents’ willingness to vaccinate. Conclusions: Attitudes regarding their child being vaccinated against HPV were positive among Polish parents, even though awareness and knowledge of HPV in this group were low. Most of the significant factors that influenced their willingness were modifiable, such as being informed about HPV and having positive attitudes toward vaccines. Future interventions should focus specifically on vulnerable subgroups, such as unemployed

  10. Early direct and indirect impact of quadrivalent HPV (4HPV) vaccine on genital warts: a systematic review.

    Science.gov (United States)

    Mariani, Luciano; Vici, Patrizia; Suligoi, Barbara; Checcucci-Lisi, Giovanni; Drury, Rosybel

    2015-01-01

    Since 2007, many countries have implemented national human papillomavirus (HPV) vaccination programs with the quadrivalent HPV (4HPV) vaccine that has been shown to be efficacious in clinical trials involving 25,000 subjects. Two vaccine serotypes, HPV16 and 18, are responsible for cervical cancer and other HPV-related cancers, but the impact of the 4HPV vaccine on these cancers cannot be seen immediately as there is a considerable lag between infection with HPV and cancer development. The other two serotypes, HPV6 and 11, are responsible for genital warts (GWs), which develop within a few months after infection, making GWs an early clinical endpoint for the assessment of the impact of 4HPV vaccination. We performed a systematic literature search in PubMed to identify all published studies on 4HPV vaccination, including those that assessed the impact of 4HPV vaccination programs on the incidence of GWs at a population level around the world. A total of 354 records were identified in the PubMed search. After screening and obtaining full papers for 56 publications, 16 publications presenting data on the impact or effectiveness of 4HPV vaccination on GWs were identified. These reported data on the impact or effectiveness of 4HPV in six countries [Australia (n = 6), New Zealand (n = 2), United States (n = 3), Denmark (n = 2), Germany (n = 1), and Sweden (n = 2)]. In Australia, no GWs were diagnosed in women aged <21 years who reported being vaccinated. A 92.6% reduction in GWs incidence was reported for all women in this age group, where the vaccine uptake rate (VUR) was 70% for 3 doses. The highest reductions were reported in countries with high VURs, mostly through school-based vaccination programs, although high VURs were obtained with some non-school-based programs. The results are coherent with the GWs incidence reduction reported in clinical trials and are an early indicator of what can be expected for the long-term clinical impact on vaccine-type HPV

  11. Estimating effectiveness of HPV vaccination against HPV infection from post-vaccination data in the absence of baseline data.

    Science.gov (United States)

    Vänskä, Simopekka; Söderlund-Strand, Anna; Uhnoo, Ingrid; Lehtinen, Matti; Dillner, Joakim

    2018-04-28

    HPV vaccination programs have been introduced in large parts of the world, but monitoring of effectiveness is not routinely performed. Many countries introduced vaccination programs without establishing the baseline of HPV prevalences. We developed and validated methods to estimate protective effectiveness (PE) of vaccination from the post-vaccination data alone using references, which are invariant under HPV vaccination. Type-specific HPV prevalence data for 15-39 year-old women were collected from the pre- and post-vaccination era in a region in southern Sweden. In a region in middle Sweden, where no baseline data had been collected, only post-vaccination data was collected. The age-specific baseline prevalence of vaccine HPV types (vtHPV, HPV 6, 11, 16, 18) were reconstructed as Beta distributions from post-vaccination data by applying the reference odds ratios between the target HPV type and non-vaccine-type HPV (nvtHPV) prevalences. Older non-vaccinated age cohorts and the southern Sweden region were used as the references. The methods for baseline reconstructions were validated by computing the Bhattacharyya coefficient (BC), a measure for divergence, between reconstructed and actual observed prevalences for vaccine HPV types in Southern Sweden, and in addition, for non-vaccine types in both regions. The PE estimates among 18-21 year-old women were validated by comparing the PE estimates that were based on the reconstructed baseline prevalences against the PE estimates based on the actual baseline prevalences. In Southern Sweden the PEs against vtHPV were 52.2% (95% CI: 44.9-58.5) using the reconstructed baseline and 49.6% (43.2-55.5) using the actual baseline, with high BC 82.7% between the reconstructed and actual baseline. In the middle Sweden region where baseline data was missing, the PE was estimated at 40.5% (31.6-48.5). Protective effectiveness of HPV vaccination can be estimated from post-vaccination data alone via reconstructing the baseline

  12. HPV and anal cancer in HIV-infected individuals: a review

    NARCIS (Netherlands)

    Schim van der Loeff, Maarten F.; Mooij, Sofie H.; Richel, Oliver; de Vries, Henry J. C.; Prins, Jan M.

    2014-01-01

    HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade

  13. HPV vaccine awareness and the association of trust in cancer information from physicians among males.

    Science.gov (United States)

    Cooper, Dexter L; Hernandez, Natalie D; Rollins, Latrice; Akintobi, Tabia Henry; McAllister, Calvin

    2017-05-09

    Black and Hispanic men are diagnosed with more HPV-related cancers and at later stages compared to other racial/ethnic groups. Physician communication with men about HPV vaccination may be beneficial to increasing HPV vaccinations and decreasing HPV transmission. The purpose of this study was to examine HPV and HPV vaccine awareness among men by race, and the association between trust in cancer information from physicians and ever hearing about HPV and the HPV vaccine. U.S. adult males (age 18+) were identified from the 2014 Health Information National Trends Survey (HINTS) (n=1203). Binomial logistic regression models assessed the influences of race/ethnicity and trust of cancer information from physicians on men having heard of HPV and the HPV vaccination. Approximately 50% of the sample had never heard of HPV and 53% had never heard of the vaccine. Black men were less likely to know that HPV is sexually transmitted compared to White and Hispanic men (pcancer information compared to White and Black men (pawareness about HPV among men. Furthermore, statistically significant racial/ethnic differences were found in HPV vaccine knowledge and trust in receiving cancer information from physicians. Future interventions should include community-based approaches and improved physicians' HPV-related communication to increase knowledge and uptake of the HPV vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Possible Synergistic Interactions Among Multiple HPV Genotypes in Women Suffering from Genital Neoplasia

    Science.gov (United States)

    Hajia, Massoud; Sohrabi, Amir

    2018-03-27

    Objective: Persistence of HPV infection is the true cause of cervical disorders. It is reported that competition may exist among HPV genotypes for colonization. This survey was designed to establish the multiple HPV genotype status in our community and the probability of multiple HPV infections involvement. Methods: All multiple HPV infections were selected for investigation in women suffering from genital infections referred to private laboratories in Tehran, Iran. A total of 160 multi HPV positive specimens from cervical scraping were identified by the HPV genotyping methods, "INNO-LiPA and Geno Array". Result: In present study, HPV 6 (LR), 16 (HR), 53 (pHR), 31 (HR) and 11 (LR) were included in 48.8% of detected infections as the most five dominant genotypes. HPV 16 was detected at the highest rate with genotypes 53, 31 and 52, while HPV 53 appeared linked with HPV 16, 51 and 56 in concurrent infections. It appears that HPV 16 and 53 may have significant tendencies to associate with each other rather than with other genotypes. Analysis of the data revealed there may be some synergistic interactions with a few particular genotypes such as "HPV 53". Conclusion: Multiple HPV genotypes appear more likely to be linked with development of cervical abnormalities especially in patients with genital infections. Since, there are various patterns of dominant HPV genotypes in different regions of world, more investigations of this type should be performed for careHPV programs in individual countries. Creative Commons Attribution License

  15. The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model.

    Science.gov (United States)

    Chesson, Harrell W; Markowitz, Lauri E; Hariri, Susan; Ekwueme, Donatus U; Saraiya, Mona

    2016-06-02

    The objective of this study was to assess the incremental costs and benefits of the 9-valent HPV vaccine (9vHPV) compared with the quadrivalent HPV vaccine (4vHPV). Like 4vHPV, 9vHPV protects against HPV types 6, 11, 16, and 18. 9vHPV also protects against 5 additional HPV types 31, 33, 45, 52, and 58. We adapted a previously published model of the impact and cost-effectiveness of 4vHPV to include the 5 additional HPV types in 9vHPV. The vaccine strategies we examined were (1) 4vHPV for males and females; (2) 9vHPV for females and 4vHPV for males; and (3) 9vHPV for males and females. In the base case, 9vHPV cost $13 more per dose than 4vHPV, based on available vaccine price information. Providing 9vHPV to females compared with 4vHPV for females (assuming 4vHPV for males in both scenarios) was cost-saving regardless of whether or not cross-protection for 4vHPV was assumed. The cost per quality-adjusted life year (QALY) gained by 9vHPV for both sexes (compared with 4vHPV for both sexes) was < $0 (cost-saving) when assuming no cross-protection for 4vHPV and $8,600 when assuming cross-protection for 4vHPV. Compared with a vaccination program of 4vHPV for both sexes, a vaccination program of 9vHPV for both sexes can improve health outcomes and can be cost-saving.

  16. PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

    Science.gov (United States)

    Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

    2013-01-01

    Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

  17. PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

    Science.gov (United States)

    Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

    2013-01-04

    Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

  18. A novel p53 mutational hotspot in skin tumors from UV-irradiated Xpc mutant mice alters transactivation functions.

    Science.gov (United States)

    Inga, Alberto; Nahari, Dorit; Velasco-Miguel, Susana; Friedberg, Errol C; Resnick, Michael A

    2002-08-22

    A mutation in codon 122 of the mouse p53 gene resulting in a T to L amino acid substitution (T122-->L) is frequently associated with skin cancer in UV-irradiated mice that are both homozygous mutant for the nucleotide excision repair (NER) gene Xpc (Xpc(-/-)) and hemizygous mutant for the p53 gene. We investigated the functional consequences of the mouse T122-->L mutation when expressed either in mammalian cells or in the yeast Saccharomyces cerevisiae. Similar to a non-functional allele, high expression of the T122-->L allele in p53(-/-) mouse embryo fibroblasts and human Saos-2 cells failed to suppress growth. However, the T122-->L mutant p53 showed wild-type transactivation levels with Bax and MDM2 promoters when expressed in either cell type and retained transactivation of the p21 and the c-Fos promoters in one cell line. Using a recently developed rheostatable p53 induction system in yeast we assessed the T122-->L transactivation capacity at low levels of protein expression using 12 different p53 response elements (REs). Compared to wild-type p53 the T122-->L protein manifested an unusual transactivation pattern comprising reduced and enhanced activity with specific REs. The high incidence of the T122-->L mutant allele in the Xpc(-/-) background suggests that both genetic and epigenetic conditions may facilitate the emergence of particular functional p53 mutations. Furthermore, the approach that we have taken also provides for the dissection of functions that may be retained in many p53 tumor alleles.

  19. Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes

    International Nuclear Information System (INIS)

    Holmstroem, Therese E.; Mattsson, Charlotte L.; Wang, Yanling; Iakovleva, Irina; Petrovic, Natasa; Nedergaard, Jan

    2010-01-01

    In many cell types, G-protein-coupled receptor (GPCR)-induced Erk1/2 MAP kinase activation is mediated via receptor tyrosine kinase (RTK) transactivation, in particular via the epidermal growth factor (EGF) receptor. Lysophosphatidic acid (LPA), acting via GPCRs, is a mitogen and MAP kinase activator in many systems, and LPA can regulate adipocyte proliferation. The mechanism by which LPA activates the Erk1/2 MAP kinase is generally accepted to be via EGF receptor transactivation. In primary cultures of brown pre-adipocytes, EGF can induce Erk1/2 activation, which is obligatory and determinant for EGF-induced proliferation of these cells. Therefore, we have here examined whether LPA, via EGF transactivation, can activate Erk1/2 in brown pre-adipocytes. We found that LPA could induce Erk1/2 activation. However, the LPA-induced Erk1/2 activation was independent of transactivation of EGF receptors (or PDGF receptors) in these cells (whereas in transformed HIB-1B brown adipocytes, the LPA-induced Erk1/2 activation indeed proceeded via EGF receptor transactivation). In the brown pre-adipocytes, LPA instead induced Erk1/2 activation via two distinct non-transactivational pathways, one G i -protein dependent, involving PKC and Src activation, the other, a PTX-insensitive pathway, involving PI3K (but not Akt) activation. Earlier studies showing LPA-induced Erk1/2 activation being fully dependent on RTK transactivation have all been performed in cell lines and transfected cells. The present study implies that in non-transformed systems, RTK transactivation may not be involved in the mediation of GPCR-induced Erk1/2 MAP kinase activation.

  20. Identification of multiple HPV types on spermatozoa from human sperm donors

    DEFF Research Database (Denmark)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob

    2011-01-01

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV...... according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive...

  1. Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xiangru Wen

    Full Text Available Magnetic poly (D,L-lactide-co-glycolide (PLGA/lipid nanoparticles (MPLs were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol (DSPE-PEG-NH2, and magnetic nanoparticles (NPs, and then conjugated to trans-activating transcriptor (TAT peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES, naringin (NAR, and glutathione (GSH were encapsulated in MPLs with drug loading capacity (>10% and drug encapsulation efficiency (>90%. The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

  2. The regulation of transactivator of transcription on the activity of DNA-PKcs promoter

    International Nuclear Information System (INIS)

    Yang Tianyi; Zhang Shimeng; Qin Xia; Li Bing; Liu Xiaodan; Zhou Pingkun

    2012-01-01

    Objective: To explore the influence of human immunodeficiency virus transactivator of transcription (TAT) on the promoter activity of DNA dependent protein kinase catalytic subunit (DNA-PKcs). Methods: The truncated promoters of DNA-PKcs were cloned by PCR from the template DNA from HeLa genomic DNA, and the pGL3-basic-DNA-PKcs promoter reporter plasmids were constructed. The activity of DNA-PKcs promoters was detected by dual-luciferase reporter assay system. A Lac-repressor and Lacoperator based green fluorescent protein imaging system was used to assay the chromatin remodeling activity. Results: A series of reporter plasmids harboring the truncated promoters of DNA-PKcs from -939 bp to -1 bp were constructed. The sequence of -64 bp to-1 bp was identified as a critical element for the activity of DNA-PKes promoter. TAT can suppress the activity of DNA-PKcs promoter. TAT participates in the regulation of the large scale chromatin relaxation. Ionizing radiation attenuates the activity of TAT played in the chromatin remodeling. Conclusion: TAT represses the promoter activity of DNA repair protein DNA-PKcs, and also play a role of large scale chromatin remodeling which can te attenuated by ionizing radiation. (authors)

  3. Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor

    International Nuclear Information System (INIS)

    Wang, C.-P.; Lee, Y.-F.; Chang, C.; Lee, H.-J.

    2006-01-01

    The human testicular receptor 4 (TR4) shares structural homology with members of the nuclear receptor superfamily. Some other members of this superfamily were able to regulate the transcriptional activity of the human oxytocin (OXT) promoter by binding to the first DR0 regulatory site. However, little investigation was conducted systematically in the study of the second dDR4 site of OXT proximal promoter, and the relationship between the first and the second sites of OXT promoter. Here, we demonstrated for the first time that TR4 could increase the proximal promoter activity of the human OXT gene via DR0, dDR4, and OXT (both DR0 and dDR4) elements, respectively. TR4 might induce OXT gene expression through the OXT element in a dose-dependent manner. However, there is no synergistic effect between DR0 and dDR4 elements during TR4 transactivation. Taken together, these results suggested that TR4 should be one of important regulators of OXT gene expression

  4. A role for NF-κB–dependent gene transactivation in sunburn

    Science.gov (United States)

    Abeyama, Kazuhiro; Eng, William; Jester, James V.; Vink, Arie A.; Edelbaum, Dale; Cockerell, Clay J.; Bergstresser, Paul R.; Takashima, Akira

    2000-01-01

    Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage. PMID:10862790

  5. A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms.

    Science.gov (United States)

    Gustafson, Chelsea L; Parsley, Nicole C; Asimgil, Hande; Lee, Hsiau-Wei; Ahlbach, Christopher; Michael, Alicia K; Xu, Haiyan; Williams, Owen L; Davis, Tara L; Liu, Andrew C; Partch, Carrie L

    2017-05-18

    The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Methylation of class II transactivator gene promoter IV is not associated with susceptibility to Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lincoln Matthew R

    2008-07-01

    Full Text Available Abstract Background Multiple sclerosis (MS is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology. Methods In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR. Results No methylation or sequence variation of the MHC2TA promoter pIV was found. Conclusion The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.

  7. Enhanced human somatic cell reprogramming efficiency by fusion of the MYC transactivation domain and OCT4

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2017-12-01

    Full Text Available The development of human induced pluripotent stem cells (iPSCs holds great promise for regenerative medicine. However the iPSC induction efficiency is still very low and with lengthy reprogramming process. We utilized the highly potent transactivation domain (TAD of MYC protein to engineer the human OCT4 fusion proteins. Applying the MYC-TAD-OCT4 fusion proteins in mouse iPSC generation leads to shorter reprogramming dynamics, with earlier activation of pluripotent markers in reprogrammed cells than wild type OCT4 (wt-OCT4. Dramatic enhancement of iPSC colony induction efficiency and shortened reprogramming dynamics were observed when these MYC-TAD-OCT4 fusion proteins were used to reprogram primary human cells. The OCT4 fusion proteins induced human iPSCs are pluripotent. We further show that the MYC Box I (MBI is dispensable while both MBII and the linking region between MBI/II are essential for the enhanced reprogramming activity of MYC-TAD-OCT4 fusion protein. Consistent with an enhanced transcription activity, the engineered OCT4 significantly stimulated the expression of genes specifically targeted by OCT4-alone, OCT4/SOX2, and OCT4/SOX2/KLF4 during human iPSC induction, compared with the wt-OCT4. The MYC-TAD-OCT4 fusion proteins we generated will be valuable tools for studying the reprogramming mechanisms and for efficient iPSC generation for humans as well as for other species.

  8. Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Zhiqiang; Su, Lijing; Pei, Jimin; Grishin, Nick V.; Zhang, Hong (UTSMC)

    2017-08-01

    In the canonical clock model, CLOCK:BMAL1-mediated transcriptional activation is feedback regulated by its repressors CRY and PER and, in association with other coregulators, ultimately generates oscillatory gene expression patterns. How CLOCK:BMAL1 interacts with coregulator(s) is not well understood. Here we report the crystal structures of the mouse CLOCK transactivating domain Exon19 in complex with CIPC, a potent circadian repressor that functions independently of CRY and PER. The Exon19:CIPC complex adopts a three-helical coiled-coil bundle conformation containing two Exon19 helices and one CIPC. Unique to Exon19:CIPC, three highly conserved polar residues, Asn341 of CIPC and Gln544 of the two Exon19 helices, are located at the mid-section of the coiled-coil bundle interior and form hydrogen bonds with each other. Combining results from protein database search, sequence analysis, and mutagenesis studies, we discovered for the first time that CLOCK Exon19:CIPC interaction is a conserved transcription regulatory mechanism among mammals, fish, flies, and other invertebrates.

  9. Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum.

    Science.gov (United States)

    Zhou, Xiaolong; Khan, Sikandar G; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; Compe, Emmanuel; Egly, Jean-Marc; DiGiovanna, John J; Kraemer, Kenneth H

    2013-08-01

    XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD.

  10. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    International Nuclear Information System (INIS)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-01-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection

  11. Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England.

    Science.gov (United States)

    Mesher, D; Soldan, K; Howell-Jones, R; Panwar, K; Manyenga, P; Jit, M; Beddows, S; Gill, O N

    2013-12-17

    Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  12. Alcohol consumption and prevalence of human papillomavirus (HPV) infection among US men in the HPV in Men (HIM) study.

    Science.gov (United States)

    Schabath, Matthew B; Thompson, Zachary J; Egan, Kathleen M; Torres, B Nelson; Nguyen, Anthony; Papenfuss, Mary R; Abrahamsen, Martha E; Giuliano, Anna R

    2015-02-01

    Moderate alcohol consumption can impair host defence against viral infections. The objective of this cross-sectional analysis was to assess the association between alcohol intake and prevalent human papillomavirus (HPV) infection among US men enrolled in the HPV in Men (HIM) study using quantitative alcohol intake measured from a Food Frequency Questionnaire. The HIM study is a prospective, multinational study of the natural history of HPV infection. For this report, we restricted our analyses to men from the US cohort (N = 1313). Samples from the corona of glans penis, penile shaft and scrotum were combined for HPV DNA testing. Self-reported alcohol intake was quantified by grams of alcohol intake per day. Multivariable prevalence ratios (mPRs) were used to assess the association between alcohol intake and HPV infections. Prevalent infections were significantly higher among men in the highest quartile of alcohol intake and multivariable models revealed that the highest quartile of alcohol intake was associated with significantly increased risks for any (mPR = 1.13; 95% CI 1.00 to 1.27) HPV types and oncogenic (mPR = 1.35; 95% CI 1.08 to 1.68) HPV types. The fourth quartile of alcohol intake was associated with elevated risks for prevalent HPV infection across all strata of number of sexual partners and among never-smokers and current smokers, but not among former smokers. These results demonstrate that high intake of alcohol is associated with an increased risk for prevalent HPV infections among men. The biological role that alcohol plays in genital HPV infection remains understudied and limited epidemiological data exist, especially among men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

    Science.gov (United States)

    Gemigniani, Franco; Hernández-Losa, Javier; Ferrer, Berta; García-Patos, Vicente

    2015-12-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine. © 2015 Japanese Dermatological Association.

  14. Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin.

    Science.gov (United States)

    Depuydt, C E; Beert, J; Bosmans, E; Salembier, G

    2016-12-01

    In the natural history of HPV infections, the HPV virions can induce two different pathways, namely the infec- tious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that can both lead to cervical cancer and/or temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer.

  15. High frequency of multiple HPV types in cervical specimens from Danish women

    DEFF Research Database (Denmark)

    Mejlhede, Nina; Bonde, Jesper; Fomsgaard, Anders

    2009-01-01

    distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using...... microarray technology, we found that 49% of the HPV-positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high-risk HPV type was HPV-16, which was found in 25% of the HPV-positive cervical specimens. Among the HPV positive...... CIN2+ diagnosed women, 48% were HPV-16 positive. Women younger than 30 years of age had a higher frequency of multiple infections (61%) than women older than 30 years (39%). We conclude that cervical infection with multiple HPV types is common among women in all age groups and among women...

  16. Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine.

    Science.gov (United States)

    Chesson, Harrell W; Laprise, Jean-François; Brisson, Marc; Markowitz, Lauri E

    2016-06-01

    We estimated the potential impact and cost-effectiveness of providing 3-doses of nonavalent human papillomavirus (HPV) vaccine (9vHPV) to females aged 13-18 years who had previously completed a series of quadrivalent HPV vaccine (4vHPV), a strategy we refer to as "additional 9vHPV vaccination." We used 2 distinct models: (1) the simplified model, which is among the most basic of the published dynamic HPV models, and (2) the US HPV-ADVISE model, a complex, stochastic, individual-based transmission-dynamic model. When assuming no 4vHPV cross-protection, the incremental cost per quality-adjusted life-year (QALY) gained by additional 9vHPV vaccination was $146 200 in the simplified model and $108 200 in the US HPV-ADVISE model ($191 800 when assuming 4vHPV cross-protection). In 1-way sensitivity analyses in the scenario of no 4vHPV cross-protection, the simplified model results ranged from $70 300 to $182 000, and the US HPV-ADVISE model results ranged from $97 600 to $118 900. The average cost per QALY gained by additional 9vHPV vaccination exceeded $100 000 in both models. However, the results varied considerably in sensitivity and uncertainty analyses. Additional 9vHPV vaccination is likely not as efficient as many other potential HPV vaccination strategies, such as increasing primary 9vHPV vaccine coverage. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. Pharmacists’ Attitudes and Perceived Barriers to Human Papillomavirus (HPV) Vaccination Services

    OpenAIRE

    Hastings, Tessa J.; Hohmann, Lindsey A.; McFarland, Stuart J.; Teeter, Benjamin S.; Westrick, Salisa C.

    2017-01-01

    Use of non-traditional settings such as community pharmacies has been suggested to increase human papillomavirus (HPV) vaccination uptake and completion rates. The objectives of this study were to explore HPV vaccination services and strategies employed by pharmacies to increase HPV vaccine uptake, pharmacists’ attitudes towards the HPV vaccine, and pharmacists’ perceived barriers to providing HPV vaccination services in community pharmacies. A pre-piloted mail survey was sent to 350 randomly...

  18. Factors associated with HPV vaccination among adult women in Quebec.

    Science.gov (United States)

    Kiely, Marilou; Sauvageau, Chantal; Dubé, Eve; Deceuninck, Genevieve; De Wals, Philippe

    2013-07-01

    Human papillomavirus (HPV) infections are the most common sexually transmitted infections in North America and are associated with cervical cancer. A publicly-funded HPV immunization program was launched in the province of Quebec, Canada, in the fall of 2008. The aim of this study was to explore factors associated with HPV immunization among young adult women not targeted by this program. A questionnaire was mailed to 2400 24-y-old women randomly selected from the Quebec provincial health insurance database and 56% responded. Factors associated with vaccination status were analyzed using a multivariate logistic regression model. Few women had received at least one dose of HPV vaccine among the 1347 respondents. Age at first sexual intercourse ≥ 20 y, participating in cervical cancer screening, higher education level, being born in Quebec and some positive beliefs about HPV were associated with vaccination. The rate of immunization in women who had to pay for the HPV vaccine was very low and was associated with characteristics that are generally associated with a lower risk for HPV infection and cervical cancer. Efforts are needed to reach at-risk adult women.

  19. Public knowledge and attitudes towards Human Papilloma Virus (HPV) vaccination

    Science.gov (United States)

    Walsh, Charlotte Devereaux; Gera, Aradhana; Shah, Meeraj; Sharma, Amit; Powell, Judy E; Wilson, Sue

    2008-01-01

    Background Human Papilloma Virus (HPV) vaccine has undergone successful trials and has recently been approved for use for the primary prevention of cervical cancer. The aim of this study was to determine knowledge and attitudes towards HPV vaccination. Methods Semi-structured interview and questionnaire delivered in a street survey. Standardised HPV-related statements used to measure HPV knowledge and attitudes to vaccination. The setting was three different areas of Birmingham, to target a mix of social class and ethnicity. The sample population was composed of 16–54 year olds. Results A total of 420 participants were recruited. Poor knowledge of HPV and its links with cervical cancer were observed. 81% had a knowledge score of zero. Knowledge about HPV was associated with different ethnic group and socio-economic group. The majority (88%) of participants were in favour of vaccination, with 83.6% indicating that they would allow a child under their care to be vaccinated. Conclusion Initial responses to the proposed HPV vaccination within the UK public are favourable. However, knowledge levels are poor and media and health professional promotion are required to raise awareness. PMID:18947430

  20. Bogarting that joint might decrease oral HPV among cannabis users.

    Science.gov (United States)

    Zwenger, S R

    2009-12-01

    Human papilloma virus (HPV) has many known strains, two of the most well studied perhaps being the high-risk types 16 and 18. These strains have attracted more interest because they are known to disrupt tumour-suppressor genes that control the cell cycle, rendering those genes less effective at keeping cell division in check.Within the last decade, an increase in oral hpv-linked cancers of the throat and tongue has been attributed to exposure and contraction of hpv through oral sex, most notably in younger people. An understudied and arguably equal contributor to oral hpv infection might be indirect contact with an infected person. Presented here is a brief but important perspective on the relationship between cannabis use and oral cancer. The development of oral cancer is not a result of smoking cannabis per se; rather, it is hypothesized to be a result of contracting hpv through various forms of sharing and passing joints and other smoking apparatuses. Therefore, it is hypothesized that bogarting (and not passing) joints might decrease oral hpv among cannabis smokers. Future research should therefore investigate the prevalence of oral hpv in cannabis smokers to better understand its epidemiology.

  1. Awareness of human papillomavirus after introduction of HPV vaccination

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Nygård, Mari; Stensen, Signe

    2017-01-01

    -2005 (prevaccination survey, n=54 079, response rate 71.3%). Correlates of HPV awareness in the postvaccination survey were assessed by logistic regression. In all countries and age groups, awareness of HPV increased from the prevaccination to the postvaccination survey. In the postvaccination survey, HPV awareness......: odds ratio (OR)=0.45, 95% confidence interval (CI): 0.42-0.48], being a virgin (vs. nonvirgins: OR=0.74, 95% CI: 0.66-0.83), never having used condoms (vs. ever: OR=0.62, 95% CI: 0.56-0.67), nonuse of contraception at first intercourse (vs. use: OR=0.83, 95% CI: 0.79-0.88) and daily smoking (vs. never......: OR=0.86, 95% CI: 0.80-0.92). HPV awareness in Scandinavia has increased since the introduction of HPV vaccination. However, 24-38% of Scandinavian women still have never heard of HPV. Future information efforts should target groups with low HPV awareness....

  2. Examining the association between oral health and oral HPV infection.

    Science.gov (United States)

    Bui, Thanh Cong; Markham, Christine M; Ross, Michael Wallis; Mullen, Patricia Dolan

    2013-09-01

    Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25-1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.

  3. HPV vaccine acceptability in high-risk Greek men.

    Science.gov (United States)

    Hoefer, Lea; Tsikis, Savas; Bethimoutis, George; Nicolaidou, Electra; Paparizos, Vassilios; Antoniou, Christina; Kanelleas, Antonios; Chardalias, Leonidas; Stavropoulos, Georgios-Emmanouil; Schneider, John; Charnot-Katsikas, Angella

    2018-01-02

    HPV is associated with malignancy in men, yet there is a lack of data on HPV knowledge, vaccine acceptability, and factors affecting vaccine acceptability in Greek men. This study aims to identify determinants of knowledge and willingness to vaccinate against HPV among high-risk Greek men. Men (n = 298) between the ages of 18 and 55 were enrolled from the STI and HIV clinics at "Andreas Syggros" Hospital in Athens, Greece from July-October 2015. Participants completed a survey on demographics, economic factors, sexual history, HPV knowledge, and vaccine acceptability. The majority of participants were younger than 40 (76.6%) and unmarried (84.6%). Our sample was 31.2% MSM (men who have sex with men), and 20.1% were HIV-positive. Most participants (>90%) were aware that HPV is highly prevalent in both men and women; however, fewer identified that HPV causes cancers in both sexes (68%) and that vaccination protects men and women (67%). Amongst participants, 76.7% were willing to vaccinate themselves against HPV, 71.4% an adolescent son, and 69.3% an adolescent daughter. HIV-positive men were more likely to be willing to vaccinate themselves (OR 2.83, p = .015), a son (OR 3.3, p = .015) or a daughter (3.01, p = .020). Higher income levels were associated with increased willingness to vaccinate oneself (OR 1.32, p = .027), a son (1.33, p = .032) or daughter (1.34, p = .027). Although there is a HPV knowledge gap, HPV vaccine acceptability is high despite lack of vaccine promotion to Greek men. Future studies should include lower-risk men to adequately inform public health efforts.

  4. Human papillomavirus (HPV) information needs: a theoretical framework

    Science.gov (United States)

    Marlow, Laura A V; Wardle, Jane; Waller, Jo; Grant, Nina

    2009-01-01

    Background With the introduction of human papillomavirus (HPV) testing and vaccination in the UK, health professionals will start to receive questions about the virus from their patients. This study aimed to identify the key questions about HPV that British women will ask when considering having an HPV test or vaccination. Methods Face-to-face interviews were carried out with 21 women to discover what they wanted to know about HPV. A thematic framework approach was used to analyse the data and identify key themes in women's HPV knowledge requirements. Results Women's questions about HPV fell into six areas: identity (e.g. What are the symptoms?), cause (e.g. How do you get HPV?), timeline (e.g. How long does it last?), consequences (e.g. Does it always cause cervical cancer?) and control-cure (e.g. Can you prevent infection?). In addition, they asked procedural questions about testing and vaccination (e.g. Where do I get an HPV test?). These mapped well onto the dimensions identified in Leventhal's description of lay models of illness, called the 'Common Sense Model' (CSM). Discussion and conclusions These results indicated that the majority of the questions women asked about HPV fitted well into the CSM, which therefore provides a structure for women's information needs. The findings could help health professionals understand what questions they may be expected to answer. Framing educational materials using the CSM themes may also help health educators achieve a good fit with what the public want to know. PMID:19126314

  5. Comparison of two commercial assays for detection of human papillomavirus (HPV) in cervical scrape specimens: validation of the Roche AMPLICOR HPV test as a means to screen for HPV genotypes associated with a higher risk of cervical disorders.

    NARCIS (Netherlands)

    Ham, M.A.P.C. van; Bakkers, J.M.J.E.; Harbers, G.; Quint, W.G.V.; Massuger, L.F.A.G.; Melchers, W.J.G.

    2005-01-01

    Certain high-risk (HR) human papillomavirus (HPV) types are a necessary cause for the development of cervical disorders. Women with persistent HR HPV infections have an increased risk of developing high-grade cervical lesions, compared with those who have no or low-risk HPV infections. Therefore,

  6. Estimation of the epidemiological burden of HPV-related anogenital cancers, precancerous lesions, and genital warts in women and men in Europe: Potential additional benefit of a nine-valent second generation HPV vaccine compared to first generation HPV vaccines

    Directory of Open Access Journals (Sweden)

    Susanne Hartwig

    2015-12-01

    Full Text Available Introduction: A second generation HPV vaccine has been developed for the prevention of anogenital cancers and precancerous lesions of the cervix, vulva, vagina, anus and of genital warts due to nine HPV types.We estimated the annual burden of these diseases attributable to the nine HPV types compared to HPV types from first generation vaccines in women and men in Europe. Material and methods: Incidence rates from the IARC database, cancer registries, the literature and Eurostat population data were used.The burden attributable to the HPV types targeted by both vaccines was estimated by applying the relative contribution of the respective HPV types from epidemiological studies. Results: In 2013, the number of new anogenital HPV-attributable cancers was 44,480 with 39,494 of these cases related to second vs. 33,285 to first generation vaccine types.Among the 284,373 to 541,621 new HPV-attributable anogenital precancerous lesions 235,364–448,423 and 135,025–256,830 were estimated to be related to second and first generation vaccine types, respectively.The annual number of new genital warts was 753,608–935,318, with 90% related to HPV6/11. Conclusions: These data demonstrate how the large public health impact that was achieved by the first generation HPV vaccines could be further increased by second generation vaccines. Keywords: HPV, Burden of disease, Cancer, Precancerous lesions, Genital warts, HPV vaccine

  7. HPV prevalence in a Mid-European oral squamous cell cancer population: a cohort study.

    Science.gov (United States)

    Dalla Torre, Daniel; Burtscher, Doris; Soelder, Elisabeth; Offermanns, Vincent; Rasse, Michael; Puelacher, Wolfgang

    2018-04-29

    HPV infection has been investigated intensively regarding oropharyngeal carcinoma. However, there is still lack of knowledge about the impact of oral HPV infections concerning oral squamous cell carcinoma. The present study investigates the prevalence of oral HPV infection in such patients, identifying possible differences between HPV+ and HPV- patients. 106 consequent patients were investigated. After completion of a study questionnaire regarding risk factors, a brush smear sample was taken in each subject to identify the individual oral HPV status (overall/low risk/high risk). 35.8% of the patients were tested positive for HPV in the oral cavity (14% low risk, 28.3% high risk). Patients with oral HPV infection and high risk HPV infection were significantly younger (pHPV infection. Finally, patients with high risk oral HPV infection had experienced more tooth extractions during their lifetime. Oral HPV infections may influence the course of disease of oral squamous cell carcinoma as HPV+ patients are about 10 years younger. It seems that high alcohol consumption facilitates high risk HPV infection. It may be presumed that both alcohol consumption and high risk oral HPV infection act synergistically, explaining earlier cancer onset. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Knowledge, Awareness and Attitude on HPV, HPV Vaccine and Cervical Cancer among the College Students in India.

    Science.gov (United States)

    Rashid, Shazia; Labani, Satyanarayana; Das, Bhudev C

    2016-01-01

    Infection of specific high risk Human papillomaviruses (HPVs) is known to cause cervical cancer and two prophylactic vaccines have been developed against two major high risk HPV types 16 and 18 for prevention of cervical cancer. Because of societal, religious and ethical issues associated with the vaccination of adolescent girls in India together with lack of awareness about HPV and HPV vaccines, no successful HPV immunization program has been employed in India. To determine knowledge, awareness and attitude of college students on HPV, HPV vaccine and cervical cancer. A questionnaire-based survey was conducted in a total of 1580 undergraduate students between the age group 16-26 years comprising 684 girls and 876 boys. Out of a total of 1580 students, girls had more knowledge about cervical cancer (82.45%, pawareness about cervical cancer (81.89%, pawareness compared to boys. Analysis of odds ratio (ORs) along with 95% CI showed older girls with 1.2 to 3 fold (pawareness campaigns to augment HPV immunization program for control of cervical cancer in India.

  9. Applying a gender lens on human papillomavirus infection: cervical cancer screening, HPV DNA testing, and HPV vaccination.

    Science.gov (United States)

    Branković, Ivan; Verdonk, Petra; Klinge, Ineke

    2013-02-08

    Our aim is to provide a state-of-the-art overview of knowledge on sex (biological) and gender (sociocultural) aspects of Human papillomavirus (HPV) and cervical cancer for educational purposes. Considerable disparities exist in cervical cancer incidences between different subgroups of women. We provide an outline on the crucial issues and debates based on the recent literature published in leading gender medicine journals. Intersectionality was applied in order to help categorise the knowledge. Key terms (HPV, cervical cancer) were screened in Gender Medicine, Journal of Women's Health and Women & Health from January 2005-June 2012. Additional searches were conducted for topics insufficiently mentioned, such as HPV vaccination of boys. In total, 71 publications were included (56 original papers, four reviews, six reports, three commentaries, one editorial and one policy statement). Research reveals complexity in the way various subgroups of women adhere to cervical screening. Less educated women, older women, uninsured women, homeless women, migrant women facing language barriers, women who have sex with women and obese women participate in Pap smears less frequently. A series of barriers can act to impede decisions to vaccinate against HPV. Both male and female controlled preventive methods and treatment measures should be developed in order to tackle HPV infection and different strategies are needed for different subgroups. A substantial discussion and research on alternative methods of prevention was and is lacking. In future research, sex and gender aspects of HPV-related diseases of boys and men as well as subgroup differences in HPV risk need to be addressed.

  10. Psychosocial correlates of HPV vaccine acceptability in college males: A cross-sectional exploratory study

    Directory of Open Access Journals (Sweden)

    Ovidiu Tatar

    2017-12-01

    Full Text Available Background: Most college males are not immunized against the human papillomavirus (HPV and are at high risk of HPV infection. Most research of correlates of HPV vaccine acceptability in college males has assessed vaccine acceptability as a binary outcome, e.g., vaccinated or not vaccinated, without considering that some students may not even be aware that the HPV vaccine can be given to males. Our objective was to evaluate the psychosocial correlates of HPV acceptability in college males, based on multiple stages of HPV decision-making. Methods: We used an online questionnaire to collect data from college men aged 18–26 enrolled at three Canadian universities between September 2013 and April 2014. Vaccine acceptability assessment was informed by the six-stage decision-making Precaution Adoption Process Model (PAPM. We sought information on socio-demographics, health behaviors, HPV vaccine benefits and barriers, worry, susceptibility, severity related to HPV infection and social norms. HPV and HPV vaccine knowledge was measured with validated scales. Psychosocial correlates of HPV vaccine acceptability were assessed with bivariate and multivariate multinomial logistic regression. Actual and perceived HPV and HPV vaccine knowledge scores were calculated. Results: The final sample size was 428. Most male college students were unaware that the HPV vaccine could be given to males, unengaged or undecided about getting the HPV vaccine. Significant correlates of higher HPV vaccine acceptability were: increased HPV knowledge, having discussed the HPV vaccine with a healthcare provider, and social norms. Being in an exclusive sexual relationship was significantly associated with lower HPV vaccine acceptability. Students' actual HPV and HPV vaccine knowledge was low and positively correlated to their perception about their HPV knowledge. Conclusions: We provided a fine-tuned analysis of psychosocial correlates of HPV vaccine acceptability in college

  11. Conformational control of the binding of the transactivation domain of the MLL protein and c-Myb to the KIX domain of CREB.

    Directory of Open Access Journals (Sweden)

    Elif Nihal Korkmaz

    Full Text Available The KIX domain of CBP is a transcriptional coactivator. Concomitant binding to the activation domain of proto-oncogene protein c-Myb and the transactivation domain of the trithorax group protein mixed lineage leukemia (MLL transcription factor lead to the biologically active ternary MLL∶KIX∶c-Myb complex which plays a role in Pol II-mediated transcription. The binding of the activation domain of MLL to KIX enhances c-Myb binding. Here we carried out molecular dynamics (MD simulations for the MLL∶KIX∶c-Myb ternary complex, its binary components and KIX with the goal of providing a mechanistic explanation for the experimental observations. The dynamic behavior revealed that the MLL binding site is allosterically coupled to the c-Myb binding site. MLL binding redistributes the conformational ensemble of KIX, leading to higher populations of states which favor c-Myb binding. The key element in the allosteric communication pathways is the KIX loop, which acts as a control mechanism to enhance subsequent binding events. We tested this conclusion by in silico mutations of loop residues in the KIX∶MLL complex and by comparing wild type and mutant dynamics through MD simulations. The loop assumed MLL binding conformation similar to that observed in the KIX∶c-Myb state which disfavors the allosteric network. The coupling with c-Myb binding site faded, abolishing the positive cooperativity observed in the presence of MLL. Our major conclusion is that by eliciting a loop-mediated allosteric switch between the different states following the binding events, transcriptional activation can be regulated. The KIX system presents an example how nature makes use of conformational control in higher level regulation of transcriptional activity and thus cellular events.

  12. Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus and Binds to the Transactivation Domain of STAT2.

    Directory of Open Access Journals (Sweden)

    Jennifer H Stuart

    2016-12-01

    Full Text Available The type I interferon (IFN response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells. Ectopic expression of C6 inhibits the induction of interferon stimulated genes (ISGs in response to IFNα treatment at both the mRNA and protein level. C6 inhibits the IFNα-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT signalling pathway at a late stage, downstream of STAT1 and STAT2 phosphorylation, nuclear translocation and binding of the interferon stimulated gene factor 3 (ISGF3 complex to the interferon stimulated response element (ISRE. Mechanistically, C6 associates with the transactivation domain of STAT2 and this might explain how C6 inhibits the type I IFN signalling very late in the pathway. During virus infection C6 reduces ISRE-dependent gene expression despite the presence of the viral protein phosphatase VH1 that dephosphorylates STAT1 and STAT2. The ability of a cytoplasmic replicating virus to dampen the immune response within the nucleus, and the ability of viral immunomodulators such as C6 to inhibit multiple stages of the innate immune response by distinct mechanisms, emphasizes the intricacies of host-pathogen interactions and viral immune evasion.

  13. Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia.

    Science.gov (United States)

    Bogani, Giorgio; Martinelli, Fabio; Ditto, Antonino; Taverna, Francesca; Lombardo, Claudia; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Fontanella, Caterina; Sabatucci, Ilaria; Borghi, Chiara; Recalcati, Dario; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

    2017-03-01

    High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Awareness, knowledge and beliefs about HPV, cervical cancer and HPV vaccines among nurses in Cameroon: an exploratory study.

    Science.gov (United States)

    Wamai, Richard G; Ayissi, Claudine Akono; Oduwo, Geofrey O; Perlman, Stacey; Welty, Edith; Welty, Thomas; Manga, Simon; Onyango, Monica A; Ogembo, Javier Gordon

    2013-10-01

    While it is known that sub-Saharan African countries face multiple obstacles such as cost in adopting vaccination against human papillomavirus (HPV), the crucial role nurses can play in implementing such programs has not been adequately examined. To investigate the knowledge and awareness of HPV, primary cause of cervical cancer and HPV vaccine among nurses working at four Cameroon Baptist Convention Health Services facilities, and to explore what factors influence nurses' willingness to inform and recommend HPV vaccine to adolescents and parents attending clinics. A structured questionnaire survey was administered to a convenience sample of nursing staff working at the four health facilities. Of 192 eligible nurses 76 (39.6%) participated in the study. There were moderately low levels of knowledge about HPV infection and prevention of cervical cancer, but a moderately high level of knowledge about HPV vaccine. Although 90.8% acknowledged that cervical cancer is directly linked to HPV infection, nearly 32% failed to identify it as a sexually transmitted infection (STI), while 43.4% believed it is an uncommon infection. Willingness to recommend the HPV vaccine was moderate, with 69.7% intentionally initiating discussions with patients about the subject. The most important factors considered when deciding to recommend the vaccine included effectiveness (56.6%) and side effects/safety (11.8%). Cost was less of a concern (6.6%), likely due to the availability of donated vaccine. Despite high awareness about HPV, more education about the virus, cervical cancer and the vaccine are required to further increase nurses' willingness to recommend the vaccine and strengthen strategies for reaching adolescents through nurses in Cameroon. Published by Elsevier Ltd.

  15. Biopower, Normalization, and HPV: A Foucauldian Analysis of the HPV Vaccine Controversy.

    Science.gov (United States)

    Engels, Kimberly S

    2016-09-01

    This article utilizes the Foucauldian concepts of biopower and normalization to give an analysis of the debate surrounding the controversial administration of the HPV vaccine to adolescents. My intention is not to solve the problem, rather to utilize a Foucauldian framework to bring various facets of the issue to light, specifically the way the vaccine contributes to strategies of power in reference to how young adults develop within relationships of power. To begin, the article provides an overview of the Foucauldian concepts of biopower and normalization, including how these two strategies of power were present in the administration of the smallpox vaccine in the 19th century. Next, information about HPV and the history of the current controversy in the United States is presented. Lastly, the article presents an analysis of the strategies of biopower and normalization present in the debate on HPV, including an emphasis on how the vaccination is similar to, and different from, 19th century smallpox vaccination. It also explores the way that mechanisms of disease control affect and are affected by individual subjects, in this case, adolescents.

  16. HPV vaccination coverage of teen girls: the influence of health care providers.

    Science.gov (United States)

    Smith, Philip J; Stokley, Shannon; Bednarczyk, Robert A; Orenstein, Walter A; Omer, Saad B

    2016-03-18

    Between 2010 and 2014, the percentage of 13-17 year-old girls administered ≥3 doses of the human papilloma virus (HPV) vaccine ("fully vaccinated") increased by 7.7 percentage points to 39.7%, and the percentage not administered any doses of the HPV vaccine ("not immunized") decreased by 11.3 percentage points to 40.0%. To evaluate the complex interactions between parents' vaccine-related beliefs, demographic factors, and HPV immunization status. Vaccine-related parental beliefs and sociodemographic data collected by the 2010 National Immunization Survey-Teen among teen girls (n=8490) were analyzed. HPV vaccination status was determined from teens' health care provider (HCP) records. Among teen girls either unvaccinated or fully vaccinated against HPV, teen girls whose parent was positively influenced to vaccinate their teen daughter against HPV were 48.2 percentage points more likely to be fully vaccinated. Parents who reported being positively influenced to vaccinate against HPV were 28.9 percentage points more likely to report that their daughter's HCP talked about the HPV vaccine, 27.2 percentage points more likely to report that their daughter's HCP gave enough time to discuss the HPV shot, and 43.4 percentage points more likely to report that their daughter's HCP recommended the HPV vaccine (pteen girls administered 1-2 doses of the HPV vaccine, 87.0% had missed opportunities for HPV vaccine administration. Results suggest that an important pathway to achieving higher ≥3 dose HPV vaccine coverage is by increasing HPV vaccination series initiation though HCP talking to parents about the HPV vaccine, giving parents time to discuss the vaccine, and by making a strong recommendation for the HPV. Also, HPV vaccination series completion rates may be increased by eliminating missed opportunities to vaccinate against HPV and scheduling additional follow-up visits to administer missing HPV vaccine doses. Published by Elsevier Ltd.

  17. Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays.

    Science.gov (United States)

    Zhang, Lahong; Dai, Yibei; Chen, Jiahuan; Hong, Liquan; Liu, Yuhua; Ke, Qiang; Chen, Yiwen; Cai, Chengsong; Liu, Xia; Chen, Zhaojun

    2018-01-01

    A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections. © 2017 Wiley Periodicals, Inc.

  18. A randomized controlled trial of Human Papillomavirus (HPV testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial

    Directory of Open Access Journals (Sweden)

    Smith Laurie W

    2010-03-01

    Full Text Available Abstract Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5% were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%. In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%. Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  19. A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)

    International Nuclear Information System (INIS)

    Ogilvie, Gina S; Cook, Darrel A; Mei, Wendy; Stuart, Gavin CE; Franco, Eduardo L; Coldman, Andrew J; Niekerk, Dirk J van; Krajden, Mel; Martin, Ruth E; Ehlen, Thomas G; Ceballos, Kathy; Peacock, Stuart J; Smith, Laurie W; Kan, Lisa

    2010-01-01

    In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  20. Human Papilloma Virus (HPV) Infection and HPV Vaccination: Assessing the Level of Knowledge among Students of the University of Medicine and Pharmacy of Tirgu Mures, Romania

    OpenAIRE

    Septimiu Voidazan; Silviu-Horia Morariu; Monica Tarcea; Horațiu Moldovan; Minodora Dobreanu

    2016-01-01

    Introduction: Human Papilloma Virus (HPV) infection, a cause in the development of cervical cancer, remains a topic of great interest. About 80% of sexually active women are at risk of acquiring an HPV infection at some point in life, the peak incidence of infection having been identified in young women. The aim of the study was to assess medical students’ knowledge and attitudes about sexually transmitted diseases, HPV infection, HPV vaccinations, and the students’ sexual behaviour. Material...

  1. DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

    Science.gov (United States)

    Murphy, Shawn P; Holtz, Renae; Lewandowski, Nicole; Tomasi, Thomas B; Fuji, Hiroshi

    2002-09-15

    MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA). Analysis of stable hybrids suggests that CIITA expression is repressed by a dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA and class II expression in class II negative L1210 cells, and this effect appears to be restricted to transformed cell lines derived from the early stages of B cell ontogeny. Transient transfection assays demonstrated that the CIITA type III promoter is active in class II(-) L1210 cells, despite the fact that the endogenous gene is not expressed, which suggests that these cells have all of the transacting factors necessary for CIITA transcription. An inverse correlation between methylation of the CIITA transcriptional regulatory region and CIITA expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment activated CIITA expression in class II-negative L1210 cells. Collectively, our results suggest that 1) CIITA gene expression is repressed in class II(-) L1210 cells by methylation of the CIITA upstream regulatory region, and 2) treatment with DNA-alkylating agents overcomes methylation-based silencing of the CIITA gene in L1210 cells.

  2. Frontotemporal dementia with trans-activation response DNA-binding protein 43 presenting with catatonic syndrome.

    Science.gov (United States)

    Watanabe, Ryohei; Kawakami, Ito; Onaya, Mitsumoto; Higashi, Shinji; Arai, Nobutaka; Akiyama, Haruhiko; Hasegawa, Masato; Arai, Tetsuaki

    2017-11-07

    Catatonia is a clinical syndrome characterized by symptoms such as immobility, mutism, stupor, stereotypy, echophenomena, catalepsy, automatic obedience, posturing, negativism, gegenhalten and ambitendency. This syndrome occurs mostly in mood disorder and schizophrenic patients, and is related to neuronal dysfunction involving the frontal lobe. Some cases of frontotemporal dementia (FTD) with catatonia have been reported, but these cases were not examined by autopsy. Here, we report on a FTD case which showed catatonia after the first episode of brief psychotic disorder. At the age of 58, the patient had a sudden onset of disorganized behavior and meaningless speech. Psychotropic drugs were effective for catatonic symptoms. However, after remission apathy, hyperorality, socially inappropriate behavior, hoarding, and an instinctive grasp reaction appeared and persisted. Brain MRI showed significant atrophy of the bilateral fronto-temporal lobes. A neuropathological examination revealed extensive trans-activation response DNA-binding protein 43 (TDP-43) positive neurocytoplasmic inclusions and dystrophic neurites in the brain, including the cerebral cortex, basal ganglia, and brainstem. Pathological diagnosis was frontotemporal lobar degeneration (FTLD) with TDP-43 (FTLD-TDP) type C, which was also confirmed by the band pattern of C-terminal fragments of TDP-43 on western blotting of sarkosyl-insoluble fractions extracted from the frozen brain. Dysfunction of the thalamus, globus pallidus, supplementary motor area, amygdala and cingulate cortex have been said to be related to the catatonic syndrome. In this case, these areas were affected, showing abnormal TDP-43-positive structures. Further studies are expected to confirm further clinical - pathological correlations to FTLD. © 2017 Japanese Society of Neuropathology.

  3. Genotype-Specific Clearance of Genital Human Papillomavirus (HPV) Infections among Mothers in the Finnish Family HPV Study▿

    OpenAIRE

    Louvanto, Karolina; Syrjänen, Kari J.; Rintala, Marjut A. M.; Grénman, Seija E.; Syrjänen, Stina M.

    2010-01-01

    The majority of cervical human papillomavirus (HPV) infections in young women are transient, but whether the clearance differs among different HPV genotypes and the different factors predicting genotype-specific clearance are partly unknown. In the Finnish Family HPV Study, 131 of 252 women (mean age, 25.5 years) cleared their infection during the prospective follow-up of 6 years (median, 62.4 months; range, 1.6 to 94.5 months). Cervical scrapings collected at each visit were tested for 24 lo...

  4. A systems biology analysis of the changes in gene expression via silencing of HPV-18 E1 expression in HeLa cells.

    Science.gov (United States)

    Castillo, Andres; Wang, Lu; Koriyama, Chihaya; Eizuru, Yoshito; Jordan, King; Akiba, Suminori

    2014-10-01

    Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.

  5. Comparison of the immunogenicity of Cervarix(®) and Gardasil(®) human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults

    DEFF Research Database (Denmark)

    Toft, Lars; Tolstrup, Martin; Müller, Martin

    2014-01-01

    (®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross......-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross...

  6. No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors

    NARCIS (Netherlands)

    Woestenberg, Petra J.; King, Audrey J.; van der Sande, Marianne A. B.; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R. M.; Hoebe, Christian J. P. A.; Bogaards, Johannes A.; van Benthem, Birgit H. B.; Adema, D.; Buist-Arkema, R.; Beerens, A.; Luijt, D.; Meijer, S.; Schirm, J.; Buiting, A.; Peeters, M.; Rossen, J.; Verbakel, H.; van Esch, P.; Verweij, J.; van der Eijk, A.; Huisman, R.; Kerkhof, C.; Korff, H.; Schutten, M.; Velzing, J.; Verduyn-Lunel, F.; Lakbiach, S.; van Rosmalen, P.; Schuurman, R.; Abma, D.; Adams, K.; Bruisten, S.; Linde, I.; Oostvogel, P.; Touwen, C.; Vermeulen, W.; Brink, A.; Nelissen, J.; Wolffs, P.; Duijvendijk, N.; Schneeberger, P.; Dinnissen-van Poppel, M.; Melchers, W.; Poort, Y.; Hooghiemstra, M.; Huisman, H.; Weel, J.; Stam, J.

    2017-01-01

    Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity

  7. No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors

    NARCIS (Netherlands)

    Woestenberg, Petra J.; King, Audrey J.; van der Sande, Marianne A B; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R M; Hoebe, Christian J P A; Bogaards, Johannes A.; van Benthem, Birgit H B

    OBJECTIVES: Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11

  8. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

    DEFF Research Database (Denmark)

    Olsson, Sven-Eric; Kjaer, Susanne K; Sigurdsson, Kristján

    2009-01-01

    Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL((R))/SILGARD((R))) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical...

  9. An analysis of HPV infection incidence and clearance by genotype and age in men: The HPV Infection in Men (HIM) Study.

    Science.gov (United States)

    Ingles, Donna J; Lin, Hui-Yi; Fulp, William J; Sudenga, Staci L; Lu, Beibei; Schabath, Matthew B; Papenfuss, Mary R; Abrahamsen, Martha E; Salmeron, Jorge; Villa, Luisa L; Ponce, Eduardo Lazcano; Giuliano, Anna R

    2015-12-01

    Genital HPV infection in men causes benign and cancerous lesions, the incidence of which differs by age. The goal of this work was to comprehensively evaluate incidence and clearance of individual HPV genotypes among men by age group. HIV-negative men ages 18-70 with no history of anogenital cancer were recruited for the HPV Infection in Men (HIM) Study . Participants completed clinical exams and questionnaires every six months for up to ~4 years. Genital specimens underwent HPV genotyping, with associations between age and HPV assessed using Cox analyses. 4085 men were followed for a median of 48.6 months (range: 0.3-94.0). Significantly lower HPV incidence rates were observed among the oldest age group (55-70 years) for grouped high-risk (incidence rate ratio [IRR]=0.71), HPV16 (IRR=0.54), grouped low-risk (IRR=0.74), and HPV6 (IRR=0.57) infections compared to men ages 18-24. However, incidence of the grouped 9-valent HPV vaccine types remained constant across the lifespan. Likelihood of HPV6 and HPV16 clearance remained constant until age 54, then increased significantly for men ages 55-70 (adjusted hazard ratio [AHR]=1.92 and 1.65, respectively). Men remain susceptible to HPV infections throughout their lifespan, highlighting the need for prevention efforts with long-lasting duration.

  10. Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: Design, methods and preliminary results of the HERITAGE study.

    Science.gov (United States)

    Trottier, Helen; Mayrand, Marie-Hélène; Coutlée, François; Monnier, Patricia; Laporte, Louise; Niyibizi, Joseph; Carceller, Ana-Maria; Fraser, William D; Brassard, Paul; Lacroix, Jacques; Francoeur, Diane; Bédard, Marie-Josée; Girard, Isabelle; Audibert, François

    2016-12-01

    Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3-6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women (45%[95%CI:37-53%]) and in placentas (14%[8-21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5-22%]. HPV was detected in children in multiple sites including the conjunctiva (5%[10-14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA

    International Nuclear Information System (INIS)

    Caselmann, W.H.; Meyer, M.; Kekule, A.S.; Lauer, U.; Hofschneider, P.H.; Koshy, R.

    1990-01-01

    The X gene of wild-type hepatitis B virus or integrated DNA has recently been shown to stimulate transcription of a variety of enhancers and promoters. To further delineate the viral sequences responsible for trans-activation in hepatomas, the authors cloned the single hepatitis B virus insert from human hepatocellular carcinoma DNA M1. The plasmid pM1 contains 2004 base of hepatitis B virus DNA subtype adr, including truncated preS/S sequences and the enhancer element. The X promoter and 422 nucleotides of the X coding region are present. The entire preC/C gene is deleted. In transient cotransfection assays using Chang liver cells (CCL 13), pM1 DNA exerts a 6- to 10-fold trans-activating effect on the expression of the pSV2CAT reporter plasmid. The transactivation occurs by stimulation of transcription and is dependent on the simian virus 40 enhancer in the reporter plasmid. Deletion analysis of pM1 subclones reveals that the transactivator is encoded by preS/S and not by X sequences. A frameshift mutation within the preS2 open reading frame shows that this portion is indispensable for the trans-activating function. Initiation of transcription has been mapped to the S1 promoter. A comparable trans-activating effect is also observed with cloned wild-type hepatitis B virus sequences similarly truncated. These results show that a transcriptional trans-activator function not present in the intact gene is generated by 3' truncation of integrated hepatitis B virus DNA preS/S sequences

  12. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

    Science.gov (United States)

    Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

    2016-01-04

    The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Anticipated Regret and Omission Bias in HPV Vaccination Decisions

    DEFF Research Database (Denmark)

    Jensen, Niels Holm

    2017-01-01

    This study investigated effects of anticipated regret on parents’ HPV vaccination intentions and effects of omission bias on HPV vaccination intentions and vaccine uptake. An online survey was completed by 851 parents of adolescent girls in Denmark, a country where HPV vaccine safety is currently...... heavily debated. Multivariate regression analyses revealed anticipated inaction regret as a significant positive predictor of vaccination intentions, and, anticipated action regret as a significant negative predictor of vaccination intentions. Multivariate analyses also revealed omission bias...... in a hypothetical vaccination vignette as a significant negative predictor of HPV vaccination intention as well as vaccine uptake. Finally, the study tested effects of anticipated regret and omission bias on evaluations of two extisting Danish pro-vaccine campaign videos. Here, the result revealed anticipated...

  14. Does HPV status influence survival after vulvar cancer?

    DEFF Research Database (Denmark)

    Rasmussen, Christina Louise; Sand, Freja Laerke; Hoffmann Frederiksen, Marie

    2018-01-01

    High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV...... status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic...... search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I2...

  15. The HPV vaccine - What the family practitioner needs to know

    African Journals Online (AJOL)

    integration of the virus into the replicative mechanisms of the basal cells, the impact of ... vertical transmission of HPV infection and my lead to significant airway ... or excisional strategies with the intention to decrease the likelihood of invasive ...

  16. HPV Vaccine Awareness, Barriers, Intentions, and Uptake in Latina Women.

    Science.gov (United States)

    Lechuga, Julia; Vera-Cala, Lina; Martinez-Donate, Ana

    2016-02-01

    Latina women are at heightened risk of cervical cancer incidence and mortality. The human papillomavirus (HPV) is the principal cause of the majority of cervical cancer cases. A vaccine that protects against HPV was licensed in 2006. Eight years post-licensure, mixed research findings exist regarding the factors that predict vaccine uptake in Latinas. We conducted a population-based phone survey with a random sample of 296 Latinas living in a Midwestern U.S. City. Intention to vaccinate was significantly associated with health care provider recommendations, worry about side effects, knowing other parents have vaccinated, perceived severity of HPV, and worry that daughter may become sexually active following vaccination. Worry that daughter may become sexually active was the only factor related to vaccine uptake. Findings suggest that training providers to discuss the low risk of severe side effects, consequences of persistent HPV, and sexuality related concerns with Latino women may encourage vaccination.

  17. All Adventurous Women Do: HPV, Narrative, and HBO's Girls.

    Science.gov (United States)

    Rogers, Brian

    2016-01-01

    This study looks at media portrayals of sexual health through the popular HBO television show Girls. This rhetorical criticism of Girls delineates two emergent narrative themes. First, the show repeatedly discusses human papillomavirus (HPV) in terms of its severity, but it oscillates in terms of representing the degree of significance. Second, the show frames the source of infection as more important than other concerns related to HPV. Ultimately, this analysis demonstrates that Girls perpetuates a problematic narrative plot structure related to issues of HPV transmission; it also provides a largely scientifically accurate portrayal of HPV and promotes open and frank discussions of sexual health. It is argued that mediated narratives, such as Girls, might have the potential to transform social attitudes and actions and should thereby garner attention from health communication scholars and public health advocates.

  18. Effect of School-based Human Papillomavirus (HPV) Vaccination on ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    assessed girls' knowledge of cervical cancer and HPV vaccine, and their acceptance of future vaccination of ... studies involve parents and young adults. The ... vaccine was delivered during the routine Child ... and attitudes about the vaccine.

  19. Social media microblogs as an HPV vaccination forum.

    Science.gov (United States)

    Zhang, Chupei; Gotsis, Marientina; Jordan-Marsh, Maryalice

    2013-11-01

    The 2006 US FDA approval of the human papillomavirus (HPV) vaccine brought new hope for cancer prevention. Gardasil and Cervarix are widely available vaccines that can deter HPV infection, which causes 70% of cervical cancer. Acceptance of vaccination varies due to a lack of HPV awareness and HPV vaccine knowledge. Recent observations of the Chinese microblog "SinaWeibo" suggest a new approach to engage health professionals and consumer website bloggers. Websites that present the latest fashion, fitness or beauty news and ways to obtain "deals" have created informative blogs or online communities that appeal to female users. Some users raise health questions of their peers. Health professionals, as website bloggers, can introduce vaccine news or respond to conversations between bloggers and their followers. By transforming medical vocabulary into ordinary chat, microblogs may promote efficiency in vaccine education and communication. A web-based, interactive social media-microblog could offer an ideal platform to speed up information dissemination and increase targeted communication.

  20. Genetic susceptibility to HPV infection and cervical cancer

    Directory of Open Access Journals (Sweden)

    Maciag P.C.

    1999-01-01

    Full Text Available Squamous cell carcinoma of the cervix (SCCC is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV is the major risk factor to develop malignant lesions in the cervix. Polymorphisms of the MHC and p53 genes seem to influence the outcome of HPV infection and progression to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53 and mediates its degradation by the ubiquitin pathway. The role of these polymorphisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.

  1. The high-risk HPV infection and urinary system tumor

    Directory of Open Access Journals (Sweden)

    Yang Wenyan

    2018-04-01

    Full Text Available HPV is classified into high-risk and low-risk types depending on its probability of leading to tumorigenesis. Many studies have shown that HPV infection, especially the infection caused by the high-risk type, is always related to prostate cancer, bladder cancer, penile cancer, testicular cancer, and other urinary system tumors. However, previous studies differed in sexual openness and racial genetic susceptibility of the study object, sample size, and experimental methods. Hence, the correlation between high-risk HPV infection and urinary system tumors remains controversial. The early open reading frame of the HPV genome is composed of E1–E7, among which E6 and E7 are the key transfer proteins. The combination of these proteins with oncogene and anti-oncogene may be one of the mechanisms leading to tumorigenesis.

  2. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    International Nuclear Information System (INIS)

    Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela; Banks, Lawrence

    2014-01-01

    The HPV-16 E6 and E6 ⁎ proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6 ⁎ . Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8

  3. THE HPV STATUS IN BLADDER CANCER, TUMOR MORPHOLOGICAL CHARACTERISTICS, AND CLINICAL FEATURES OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    D. A. Golovina

    2014-01-01

    Full Text Available The data of medical records of 101 patients with urothelial bladder cancer (BC were compared with the results of laboratory detection of human papillomaviruses (HPV in the tumor tissue samples taken from these patients during transurethral resection. DNA of HPV 16, the major type of the virus responsible for the occurrence of cervical cancer, was previously detected in 38 samples; and oncogenes E6 and E7 mRNA and HPV 16 E7 oncoprotein were found in 13 of these samples. Comparison of HPV-positive and HPV-negative groups revealed that HPV-positive BC showed higher cell anaplasia than HPV-negative one; moreover, primary cancer was HPV-positive more frequently than recurrent cancer. Sex, age, muscular layer invasion did not correlate with the HPV positivity of BC. 

  4. THE HPV STATUS IN BLADDER CANCER, TUMOR MORPHOLOGICAL CHARACTERISTICS, AND CLINICAL FEATURES OF THE DISEASE

    Directory of Open Access Journals (Sweden)

    D. A. Golovina

    2014-07-01

    Full Text Available The data of medical records of 101 patients with urothelial bladder cancer (BC were compared with the results of laboratory detection of human papillomaviruses (HPV in the tumor tissue samples taken from these patients during transurethral resection. DNA of HPV 16, the major type of the virus responsible for the occurrence of cervical cancer, was previously detected in 38 samples; and oncogenes E6 and E7 mRNA and HPV 16 E7 oncoprotein were found in 13 of these samples. Comparison of HPV-positive and HPV-negative groups revealed that HPV-positive BC showed higher cell anaplasia than HPV-negative one; moreover, primary cancer was HPV-positive more frequently than recurrent cancer. Sex, age, muscular layer invasion did not correlate with the HPV positivity of BC. 

  5. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    Energy Technology Data Exchange (ETDEWEB)

    Manzo-Merino, Joaquin [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Massimi, Paola [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy); Lizano, Marcela, E-mail: lizanosoberon@gmail.com [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Banks, Lawrence, E-mail: banks@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)

    2014-02-15

    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  6. Change in knowledge of women about cervix cancer, human papilloma virus (HPV) and HPV vaccination due to introduction of HPV vaccines.

    Science.gov (United States)

    Donders, Gilbert G G; Bellen, Gert; Declerq, Ann; Berger, Judith; Van Den Bosch, Thierry; Riphagen, Ine; Verjans, Marcel

    2009-07-01

    Test knowledge of HPV, cervix cancer awareness and acceptance of HPV vaccination of women now and a year ago. Questionnaires were filled out by 305 women visiting four gynaecologists of the Regional Hospital Heilig Hart, Tienen, Belgium during two subsequent weeks. Fisher T or Chi(2) were used as statistical methods to compare the data with the survey of 381 women exactly one year before. Knowledge about HPV as a cause of cervix cancer and the presence of a vaccine rose from roughly 50% in 2007 to over 80% in 2008 (pwomen below 26 years had now acquired almost equivalent knowledge to older women about the virus, cervix cancer and the vaccine, but they were far less likely to accept the vaccine due to its cost, unless it would be reimbursed (OR 4.2 (1.6-11) p=0.0055). One year after introduction of the first two HPV vaccines, over 75% of women attending an ambulatory gynaecology clinic know HPV causes cervix cancer and that you can get vaccinated against it. Compared with a year earlier, young and lower educated women had dramatically improved their knowledge. However, women below 26 years are less prepared to pay the cost for vaccination if it is not reimbursed.

  7. An Examination of HPV16 Natural Immunity in Men Who Have Sex with Men (MSM) in the HPV in Men (HIM) Study.

    Science.gov (United States)

    Beachler, Daniel C; Pinto, Ligia A; Kemp, Troy J; Nyitray, Alan G; Hildesheim, Allan; Viscidi, Raphael; Schussler, John; Kreimer, Aimée R; Giuliano, Anna R

    2018-04-01

    Background: Evidence suggests that natural antibodies developed after HPV16 infection may protect some women but not men against subsequent HPV16 reacquisition. Less is known whether antibodies developed following HPV16 infection are protective among men who have sex with men (MSM). Methods: Four hundred seventy-five MSM from the Human Papillomavirus Infection in Men (HIM) study were tested for serum antibodies to HPV16 L1 using enzyme-linked immunosorbent assays, and for anal and genital HPV16 DNA using PCR consensus primer system (PGMY 09/11). Adjusted Cox regression was used to evaluate whether baseline HPV16 seropositivity impacts subsequent genital or anal HPV16 DNA. Results: The risk of subsequent genital HPV16 [aHR = 1.05, 95% confidence interval (CI) = 0.66-1.68] and anal HPV16 infections among MSM (aHR = 2.34, 95% CI = 0.92-5.98) was similar or nonsignificantly higher in HPV16-seropositive than HPV16-seronegative MSM. The risk of genital HPV16 was also similar between HPV16-seronegative and HPV16-seropositive MSM in the highest tertile of HPV16 antibody levels and when restricting to those with new sex partners during follow-up ( P > 0.20). Among the 118 MSM who were HPV16 seropositive, 90% remained HPV16 seropositive up to 4 years later. When tested together, MSM with the highest antibody titers (top tertile) had similar levels to females (mean = 130.3 vs. 134.5 EU/mL, P = 0.84). Conclusions: Despite years of HPV16 seropositivity persistence and antibody titers comparable with females, this study suggested no evidence of HPV16 natural antibodies protecting against subsequent genital or anal HPV16 infection in MSM. Impact: This could help partially explain the high incidence of genital and anal HPV16 infection and related anal cancer seen in middle-aged and older MSM. Cancer Epidemiol Biomarkers Prev; 27(4); 496-502. ©2018 AACR . ©2018 American Association for Cancer Research.

  8. Barriers, facilitators, and potential strategies for increasing HPV vaccination: A statewide assessment to inform action

    Directory of Open Access Journals (Sweden)

    Kathleen B. Cartmell

    2018-06-01

    Full Text Available Objective: The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. Design: An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. Results: Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1 addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2 advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3 coordination of efforts. Discussion: A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state. Keywords: HPV, HPV vaccines, Cervical cancer, Prevention, Health systems, Barriers, Facilitators, Strategies, South Carolina

  9. Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17–36

    Directory of Open Access Journals (Sweden)

    Stephanie M. Bywaters

    2017-11-01

    Full Text Available The currently available nonavalent human papillomavirus (HPV vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs (H16.V5, H16.U4 and H16.7E and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17–36. The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers.

  10. Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17-36.

    Science.gov (United States)

    Bywaters, Stephanie M; Brendle, Sarah A; Tossi, Kerstin P; Biryukov, Jennifer; Meyers, Craig; Christensen, Neil D

    2017-11-10

    The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17-36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers.

  11. NF-Y loss triggers p53 stabilization and apoptosis in HPV18-positive cells by affecting E6 transcription

    OpenAIRE

    Benatti, Paolo; Basile, Valentina; Dolfini, Diletta; Belluti, Silvia; Tomei, Margherita; Imbriano, Carol

    2016-01-01

    The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonical motif within the URR and activates viral gene expression. In addition, NF-Y indirectly up-regulat...

  12. Impact of HPV vaccination with Gardasil® in Switzerland.

    Science.gov (United States)

    Jacot-Guillarmod, Martine; Pasquier, Jérôme; Greub, Gilbert; Bongiovanni, Massimo; Achtari, Chahin; Sahli, Roland

    2017-12-22

    Gardasil®, a quadrivalent vaccine targeting low-risk (6, 11) and high-risk (16, 18) human papillomaviruses (HPV), has been offered to 11-14 year-old schoolgirls in Switzerland since 2008. To evaluate its success and its potential impact on cervical cancer screening, HPV genotypes were examined in 18-year-old girls five years later (sub-study 1) and in outpatients participating to cervical cancer screening before and after vaccine implementation (sub-study 2). For sub-study 1, 3726 females aged 18 in 2013 were invited to fill a questionnaire on personal demographics and HPV risk factors and to provide a self-collected cervicovaginal sample for HPV genotyping and Chlamydia trachomatis PCR. Personal data were evaluated by univariable and multivariable statistics. In sub-study 2, the proportion of the vaccine-type HPV among anogenital HPV was examined with archived genotyping data of 8039 outpatients participating to cervical cancer screening from 1999 till 2015. The yearly evolution of this proportion was evaluated by segmented logistic regression. 690 (18.5%) women participated to sub-study 1 and 327 (8.8%) provided a self-collected sample. Prevalence of Chlamydia trachomatis (4.6%) and demographics confirmed that the subjects were representative of sexually-active Swiss young women. Vaccine (five-year coverage: 77.5%) was preferentially accepted by contraceptive-pill users (P = 0.001) and samples were mainly provided by sexually-active subjects (P Switzerland. Our data suggest that cervical cancer screening is now entering a stage of reduced proportion of HPV16 and/or 18 in samples reported positive by cytology. In view of the high likelihood of reduced clinical specificity of cytology, primary screening modalities involving HPV testing and cytology should now be re-evaluated in Switzerland.

  13. African American Parents’ HPV Vaccination Intent and Concerns

    OpenAIRE

    Sanders Thompson, Vetta L.; Arnold, Lauren D.; Notaro, Sheri R.

    2012-01-01

    This study describes attitudes and social and environmental factors that affect African American parents’ intent to vaccinate their daughters against human papillomavirus (HPV). Thirty African American parents of daughters aged nine to 17 years and no history of HPV infection completed semi-structured interviews. Interviews addressed factors that influenced intent to vaccinate, perception of community norms related to vaccination, vaccination scenarios involving place of vaccination, and vacc...

  14. Parent perceptions of dentists' role in HPV vaccination.

    Science.gov (United States)

    Lazalde, Gabriela E; Gilkey, Melissa B; Kornides, Melanie L; McRee, Annie-Laurie

    2018-01-25

    Offering HPV vaccine in settings beyond the traditional medical home holds promise for increasing the currently low levels of coverage. As adolescents frequently visit dentists, dental practices may be one such alternative vaccination setting. This study assessed parent attitudes about the roles dental providers could play in HPV prevention, including vaccine provision. In September 2016, we conducted an online survey using a national sample (n = 1209) of U.S. parents of adolescent children aged 11-17. Adolescents' mean age was 14; 53% were male and 62% were non-Hispanic white. We identified correlates of parents' comfort with dentists as HPV vaccinators using multivariable logistic regression. Overall, 23% of parents reported that they would feel comfortable with their child receiving HPV vaccine from a dentist. In multivariable analyses, parents had greater odds of being comfortable if they had higher trust in their child's primary care provider (OR = 1.27, 95% CI: 0.96-1.68) and lower odds if their child was female (OR = 0.65, 95% CI: 0.50-0.86). Convenience (20%) and oral health expertise (20%) were the most commonly cited benefits of dentists administering the vaccine. Wanting their child's regular provider to administer and track vaccinations (61% and 58%, respectively), and lack of insurance coverage (30%) were the most commonly cited concerns. Parents expressed somewhat greater comfort with roles dentists might play in promoting HPV vaccination other than vaccine delivery, such as providing education. Parents in this sample had low comfort with dentists as HPV vaccinators. Findings from this study highlight potential concerns to be addressed before dental practices consider offering HPV vaccination in the future. Further research should assess dentists' perspectives and explore alternative roles for dental providers in HPV prevention efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. HPV infection in premalign and malign cervical lesions

    Directory of Open Access Journals (Sweden)

    Hakan Yetimalar

    2009-12-01

    Full Text Available Aim: Our aim is to detect the incidence and rate of high risk HPV-DNA in patients with cervical cancer,HGSIL,LGSIL or ASCUS and compare those findings with patients presenting with totally benign servical smears as well as to search for the factors influencing these rates. Materials and Methods: 85 patients with cytologic and histologic proven cervical carcinoma, HGSIL, LGSIL, ASCUS and 178 patients with totally benign (normal or infecton smear results as a control group who attented to Atatürk Training and Research Hospital 3rd Obstetrics and Gynecology Clinics between the dates of January 2006- July 2008 were included to our study. Within these patients age, first sexual intercourse, age, smoking habit, number of sexual partners, age of menarche and contraception methods were recorded. Pap smears and smears for detection of high risk HPV were taken concurrently from cervical transformation zone and external cervical ostium and the incidence of high risk HPV-DNA were examined. Results: High risk HPV DNA rate was detected as 65.2% positive in cervical carcinoma patients in our study. High risk HPV-DNA was positive in 54.8% of patients with HGSIL while it was positive in 25% of patients with LGSIL. High risk HPV-DNA was positive in 5% of patients with benign cervical cytology results. Discussion: The positivity rates of high risk HPV-DNA results in cervical carcinoma, HGSIL, LGSIL patients and in patients with benign cervical cytologies were statistically significant. When the age of menarche and contraception method were considered the HPV-DNA positivity rates’ differences were statistically insignificant.The differences for the age of first sexual intercourse, number of sexual partners, age and smoking habits were statistically significant.

  16. Significance of Compression in Binucleation while Differentiating Reactive Cellular Changes Between Human Papillomavirus and Candida Infections

    Science.gov (United States)

    Okodo, Mitsuaki; Okayama, Kaori; Fukui, Tadasi; Shiina, Natsuko; Caniz, Timothy; Yabusaki, Hiromi; Fujii, Masahiko

    2017-09-27

    Purpose: Binucleation is a reactive cellular change (RCC) in Pap smears due to Candida infection. However, the origin of these binucleated cells as RCCs remains unclear. The purpose of this study was to examine binucleation in patients negative for intraepithelial lesion or malignancy (NILM) and infected with Candida and those infected with high-risk human papillomavirus (hr-HPV) and to clarify the origin of the binucleated cells. Methods: A total of 115 endocervical swab specimens with a combined diagnosis of NILM, Candida infection, and RCCs were used for this study. Pap smears were used to identify binucleated cells and then separate them into two groups, compression-positive and compression-negative. In addition, hr-HPV was detected using polymerase chain reaction (PCR) with a specific primer on the DNA extracted from the remaining residual cytology specimens. To make the hr-HPV-infected binucleated cells visible, an in situ PCR assay was performed on the Pap smear. Result: Of the 115 specimens, 69.6% contained binucleated cells, 26 (32.5%) showed only the compressed form, 35 (43.8%) showed only the non-compressed form, and 19 showed both the compressed and non-compressed forms of binucleated cells. Also, 34 specimens (29.6%) were positive for hr-HPV. The sensitivity and specificity of compression-positive binucleated cells were 91.2% and 82.7% (p compression-negative group (p = 0.156). Also, 34 cases with hr-HPV contained 99 compression-positive and 24 compression-negative cells. The hr-HPV-positive cells accounted for 68 (68.7%) of the 99 compression-positive and 2 (8.3%) of the 24 compression-negative binucleated cells as determined by an in situ PCR assay for hr-HPV. The relationship between compression and hr-HPV was statistically significant (p Compression-positive binucleated cells may be present as a result of hr-HPV infection and not RCC, which is caused due to inflammation in NILM cases infected with Candida. Creative Commons Attribution License

  17. Human papillomavirus load in benign HPV-associated oral lesions from HIV/AIDS individuals.

    Science.gov (United States)

    Camacho-Aguilar, S; Ramírez-Amador, V; Rosendo-Chalma, P; Guido-Jiménez, M; García-Carrancá, A; Anaya-Saavedra, G

    2018-03-01

    Although HPV emerged as a crucial carcinogenic and prognostic biomarker in head and neck cancer, and considering the increase in HPV-associated oral lesions (HPV-OLs) in HIV individuals, molecular information about HPV-OLs is scarce; thus, our aim was to determine viral loads in HPV-OLs from HIV/AIDS individuals. HIV/AIDS subjects with HPV-OL were included in this cross-sectional study. Following informed consent, biopsies were obtained. HPV detection and typing were carried out by PCR and sequencing (MY09/11, GP5+/6+). HPV-13 and HPV-32 loads were determined by a high-resolution melting assay. For statistical analysis, X 2 , Fisher's exact, and Mann-Whitney U tests were applied, using SPSS software (v.23). Twenty-nine HIV subjects (median age 38 years, 93% males) were included. Most were AIDS individuals (72.4%) under HAART (89.7%). Twenty-two (75.9%) participants had more than one HPV-OL (four with florid presentations), mostly multifocal epithelial hyperplasia (62%), being HPV-13 (26%) and HPV-32 (31%) the most frequent types. HPV load was higher in individuals with multiple HPV-OLs than in solitary lesions (4.9 vs. 3.2 Log 10 copies/ml, p = .090) and in HPV-32 + than in HPV-13 + (8.3 vs. 6.4 Log 10 copies/ml, p = .014). Multiple HPV-OLs showed high HPV loads, possibly indicating transcriptional activity of the virus; however, in the HIV setting, the individual and local immunological response could be the key process. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  18. Identification of human papillomavirus (HPV) subtype in oral cancer patients through microarray technology.

    Science.gov (United States)

    Kim, Soung Min; Kwon, Ik Jae; Myoung, Hoon; Lee, Jong Ho; Lee, Suk Keun

    2018-02-01

    Human papilloma virus (HPV) is the main source of cervical cancer. Many recent studies have revealed the prevalence and prognosis of HPV associated with oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the prevalence and prognosis of HPV associated with OSCC according to HPV and tumor types. We used a DNA chip kit (MY-HPV chip kit ® , Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187 patients. The prevalence was determined by Chi-square and Fisher's exact tests, and the prognosis was calculated by the Kaplan-Meier method and the log-rank test. The overall prevalence of HPV in OSCC was 7.0% for all HPV positives and 4.3% for high-risk HPV positives. The prevalence of HPV was significantly higher in individuals under 65 years old and in those with tumors in the tongue and gum regions. The prognosis did not differ between the HPV-positive and -negative groups. Although the prevalence of HPV-positive cases in OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV-associated OSCC should be considered in the evaluation and treatment of oral cancer patients. In addition, separating high- and low-risk groups based on the HPV status of other body parts might not be appropriate. The DNA microarray method can accurately detect known HPV subtypes simultaneously, but has limitations in detecting new subtypes. Vaccines can also be used to prevent HPV-associated OSCC in patients, so further studies on the prognosis and efficacy of vaccines should be undertaken.

  19. High risk HPV testing following treatment for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Molloy, M; Comer, R; Rogers, P; Dowling, M; Meskell, P; Asbury, K; O'Leary, M

    2016-11-01

    To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

  20. Managing uncertainty: healthcare professionals' meanings regarding the HPV vaccine.

    Science.gov (United States)

    Todorova, Irina; Alexandrova-Karamanova, Anna; Panayotova, Yulia; Dimitrova, Elitsa; Kotzeva, Tatyana

    2014-02-01

    New preventive technologies such as vaccines offer insight into psychological, social, and cultural landscapes. Providers have a key role in parents' decisions for vaccinating their children. Yet, perspectives from providers regarding the human papillomavirus (HPV) vaccine, or vaccination in general, are rarely sought Our objective in this paper is to understand how the HPV vaccine is perceived by health care providers and the multiple contextual meanings it elicits. We conducted interviews with 20 health care professionals in Bulgaria about their attitudes and practices related to HPV vaccination and their recommendations for policies. The verbatim-transcribed interviews were analyzed through narrative analysis, with a special focus on language. We illustrate providers' contradictory and contextualized constructions of the vaccine and the narrative strategies they use to manage any uncertainty it elicits. These include being advocates and missionaries for preventive health, confirming their trust in the medical profession and professional organizations, challenging patients' concerns with rational explanations, normalizing the risk of medical innovations, and avoiding the sexual nature of HPV transmission. The introduction of a vaccine to prevent HPV infection, and by implication, possibly cervical and other cancers, created hope, and at the same time, intensified confusion and uncertainty. Providers have been frustrated for years with the rising mortality from cervical cancer in Bulgaria, and their perceived powerlessness in affecting this. HPV vaccination, on the other hand, seems relatively simple and "taming uncertainty" positions them as instrumental in limiting (or even eliminating) morbidity and mortality in future generations.

  1. [HPV Vaccination Program - The History and Recent Progress].

    Science.gov (United States)

    Yoshikawa, Hiroyuki

    2017-09-01

    Four years have passed since HPV vaccination "crisis" occurred in June 2013. In Japan,a publicly funded HPV vaccination program for adolescent females aged 12-16 years began in December 2010. However,the Japanese government withdrew its recommendation for HPV vaccination in June, 2013 because news reports on potential adverse effects of HPV vaccines without any medical evidence appeared repeatedly. The vaccination coverage among adolescent females decreased quickly from around 70%in females born between 1994 and 1999 to only 1%in females born since 2001 over the country. The suspension of recommendation for vaccination has continued to the present,though there is no scientific or epidemiologic evidence to demonstrate the causal linkage between post-vaccination symptoms and the HPV vaccines. Very recently,an ecological investigation reported that similar symptoms also occur in unvaccinated adolescents in Japan. Medical organizations in Japan are also calling for a resumption of the HPV vaccination program. Now,the resumption of the recommendation needs a political judgment.

  2. hpvPDB: An Online Proteome Reserve for Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Satish Kumar

    2013-12-01

    Full Text Available Human papillomavirus (HPV infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.

  3. Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

    Science.gov (United States)

    Forinash, Alicia B; Yancey, Abigail M; Pitlick, Jamie M; Myles, Thomas D

    2011-02-01

    To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy. PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information. All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated. Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials. Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk. © 2011 SAGE Publications.

  4. Suppression of Innate Immune Response by Primary Human Keratinocytes Expressing HPV-16 E6 and E7

    National Research Council Canada - National Science Library

    Guess, Jennifer L

    2005-01-01

    Human papillomavims (HPV) types infect the skin and mucosal epithelium. Lesions resulting from HPV infection can linger for months or years suggesting that HPV - presence goes unnoticed by the host immune system...

  5. Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination intervention for young adult gay and bisexual men.

    Science.gov (United States)

    McRee, Annie-Laurie; Shoben, Abigail; Bauermeister, Jose A; Katz, Mira L; Paskett, Electra D; Reiter, Paul L

    2018-01-10

    Effective interventions to promote human papillomavirus (HPV) vaccination are needed, particularly among populations at increased risk of HPV-related disease. We developed and pilot tested a web-based intervention, Outsmart HPV, to promote HPV vaccination among young gay and bisexual men (YGBM). In 2016, we recruited a national sample (n = 150) of YGBM ages 18-25 in the United States who had not received any doses of HPV vaccine. Participants were randomized to receive either standard HPV vaccination information (control) or population-targeted, individually-tailored content (Outsmart HPV intervention). We assessed between group differences in HPV vaccination attitudes and beliefs immediately following the intervention using multiple linear regression. There were no differences in HPV vaccination attitudes, beliefs and intentions between groups at baseline. Compared to participants in the control group, intervention participants reported: greater perception that men who have sex with men are at higher risk for anal cancer relative to other men (b = 0.34); greater HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV vaccine (b = -0.34) on posttest surveys (all p HPV intervention (all > 4.4 on a 5-point scale). Findings from this study provide preliminary support for a brief, tailored web-based intervention in improving HPV vaccination attitudes and beliefs among YGBM. An important next step is to determine the effects of Outsmart HPV on HPV vaccine uptake. ClinicalTrials.gov identifier NCT02835755. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice.

    Science.gov (United States)

    Araújo, Rita; Santos, Joana M O; Fernandes, Mara; Dias, Francisca; Sousa, Hugo; Ribeiro, Joana; Bastos, Margarida M S M; Oliveira, Paula A; Carmo, Diogo; Casaca, Fátima; Silva, Sandra; Medeiros, Rui; Gil da Costa, Rui M

    2018-02-01

    Persistent human papillomavirus (HPV) infection is associated with the development of certain types of cancer and the dysregulation of microRNAs has been implicated in HPV-associated carcinogenesis. This is the case of microRNA-146a (miR-146a), which is thought to regulate tumor-associated inflammation. We sought to investigate the expression levels of miR-146a during HPV16-mediated carcinogenesis using skin samples from K14-HPV16 transgenic mice which develop the consecutive phases of the carcinogenesis process. Female transgenic (HPV +/- ) and wild-type (HPV -/- ) mice were sacrificed at 24-26 weeks-old or 28-30 weeks-old. Chest and ear skin samples from HPV +/- and HPV -/- mice were histologically classified and used for microRNA extraction and quantification by qPCR. Chest skin samples from 24 to 26 weeks-old HPV +/- mice presented diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while at 28-30 weeks-old all (100.0%) HPV +/- animals showed epidermal dysplasia. All HPV +/- ear skin samples showed carcinoma in situ (CIS). MiR-146a expression levels were higher in HPV +/- compared to HPV -/- mice (p = 0.006). There was also an increase in miR-146a expression in dysplastic skin lesions compared with hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease in miR-146a expression when compared to samples showing epidermal hyperplasia (p = 0.018) and epidermal dysplasia (p = 0.009). These results suggest that HPV16 induces the overexpression of miR-146a in the initial stages of carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at later stages (CIS). Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis.

  7. HPV E6 and E7 in hypoxia mediated tumorigenesis in cervical epithelial cells

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell; Graeber, Thomas G.; Peehl, Donna M.; Giaccia, Amato J.

    1996-01-01

    Objective: In our previous work, we found that hypoxia induces apoptosis in oncogenically transformed rodent cells and loss of the p53 tumor suppressor gene significantly reduces hypoxia induced cell death. In this report, we show that transformation of wild-type p53 expressing primary cervical epithelial cells with the E6 and E7 genes from high risk human papillomavirus (HPV) type 16 dramatically enhances their susceptibility to hypoxia induced apoptosis. Materials and Methods: Sub confluent primary normal human cervical epithelial cells and normal human fibroblasts were infected with retroviral vectors containing HPV16 E6 and E7 and the neomycin selectable marker using previously described techniques. Clones were selected and isolated in neomycin containing media. Exponentially growing cells were treated with hypoxia (0.02% O 2 ) using specially designed chambers, irradiated (800 cGy) using a cesium source, or grown under aerobic conditions (20% O 2 ) as a control. After treatment, cells were stained with Hoescht and propidium iodide and viewed with a fluorescent microscope for analysis of apoptotic cells. To determine increase in expression of p53, immuno blots were performed using whole cell extracts. Results: After a 48 hour exposure to hypoxic conditions, 40% of E6 and E7 transformed cervical cells exhibit morphologic features indicative of apoptosis, compared to 5% of untransformed cervical cells. Exposure of HPV E6 and E7 transformed cells to ionizing radiation, however, did not initiate apoptosis. Immunoblot assays show induction of p53 under hypoxic conditions but not by ionizing radiation, indicating that hypoxia is able to induce p53 in the presence of E6 and that hypoxia activates p53 by a pathway which is distinct from that of ionizing radiation. Furthermore, hypoxia did not induce apoptosis in normal human fibroblasts transformed with E6 and E7, suggesting that the cellular response to hypoxia is influenced by the cell type. Conclusion: These results

  8. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

    Science.gov (United States)

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

    2018-04-01

    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  9. The potential role of HPV vaccination in the prevention of infectious complications of pregnancy

    DEFF Research Database (Denmark)

    Bonde, Ulla; Jøergensen, Jan Stener; Mogensen, Ole

    2014-01-01

    There is now incontrovertible evidence that HPV is the cause of almost all cases of genital warts, cervical dysplasia and cervical cancer. Moreover the current review of the recent literature on HPV in relation to pregnancy found strong indications that HPV plays an important role in adverse...... outcomes of pregnancy. HPV may contribute to infertility and may increase the risk of miscarriage. Recent studies indicate a significant rate of vertical transmission of HPV between mother and child but whether the mode of delivery makes a difference to the risk of transmission remains unknown. HPV...

  10. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells.

    Science.gov (United States)

    Kim, Dong-Hyun; Jarvis, Roger M; Allwood, J William; Batman, Gavin; Moore, Rowan E; Marsden-Edwards, Emma; Hampson, Lynne; Hampson, Ian N; Goodacre, Royston

    2010-12-01

    It has been shown that the HIV protease inhibitors indinavir and lopinavir may have activity against the human papilloma virus (HPV) type 16 inhibiting HPV E6-mediated proteasomal degradation of p53 in cultured cervical carcinoma cells. However, their mode and site of action is unknown. HPV-negative C33A cervical carcinoma cells and the same cells stably transfected with E6 (C33AE6) were exposed to indinavir and lopinavir at concentrations of 1 mM and 30 μM, respectively. The intracellular distribution of metabolites and metabolic changes induced by these treatments were investigated by Raman microspectroscopic imaging combined with the analysis of cell fractionation products by liquid chromatography-mass spectrometry (LC-MS). A uniform cellular distribution of proteins was found in drug-treated cells irrespective of cell type. Indinavir was observed to co-localise with nucleic acid in the nucleus, but only in E6 expressing cells. Principal components analysis (PCA) score maps generated on the full Raman hypercube and the corresponding PCA loadings plots revealed that the majority of metabolic variations influenced by the drug exposure within the cells were associated with changes in nucleic acids. Analysis of cell fractionation products by LC-MS confirmed that the level of indinavir in nuclear extracts was approximately eight-fold greater than in the cytoplasm. These data demonstrate that indinavir undergoes enhanced nuclear accumulation in E6-expressing cells, which suggests that this is the most likely site of action for this compound against HPV.

  11. Transactivation of the proenkephalin gene promoter by the Tax sub 1 protein of human T-cell lymphotropic virus type I

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, J.B. (National Heart, Lung, and Blood Inst., Bethesda, MD (United States)); Dave, H.P.G. (National Inst. of Health, Bethesda, MD (United States))

    1992-02-01

    Human T-cell lymphotropic virus type I (HTLV-I), an etiologic agent for adult T-cell leukemia, is strongly associated with certain neurological diseases. The HTLV-I genome encodes a protein, Tax{sub 1}, that transactivates viral gene transcription. CD4-positive T helper lymphocytes express the proenkephalin gene, and enkephalins have been implicated as neuroimmunomodulators. The authors have investigated the effect of Tax{sub 1} on the proenkephalin gene promoter in C6 rat glioma cells and demonstrated its transactivation. Analysis using 5{prime} deletion mutants of the promoter region showed that sequences upstream of base pair - 190 are necessary for maximal transactivation. Forskolin, a cAMP modulator, synergistically increased Tax{sub 1}-mediated transactivation of the proenkephalin promoter. Neither Tax{sub 1} transactivation alone nor Tax{sub 1}/cAMP synergism exclusively involved cAMP-responsive elements. Endogenous proenkephalin gene expression increased in Tax{sub 1}-expressing C6 cells. Since HTLV-I infects lymphocytes, which express proenkephalin mRNA, Tax{sub 1} transregulation of proenkephalin expression may provide bidirectional communication between the nervous and immune systems in HTLV-I-related diseases.

  12. Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation

    International Nuclear Information System (INIS)

    Nanao-Hamai, Michiko; Son, Bo-Kyung; Hashizume, Tsuyoshi; Ogawa, Sumito; Akishita, Masahiro

    2016-01-01

    Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2. In human aortic smooth muscle cells, physiological levels of E2 inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner. This inhibitory effect was significantly abolished by MPP, an ERα-selective antagonist, and ERα siRNA, but not by PHTPP, an ERβ-selective antagonist, and ERβ siRNA, implicating an ERα-dependent action. Apoptosis, an essential process for Pi-induced VSMC calcification, was inhibited by E2 in a concentration-dependent manner and further, MPP abolished this inhibition. Mechanistically, E2 restored the inhibited expression of Gas6 and phospho-Akt in Pi-induced apoptosis through ERα. Furthermore, E2 significantly activated Gas6 transcription, and MPP abrogated this E2-dependent Gas6 transactivation. E2-BSA failed to activate Gas6 transcription and to inhibit Ca deposition in VSMC, suggesting beneficial actions of genomic signaling by E2/nuclear ERα. Taken together, these results indicate that E2 exerts inhibitory effects on VSMC apoptosis and calcification through ERα-mediated Gas6 transactivation. These findings indicate a potential therapeutic strategy for the prevention of vascular calcification, especially in postmenopausal women. - Highlights: • E2 inhibits Pi-induced calcification in vascular smooth muscles cells. • E2 inhibits Pi

  13. DNA of HPV and antibodies toward the protein E7 of HPV 16 as prediction factors in women with cervical cancer submitted to radiotherapy

    International Nuclear Information System (INIS)

    Bravo, Maria Mercedes; Combita R, Alba Lucia; Molano L, Monica; Gonzalez Florez, Hector; Orozco D, Oscar

    2002-01-01

    The effects of HPV infection on intrinsic tumor cell sensitivity to radiation therapy (RT) are not clear. Antibodies to HPV16-E7 protein are consistently detected in cervical cancer patients, the changes in the levels of these antibodies after RT thus may have prognostic implications. The aim of this study was to evaluate the antibodies to HPV16-E7 protein and the HPV status in cervical cancer patients before and after RT and to correlate these with clinic pathological parameters. Antibodies to peptide E7 and HPV DNA status before and after RT could have prognosis significance for patients with locally advanced uterine cervical carcinoma

  14. Teenagers' knowledge about HPV infection and HPV vaccination in the first year of the public vaccination programme.

    Science.gov (United States)

    Sopracordevole, F; Cigolot, F; Gardonio, V; Di Giuseppe, J; Boselli, F; Ciavattini, A

    2012-09-01

    The aim of this study was to assess teens' knowledge of HPV infection and vaccination one year after the initiation of the public vaccination programme and information campaign on the disease and the opportunity of vaccination. Between 15 May and 15 June 2009, a survey was carried out on 1,105 teenagers attending high schools in a town in the northeast of Italy by means of an anonymous and unannounced questionnaire covering the knowledge of HPV infection, transmission, prevention, vaccination and post-vaccination behaviours. Only 75% of teens knew what HPV infection is (92% of girls vs 51% of boys, p teens aware of HPV vaccination, 7.6% of girls and 21.8% of boys believe that it can prevent AIDS (p Teens' knowledge about HPV infection and vaccination remains insufficient, despite a broad information campaign. Erroneous information may increase risky sexual behaviours. Without complete information about HPV infection and vaccination and information about other sexually-transmitted diseases, the latter might become difficult to control among teenagers, while some misunderstandings about the usefulness of secondary prevention might linger.

  15. Detection of oral HPV infection - Comparison of two different specimen collection methods and two HPV detection methods.

    Science.gov (United States)

    de Souza, Marjorie M A; Hartel, Gunter; Whiteman, David C; Antonsson, Annika

    2018-04-01

    Very little is known about the natural history of oral HPV infection. Several different methods exist to collect oral specimens and detect HPV, but their respective performance characteristics are unknown. We compared two different methods for oral specimen collection (oral saline rinse and commercial saliva kit) from 96 individuals and then analyzed the samples for HPV by two different PCR detection methods (single GP5+/6+ PCR and nested MY09/11 and GP5+/6+ PCR). For the oral rinse samples, the oral HPV prevalence was 10.4% (GP+ PCR; 10% repeatability) vs 11.5% (nested PCR method; 100% repeatability). For the commercial saliva kit samples, the prevalences were 3.1% vs 16.7% with the GP+ PCR vs the nested PCR method (repeatability 100% for both detection methods). Overall the agreement was fair or poor between samples and methods (kappa 0.06-0.36). Standardizing methods of oral sample collection and HPV detection would ensure comparability between future oral HPV studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The role of inflammation in HPV infection of the Oesophagus

    International Nuclear Information System (INIS)

    Schäfer, Georgia; Kabanda, Siti; Rooyen, Beverly van; Marušič, Martina Bergant; Banks, Lawrence; Parker, M Iqbal

    2013-01-01

    Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-α-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-α-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. This study showed that although the carcinogen benzo

  17. Population-based prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark

    DEFF Research Database (Denmark)

    Kjaer, Susanne K.; Breugelmans, Gabrielle; Munk, Christian

    2008-01-01

    /11. Prevalence of high-risk HPV types increased from 19.2% in women with normal cytology to 100% in women with cervical intraepithelial neoplasia grade 3 (CIN3)/cervical cancer. HPV 16 was the most prevalent type (6.0% of all women), and was also the most prevalent in women with HSIL (35.1%) and CIN3 (53......-grade squamous intraepithelial lesion and 1.6% had high-grade squamous intraepithelial lesion (HSIL). The HPV prevalence was 26.4% with a peak in women 20-24 years (50.2%) and then decreased without a second peak in older women. Among the youngest women (15-19 years), 14% had HPV 16/18 and 16% had HPV 6.......2%). Other common HPV types in women with CIN3 included HPV 52, 51, 31, 33 and 18. HPV 16/18 alone was present in 23% of CIN3 lesions and 67% of cervical cancers, and HPV 16/18 together with other high-risk HPV types was present in 41% of CIN3 lesions. This suggests that an efficacious HPV 16/18 vaccine...

  18. The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

    Science.gov (United States)

    Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

    2013-01-01

    The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

  19. HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan.

    Science.gov (United States)

    Adilbay, Dauren; Adilbayev, Galim; Kidirbayeva, Gulzhan; Shipilova, Viktoria; Sadyk, Zhanat; Koyanbekova, Gulsum; Sokolenko, Ekaterina; Klozar, Jan

    2018-01-01

    Human papillomavirus (HPV) is an important etiologic factor in different cancers of anogenital region and also in a fraction of head and neck cancers (HNC) particularly oropharyngeal tumors. The HPV16 genotype associated with the majority of HPV-related head and neck carcinomas. Th incidence of oropharyngeal cancer is increasing in many countries, and the rate of HPV positive tumors is about 70% in Europe and North America. Little known about the prevalence of HPV in HNC in Central Asia. It's a prospective analysis of patients with verified oral or oropharyngeal cancer. Sociodemographic and clinical data obtained on admission to treatment. The diagnosis of HPV positivity assessed by both the P16 expression on immunohistochemistry(IHC) and polymerase chain reaction (PCR)with HPV DNA detection and HR HPV type determination. Seventy six patients with oral and oropharyngeal cancer tested for HPV. Forteen cases were positive for HPV by PCR and 15 cases by P16 IHC. Of the 35 oropharyngeal tumors, nine were HPV DNA and p16 IHC positive, giving the rate of 25.7%. Of the 41 oral tumors, five were HPV DNA and six p16 IHC positive, giving the rate of 12.2%. It is the first study mapping prevalence of HPV positivity in oral and oropharyngeal cancer in the Central Asian region. The rate of HPV positivity was higher in oropharyngeal than in oral cancer, the nonsmokers were significantly more frequent in the HPV positive group and HPV 16 was the most frequent type. However, the HPV positivity rates are lower than referred in the western world.

  20. Surgical staging identified false HPV-negative cases in a large series of invasive cervical cancers.

    Science.gov (United States)

    Petry, Karl Ulrich; Liebrich, Clemens; Luyten, Alexander; Zander, Martina; Iftner, Thomas

    2017-12-01

    We examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population. We prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping. HC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV-53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV-DNA with all tests. The main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations. Retrospective analyses without surgical staging may overestimate the proportion of HPV negative cervical cancers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. HPV type infection in different anogenital sites among HIV-positive Brazilian women

    Directory of Open Access Journals (Sweden)

    Donadi Eduardo Antonio

    2008-03-01

    Full Text Available Abstract Objectives To evaluate the prevalence of human papillomavirus (HPV types, and risk factors for HPV positivity across cervix, vagina and anus, we conducted a study among 138 women with human immunodeficiency virus (HIV. Goal Compare the prevalence of different HPV types and the risk factors for HPV positivity in three sites. Results The most frequently detected HPV types in all sites were, in decreasing order, HPV16, 53, 18, 61 and 81. Agreement between the cervix and vagina was good (kappa 0.60 – 0.80 for HPV16 and 53 and excellent (Kappa > 0.80 for HPV18 and 61. HPV positivity was inversely associated with age for all combinations including the anal site. Conclusion In HIV positive women, HPV18 is the most spread HPV type found in combinations of anal and genital sites. The relationship of anal to genital infection has implications for the development of anal malignancies. Thus, the efficacy of the current HPV vaccine may be considered not only for the cervix, but also for prevention of HPV18 anal infection among immunossuppressed individuals.

  2. Chimeric L2-Based Virus-Like Particle (VLP Vaccines Targeting Cutaneous Human Papillomaviruses (HPV.

    Directory of Open Access Journals (Sweden)

    Bettina Huber

    Full Text Available Common cutaneous human papillomavirus (HPV types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas, but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa 17-36 on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross- protected against beta HPV5/20/24/38/96/16 (but not type 76, while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target

  3. An evaluation of clinical performance of FTA cards for HPV 16/18 detection using cobas 4800 HPV Test compared to dry swab and liquid medium.

    Science.gov (United States)

    Dong, Li; Lin, Chunqing; Li, Li; Wang, Margaret; Cui, Jianfeng; Feng, Ruimei; Liu, Bin; Wu, Zeni; Lian, Jia; Liao, Guangdong; Chen, Wen; Qiao, Youlin

    2017-09-01

    Effective dry storage and transport media as an alternative to conventional liquid-based medium would facilitate the accessibility of women in the low-resource settings to human papillomavirus (HPV)- based cervical cancer screening. To evaluate analytical and clinical performance of indicating FTA™ Elute Cartridge (FTA card) for the detection of HPV16/18 and cervical precancerous lesions and cancer compared to dry swab and liquid medium. Ninety patients with abnormal cytology and/or HPV infection were included for analysis. Three specimens of cervical exfoliated cells from each woman were randomly collected by FTA card, dry swab or liquid-based medium prior to colposcopy examination. The subsequent HPV DNA tests were performed on cobas 4800 HPV platform. High-risk HPV (hrHPV) positivity rate was 63.3%, 62.2% and 65.6% for samples collected by FTA card, dry swab and liquid medium, respectively. The overall agreements and kappa values for the detection of hrHPV, HPV 16 and HPV 18 between FTA card and liquid-based medium were 88.9% (κ=0.76), 97.8% (κ=0.94) and 100% (κ=1.0),respectively; between FTA card and dry swab were 92.1% (κ=0.83), 94.5% (κ=0.87) and 100% (κ=1.0), respectively. The performances of hrHPV tested by FTA card, dry swab, and liquid-based medium for detecting CIN2+ were comparable in terms of the sensitivity and specificity. The specificity of detection of CIN2+ by HPV16/18 increased by approximately 40% compared to hrHPV for any medium albeit at cost of a moderate loss of sensitivity. Dry medium might offer an alternative to conventional liquid-based medium in the HPV-based cervical cancer screening program especially in low-resource settings but still needs further evaluation. Copyright © 2017. Published by Elsevier B.V.

  4. HPV vaccination and sexual behavior in a community college sample.

    Science.gov (United States)

    Marchand, Erica; Glenn, Beth A; Bastani, Roshan

    2013-12-01

    Many US parents are concerned that vaccinating daughters against human papillomavirus (HPV) will communicate implicit approval for sexual activity and be associated with early or risky sexual behavior (Scarinci et al. in J Womens Health 16(8):1224-1233, 2007; Schuler et al. in Sex Transm Infect 87:349-353, 2011). The aims of this study were to understand (a) whether the HPV vaccine was associated with risky sexual behavior among a diverse sample of female adolescents and young adults, and (b) to better understand the chronology of HPV vaccination and sexual behavior. An anonymous web-based survey was used to collect data from 114 female community college students. T test and Chi square analyses were used to compare vaccinated and unvaccinated groups on age at first intercourse and proportion who had ever had sexual intercourse. Linear multiple regression was used to predict frequency of condom use and number of sexual partners in the past year, using vaccination status and demographic factors as predictors. About 38% reported receiving at least one dose of the HPV vaccine. Many of those vaccinated (45%) received the vaccine after having initiated sexual activity. The proportion of women who were sexually experienced did not differ by HPV vaccine status, nor did age at first intercourse, number of partners in the past year, or frequency of condom use. Current findings suggest that HPV vaccination is not associated with riskier sexual activity for the young women in this sample. Adolescents and their parents may benefit from education about the need to receive the HPV vaccine before onset of sexual activity.

  5. Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

    Science.gov (United States)

    Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2017-08-01

    We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

  6. Recurrent Skin and Lung Infections in Autosomal Dominant Hyper IgE Syndrome with Transactivation Domain STAT3 Mutation

    Directory of Open Access Journals (Sweden)

    Chad J. Cooper

    2014-01-01

    Full Text Available Background. Hyper IgE is a rare systemic disease characterized by the clinical triad of high serum levels of IgE (>2000 IU/mL, eczema, and recurrent staphylococcal skin and lung infections. The presentation of hyper IgE syndrome is highly variable, which makes it easy to confuse the diagnosis with that of severe atopy or other rare immunodeficiency disorders. Case Report. A 23-year-old Hispanic presented with history of frequent respiratory and gastrointestinal infections as a child and multiple episodes of skin and lung infections (abscess with Staphylococcus aureus throughout his adult life. He had multiple eczematous lesions and folliculitis over his entire body, oral/esophageal candidiasis, and retention of his primary teeth. The IgE was elevated (>5000 IU/mL. Genetic mutation analysis revealed a mutation affecting the transactivation domain of the STAT3 gene. Conclusion. The hallmark of hyper IgE syndrome is serum IgE of >2000 IU/mL. Hyper IgE syndrome is a genetic disorder that is either autosomal dominant or recessive. A definite diagnosis can be made with genetic mutation analysis, and in this case, it revealed a very rare finding of the transactivation domain STAT3 mutation. Hyper IgE syndrome is a challenge for clinicians in establishing a diagnosis in suspected cases.

  7. Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.

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    Lukas E Dow

    Full Text Available Tetracycline or doxycycline (dox-regulated control of genetic elements allows inducible, reversible and tissue specific regulation of gene expression in mice. This approach provides a means to investigate protein function in specific cell lineages and at defined periods of development and disease. Efficient and stable regulation of cDNAs or non-coding elements (e.g. shRNAs downstream of the tetracycline-regulated element (TRE requires the robust expression of a tet-transactivator protein, commonly the reverse tet-transactivator, rtTA. Most rtTA strains rely on tissue specific promoters that often do not provide sufficient rtTA levels for optimal inducible expression. Here we describe the generation of two mouse strains that enable Cre-dependent, robust expression of rtTA3, providing tissue-restricted and consistent induction of TRE-controlled transgenes. We show that these transgenic strains can be effectively combined with established mouse models of disease, including both Cre/LoxP-based approaches and non Cre-dependent disease models. The integration of these new tools with established mouse models promises the development of more flexible genetic systems to uncover the mechanisms of development and disease pathogenesis.

  8. Flock House virus subgenomic RNA3 is replicated and its replication correlates with transactivation of RNA2

    International Nuclear Information System (INIS)

    Eckerle, Lance D.; Albarino, Cesar G.; Ball, L. Andrew.

    2003-01-01

    The nodavirus Flock House virus has a bipartite genome composed of RNAs 1 and 2, which encode the catalytic component of the RNA-dependent RNA polymerase (RdRp) and the capsid protein precursor, respectively. In addition to catalyzing replication of the viral genome, the RdRp also transcribes from RNA1 a subgenomic RNA3, which is both required for and suppressed by RNA2 replication. Here, we show that in the absence of RNA1 replication, FHV RdRp replicated positive-sense RNA3 transcripts fully and copied negative-sense RNA3 transcripts into positive strands. The two nonstructural proteins encoded by RNA3 were dispensable for replication, but sequences in the 3'-terminal 58 nucleotides were required. RNA3 variants that failed to replicate also failed to transactivate RNA2. These results imply that RNA3 is naturally produced both by transcription from RNA1 and by subsequent RNA1-independent replication and that RNA3 replication may be necessary for transactivation of RNA2

  9. Direct interaction of TFIIB and the IE protein of equine herpesvirus 1 is required for maximal trans-activation function

    International Nuclear Information System (INIS)

    Albrecht, Randy A.; Jang, Hyung K.; Kim, Seong K.; O'Callaghan, Dennis J.

    2003-01-01

    Recently, we reported that the immediate-early (IE) protein of equine herpesvirus 1 (EHV-1) associates with transcription factor TFIIB [J. Virol. 75 (2001), 10219]. In the current study, the IE protein purified as a glutathione-S-transferase (GST) fusion protein was shown to interact directly with purified TFIIB in GST-pulldown assays. A panel of TFIIB mutants employed in protein-binding assays revealed that residues 125 to 174 within the first direct repeat of TFIIB mediate its interaction with the IE protein. This interaction is physiologically relevant as transient transfection assays demonstrated that (1) exogenous native TFIIB did not perturb IE protein function, and (2) ectopic expression of a TFIIB mutant that lacked the IE protein interactive domain significantly diminished the ability of the IE protein to trans-activate EHV-1 promoters. These results suggest that an interaction of the IE protein with TFIIB is an important aspect of the regulatory role of the IE protein in the trans-activation of EHV-1 promoters

  10. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Rossing, Maria; Andersen, Ditte

    2012-01-01

    of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e. g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e. g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed...... the suppression of DNA repair by HPV11 and -16, and downregulation of cytoskeleton genes by all HPV types. Various signalling pathways were affected by the HPVs: IL-2 by HPV11; JAK-STAT by HPV16; and TGF-beta, NOTCH and tyrosine kinase signalling by HPV45. This study uncovered novel strategies employed by HPV...... to establish infection and promote uncontrolled growth....

  11. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis.

    Science.gov (United States)

    Tjon Pian Gi, Robin E A; San Giorgi, Michel R M; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M; Schuuring, Ed M D; van den Heuvel, Edwin R; van der Laan, Bernard F A M; Dikkers, Frederik G

    2016-10-01

    Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p immunological increase can cause decrease in number of surgeries.

  12. Knowledge, Practice and Acceptability of HPV Vaccine by Mothers of Adolescent Girls in Ilorin, Nigeria

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    Kikelomo T. Adesina

    2018-03-01

    Conclusion: There is poor knowledge of HPV and practice of vaccination among mothers in llorin. Willingness of mothers to vaccinate their daughters is suboptimal. Mother's knowledge is an important determinant of HPV vaccination of adolescents.

  13. THE ROLE OF INTERFERON ALPHA-2b IN REDUCING OF VIRAL LOAD IN HPV INFECTED WOMEN

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    Кристина Владимировна Марочко

    2017-05-01

    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  14. HPV-11 variability, persistence and progression to genital warts in men: the HIM study.

    Science.gov (United States)

    Flores-Díaz, Ema; Sereday, Karen A; Ferreira, Silvaneide; Sirak, Bradley; Sobrinho, João Simão; Baggio, Maria Luiza; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L; Sichero, Laura

    2017-09-01

    HPV-11 and HPV-6 are the etiological agents of about 90 % of genital warts (GWs). The intra-typic variability of HPV-11 and its association with infection persistence and GW development remains undetermined. Here, HPV infection in men (HIM) participants who had an HPV-11 genital swab and/or GW, preceded or not by a normal skin genital swab were analysed. Genomic variants were characterized by PCR-sequencing and classified within lineages (A, B) and sublineages (A1, A2, A3, A4). HPV-11 A2 variants were the most frequently detected in the genital swab samples from controls and in both genital swabs and GW samples from cases. The same HPV-11 variant was detected in the GW sample and its preceding genital swab. There was a lack of association between any particular HPV-11 variant and the increased risk for GW development.

  15. HPV type-related chromosomal profiles in high-grade cervical intraepithelial neoplasia

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    Bierkens Mariska

    2012-01-01

    Full Text Available Abstract Background The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3] result from a persistent infection with high-risk human papillomavirus (hrHPV types and the accumulation of (epigenetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. Methods Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (≥ 5 years. Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. Results Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31 in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR Conclusions Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is

  16. Wireless Cellular Mobile Communications

    OpenAIRE

    Zalud, V.

    2002-01-01

    In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

  17. MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer

    International Nuclear Information System (INIS)

    Chapman, Bhavana V.; Wald, Abigail I.; Akhtar, Parvez; Munko, Ana C.; Xu, Jingjing; Gibson, Sandra P.; Grandis, Jennifer R.; Ferris, Robert L.; Khan, Saleem A.

    2015-01-01

    Transwell migration of SCCHN cell lines, indicating that the miR-363-induced migration attenuation of SCCHN cells may act through MYO1B downregulation. These findings demonstrate that the overexpression of miR-363 reduces cellular migration in head and neck cancer and reveal the biological relationship between miR-363, myosin 1b, and HPV-positive SCCHN. The online version of this article (doi:10.1186/s12885-015-1888-3) contains supplementary material, which is available to authorized users

  18. Anal HPV infection in HIV-positive men who have sex with men from China.

    Directory of Open Access Journals (Sweden)

    Lei Gao

    Full Text Available BACKGROUND: Anal HPV infection, which contributes to the development of anal warts and anal cancer, is well known to be common among men who have sex with men (MSM, especially among those HIV positives. However, HIV and anal HPV co-infection among MSM has not been addressed in China. METHODS: A cross-sectional study was conducted in Beijing and Tianjin, China. Study participants were recruited using multiple methods with the collaboration of local volunteer organizations. Blood and anal swabs were collected for HIV-1 serological test and HPV genotyping. RESULTS: A total of 602 MSM were recruited and laboratory data were available for 578 of them (96.0%. HIV and anal HPV prevalence were 8.5% and 62.1%, respectively. And 48 MSM (8.3% were found to be co-infected. The HPV genotypes identified most frequently were HPV06 (19.6%, HPV16 (13.0%, HPV52 (8.5% and HPV11 (7.6%. Different modes of HPV genotypes distribution were observed with respect to HIV status. A strong dose-response relationship was found between HIV seropositivity and multiplicity of HPV genotypes (p<0.001, which is consistent with the observation that anal HPV infection was an independent predictor for HIV infection. CONCLUSIONS: A high prevalence of HIV and anal HPV co-infection was observed in the MSM community in Beijing and Tianjin, China. Anal HPV infection was found to be independently associated with increased HIV seropositivity, which suggests the application of HPV vaccine might be a potential strategy to reduce the acquisition of HIV infection though controlling the prevalence of HPV.

  19. Prevalence of type-specific HPV among female university students from northern Brazil

    OpenAIRE

    Vieira, Rodrigo Covre; Monteiro, Jeniffer do Socorro Valente; Manso, Est?fane Primo; dos Santos, Maria Renata Mendon?a; Tsutsumi, Mihoko Yamamoto; Ishikawa, Edna Aoba Yassui; Ferrari, Stephen Francis; Lima, Karla Val?ria Batista; de Sousa, Ma?sa Silva

    2015-01-01

    Background Human papillomavirus (HPV) infection is associated with cervical cancer, the most frequent cancer in women from northern Brazil. Assessment of the short-term impact of HPV vaccination depends on the availability of data on the prevalence of type-specific HPV in young women in the pre-immunization period, although these data are currently unavailable for the study region. The aim of this study was to estimate the distribution of all mucosal HPV genotypes, including low- and high-ris...

  20. [HPV vaccination: active offer in an Italian region].

    Science.gov (United States)

    Terracciano, Elisa; D'Alò, Gian Loreto; Aquilani, Silvia; Aversa, Anna Maria; Bartolomei, Giuseppina; Calenda, Maria Gabriella; Catapano, Raffaele; Compagno, Silvio; Della Rovere, Piera; Fraioli, Angelo; Ieraci, Roberto; Reggiani, Daniela; Sgricia, Stefano; Spadea, Antonietta; Zaratti, Laura; Franco, Elisabetta

    2017-01-01

    Human Papillomavirus is responsible for 4.8% of cancers, and is the main cause of cervical cancer. Cervical cancer can be reduced by mean of secondary prevention (PAP-test, HPV-DNA test), while through primary prevention (anti-HPV vaccine) the incidence of other HPV-attributable cancers can also be reduced. In Italy, anti-HPV vaccination is part of the immunization schedule in girls since 2008, and in 2017 it was extended to boys. However, vaccine coverage is decreasing nationwide. This study aims to examine anti-HPV vaccination practices in Health care services of Lazio Region, Italy. Questionnaires were sent or administered directly to those in charge of vaccinations. Data, collected from 11/12 (92%) Lazio Local Health Units and from 116 vaccination centers, show a remarkable diversity in the offer: 41% of the centers open only 1-2 days/week, 42% only in the morning, and only 7% are open on Saturday. Vaccination is available by reservation only in 62% of the centers, while vaccines are not administered to ≥18 years subjects in 33%; 93% of the centers call actively the girls in the target cohort, while 70% and 94% recall the patients who had not received the first or the second dose of vaccine, respectively. Collaboration with family physicians and/or pediatricians was declared by 80% of the centers. Vaccine coverage could probably be improved by addressing the highlighted critical issues and applying best practices widely.

  1. Epidemiology and costs of HPV infection: review of the evidence

    Directory of Open Access Journals (Sweden)

    Francesco Bamfi

    2008-12-01

    Full Text Available HPV infection is a well-established cause of both benign and malign diseases. The HPV 16 and 18 genotypes are most commonly associated with cervical cancer whereas the HPV 6 and 11 genotypes are most commonly associated with anogenital warts. In Italy are currently approved two types of vaccine: Gardasil® is a tetravalent HPV 6, 11, 16 and 18 vaccine that prevents cervix cancer and genital warts, Cervarix® is a bivalent HPV 16 and 18 genotype vaccine that protects against cervical cancer and pre cancer forms. Aim of present study was to collect the available epidemiological data and the impact on the Italian National Health Service (NHS budget of genital warts pathology. In Italy 40,000 genital warts cases per year could be estimated in the female population. The management cost in charge of Italian NHS for the female pathology is evaluated around 7 millions €. Comparing the available evidence NHS costs for genital wart pathology represent 3-4% of the total amount for prevention and treatment of cervix cancer.

  2. HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers.

    Science.gov (United States)

    Di Domenico, Marina; Giovane, Giancarlo; Kouidhi, Soumaya; Iorio, Rosamaria; Romano, Maurizio; De Francesco, Francesco; Feola, Antonia; Siciliano, Camilla; Califano, Luigi; Giordano, Antonio

    2017-03-31

    Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.

  3. Vaginosis-associated bacteria and its association with HPV infection.

    Science.gov (United States)

    Romero-Morelos, Pablo; Bandala, Cindy; Jiménez-Tenorio, Julián; Valdespino-Zavala, Mariana; Rodríguez-Esquivel, Miriam; Gama-Ríos, Reyna Anaid; Bandera, Artfy; Mendoza-Rodríguez, Mónica; Taniguchi, Keiko; Marrero-Rodríguez, Daniel; López-Romero, Ricardo; Ramón-Gallegos, Eva; Salcedo, Mauricio

    2018-03-12

    Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  4. Interferon-β induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Jiarong Zhang

    Full Text Available Infection by human papillomavirus (HPV can cause cervical intraepithelial neoplasia (CIN and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-β can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-β inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level.

  5. Biomechanics of cellular solids.

    Science.gov (United States)

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  6. School Nurses' Professional Practice in the HPV Vaccine Decision-Making Process

    Science.gov (United States)

    Rosen, Brittany L.; Ashwood, Daniel; Richardson, George B.

    2016-01-01

    Because U.S. human papillomavirus (HPV) vaccination rates remain low, we evaluated school nurses' knowledge, attitudes, perceptions of their role as opinion leaders, self-efficacy, intention, and professional practice regarding the HPV vaccine and determined if these variables influenced their professional practice concerning the HPV vaccine. We…

  7. Distribution of HPV genotypes in cervical cancer in multi- ethnic Malaysia.

    Science.gov (United States)

    Hamzi Abdul Raub, Sayyidi; Isa, Nurismah Md; Zailani, Hatta Ahmad; Omar, Baharudin; Abdullah, Mohamad Farouk; Mohd Amin, Wan Anna; Noor, Rushdan Md; Ayub, Mukarramah Che; Abidin, Zainal; Kassim, Fauziah; Vicknesh, Visvalingam; Zakaria, Zubaidah; Kamaluddin, Muhammad Amir; Tan, Geok Chin; Syed Husain, Sharifah Noor Akmal

    2014-01-01

    Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim was to determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnic population. This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes. Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (pMalaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.

  8. Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts.

    Science.gov (United States)

    Hu, Zhili; Liu, Lishi; Zhang, Wenjing; Liu, Hui; Li, Junpeng; Jiang, Lifen; Zeng, Kang

    2018-03-01

    Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Sexual behaviour and HPV in young women. The pre-vaccine era.

    NARCIS (Netherlands)

    Lenselink, C.H.

    2010-01-01

    Worldwide mass vaccination with HPV vaccines will most certainly change HPV epidemiology. Monitoring these changes on a population level may prove crucial in assessing overall HPV vaccine efficacy. To provide a basis for understanding possible future shifts in genotypes, as well as to provide

  10. HPV Vaccine Acceptance in a Clinic-Based Sample of Women in the Rural South

    Science.gov (United States)

    Brandt, Heather M.; Sharpe, Patricia A.; McCree, Donna H.; Wright, Marcie S.; Davis, Jennifer; Hutto, Brent E.

    2009-01-01

    Background: Human papillomavirus (HPV) is a very common sexually transmitted infection linked to cervical disease. Vaccines for some types of HPV were in development at the time of the study. Purpose: The study examined HPV vaccine acceptability among underserved women in a rural region of the southeastern U.S. with high rates of cervical cancer…

  11. Identifying Health Beliefs Influencing Hispanic College Men's Willingness to Vaccinate against HPV

    Science.gov (United States)

    Stephens, Dionne P.; Thomas, Tami L.; Eaton, Asia

    2016-01-01

    This study identifies health beliefs influencing Hispanic college men's human papillomavirus (HPV) vaccine uptake decision making processes. Hispanic college men were interviewed about their HPV vaccine knowledge, and information seeking behaviors. Overall, participants did not view HPV infection or vaccination as an immediate concern or priority;…

  12. High prevalence of co-infection between human papillomavirus (HPV) 51 and 52 in Mexican population.

    Science.gov (United States)

    Gallegos-Bolaños, Jazbet; Rivera-Domínguez, Jessica Alejandra; Presno-Bernal, José Miguel; Cervantes-Villagrana, Rodolfo Daniel

    2017-08-08

    Human papillomavirus (HPV) is associated with the genesis of cervical carcinoma. The co-infection among HPV genotypes is frequent, but the clinical significance is controversial; in Mexico, the prevalence and pattern of co-infection differ depending on the geographic area of study. We analyzed the mono- and co-infection prevalence of multiple HPV genotypes, as well as preferential interactions among them in a Mexico City sample population. This study was designed as a retrospective cohort study. Cervical cytology samples from 1163 women and 166 urethral scraping samples of men were analyzed between 2010 and 2012. The detection of HPV infection was performed using the hybrid capture and the genotyping was by PCR (HPV 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52). 36% of women were HPV-positive and the most prevalent genotypes were HPV 51, 52, 16, and 33 (42, 38, 37, and 34%, respectively). The prevalence of co-infection was higher (75.37%) than mono-infection in women HPV positives. All genotypes were co-infected with HPV 16, but the co-infection with 51-52 genotypes was the most frequent combination in all cases. The co-infection was very common; each HPV genotype showed different preferences for co-infection with other genotypes, HPV 51-52 co-infection was the most frequent. The HPV 16, 33, 51 and 52 were the most prevalent and are a public health concern to the Mexican population.

  13. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis

    NARCIS (Netherlands)

    Tjon Pian Gi, Robin E. A.; San Giorgi, Michel R. M.; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M.; Schuuring, Ed M. D.; van den Heuvel, Edwin R.; van der Laan, Bernard F. A. M.; Dikkers, Frederik G.

    2016-01-01

    Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(A (R))) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was

  14. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis

    NARCIS (Netherlands)

    Tjon Pian Gi, R.E.A.; San Giorgi, M.R.M.; Pawlita, M.; Michel, A.; van Hemel, B.M.; Schuuring, E.M.D.; van den Heuvel, E.R.; van der Laan, B.F.A.M.; Dikkers, F.G.

    2016-01-01

    Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil®) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was

  15. Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

    Science.gov (United States)

    Petrelli, Alessio; Di Napoli, Anteo; Giorgi Rossi, Paolo; Rossi, Alessandra; Luccini, Daniele; Di Marco, Ilaria; Traoré, Amadou Laico; Gillio Tos, Anna; Trevisan, Morena; Mirisola, Concetta; Costanzo, Gianfranco

    2016-10-01

    In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

  16. HPV vaccination to prevent oropharyngeal carcinoma : What can be learned from anogenital vaccination programs?

    NARCIS (Netherlands)

    Takes, Robert P.; Wierzbicka, Malgorzata; D'Souza, Gypsyamber; Jackowska, Joanna; Silver, Carl E.; Rodrigo, Juan P.; Dikkers, Frederik G.; Olsen, Kerry D.; Rinaldo, Alessandra; Brakenhoff, Ruud H.; Ferlito, Alfio

    2015-01-01

    Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was

  17. Den HPV-relaterede sygdomsbyrde hos mænd er stor og kan forebygges

    DEFF Research Database (Denmark)

    Kiellberg Larsen, Helle; Kofoed, Kristian; Sand, Carsten

    2013-01-01

    Human papillomavirus (HPV) is a highly prevalent sexually transmitted infection. High-risk HPV causes penile cancer and a substantial proportion of oropharyngeal and anal malignancy in men. Low-risk types of HPV cause anogenital warts. The incidence of oropharyngeal and anal cancers is increasing...

  18. Knowledge, attitudes and barriers for human papilloma virus (HPV) vaccines among Malaysian women.

    Science.gov (United States)

    Al-Dubai, Sami Abdo Radman; Alshagga, Mustafa Ahmed; Al-Naggar, Redhwan Ahmed; Al-Jashamy, Karim; Baobaid, Mohammed Faez; Tuang, Chua Pie; Abd Kadir, Samiah Yasmin

    2010-01-01

    A cross-sectional study was conducted among 300 Malaysian women in the obstetrics and gynecology outpatient clinic in a selected hospital in Bangi, Selangor to determine the level of knowledge of HPV and HPV vaccines, attitudes toward HPV vaccination and barriers of being vaccinated. Factors associated with knowledge and attitudes were also addressed with a questionnaire. Seventy eight women (26%) had heard about the HPV virus and 65 about HPV vaccines (21.7%). Marital status was associated significantly with awareness of HPV and HPV vaccine (p=0.002, p=0.002; respectively), in addition to level of education (p=0.042). The percentages of women who reported correct answers for the questions on knowledge of HPV and HPV vaccine ranged from 12% to 25%. One hundred fifty nine respondents (53%) had a positive attitude toward HPV vaccination. Age, marital status, and level of education were associated significantly with attitude (plevel of knowledge of HPV and HPV vaccine. Education of population is highly recommended and barriers to being vaccinated should be dealt with seriously.

  19. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  20. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Meghna Verma

    Full Text Available Human immunodeficiency virus (HIV-infected patients are at an increased risk of co-infection with human papilloma virus (HPV, and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1 cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  1. Human papillomavirus type 16 E6-specific antitumor immunity is induced by oral administration of HPV16 E6-expressing Lactobacillus casei in C57BL/6 mice.

    Science.gov (United States)

    Lee, Tae-Young; Kim, Yang-Hyun; Lee, Kyung-Soon; Kim, Jeong-Ki; Lee, Il-Han; Yang, Jai-Myung; Sung, Moon-Hee; Park, Jong-Sup; Poo, Haryoung

    2010-11-01

    Given that local cell-mediated immunity (CMI) against the human papillomavirus type 16 E6 (HPV16 E6) protein is important for eradication of HPV16 E6-expressing cancer cells in the cervical mucosa, the HPV16 E6 protein may be a target for the mucosal immunotherapy of cervical cancer. Here, we expressed the HPV16 E6 antigen on Lactobacillus casei (L. casei) and investigated E6-specific CMI following oral administration of the L. casei-PgsA-E6 to mice. Surface expression of HPV16 E6 antigens was confirmed and mice were orally inoculated with the L. casei-PgsA or the L. casei-PgsA-E6. Compared to the L. casei-PgsA-treated mice, significantly higher levels of serum IgG and mucosal IgA were observed in L. casei-PgsA-E6-immunized mice; these differences were significantly enhanced after boost. Consistent with this, systemic and local CMI were significantly increased after the boost, as shown by increased counts of IFN-gamma-secreting cells in splenocytes, mesenteric lymph nodes (MLN), and vaginal samples. Furthermore, in the TC-1 tumor model, animals receiving the orally administered L. casei-PgsA-E6 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. We also found that L. casei-PgsA-E6-induced antitumor effect was decreased by in vivo depletion of CD4(+) or CD8(+) T cells. Collectively, these results indicate that the oral administration of lactobacilli bearing the surface-displayed E6 protein induces T cell-mediated cellular immunity and antitumor effects in mice.

  2. The expression patterns of p53 and p16 and an analysis of a possible role of HPV in primary adenocarcinoma of the urinary bladder.

    Directory of Open Access Journals (Sweden)

    Riley E Alexander

    Full Text Available BACKGROUND: Primary adenocarcinoma of the urinary bladder is rare. The molecular and cellular events leading to its pathogenesis are not well delineated. The goal of this study was to investigate p53 and p16 expression, as well as HPV status, in a relatively large series of primary bladder adenocarcinomas. MATERIALS AND METHODS: Thirty six cases of urinary bladder adenocarcinoma were chosen from participating institutions. The diagnosis and available clinical history were reviewed in each case. Immunostains for p53, p16 and HPV and high-risk and low-risk HPV-ISH were performed on all tumors. RESULTS: Patients had an average age of 61 years with a male predominance (1.5 ∶ 1 male ∶ female ratio. The average tumor size in cystectomy specimens was 4.3 cm. Of the cases managed by transurethral resection, 40% were pT2 at the time of diagnosis. In cystectomy specimens, 77% were either pT3 or pT4. Strong nuclear p16 expression was seen in 67% of all cases and p53 expression was present in 58% of the cases. Expression of both markers was seen in 33% of cases. Expression of p16 or p53 alone was present in 12 (33% and 9 (25% cases, respectively. Neither marker was expressed in only 3 (8% of the tumors. No significant correlation between clinical variables and any of the markers we studied was identified. No HPV infection was detected in any case. CONCLUSIONS: Expression of p53 and/or p16 is very common in urinary bladder adenocarcinoma. These findings implicate a high likelihood that alterations in these cell cycle proteins contribute to the pathogenesis of these tumors. Despite frequent immunohistochemical labeling for p16, no evidence of HPV infection was found.

  3. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

    Energy Technology Data Exchange (ETDEWEB)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín [Programa de Doctorado en Ciencias Biomédicas, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, México (Mexico); Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México 07360, México (Mexico); Ocadiz-Delgado, Rodolfo; García-Villa, Enrique [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México 07360, México (Mexico); Bonilla-Delgado, José [Unidad de Investigación, Hospital Juárez de México, Ciudad de México 07760, México (Mexico); Lagunas-Martínez, Alfredo [División de Biología Molecular de Patógenos, CISEI, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México (Mexico); and others

    2016-12-15

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E{sub 2}) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E{sub 2} on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E{sub 2} in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. -- Graphical abstract: The HPV16 E7 oncoprotein and 17β-estradiol are involved in the upregulation of Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal ability of cancer stem cells in cervical cancer. - Highlights: •The HPV16 E7 oncoprotein enhances cellular proliferation and dedifferentiation. •The E7 oncoprotein induces stemness-related genes expression in vivo and in vitro. •The 17β-estradiol induces stemness-related genes expression in vivo. •The HPV16 E7 oncoprotein is involved in the cell self-renewal of cancer cells.

  4. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

    International Nuclear Information System (INIS)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Ocadiz-Delgado, Rodolfo; García-Villa, Enrique; Bonilla-Delgado, José; Lagunas-Martínez, Alfredo

    2016-01-01

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E 2 ) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E 2 on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E 2 in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. -- Graphical abstract: The HPV16 E7 oncoprotein and 17β-estradiol are involved in the upregulation of Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal ability of cancer stem cells in cervical cancer. - Highlights: •The HPV16 E7 oncoprotein enhances cellular proliferation and dedifferentiation. •The E7 oncoprotein induces stemness-related genes expression in vivo and in vitro. •The 17β-estradiol induces stemness-related genes expression in vivo. •The HPV16 E7 oncoprotein is involved in the cell self-renewal of cancer cells.

  5. Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia.

    Directory of Open Access Journals (Sweden)

    Turid Omland

    Full Text Available Patients with recurrent respiratory papillomatosis (RRP in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma. High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99, as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91. In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

  6. Predicting Individual Affect of Health Interventions to Reduce HPV Prevalence

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Courtney D.; Mihalcea, Rada; Mikler, Armin R.; Sanfilippo, Antonio P.

    2011-04-01

    Recently, human papilloma virus has been implicated to cause several throat and oral cancers and hpv is established to cause most cervical cancers. A human papilloma virus vaccine has been proven successful to reduce infection incidence in FDA clinical trials and it is currently available in the United States. Current intervention policy targets adolescent females for vaccination; however, the expansion of suggested guidelines may extend to other age groups and males as well. This research takes a first step towards automatically predicting personal beliefs, regarding health intervention, on the spread of disease. Using linguistic or statistical approaches, sentiment analysis determines a texts affective content. Self-reported HPV vaccination beliefs published in web and social media are analyzed for affect polarity and leveraged as knowledge inputs to epidemic models. With this in mind, we have developed a discrete-time model to facilitate predicting impact on the reduction of HPV prevalence due to arbitrary age and gender targeted vaccination schemes.

  7. Value for money from HPV vaccination and cervical screening

    DEFF Research Database (Denmark)

    Ashton, Toni; Sopina, Elizaveta (Liza)

    2012-01-01

    Introduction of human papillomavirus (HPV) vaccination programs raises some important questions about the future organization of cervical screening programs. Two studies - from NZ and Canada - have addressed the question of what combination of vaccination and screening strategies might be most cost......-effective in preventing cervical cancer. Both studies indicate that some modifications to existing screening programs may be desirable as immunized females enter these programs. Variables in HPV vaccination that are likely to be particularly important for determining the future cost-effectiveness of cervical screening...... programs include: vaccine uptake rate, compliance with full doses, timely completion of doses, duration of protection, male vaccination and HPV infection rate. If value for money is to be achieved, it is important that the appropriate data are collected so that policy makers can consider the combined...

  8. African American parents' HPV vaccination intent and concerns.

    Science.gov (United States)

    Sanders Thompson, Vetta L; Arnold, Lauren D; Notaro, Sheri R

    2012-02-01

    This study describes attitudes and social and environmental factors that affect African American parents' intent to vaccinate their daughters against human papillomavirus (HPV). Thirty African American parents of daughters aged nine to 17 years and no history of HPV infection completed semi-structured interviews. Interviews addressed factors that influenced intent to vaccinate, perception of community norms related to vaccination, vaccination scenarios involving place of vaccination, and vaccination prior to or after the child's initiation of sexual activity. A recurring theme was the influence of physician recommendation on African American parents' intent to obtain HPV vaccination for their daughters. Most parents reported that they could overcome barriers to vaccination, except vaccine costs and lack of insurance. While religious beliefs were important to parents, they reported that they would not interfere with vaccination decisions; fears of early sexuality due to vaccination were limited. The implications of these findings are discussed.

  9. Molecular events leading to HPV-induced high grade neoplasia

    Directory of Open Access Journals (Sweden)

    Saskia M. Wilting

    2016-12-01

    Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

  10. [HPV diagnosis: woman's process of interaction with her partner].

    Science.gov (United States)

    Vargens, Octavio Muniz da Costa; Silva, Carla Marins; Azevedo E Silva, Gulnar; Girianelli, Vânia Reis

    2013-01-01

    This is a descriptive research, with qualitative approach, which aimed at analyze the interaction process between woman and her partner starting from the diagnosis of infection by the human papilomavirus (HPV). It was accomplished in 13 communities in the cities of Duque de Caxias and Nova Iguaçu, Rio de Janeiro state, Brazil, from October/2006 to September/2008. Twenty women, diagnosed with HPV infection related to oncogenic high risk, were interviewed. The Symbolic Interactionism and Grounded Theory perspectives guided data collection and analysis. The results revealed that the HPV diagnosis means serious challenges in the women's relationship with her partner mainly regarding to the adoption of preventive initiatives. It is concluded that these issues lead to the need of a humanized care in order to favor the women's empowerment.

  11. Transactivation of a cellular promoter by the NS1 protein of the parvovirus minute virus of mice through a putative hormone-responsive element.

    OpenAIRE

    Vanacker, J M; Corbau, R; Adelmant, G; Perros, M; Laudet, V; Rommelaere, J

    1996-01-01

    The promoter of the thyroid hormone receptor alpha gene (c-erbA-1) is activated by the nonstructural protein 1 (NS1) of parvovirus minute virus of mice (prototype strain [MVMp]) in ras-transformed FREJ4 cells that are permissive for lytic MVMp replication. This stimulation may be related to the sensitivity of host cells to MVMp, as it does not take place in parental FR3T3 cells, which are resistant to the parvovirus killing effect. The analysis of a series of deletion and point mutants of the...

  12. An enhanceosome containing the Jun B/Fra-2 heterodimer and the HMG-I(Y) architectural protein controls HPV 18 transcription.

    Science.gov (United States)

    Bouallaga, I; Massicard, S; Yaniv, M; Thierry, F

    2000-11-01

    Recent studies have reported new mechanisms that mediate the transcriptional synergy of strong tissue-specific enhancers, involving the cooperative assembly of higher-order nucleoprotein complexes called enhanceosomes. Here we show that the HPV18 enhancer, which controls the epithelial-specific transcription of the E6 and E7 transforming genes, exhibits characteristic features of these structures. We used deletion experiments to show that a core enhancer element cooperates, in a specific helical phasing, with distant essential factors binding to the ends of the enhancer. This core sequence, binding a Jun B/Fra-2 heterodimer, cooperatively recruits the architectural protein HMG-I(Y) in a nucleoprotein complex, where they interact with each other. Therefore, in HeLa cells, HPV18 transcription seems to depend upon the assembly of an enhanceosome containing multiple cellular factors recruited by a core sequence interacting with AP1 and HMG-I(Y).

  13. Linearizable cellular automata

    International Nuclear Information System (INIS)

    Nobe, Atsushi; Yura, Fumitaka

    2007-01-01

    The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

  14. Using HPV prevalence to predict cervical cancer incidence.

    Science.gov (United States)

    Sharma, Monisha; Brun