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Sample records for human papillomavirus type-16

  1. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

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    Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

    2009-07-01

    Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  2. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

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    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  3. Characterization of human papillomavirus type 16 pseudovirus containing histones.

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    Kim, Hyoung Jin; Kwag, Hye-Lim; Kim, Hong-Jin

    2016-08-27

    Pseudoviruses (PsVs) that encapsidate a reporter plasmid DNA have been used as surrogates for native human papillomavirus (HPV), whose continuous production is technically difficult. HPV PsVs have been designed to form capsids made up of the major capsid protein L1 and the minor capsid proteins L2. HPV PsVs have been produced in 293TT cells transfected with plasmid expressing L1 and L2 protein and plasmid containing the reporter gene. Several studies have suggested that naturally occurring HPV virions contain cellular histones, and histones have also been identified in mature HPV PsVs. However, the effect of the histones on the properties of the PsVs has not been investigated. Using heparin chromatography, we separated mature HPV type 16 PsVs into three fractions (I, II, and III) according to their heparin-binding affinities. The amounts of cellular histone and cellular nucleotides per PsV were found to increase in the order fraction I, II and III. It appeared that PsVs in fraction I contains just small amount of cellular histone in Western blot analysis. The proportions of the three fractions in PsV preparations were 83.4, 7.5, and 9.1 % for fraction I, II, and III PsVs, respectively. In the electron microscope PsVs in fraction I appeared to have a more condensed structure than those in fractions II and III. Under the electron microscope fraction II and III PsVs appeared to be covered by substantial amounts of cellular histone while there was no visible histone covering PsVs of fraction I. Also the levels of reporter gene expression in infections of fraction II and III PsVs to 293TT cells were significantly lower than those in infections of fraction I PsV, and fraction II and III particles had significantly reduced immunogenicity. Our findings suggest that the involvement of large amounts of cellular histones during PsV formation interferes with the structural integrity of the PsVs and affects their immunogenicity. The fraction I particle therefore has the most

  4. The early noncoding region of human papillomavirus type 16 is regulated by cytoplasmic polyadenylation factors

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    Glahder, Jacob-Andreas Harald; Kristiansen, Karen; Durand, Marjorie

    2010-01-01

    All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (...

  5. Activities of E7 promoters in the human papillomavirus type 16 genome during cell differentiation

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    Hansen, Christina Neigaard; Nielsen, Lone; Norrild, Bodil

    2010-01-01

    Worldwide, one of the most common cancer forms diagnosed in women is cervical cancer induced by infections with high-risk human papillomaviruses (HPVs) with HPV type 16 (HPV-16) being the most frequently identified. The oncogenicity is caused mainly by expression of the oncogenes E6 and E7 leadin...

  6. ANTIBODIES TO HUMAN PAPILLOMAVIRUS TYPE-16 E7 RELATED TO CLINICOPATHOLOGICAL DATA IN PATIENTS WITH CERVICAL-CARCINOMA

    NARCIS (Netherlands)

    BAAY, MFD; DUK, JM; BURGER, MPM; WALBOOMERS, J; TERSCHEGGET, J; GROENIER, KH; DEBRUIJN, HWA; STOLZ, E; HERBRINK, P

    Aims-To investigate the correlation between antibodies to the transforming protein E7 of human papillomavirus (HPV) type 16 and clinicopathological indices in women with cervical squamous carcinoma. Methods-A synthetic peptide of the HPV type 16 E7 protein (amino acids 6 to 35) was used to screen

  7. Telomerase activation by the E6 gene product of human papillomavirus type 16.

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    Klingelhutz, A J; Foster, S A; McDougall, J K

    1996-03-07

    Activation of telomerase, a ribonucleoprotein complex that synthesizes telomere repeat sequences, is linked to cell immortalization and is characteristic of most cell lines and tumours. Here we show that expression of the human papillomavirus type 16 (HPV-16) E6 protein activates telomerase in early-passage human keratinocytes and mammary epithelial cells. This activation was observed in cells pre-crisis, that is, before they became immortal, and occurred within one passage of retroviral infection with vectors expressing HPV-16 E6. Studies using HPV-16 E6 mutants showed that there was no correlation between the ability of the mutants to activate telomerase and their ability to target p53 for degradation, suggesting that telomerase activation by HPV-16 E6 is p53 independent. Keratinocytes expressing wild-type HPV-16 E6 have an extended lifespan, but do not become immortal, indicating that telomerase activation and E6-mediate degradation of p53 are insufficient for their immortalization. These results show that telomerase activation is an intrinsic, but insufficient, component of transformation by HPV.

  8. Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice

    International Nuclear Information System (INIS)

    Whitehead, Mark; Öhlschläger, Peter; Almajhdi, Fahad N; Alloza, Leonor; Marzábal, Pablo; Meyers, Ann E; Hitzeroth, Inga I; Rybicki, Edward P

    2014-01-01

    Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer. In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV - type 16 – the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera®, a self-assembly domain of the maize γ-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems. High-level expression of the HPV 16E7SH protein fused to Zera® in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression. The fusion of 16E7SH to the Zera® peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera® PBs

  9. Heterologous production of human papillomavirus type-16 L1 protein by a lactic acid bacterium

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    Bermúdez-Humarán Luis G

    2009-08-01

    Full Text Available Abstract Background The expression of vaccine antigens in lactic acid bacteria (LAB is a safe and cost-effective alternative to traditional expression systems. In this study, we investigated i the expression of Human papillomavirus type 16 (HPV-16 L1 major capsid protein in the model LAB Lactococcus lactis and ii the ability of the resulting recombinant strain to produce either capsomer-or virus-like particles (VLPs. Results and conclusion HPV-16 L1 gene was cloned into two vectors, pCYT and pSEC, designed for controlled intra- or extracellular heterologous expression in L. lactis, respectively. The capacity of L. lactis harboring either pCYT:L1 or pSEC:L1 plasmid to accumulate L1 in the cytoplasm and supernatant samples was confirmed by Western blot assays. Electron microscopy analysis suggests that, L1 protein produced by recombinant lactococci can self-assemble into structures morphologically similar to VLPs intracellularly. The presence of conformational epitopes on the L. lactis-derived VLPs was confirmed by ELISA using an anti-HPV16 L1 capsid antigen antibody. Our results support the feasibility of using recombinant food-grade LAB, such as L. lactis, for the production of L1-based VLPs and open the possibility for the development of a new safe mucosal vector for HPV-16 prophylactic vaccination.

  10. Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection.

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    Skeate, Joseph G; Porras, Tania B; Woodham, Andrew W; Jang, Julie K; Taylor, Julia R; Brand, Heike E; Kelly, Thomas J; Jung, Jae U; Da Silva, Diane M; Yuan, Weiming; Kast, W Martin

    2016-02-01

    Herpes simplex virus (HSV) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (HPV) is now the accepted causative agent, the epidemiological link between HSV and HPV-associated cancers persists. The annexin A2 heterotetramer (A2t) has been shown to mediate infectious HPV type 16 (HPV16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (SLPI), an endogenous A2t ligand, inhibits HPV16 uptake and infection. Interestingly, HSV infection induces a sustained downregulation of SLPI in epithelial cells, which we hypothesized promotes HPV16 infection through A2t. Here, we show that in vitro infection of human keratinocytes with HSV-1 or HSV-2, but not with an HSV-1 ICP4 deletion mutant that does not downregulate SLPI, leads to a >70% reduction of SLPI mRNA and a >60% decrease in secreted SLPI protein. Consequently, we observed a significant increase in the uptake of HPV16 virus-like particles and gene transduction by HPV16 pseudovirions (two- and 2.5-fold, respectively) in HSV-1- and HSV-2-infected human keratinocyte cell cultures compared with uninfected cells, whereas exogenously added SLPI reversed this effect. Using a SiMPull (single-molecule pulldown) assay, we demonstrated that endogenously secreted SLPI interacts with A2t on epithelial cells in an autocrine/paracrine manner. These results suggested that ongoing HSV infection and resultant downregulation of local levels of SLPI may impart a greater susceptibility for keratinocytes to HPV16 infection through the host cell receptor A2t, providing a mechanism that may, in part, provide an explanation for the aetiological link between HSV and HPV-associated cancers.

  11. Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection.

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    Woodham, Andrew W; Taylor, Julia R; Jimenez, Andrew I; Skeate, Joseph G; Schmidt, Thomas; Brand, Heike E; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro. A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry. A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding. These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Ultrasensitive quantitation of human papillomavirus type 16 E6 oncogene sequences by nested real time PCR

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    López-Revilla Rubén

    2010-05-01

    Full Text Available Abstract Background We have developed an ultrasensitive method based on conventional PCR preamplification followed by nested amplification through real time PCR (qPCR in the presence of the DNA intercalating agent EvaGreen. Results Amplification mixtures calibrated with a known number of pHV101 copies carrying a 645 base pair (bp-long insert of the human papillomavirus type 16 (HPV16 E6 oncogene were used to generate the E6-1 amplicon of 645 bp by conventional PCR and then the E6-2 amplicon of 237 bp by nested qPCR. Direct and nested qPCR mixtures for E6-2 amplification corresponding to 2.5 × 102-2.5 × 106 initial pHV101 copies had threshold cycle (Ct values in the ranges of 18.7-29.0 and 10.0-25.0, respectively. The Ct of qPCR mixtures prepared with 1/50 volumes of preamplified mixtures containing 50 ng of DNA of the SiHa cell line (derived from an invasive cervical cancer with one HPV16 genome per cell was 19.9. Thermal fluorescence extinction profiles of E6-2 amplicons generated from pHV101 and SiHa DNA were identical, with a peak at 85.5°C. Conclusions Our method based on conventional preamplification for 15 cycles increased 10,750 times the sensitivity of nested qPCR for the quantitation of the E6 viral oncogene and confirmed that the SiHa cell line contains one E6-HPV16 copy per cell.

  13. Human papillomavirus type 16 molecular variants in Guarani Indian women from Misiones, Argentina.

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    Tonon, Sergio Andrés; Basiletti, Jorge; Badano, Ines; Alonio, Lidia Virginia; Villa, Luisa Lina; Teyssie, Angélica Rita; Picconi, María Alejandra

    2007-01-01

    To identify human papillomavirus type 16 (HPV16) E6 and L1 molecular variants infecting Guarani Indian women settled in Misiones, Argentina, a region with a high prevalence of cervical cancer. Some intratypic molecular variants of HPV16 have been associated with greater oncogenic risk, but their implication in the etiology of cervical cancer is still uncertain. Seventy HPV16 positive cervical samples from Guarani Indian women settled in two different areas of Misiones, Argentina, (34 from the northern area and 36 from the central area), were analyzed. Thirty-seven had normal cytology, 18 had a low-grade squamous intraepithelial lesion (LGSIL), and 15 a high-grade squamous intraepithelial lesion (HGSIL). HPV16 E6 and L1 molecular variants were identified by PCR, followed by dot blot hybridization with 23 and 12 biotinylated oligonucleotide probes, respectively. The frequency of HPV16 variants over the Guarani population was 51% EP (European prototype), 32% E-350G, 9% Af1-a (African 1), 4% E-6862C, 3% Af2-a, and 1% AA-a (Asian-American). The distribution of variants was not homogeneous in the two areas under analysis, with the northern area being more diverse showing 74% of European variants, while the central area presented exclusively E variants. No statistically significant association was found between any particular variant and grade of cervical lesion. This study reports for the first time HPV16 E6 and L1 molecular variants infecting women from an aboriginal community inhabiting a rainforest region of South America. The presence of E class variants could be attributed primarily to contacts with the Spanish conquerors, and Af variants from African slaves introduced later in the South American continent.

  14. Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16

    Czech Academy of Sciences Publication Activity Database

    Šmahel, M.; Sobotková, E.; Bubeník, Jan; Šímová, Jana; Žák, R.; Ludvíková, V.; Mikyšková, Romana; Kovařík, J.; Jelínek, F.; Povýšil, C.; Marinov, J.; Vonka, V.

    2001-01-01

    Roč. 84, č. 3 (2001), s. 374-380 ISSN 0007-0920 R&D Projects: GA MZd NC5900; GA MZd NC5526; GA ČR GA312/99/0542; GA ČR GA312/98/0826 Institutional research plan: CEZ:AV0Z5052915 Keywords : human papillomavirus * E6/E7 oncogenes * cell transformation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.942, year: 2001

  15. The 3' region of Human Papillomavirus type 16 early mRNAs decrease expression

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    Vinther, J.; Rosenstierne, M.W.; Kristiansen, Karen

    2005-01-01

    Background: High risk human papillomavirus (HR-HPV) infects mucosal surfaces and HR-HPV infection is required for development of cervical cancer. Accordingly, enforced expression of the early HR-HPV proteins can induce immortalisation of human cells. In most cervical cancers and cervical cancer...... cell lines the HR-HPV double stranded DNA genome has been integrated into the host cell genome. Methods: We have used a retroviral GUS reporter system to generate pools of stably transfected HaCaT and SiHa cells. The HPV-16 early sequences that are deleted upon integration of the HPV-16 genome...

  16. The Human Papillomavirus Type 16 E6 Oncoprotein Activates mTORC1 Signaling and Increases Protein Synthesis ▿ †

    OpenAIRE

    Spangle, Jennifer M.; Münger, Karl

    2010-01-01

    The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y....

  17. Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage

    International Nuclear Information System (INIS)

    Park, Jung Wook; Nickel, Kwangok P.; Torres, Alexandra D.; Lee, Denis; Lambert, Paul F.; Kimple, Randall J.

    2014-01-01

    Background and purpose: Patients with human papillomavirus related (HPV+) head and neck cancers (HNCs) demonstrate improved clinical outcomes compared to traditional HPV negative (HPV−) HNC patients. We have recently shown that HPV+ HNC cells are more sensitive to radiation than HPV− HNC cells. However, roles of HPV oncogenes in regulating the response of DNA damage repair remain unknown. Material and methods: Using immortalized normal oral epithelial cell lines, HPV+ HNC derived cell lines, and HPV16 E7-transgenic mice we assessed the repair of DNA damage using γ-H2AX foci, single and split dose clonogenic survival assays, and immunoblot. The ability of E7 to modulate expression of proteins associated with DNA repair pathways was assessed by immunoblot. Results: HPV16 E7 increased retention of γ-H2AX nuclear foci and significantly decreased sublethal DNA damage repair. While phospho-ATM, phospho-ATR, Ku70, and Ku80 expressions were not altered by E7, Rad51 was induced by E7. Correspondingly, HPV+ HNC cell lines showed retention of Rad51 after γ-radiation. Conclusions: Our findings provide further understanding as to how HPV16 E7 manipulates cellular DNA damage responses that may underlie its oncogenic potential and influence the altered sensitivity to radiation seen in HPV+ HNC as compared to HPV− HNC

  18. Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis.

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    DiGiuseppe, Stephen; Luszczek, Wioleta; Keiffer, Timothy R; Bienkowska-Haba, Malgorzata; Guion, Lucile G M; Sapp, Martin J

    2016-05-31

    During the entry process, the human papillomavirus (HPV) capsid is trafficked to the trans-Golgi network (TGN), whereupon it enters the nucleus during mitosis. We previously demonstrated that the minor capsid protein L2 assumes a transmembranous conformation in the TGN. Here we provide evidence that the incoming viral genome dissociates from the TGN and associates with microtubules after the onset of mitosis. Deposition onto mitotic chromosomes is L2-mediated. Using differential staining of an incoming viral genome by small molecular dyes in selectively permeabilized cells, nuclease protection, and flotation assays, we found that HPV resides in a membrane-bound vesicle until mitosis is completed and the nuclear envelope has reformed. As a result, expression of the incoming viral genome is delayed. Taken together, these data provide evidence that HPV has evolved a unique strategy for delivering the viral genome to the nucleus of dividing cells. Furthermore, it is unlikely that nuclear vesicles are unique to HPV, and thus we may have uncovered a hitherto unrecognized cellular pathway that may be of interest for future cell biological studies.

  19. Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Leminen, A.; Paavonen, J.; Vesterinen, E.; Wahlstroem, T.R.; Rantala, I.; Lehtinen, M.

    1991-01-01

    Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35 S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival

  20. Redetection of human papillomavirus type 16 infections of the cervix in mid-adult life

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    Aaron Ermel

    2018-06-01

    Full Text Available Purpose: To assess whether HPV 16 originally detected in adolescent women can be redetected in adulthood. Methods: A convenience sample of 27 adult women with known HPV 16 detection during adolescence was assessed for HPV 16 redetection. A comparison of the long control region (LCR DNA sequences was performed on some of the original and redetected HPV 16 isolates. Results: Median age at reenrollment was 27.5 years (interquartile range of 26.7–29.6. Reenrollment occurred six years on average after the original HPV 16 detection. Eleven of 27 women had HPV 16 redetected. Some of these HPV 16 infections had apparently cleared during adolescence. LCR sequencing was successful in paired isolates from 6 women; in 5 of 6 cases the redetected HPV 16 isolates were identical to those detected during adolescence, Conclusions: HPV 16 may be episodically detected in young women, even over long time periods. HPV 16 redetection with identical LCR sequences suggests low-level persistent infection rather than true clearance, although newly acquired infection with an identical HPV 16 isolate cannot be excluded. However, this study suggests that a new HPV 16-positive test in a clinical setting may not indicate a new infection. Keywords: Human papillomavirus (HPV, Redetection, Latency, Long control region, Sequencing

  1. An enhanced heterologous virus-like particle for human papillomavirus type 16 tumour immunotherapy.

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    Khairunadwa Jemon

    Full Text Available Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV virus-like particle (VLP-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48-57 from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25 or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.

  2. The Human Papillomavirus Type 16 E6 Gene Alone Is Sufficient To Induce Carcinomas in Transgenic Animals

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    Song, Shiyu; Pitot, Henry C.; Lambert, Paul F.

    1999-01-01

    High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated the role that the E6 gene plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy. PMID:10364340

  3. Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16—Involvement of Tetraspanin-Enriched Microdomains (TEMs)

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    Spoden, Gilles; Freitag, Kirsten; Husmann, Matthias; Boller, Klaus; Sapp, Martin; Lambert, Carsten; Florin, Luise

    2008-01-01

    Background Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. Methodology/Principal Findings Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs) in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. Conclusions/Significance Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16. PMID:18836553

  4. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs.

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    Gilles Spoden

    Full Text Available BACKGROUND: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16, the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. CONCLUSIONS/SIGNIFICANCE: Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV and hepatitis C virus (HCV. However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16.

  5. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs).

    Science.gov (United States)

    Spoden, Gilles; Freitag, Kirsten; Husmann, Matthias; Boller, Klaus; Sapp, Martin; Lambert, Carsten; Florin, Luise

    2008-10-02

    Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs) in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16.

  6. LOCALIZATION OF HUMAN PAPILLOMAVIRUS TYPE-16 DNA USING THE POLYMERASE CHAIN-REACTION IN THE CERVIX UTERI OF WOMEN WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

    NARCIS (Netherlands)

    Cornelissen, M. T.; van den Tweel, J. G.; Struyk, A. P.; Jebbink, M. F.; Briët, M.; van der Noordaa, J.; ter Schegget, J. T.

    1989-01-01

    The localization of human papillomavirus type 16 (HPV-16) DNA throughout the cervix uteri of women with cervical intraepithelial neoplasia (CIN) was studied by utilizing the polymerase chain reaction technique directly on histologically defined sections of paraffin-embedded cervical tissue obtained

  7. Genetic immunization against cervical carcinoma : induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7

    NARCIS (Netherlands)

    Daemen, T; Pries, F; Bungener, L; Kraak, M; Regts, J; Wilschut, J

    infection of genital epithelial cells with human papillomavirus (HPV) types 16 and 18 is closely associated with the development of cervical carcinoma. The transforming potential of these high-risk HPVs depends on the expression of the E6 and E7 early viral gene products. Since the expression of E6

  8. Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis.

    Directory of Open Access Journals (Sweden)

    Nor Malia Abd Warif

    Full Text Available It has previously been shown that expression of human papillomavirus type 16 (HPV E7 in epidermis causes hyperplasia and chronic inflammation, characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is strongly immune suppressed and is not rejected when transplanted onto immune competent mice. Professional antigen presenting cells are considered essential for initiation of the adaptive immune response that results in graft rejection. Langerhans cells (LC are the only antigen presenting cells located in normal epidermis and altered phenotype and function of these cells may contribute to the immune suppressive microenvironment. Here, we show that LC are atypically activated as a direct result of E7 expression in the epidermis, and independent of the presence of lymphocytes. The number of LC was significantly increased and the LC are functionally impaired, both in migration and in antigen uptake. However when the LC were extracted from K14E7 skin and matured in vitro they were functionally competent to present and cross-present antigen, and to activate T cells. The ability of the LC to present and cross-present antigen following maturation supports retention of full functional capacity when removed from the hyperplastic skin microenvironment. As such, opportunities are afforded for the development of therapies to restore normal LC function in hyperplastic skin.

  9. Inverse association between methylation of human papillomavirus type 16 DNA and risk of cervical intraepithelial neoplasia grades 2 or 3.

    Directory of Open Access Journals (Sweden)

    Long Fu Xi

    Full Text Available The clinical relevance of human papillomavirus type 16 (HPV16 DNA methylation has not been well documented, although its role in modulation of viral transcription is recognized.Study subjects were 211 women attending Planned Parenthood clinics in Western Washington for routine Papanicolaou screening who were HPV16 positive at the screening and/or subsequent colposcopy visit. Methylation of 11 CpG dinucleotides in the 3' end of the long control region of the HPV16 genome was examined by sequencing the cloned polymerase chain reaction products. The association between risk of CIN2/3 and degree of CpG methylation was estimated using a logistic regression model.CIN2/3 was histologically confirmed in 94 (44.5% of 211 HPV16 positive women. The likelihood of being diagnosed as CIN2/3 increased significantly with decreasing numbers of methylated CpGs (meCpGs in the 3' end of the long control region (P(for trend = 0.003. After adjusting for HPV16 variants, number of HPV16-positive visits, current smoking status and lifetime number of male sex partners, the odds ratio for the association of CIN2/3 with ≥4 meCpGs was 0.31 (95% confidence interval, 0.12-0.79. The proportion of ≥4 meCpGs decreased appreciably as the severity of the cervical lesion increased (P(for trend = 0.001. The inverse association remained similar when CIN3 was used as the clinical endpoint. Although not statistically significant, the ≥4 meCpGs-related risk reduction was more substantial among current, as compared to noncurrent, smokers.Results suggest that degree of the viral genome methylation is related to the outcome of an HPV16 cervical infection.

  10. Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico

    Science.gov (United States)

    López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

    2009-01-01

    Background In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Results Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. Conclusion We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype. PMID:19216802

  11. Comparison of different assays to assess human papillomavirus (HPV) type 16- and 18-specific antibodies after HPV infection and vaccination

    NARCIS (Netherlands)

    Scherpenisse, Mirte; Schepp, Rutger M.; Mollers, Madelief; Mooij, Sofie H.; Meijer, Chris J. L. M.; Berbers, Guy A. M.; van der Klis, Fiona R. M.

    2013-01-01

    We compared the measurement of human papillomavirus (HPV)-specific serum antibody levels with the virus-like-particle multiplex immunoassay (VLP-MIA), competitive Luminex immunoassay (cLIA), and glutathione S-transferase (GST) L1-based MIA. Using a large panel of serum samples, these assays showed

  12. Production of human papillomavirus type16 E7 oncoprotein fused with ß-glucuronidase in transgenic tomato and potato

    Czech Academy of Sciences Publication Activity Database

    Bříza, Jindřich; Pavingerová, Daniela; Vlasák, Josef; Ludvíková, V.; Niedermeierová, Hana

    2007-01-01

    Roč. 51, č. 2 (2007), s. 268-276 ISSN 0006-3134 R&D Projects: GA ČR GA521/05/2092 Institutional research plan: CEZ:AV0Z50510513 Keywords : transgenic plants * human papillomavirus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.259, year: 2007

  13. The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.

    Science.gov (United States)

    Spangle, Jennifer M; Münger, Karl

    2010-09-01

    The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.

  14. Potato virus X displaying the E7 peptide derived from human papillomavirus type 16: a novel position for epitope presentation

    Czech Academy of Sciences Publication Activity Database

    Vaculík, Petr; Plchová, Helena; Moravec, Tomáš; Hoffmeisterová, Hana; Čeřovská, Noemi; Šmahel, M.

    2015-01-01

    Roč. 120, č. 2 (2015), s. 671-680 ISSN 0167-6857 R&D Projects: GA ČR(CZ) GAP501/12/1761 Grant - others:European Regional Development Fund(XE) CZ.2.16/3.1.00/24014 Institutional support: RVO:61389030 Keywords : Potato virus X * Human papillomavirus * Nicotiana benthamiana Subject RIV: EE - Microbiology, Virology Impact factor: 2.390, year: 2015

  15. Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA

    International Nuclear Information System (INIS)

    Smits, H.L.; Raadsheer, E.; Rood, I.; Mehendale, S.; Slater, R.M.; van der Noordaa, J.; Ter Schegget, J.

    1988-01-01

    Human embryonic fibroblasts with a large deletion (11p11.11p15.1) in the short arm of one chromosome 11 (del-11 cells) appeared to be susceptible to transformation by early human papillomavirus type 16 (HPV-16) DNA, whereas diploid human embryonic fibroblasts were not. This difference in susceptibility might be explained by the absence of a tumor suppressor gene located within the deleted part on the short arm of chromosome 11. The presence of abundant viral early-gene transcripts in transformed cells suggests that transformation was induced by an elevated level of an HPV-16 early-gene product(s). The low transcriptional activity of HPV-16 in diploid cells may indicate that cellular genes affect viral transcription. Interruption of the HPV-16 E2 early open reading frame is probably required for high-level HPV-16 early-gene expression driven from the homologous enhancer-promoter region

  16. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Stephen Jacques

    2010-01-01

    ABSTRACT: Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18 is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin...... embedded (FFPE) sections of cervical cancer. Tissue blocks from 35 cases of in situ or invasive cervical squamouscell carcinoma and surrogate FFPE sections containing the cell lines HeLa and SiHa were tested for HPV 16 and HPV18 and for the housekeeping gene beta-actin by conventional PCR using type...

  17. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Steven

    2010-01-01

    ABSTRACT: Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18, is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin...... embedded (FFPE) sections of cervical cancer.Tissue blocks from 35 cases of in situ or invasive cervical squamous cell carcinoma and surrogate FFPE sections containing the cell lines HeLa and SiHa were tested for HPV 16 and HPV18 by conventional PCR using type specific primers, and for the housekeeping gene...

  18. Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

    OpenAIRE

    Miyasaka, M; Takami, Y; Inoue, H; Hakura, A

    1991-01-01

    The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed ph...

  19. Pap smear cytology and identification of Human Papillomavirus (HPV) type 16 and 18 in multiparity women at Aviati Clinic Padang Bulan Medan

    Science.gov (United States)

    Anggraini, D. R.; Feriyawati, L.; Fitrie, A. A.; Ginting, R. N. A.

    2018-03-01

    Cervical cancer is the second most frequent cancer in woman in developing countries and one of the most crucial health problems in the world. Human Papillomavirus (HPV) is an agent for sexually transmitted disease which is an act of cervical cancer, especially high-risk of HPV type 16 and 18. In this study, we investigated the Pap smear cytology features and identification of HPV types 16 and18 in multiparity women at Aviati Clinic Padang Bulan, Medan. Samples are cervical swabs of 50 multiparity women who met the inclusion criteria (childbirth ≥ three times) was included in the study. Pap smear examination was conducted using Papanicolaou staining and identification of HPV types 16 and 18 using the Polymerase Chain Reactive (PCR) methods. Pap smearcytology showed 80% Negative for intraepithelial lesion or malignancy (NILM) with inflammation and 20% NILM. The result of PCR amplification showed that there weren’t specific band DNA was found at band 414bp and 216bp. That means there weren’t cervical swabs sample had DNA of HPV type 16 and 18.

  20. Electrochemical detection of human papillomavirus DNA type 16 using a pyrrolidinyl peptide nucleic acid probe immobilized on screen-printed carbon electrodes.

    Science.gov (United States)

    Jampasa, Sakda; Wonsawat, Wanida; Rodthongkum, Nadnudda; Siangproh, Weena; Yanatatsaneejit, Pattamawadee; Vilaivan, Tirayut; Chailapakul, Orawon

    2014-04-15

    An electrochemical biosensor based on an immobilized anthraquinone-labeled pyrrolidinyl peptide nucleic acid (acpcPNA) probe was successfully developed for the selective detection of human papillomavirus (HPV) type 16 DNA. A 14-mer acpcPNA capture probe was designed to recognize a specific 14 nucleotide region of HPV type 16 L1 gene. The redox-active label anthraquinone (AQ) was covalently attached to the N-terminus of the acpcPNA probe through an amide bond. The probe was immobilized onto a chitosan-modified disposable screen-printed carbon electrode via a C-terminal lysine residue using glutaraldehyde as a cross-linking agent. Hybridization with the target DNA was studied by measuring the electrochemical signal response of the AQ label using square-wave voltammetric analysis. The calibration curve exhibited a linear range between 0.02 and 12.0 µM with a limit of detection and limit of quantitation of 4 and 14 nM, respectively. This DNA sensing platform was successfully applied to detect the HPV type 16 DNA from a PCR amplified (240 bp fragment of the L1 gene) sample derived from the HPV type 16 positive human cancer cell line (SiHa), and failed to detect the HPV-negative c33a cell line. The sensor probe exhibited very high selectivity for the complementary 14 base oligonucleotide over the non-complementary oligonucleotides with sequences derived from HPV types 18, 31 and 33. The proposed sensor provides an inexpensive tool for the early stage detection of HPV type 16, which is an important biomarker for cervical cancer. © 2013 Elsevier B.V. All rights reserved.

  1. Human Papillomavirus Type 16 E6 and E7 Oncoproteins Act Synergistically to Cause Head and Neck Cancer in Mice

    Science.gov (United States)

    Jabbar, Sean; Strati, Katerina; Shin, Myeong Kyun; Pitot, Henry C.; Lambert, Paul F.

    2010-01-01

    High-risk human papillomaviruses (HPVs) contribute to cervical and other anogenital cancers, and they are also linked etiologically to a subset of head and neck squamous cell carcinomas (HNSCC). We previously established a model for HPV-associated HNSCC in which we treated transgenic mice expressing the papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing HNSCC, and its dominance masked any potential oncogenic contribution of E6, a second papillomaviral oncoprotein commonly expressed in human cancers. In the current study, we shortened the duration of treatment with 4-NQO to reduce the incidence of cancers and discovered a striking synergy between E6 and E7 in causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer. PMID:20797753

  2. Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection.

    Directory of Open Access Journals (Sweden)

    Andreea Popa

    2015-02-01

    Full Text Available Trafficking of human papillomaviruses to the Golgi apparatus during virus entry requires retromer, an endosomal coat protein complex that mediates the vesicular transport of cellular transmembrane proteins from the endosome to the Golgi apparatus or the plasma membrane. Here we show that the HPV16 L2 minor capsid protein is a retromer cargo, even though L2 is not a transmembrane protein. We show that direct binding of retromer to a conserved sequence in the carboxy-terminus of L2 is required for exit of L2 from the early endosome and delivery to the trans-Golgi network during virus entry. This binding site is different from known retromer binding motifs and can be replaced by a sorting signal from a cellular retromer cargo. Thus, HPV16 is an unconventional particulate retromer cargo, and retromer binding initiates retrograde transport of viral components from the endosome to the trans-Golgi network during virus entry. We propose that the carboxy-terminal segment of L2 protein protrudes through the endosomal membrane and is accessed by retromer in the cytoplasm.

  3. Methylated Host Cell Gene Promoters and Human Papillomavirus Type 16 and 18 Predicting Cervical Lesions and Cancer.

    Directory of Open Access Journals (Sweden)

    Nina Milutin Gašperov

    Full Text Available Change in the host and/or human papillomavirus (HPV DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP. The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5'LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters' methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.

  4. E6AP is Required for Human Papillomavirus type 16 E6 to Cause Cervical Cancer in Mice

    Science.gov (United States)

    Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

    2010-01-01

    High-risk human papillomaviruses cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins including Bak, E6BP1, E6TP1, and proteins that contain PDZ domains such as hScrib and hDlg. Many of these activities are thought to contribute to E6’s role in carcinogenesis. E6’s interaction with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through E6’s ability to recruit the ubiquitin ligase, E6AP into complexes with these cellular proteins resulting in their ubiquitin–mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating E6's acute and oncogenic phenotypes, including induction of epithelial hyperplasia, abrogation of DNA damage response and induction of cervical cancer. Loss of E6AP had no discernable effect on E6's ability to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of E6’s oncogenic potential in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. PMID:20530688

  5. Dating the origin and dispersal of Human Papillomavirus type 16 on the basis of ancestral human migrations.

    Science.gov (United States)

    Zehender, Gianguglielmo; Frati, Elena Rosanna; Martinelli, Marianna; Bianchi, Silvia; Amendola, Antonella; Ebranati, Erika; Ciccozzi, Massimo; Galli, Massimo; Lai, Alessia; Tanzi, Elisabetta

    2016-04-01

    A major limitation when reconstructing the origin and evolution of HPV-16 is the lack of reliable substitution rate estimates for the viral genes. On the basis of the hypothesis of human HPV-16 co-divergence, we estimated a mean evolutionary rate of 1.47×10(-7) (95% HPD=0.64-2.47×10(-7)) subs/site/year for the viral LCR region. The results of a Bayesian phylogeographical analysis suggest that the currently circulating HPV-16 most probably originated in Africa about 110 thousand years ago (Kya), before giving rise to four known geographical lineages: the Asian/European lineage, which most probably originated in Asia a mean 38 Kya, and the Asian/American and two African lineages, which probably respectively originated about 33 and 27 Kya. These data closely reflect current hypotheses concerning modern human expansion based on studies of mitochondrial DNA phylogeny. The correlation between ancient human migration and the present HPV phylogeny may be explained by the co-existence of modes of transmission other than sexual transmission. Copyright © 2016. Published by Elsevier B.V.

  6. Identification and characterization of a cluster of transcription start sites located in the E6 ORF of human papillomavirus type 16

    DEFF Research Database (Denmark)

    Rosenstierne, Maiken W; Vinther, Jeppe; Hansen, Christina N

    2003-01-01

    Human papillomavirus type 16 (HPV-16) is the prototype strain among the malignant types of HPV in the western world. The main promoter, P97, located in front of the E6 ORF, has been shown to control expression of the oncogenes E6 and E7. These oncogenes are expressed continuously in HPV-16......-transformed cells. In contrast to malignant HPV types, non-malignant HPV types have separate promoters driving the expression of E6 and E7. Experiments have shown that the translation of E7 is more efficient from monocistronic than bicistronic transcripts encoding both E6 and E7. Here, identification...... of a cluster of transcription start sites located in the E6 ORF of HPV-16 is presented. Transcripts from this region contain the E7 ORF as the first reading frame. The cluster consists of multiple transcription start sites located around nt 441. Additional transcription start sites were identified in a cluster...

  7. Zinc finger arrays binding human papillomavirus types 16 and 18 genomic DNA: precursors of gene-therapeutics for in-situ reversal of associated cervical neoplasia

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2012-07-01

    Full Text Available Abstract Background Human papillomavirus (HPV types 16 and 18 are the high-risk, sexually transmitted infectious causes of most cervical intraepithelial neoplasias (CIN or cancers. While efficacious vaccines to reduce the sexual acquisition of these high-risk HPVs have recently been introduced, no virus-targeted therapies exist for those already exposed and infected. Considering the oncogenic role of the transforming (E6 and E7 genes of high-risk HPVs in the slow pathogenesis of cervical cancer, we hypothesize that timely disruption or abolition of HPV genome expression within pre-cancerous lesions identified at screening may reverse neoplasia. We aimed to derive model zinc finger nucleases (ZFNs for mutagenesis of the genomes of two high-risk HPV (types 16 & 18. Methods and results Using ZiFiT software and the complete genomes of HPV types16 and 18, we computationally generated the consensus amino acid sequences of the DNA-binding domains (F1, F2, & F3 of (i 296 & 327 contextually unpaired (or single three zinc-finger arrays (sZFAs and (ii 9 & 13 contextually paired (left and right three- zinc-finger arrays (pZFAs that bind genomic DNA of HPV-types 16 and 18 respectively, inclusive of the E7 gene (s/pZFAHpV/E7. In the absence of contextually paired three-zinc-finger arrays (pZFAs that bind DNA corresponding to the genomic context of the E6 gene of either HPV type, we derived the DNA binding domains of another set of 9 & 14 contextually unpaired E6 gene-binding ZFAs (sZFAE6 to aid the future quest for paired ZFAs to target E6 gene sequences in both HPV types studied (pZFAE6. This paper presents models for (i synthesis of hybrid ZFNs that cleave within the genomic DNA of either HPV type, by linking the gene sequences of the DNA-cleavage domain of the FokI endonuclease FN to the gene sequences of a member of the paired-HPV-binding ZFAs (pZFAHpV/E7 + FN, and (ii delivery of the same into precancerous lesions using HPV-derived viral plasmids or

  8. Immortalization of normal human embryonic fibroblasts by introduction of either the human papillomavirus type 16 E6 or E7 gene alone.

    Science.gov (United States)

    Yamamoto, Akito; Kumakura, Shin-ichi; Uchida, Minoru; Barrett, J Carl; Tsutsui, Takeki

    2003-09-01

    The ability of the human papillomavirus type 16 (HPV-16) E6 or E7 gene to induce immortalization of normal human embryonic fibroblast WHE-7 cells was examined. WHE-7 cells at 9 population doublings (PD) were infected with retrovirus vectors encoding either HPV-16 E6 or E7 alone or both E6 and E7 (E6/E7). One of 4 isolated clones carrying E6 alone became immortal and is currently at >445 PD. Four of 4 isolated clones carrying E7 alone escaped from crisis and are currently at >330 PD. Three of 5 isolated clones carrying E6/E7 were also immortalized and are currently at >268 PD. The immortal clone carrying E6 only and 2 of the 3 immortal clones carrying E6/E7 expressed a high level of E6 protein, and all the immortal clones carrying E7 alone and the other immortal clone carrying E6/E7 expressed a high level of E7 protein when compared to their mortal or precrisis clones. The immortal clones expressing a high level of E6 or E7 protein were positive for telomerase activity or an alternative mechanism of telomere maintenance, respectively, known as ALT (alternative lengthening of telomeres). All the mortal or precrisis clones were negative for both phenotypes. All the immortal clones exhibited abrogation of G1 arrest after DNA damage by X-ray irradiation. The expression of INK4a protein (p16(INK4a)) was undetectable in the E6-infected mortal and immortal clones, whereas Rb protein (pRb) was hyperphosphorylated only in the immortal clone. The p16(INK4a) protein was overexpressed in all the E7-infected immortal clones and their clones in the pre-crisis period as well as all the E6/E7-infected mortal and immortal clones, but the pRb expression was downregulated in all of these clones. These results demonstrate for the first time to our knowledge that HPV-16 E6 or E7 alone can induce immortalization of normal human embryonic fibroblasts. Inactivation of p16(INK4a)/pRb pathways in combination with activation of a telomere maintenance mechanism is suggested to be necessary for

  9. The E7 oncoprotein of high-risk human papillomavirus type 16 enters the nucleus via a nonclassical Ran-dependent pathway

    International Nuclear Information System (INIS)

    Angeline, Michael; Merle, Eric; Moroianu, Junona

    2003-01-01

    E7, the major transforming protein of high-risk human papillomavirus (HPV), type 16, binds and inactivates the retinoblastoma protein (pRb), and the Rb-related proteins p107 and p130. HPV16 E7 is a nuclear protein lacking a classical basic nuclear localization signal. In this study we investigated the nuclear import of HPV16 E7 oncoprotein in digitonin-permeabilized HeLa cells. HPV16 E7 nuclear import was independent of pRb, as an E7 ΔDLYC variant defective in pRb binding was imported into the nuclei of digitonin-permeabilized cells as efficiently as wild-type E7 in the presence of exogenous cytosol. Interestingly, we discovered that HPV16 E7 is imported into the nuclei via a novel pathway different from those mediated by Kap α2β1 heterodimers, Kap β1, or Kap β2. Nuclear accumulation of E7 required Ran and was not inhibited by the RanG19V-GTP variant, an inhibitor of Kap β mediated import pathways. Together the data suggest that HPV16 E7 translocates through the nuclear pores via a nonclassical Ran-dependent pathway, independent of the main cytosolic Kap β import receptors

  10. Human papillomavirus type 16 E2 and E6 are RNA-binding proteins and inhibit in vitro splicing of pre-mRNAs with suboptimal splice sites

    International Nuclear Information System (INIS)

    Bodaghi, Sohrab; Jia Rong; Zheng Zhiming

    2009-01-01

    Human papillomavirus type 16 (HPV16) genome expresses six regulatory proteins (E1, E2, E4, E5, E6, and E7) which regulate viral DNA replication, gene expression, and cell function. We expressed HPV16 E2, E4, E6, and E7 from bacteria as GST fusion proteins and examined their possible functions in RNA splicing. Both HPV16 E2, a viral transactivator protein, and E6, a viral oncoprotein, inhibited splicing of pre-mRNAs containing an intron with suboptimal splice sites, whereas HPV5 E2 did not. The N-terminal half and the hinge region of HPV16 E2 as well as the N-terminal and central portions of HPV16 E6 are responsible for the suppression. HPV16 E2 interacts with pre-mRNAs through its C-terminal DNA-binding domain. HPV16 E6 binds pre-mRNAs via nuclear localization signal (NLS3) in its C-terminal half. Low-risk HPV6 E6, a cytoplasmic protein, does not bind RNA. Notably, both HPV16 E2 and E6 selectively bind to the intron region of pre-mRNAs and interact with a subset of cellular SR proteins. Together, these findings suggest that HPV16 E2 and E6 are RNA binding proteins and might play roles in posttranscriptional regulation during virus infection

  11. Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer

    Directory of Open Access Journals (Sweden)

    Shirish Shukla

    2014-01-01

    Full Text Available Background & objectives: High-risk human papilloma virus (HR-HPV infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions. Methods: Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30 and high grade (HSIL, 30, and invasive carcinoma, (squamous cell carcinoma SCC, 70 cases. Results: Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60 and cancer cases (29/70, HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load. Interpretation & conclusions: Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.

  12. 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.

  13. Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice.

    Science.gov (United States)

    Poo, Haryoung; Pyo, Hyun-Mi; Lee, Tae-Young; Yoon, Sun-Woo; Lee, Jong-Soo; Kim, Chul-Joong; Sung, Moon-Hee; Lee, Seung-Hoon

    2006-10-01

    The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice. Copyright 2006 Wiley-Liss, Inc.

  14. Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA.

    Science.gov (United States)

    Castellsagué, Xavier; Naud, Paulo; Chow, Song-Nan; Wheeler, Cosette M; Germar, Maria Julieta V; Lehtinen, Matti; Paavonen, Jorma; Jaisamrarn, Unnop; Garland, Suzanne M; Salmerón, Jorge; Apter, Dan; Kitchener, Henry; Teixeira, Julio C; Skinner, S Rachel; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Peters, Klaus; Tjalma, Wiebren A A; Safaeian, Mahboobeh; Raillard, Alice; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

    2014-08-15

    We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  15. Prognostic value of pretreatment 18F-FDG PET/CT and human papillomavirus type 16 testing in locally advanced oropharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Cheng, Nai-Ming; Yen, Tzu-Chen; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Lin, Chien-Yu; Huang, Chung-Guei; Ng, Shu-Hang; Wang, Hung-Ming; Hsu, Cheng-Lung; Liao, Chun-Ta

    2012-01-01

    Human papillomavirus type 16 (HPV-16) positivity is associated with favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report here a study of the prognostic significance of 18 F-FDG PET/CT functional parameters and HPV-16 infection in OPSCC patients. We retrospectively analysed 60 patients with stage III or IV OPSCC who had had a pretherapy 18 F-FDG PET/CT scan and had completed concurrent chemoradiotherapy (n = 58) or curative radiotherapy (n = 2). All patients were followed up for ≥24 months or until death. We determined total lesion glycolysis (TLG) and the maximal standardized uptake values (SUV max ) of the primary tumour and neck lymph nodes from the pretherapy 18 F-FDG PET/CT scan. Optimal cut-offs of the 18 F-FDG PET/CT parameters were obtained by receiver operating characteristic (ROC) curve analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to determine HPV infection status. The pretherapy tumour biopsies were positive for HPV-16 in 12 patients (20.0 %). Cox regression analyses revealed HPV-16 positivity and tumour TLG >135.3 g to be independently associated with overall survival (p = 0.027 and 0.011, respectively). However, only tumour TLG >135.3 g was independently associated with progression-free survival, disease-free survival and locoregional control (p = 0.011, 0.001 and 0.034, respectively). A scoring system was formulated to define distinct overall survival groups using tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG ≤135.3 g experienced better survival than those with tumour TLG >135.3 g and no HPV infection (p = 0.001). Tumour TLG was an independent predictor of survival in patients with locally advanced OPSCC. A scoring system was developed and may serve as a risk stratification strategy for guiding therapy. (orig.)

  16. A Bivariate Mixture Model for Natural Antibody Levels to Human Papillomavirus Types 16 and 18: Baseline Estimates for Monitoring the Herd Effects of Immunization.

    Directory of Open Access Journals (Sweden)

    Margaretha A Vink

    Full Text Available Post-vaccine monitoring programs for human papillomavirus (HPV have been introduced in many countries, but HPV serology is still an underutilized tool, partly owing to the weak antibody response to HPV infection. Changes in antibody levels among non-vaccinated individuals could be employed to monitor herd effects of immunization against HPV vaccine types 16 and 18, but inference requires an appropriate statistical model. The authors developed a four-component bivariate mixture model for jointly estimating vaccine-type seroprevalence from correlated antibody responses against HPV16 and -18 infections. This model takes account of the correlation between HPV16 and -18 antibody concentrations within subjects, caused e.g. by heterogeneity in exposure level and immune response. The model was fitted to HPV16 and -18 antibody concentrations as measured by a multiplex immunoassay in a large serological survey (3,875 females carried out in the Netherlands in 2006/2007, before the introduction of mass immunization. Parameters were estimated by Bayesian analysis. We used the deviance information criterion for model selection; performance of the preferred model was assessed through simulation. Our analysis uncovered elevated antibody concentrations in doubly as compared to singly seropositive individuals, and a strong clustering of HPV16 and -18 seropositivity, particularly around the age of sexual debut. The bivariate model resulted in a more reliable classification of singly and doubly seropositive individuals than achieved by a combination of two univariate models, and suggested a higher pre-vaccine HPV16 seroprevalence than previously estimated. The bivariate mixture model provides valuable baseline estimates of vaccine-type seroprevalence and may prove useful in seroepidemiologic assessment of the herd effects of HPV vaccination.

  17. Cyclophilins facilitate dissociation of the human papillomavirus type 16 capsid protein L1 from the L2/DNA complex following virus entry.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Williams, Carlyn; Kim, Seong Man; Garcea, Robert L; Sapp, Martin

    2012-09-01

    Human papillomaviruses (HPV) are composed of the major and minor capsid proteins, L1 and L2, that encapsidate a chromatinized, circular double-stranded DNA genome. At the outset of infection, the interaction of HPV type 16 (HPV16) (pseudo)virions with heparan sulfate proteoglycans triggers a conformational change in L2 that is facilitated by the host cell chaperone cyclophilin B (CyPB). This conformational change results in exposure of the L2 N terminus, which is required for infectious internalization. Following internalization, L2 facilitates egress of the viral genome from acidified endosomes, and the L2/DNA complex accumulates at PML nuclear bodies. We recently described a mutant virus that bypasses the requirement for cell surface CyPB but remains sensitive to cyclosporine for infection, indicating an additional role for CyP following endocytic uptake of virions. We now report that the L1 protein dissociates from the L2/DNA complex following infectious internalization. Inhibition and small interfering RNA (siRNA)-mediated knockdown of CyPs blocked dissociation of L1 from the L2/DNA complex. In vitro, purified CyPs facilitated the dissociation of L1 pentamers from recombinant HPV11 L1/L2 complexes in a pH-dependent manner. Furthermore, CyPs released L1 capsomeres from partially disassembled HPV16 pseudovirions at slightly acidic pH. Taken together, these data suggest that CyPs mediate the dissociation of HPV L1 and L2 capsid proteins following acidification of endocytic vesicles.

  18. Prognostic value of pretreatment {sup 18}F-FDG PET/CT and human papillomavirus type 16 testing in locally advanced oropharyngeal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Nai-Ming; Yen, Tzu-Chen [Chang Gung University College of Medicine, Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taipei (China); Chang, Joseph Tung-Chieh; Tsan, Din-Li; Lin, Chien-Yu [Chang Gung University College of Medicine, Department of Radiation Oncology, Chang Gung Memorial Hospital, Taipei (China); Huang, Chung-Guei [Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Laboratory Medicine, Taipei (China); Ng, Shu-Hang [Chang Gung University College of Medicine, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Taipei (China); Wang, Hung-Ming; Hsu, Cheng-Lung [Chang Gung University College of Medicine, Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei (China); Liao, Chun-Ta [Chang Gung University College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taipei (China)

    2012-11-15

    Human papillomavirus type 16 (HPV-16) positivity is associated with favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report here a study of the prognostic significance of {sup 18}F-FDG PET/CT functional parameters and HPV-16 infection in OPSCC patients. We retrospectively analysed 60 patients with stage III or IV OPSCC who had had a pretherapy {sup 18}F-FDG PET/CT scan and had completed concurrent chemoradiotherapy (n = 58) or curative radiotherapy (n = 2). All patients were followed up for {>=}24 months or until death. We determined total lesion glycolysis (TLG) and the maximal standardized uptake values (SUV{sub max}) of the primary tumour and neck lymph nodes from the pretherapy {sup 18}F-FDG PET/CT scan. Optimal cut-offs of the {sup 18}F-FDG PET/CT parameters were obtained by receiver operating characteristic (ROC) curve analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to determine HPV infection status. The pretherapy tumour biopsies were positive for HPV-16 in 12 patients (20.0 %). Cox regression analyses revealed HPV-16 positivity and tumour TLG >135.3 g to be independently associated with overall survival (p = 0.027 and 0.011, respectively). However, only tumour TLG >135.3 g was independently associated with progression-free survival, disease-free survival and locoregional control (p = 0.011, 0.001 and 0.034, respectively). A scoring system was formulated to define distinct overall survival groups using tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG {<=}135.3 g experienced better survival than those with tumour TLG >135.3 g and no HPV infection (p = 0.001). Tumour TLG was an independent predictor of survival in patients with locally advanced OPSCC. A scoring system was developed and may serve as a risk stratification strategy for guiding therapy. (orig.)

  19. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant.

    NARCIS (Netherlands)

    Pedersen, C.; Petaja, T.; Strauss, G.; Rumke, H.C.; Poder, A.; Richardus, J.H.; Spiessens, B.; Descamps, D.; Hardt, K.; Lehtinen, M.; Dubin, G.

    2007-01-01

    PURPOSE: In female individuals 15-25-years of age, the AS04-containing human papillomavirus (HPV)-16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention will

  20. Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind.

    Science.gov (United States)

    Chan, S Y; Ho, L; Ong, C K; Chow, V; Drescher, B; Dürst, M; ter Meulen, J; Villa, L; Luande, J; Mgaya, H N

    1992-04-01

    We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries--Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group-internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The

  1. Association between free testosterone levels and anal human papillomavirus types 16/18 infections in a cohort of men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Hilary K Hsu

    Full Text Available Human papillomavirus (HPV types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs. Overall, IAC rates are highest among men who have sex with men (MSM, especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown.Free testosterone (FT was measured in serum from 340 Multicenter AIDS Cohort Study (MACS participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing.Participants were, on average, 60 (+5.4 years of age, White (86%, and HIV-uninfected (56%; Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence=17.1%, HPV18=9.1%. In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24 higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37 higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/18 infection in unadjusted and adjusted analyses.Higher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years

  2. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    OpenAIRE

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2...

  3. Transient expression of Human papillomavirus type 16 L2 epitope fused to N- and C-terminus of coat protein of Potato virus X in plants

    Czech Academy of Sciences Publication Activity Database

    Čeřovská, Noemi; Hoffmeisterová, Hana; Moravec, Tomáš; Plchová, Helena; Folwarczna, Jitka; Synková, Helena; Ryšlavá, H.; Ludvíková, V.; Šmahel, M.

    2012-01-01

    Roč. 37, č. 1 (2012), s. 125-133 ISSN 0250-5991 R&D Projects: GA ČR GA521/06/0973; GA ČR GA521/09/1525 Institutional research plan: CEZ:AV0Z50380511 Keywords : Human papillomavirus (HPV-16) * L2-and E7-derived epitopes * transient expression Subject RIV: FD - Oncology ; Hematology Impact factor: 1.759, year: 2012

  4. The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-γ

    International Nuclear Information System (INIS)

    Zhang Benyue; Li Ping; Wang Exing; Brahmi, Zacharie; Dunn, Kenneth W.; Blum, Janice S.; Roman, Ann

    2003-01-01

    Major histocompatibility complex (MHC) class II antigens are expressed on human foreskin keratinocytes (HFKs) following exposure to interferon gamma. The expression of MHC class II proteins on the cell surface may allow keratinocytes to function as antigen-presenting cells and induce a subsequent immune response to virus infection. Invariant chain (Ii) is a chaperone protein which plays an important role in the maturation of MHC class II molecules. The sequential degradation of Ii within acidic endocytic compartments is a key process required for the successful loading of antigenic peptide onto MHC class II molecules. Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late endosomes in HFKs, the E5 protein may be able to affect proper peptide loading onto the MHC class II molecule. To test this hypothesis, HFKs were infected with either control virus or a recombinant virus expressing HPV16 E5 and the infected cells were subsequently treated with interferon-γ. ELISAs revealed a decrease of MHC class II expression on the surface of E5-expressing cells compared with control virus-infected cells after interferon treatment. Western blot analysis showed that, in cells treated with interferon gamma, E5 could prevent the breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC class II dimers, correlating with diminished surface MHC class II expression. These data suggest that HPV16 E5 may be able to decrease immune recognition of infected keratinocytes via disruption of MHC class II protein function

  5. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant

    DEFF Research Database (Denmark)

    Pedersen, Court; Petaja, Tiina; Strauss, Gitte

    2007-01-01

    will require prophylactic vaccination against oncogenic HPV 16 and 18 before the onset of sexual activity in early adolescent girls. To establish the feasibility of vaccination in girls 10-14 years of age, we compared the immunogenicity and safety in early adolescent female individuals to those 15-25 years...... measured by enzyme-linked immunosorbent assay. Vaccine safety was assessed at 7 or 30 days after each dose; serious adverse events were recorded during the entire study period. RESULTS: Both age groups achieved 100% seroconversion for HPV 16 and 18. Participants in the group aged 10-14 years were not only......PURPOSE: In female individuals 15-25-years of age, the AS04-containing human papillomavirus (HPV)-16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention...

  6. A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

    International Nuclear Information System (INIS)

    Granadillo, Milaid; Torrens, Isis; Guerra, Maribel

    2012-01-01

    Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF 32-51 ) linked to human papillomavirus 16 E7 antigen (LALF 32-51 -E7). In this work, we demonstrated that the immunization with LALF 32-51 -E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8 +T -cell response. The finding that therapeutic immunization with LALF 32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF 32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8 +T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application

  7. Cervical Cancers Require the Continuous Expression of the Human Papillomavirus Type 16 E7 Oncoprotein Even in the Presence of the Viral E6 Oncoprotein

    Science.gov (United States)

    Jabbar, Sean F.; Park, Soyeong; Schweizer, Johannes; Berard-Bergery, Marthe; Pitot, Henry C.; Lee, Denis; Lambert, Paul F.

    2012-01-01

    High-risk human papillomaviruses (HPV), such as HPV-16, are etiologic agents of a variety of anogenital and oral malignancies, including nearly all cases of cervical cancer. Cervical cancers arising in transgenic mice that express HPV-16 E7 in an inducible manner require the continuous expression of E7 for their maintenance. However, in HPV-associated cancers in vivo, E6 and E7 invariably are co-expressed. In this study, we investigated whether cervical cancers rely on the continuous expression of E7 in the context of constitutively expressed E6. We placed the inducible HPV-16 E7 transgene onto a background in which HPV-16 E6 was constitutively expressed. In transgenic mice with high-grade cervical dysplastic lesions and cervical cancer, repressing the expression of E7 led to the regression of all cancers and the vast majority of high-grade dysplastic lesions. In addition, cervical cancers were occasionally observed in transgenic mice in which E7 was repressed and then re-expressed. Our findings therefore indicate that even in the presence of constitutively expressed E6, the continuous expression of E7 is required for the maintenance of cervical cancers and most precancerous lesions. These data have important implications for the potential clinical use of drugs designed to inhibit the expression and/or function of E7 to treat HPV-associated cancers. PMID:22700879

  8. Prevalence and risk factors of human papillomavirus infection types 16/18/45 in a cohort of French females aged 15–23 years

    Directory of Open Access Journals (Sweden)

    Ariane Baudu

    2014-03-01

    Full Text Available Investigation of the prevalence and risk factors of human papillomavirus (HPV infection is the basis for developing prophylactic strategies against cervical cancer, especially for young women. This study aimed to assess the prevalence and risk factors of HPV infection among a cohort of sexually active young French women eligible for catch-up vaccination. Between 1997 and 2007, 2163 women aged 15–23 years attending consultations at the department of gynecology in the Hospital of Besançon (France were screened for high risk HPV (HR HPV infection. Risk factors were investigated through a questionnaire sent to all participants in 2010. HPV DNA was detected by HC2 and Probe Set assays. The overall prevalence for HR HPV and HPV16, 18 and/or HPV45 was 44.6% (95% CI, 42.5–46.7% and 19% (95% CI, 17.3–20.7%, respectively. The response rate to the questionnaire was 22.6%. The prevalence of independent risk factors (age older than 19, smoking, and oral contraception for HPV 16/18/45 infection in this population was less than 20%. Based on this study, HPV vaccination should be offered not only to teenage girls, but also to young women, regardless of their sexual activity.

  9. Molecular Docking Explains Atomic Interaction between Plant-originated Ligands and Oncogenic E7 Protein of High Risk Human Papillomavirus Type 16

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    Satish Kumar

    2014-12-01

    Full Text Available Cervical cancer caused by Human papillomavirus (HPV is one of the leading causes of cancer mortality in women worldwide, particularly in the developing countries. In the last few decades, various compounds from plant origin such as Curcumin, Epigallocatechin gallate (EGCG, Jaceosidin, Resveratrol etc. have been used as anti cancer therapeutic agents. Different studies have shown these plant-originated compounds are able to suppress HPV infection. The E6 and E7 oncoproteins of high-risk HPV play a key role in HPV related cancers. In this study, we explored these ligands from plants origin against E7 oncoprotein of high risk HPV 16, which is known to inactivate tumor suppressor pRb protein. A robust homology model of HPV 16 E7 was built to foresee the interaction mechanism of E7 oncoprotein with these ligands using structure-based drug designing approach. Docking studies demonstrate the interaction of these ligands with pRb binding site of E7 protein by residues Tyr52, Asn53, Val55, Phe57, Cys59, Ser63, Thr64, Thr72, Arg77, Glu80 and Asp81 and help restoration of pRb functioning. This in silico based atomic interaction between these ligands and E7 protein may assist in validating the plant-originated ligands as effective drugs against HPV.

  10. The PDZ Ligand Domain of the Human Papillomavirus Type 16 E6 Protein Is Required for E6's Induction of Epithelial Hyperplasia In Vivo

    Science.gov (United States)

    Nguyen, Marie L.; Nguyen, Minh M.; Lee, Denis; Griep, Anne E.; Lambert, Paul F.

    2003-01-01

    Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6WT) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6Δ146-151, from the human keratin 14 (K14) promoter. The K14E6Δ146-151 mice exhibit a radiation response similar to that of the K14E6WT mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6Δ146-151 mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. PMID:12768014

  11. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression.

    Science.gov (United States)

    Woodham, Andrew W; Raff, Adam B; Raff, Laura M; Da Silva, Diane M; Yan, Lisa; Skeate, Joseph G; Wong, Michael K; Lin, Yvonne G; Kast, W Martin

    2014-05-15

    High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

  12. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

    Science.gov (United States)

    Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin

    2014-01-01

    High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cellsin a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the antigen presenting cells of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. Here, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by siRNA downregulation of A2t, significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein. PMID:24719459

  13. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    Science.gov (United States)

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future. PMID:21865393

  14. Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes.

    Science.gov (United States)

    Hyland, Paula L; McDade, Simon S; McCloskey, Rachel; Dickson, Glenda J; Arthur, Ken; McCance, Dennis J; Patel, Daksha

    2011-11-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

  15. LOW MOLECULAR MASS POLYPEPTIDE AND TRANSPORTER ANTIGEN PEPTIDE GENES POLYMORPHISM AS THE RISK FACTORS OF CERVICAL CANCER WHICH CAUSED BY HUMAN PAPILLOMAVIRUS TYPE-16 INFECTION IN BALI

    Directory of Open Access Journals (Sweden)

    I N. B. Mahendra

    2015-12-01

    Full Text Available Background: Until recently, cervical cancer is one of the major problem in women’s health issue related to its high incidence and mortality rate. The etiology of cervical cancer is the high risk oncogenic group of Human Papillomavirus (HPV, especially HPV-16 and 18 and its phylogenies. Meanwhile in Bali, more than 50% of infection are caused by HPV-16 infection. The main objective of this study was to investigate the role of LMP-2, LMP-7, TAP-1 and TAP-2 gene polymorphism as the risk factor in the cervical cancer carcinogenesis that is caused by HPV-16 infection. Method: A nested non-paired case-control study was conducted at Obstetric and Gynecologic Department Sanglah General Hospital, Bali-Indonesia from March 1 until August 31, 2013. Laboratory testing was carried out at Laboratory of Histopathology Leiden University Medical Centre, Netherlands,. Results: A total of 40 samples were collected, consist of 20epithelial cervical cancer patients with positive HPV-16 infection as the case group and 20 non-cervical cancer patients with positive HPV-16 infection as the control group. Women infected by HPV-16 with LMP-7 gene polymorphism had a higher risk (OR=7.36, CI 95%=1.38-40.55, p=0.013 to be diagnosed with cervical cancer. Balinese women who were infected by HPV-16 with TAP-2 gene polymorphism had a higher risk (OR= 9.33, CI 95%=2.18-39.96, p=0.001 to be diagnosed with cervical cancer. Meanwhile, Balinese women who were infected by HPV-16 with LMP-7 and TAP-2 genes polymorphism had a higher risk (OR=12.67, CI 95%=1.40-114.42, p=0.020 to be diagnosed with cervical cancer. As the result, it was shown that both of this gene polymorphism was working synergistically. Conclusion: TAP-2 and LMP-7 genes polymorphism play a role in the carcinogenesis mechanism of cervical cancer that is caused by HPV-16 infection in Bali. Meanwhile, LMP-2 and TAP-1 genes polymorphism were not found to play a role in the immunology pathway of cervical cancer that is

  16. Cost-effectiveness of human papillomavirus vaccine in reducing the risk of cervical cancer in Ireland due to HPV types 16 and 18 using a transmission dynamic model

    DEFF Research Database (Denmark)

    Usher, C.; Tilson, L.; Olsen, J.

    2008-01-01

    We evaluated the cost-effectiveness of combining a cervical cancer screening programme with a national HPV vaccination programme compared to a screening programme alone to prevent cervical dysplasia and cervical cancer related to HPV types 16 and 18 in the Irish healthcare setting. The incrementa...... per LYG was ((sic)3400 to E38,400). This suggests that vaccination against HPV types 16 and 18 would be cost-effective from the perspective of the Irish healthcare payer. (C) 2008 Elsevier Ltd. All rights reserved......We evaluated the cost-effectiveness of combining a cervical cancer screening programme with a national HPV vaccination programme compared to a screening programme alone to prevent cervical dysplasia and cervical cancer related to HPV types 16 and 18 in the Irish healthcare setting. The incremental...... cost effectiveness of vaccination strategies for 12-year-old females (base-case) and 12-26-year-old catch-up vaccination strategies were examined. The base-case incremental cost-effectiveness ratio was (sic)17,383/LYG. Using a probabilistic sensitivity analysis about the base-case, the 95% CI for cost...

  17. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

    Directory of Open Access Journals (Sweden)

    M.O. Diniz

    2011-05-01

    Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

  18. Human Papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

    Science.gov (United States)

    Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.; Marker, Daniel F.; Schreiner, Cynthia N.; Strickland, David A.; Wilton, Katelynn M.; Mondal, Sumona; Woodworth, Craig D.

    2012-01-01

    The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. PMID:22284893

  19. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, M. F.; Duk, J. M.; Burger, M. P.; de Bruijn, H. W.; Stolz, E.; Herbrink, P.

    1999-01-01

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  20. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  1. 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 ...

  2. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    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 ...

  3. Overall human papilloma virus and types 16/18 prevalence in women with normal cervical cytology in Serbia: is it time for human papillomavirus testing and/or vaccination?

    Science.gov (United States)

    Malisic, Emina; Brotto, Ksenija; Krivokuca, Ana; Cavic, Milena; Jankovic, Radmila

    2014-01-01

    Infection with high-risk human papilloma viruses (HR-HPV), especially types 16/18, is the main factor in cervical carcinogenesis. Although the incidence of cervical cancer in Serbia is among the highest ones in Europe, data about HPV infection are insufficient. The aim of this study was to investigate the presence of overall and HPV16/18 infections in women with healthy appearance and cytologically (Pap) normal cervix. The study was performed on women who participated in this cervical cancer screening pilot study. Cervical HPV infection was detected by GP5+/6+ PCR. HPV16/18 were detected by amplification of E7/E1 viral gene, respectively. In 350 women we got the following results: cytological abnormalities (10.3%); visible cervical changes (20.3%); previous precancerous lesion (2.3%); normal Pap and speculum finding without history of precancerous lesion (67.1%). In the last group overall HPV prevalence was 41.3%, with 10.5% HPV16 and 23.7% HPV18. The rate of multiple HPV16 plus HPV18 infections was 2.6%. HR-HPV16/18 comprised 31.6% of the total HPV positive participants. Owing to the high prevalence of overall and HPV16/18 infections in women with healthy appearance and cytologically normal cervix, we postulate that testing/ prophylaxis for these HR-HPV types could be introduced in cervical cancer screening and preventive programmes in Serbia.

  4. Human papillomavirus molecular biology.

    Science.gov (United States)

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes.

    Science.gov (United States)

    Creek, K E; Geslani, G; Batova, A; Pirisi, L

    1995-01-01

    Retinoids (vitamin A and its natural and synthetic derivatives) have shown potential as chemopreventive agents, and diets poor in vitamin A and/or its precursor beta-carotene have been linked to an increased risk of cancer at several sites including the cervix. Human papillomavirus (HPV) plays an important role in the etiology of cervical cancer. We have developed an in vitro model of cancer progression using human keratinocytes (HKc) immortalized by HPV16 DNA (HKc/HPV16). Although immortal, early passage HKc/HPV16, like normal HKc, require epidermal growth factor (EGF) and bovine pituitary extract (BPE) for proliferation and undergo terminal differentiation in response to serum and calcium. However, following prolonged culture, growth factor independent HKc/HPV16 lines that no longer require EGF and BPE can be selected (HKc/GFI). Further selection of HKc/GFI produces lines that are resistant to serum- and calcium- induced terminal differentiation (HKc/DR). HKc/DR, but not early passage HKc/HPV16, are susceptible to malignant conversion following transfection with viral Harvey ras or Herpes simplex virus type II DNA. We have investigated the sensitivity of low to high passage HKc/HPV16 and HKc/GFI to growth control by all-trans-retinoic acid (RA, an active metabolite of vitamin A). Early passage HKc/HPV16 are very sensitive to growth inhibition by RA, and in these cells RA decreases the expression of the HPV16 oncogenes E6 and E7. However, as the cells progress in culture they lose their sensitivity to RA. Growth inhibition by RA may be mediated through the cytokine transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation. RA treatment of HKc/HPV16 and HKc/GFI results in a dose-and time-dependent induction (maximal of 3-fold) in secreted levels of TGF-beta. Also, Northern blot analysis of mRNA isolated from HKc/HPV16 demonstrated that RA treatment induced TGF-beta 1 and TGF-beta 2 expression about 3- and 50-fold, respectively

  6. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.

    Science.gov (United States)

    Harper, Diane M; Franco, Eduardo L; Wheeler, Cosette; Ferris, Daron G; Jenkins, David; Schuind, Anne; Zahaf, Toufik; Innis, Bruce; Naud, Paulo; De Carvalho, Newton S; Roteli-Martins, Cecilia M; Teixeira, Julio; Blatter, Mark M; Korn, Abner P; Quint, Wim; Dubin, Gary

    Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions. We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity. In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic. The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.

  7. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...

  8. Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

    DEFF Research Database (Denmark)

    Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid

    2004-01-01

    Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induc......Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation......, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge...

  9. Human papillomavirus associated oropharyngeal cancer

    International Nuclear Information System (INIS)

    Stefanicka, P.

    2015-01-01

    Recently, there is substantial epidemiological, molecular-pathological and experimental evidence indicating that some of the high-risk human papillomavirus (HR-HPV), especially HPV type 16, are etiologically related to a subset of head and neck squamous cell carcinomas, in particular, those arising from the oropharynx. Incidence of oropharyngeal cancer is increasing in direct opposition to a decreasing incidence of all other head and neck cancers. The prognosis of patients with HPV associated oropharyngeal cancer is significantly better compare to patients with non associated oropharyngeal cancers. Patients with HPV-positive oropharyngeal cancer respond better to radiotherapy, surgery, chemoradiotherapy. Therefore, the presence of HPV in tumor is the most important prognostic factor in patients with oropharyngeal cancers. These findings have prompted the need for change of treatment strategies in these patients. The goal is selective de-intensified treatment stratified for HPV status. (author)

  10. Human papillomavirus type-16 variants in Quechua aboriginals from Argentina.

    Science.gov (United States)

    Picconi, María Alejandra; Alonio, Lidia Virginia; Sichero, Laura; Mbayed, Viviana; Villa, Luisa Lina; Gronda, Jorge; Campos, Rodolfo; Teyssié, Angélica

    2003-04-01

    Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical cancer (ICC), and 36 samples from women with normal colposcopy and cytology. HPV genome variability was examined in the L1 and E6 genes by PCR-hybridization. In a subset of 20 samples, a LCR fragment was also analyzed by PCR-sequencing. Most variants belonged to the European branch with subtle differences that depended on the viral gene fragment studied. Only about 10% of the specimens had non-European variants, including eight Asian-American, two Asian, and one North-American-1. E6 gene analysis revealed that 43% of the samples were identical to HPV-16 prototype, while 57% corresponded to variants. Interestingly, the majority (87%) of normal smears had HPV-16 prototype, whereas variants were detected mainly in SIL and ICC. LCR sequencing yielded 80% of variants, including 69% of European, 19% Asian-American, and 12% Asian. We identified a new variant, the Argentine Quechua-51 (AQ-51), similar to B-14 plus two additional changes: G7842-->A and A7837-->C; phylogenetic inference allocated it in the Asian-American branch. The high proportion of European variants may reflect Spanish colonial influence on these native Inca descendants. The predominance of HPV-16 variants in pathologic samples when compared to normal controls could have implications for the natural history of cervical lesions. Copyright 2003 Wiley-Liss, Inc.

  11. Transient expression of Human papillomavirus type 16 L2 epitope ...

    Indian Academy of Sciences (India)

    2012-01-11

    Jan 11, 2012 ... 2Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030, 12840 Prague, .... by M Sapp, Institute for Medical Microbiology, Johannes ..... and J Stasikova for their excellent technical assistance.

  12. Human papillomavirus E6 and E7 oncoproteins as risk factors

    Indian Academy of Sciences (India)

    Prakash

    J. Biosci. 34(1), March 2009. 1. Introduction. Human papillomavirus (HPV) is a double-stranded DNA virus that ..... contact and loss of cell polarity (Watson et al 2003; Thomas ..... Arrand JR 1995 Translation of the human papillomavirus type 16.

  13. Human papillomaviruses and cancer

    International Nuclear Information System (INIS)

    Haedicke, Juliane; Iftner, Thomas

    2013-01-01

    Human papillomaviruses (HPV) are small oncogenic DNA viruses of which more than 200 types have been identified to date. A small subset of these is etiologically linked to the development of anogenital malignancies such as cervical cancer. In addition, recent studies established a causative relationship between these high-risk HPV types and tonsillar and oropharyngeal cancer. Clinical management of cervical cancer and head and neck squamous cell carcinomas (HNSCCs) is largely standardized and involves surgical removal of the tumor tissue as well as adjuvant chemoradiation therapy. Notably, the response to therapeutic intervention of HPV-positive HNSCCs has been found to be better as compared to HPV-negative tumors. Although the existing HPV vaccine is solely licensed for the prevention of cervical cancer, it might also have prophylactic potential for the development of high-risk HPV-associated HNSCCs. Another group of viruses, which belongs to the beta-HPV subgroup, has been implicated in nonmelanoma skin cancer, however, the etiology remains to be established. Treatment of HPV-induced nonmelanoma skin cancer is based on local excision. However, topically applied immune-modulating substances represent non-surgical alternatives for the management of smaller cutaneous tumors. In this review we present the current knowledge of the role of HPV in cancer development and discuss clinical management options as well as targets for the development of future intervention therapies

  14. Human papillomavirus gene expression

    International Nuclear Information System (INIS)

    Chow, L.T.; Hirochika, H.; Nasseri, M.; Stoler, M.H.; Wolinsky, S.M.; Chin, M.T.; Hirochika, R.; Arvan, D.S.; Broker, T.R.

    1987-01-01

    To determine the role of tissue differentiation on expression of each of the papillomavirus mRNA species identified by electron microscopy, the authors prepared exon-specific RNA probes that could distinguish the alternatively spliced mRNA species. Radioactively labeled single-stranded RNA probes were generated from a dual promoter vector system and individually hybridized to adjacent serial sections of formalin-fixed, paraffin-embedded biopsies of condylomata. Autoradiography showed that each of the message species had a characteristic tissue distribution and relative abundance. The authors have characterized a portion of the regulatory network of the HPVs by showing that the E2 ORF encodes a trans-acting enhancer-stimulating protein, as it does in BPV-1 (Spalholz et al. 1985). The HPV-11 enhancer was mapped to a 150-bp tract near the 3' end of the URR. Portions of this region are duplicated in some aggressive strains of HPV-6 (Boshart and zur Hausen 1986; Rando et al. 1986). To test the possible biological relevance of these duplications, they cloned tandem arrays of the enhancer and demonstrated, using a chloramphenicol acetyltransferase (CAT) assay, that they led to dramatically increased transcription proportional to copy number. Using the CAT assays, the authors found that the E2 proteins of several papillomavirus types can cross-stimulate the enhancers of most other types. This suggests that prior infection of a tissue with one papillomavirus type may provide a helper effect for superinfection and might account fo the HPV-6/HPV-16 coinfections in condylomata that they have observed

  15. Giant condyloma acuminate due human papilloma virus type 16 in an infant successfully treated with topical imiquimod therapy

    Directory of Open Access Journals (Sweden)

    Meltem Dinleyici

    2015-12-01

    Full Text Available Anogenital warts related to human papillomavirus (HPV have been observed in children. Definition of the transmission mode, therapy, and follow-up for long term potential complications is important. A 27-month old girl was admitted with multiple pedunculated red-purple colored cauliflower-like lesions of 1.5 years duration. Clinical/histopathological and microbiological diagnosis was condyloma acuminate due to HPV type 16. After 12 weeks of imiquimod 5% cream application (pea-sized overnight three times per week, the perianal warts had completely disappeared. The mode of transmission of HPV 16 in our case was probably horizontal, related to the sharing of common personal hygiene items in the women’s shelter. We report herein the case of an infant living in a women’s shelter with giant condyloma acuminata due to HPV 16, which was successfully treated with topical imiquimod therapy. This patient should be followed up for recurrence and potential malignant lesions related to HPV type 16.

  16. [Human papillomavirus infection and adolescence].

    Science.gov (United States)

    Sam Soto, Selene; de la Peña y Carranza, Alejandro Ortiz; Plascencia, Josefina Lira

    2011-04-01

    Infection with human papillomavirus has increased dramatically in recent years. The highest prevalence rates are among adolescents and young women, reflecting changes in sexual behavior associated with biological factors in adolescent development. Adolescents who begin sexual activity early are at greater risk of precursor lesions and cervical cancer. There are adolescents with special circumstances, where no early decision should be delayed cervical cytology and in whom it is important to initiate consultations and periodic reviews with a preventive approach. Cervical cancer can be avoided when the diagnosis and treatment of precursor lesions is early. Despite efforts at sex education based on "safe sex" with the correct use of condoms has not been able to reduce the incidence of infections with human papillomavirus in adolescents. While better than nothing, condom use is not 100% reliable. Studies show that consistent and correct use provides protection against the human papillomavirus only 70%. In Mexico, reported an overall ratio of actual use of condoms from 24.6%. It is clear that the physician who provides care for adolescents plays a fundamental role in sex education. The key to future prevention of cervical cancer and its precursor lesions could be the vaccination.

  17. Prevention of carcinoma of cervix with human papillomavirus vaccine.

    Science.gov (United States)

    Gavarasana, S; Kalasapudi, R S; Rao, T D; Thirumala, S

    2000-01-01

    Carcinoma of cervix is the most common cancer found among the women of India. Though cervical cytology screening was effective in preventing carcinoma of cervix in developed nations, it is considered unsuitable in developing countries. Recent research has established an etiological link between human papillomavirus infection and carcinoma of cervix. In this review, an attempt is made to answer the question, 'whether carcinoma of cervix can be prevented with human papillomavirus vaccine?' Literature search using Pubmed and Medline was carried out and relevant articles were reviewed. There is ample experimental evidence to show that DNA of human papillomavirus integrates with cervical cell genome. Viral genes E6 and E7 of HPV type 16 and 18 inactivate p53 function and Rb gene, thus immortalize the cervical epithelial cells. Recombinant vaccines blocked the function of E6 and E7 genes preventing development of papillomas in animals. Vaccination with HPV-VLPs encoding for genes of E6 and E7 neutralizes HPV integrated genome of malignant cells of uterine cervix. Based on experimental evidence, it is possible to prevent carcinoma of cervix with human papillomavirus vaccine, Further research is necessary to identify a effective and safe HPV vaccine, routes of administration and characteristics of potential beneficiaries.

  18. Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

    International Nuclear Information System (INIS)

    Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid; Gjerloev, Simon; Birk, Jesper; Roepke, Carsten; Norrild, Bodil

    2004-01-01

    Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induction of cell death. We have used the osteosarcoma cell line U2OS cells provided with E7 and the cdk2 inhibitor p21 (cip1/waf1) under inducible control, as a model system for the analysis of E7-mediated apoptosis. Our data shows that simultaneous expression of E7 and p21 proteins induces cell death, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge, this is the first time a role for cathepsin B is reported in HPV-induced apoptotic signalling

  19. 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

  20. [Human papillomavirus nonavalent vaccine. Update 2017].

    Science.gov (United States)

    Bosch, F X; Moreno, D; Redondo, E; Torné, A

    Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Epigenetics of human papillomaviruses

    International Nuclear Information System (INIS)

    Johannsen, Eric; Lambert, Paul F.

    2013-01-01

    Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous or mucosal epithelia in which they cause warts, self-contained benign lesions that commonly regress. The HPV life cycle is intricately tied to the differentiation of the host epithelium it infects. Mucosotropic HPVs are the most common sexually transmitted pathogen known to mankind. A subset of the mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with numerous cancers of the anogenital tract, most notably the cervix, as well as a growing fraction of head and neck cancers. In these cancers, the HPV genome, which normally exists an a double stranded, circular, nuclear plasmid, is commonly found integrated into the host genome and expresses two viral oncogenes, E6 and E7, that are implicated in the development and maintainance of the cancers caused by these high risk HPVs. Numerous studies, primarily on the high risk HPV16, have documented that the methylation status of the viral genome changes not only in the context of the viral life cycle but also in the context of the progressive neoplastic disease that culminates in cancer. In this article, we summarize the knowledge gained from those studies. We also provide the first analysis of available ChIP-seq data on the occupancy of both epigentically modified histones as well as transcription factors on the high risk HPV18 genome in the context of HeLa cells, a cervical cancer-derived cell line that has been the subject of extensive analyses using this technique. - Highlights: • Methylation status of HPV genomes is dynamic. • Changes are seen in both the viral life cycle and neoplasia. • Histone modification status at LCR is predictive of transcription factor occupancy. • Novel transcription factor binding noted by ChIP-seq

  2. Epigenetics of human papillomaviruses

    Energy Technology Data Exchange (ETDEWEB)

    Johannsen, Eric [Department of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); Lambert, Paul F., E-mail: plambert@wisc.edu [Department of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States)

    2013-10-15

    Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous or mucosal epithelia in which they cause warts, self-contained benign lesions that commonly regress. The HPV life cycle is intricately tied to the differentiation of the host epithelium it infects. Mucosotropic HPVs are the most common sexually transmitted pathogen known to mankind. A subset of the mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with numerous cancers of the anogenital tract, most notably the cervix, as well as a growing fraction of head and neck cancers. In these cancers, the HPV genome, which normally exists an a double stranded, circular, nuclear plasmid, is commonly found integrated into the host genome and expresses two viral oncogenes, E6 and E7, that are implicated in the development and maintainance of the cancers caused by these high risk HPVs. Numerous studies, primarily on the high risk HPV16, have documented that the methylation status of the viral genome changes not only in the context of the viral life cycle but also in the context of the progressive neoplastic disease that culminates in cancer. In this article, we summarize the knowledge gained from those studies. We also provide the first analysis of available ChIP-seq data on the occupancy of both epigentically modified histones as well as transcription factors on the high risk HPV18 genome in the context of HeLa cells, a cervical cancer-derived cell line that has been the subject of extensive analyses using this technique. - Highlights: • Methylation status of HPV genomes is dynamic. • Changes are seen in both the viral life cycle and neoplasia. • Histone modification status at LCR is predictive of transcription factor occupancy. • Novel transcription factor binding noted by ChIP-seq.

  3. Porokeratoma: A Possible Association with Human Papillomavirus Infection

    Directory of Open Access Journals (Sweden)

    Patricia Caseiro Silverio

    2015-04-01

    Full Text Available Porokeratoma is a rare, relatively newly described and still unclear entity. Here, we describe the case of a 52-year-old male patient who presented with four well-defined, verrucous and hyperkeratotic lesions. Microscopically, one of the lesions showed acanthopapillomatosis overlying compact orthokeratosis. Prominent broad and confluent cornoid lamellae were present, with no granular layer and some dyskeratotic keratinocytes. PCR sequencing and in situ hybridization revealed the presence of human papillomavirus (HPV type 16 in the lesion. The association of porokeratoma and HPV infection has not previously been reported.

  4. Human papillomavirus and genital cancer

    Directory of Open Access Journals (Sweden)

    Rapose Alwyn

    2009-01-01

    Full Text Available Human papillomavirus (HPV is one of the most common sexually transmitted infections world-wide. Low-risk HPV-types are associated with genital warts. Persistent infection with high-risk HPV-types is associated with genital cancers. Smoking and HIV infection have consistently been associated with longer duration of HPV infection and risk for genital cancer. There is an increasing incidence of anal cancers, and a close association with HPV infection has been demonstrated. Receptive anal sex and HIV-positive status are associated with a high risk for anal cancer. Two HPV vaccines are now available and offer protection from infection by the HPV-types included in the vaccine. This benefit is maximally seen in young women who were uninfected prior to vaccination.

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

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

    Medline Plus

    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 ...

  10. 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 ...

  11. Public awareness of human papillomavirus.

    Science.gov (United States)

    Cuschieri, K S; Horne, A W; Szarewski, A; Cubie, H A

    2006-01-01

    The main objective of this study was to review the evidence relating to the level of awareness of human papillomavirus (HPV) in the general population and the implications for the potential introduction of HPV vaccination and HPV testing as part of screening. PubMed search performed on terms: 'HPV education', 'HPV awareness' 'Genital Warts Awareness' Results: Public awareness of HPV is generally very low, particularly with respect to its relation to abnormal smears and cervical cancer although knowledge levels vary to some extent according to sociodemographic characteristics. There is also much confusion around which types cause warts and the types that can cause cancer. The sexually transmissible nature of the infection is of major concern and confusion to women. Due to the lack of current awareness of HPV, significant education initiatives will be necessary should HPV vaccination and/or HPV testing be introduced. Organized edification of health-care workers and the media, who constitute the two most preferred sources of information, will be crucial.

  12. Adolescent Male Human Papillomavirus Vaccination

    Directory of Open Access Journals (Sweden)

    Vivian C. Nanagas MD, MSc

    2016-04-01

    Full Text Available Objective. To determine male vaccination rates with quadrivalent human papillomavirus vaccine (HPV4 before and after the October 2011 national recommendation to routinely immunize adolescent males. Methods. We reviewed HPV4 dose 1 (HPV4-1 uptake in 292 adolescent males in our urban clinic prior to national recommendations and followed-up for HPV4 series completion rates. After national recommendation, 248 urban clinic and 247 suburban clinic males were reviewed for HPV4-1 uptake. Factors associated with HPV4-1 refusal were determined with multiple logistic regression. Results. Of the initial 292 males, 78% received HPV4-1 and 38% received the 3-dose series. After recommendation, HPV4-1 uptake was 59% and 7% in urban and suburban clinics, respectively. Variables associated with HPV4-1 uptake/refusal included time period, race, type of insurance, and receipt of concurrent vaccines. Conclusions. HPV4-1 vaccination rates in our urban clinic were high before and after routine HPV vaccine recommendations for adolescent males. Our vaccination rates were much higher than in a suburban practice.

  13. 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) ...

  14. Retinol as a micronutrients related to cervical local immunity: The expression of tumor necrosis factor-alpha specifically stimulated with E6 epitope of human papillomavirus type-16 and ratio of CD4+/CD8+ T cell in natural history of cervical cancer

    Science.gov (United States)

    Utami, T. W.; Aziz, M. F.; Ibrahim, F.; Andrijono

    2017-08-01

    Retinol is one of the antioxidant micronutrients that plays essential roles in the immune system, by preventing the persistence of modulating CD4+ and CD8+ T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-α) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF-α induces carcinogenesis. The ratio of CD4+ cells to CD8+ T cells and adequate TNF-α production in acute HPV infection are key points for clearance. The aim of this research is to analyze the sufficiency level of retinol deposit, the expression of TNF-α, and the ratio of CD4+: CD8+ T cells in a normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group. The sufficiency level of retinol deposit was analyzed from peripheral blood using the ELISA method. The cervico-vaginal secretions, which were incubated for 24 hours, were stimulated specifically by E6 epitope HPV type-16, measuring TNF-α expression semi-quantitatively by the ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method. The sufficient level of retinol deposit in a normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF-α in normal cervix group was 10%, while for cervical cancer it was 75% (OR 27.00; p CD4+: CD8+ T cells in the normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There was no high ratio of CD4+: CD8+ T cells in clearance (OR 1.22) and persistent (OR 0.95) HPV subclinical infection groups. This study was able to prove that the normal cervix group has the highest retinol deposit sufficiency level and the cervical cancer group has the highest TNF-α expression (OR 27; p < 0.001). The lowest of retinol deposit sufficiency level was not in cervical cancer, but in the persistent HPV subclinical infection group (OR 11.33). There was

  15. Global challenges of implementing human papillomavirus vaccines

    Directory of Open Access Journals (Sweden)

    Mishra Amrita

    2011-06-01

    Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

  16. Subclinical human papillomavirus infection of the cervix

    International Nuclear Information System (INIS)

    Al-Waiz, M.; Al-Saadi, Rabab N.; Al-Saadi, Zahida A.; Al-Rawi, Faiza A.

    2001-01-01

    A prospective study to investigate a group of Iraqi woman with proved genital vulval warts, to seek evidence of human papillomavirus infection in apparently normal looking cervixes and to investigate the natural history of infection. From December 1997 to August 1998, 20 women with vulval warts were enrolled along with 20 aged-matched control cases without warts. Their ages ranged between 19-48 years with a mean of 30.4 years, (+/- standard deviation = 2.3) for patients and 18-48 years with a mean of 29.7 (+/- standard deviation = 2.7) for the control group. General and gynecological examinations were carried out. Cervical swabs for associated genital infection, papilloma smears, speculoscopy and directed punch biopsies were carried out to detect subclinical human papillomavirus infections of the cervix and associated intraepithelial neoplasm. Cytology results showed that 11 (55%) of patients had evidence of cervical infection by human papillomavirus, 6 (30%) showed mild dysplastic changes, 3 (15%) showed moderate dysplastic changes, whilst 2 (10%) showed no dysplastic changes. Speculoscopy and acetowhitening was positive in 11 (55%) and collated histological results showed evidence of human papillomavirus infection in 9 patients (45%). As for the control group one case (5%) had evidence of human papillomavirus infection. Subclinical human papillomavirus infection is more common than was previously thought among Iraqi women. It may appear alone or in association with vulval or exophytic cervical warts, or both, and may be more common than the clinically obvious disease. Speculoscopy as an adjunctive method to colposcopy was found to be a simple and an easy to perform technique. Its combination with cytology gave relatively good results when it was used as a triage instrument, and may have a more promising performance in the future. (author)

  17. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen

    2014-01-01

    HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....

  18. Human Papillomavirus types distribution among women with ...

    African Journals Online (AJOL)

    Introduction: cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. Aim: to determine the ...

  19. Human papillomavirus DNA in aerodigestive squamous carcinomas ...

    African Journals Online (AJOL)

    A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...

  20. Human papillomavirus genotypes and clinical management of ...

    African Journals Online (AJOL)

    Background. Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral disease in the world. HPV infection of the genital epithelium is associated with genital warts and malignancies of the lower genital tract. Objectives. To describe the distribution, phenotypic appearance and HPV type ...

  1. Functional Crosstalk between Human Papillomaviruses and Lentiviruses

    OpenAIRE

    Pryszlak, Anna Marta

    2016-01-01

    Human papillomaviruses (HPVs) and human immunodeficiency virus‐1 (HIV‐1) are human pathogens of high biomedical significance worldwide. Interestingly, increasing epidemiological evidence indicates that individuals with active HPV infections possess an enhanced risk of being infected by HIV‐1. These findings raise the possibility that HPVs may directly or indirectly increase the pathogenicity of lentiviruses, such as HIV‐1. Using a Vesicular Stomatitis Virus‐G‐(VSV‐G)‐pseudotype...

  2. Rapid enrichment of human papillomavirus (HPV)-specific polyclonal T cell populations for adoptive immunotherapy of cervical cancer

    NARCIS (Netherlands)

    de Jong, Annemieke; van der Hulst, Jeanette M.; Kenter, Gemma G.; Drijfhout, Jan Wouter; Franken, Kees L. M. C.; Vermeij, Pieter; Offringa, Rienk; van der Burg, Sjoerd H.; Melief, Cornelis J. M.

    2005-01-01

    The majority of cervical cancers are caused by human papillomavirus type 16 (HPV16). Cervical cancer is associated with an ineffective host immune response against the HPV16 oncoproteins, characterized by the lack of the strong E6-specific T-helper type 1 (Th1) immunity that is generally present in

  3. Cancer Registries and Monitoring the Impact of Prophylactic Human Papillomavirus Vaccines: The Potential Role

    OpenAIRE

    Saraiya, Mona; Goodman, Marc T.; Datta, S. Deblina; Chen, Vivien W.; Wingo, Phyllis A.

    2008-01-01

    The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic ...

  4. Human papillomavirus vaccination in the prevention of cervical neoplasia.

    LENUS (Irish Health Repository)

    Astbury, Katharine

    2012-02-01

    Cervical cancer remains a major cause of morbidity and mortality for women worldwide. Although the introduction of comprehensive screening programs has reduced the disease incidence in developed countries, it remains a major problem in the developing world. The recent licensing of 2 vaccines against human papillomavirus (HPV) type 16 and HPV-18, the viruses responsible for 70% of cervical cancer cases, offers the hope of disease prevention. In this article, we review the role of HPV in the etiology of cervical cancer and the evidence to support the introduction of vaccination programs in young women and discuss the potential obstacles to widespread vaccination. In addition, we discuss the issues that remain to be elucidated, including the potential need for booster doses of the vaccine and the role of concomitant vaccination in men.

  5. Economic evaluation of human papillomavirus vaccination in the United Kingdom.

    Science.gov (United States)

    Jit, Mark; Choi, Yoon Hong; Edmunds, W John

    2008-07-17

    To assess the cost effectiveness of routine vaccination of 12 year old schoolgirls against human papillomavirus infection in the United Kingdom. Economic evaluation. UK. Population Schoolgirls aged 12 or older. Costs, quality adjusted life years (QALYs), and incremental cost effectiveness ratios for a range of vaccination options. Vaccinating 12 year old schoolgirls with a quadrivalent vaccine at 80% coverage is likely to be cost effective at a willingness to pay threshold of pound30,000 (euro37,700; $59,163) per QALY gained, if the average duration of protection from the vaccine is more than 10 years. Implementing a catch-up campaign of girls up to age 18 is likely to be cost effective. Vaccination of boys is unlikely to be cost effective. A bivalent vaccine with the same efficacy against human papillomavirus types 16 and 18 costing pound13- pound21 less per dose (depending on the duration of vaccine protection) may be as cost effective as the quadrivalent vaccine although less effective as it does not prevent anogenital warts. Routine vaccination of 12 year old schoolgirls combined with an initial catch-up campaign up to age 18 is likely to be cost effective in the UK. The results are robust to uncertainty in many parameters and processes. A key influential variable is the duration of vaccine protection.

  6. Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, J; Li, J; Huang, H; Fu, Y

    1998-12-01

    To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

  7. Safety of human papillomavirus vaccines: a review

    OpenAIRE

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage ra...

  8. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  9. Giant magnetoimpedance-based microchannel system for quick and parallel genotyping of human papilloma virus type 16/18

    Science.gov (United States)

    Yang, Hao; Chen, Lei; Lei, Chong; Zhang, Ju; Li, Ding; Zhou, Zhi-Min; Bao, Chen-Chen; Hu, Heng-Yao; Chen, Xiang; Cui, Feng; Zhang, Shuang-Xi; Zhou, Yong; Cui, Da-Xiang

    2010-07-01

    Quick and parallel genotyping of human papilloma virus (HPV) type 16/18 is carried out by a specially designed giant magnetoimpedance (GMI) based microchannel system. Micropatterned soft magnetic ribbon exhibiting large GMI ratio serves as the biosensor element. HPV genotyping can be determined by the changes in GMI ratio in corresponding detection region after hybridization. The result shows that this system has great potential in future clinical diagnostics and can be easily extended to other biomedical applications based on molecular recognition.

  10. Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009–2013

    Science.gov (United States)

    Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G.J.

    2016-01-01

    In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009–2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level. PMID:26692336

  11. Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013.

    Science.gov (United States)

    Cameron, Ross L; Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G J

    2016-01-01

    In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009-2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level.

  12. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  13. Epitope design of L1 protein for vaccine production against Human Papilloma Virus types 16 and 18.

    Science.gov (United States)

    Baidya, Sunanda; Das, Rasel; Kabir, Md Golam; Arifuzzaman, Md

    2017-01-01

    Cervical cancer accounts for about two-thirds of all cancer cases linked etiologically to Human Papilloma Virus (HPV). 15 oncogenic HPV types can cause cervical cancer, of which HPV16 and HPV18 combinedly account for about 70% of it. So, effective epitope design for the clinically relevant HPV types 16 and 18 would be of major medical benefit. Here, a comprehensive analysis is carried out to predict the epitopes against HPV types 16 and 18 through "reverse vaccinology" approach. We attempted to identify the evolutionarily conserved regions of major capsid protein (L1) as well as minor capsid protein (L2) of HPV and designed epitopes within these regions. In this study, we analyzed about 49 and 27 sequences of HPV L2 and L1 proteins respectively. Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18. We had selected HLA-A*0201, DRB1*1501, DQB1*0602, DRB1*0401 and DQB1*0301 alleles for the prediction of T cell epitopes of L1 of HPV 16 and 18. Finally, we reported that predicted epitope sequences EEYDLQFIFQLCKITLTA, and RHGEEYDLQFIFQLCKITLTA of L1 protein of HPV 16, and LPDPNKF, PETQRLVWAC, PVPGQYDA, YNPETQRLVWAC, DTGYGAMD, PVPGQYDATK, KQDIPKVSAYQYRVFRV, RDNVSVDYKQTQLCI and YSRHVEEYDLQFIF of L1 protein of HPV 18 could be therapeutic tools for vaccine design against HPV.

  14. Beta-catenin accelerates human papilloma virus type-16 mediated cervical carcinogenesis in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Gülay Bulut

    Full Text Available Human papilloma virus (HPV is the principal etiological agent of cervical cancer in women, and its DNA is present in virtually all of these tumors. However, exposure to the high-risk HPV types alone is insufficient for tumor development. Identifying specific collaborating factors that will lead to cervical cancer remains an unanswered question, especially because millions of women are exposed to HPV. Our earlier work using an in vitro model indicated that activation of the canonical Wnt pathway in HPV-positive epithelial cells was sufficient to induce anchorage independent growth. We therefore hypothesized that constitutive activation of this pathway might function as the "second hit." To address this possibility, we developed two double-transgenic (DT mouse models, K14-E7/ΔN87βcat and K14-HPV16/ΔN87βcat that express either the proteins encoded by the E7 oncogene or the HPV16 early region along with constitutively active β-catenin, which was expressed by linking it to the keratin-14 (K14 promoter. We initiated tumor formation by treating all groups with estrogen for six months. Invasive cervical cancer was observed in 11% of the K14-ΔN87βcat mice, expressing activated β-catenin and in 50% of the animals expressing the HPV16 E7 oncogene. In double-transgenic mice, coexpression of β-catenin and HPV16 E7 induced invasive cervical cancer at about 7 months in 94% of the cases. We did not observe cervical cancer in any group unless the mice were treated with estrogen. In the second model, K14-HPV16 mice suffered cervical dysplasias, but this phenotype was not augmented in HPV16/ΔN87βcat mice. In summary, the phenotypes of the K14-E7/ΔN87βcat mice support the hypothesis that activation of the Wnt/β-catenin pathway in HPV-associated premalignant lesions plays a functional role in accelerating cervical carcinogenesis.

  15. Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer : A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study

    NARCIS (Netherlands)

    Kreimer, Aimee R.; Brennan, Paul; Kuhs, Krystle A. Lang; Waterboer, Tim; Clifford, Gary; Franceschi, Silvia; Michel, Angelika; Willhauck-Fleckenstein, Martina; Riboli, Elio; Castellsague, Xavier; Hildesheim, Allan; Fortner, Renee Turzanski; Kaaks, Rudolf; Palli, Domenico; Ljuslinder, Ingrid; Panico, Salvatore; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Peeters, Petra H.; Cross, Amanda J.; Bueno-de-Mesquita, H. Bas; Vineis, Paolo; Larranaga, Nerea; Pala, Valeria; Sanchez, Maria-Jose; Navarro, Carmen; Barricarte, Aurelio; Tumino, Rosario; Khaw, Kay-Tee; Wareham, Nicholas; Boeing, Heiner; Steffen, Annika; Travis, Ruth C.; Ramon Quiros, J.; Weiderpass, Elisabete; Pawlita, Michael; Johansson, Mattias

    2015-01-01

    Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The

  16. [Demyelinating disease and vaccination of the human papillomavirus].

    Science.gov (United States)

    Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L

    2011-04-16

    Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

  17. Misconception: human papillomavirus vaccine and infertility.

    Science.gov (United States)

    Schuler, Christine L; Hanley, Chassidy J; Coyne-Beasley, Tamera

    2014-02-01

    This study sought to determine if parents of males express concerns about vaccine-associated infertility (VAI) with the human papillomavirus (HPV) vaccine and to understand the impact of those concerns. Parents of sons were surveyed to determine VAI concerns. Logistic regression was used to find if parents worried about VAI had lower knowledge of HPV disease, more concern for side effects, lacked information about vaccination, or had lower intention to vaccinate. In all, 39% of parents were worried about VAI. Parents worried about VAI had similar knowledge of HPV compared with other parents. Parents worried about VAI had twice the odds of agreeing the vaccine may cause side effects and agreeing they did not have enough information compared to their counterparts. Parents worried about VAI less often intended to vaccinate sons than other parents. These findings suggest many parents worry about VAI in sons with HPV vaccine.

  18. New treatments for human papillomavirus infection.

    Science.gov (United States)

    Muñoz-Santos, C; Pigem, R; Alsina, M

    2013-12-01

    Human papillomavirus infection is very common. In this article, we review the latest developments in the treatment of lesions caused by this virus, with a particular focus on anogenital warts. Sinecatechins and new imiquimod formulations are among the most significant new developments. Others include photodynamic therapy and intralesional immunotherapy, but there is insufficient evidence to recommend their routine use. Finally, while therapeutic vaccines and inhibitory molecules appear to hold great promise, they are still in the early phases of investigation. More studies are needed, and these should have similar designs, larger samples, and sufficiently long follow-up periods to enable the direct comparison of the short-term and long-term effectiveness of different treatment options. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  19. Human papillomavirus types and recurrent cervical warts

    Energy Technology Data Exchange (ETDEWEB)

    Nuovo, G.J. (Columbia Presbyterian Medical Center, New York, NY (USA)); Pedemonte, B.M. (Harlem Hospital Medical Center, New York, NY (USA))

    1990-03-02

    The authors analyzed cervical intraepithelial neoplasias (CINs) detected after cryotherapy to determine if recurrence is associated with the same human papillomavirus (HPV) type found in the original lesion. Eight women had detectable HPV DNA in CINs that occurred after ablation of another CIN, and for each patient the HPV type in the pretreatment lesion was different from that in the CIN that appeared after cryotherapy. This compares with 12 women who had HPV detected in two or more CINs present at the same time, 11 of whom had the same HPv type noted. they concluded that although multiple, simultaneous CINs in a woman often contain the same HPV type, recurrent CINs that occur after cryotherapy contain an HPV type different from that present in the pretreatment lesion.

  20. Human papillomavirus types and recurrent cervical warts

    International Nuclear Information System (INIS)

    Nuovo, G.J.; Pedemonte, B.M.

    1990-01-01

    The authors analyzed cervical intraepithelial neoplasias (CINs) detected after cryotherapy to determine if recurrence is associated with the same human papillomavirus (HPV) type found in the original lesion. Eight women had detectable HPV DNA in CINs that occurred after ablation of another CIN, and for each patient the HPV type in the pretreatment lesion was different from that in the CIN that appeared after cryotherapy. This compares with 12 women who had HPV detected in two or more CINs present at the same time, 11 of whom had the same HPv type noted. they concluded that although multiple, simultaneous CINs in a woman often contain the same HPV type, recurrent CINs that occur after cryotherapy contain an HPV type different from that present in the pretreatment lesion

  1. School-based human papillomavirus vaccination: An opportunity to ...

    African Journals Online (AJOL)

    School-based human papillomavirus vaccination: An opportunity to increase knowledge about cervical cancer and improve uptake of ... Poor knowledge about cervical cancer plays a role in limiting screening uptake. HPV ... Article Metrics.

  2. Detection of human papillomavirus DNA with in situ hybridisation in ...

    African Journals Online (AJOL)

    present study was undertaken to determine the prevalence of human papillomavirus (HPV) DNA in oral squamous carcinoma in the west of the Northern ... Immunocytochemistry for viral antigen was negative in all the specimens. HPV-18 was ...

  3. Evaluation of human papillomavirus elimination from cervix uteri by infrared laser exposure.

    Science.gov (United States)

    Dymkovets, V P; Ezhov, V V; Manykin, A A; Belov, S V; Danileiko, Yu K; Osiko, V V; Salyuk, V A

    2011-12-01

    Elimination of types 16 and 18 human papilloma virus from the surface of cervix uteri for secondary prevention of cervical cancer was evaluated. The method is protected by patent of invention of the Russian Federation. Infrared laser therapy of cervix uteri was carried out in patients with precancer diseases of cervix uteri at Department of Gynecology of Municipal Clinical Hospital No. 52 (Moscow). Papillomavirus infection was eliminated using a Russian diode laser (lambda=1.06 μ, radiation power 10 W) with a collimating headpiece using carbon die at a distance of 10-12 cm from the exposed surface. The treatment resulted in a high percentage of elimination of types 16 and 18 oncogenic virus 4-6 weeks and during delayed periods after exposure.

  4. Production of Human Papilloma Virus Type 16 E6 Oncoprotein as a Recombinant Protein in Eukaryotic Cells

    Science.gov (United States)

    Mirshahabi, H; Soleimanjahi, H; Pourpak, Z; Meshkat, Z; Hassan, ZM

    2012-01-01

    Background Cervical cancer is one of the most important and widespread cancer which affects women. There are several causes of cervical cancer; among them HPV types 16 and 18 are the most prominent ones which are recurrent and persistent infections. These genotypes are currently about 70% of cervical cancer causes in developing countries. Due to the importance of these viruses in cervical cancer, we pioneered the production of Human Papilloma Virus type16 E6 oncoprotein as a recombinant protein in order to develop a vaccine. Two HPV oncoproteins, E6 and E7, are consistently expressed in HPV-associated cancer cells and are responsible for malignant transformation. These oncogenic proteins represent ideal target antigens for developing vaccine and immunotherapeutic strategies against HPV-associated neoplasm. Methods In the present study, the cloned E6-oncoprotein of HPV16 in pTZ57R/T-E6 vector was used to produce professional expression vector. The target gene was subcloned in a eukaryotic expression vector. The pcDNA3-E6 vector was propagated in E.coli strain DH5α and transfected into CHO cells 72 hours post-transfection. Results The transfected cells were harvested; mRNA detection and the interest protein production were confirmed by western blot analysis using specific anti E6 monoclonal antibody. Conclusion HPV16-E6 target protein recognized by specific antibody could be an appropriate form of protein, which can be used for further studies. Due to potential effect of this protein, its DNA construction can be used for DNA vaccine in future studies. PMID:25780534

  5. Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity

    Directory of Open Access Journals (Sweden)

    Coccia Raffaella

    2009-01-01

    Full Text Available Abstract Background Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinase-positive amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5 oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the trans-membrane Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this interaction has functional consequences on cell metabolism and phenotype. Methods The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14 by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored. Results We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs. Conclusion Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these

  6. Oropharyngeal perinatal colonization by human papillomavirus.

    Science.gov (United States)

    Sánchez-Torices, María Soledad; Corrales-Millan, Rocío; Hijona-Elosegui, Jesús J

    2016-01-01

    Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery. The aim of our research was to study maternal-foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries. The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined. The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%. The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  7. Enhancement of human papilloma virus type 16 E7 specific T cell responses by local invasive procedures in patients with (pre)malignant cervical neoplasia

    NARCIS (Netherlands)

    Visser, Jeroen; van Baarle, D; Hoogeboom, BN; Reesink, N; Klip, H; Schuuring, E; Nijhuis, E; Pawlita, M; Bungener, L; de Vries-Idema, J; Nijman, H; Miedema, F; Daemen, T; van der Zee, A

    2006-01-01

    It has been suggested that local invasive procedures may alter the natural course of (pre)malignant cervical disease. This could be due to partial excision of the lesions, or via induction of cellular immunity against human papillomavirus (HPV) by the local invasive procedures. We studied the

  8. Optimization of multimeric human papillomavirus L2 vaccines.

    Directory of Open Access Journals (Sweden)

    Subhashini Jagu

    Full Text Available We sought to define the protective epitopes within the amino terminus of human papillomavirus (HPV type 16 minor capsid protein L2. Passive transfer of mice with rabbit antisera to HPV16 L2 peptides 17-36, 32-51 and 65-81 provided significant protection against vaginal HPV16 challenge, whereas antisera to 47-66, 108-120 or 373-392 did not. Vaccination with L1 virus-like particles induces a high titer, but generally type-restricted neutralizing antibody response. Conversely, vaccination with L2 11-88, especially multimers thereof, induces antibodies that neutralize a broad range of papillomavirus types, albeit at lower titers than for L1 VLP. With the intent of enhancing the immunogenicity and the breadth of protection by focusing the immune response to the key protective epitopes, we designed L2 fusion proteins consisting of residues ∼11-88 of eight divergent mucosal HPV types 6, 16, 18, 31, 39, 51, 56, 73 (11-88×8 or residues ∼13-47 of fifteen HPV types (13-47×15. The 11-88×8 was significantly more immunogenic than 13-47×15 in Balb/c mice regardless of the adjuvant used, suggesting the value of including the 65-81 protective epitope in the vaccine. Since the L2 47-66 peptide antiserum failed to elicit significant protection, we generated an 11-88×8 construct deleted for this region in each subunit (11-88×8Δ. Mice were vaccinated with 11-88×8 and 11-88×8Δ to determine if deletion of this non-protective epitope enhanced the neutralizing antibody response. However, 11-88×8Δ was significantly less immunogenic than 11-88×8, and even the addition of a known T helper epitope, PADRE, to the construct (11-88×8ΔPADRE failed to recover the immunogenicity of 11-88×8 in C57BL/6 mice, suggesting that while L2 47-66 is not a critical protective or T helper epitope, it nevertheless contributes to the immunogenicity of the L2 11-88×8 multimer vaccine.

  9. Safety of human papillomavirus vaccines: a review.

    Science.gov (United States)

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-05-01

    Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence.

  10. Human papillomavirus vaccination among adolescents in Georgia.

    Science.gov (United States)

    Underwood, Natasha L; Weiss, Paul; Gargano, Lisa M; Seib, Katherine; Rask, Kimberly J; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M; Sales, Jessica M

    2015-01-01

    Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011-2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time.

  11. Human Papillomavirus and Vaccination in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Kung-Liahng Wang

    2007-12-01

    Full Text Available Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN] evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3 and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA and bivalent Cervarix (GlaxoSmithKline, London, UK. This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer.

  12. Human papillomavirus enigmas and persistent questions

    Directory of Open Access Journals (Sweden)

    William Edridge

    2016-09-01

    Full Text Available Since the 1970s the association between cancer and the human papillomavirus (HPV has been known. Zur Hausen’s belatedly awarded Nobel prize bears testament to this. We know that HPV is associated with cervical cancer, vulval cancer, anal cancer, vulvovaginal warts, and other non-gynaecological cancers. The place of HPV in the modern management of gynaecology may at first seem clear. Vaccination with the bivalent vaccine against HPV 16 and 18 (Cervarix, GlaxoSmithKline (GSK may prevent cervical, vulval and some anal cancers; vaccination with the quadrivalent vaccine (Gardasil, Merck may prevent those conditions plus warts. The 9-valent vaccine (Gardasil 9, Merck is currently recommended, as are the other two, by the American College of Obstetricians and Gynaecologists (ACOG.[1] The UK initiated vaccination with the bivalent vaccine and now recommends the quadrivalent vaccine.[2] So far studies have demonstrated a significant decrease in dysplasia and warts, particularly in HPV- naive subjects. Whether these benefits translate to the prevention of cervical and other cancers has not yet been shown, but if one considers the natural history of the progression of dysplasia to cancer, this is quite reasonably presumed.

  13. Human Papillomavirus and Tonsillar and Base of Tongue Cancer

    Directory of Open Access Journals (Sweden)

    Torbjörn Ramqvist

    2015-03-01

    Full Text Available In 2007, human papillomavirus (HPV type 16 was recognized as a risk factor by the International Agency for Research on Cancer, for oropharyngeal squamous cell carcinoma (OSCC, where tonsillar and base of tongue cancer (TSCC and BOTSCC dominate. Furthermore, patients with HPV-positive TSCC and BOTSCC, had a much better clinical outcome than those with corresponding HPV-negative cancer and other head and neck cancer. More specifically, survival was around 80% for HPV-positive TSCC and BOTSCC vs. 40% five-year disease free survival, for the corresponding HPV-negative tumors with conventional radiotherapy and surgery, while this could not be observed for HPV-positive OSCC at other sites. In addition, the past 20–40 years in many Western Countries, the incidence of HPV-positive TSCC and BOTSCC has risen, and >70% are men. This has resulted in a relative increase of patients with HPV-positive TSCC and BOTSCC that may not need the intensified chemo-radiotherapy (with many more severe debilitating side effects often given today to patients with head and neck cancer. However, before tapering therapy, one needs to enable selection of patients for such treatment, by identifying clinical and molecular markers that together with HPV-positive status will better predict patient prognosis and response to therapy. To conclude, there is a new increasing group of patients with HPV-positive TSCC and BOTSCC with good clinical outcome, where options for better-tailored therapy are needed. For prevention, it would be of benefit to vaccinate both girls and boys against HPV16 infection. For potential future screening the ways to do so need optimizing.

  14. Longitudinal Psychosocial Adjustment of Women to Human Papillomavirus Infection.

    Science.gov (United States)

    Hsu, Yu-Yun; Wang, Wei-Ming; Fetzer, Susan Jane; Cheng, Ya-Min; Hsu, Keng-Fu

    2018-05-29

    The aim of this study was to examine the psychosocial adjustment trajectory, focusing on psychological distress, sexual relationships and health care information, as well as factors which have an impact on adjustment on receiving a positive diagnosis of human papillomavirus infection. Human papillomavirus is a common sexually transmitted infection in females. To date, knowledge of the longitudinal psychosocial response to the diagnosis of human papillomavirus is limited. A prospective longitudinal design was conducted with a convenience sample. Women aged 20-65 years old were followed at one, 6 and 12 months after a diagnosis of HPV. Participants completed measures of initial emotional distress and followed-up psychosocial adjustment. A mixed-effects model was applied to analyze the longitudinal changes in psychosocial adjustment. Seventy human papillomavirus positive women participated in the study with nearly 20% of the women reporting emotional distress during their first visit. Mixed-effects model analyses showed that a trajectory of psychosocial adjustment in health care orientation, sexual relationship and psychosocial distress occur from one to 6 months after HPV diagnosis. However, a declining trend from 6-12 months was significant in health care orientation. Initial emotional distress was associated with changes in psychological adjustment. Psychosocial adjustment to human papillomavirus was worse at one month compared with 6 and 12 months after diagnosis. Healthcare providers should offer health information and psychosocial support to women according to their disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Inactivation of high-risk human papillomaviruses by Holder pasteurization: implications for donor human milk banking.

    Science.gov (United States)

    Donalisio, Manuela; Cagno, Valeria; Vallino, Marta; Moro, Guido E; Arslanoglu, Sertac; Tonetto, Paola; Bertino, Enrico; Lembo, David

    2014-01-01

    Several studies have recently reported the detection of oncogenic human papillomaviruses (HPV) in human milk of a minority of lactating mothers. These findings raised safety concerns in the context of human donor milk banking given the potential risk of HPV transmission to recipient infants. The aim of this study was to investigate whether the Holder pasteurization, a procedure currently in use in human donor milk banks for milk pasteurization, completely inactivates high-risk and low-risk HPV. HPV pseudoviruses (PsV) were generated, spiked into cell culture medium or donor human milk and subjected to thermal inactivation. HPV PsV infectivity and morphological integrity was analyzed by cell-based assay and by electron microscopy, respectively. The Holder pasteurization completely inactivated the infectivity of high-risk (types 16 and 18) and low-risk (type 6) HPV both in cell culture medium and in human milk causing PsV particle disassembly. The results presented here indicate that the Holder pasteurization is an efficient procedure to inactivate high-risk and low-risk HPV thus preventing the potential risk of their transmission through human donor milk.

  16. Human papillomavirus detection in cervical scrapes from women attended in the Family Health Program

    Directory of Open Access Journals (Sweden)

    Everton Faccini Augusto

    2014-01-01

    Full Text Available OBJECTIVES: to survey the prevalence of human papillomavirus, associated risk factors and genotype distribution in women who were referred to cervical cancer screening when attended in a Family Health Program. METHOD: we conducted a cross-sectional survey, investigating 351 women. Polymerase chain reaction for DNA amplification and restriction fragment length polymorphism analysis were used to detect and typify the papillomavirus. RESULTS: virus infection was detected in 8.8% of the samples. Among the 21 different genotypes identified in this study, 14 were high risk for cervical cancer, and the type 16 was the most prevalent type. The infection was associated with women who had non-stable sexual partners. Low risk types were associated with younger women, while the high risk group was linked to altered cytology. CONCLUSION: in this sample attended a Family Health Program, we found a low rate of papillomavirus infection. Virus frequency was associated to sexual behavior. However, the broad range of genotypes detected deserves attention regarding the vaccine coverage, which includes only HPV prevalent types.

  17. [Molecular aspects of human papillomaviruses and their relation to uterine cervix cancer].

    Science.gov (United States)

    García-Carrancá, A; Gariglio, P V

    1993-01-01

    Papillomaviruses (wart viruses) are responsible for the development of benign and malignant epithelial lesions in mammals. More than 60 different types of human papillomaviruses (HPVs) have been isolated to date. Some of them are major candidates as etiologic agents in cervical cancer. DNA from HPV types 16, 18 and 33 is usually found integrated in about 90 percent of genital carcinomas. Integration of the viral DNA into the cellular genome may be an important step towards the development of malignancy. Two early genes of HPVs (E6 y E7) are involved in cellular transformation. Another early gene (E2) participates in gene control by directly binding to conserved DNA motifs in the viral genome. Several protein factors of viral and cellular origin interact with the regulatory region of HPVs and participate in the regulation transcription of oncogenes E6 and E7. Cellular factors, such as immune system and oncogene and anti-oncogene alterations, seem to play an important role in papillomavirus-associated cervical carcinogenesis.

  18. Incidence of low risk human papillomavirus in oral cancer: a real time PCR study on 278 patients.

    Science.gov (United States)

    Palmieri, A; Scapoli, L; Martinelli, M; Pezzetti, F; Girardi, A; Spinelli, G; Lucchese, A; Carinci, F

    2011-01-01

    Squamous cell carcinoma is the most frequent malignant tumour of the oral cavity. It is widely known that tobacco and alcohol consumption are the major causes of the development of oral squamous cell carcinoma (OSCC). The human papilloma virus infection has also been postulated as a risk factor for squamous cell carcinoma, although conflicting results have been reported. The aim of this study is to evaluate the presence of high-risk and low-risk type human papillomavirus in a large sample of squamous cell carcinoma limited to the oral cavity by means of quantitative real-time polymerase chain reaction. Data were obtained from 278 squamous cell carcinoma limited to oral cavity proper. Sequencing revealed that 5 samples were positive for HPV type 16, 5 for HPV type 11, and 1 for HPV type 6. Human papillomavirus 11 was detected in 5 tumours out of the 278 examined. The prevalence rate for Human papillomavirus 11 was 1.8% (C.I. 0.7-3.9). The matched case-controls analysis indicated that the prevalence among controls did not significantly differ with respect to cases and that Human papillomavirus 11 alone did not correlate with squamous cell carcinoma.

  19. [Human papillomavirus vaccine. Efficacy and safety].

    Science.gov (United States)

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Interleukin-2 and dendritic cells as adjuvants for surgical therapy of tumours associated with human papillomavirus type 16

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan; Mikyšková, Romana; Vonka, V.; Mendoza, Luis; Šímová, Jana; Šmahel, M.; Indrová, Marie

    2003-01-01

    Roč. 21, 9-10 (2003), s. 891-896 ISSN 0264-410X R&D Projects: GA MZd NC7148; GA ČR GA301/00/0114; GA ČR GA301/01/0985; GA AV ČR IAA7052002; GA AV ČR IAA5052203 Grant - others:Liga proti rakovině(CZ) - Institutional research plan: CEZ:AV0Z5052915 Keywords : interleukin-2 * HPV 16 * dendritic cells Subject RIV: FD - Oncology ; Hematology Impact factor: 3.007, year: 2003

  1. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yueyang [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

  2. Expression of LIGHT/TNFSF14 Combined with Vaccination against Human Papillomavirus Type 16 E7 Induces Significant Tumor Regression

    Science.gov (United States)

    Kanodia, Shreya; Da Silva, Diane M.; Karamanukyan, Tigran; Bogaert, Lies; Fu, Yang-Xin; Kast, W. Martin

    2010-01-01

    LIGHT, a ligand for the lymphotoxin-beta receptor, establishes lymphoid-like tissues inside tumor sites and recruits naïve T-cells into the tumor. However, whether these infiltrating T-cells are specific for tumor antigens is not known. We hypothesized that therapy with LIGHT can expand functional tumor-specific CD8+ T-cells that can be boosted using HPV16E6E7-Venezuelan Equine Encephalitis Virus Replicon Particles (HPV16-VRP) and that this combined therapy can eradicate HPV16-induced tumors. Our data show that forced expression of LIGHT in tumors results in an increase in expression of interferon gamma (IFNg) and chemottractant cytokines such as IL-1a, MIG and MIP-2 within the tumor and that this tumor microenvironment correlates with an increase in frequency of tumor-infiltrating CD8+ T-cells. Forced expression of LIGHT also results in the expansion of functional T-cells that recognize multiple tumor-antigens, including HPV16 E7, and these T-cells prevent the outgrowth of tumors upon secondary challenge. Subsequent boosting of E7-specific T-cells by vaccination with HPV16-VRP significantly increases their frequency in both the periphery and the tumor, and leads to the eradication of large well-established tumors, for which either treatment alone is not successful. These data establish the safety of Ad-LIGHT as a therapeutic intervention in pre-clinical studies and suggest that patients with HPV16+ tumors may benefit from combined immunotherapy with LIGHT and antigen-specific vaccination. PMID:20460520

  3. Genetic variability in E6 and E7 oncogenes of human papillomavirus Type 16 from Congolese cervical cancer isolates

    OpenAIRE

    Boumba, Luc Magloire Anicet; Assoumou, Samira Zoa; Hilali, Lahoucine; Mambou, Jean Victor; Moukassa, Donatien; Ennaji, Mustapha Moulay

    2015-01-01

    Background The molecular epidemiological studies showed that some variants of HPV-16, distributed geographically, would present a higher risk of causing cervical cancer. This study aimed to analyze nucleotide changes of HPV-16 E6 and E7 genomic regions from infected Southwestern Congolese women. Methods DNA of twenty HPV-16 isolates was analyzed by amplifying the E6 and E7 genes using type-specific primers PCR and direct sequencing. The sequences obtained were aligned with the HPV-16 GenBank ...

  4. Long-term persistence of oral human papillomavirus type 16: the HPV Infection in Men (HIM) study.

    Science.gov (United States)

    Pierce Campbell, Christine M; Kreimer, Aimée R; Lin, Hui-Yi; Fulp, William; O'Keefe, Michael T; Ingles, Donna J; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2015-03-01

    Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4-NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. ©2015 American Association for Cancer Research.

  5. Human papillomavirus-associated cancers: A growing global problem

    OpenAIRE

    Bansal, Anshuma; Singh, Mini P; Rai, Bhavana

    2016-01-01

    Human papillomavirus (HPV) infection is linked with several cancers such as cancer cervix, vagina, vulva, head and neck, anal, and penile carcinomas. Although there is a proven association of HPV with these cancers, questions regarding HPV testing, vaccination, and treatment of HPV-related cancers continue to remain unanswered. The present article provides an overview of the HPV-associated cancers.

  6. Prevalence of Human Papillomavirus Type 58 in Women With or ...

    African Journals Online (AJOL)

    lesions.[7,8] Among these, at least 15 are considered high‑risk. HPV (HR‑HPV) and are strongly associated with progression. Prevalence of Human Papillomavirus Type 58 in Women With or Without Cervical Lesions in. Northeast Brazil. Fernandes JV, Carvalho MGF1, de Fernandes TAAM2, Araújo JMG, Azevedo PRM3,.

  7. False-positive Human Papillomavirus DNA tests in cervical screening

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Pribac, Igor; Lynge, Elsebeth

    2011-01-01

    Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus (HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated...

  8. Age-specific prevalence of cervical human papillomavirus infection ...

    African Journals Online (AJOL)

    This cross-sectional study describes the age-specific prevalence of human papillomavirus (HPV) infection and cytological abnormalities among this urban and peri-urban population. Method. Over the period March 2009 - September 2011, 1 524 women attending public sector primary healthcare clinics were invited to

  9. Knowledge of Human Papillomavirus Infection and Acceptability of ...

    African Journals Online (AJOL)

    Introduction: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and has been implicated in over 70% of cases of cervical cancer. This study assessed the knowledge of HPV infection and acceptability of HPV vaccination among nursing students in Benin City. Methodology: A ...

  10. An Overview of Quadrivalent Human Papillomavirus Vaccine Safety

    DEFF Research Database (Denmark)

    Vichnin, Michelle; Bonanni, Paolo; Klein, Nicola P

    2015-01-01

    BACKGROUND: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6...

  11. Prevalence and Risk Factors of High Risk Human Papillomavirus ...

    African Journals Online (AJOL)

    Cervical cancer is the most common female cancer in northern Nigeria, yet the pattern of infection with human papillomavirus, the principal aetiologic agent is unknown. This was a preliminary study conducted in two referral hospitals in order to establish base-line data on the prevalence and risk factors for the infection in ...

  12. Human papillomavirus and tar hypothesis for squamous cell cervical ...

    Indian Academy of Sciences (India)

    2010-08-09

    Aug 9, 2010 ... Keywords. Cervical cancer; co-factors; human papillomavirus; tar-based vaginal douche; tobacco smoke; wood smoke. Author Affiliations. Christina Bennett1 Allen E Kuhn2 Harry W Haverkos3. Indiana University School of Medicine, Indianapolis, Indiana 46202-5149, USA; Suite 300, Hamilton Mason Road ...

  13. Diagnosing Human Papillomavirus and Human Papillomavirus Type 16 By Real-Time PCR in Patient Undergone to Colposcopy and Significance of the Diagnosis

    Directory of Open Access Journals (Sweden)

    Sibel Özdaş

    2013-06-01

    Full Text Available Objective: It is aimed to determine presence of HPV and HPV 16 by Real-Time PCR in cervical smears obtained from patients during colposcopic examination who had referred to outpatient clinic of Gynecology and Obstetrics Department due to various complaints and to examine interrelation between positive test results and clinical data. Method: Sixty patients were included in the study who were referred to outpatient clinic due to vary complaints and who had been decided to undergo to colposcopic examination. DNA was obtained from each smear sample by phenol-chloroform-isoamylalcohol method. L1 region was replicated in amplification process using MY09/MY11 primers. Products for Nested Real time PCR were studied in Ligth Cycler equipment by GP5+/GP6+ primers and Cyanine-5 labeled HPV 16 DNA specific probe. Real time PCR products were undergone melting curve analysis by LigthCycler software version 3.5.3. HPV DNA positivity and HPV 16 positivity were determined at 78-82°C and 68°C, respectively. Results: No statistically significant difference could be detected between HPV positivity, HPV 16 in and types other than HPV 16 control group and patients with positive test result as a consequence of colposcopic examination. Again, no statistically significant difference could be detected between HPV positivity and status of parity, result of PAP test, marital status and age of patient. Conclusion: No statistically significant difference could be detected between HPV positivity, HPV 16 in and types other than HPV 16 control group and patients with positive test result as a consequence of colposcopic examination. Again, no statistically difference could be detected between HPV positivity and result of PAP smear test, marital status, age of patient and smoking but statistically significant difference could be detected between types other than HPV 16 and status of parity (respectively; χ2=0.821, p=0.365; χ2=0.752, p=0.564; χ2=0.364, p=0.834; χ2= 6.835, p=0.033.

  14. Identification and validation of human papillomavirus encoded microRNAs.

    Directory of Open Access Journals (Sweden)

    Kui Qian

    Full Text Available We report here identification and validation of the first papillomavirus encoded microRNAs expressed in human cervical lesions and cell lines. We established small RNA libraries from ten human papillomavirus associated cervical lesions including cancer and two human papillomavirus harboring cell lines. These libraries were sequenced using SOLiD 4 technology. We used the sequencing data to predict putative viral microRNAs and discovered nine putative papillomavirus encoded microRNAs. Validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38 and one by HPV 68. The expression of HPV 16 microRNAs was further confirmed by in situ hybridization, and colocalization with p16INK4A was established. Prediction of cellular target genes of HPV 16 encoded microRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development, and cancer. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene and one in the LCR region. This is the first report to show that papillomaviruses encode their own microRNA species. Importantly, microRNAs were found in libraries established from human cervical disease and carcinoma cell lines, and their expression was confirmed in additional tissue samples. To our knowledge, this is also the first paper to use in situ hybridization to show the expression of a viral microRNA in human tissue.

  15. Frequency of human papillomavirus infection in patients with gastrointestinal cancer.

    Science.gov (United States)

    Roesch-Dietlen, F; Cano-Contreras, A D; Sánchez-Maza, Y J; Espinosa-González, J M; Vázquez-Prieto, M Á; Valdés-de la O, E J; Díaz-Roesch, F; Carrasco-Arroniz, M Á; Cruz-Palacios, A; Grube-Pagola, P; Sumoza-Toledo, A; Vivanco-Cid, H; Mellado-Sánchez, G; Meixueiro-Daza, A; Silva-Cañetas, C S; Carrillo-Toledo, M G; Lagunes-Torres, R; Amieva-Balmori, M; Gómez-Castaño, P C; Reyes-Huerta, J U; Remes-Troche, J M

    2018-02-15

    Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  16. Evaluation of immunological cross-reactivity between clade A9 high-risk human papillomavirus types on the basis of E6-Specific CD4+ memory T cell responses

    NARCIS (Netherlands)

    van den Hende, Muriel; Redeker, Anke; Kwappenberg, Kitty M. C.; Franken, Kees L. M. C.; Drijfhout, Jan W.; Oostendorp, Jaap; Valentijn, A. Rob P. M.; Fathers, Loraine M.; Welters, Marij J. P.; Melief, Cornelis J. M.; Kenter, Gemma G.; van der Burg, Sjoerd H.; Offringa, Rienk

    2010-01-01

    CD4(+) T cell responses against the E6 oncoprotein of human papillomavirus (HPV) type 16 and 5 closely related members of clade A9 (HPV31, 33, 35, 52, and 58) were charted in peripheral blood mononuclear cell cultures from healthy subjects and patients who underwent HPV16 E6/E7-specific vaccination.

  17. Human papillomavirus and gastrointestinal cancer in Iranian population: A systematic review and meta-analysis.

    Science.gov (United States)

    Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima

    2017-01-01

    Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.

  18. Analysis of cis-elements that facilitate extrachromosomal persistence of human papillomavirus genomes

    International Nuclear Information System (INIS)

    Pittayakhajonwut, Daraporn; Angeletti, Peter C.

    2008-01-01

    Human papillomaviruses (HPVs) are maintained latently in dividing epithelial cells as nuclear plasmids. Two virally encoded proteins, E1, a helicase, and E2, a transcription factor, are important players in replication and stable plasmid maintenance in host cells. Recent experiments in yeast have demonstrated that viral genomes retain replication and maintenance function independently of E1 and E2 [Angeletti, P.C., Kim, K., Fernandes, F.J., and Lambert, P.F. (2002). Stable replication of papillomavirus genomes in Saccharomyces cerevisiae. J. Virol. 76(7), 3350-8; Kim, K., Angeletti, P.C., Hassebroek, E.C., and Lambert, P.F. (2005). Identification of cis-acting elements that mediate the replication and maintenance of human papillomavirus type 16 genomes in Saccharomyces cerevisiae. J. Virol. 79(10), 5933-42]. Flow cytometry studies of EGFP-reporter vectors containing subgenomic HPV fragments with or without a human ARS (hARS), revealed that six fragments located in E6-E7, E1-E2, L1, and L2 regions showed a capacity for plasmid stabilization in the absence of E1 and E2 proteins. Interestingly, four fragments within E7, the 3' end of L2, and the 5' end of L1 exhibited stability in plasmids that lacked an hARS, indicating that they possess both replication and maintenance functions. Two fragments lying in E1-E2 and the 3' region of L1 were stable only in the presence of hARS, that they contained only maintenance function. Mutational analyses of HPV16-GFP reporter constructs provided evidence that genomes lacking E1 and E2 could replicate to an extent similar to wild type HPV16. Together these results support the concept that cellular factors influence HPV replication and maintenance, independently, and perhaps in conjunction with E1 and E2, suggesting a role in the persistent phase of the viral lifecycle

  19. Progress toward implementation of human papillomavirus vaccination--the Americas, 2006-2010.

    Science.gov (United States)

    2011-10-14

    Cervical cancer is a major cause of morbidity and mortality in the Americas, where an estimated 80,574 new cases and 36,058 deaths were reported in 2008, with 85% of this burden occurring in Latin America and the Caribbean. Two oncogenic human papillomavirus (HPV) types (16 and 18) cause approximately 70% of cervical cancers and a substantial proportion of other HPV-related cancers. HPV vaccination provides an opportunity to greatly reduce cervical cancer burden through primary prevention of HPV infection. This report summarizes the progress toward HPV vaccine introduction in the Americas, focusing on countries that have introduced the vaccine in national or regional immunization programs. As of January 2011, four countries in the Americas had introduced HPV vaccine. Overcoming issues related to financing and delivery of HPV vaccine remains a key public health challenge to more widespread implementation of HPV vaccination in the Americas.

  20. Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Hørding, U; Nielsen, H W

    1994-01-01

    sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace......Epidemiological features suggest that the risk of testicular cancer may be related to exposure to unknown infectious agents, including viruses. Therefore a series of twenty specimens of testicular germ cell tumours, including preinvasive carcinoma in-situ, were tested for the presence of DNA...... of EBV DNA was revealed in one of two experiments. These samples were examined by immunohistochemical staining with specific antibodies raised against the EBV protein products and in-situ hybridization with specific molecular probes, and were confirmed to be negative. The study indicates...

  1. Electrochemical paper-based peptide nucleic acid biosensor for detecting human papillomavirus

    Energy Technology Data Exchange (ETDEWEB)

    Teengam, Prinjaporn [Program in Petrochemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330 (Thailand); Siangproh, Weena [Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, 10110 (Thailand); Tuantranont, Adisorn [Nanoelectronics and MEMS Laboratory, National Electronics and Computer Technology Center, Pathumthani, 12120 (Thailand); Henry, Charles S. [Department of Chemistry, Colorado State University, Fort Collins, CO, 80523 (United States); Vilaivan, Tirayut [Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330 (Thailand); Chailapakul, Orawon, E-mail: corawon@chula.ac.th [Electrochemistry and Optical Spectroscopy Research Unit, Department of Chemistry, Chulalongkorn University, Pathumwan, Bangkok, 10330 (Thailand); Nanotec-CU Center of Excellence on Food and Agriculture, Bangkok, 10330 (Thailand)

    2017-02-01

    A novel paper-based electrochemical biosensor was developed using an anthraquinone-labeled pyrrolidinyl peptide nucleic acid (acpcPNA) probe (AQ-PNA) and graphene-polyaniline (G-PANI) modified electrode to detect human papillomavirus (HPV). An inkjet printing technique was employed to prepare the paper-based G-PANI-modified working electrode. The AQ-PNA probe baring a negatively charged amino acid at the N-terminus was immobilized onto the electrode surface through electrostatic attraction. Electrochemical impedance spectroscopy (EIS) was used to verify the AQ-PNA immobilization. The paper-based electrochemical DNA biosensor was used to detect a synthetic 14-base oligonucleotide target with a sequence corresponding to human papillomavirus (HPV) type 16 DNA by measuring the electrochemical signal response of the AQ label using square-wave voltammetry before and after hybridization. It was determined that the current signal significantly decreased after the addition of target DNA. This phenomenon is explained by the rigidity of PNA-DNA duplexes, which obstructs the accessibility of electron transfer from the AQ label to the electrode surface. Under optimal conditions, the detection limit of HPV type 16 DNA was found to be 2.3 nM with a linear range of 10–200 nM. The performance of this biosensor on real DNA samples was tested with the detection of PCR-amplified DNA samples from the SiHa cell line. The new method employs an inexpensive and disposable device, which easily incinerated after use and is promising for the screening and monitoring of the amount of HPV-DNA type 16 to identify the primary stages of cervical cancer. - Highlights: • A paper-based DNA biosensor using AQ-PNA probe and G-PANI modified electrode was first developed. • This developed DNA biosensor was highly specific over the non-complementary DNA. • This sensor was successfully applied to detect the HPV-DNA type 16 obtained from cancer cell lines. • This sensor is inexpensive and

  2. Detection of human papillomavirus in oral warts using in situ hybridization

    Directory of Open Access Journals (Sweden)

    Suzana Orsini Machado de Sousa

    2008-01-01

    Full Text Available Objective: The human papillomavirus is a group of DNA epitheliotrophic viruses associated with the etiology of benign and malignant oral warts. More than 100 types have been identified and among them, 24 have been found into the oral cavity. The aim of this study was to analyze human papillomavirus prevalence and its subtypes in 50 oral warts, of which 20 were squamous papillomas, 17 condylomaacuminatum and 13 verruca vulgaris. Method: In situ hybridization was used with biotinylated DNA probes for wide-spectrum HPV and with specific probes for human papillomavirus 6/11, human papillomavirus 16/18 and human papillomavirus 31/33. Results: Human papillomavirus was present in ten (20% of the 50 oral wart cases, 03 (3/20 squamous papillomas, 05 (5/17 condyloma acuminatum and 02 (2/13 verruca vulgaris. Of these, 8 (16% were positive to the HPV probe 6/11 being 5 condyloma acuminatum, 1 squamous papilloma and 2 verruca vulgaris. Three cases (6% demonstrated positivity to the human papillomavirus probe 16/18, with 2 being cases of condyloma and the other a case of squamous papilloma. Of the six positive cases to the human papillomavirus probe 31/33, (12% 4 were condyloma acuminatum and 2 squamous papillomas. Conclusion: The human papillomavirus expression (20% found in this study was low, but within the average found in the literature. Nonetheless, in addition to in situ hybridization, other methods may be necessary for confirming the presence of human papillomavirus.

  3. Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Woodworth, C.D.; Doniger, J.; DiPaolo, J.A.

    1989-01-01

    Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

  4. The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review.

    Science.gov (United States)

    Coles, Victoria A H; Patel, Ajay S; Allen, Felicity L; Keeping, Sam T; Carroll, Stuart M

    2015-10-01

    Since the 2008 introduction of the human papillomavirus (HPV) vaccination programme for adolescent girls in the UK, parents and other groups have expressed fears that immunisation condones sexual activity, promotes promiscuity and encourages risky sexual behaviour. This study aimed to explore whether HPV vaccination programmes have increased knowledge surrounding HPV and associated disease and whether uptake has influenced sexual behaviour. MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases were interrogated. Studies of behaviour, attitudes and knowledge associated with HPV vaccination (or vaccination intent) in subjects of any age and gender in programmes reflective of UK practice were included in the review (n = 58). The evidence regarding the association of HPV vaccination with high-risk sexual behaviour was varied, primarily due to the heterogeneous nature of the included studies. Young females typically exhibited better knowledge than males, and vaccinated respondents (or those with vaccination intent) had higher levels of knowledge than the unvaccinated. However, knowledge surrounding HPV and genital warts was generally poor. This review highlights the need to provide effective education regarding the HPV vaccine and HPV-associated disease to adolescents of vaccination age, nurses, teachers, parents and guardians to ultimately allow informed decisions to be made regarding receipt of the HPV vaccine. © The Author(s) 2015.

  5. Papillomavirus genomes in human cervical carcinoma: Analysis of their integration and transcriptional activity

    International Nuclear Information System (INIS)

    Matulic, M.; Soric, J.

    1994-01-01

    Eighty-four biopsies derived from cervical tissues were analyzed for the presence of human papillomavirus (HPV) DNA types 6, 16 and 18 using Southern blot hybridization. HPV 6 was found in none of the cervical biopsies, and HPV types 16 and 18 were found in 44% of them. The rate of HPV 16/18 positive samples increased proportionally to the severity of the lesion. In normal tissue there were no positive samples, in mild and moderate dysplasia HPV 16/18 was present in 20% and in severe dysplasia and invasive carcinomas in 37 and 50%, respectively. In biopsies from 13 cases with squamous cell carcinoma of the uterine cervix and CIN III lesions HPV 16 was integrated within the host genome. It was concluded that the virus could be integrated at variable, presumably randomly selected chromosomal loci and with different number of copies. Transcription of HPV 16 and 18 was detected in one cervical cancer in HeLa cells, respectively. These results imply that HPV types 16 and 18 play an etiological role in the carcinogenesis of human cervical epithelial cells. (author)

  6. The human papillomavirus immunisation programme and sexual behaviour

    OpenAIRE

    Forster, A. S.

    2011-01-01

    The introduction of human papillomavirus (HPV) vaccination has caused some parents to report concern that their daughters may change their sexual behaviour following vaccination. This concern consistently relates to vaccination acceptance, but had not been investigated in detail. Accordingly, five studies addressed the thesis objective: to explore parents’ concern about adolescent sexual behaviour following HPV vaccination in the context of the UK immunisation programme and to ...

  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. Knowledge, attitudes and practices about human papillomavirus in educated adolescents

    OpenAIRE

    Castro Reyes Elkin Mauricio; Miranda Machado Pablo Andrés; Borre Arrieta Orlando

    2012-01-01

    Introduction: cervical cancer (CC) is the second most frequent cancer in women in theworld, South America and Colombia. It represents the fourth cause of death by cancerin the world, the third cause in South America and the first cause in Colombia. The interesanprincipalrisk factor is the persistent infection with the Human Papillomavirus (HPV). TheCC can be prevented and the patient can be treated if it is detected early.Objective: to establish the knowledge, attitudes and practices about Hu...

  9. Knowledge and attitudes about human papillomavirus and vaccination

    OpenAIRE

    Silva, Priscila Mendonça Carneiro da; Silva, Izabele Maria Barbosa; Interaminense, Iris Nayara da Conceição Souza; Linhares, Francisca Márcia Pereira; Serrano, Solange Queiroga; Pontes, Cleide Maria

    2018-01-01

    Abstract Objective: Uncover knowledge and attitudes of girls, mothers, teachers and health professionals about human papillomavirus and vaccination. Method: A qualitative study carried out by means of focus groups in public elementary schools and health units of Sanitary District IV from Recife-PE, Brazil, between June and July 2015. The sample was six schoolchildren, ten adolescents, nine mothers, ten teachers, thirteen health professionals and seven community health agents. Speeches were ...

  10. Transmissioon of and infektion with human papillomavirus in the oropharynx

    DEFF Research Database (Denmark)

    Bohr, Anne; Grønhøj, Christian; Lajer, Christel

    2017-01-01

    The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is rising in the Western world, but little is known about transmission of the infection and the premalignant phase of the disease. In this article there is an overview of current knowledge with focus on transmission of HP...... and risk factors which may lead to persistent infection and eventually cancer. Furthermore, there is a discussion about issues concerning the ability to measure and detect infection and the premalignant stadium in the oropharyngeal tissue....

  11. Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

    Science.gov (United States)

    Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

    2017-08-01

    Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

  12. [Esophageal papilloma: case report, molecular identification of human papillomavirus and literature review].

    Science.gov (United States)

    Barbaglia, Yanina; Jiménez, Félix; Tedeschi, Fabián; Zalazar, Fabián

    2013-09-01

    sophageal squamous papilloma is an uncommon, usually asymptomatic, benign tumor of the squamous epithelium consisting of a raised, sessile, small and round (smooth or rough) lesion. The prevalence is between 0.01 and 0.45% of cases, with a male/female ratio of 3:1. The etiology and pathogenesis appear to be a mechanical or chemical irritation of the mucosa in addition to the presence of human papillomavirus (HPV), important agent in the evolution to a squamous carcinoma, especially HPV types 16 and 18. In this paper, we describe a case of esophageal papilloma whose diagnosis involved endoscopic images, pathological studies and detection of viral DNA by polymerase chain reaction. By using molecular techniques (PCR-RFLP) a profile consistent with HPV type 16 has been obtained. The patient underwent polypectomy and currently, after 3 years of diagnosis, he remains asymptomatic. This work is one of the first national reports of a patient with esophageal papilloma in which one of the most frequently HPV genotypes associated with esophageal carcinoma (HPV 16) has been detected.

  13. Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Natalie Kash

    2015-04-01

    Full Text Available Since the discovery of the causal association between human papillomavirus (HPV and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18 responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11 which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease.

  14. Host control of human papillomavirus infection and disease.

    Science.gov (United States)

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  15. Prevalence and relationship of human papilloma virus type 16 and type 18 with oral squamous cell carcinoma and oral leukoplakia in fresh scrappings: a PCR study.

    Science.gov (United States)

    Mathew, Asok; Mody, R N; Patait, Mahendra R; Razooki, Ali A; Varghese, Nisha T; Saraf, Kedar

    2011-05-01

    It has been always an area of diffuse clarity when you study malignancy and its pathogenesis. Recently, it has invited lot of interest among the researchers about the possibility of role of viruses in the initiation of carcinogenesis. Recent advances in the field of molecular biology and biotechnology have solved some problems with regard to pathogenesis. Human papilloma virus (HPV) and its role in the initiation of malignancy in the cervix is proven almost beyond doubt. The present study is aimed at the role of two types of HPV 16 and 18 in the initiation of oral premalignant and squamous cell carcinoma. The study also aims at using polymerase chain reaction (PCR) in finding out the prevalence of these types diagnosed histologically as oral leukoplakia and oral squamous cell carcinoma and prevalence of its association with the habit of tobacco use. In the present study, 45 patients having histopathologically confirmed oral squamous cell carcinoma in the age range of 32-85 years were selected along with 20 histopathologically confirmed oral leukoplakia in the age range 22-66 years. All the samples were subjected to polymerase chain reaction. The PCR reaction was carried out in PTC 200 thermo-cycler [MJ Research Inc, Watertown, MA, USA]. The site prevalence and co-infection rate of these two types of viruses are being analyzed using very simple non-invasive scrapings obtained from fresh scrapings and found to be really high. It was also observed that 73.3% (33/45) of the oral squamous cell carcinoma patients were positive for oral HPV type 16 while 71.1% (32/45) were positive for HPV type 18 infection and 57.7% (26/45) were found to have both HPV type 16 and HPV type 18 infections. HPV type 16, 18, and co-infection of both types showed high prevalence in oral squamous cell carcinoma.The prevalence of HPV type 18 was found to be higher than HPV type 16 and co-infection in oral leukoplakia. It was observed that the tongue and palate lesions in the oral squamous cell

  16. Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

    Directory of Open Access Journals (Sweden)

    Arnouk Hilal

    2009-08-01

    Full Text Available Abstract Background Infection with high-risk type human papilloma viruses (HPVs is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. Results Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE. The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23% of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2% were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1; and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27. Conclusion This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.

  17. Human papillomavirus vaccine and cervical cancer prevention: practice and policy implications for pharmacists.

    Science.gov (United States)

    McIntosh, Jennifer; Sturpe, Deborah A; Khanna, Niharika

    2008-01-01

    To review the epidemiology and natural history of human papillomavirus (HPV), summarize relevant clinical trials of the prophylactic HPV vaccines, and describe the practice and policy implications that HPV vaccine represents for pharmacists. Search of Medline through June 2007 using keywords human papillomavirus vaccine, Gardasil, and Cervarix; meeting abstracts; bibliographies from selected articles; and National Institutes of Health clinical trials registry. English language review articles, clinical trials, and published abstracts were considered for inclusion. HPV is a sexually transmitted infection that is necessary for the development of cervical cancer, and types 16 and 18 are associated with 70% of cases of invasive cervical cancer worldwide. A quadrivalent prophylactic vaccine against HPV-6, -11, -16, and -18 is currently available, and a bivalent vaccine targeting HPV-16 and -18 is under review by the Food and Drug Administration. Both are highly effective at preventing persistent HPV infection and precancerous lesions caused by vaccine-specific HPV. HPV vaccine is currently indicated for girls aged 9 to 26 years, but ongoing trials are evaluating the efficacy in other populations. Implementation of a vaccine administration program is an area of opportunity for new policies to include pharmacists in the administration of prophylactic HPV vaccines. Pharmacists are allowed to administer vaccinations in 46 states and can potentially play a role in HPV vaccine administration. For this to happen, however, multiple legal and regulatory changes must occur. Prophylactic HPV vaccines safely and effectively prevent HPV infection and precancerous lesions in the cervix. The availability of these vaccines also create new clinical opportunities for community pharmacists, provided needed legal, regulatory, and policy changes are made.

  18. Human papillomavirus testing and genotyping in cervical screening

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Lynge, Elsebeth; Bonde, Jesper

    2011-01-01

    the incidence of cervical cancer, but has a low sensitivity for high-grade cervical intraepithelial neoplasia (CIN) and requires frequent testing. Several HPV tests have become available commercially. They appear to be more sensitive for high-grade CIN, and may further reduce the incidence of cervical cancer......Mass vaccination against human papillomavirus (HPV) genotypes 16 and 18 will, in the long term, reduce the incidence of cervical cancer, but screening will remain an important cancer control measure in both vaccinated and unvaccinated women. Since the 1960s, cytology screening has helped to reduce...

  19. Vaccines for human papillomavirus infection: A critical analysis

    Directory of Open Access Journals (Sweden)

    Nath Amiya

    2009-01-01

    Full Text Available This article takes a critical look at the pros and cons of human papillomavirus (HPV vaccines. There is enough evidence to suggest that the prophylactic vaccines are efficacious in preventing various benign and malignant conditions (including cervical cancers caused by HPV. Even though the vaccine is costly, hypothetical analysis has shown that HPV vaccination will be cost effective in the long run. Therapeutic HPV vaccines used to treat established disease are still undergoing evaluation in clinical studies, and results seem to be encouraging. Although several countries have started mandatory vaccination programs with the prophylactic HPV vaccines, conservatives have voiced concerns regarding the moral impact of such vaccination programs.

  20. Human papillomavirus in the oral cavity of children.

    Science.gov (United States)

    Pinheiro, Raquel dos Santos; de França, Talita Ribeiro Tenório; Ferreira, Dennis de Carvalho; Ribeiro, Camila Maria Beder; Leão, Jair Carneiro; Castro, Gloria Fernanda

    2011-02-01

    The aim of this literature review was to identify studies conducted on the oral Human papillomavirus (HPV) infection in children. An electronic database search was performed using the terms 'oral HPV' and 'children'. The studies on the prevalence of oral HPV in children worldwide, descriptive studies, case reports, studies on the association of oral HPV and risk factors and transmission of HPV were included. The presence of HPV in oral mucosa of children should be investigated in virtue of the various forms of transmission, and the possibility of sexual abuse eliminated, and also of its possible relation with oral carcinoma pathogenesis in children. © 2010 John Wiley & Sons A/S.

  1. Overview of the Global Vaccination against Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Leyla S. Namazova-Baranova

    2018-01-01

    Full Text Available The article presents an overview of the current status of the vaccination against Human Papillomavirus (HPV in the world. It describes different approaches to expanding the coverage with HPV vaccination at different national levels by inclusion of the vaccine in National Immunization Programmes. Moreover, the principal ways of project financing in different regions of the world are referred to. The results of the implemented vaccination against HPV in the pioneer countries provide the conclusions on the current situation of HPV vaccination in the world and strategies demonstrating its effectiveness.

  2. Perception, acceptance and uptake of Human papillomavirus ...

    African Journals Online (AJOL)

    Parental approval and readiness for HPV vaccine uptake were found to be significantly associated (p =0.000). Since knowledge about Human Papilloma Virus Vaccination is quite low, there is need to increase awareness about the Vaccination among female adolescents and their mothers. Also, peer educators in schools ...

  3. [High oncogenic risk human papillomavirus and urinary bladder cancer].

    Science.gov (United States)

    Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N

    2017-07-01

    To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.

  4. 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.

  5. Human papillomavirus type 45 propagation, infection, and neutralization

    International Nuclear Information System (INIS)

    McLaughlin-Drubin, Margaret E.; Wilson, Susan; Mullikin, Brian; Suzich, JoAnn; Meyers, Craig

    2003-01-01

    The organotypic (raft) culture system has allowed the study of the entire differentiation-dependent life cycle of human papillomaviruses (HPVs), including virion morphogenesis. We introduced linearized HPV45 genomic DNA into primary keratinocytes, where it recircularized and maintained episomally at a range of 10-50 copies of HPV genomic DNA. Following epithelial stratification and differentiation in organotypic culture, virion morphogenesis occurred. HPV45 virions were purified from raft cultures and were able to infect keratinocytes in vitro. By testing a panel of HPV VLP antisera, we were able to demonstrate that the infection was neutralized not only with human HPV45 VLP-specific antiserum, but also with human HPV18 VLP-specific antiserum, demonstrating serological cross-reactivity between HPV18 and HPV45

  6. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants

    Directory of Open Access Journals (Sweden)

    Bedia Dinc

    Full Text Available OBJECTIVE: Human cytomegalovirus (CMV is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2 and human papillomavirus (HPV are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. METHODS: One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8 applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8 were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. RESULTS: Three patients (3/134; 2.2% were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %. CONCLUSION: HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  7. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants.

    Science.gov (United States)

    Dinc, Bedia; Bozdayi, Gulendam; Biri, Aydan; Kalkanci, Ayse; Dogan, Bora; Bozkurt, Nuray; Rota, Seyyal

    2010-01-01

    Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8) applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8) were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. Three patients (3/134; 2.2%) were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %). HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  8. Evasion of host immune defenses by human papillomavirus.

    Science.gov (United States)

    Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun

    2017-03-02

    A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Human papillomavirus cervical infection in Guarani Indians from the rainforest of Misiones, Argentina.

    Science.gov (United States)

    Tonon, Sergio Andrés; Picconi, María Alejandra; Zinovich, Jorge Bruno; Nardari, Wanda; Mampaey, Mariana; Badano, Inés; Di Lello, Federico; Galuppo, Juan Antonio; Alonio, Lidia Virginia; Teyssie, Angélica Rita

    2004-01-01

    To evaluate the prevalence of human papillomavirus (HPV) cervical infection in women from the South American Guarani Indian tribe located in the rain forest of Misiones, north-eastern Argentina; a region with a high incidence of cervical carcinoma. A cross-sectional cytological and HPV screening of sexually active Guarani women from nine Indian settlements was conducted. Demographic data, information about sexual behavior, and gynaecological history were recorded. Fresh cervical specimens from 239 patients were collected, of which 207 were included in this study. Cytology and microbiological detection were carried out by the Papanicolaou and Gram stain methods, respectively. HPV detection and typing were analyzed by PCR and RFLP. Pap smears in 96% of all patients showed an inflammatory pattern. A possible etiologic agent was found in 58% of cases: 52% Trichomonas vaginalis, 35% Gardnerella vaginalis and 13% Candida sp. Seven cases had cytological changes compatible with Low Grade Intraepithelial Lesion (LGSIL), one with High Grade Intraepithelial Lesion (HGSIL) and one in situ cervical cancer. The prevalence for generic HPV infection was 64% (133/207). Genotyping gave a 26% prevalence for HPV types 16/18, 13% for types 6/11 and 30% for other types, with nine mixed infections. This work reports for the first time the prevalence of cervical HPV infection in Guarani women. Nearly all Guarani women had some grade of cervical disease. Generic HPV infection prevalence was elevated (64%), with predominance of high risk types 16/18. A large variety of viral types was detected, including high to intermediate risk types not found previously in the region.

  10. Clinicopathological aspects and prevalence of human papillomavirus in anal cancer

    Directory of Open Access Journals (Sweden)

    Marina Tayla Mesquita Aguiar

    2014-04-01

    Full Text Available Anal cancer is relatively rare; however, its incidence has increased in recent years. Several risk factors are associated with the development of anal cancer, including age older than 50 years, low-fiber diet, chronic anal fistulas, smoking, multiple partners, anal intercourse practice, Human Immunodeficiency Virus infection and immunosuppression. However, the presence of human papillomavirus represents the main risk factor for the development of anal cancer. The aim of this study was to evaluate the clinicopathological aspects of a series of patients with anal carcinomas diagnosed in Hospital Araújo Jorge, Goiânia-Goiás, as well as the prevalence of human papillomavirus genome in these tumors. Clinical, pathological and socio-demographic data were collected from the respective medical files and paraffin blocks containing anal carcinomas specimens were used for DNA extraction and detection of human papillomavirus, by means of polymerase chain reaction, using short PCR fragment primers. Forty-three cases were selected and had the data analyzed, while 38 cases were tested for human papillomavirus genome detection. Among the evaluated patients, 62.8% were women; 53.4% of tumors were squamous cell carcinoma and 46.5% of the patients were aged between 60 and 75 years. Risk factors, such as smoking (39.5% and alcoholism (20.9% were recorded in the studied group. Lymph node metastases were detected in 30.2% of cases and 7.0% had distant metastasis. The detection of human papillomavirus DNA was positive in 76% of cases assessed and this was significantly associated with squamous cell carcinomas. Aggressive behavior and advanced stage of anal cancer described in this study highlight the need for preventive measures that contemplate these tumors, including vaccination against human papillomavirus. Resumo: O câncer anal é relativamente raro, entretanto, sua incidência aumentou nos últimos anos. Vários fatores de risco são associados ao

  11. Multiplex polymerase chain reaction for the detection of high-risk-human papillomavirus types in formalin-fixed paraffin-embedded cervical tissues

    Directory of Open Access Journals (Sweden)

    Mini P Singh

    2017-01-01

    Full Text Available Detecting high-risk-human papillomavirus (HPV types has become an integral part of the cervical cancer screening programmes. This study aimed to develop a multiplex polymerase chain reaction (PCR for identification of HPV types 16 and 18 along with the beta globin gene in formalin-fixed and paraffin-embedded cervical biopsy specimens. A total of 59 samples from patients with cervical abnormalities were tested. HPV 16 positivity was 50% in cervical cancers and 52.9% in cervical intraepithelial neoplasia. Our multiplex PCR protocol can be used as a simple and cost-effective tool for high-risk-HPV detection in cervical cancer screening programmes.

  12. Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia

    DEFF Research Database (Denmark)

    Nygard, Mari; Hansen, Bo Terning; Dillner, Joakim

    2014-01-01

    BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination...... with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order...... to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias...

  13. CO2 laser vaporization in the treatment of cervical human papillomavirus infection in women with abnormal Papanicolaou smears

    DEFF Research Database (Denmark)

    Ruge, S; Felding, C; Skouby, S O

    1992-01-01

    In a randomized study, we have evaluated the treatment of cervical human papillomavirus (HPV) lesions by CO2 laser vaporization. Fifty patients with abnormal Papanicolaou smears and histological evidence of cervical HPV infection associated or not with cervical intraepithelial neoplasia (CIN) grade...... I were randomized to either a treatment or a control group. The cervical swabs were obtained every 3 months in both groups and examined for HPV type 16 DNA by the polymerase chain reaction. After a follow-up period of 12 months no significant differences were found between the laser treatment...... in their cervical smears at 12 months' follow-up was identical in the two groups, supporting the hypothesis that HPV is a persistent infection during which the virus is widespread in the vaginal epithelium....

  14. Cancer registries and monitoring the impact of prophylactic human papillomavirus vaccines: the potential role.

    Science.gov (United States)

    Saraiya, Mona; Goodman, Marc T; Datta, S Deblina; Chen, Vivien W; Wingo, Phyllis A

    2008-11-15

    The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic endpoints, namely, anogenital cancers and some oral cavity/oropharyngeal cancers. There also has been some data collection on cancer precursors; however, this activity has been inconsistent and of lower priority. Because effectiveness against HPV-associated cancers will not be measurable for several decades, strengthening and possibly expanding the capacity of registries to collect precancer data, which are earlier manifestations of infection, must be considered. Collecting type-specific data on HPV-associated precancers and cancers. While keeping in mind the current limitations of registry operations, they discuss resources that may be needed to implement and sustain these types of activities.

  15. Human papillomavirus infection among women attending health facilities in the Kingdom of Bahrain

    International Nuclear Information System (INIS)

    Hajjaj, Aida A.; Senok, Abiola C.; Al-Mahmeed, Ali E.; Botta, Giuseppe A.; Issa, Abdulla A.; Arzes, Alessandra

    2006-01-01

    To investigate the occurrence of human papillomavirus (HPV) infection and the associated risk factors in Bahrain's female population. This study was carried out between March to December 2004, which includes cervical scrapings for Pap smear and HPV-DNA testing using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis, obtained from 100 women attending the Gynecology Clinic at Salmaniya Medical Center and Sheikh Sabah Health Center in the Kingdom of Bahrain. We distributed questionnaires that include the sociodemographic data as well as information on risk factors such as smoking, parity, and the contraceptive used. Eleven women (11%) with normal cytology were HPV-positive. The RFLP analysis detected HPV-types 16, 18, 45, 62 and 53. Positive women were significantly older (43.3+-10.1 years) than negatives (36.5+-9.9 years; p=0.04), however, there was no difference in age of first sexual contact (positive: 18.1+-5.7 years versus negative: 20.6 +- 4.4 years). Polygamy, smoking and hormonal contraception was not identified as risk factors, but positive women showed higher parity. In this study on HPV infection in Behrain, the 11% positivity with high risk HPV types, in the presence of normal cytology suggests that in addition to the cervical cancer screening program, offer of HPV testing deserves consideration. (author)

  16. The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

    Science.gov (United States)

    Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise

    2016-08-31

    Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

  17. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Science.gov (United States)

    van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186

  18. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

    Science.gov (United States)

    Posner, M R; Lorch, J H; Goloubeva, O; Tan, M; Schumaker, L M; Sarlis, N J; Haddad, R I; Cullen, K J

    2011-05-01

    The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

  19. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Directory of Open Access Journals (Sweden)

    Stephanie van de Wall

    2015-03-01

    Full Text Available The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV targeting human papillomavirus (HPV. Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7 via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

  20. Immune evasion mechanisms of human papillomavirus: An update.

    Science.gov (United States)

    Steinbach, Alina; Riemer, Angelika B

    2018-01-15

    Human papillomavirus (HPV) is the most frequently sexually transmitted agent in the world. It can cause cervical and other anogenital malignancies, and oropharyngeal cancer. HPV has the unique ability to persist in the host's epithelium for a long time-longer than most viruses do-which is necessary to complete its replication cycle. To this end, HPV has developed a variety of immune evasion mechanisms, which unfortunately also favor the progression of the disease from infection to chronic dysplasia and eventually to cancer. This article summarizes the current knowledge about HPV immune evasion strategies. A special emphasis lies in HPV-mediated changes of the antigen processing machinery, which is generating epitopes for T cells and contributes to the detectability of infected cells. © 2017 UICC.

  1. Young Hispanic Men and Human Papillomavirus Vaccination Choices.

    Science.gov (United States)

    Thomas, Tami L; Stephens, Dionne P; Johnson-Mallard, Versie; Higgins, Melinda

    2016-03-01

    This exploratory descriptive study examined perceived vulnerabilities to human papillomavirus (HPV) and the correlation to factors influencing vaccine beliefs and vaccine decision making in young Hispanic males attending a large public urban university. Only 24% of participants believed that the HPV vaccine could prevent future problems, and 53% said they would not be vaccinated. The best predictors of HPV vaccination in young Hispanic men were agreement with doctor recommendations and belief in the vaccine's efficacy. Machismo cultural norms influence young Hispanic men's HPV-related decision making, their perceptions of the vaccine, and how they attitudinally act on what little HPV information they have access to. This study provides culturally relevant information for the development of targeted health education strategies aimed at increasing HPV vaccination in young Hispanic men. © The Author(s) 2014.

  2. Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

    DEFF Research Database (Denmark)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia

    2007-01-01

    PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....

  3. Social representations of human papillomavirus in Bogotá, Colombia.

    Science.gov (United States)

    Wiesner, Carolina; Acosta, Jesús; Díaz Del Castillo, Adriana; Tovar, Sandra

    2012-01-01

    Identifying DNA of Human papillomavirus (HPV) has been proposed as a new screening method for cervical cancer control. Conventionally, health education for screening programs is based on scientific information without considering any community cognitive processes. We examine HPV social representations of 124 men and women from diverse educational status living in Bogotá, Colombia. The social representation of HPV involves a series of figurative nuclei derived from meanings linked to scientific information. While women focused on symbols associated to contagion, men focused on its venereal character. Figurative nuclei also included long-term uncertainty, need or urgent treatment, and feelings of imminent death associated with cancer and chronic sexually transmitted infections. The social representation of HPV impeded many participants from clearly understanding written information about HPV transmission, clearance, and cancer risk; they are built into a framework of values, which must be deconstructed to allow women full participation in HPV screening programs.

  4. The Spanish human papillomavirus vaccine consensus group: a working model.

    Science.gov (United States)

    Cortés-Bordoy, Javier; Martinón-Torres, Federico

    2010-08-01

    Successful implementation of Human Papillomavirus (HPV) vaccine in each country can only be achieved from a complementary and synergistic perspective, integrating all the different points of view of the diverse related professionals. It is this context where the Spanish HPV Vaccine Consensus Group (Grupo Español de Consenso sobre la Vacuna VPH, GEC-VPH) was created. GEC-VPH philosophy, objectives and experience are reported in this article, with particular attention to the management of negative publicity and anti-vaccine groups. Initiatives as GEC-VPH--adapted to each country's particular idiosyncrasies--might help to overcome the existing barriers and to achieve wide and early implementation of HPV vaccination.

  5. Health awareness among young women vaccinated against human papillomavirus infections

    Directory of Open Access Journals (Sweden)

    Beata Bąk

    2014-04-01

    Full Text Available Introduction : Genital human papillomavirus (HPV infections are essentials factors in the development of cervical cancer. Human papillomavirus vaccines can contribute to reducing the high incidence of this disease, provided that this form of prophylaxis is commonly accepted. Participation in vaccinations is restricted by the belief that their implementation and consequent feeling of safety will reduce women’s participation in other forms of cervical carcinoma prophylaxis and will encourage them to be sexually promiscuous. Aim of the research study : To determine the awareness of cervical carcinoma prophylaxis among young women vaccinated against HPV by comparing them with a group of unvaccinated women. Material and methods: The survey covered a group of 210 young women in the age range 18 to 20 years, who were vaccinated against HPV. Within the framework of comparison, the survey covered a group of 255 young HPV-unvaccinated women, adequately selected in respect of age and education. Results: The HPVvaccinated women declared participation in medical check-ups and cytological tests no less frequently than the unvaccinated women. In both groups, the usage of condoms, sexual partners hygiene, monogamy and smoking abstinence were determined as behaviours limiting the occurrence of cervical carcinoma. Conclusions: Awareness of the application of supplementary prophylaxis of cervical carcinoma was high among the HPV vaccinated woman and did not differ from the unvaccinated woman’s awareness. Young women did not show a tendency for promiscuous behaviours, and were more likely touse condoms in the prevention of cervical carcinoma than were the unvaccinated woman.

  6. 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® ...

  7. 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® ...

  8. Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta-analysis of observational studies

    DEFF Research Database (Denmark)

    Svahn, Malene F; Faber, Mette Tuxen; Christensen, Jane

    2014-01-01

    The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue....

  9. Laboratory production in vivo of infectious human papillomavirus type 11

    International Nuclear Information System (INIS)

    Kreider, J.W.; Howett, M.K.; Leure-Dupree, A.E.; Zaino, R.J.; Weber, J.A.

    1987-01-01

    Human papillomaviruses (HPV) induce among patients natural lesions which produce small amounts of virus. Infection of human cell cultures does not lead to the multiplication of virus, which also does not replicate in experimental animals. The authors have developed a unique system for the laboratory production of HPV type 11 (HPV-11). Fragments of human neonatal foreskin were infected with an extract of naturally occurring human vulvar condylomata and grafted beneath the renal capsule of athymic mice. Later (3 to 5 months), condylomatous cysts developed from those grafts. Nuclei of koilocytotic cells contained large amounts of capsid antigen and intranuclear virions. The experimentally induced condylomata were homogenized, and the virions were extracted and used to infect another generation of human foreskin grafts in athymic mice. The HPV-11 DNA content and infectivity of the natural and experimental condylomata were similar. Extracts of experimental condylomata were subjected to differential ultracentrifugation and sedimentation in CsCl density gradients. A single, opalescent band was visible at a density of 1.34 g/ml. It contained HPV virions with HPV-11 DNA. This report is the first demonstration of the laboratory production of an HPV

  10. History of human papillomavirus, warts and cancer: what do we know today?

    Science.gov (United States)

    Onon, Toli S

    2011-10-01

    Human papillomavirus has been a cause of infection in humans for thousands of years. The history of papillomaviruses, knowledge of their causative role in benign and malignant disease, and their structural characteristics have led to the development of vaccines to prevent cervical and anogenital cancers. Many questions remain unanswered before HPV vaccines can be optimised; however, the concept of virtual eradication of cervical cancer is not impossible, and remains a realistic aspiration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Human papillomavirus and tumours of the eye region

    DEFF Research Database (Denmark)

    Sjö, Nicolai Christian

    2005-01-01

    ophthalmology, lacrimal sac, tear sac, papilloma, carcinoma, papillomavirus, HPV, polymerase chain reaction, PCR, RNA, DNA, in situ hybridisation, aetiology, conjunctiva, dysplasia, sex, age, distribution......ophthalmology, lacrimal sac, tear sac, papilloma, carcinoma, papillomavirus, HPV, polymerase chain reaction, PCR, RNA, DNA, in situ hybridisation, aetiology, conjunctiva, dysplasia, sex, age, distribution...

  12. Human Papillomavirus Infection Among 2460 Men in Denmark: Prevalence in Relation to Age Using 2 Human Papillomavirus DNA Testing Methods.

    Science.gov (United States)

    Hebnes, Julie Buchholt; Munk, Christian; Nøhr, Bugge; Nielsen, Ann; Jørgensen, Hans Ole; Iftner, Thomas; Kjaer, Susanne Krüger

    2015-08-01

    It is crucial to understand the epidemiology and natural history of human papillomavirus (HPV) infection in both men and women, to prevent the increasing HPV-related disease burden in men. Data on HPV prevalence among men in the general population are limited. In this cross-sectional population-based study, we aimed to estimate genital HPV infection prevalence in Danish men using 2 different test methods. Penile swab samples from 2460 male employees and conscripts at military barracks in Denmark were tested for HPV DNA with the hybrid capture 2 (HC2) method, and a polymerase chain reaction (PCR) assay, Inno-LiPA. The overall and age- and type-specific prevalence of HPV infection with 95% confidence intervals (CIs) were estimated, and the correlation between the 2 assays was assessed. The overall HPV prevalence was 22.2% (95% CI, 20.6-23.9) in the HC2 test and 41.8% (95% CI, 39.9-43.8) with PCR. Of the PCR-positive samples, 50.9% were negative in the HC2 test. Of 183 PCR-positive samples that could not be genotyped (HPVX), 88.0% (95% CI, 83.2-92.7) were HC2 negative. The most prevalent types were HPV-51, HPV-16, HPV-66, HPV-53, and HPV-6. The prevalence of high-risk and low-risk HPV peaked among men aged 20 to 29 years, whereas the HPVX prevalence increased with age. Human papillomavirus is highly prevalent in the general male population of Denmark, with HPV-16 and HPV-51 being the most prevalent. Polymerase chain reaction detects twice as many positive samples as HC2 but includes HPVX, possibly representing cutaneous HPV types found on normal genital skin.

  13. The anti-papillomavirus activity of human and bovine lactoferricin.

    Science.gov (United States)

    Mistry, Nitesh; Drobni, Peter; Näslund, Jonas; Sunkari, Vivekananda Gupta; Jenssen, Håvard; Evander, Magnus

    2007-09-01

    Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.

  14. An association between Trichomonas vaginalis and high-risk human papillomavirus in rural Tanzanian women undergoing cervical cancer screening.

    Science.gov (United States)

    Lazenby, Gweneth B; Taylor, Peyton T; Badman, Barbara S; McHaki, Emil; Korte, Jeffrey E; Soper, David E; Young Pierce, Jennifer

    2014-01-01

    The goal of this study was to determine the prevalence of vaginitis and its association with high-risk human papillomavirus (HR HPV) in women undergoing cervical cancer screening in rural Tanzania. For the purpose of cervical cancer screening, cytology and HR HPV polymerase chain reaction data were collected from 324 women aged between 30 and 60 years. Microscopy and gram stains were used to detect yeast and bacterial vaginosis. Cervical nucleic acid amplification test specimens were collected for the detection of Trichomonas vaginalis (TV), Chlamydia trachomatis, and Neisseria gonorrhoeae. The majority of women were married (320 of 324) and reported having a single sexual partner (270 of 324); the median age of participants was 41 years. HR HPV was detected in 42 participants. Forty-seven percent of women had vaginitis. Bacterial vaginosis was the most common infection (32.4%), followed by TV (10.4%), and yeast (6.8%). In multivariable logistic regression analysis, TV was associated with an increased risk of HR HPV (odds ratio, 4.2 [95% CI, 1.7-10.3]). Patients with TV were 6.5 times more likely to have HPV type 16 than patients negative for TV (50% vs 13.3%) (odds ratio, 6.5 [95% CI, 1.1-37]). Among rural Tanzanian women who presented for cervical cancer screening, Trichomonas vaginitis was significantly associated with HR HPV infection (specifically type 16). © 2014 Published by Elsevier HS Journals, Inc.

  15. Impacts of HIV infection and long-term use of antiretroviral therapy on the prevalence of oral human papilloma virus type 16.

    Science.gov (United States)

    Amornthatree, Korntip; Sriplung, Hutcha; Mitarnun, Winyou; Nittayananta, Wipawee

    2012-04-01

    The objectives of this study were to determine (i) the prevalence and the copy numbers of oral human papilloma virus type 16 (HPV-16) in HIV-infected patients compared with non-HIV controls, and (ii) the effects of antiretroviral therapy (ART) and its duration on the virus. A cross-sectional study was carried out in HIV-infected patients with and without ART and in non-HIV controls. Saliva samples were collected, and the DNA extracted from those samples was used as a template to detect HPV-16 E6 and E7 by quantitative polymerase chain reaction. Student's t-test and ANOVA test were performed to determine the prevalence rates among groups. Forty-nine HIV-infected patients: 37 on ART (age range, 23-54 years; mean, 37 years), 12 not on ART (age range, 20-40 years; mean, 31 years), and 20 non-HIV controls (age range, 19-53 years; mean, 31 years) were enrolled. The prevalence of oral HPV-16 infection and the copy numbers of the virus were significantly higher in HIV-infected patients than in non-HIV controls when using E6 assay (geometric mean = 10696 vs. 563 copies/10(5) cells, P prevalence of oral HPV-16 infection and the copy numbers of the virus (P = 0.567). We conclude that the prevalence of oral HPV-16 infection and the copy numbers of the virus are increased by HIV infection. Neither the use of ART nor its duration significantly affected the virus. © 2011 John Wiley & Sons A/S.

  16. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

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    F. Xavier Bosch

    2007-01-01

    Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

  17. The fanconi anemia pathway limits human papillomavirus replication.

    Science.gov (United States)

    Hoskins, Elizabeth E; Morreale, Richard J; Werner, Stephen P; Higginbotham, Jennifer M; Laimins, Laimonis A; Lambert, Paul F; Brown, Darron R; Gillison, Maura L; Nuovo, Gerard J; Witte, David P; Kim, Mi-Ok; Davies, Stella M; Mehta, Parinda A; Butsch Kovacic, Melinda; Wikenheiser-Brokamp, Kathryn A; Wells, Susanne I

    2012-08-01

    High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population.

  18. Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

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    Siddiqa, Abida; Massimi, Paola; Pim, David; Broniarczyk, Justyna; Banks, Lawrence

    2018-03-15

    Human papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans -Golgi network (TGN) and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation. In addition, we also show a critical requirement for the endoplasmic reticulum (ER)-anchored protein VAP in this process. VAP plays an essential role in actin nucleation and endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic decrease in the level of endosomal tubulation induced by incoming HPV-16 virions. This is also accompanied by a marked reduction in virus infectivity. In VAP knockdown cells, we see that the defect in virus trafficking occurs after capsid disassembly but prior to localization at the trans -Golgi network, with the incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid vesicles. Taken together, these studies demonstrate that infection with HPV-16 virions induces marked alterations of endocytic transport pathways, some of which are VAP dependent and required for the endosome-to-Golgi transport of the incoming viral L2/DNA complex. IMPORTANCE Human papillomavirus infectious entry involves multiple interactions with the endocytic transport machinery. In this study, we show that incoming HPV-16 virions induce a dramatic increase in endocytic tubulation. This tubulation requires ER-associated VAP, which plays a critical role in ensuring the delivery of cargoes from the endocytic compartments to the trans -Golgi network. Indeed, the loss of

  19. A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.

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    Olivia C Demurtas

    Full Text Available The E7 protein of the Human Papillomavirus (HPV type 16, being involved in malignant cellular transformation, represents a key antigen for developing therapeutic vaccines against HPV-related lesions and cancers. Recombinant production of this vaccine antigen in an active form and in compliance with good manufacturing practices (GMP plays a crucial role for developing effective vaccines. E7-based therapeutic vaccines produced in plants have been shown to be active in tumor regression and protection in pre-clinical models. However, some drawbacks of in whole-plant vaccine production encouraged us to explore the production of the E7-based therapeutic vaccine in Chlamydomonas reinhardtii, an organism easy to grow and transform and fully amenable to GMP guidelines.An expression cassette encoding E7GGG, a mutated, attenuated form of the E7 oncoprotein, alone or as a fusion with affinity tags (His6 or FLAG, under the control of the C. reinhardtii chloroplast psbD 5' UTR and the psbA 3' UTR, was introduced into the C. reinhardtii chloroplast genome by homologous recombination. The protein was mostly soluble and reached 0.12% of total soluble proteins. Affinity purification was optimized and performed for both tagged forms. Induction of specific anti-E7 IgGs and E7-specific T-cell proliferation were detected in C57BL/6 mice vaccinated with total Chlamydomonas extract and with affinity-purified protein. High levels of tumor protection were achieved after challenge with a tumor cell line expressing the E7 protein.The C. reinhardtii chloroplast is a suitable expression system for the production of the E7GGG protein, in a soluble, immunogenic form. The production in contained and sterile conditions highlights the potential of microalgae as alternative platforms for the production of vaccines for human uses.

  20. Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 161

    Science.gov (United States)

    Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin

    2009-01-01

    Human papillomavirus (HPV) type 16 infects the epithelial layer of cervical mucosa and is causally associated with the generation of cervical cancer. Langerhans cells (LC) are the resident antigen-presenting cells at the site of infection and therefore are responsible for initiating an immune response against HPV16. On the contrary, LC exposed to HPV16 do not induce a specific T cell immune response, which leads to the immune evasion of HPV16. Demonstrating that Toll-like receptor 7 (TLR7) and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response. Surprisingly both phenotypic and functional hallmarks of activation are not observed when LC are exposed to HPV16 virus-like particles (VLP) and treated with imiquimod (TLR7 agonist). However, we found that LC are activated by 3M-002 (TLR8 agonist) and resiquimod (TLR8/7 agonist). LC exposed to HPV16 VLP and subsequently treated with 3M-002 or resiquimod highly up-regulate surface activation markers, secrete pro-inflammatory cytokines and chemokines, induce CCL21-directed migration, and initiate an HPV16-specific CD8+ T cell response. These data strongly indicate that 3M-002 and resiquimod are promising therapeutics for treatment of HPV-infections and HPV-induced cervical lesions. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third

  1. Risk factors for genital human papillomavirus among men in Tanzania

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Mwaiselage, Julius; Iftner, Thomas

    2017-01-01

    , although not being statistically significant. In conclusion, HIV is a strong risk factor for HPV among men in Tanzania. Additionally, in HIV-positive men a high BMI seems to be associated with a lower risk of HPV. Finally, we observed a tendency toward a lower risk of HPV both among HIV-positive and HIV......The objective of the study was to assess risk factors for Human Papillomavirus (HPV) among men in Tanzania, both overall and in relation to HIV status. In a cross-sectional study conducted among 1,813 men in Tanzania, penile swabs were tested for HPV using Hybrid Capture 2 (HC2). Study participants...... were offered HIV testing. Risk factors for HPV (HC2 high-risk and/or low-risk positivity) were assessed using logistic regression with adjustment for age, lifetime number of sexual partners, and HIV status. Altogether, 372 men (20.5%) were HPV-positive. Among men tested for HIV (n = 1,483), the HIV...

  2. Is Human Papillomavirus Associated with Prostate Cancer Survival?

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    Mariarosa Pascale

    2013-01-01

    Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

  3. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    Science.gov (United States)

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  4. Characteristics of Adolescents Lacking Provider-Recommended Human Papillomavirus Vaccination.

    Science.gov (United States)

    Krakow, Melinda; Beavis, Anna; Cosides, Olivia; Rositch, Anne F

    2017-05-01

    To characterize subgroups of teens in the United States for whom provider recommendation is less likely to impact human papillomavirus (HPV) vaccine initiation. We analyzed provider-verified vaccination data from the Centers for Disease Control and Prevention's 2014 National Immunization Survey-Teen. Poisson regression models identified characteristics associated with the lack of HPV vaccine initiation among teens who received a provider recommendation (n = 12,742). Top qualitative reasons for nonvaccination among teens who received a provider recommendation were summarized (n = 1,688). Among teens with provider recommendations, males, younger teens, and white teens were less likely to initiate vaccination, compared to peers. Believing the vaccine was unnecessary, concerns about safety and lack of vaccine knowledge were common reasons parents did not initiate the vaccine, despite receiving provider recommendations. These key subgroups and barriers to HPV vaccination should be targeted with interventions that complement provider recommendation to achieve broad vaccine uptake in the United States. Published by Elsevier Inc.

  5. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

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    Deirdre Therese Little MBBS, DRANZCOG, FACRRM

    2014-10-01

    Full Text Available Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence.

  6. Interstitial lung disease associated with human papillomavirus vaccination

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    Yasushi Yamamoto

    2015-01-01

    Full Text Available Vaccinations against the human papillomavirus (HPV have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix are said to have favourable safety profiles. Interstitial lung diseases (ILDs can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40's, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

  7. Estimating progression rates for human papillomavirus infection from epidemiological data.

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    Jit, Mark; Gay, Nigel; Soldan, Kate; Hong Choi, Yoon; Edmunds, William John

    2010-01-01

    A Markov model was constructed in order to estimate type-specific rates of cervical lesion progression and regression in women with high-risk human papillomavirus (HPV). The model was fitted to age- and type-specific data regarding the HPV DNA and cytological status of women undergoing cervical screening in a recent screening trial, as well as cervical cancer incidence. It incorporates different assumptions about the way lesions regress, the accuracy of cytological screening, the specificity of HPV DNA testing, and the age-specific prevalence of HPV infection. Combinations of assumptions generate 162 scenarios for squamous cell carcinomas and 54 scenarios for adenocarcinomas. Simulating an unscreened cohort of women infected with high-risk HPV indicates that the probability of an infection continuing to persist and to develop into invasive cancer depends on the length of time it has already persisted. The scenarios and parameter sets that produce the best fit to available epidemiological data provide a basis for modeling the natural history of HPV infection and disease.

  8. Human Papillomaviruses and genital co-infections in gynaecological outpatients

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    Nicosia Rosa

    2009-02-01

    Full Text Available Abstract Background High grade HPV infections and persistence are the strongest risk factors for cervical cancer. Nevertheless other genital microorganisms may be involved in the progression of HPV associated lesions. Methods Cervical samples were collected to search for human Papillomavirus (HPV, bacteria and yeast infections in gynaecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification (SDA and the other microorganisms were detected by conventional methods. Results In this cross-sectional study on 857 enrolled outpatients, statistical analyses revealed a significant association of HPV with C. trachomatis and Ureaplasma urealyticum (at high density detection, whereas no correlation was found between HPV infection and bacterial vaginosis, Streptococcus agalactiae, yeasts, Trichomonas vaginalis and U. urealyticum. Mycoplasma hominis was isolated only in a few cases both in HPV positive and negative women and no patient was infected with Neisseria gonorrhoeae. Conclusion Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. A significant association between HPV and C. trachomatis was found and interestingly also with U. urealyticum but only at a high colonization rate. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects.

  9. Long-term Study of a Quadrivalent Human Papillomavirus Vaccine

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    Ferris, Daron; Samakoses, Rudiwilai; Block, Stan L

    2014-01-01

    BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6...... objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6....../11/16/18-related disease or persistent infection of ≥12 months' duration. Acquisition of new sexual partners (among those ≥16 years) was ∼1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to ≥1 of the 4 HPV types to those vaccinated at day 1...

  10. Challenging 'girls only' publicly funded human papillomavirus vaccination programmes.

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    Law, Victoria G; Gustafson, Diana L

    2017-01-01

    This analysis examines the 'girls only' policy for publicly funded human papillomavirus (HPV) vaccination programmes. Current funding policy in most Canadian provinces covers 'girls only' with the goal of reducing mortality and morbidity rates of HPV-related cervical cancer. Recent studies indicate increasing rates of other HPV-related cancers among cisgender men and women. The HPV vaccine is proving effective against some of these cancers. Statistics on HPV vaccine uptake among individuals with different gender expressions are scarce. Critics argue that a 'girls only' HPV vaccine policy is inequitable. We add to this critique by reflecting on the gender binary embedded in such policies and produced through epidemiological studies that attend differentially to females, reinforcing exclusionary practices that leave out those who form their gender identities across the spectrum. We then draw on deontological (duties-based) and utilitarian (utility-based) frameworks to show that these gendered policies are also unethical. These challenges to the assumptions underlying 'girls only' immunization programmes have implications for nurses and the healthcare system. If we are to advance equitable and ethical health outcomes, we entreat nurses as a collective to mobilize the public to lobby federal, provincial and territorial governments to fund more inclusive HPV vaccination policies. © 2016 John Wiley & Sons Ltd.

  11. Trends in human papillomavirus-related oropharyngeal cancer in Israel.

    Science.gov (United States)

    Amit, Moran; Ilana, Kaplan; Avraham, Sharon Pelles; Binenbaum, Yoav; Bachar, Gideon; Billan, Salem; Zaarura, Suliman; Czerninski, Rakefet; Bar-Tov, Matan; Maly, Alexander; Akrish, Sharon; Gil, Ziv

    2016-04-01

    The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p Israel as approximately 3-fold lower than in Western countries. Low exposure to HPV-16, a lower rate of transformation, to cancer or protective genetic factors may contribute to the lower rate of oropharyngeal SCC in Israel. © 2015 Wiley Periodicals, Inc. Head Neck 38: E274-E278, 2016. © 2015 Wiley Periodicals, Inc.

  12. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes

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    Nigel Pereira

    2015-01-01

    Full Text Available The human papillomavirus (HPV is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.

  13. Pathogenesis of human papillomavirus-associated mucosal disease.

    Science.gov (United States)

    Groves, Ian J; Coleman, Nicholas

    2015-03-01

    Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Maternal Support for Human Papillomavirus Vaccination in Honduras

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    Langrish, Sarah M.; Cotton, Deborah J.; Simon, Carol J.

    2011-01-01

    Abstract Background Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV. Methods We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance. Results We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance. Conclusions Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance. PMID:21091226

  15. Human papillomavirus variants among Inuit women in northern Quebec, Canada.

    Science.gov (United States)

    Gauthier, Barbara; Coutlée, Francois; Franco, Eduardo L; Brassard, Paul

    2015-01-01

    Inuit communities in northern Quebec have high rates of human papillomavirus (HPV) infection, cervical cancer and cervical cancer-related mortality as compared to the Canadian population. HPV types can be further classified as intratypic variants based on the extent of homology in their nucleotide sequences. There is limited information on the distribution of intratypic variants in circumpolar areas. Our goal was to describe the HPV intratypic variants and associated baseline characteristics. We collected cervical cell samples in 2002-2006 from 676 Inuit women between the ages of 15 and 69 years in Nunavik. DNA isolates from high-risk HPVs were sequenced to determine the intratypic variant. There were 149 women that were positive for HPVs 16, 18, 31, 33, 35, 45, 52, 56 or 58 during follow-up. There were 5 different HPV16 variants, all of European lineage, among the 57 women positive for this type. There were 8 different variants of HPV18 present and all were of European lineage (n=21). The majority of samples of HPV31 (n=52) were of lineage B. The number of isolates and diversity of the other HPV types was low. Age was the only covariate associated with HPV16 variant category. These frequencies are similar to what was seen in another circumpolar region of Canada, although there appears to be less diversity as only European variants were detected. This study shows that most variants were clustered in one lineage for each HPV type.

  16. The influence of human papillomavirus on nasopharyngeal carcinoma in Japan.

    Science.gov (United States)

    Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu

    2017-06-01

    Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Parents, adolescents, children and the human papillomavirus vaccine: a review.

    Science.gov (United States)

    Walhart, T

    2012-09-01

    Human papillomavirus (HPV) is a sexually transmitted infection (STI). HPV is the most common sexually transmitted infection worldwide. It is also the most common STI in adolescents. This highlights a great clinical and public health concern that must be addressed. Parents are typically involved in the clinical decision-making process of vaccine administration to children and adolescents. Therefore, understanding the acceptability of the HPV vaccination as a method to prevent STIs and certain cancers is critical.   To present the three primary themes that emerged from the literature: parental attitudes, parental beliefs and parental barrier towards vaccinating children and adolescents with the HPV vaccine. A literature search using Scopus to determine parents' attitudes and beliefs towards vaccinating children and adolescents with the HPV vaccine. The initial search included the key search terms of 'children' and 'HPV vaccine'. The publication year was limited from 2006 to present. The three themes greatly influence parents' decisions to vaccinate their children. In the future, more attention needs to be paid to specific subgroups. Future research should include groups that are currently under-represented: fathers, urban populations, low socio-economic status and ethnic minorities. Since nurses worldwide are often sought as healthcare resources by parents in the clinical decision-making process, their understanding of the attitude, beliefs and barriers parents have towards the HPV vaccine is paramount. © 2012 The Author. International Nursing Review © 2012 International Council of Nurses.

  18. Establishment of human papillomavirus infection requires cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  19. Human Papillomavirus - Prevalence of High-Risk and Low-Risk Types among Females Aged 14-59 Years, National Health and ...

    Science.gov (United States)

    ... Archive Data & Statistics Sexually Transmitted Diseases Figure 45. Human Papillomavirus — Prevalence of High-risk and Low-risk ... on the STD Data and Statistics page . * HPV = human papillomavirus. NOTE: Error bars indicate 95% confidence interval. ...

  20. A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Myers, Julia E; Keiffer, Timothy R; DiGiuseppe, Stephen; Polk, Paula; Bodily, Jason M; Scott, Rona S; Sapp, Martin

    2018-03-01

    Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

  1. A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2018-03-01

    Full Text Available Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16. This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

  2. [Prevalence of human papillomavirus infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx].

    Science.gov (United States)

    Villagómez-Ortíz, Vicente José; Paz-Delgadillo, Diana Estela; Marino-Martínez, Iván; Ceseñas-Falcón, Luis Ángel; Sandoval-de la Fuente, Anabel; Reyes-Escobedo, Alfonso

    2016-01-01

    Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma. Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx. An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers. A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours. There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Multicenter Study of Human Papillomavirus and the Human Papillomavirus Vaccine: Knowledge and Attitudes among People of African Descent

    Directory of Open Access Journals (Sweden)

    Elizabeth Blackman

    2013-01-01

    Full Text Available Objective. To compare knowledge and attitudes of human papillomavirus (HPV and the vaccine between different cultures of African descent. Methods. A cross-sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US and the Bahamas (BHM was conducted. Results. General knowledge about HPV and the HPV vaccine differed between the two countries significantly. Bahamian respondents were less likely to have higher numbers of correct knowledge answers when compared to Americans (Adjusted Odds Ratio [Adj. OR] 0.47, 95% Confidence Interval [CI] 0.30–0.75. Older age, regardless of location, was also associated with answering fewer questions correctly (Adj. OR 0.61, 95% CI 0.40–0.92. Attitudes related to HPV vaccination were similar between the US and BHM, but nearly 80% of BHM respondents felt that children should not be able to receive the vaccine without parental consent compared to 57% of American respondents. Conclusions. Grave lack of knowledge, safety and cost concerns, and influence of parental restrictions may negatively impact vaccine uptake among African-American and Afro-Caribbean persons. Interventions to increase the vaccine uptake in the Caribbean must include medical provider and parental involvement. Effective strategies for education and increasing vaccine uptake in BHM are crucial for decreasing cervical cancer burden in the Caribbean.

  4. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    , we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...

  5. Preventing human papillomavirus-related cancers: we are all in this together.

    Science.gov (United States)

    Dilley, Sarah; Scarinci, Isabel; Kimberlin, David; Straughn, J Michael

    2017-06-01

    Human papillomavirus-related cancers, which include cervical, vulvovaginal, anal, and oropharyngeal cancers, are on the rise in the United States. Although the human papillomavirus vaccine has been on the market for 10 years, human papillomavirus vaccination rates are well below national goals. Research identified many barriers and facilitators to human papillomavirus vaccination, and provider recommendation remains the most important factor in parental and patient decisions to vaccinate. While much of the burden of human papillomavirus vaccine provision falls on pediatricians and primary care providers, they cannot do it alone. As clinicians who care for a large proportion of human papillomavirus-related conditions, obstetrician-gynecologists and other women's health care providers must share the responsibility for vaccination of eligible patients. Obstetrician-gynecologists can support the efforts to eradicate human papillomavirus-related disease in their patients and their families via multiple avenues, including providing the human papillomavirus vaccine and being community leaders in support of vaccination. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Prevalence of Human Papillomavirus Infection in Unselected SurePath Samples Using the APTIMA HPV mRNA Assay

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Preisler, Sarah; Ejegod, Ditte M

    2013-01-01

    The APTIMA Human Papillomavirus (HPV) Assay detects E6/E7 mRNA from 14 human papillomavirus genotypes. Horizon was a population-based split-sample study among well-screened women, with an aim to compare APTIMA, Hybrid Capture 2 (HC2), and liquid-based cytology (LBC) using SurePath samples. APTIMA...

  7. Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor.

    Science.gov (United States)

    Ambühl, Lea M M; Leonhard, Anne K; Widen Zakhary, Carina; Jørgensen, Annemette; Blaakaer, Jan; Dybkaer, Karen; Baandrup, Ulrik; Uldbjerg, Niels; Sørensen, Suzette

    2017-10-01

    Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. Role of Human Papillomavirus in Penile Carcinomas Worldwide.

    Science.gov (United States)

    Alemany, Laia; Cubilla, Antonio; Halec, Gordana; Kasamatsu, Elena; Quirós, Beatriz; Masferrer, Emili; Tous, Sara; Lloveras, Belén; Hernández-Suarez, Gustavo; Lonsdale, Ray; Tinoco, Leopoldo; Alejo, Maria; Alvarado-Cabrero, Isabel; Laco, Jan; Guimerà, Nuria; Poblet, Enrique; Lombardi, Luis E; Bergeron, Christine; Clavero, Omar; Shin, Hai-Rim; Ferrera, Annabelle; Felix, Ana; Germar, Julieta; Mandys, Vaclav; Clavel, Christine; Tzardi, Maria; Pons, Luis E; Wain, Vincent; Cruz, Eugenia; Molina, Carla; Mota, Jose D; Jach, Robert; Velasco, Julio; Carrilho, Carla; López-Revilla, Ruben; Goodman, Marc T; Quint, Wim G; Castellsagué, Xavier; Bravo, Ignacio; Pawlita, Michael; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia

    2016-05-01

    Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. HPV DNA prevalence and type distributions were estimated. HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV

  9. Smoking and subsequent human papillomavirus infection: a mediation analysis.

    Science.gov (United States)

    Eldridge, Ronald C; Pawlita, Michael; Wilson, Lauren; Castle, Philip E; Waterboer, Tim; Gravitt, Patti E; Schiffman, Mark; Wentzensen, Nicolas

    2017-11-01

    Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections. In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking. Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26-1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27-2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94-1.44). This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity. Published by Elsevier Inc.

  10. Oral human papillomavirus is common in individuals with Fanconi anemia.

    Science.gov (United States)

    Sauter, Sharon L; Wells, Susanne I; Zhang, Xue; Hoskins, Elizabeth E; Davies, Stella M; Myers, Kasiani C; Mueller, Robin; Panicker, Gitika; Unger, Elizabeth R; Sivaprasad, Umasundari; Brown, Darron R; Mehta, Parinda A; Butsch Kovacic, Melinda

    2015-05-01

    Fanconi anemia is a rare genetic disorder resulting in a loss of function of the Fanconi anemia-related DNA repair pathway. Individuals with Fanconi anemia are predisposed to some cancers, including oropharyngeal and gynecologic cancers, with known associations with human papillomavirus (HPV) in the general population. As individuals with Fanconi anemia respond poorly to chemotherapy and radiation, prevention of cancer is critical. To determine whether individuals with Fanconi anemia are particularly susceptible to oral HPV infection, we analyzed survey-based risk factor data and tested DNA isolated from oral rinses from 126 individuals with Fanconi anemia and 162 unaffected first-degree family members for 37 HPV types. Fourteen individuals (11.1%) with Fanconi anemia tested positive, significantly more (P = 0.003) than family members (2.5%). While HPV prevalence was even higher for sexually active individuals with Fanconi anemia (17.7% vs. 2.4% in family; P = 0.003), HPV positivity also tended to be higher in the sexually inactive (8.7% in Fanconi anemia vs. 2.9% in siblings). Indeed, having Fanconi anemia increased HPV positivity 4.9-fold (95% CI, 1.6-15.4) considering age and sexual experience, but did not differ by other potential risk factors. Our studies suggest that oral HPV is more common in individuals with Fanconi anemia. It will be essential to continue to explore associations between risk factors and immune dysfunction on HPV incidence and persistence over time. HPV vaccination should be emphasized in those with Fanconi anemia as a first step to prevent oropharyngeal cancers, although additional studies are needed to determine whether the level of protection it offers in this population is adequate. ©2015 American Association for Cancer Research.

  11. Human Papillomavirus Genome Integration and Head and Neck Cancer.

    Science.gov (United States)

    Pinatti, L M; Walline, H M; Carey, T E

    2018-06-01

    We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

  12. Molecular testing of human papillomavirus in cervical specimens

    International Nuclear Information System (INIS)

    Gazzaz, Faten Salah B.

    2007-01-01

    Objective was to improve the diagnosis of cervical neoplasia by early detection of human papillomavirus (HPV) in uterine cervix, by adding molecular testing of HPV using hybrid capture 2 (HC2) and polymerase chain reaction (PCR) tests to Papanicoalou (Pap) test. One hundred women were enrolled in this study. The mean age (mean+-SD) was 41.97+- 8.76 years and range was 27-65 years. All women had undergone cervical cytological screening with cervical cytology, HPV DNA testing by HC2 and PCR, during the period from January to December 2006, at King Abdul-Aziz University Hospital (KAAUH) and King Fahd research Center, Jeddah, Saudi Arabia. The results were obtained by HC2 for detection of HPV were 5(5%) high-risk HPV, one low-risk HPV (1%) and 94(94%) negative cases. The PCR detected only 4(4%) cases. Using the HC2 test as a reference, sensitivity, specificity, positive predictive, negative predictive values and accuracy of base line Pap were 50, 85, 17.7, 96.4 and 83%; of final Pap smear were 100, 96.8, 66.7, 100, and 97% and for PCR were 66.7, 100, 100, 97.9 and 98%. The Pap test was repeated within a year for patients with abnormal Pap test with positive HPV DNA. Combined screening by cytology and HPV testing using both HC2 and PCR sensitively detects women with existing disease. The absence of HPV DNA provides reassurance that patients are unlikely to develop cancer for several years. We suggest using Pap with HC2 and PCR in screening programs to ensure that women with the double negative result at baseline might safely be screened at longer intervals. (author)

  13. Prevalence of tonsillar human papillomavirus infections in Denmark.

    Science.gov (United States)

    Rusan, M; Klug, T E; Henriksen, J J; Bonde, J H; Fuursted, K; Ovesen, T

    2015-09-01

    The incidence of tonsillar carcinomas associated with Human Papillomavirus (HPV) infection has increased dramatically over the last three decades. In fact, currently in Scandinavia, HPV-associated cases account for over 80 % of tonsillar carcinoma cases. Yet, the epidemiology and natural history of tonsillar HPV infections remains poorly characterized. Our aim was to characterize such infections in the Danish population in tumor-free tonsillar tissue. Unlike previous studies, we considered both palatine tonsils. We examined both tonsils from 80 patients with peritonsillar abscess (n = 25) or chronic tonsillar disease (n = 55). HPV was detected by nested PCR with PGMY 09/11 and GP5+/GP6+L1 consensus primers, and typed by sequencing. Samples were also analyzed using a higher-throughput method, the CLART HPV 2 Clinical Array Assay. The overall prevalence of HPV tonsillar infection was 1.25 % (1/80, 95 % CI 0.03-6.77 %) by nested PCR, and 0 % by CLART HPV2 Clinical Array. The HPV-positive patient was a 16-year-old female with recurrent tonsillitis and tonsillar hypertrophy. The type detected was HPV6. HPV was not detected in the contralateral tonsil of this patient. Compared to cervical HPV infections in Denmark, tonsillar HPV infections are 10- to 15-fold less frequent. In the HPV-positive patient in this study, HPV was detected in only one of the tonsils. This raises the possibility that prior studies may underestimate the prevalence of HPV infections, as they do not consider both palatine tonsils.

  14. Human papillomavirus infection in women in four regions of Senegal.

    Science.gov (United States)

    Mbaye, El Hadji Seydou; Gheit, Tarik; Dem, Ahmadou; McKay-Chopin, Sandrine; Toure-Kane, Ndeye Coumba; Mboup, Souleymane; Tommasino, Massimo; Sylla, Bakary S; Boye, Cheikh Saad Bouh

    2014-02-01

    Cervical cancer is the most frequent cancer among women in Senegal. However, there are few data concerning the human papillomavirus (HPV) types inducing neoplasia and cervical cancers and their prevalence in the general population of Senegal. The aim of this study is to determine the prevalence of HPV infection in Senegalese women aged 18 years and older in Dakar Region and three other regions. Cervical samples were collected from 498 women aged 18-80 years (mean, 42.1 years) in Dakar Region. Also, 438 samples were collected from three other regions: Thiès, Saint-Louis, and Louga. The samples were screened for 21 HPV genotypes using an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG). The prevalence of high risk (HR)-HPV in Dakar Region was 17.4%. HPV 52 (3.2%) was the most prevalent HPV type, followed by HPV 31 (3.0%) and HPV 16, 45, and 53 (all 2.8%). In the Thiès, Saint-Louis, and Louga Regions, the prevalence of HR-HPV was 23.2%, 13.1%, and 19.4%, respectively. The study revealed the specificity of HPV prevalence in Dakar Region and other regions of Senegal. The observed patterns show some differences compared with other regions of the world. These findings raise the possibility that, in addition to HPV 16 and HPV 18, other HPV types should be considered for a vaccination program in Senegal. However, additional studies to determine the HPV type distribution in cervical cancer specimens in Senegal are required to further corroborate this hypothesis. © 2013 Wiley Periodicals, Inc.

  15. Evidence that human papillomavirus causes inverted papilloma is sparse.

    Science.gov (United States)

    Justice, Jeb M; Davis, Kern M; Saenz, Daniel A; Lanza, Donald C

    2014-12-01

    Controversy exists regarding the pathogenesis of inverted papilloma as it relates to the involvement of human papillomavirus (HPV). The purpose of this report is to describe the prevalence of HPV in nondysplastic, "early inverted papilloma" and to summarize HPV detection rates in the general population and in other HPV related neoplasia. This case series report characterizes consecutive inverted papilloma patients from January 2005 to August 2012 with regard to smoking history, dysplasia, and HPV detection rates. Presence or absence of low/high risk HPV was determined by standardized in situ hybridization DNA probes. Medline literature review was performed to determine the prevalence of HPV in inverted papilloma without moderate or severe dysplasia. Thirty-six consecutive patients were identified with an average age of 63.6 (range, 40-84) years; gender: 23 men, 13 women. More than half (55%) were active or former smokers (14% active and 41% former). High/low risk HPV was present in 1 in 36 (2.7%) patients and 1 in 36 (2.7%) had mild dysplasia. In the literature review: (1) HPV was detected in 16.4% of inverted papilloma without dysplasia; (2) oral cavity HPV detection was 4.2% to 11.4% in the normal population; and (3) HPV was normally detected in 85% to 95% of HPV-related neoplasia. Given histological features of inverted papilloma and comparatively low detection rates of HPV in inverted papilloma without dysplasia (2.7%), as well as the summary of the world literature, HPV is not related to the initial pathogenesis of inverted papilloma or inverted papilloma's tendency to persist or recur. It is postulated that since inverted papilloma is more an inflammatory polyp, it is susceptible to secondary HPV infection because of its metaplasia. Tobacco and other causes of respiratory epithelium remodeling are more plausible explanations for the initial tissue transformation to inverted papilloma. © 2014 ARS-AAOA, LLC.

  16. Laryngeal squamous cell papilloma is highly associated with human papillomavirus.

    Science.gov (United States)

    Orita, Yorihisa; Gion, Yuka; Tachibana, Tomoyasu; Ikegami, Kana; Marunaka, Hidenori; Makihara, Seiichiro; Yamashita, Yasuhiko; Miki, Kentaro; Makino, Takuma; Akisada, Naoki; Akagi, Yusuke; Kimura, Miyuki; Yoshino, Tadashi; Nishizaki, Kazunori; Sato, Yasuharu

    2018-04-01

    To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody. In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other. HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma.

  17. [Acceptability of human papillomavirus vaccine in mothers from Valencia (Spain)].

    Science.gov (United States)

    Navarro-Illana, P; Caballero, P; Tuells, J; Puig-Barberá, J; Diez-Domingo, J

    2015-11-01

    In October 2008, Valencian Community started its human papillomavirus (HPV) vaccination schedules for 14 year-old girls. The aim of this study is to assess knowledge about HPV infection and its vaccine among the mothers of these girls, and to identify factors associated with the willingness to vaccinate their daughters. Cross-sectional study by means of a questionnaire to mothers of girls born in 1995, and attending secondary schools in the province of Valencia during 2010-2011. Cluster stratified random sample (n=1279). percentages, confidence intervals, OR, Chi-squared and multivariate logistic regression contrasts. A total of 833 (65.1%) questionnaires were completed. The results obtained showed that, 76.6% of mothers had vaccinated their daughters against HPV; 93.8% knew about the vaccine, particularly through television (71.5%); and 78.5% received positive advice from a health professional which increased the vaccination of their daughters (OR: 2.4). There was low overall knowledge about HPV infection and vaccination. Confidence of the mothers in vaccines as a preventative method increases the HPV vaccination (OR: 3.8). The first reason for refusal was the fear of adverse events (45.6%). Apparently, the media does not influence the willingness to vaccinate. It would be desirable to minimize the perception of risk of the vaccine. Positive health advice from a health professional can have a positive effect on vaccination. There is a gap between the level of knowledge and decision-making to vaccinate. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  18. Nucleic acid tests for the detection of alpha human papillomaviruses.

    Science.gov (United States)

    Poljak, Mario; Cuzick, Jack; Kocjan, Boštjan J; Iftner, Thomas; Dillner, Joakim; Arbyn, Marc

    2012-11-20

    Testing for high-risk types of alpha human papillomaviruses (HPV) is an invaluable part of clinical guidelines for cervical carcinoma screening, management and treatment. In this comprehensive inventory of commercial tests for detection of alpha-HPV, we identified at least 125 distinct HPV tests and at least 84 variants of the original tests. However, only a small subset of HPV tests has documented clinical performance for any of the standard HPV testing indications. For more than 75% of HPV tests currently on the market, no single publication in peer-reviewed literature can be identified. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated in the lab, it is essential that the whole procedure of HPV testing is subject to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Manufacturers of HPV tests are urged to put more effort into evaluating their current and future products analytically, using international standards, and for clinical applications, using clinically validated endpoints. To assist with analytical validation, the World Health Organization is developing international standards for HPV types other than HPV16 and HPV18 and is planning development of external quality control panels specifically designed to be used for performance evaluation of current and future HPV tests. There is a need for more competitively priced HPV tests, especially for resource-poor countries, and uniform test validation criteria based on international standards should enable issuing more competitive and fair tender notices for purchasing. Automation systems allowing large-scale testing, as well as further increases in clinical performance, are the main needs in the further improvement of HPV tests. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine

  19. Introduction of human papillomavirus vaccination in Nordic countries.

    Science.gov (United States)

    Sander, Bente Braad; Rebolj, Matejka; Valentiner-Branth, Palle; Lynge, Elsebeth

    2012-02-14

    Cervical screening has helped decrease the incidence of cervical cancer, but the disease remains a burden for women. Human Papillomavirus (HPV) vaccination is now a promising tool for control of cervical cancer. Nordic countries (Denmark, Finland, Greenland, Iceland, Norway and Sweden) are relatively wealthy with predominantly publicly paid health care systems. The aim of this paper was to provide an update of the current status of introduction of HPV vaccine into the childhood vaccination programs in this region. Data on cervical cancer, cervical screening programs, childhood immunization and HPV vaccination programs for Nordic countries were searched via PubMed and various organizations. We furthermore contacted selected experts for information. The incidence of cervical cancer is highest in Greenland (25 per 100,000, age standardized, World Standard Population, ASW) and lowest in Finland (4 per 100,000 ASW) and rates in the other Nordic countries vary between 7 and 11 per 100,000 ASW. Greenland and Denmark were first to introduce HPV vaccination, followed by Norway. Vaccination programs are underway in Sweden and Iceland, while Finland has just recently recommended introduction of vaccination. HPV vaccination has been intensively debated, in particular in Denmark and Norway. In Nordic countries with a moderate risk of cervical cancer and a publicly paid health care system, the introduction of HPV vaccination was a priority issue. Many players became active, from the general public to health professionals, special interest groups, and the vaccine manufacturers. These seemed to prioritize different health care needs and weighed differently the uncertainty about the long-term effects of the vaccine. HPV vaccination posed a pressure on public health authorities to consider the evidence for and against it, and on politicians to weigh the wish for cervical cancer protection against other pertinent health issues. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. 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

  1. The Laboratory Diagnosis of Genital Human Papillomavirus Infections

    Directory of Open Access Journals (Sweden)

    François Coutlee

    2005-01-01

    Full Text Available Human papillomaviruses (HPVs are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.

  2. 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

  3. Cervical Cancer Incidence in Young U.S. Females After Human Papillomavirus Vaccine Introduction.

    Science.gov (United States)

    Guo, Fangjian; Cofie, Leslie E; Berenson, Abbey B

    2018-05-30

    Since 2006, human papillomavirus vaccine has been recommended for young females in the U.S. This study aimed to compare cervical cancer incidence among young women before and after the human papillomavirus vaccine was introduced. This cross-sectional study used data from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence-U.S. Cancer Statistics 2001-2014 database for U.S. females aged 15-34 years. This study compared the 4-year average annual incidence of invasive cervical cancer in the 4 years before human papillomavirus vaccine was introduced (2003-2006) and the 4 most recent years in the vaccine era (2011-2014). Joinpoint regression models of cervical incidence from 2001 to 2014 were fitted to identify the discrete joints (year) that represent statistically significant changes in the direction of the trend after the introduction of human papillomavirus vaccination in 2006. Data were collected in 2001-2014, released, and analyzed in 2017. The 4-year average annual incidence rates for cervical cancer in 2011-2014 were 29% lower than that in 2003-2006 (6.0 vs 8.4 per 1,000,000 people, rate ratio=0.71, 95% CI=0.64, 0.80) among females aged 15-24 years, and 13.0% lower among females aged 25-34 years. Joinpoint analyses of cervical cancer incidence among females aged 15-24 years revealed a significant joint at 2009 for both squamous cell carcinoma and non-squamous cell carcinoma. Among females aged 25-34 years, there was no significant decrease in cervical cancer incidence after 2006. A significant decrease in the incidence of cervical cancer among young females after the introduction of human papillomavirus vaccine may indicate early effects of human papillomavirus vaccination. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Health-economic modelling of human Papillomavirus vaccination

    NARCIS (Netherlands)

    Westra, Tjalke Arend

    2013-01-01

    Vaccinatie van 12-jarige meisjes tegen het humaan papillomavirus (HPV) dat baarmoederhalskanker kan veroorzaken, blijkt effectief en kosteneffectief te zijn. UMCG-onderzoeker Tjalke Westra rekende met behulp van modellen de lange termijn effecten door van verschillende HPV-vaccinatiescenario’s

  5. Significant changes in sexual behavior after a diagnosis of human papillomavirus-positive and human papillomavirus-negative oral cancer.

    Science.gov (United States)

    Taberna, Miren; Inglehart, Ronald C; Pickard, Robert K L; Fakhry, Carole; Agrawal, Amit; Katz, Mira L; Gillison, Maura L

    2017-04-01

    Sexual behavior and oral human papillomavirus (HPV) infection are risk factors for oral squamous cell carcinoma (OSCC). The effects of OSCC diagnosis and treatment on subsequent relationship stress and sexual behavior are unknown. Incident cases of HPV-positive or HPV-negative OSCC in patients who had a partnered relationship and partners of patients with oropharyngeal cancer were eligible for a study in which surveys were administered at diagnosis and at the 6-month follow-up time point to assess relationship distress, HPV transmission and concerns about health consequences, and sexual behavior. The frequency distributions of responses, stratified by tumor HPV status, were compared at baseline and follow-up. In total, 262 patients with OSCC and 81 partners were enrolled. Among the patients, 142 (54.2%) had HPV-positive OSCC, and 120 (45.8%) had HPV-negative OSCC. Relationship distress was infrequently reported, and 69% of patients felt that their relationship had strengthened since the cancer diagnosis. Both HPV-positive patients (25%) and their partners (14%) reported feelings of guilt or responsibility for the diagnosis of an HPV-caused cancer. Concern over sexual, but not nonsexual, HPV transmission to partners was reported by 50%. Significant declines in the frequency of vaginal and oral sexual behaviors were reported at follow-up, regardless of tumor HPV status. From baseline to 6 months, significant increases in abstinence from vaginal sex (from 10% to 34%; P oral sex (from 25% to 80%; P oral sex, regardless of tumor HPV status. Sexual behavior is an important quality-of-life outcome to assess within clinical trials. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:1156-1165. © 2016 American Cancer Society. © 2017 American Cancer Society.

  6. The role of sexual behavior and human papillomavirus persistence in predicting repeated infections with new human papillomavirus types.

    Science.gov (United States)

    Moscicki, Anna-Barbara; Ma, Yifei; Jonte, Janet; Miller-Benningfield, Susanna; Hanson, Evelyn; Jay, Julie; Godwin de Medina, Cheryl; Farhat, Sepideh; Clayton, Lisa; Shiboski, Stephen

    2010-08-01

    Although human papillomavirus (HPV) infections are common in young women, the rate of and risk for repeated new infections are not well documented. We examined the rate of and risks for new HPV detection in young women. We used data from an ongoing study of HPV, initiated in 1990. Sexually active women ages 12 to 22 years were eligible. Interviews on behaviors and HPV testing were done at 4-month intervals; sexually transmitted infection (STI) testing was annual or if symptomatic. Starting with first HPV detection, time to the next (second) visit (event) with detection of new HPV types, and then the second event to time to third event was calculated. Risks were determined using Cox proportional hazard model. Sixty-nine percent of 1,125 women had a second event, and of those with a second event, 63% had a third event by 3 years, respectively. Women with HPV persistence from initial visit to second event [hazard ratio (HR) = 4.51 (3.78-5.37)], an STI [HR = 1.47 (1.00-2.17)], bacterial vaginosis [HR = 1.60 (1.07-2.39)], and number of new sex partners [HR = 1.10 (1.05-1.15 per partner/mo)] were independent associations for HPV. Risks for third event were similar. This study documents the repeated nature of HPV infections in young women and their association with sexual risk behaviors. This finding underscores the lack of clinical utility of HPV testing in young women. Further studies are needed to examine host factors that lead to HPV acquisition and persistence. (c)2010 AACR.

  7. Transient expression of human papillomavirus type 16 virus-like particles in tobacco and tomato using a tobacco rattle virus expression vector

    Czech Academy of Sciences Publication Activity Database

    Šmídková, Markéta; Müller, M.; Thönes, N.; Piuko, K.; Angelisová, Pavla; Velemínský, Jiří; Angelis, Karel

    2010-01-01

    Roč. 54, č. 3 (2010), s. 451-460 ISSN 0006-3134 R&D Projects: GA ČR GA521/01/1418; GA ČR GA521/04/0971; GA AV ČR IAA6038201; GA AV ČR IBS5038304; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50380511; CEZ:AV0Z50520514 Keywords : ELISA * Lycopersicon esculentum * Nicotiana benthamiana Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.582, year: 2010

  8. A promoter within the E6 ORF of human papillomavirus type 16 contributes to the expression of the E7 oncoprotein from a monocistronic mRNA

    DEFF Research Database (Denmark)

    Glahder, Jacob-Andreas Harald; Hansen, Christina N; Vinther, Jeppe

    2003-01-01

    RNA that encodes E7 as the first open reading frame (ORF) has been identified. We recently identified a transcription initiation site within the E6 ORF of HPV-16 at nt 542. In the present study we have characterized the P542 promoter, which putatively controls monocistronic expression of E7. The monocistronic m...... from nt 226 to 409. Furthermore, the translation initiation of E7 is most abundant from the monocistronic mRNA. We have also shown that the P542 promoter is downregulated by the transcription factor activator protein 4 (AP-4) and the differentiation-dependent factor hSkn-1a, both binding downstream...... of the transcription initiation site. In conclusion, we have found that P542 is a relatively weak promoter compared with P97 and may be downregulated in differentiated epithelial cells....

  9. Prevalence of high risk human papillomavirus types 16/18 in cytologically abnormal cervical smears in Alexandria, Egypt. A cytological and molecular study

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    Mona Sobhy Elkharashy

    2013-12-01

    Conclusion: The study generates epidemiological data of prevalence of HPV 16/18 in cytologically abnormal cervical smears in women seeking routine gynecologic care at the outpatient clinics of the Obstetrics and Gynecology Department at El Shatby University. High-risk HPV DNA testing by PCR of cervical samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with abnormal cervical smears, especially among women aged 46 years and older, in menopausal women and in women complaining of PMB. Therefore, HPV DNA testing should be made use of as an adjunct to cervical smears.

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

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    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.

  11. 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

  12. Monitoring human papillomavirus prevalence in urine samples: a review

    Directory of Open Access Journals (Sweden)

    Enerly E

    2013-03-01

    Full Text Available Espen Enerly, Cecilia Olofsson, Mari NygårdDepartment of Research, Cancer Registry of Norway, Oslo, NorwayAbstract: Human papillomavirus (HPV is the main cause of cervical cancer, and many countries now offer vaccination against HPV to girls by way of government-funded national immunization programs. Monitoring HPV prevalence in adolescents could offer a near-term biological measure of vaccine impact, and urine sampling may be an attractive large-scale method that could be used for this purpose. Our objective was to provide an overview of the literature on HPV DNA detection in urine samples, with an emphasis on adolescents. We searched the PubMed database using the terms “HPV” and “urine” and identified 21 female and 14 male study populations in which HPV prevalence in urine samples was reported, four of which included only asymptomatic female adolescents. We provide herein an overview of the recruitment setting, age, urine sampling procedure, lesion type, HPV assay, and HPV prevalence in urine samples and other urogenital samples for the studies included in this review. In female study populations, concordance for any HPV type and type-specific concordance in paired urine and cervical samples are provided in addition to sensitivity and specificity. We concluded that few studies on HPV prevalence in urine samples have been performed in asymptomatic female adolescent populations but that urine samples may be a useful alternative to cervical samples to monitor changes in HPV prevalence in females in the post-HPV vaccination era. However, care should be taken when extrapolating HPV findings from urine samples to the cervix. In males, urine samples do not seem to be optimal for monitoring HPV prevalence due to a low human genomic DNA content and HPV DNA detection rate compared to other urogenital sites. In each situation the costs and benefits of HPV DNA detection in urine compared to alternative monitoring options should be carefully

  13. Human papillomas virus infection in the case of larynx carcinoma

    International Nuclear Information System (INIS)

    Makowska, W.; Rogozinski, T.; Zawadowski, J.; Waloryszak, B.

    1993-01-01

    The case of 59 year old man treated (with surgery and radiotherapy) for larynx carcinoma was presented. The potentially oncogenic human papillomavirus type 16/18 was detected in the tissue surrounding the tumor. (author)

  14. In vivo transformation of human skin with human papillomavirus type 11 from condylomatot acuminata

    International Nuclear Information System (INIS)

    Kreider, J.W.; Howett, M.K.; Lill, N.L.; Bartlett, G.L.; Zaino, R.J.; Sedlacek, T.V.; Mortel, R.

    1986-01-01

    Human papillomaviruses (HPVs) have been implicated in the development of a number of human malignancies, but direct tests of their involvement have not been possible. The authors describe a system in which human skin from various skin from various sites was infected with HPV type 11 (HPV-11) extracted from vulvar condylomata and was grafted beneath the renal capsule of athymic mice. Most of the skin grafts so treated underwent morphological transformation, resulting in the development of condylomata identical to those which occur spontaneously in patients. Foreskins responded with the most vigorous proliferative response to HPV-11. The lesions produced the characteristic intranuclear group-specific antigen of papillomaviruses. Both dot blot and Southern blot analysis of DNA from the lesions revealed the presence of HPV-11 DNA in the transformed grafts. These results demonstrate the first laboratory system for the study of the interaction of human skin with an HPV. The method may be useful in understanding the mechanisms of HPV transformation and replication and is free of the ethical restraints which have impeded study. This system will allow the direct study of factors which permit neoplastic progression of HPV-induced cutaneous lesions in human tissues

  15. Human papillomaviruses associated with epidermodysplasia verruciformis. II. Molecular cloning and biochemical characterization of human papillomavirus 3a, 8, 10, and 12 genomes.

    OpenAIRE

    Kremsdorf, D; Jablonska, S; Favre, M; Orth, G

    1983-01-01

    The DNAs of four human papillomaviruses (HPVs) that were found in the benign lesions of three patients suffering from epidermodysplasia verruciformis have been characterized. The flat wart-like lesions and the macular lesions of patient 1 contained two viruses, HPV-3a and HPV-8, respectively, whose genomes had previously been only partially characterized. The flat wart-like lesions of patient 2 and the macular lesions of patient 3 each contained a virus previously considered as belonging to t...

  16. Biology and natural history of human papillomavirus infection

    Directory of Open Access Journals (Sweden)

    Fernandes JV

    2013-01-01

    Full Text Available José Veríssimo Fernandes,1 Josélio Maria Galvão de Araújo,1 Thales Allyrio Araújo de Medeiros Fernandes21Laboratory of Molecular Biology for Infectious Diseases and Cancer, Federal University of Rio Grande do Norte, Natal, Brazil; 2Department of Biomedical Sciences, University of Rio Grande do Norte State, Mossoró, BrazilAbstract: Human papillomavirus (HPV is one of the most common causes of sexually transmitted diseases worldwide. It has been proposed that the great majority of women and men have been infected with HPV at least once during their lifetime. HPV infection is associated with a variety of clinical conditions, ranging from benign lesions to cervical cancer. In most cases, the infection is transient, where most of the individuals are healing, eliminating the virus without the presence of any clinical manifestation. Actually, more than 120 HPV types have been cataloged, of which approximately 40 can infect the mucosa of the anogenital tract and are collectively known as mucosal HPV, which are classified based on their oncogenic potential as either low- or high-risk HPV types. The low-risk HPV type causes benign hyperproliferative lesions or genital warts, with a very limited tendency for malignant progression, while the high-risk HPV type is strongly associated with premalignant and malignant cervical lesions. The HPV cycle initiates when the virus gains access to undifferentiated cells of the basement membrane of the squamous columnar junction epithelium of the ectocervix, after these regions are exposed to mechanical or chemical trauma. The basal cells in the transformation zone retain the ability to differentiate, a property required for virion production. Cervical infection with high-risk HPV typically lasts from 12 to 18 months and in most cases is cleared spontaneously. However, in some women the immune response is insufficient to eliminate the virus, resulting in a persistent, long-term infection that may progress to a

  17. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

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    Kihyuck Kwak

    Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type

  18. Human papillomavirus vaccine uptake among individuals with systemic inflammatory diseases.

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    Candace H Feldman

    Full Text Available The human papillomavirus (HPV vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients.Using a U.S. insurance claims database (2006-2012, we identified individuals 9-26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date. We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11-26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization.We identified 5,642 patients 9-26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9. We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1. Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77-0.98 compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83-1.26. The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts.In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk.

  19. Human Papillomavirus Vaccine Uptake among Individuals with Systemic Inflammatory Diseases

    Science.gov (United States)

    Feldman, Candace H.; Hiraki, Linda T.; Lii, Huichuan; Seeger, John D.; Kim, Seoyoung C.

    2015-01-01

    Objectives The human papillomavirus (HPV) vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID) who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients. Methods Using a U.S. insurance claims database (2006–2012), we identified individuals 9–26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date). We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11–26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization. Results We identified 5,642 patients 9–26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9). We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1). Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77–0.98) compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83–1.26). The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts. Conclusions In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk. PMID:25692470

  20. Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions.

    Science.gov (United States)

    Schäfer, Georgia; Graham, Lisa M; Lang, Dirk M; Blumenthal, Melissa J; Bergant Marušič, Martina; Katz, Arieh A

    2017-08-15

    Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs. However, the exact mechanism and receptors used by HPV to infect epithelial cells are controversial. The current entry model suggests that HPV initially attaches to heparan sulfate proteoglycans (HSPGs) at the cell surface, followed by conformational changes, cleavage by furin convertase, and subsequent transfer of the virus to an as-yet-unidentified high-affinity receptor. In line with this model, we established an in vitro infection system using the HSPG-deficient cell line pgsD677 together with HPV16 pseudovirions (HPV16-PsVs). While pgsD677 cells were nonpermissive for untreated HPV16-PsVs, furin cleavage of the particles led to a substantial increase in infection. Biochemical pulldown assays followed by mass spectrometry analysis showed that furin-precleaved HPV16-PsVs specifically interacted with surface-expressed vimentin on pgsD677 cells. We further demonstrated that both furin-precleaved and uncleaved HPV16-PsVs colocalized with surface-expressed vimentin on pgsD677, HeLa, HaCaT, and NIKS cells, while binding of incoming viral particles to soluble vimentin protein before infection led to a substantial decrease in viral uptake. Interestingly, decreasing cell surface vimentin by small interfering RNA (siRNA) knockdown in HeLa and NIKS cells significantly increased HPV16-PsV infectious internalization, while overexpression of vimentin had the opposite effect. The identification of vimentin as an HPV restriction factor enhances our understanding of the initial steps of HPV-host interaction and may lay the basis for the design of novel antiviral drugs preventing HPV internalization into epithelial cells. IMPORTANCE Despite HPV being a highly prevalent sexually transmitted virus causing significant disease burden worldwide, particularly cancer of the cervix, cell surface

  1. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  2. Biological relevance of human papillomaviruses in vulvar cancer.

    Science.gov (United States)

    Halec, Gordana; Alemany, Laia; Quiros, Beatriz; Clavero, Omar; Höfler, Daniela; Alejo, Maria; Quint, Wim; Pawlita, Michael; Bosch, Francesc X; de Sanjose, Silvia

    2017-04-01

    The carcinogenic role of high-risk human papillomavirus (HR-HPV) types in the increasing subset of vulvar intraepithelial neoplasia and vulvar cancer in young women has been established. However, the actual number of vulvar cancer cases attributed to HPV is still imprecisely defined. In an attempt to provide a more precise definition of HPV-driven vulvar cancer, we performed HPV-type-specific E6*I mRNA analyses available for 20 HR-/possible HR (pHR)-HPV types, on tissue samples from 447 cases of vulvar cancer. HPV DNA genotyping was performed using SPF10-LiPA 25 assay due to its high sensitivity in formalin-fixed paraffin-embedded tissues. Data on p16 INK4a expression was available for comparative analysis via kappa statistics. The use of highly sensitive assays covering the detection of HPV mRNA in a broad spectrum of mucosal HPV types resulted in the detection of viral transcripts in 87% of HPV DNA+ vulvar cancers. Overall concordance between HPV mRNA+ and p16 INK4a upregulation (strong, diffuse immunostaining in >25% of tumor cells) was 92% (K=0.625, 95% confidence interval (CI)=0.531-0.719). Among these cases, 83% were concordant pairs of HPV mRNA+ and p16 INK4a + and 9% were concordant pairs of HPV mRNA- and p16 INK4a -. Our data confirm the biological role of HR-/pHR-HPV types in the great majority of HPV DNA+ vulvar cancers, resulting in an HPV-attributable fraction of at least 21% worldwide. Most HPV DNA+ vulvar cancers were associated with HPV16 (85%), but a causative role for other, less frequently occurring mucosal HPV types (HPV26, 66, 67, 68, 70 and 73) was also confirmed at the mRNA level for the first time. These findings should be taken into consideration for future screening options as HPV-associated vulvar preneoplastic lesions have increased in incidence in younger women and require different treatment than vulvar lesions that develop from rare autoimmune-related mechanisms in older women.

  3. Risk factors for human papillomavirus exposure and co-factors for cervical cancer in Latin America and the Caribbean.

    Science.gov (United States)

    Almonte, Maribel; Albero, Ginesa; Molano, Mónica; Carcamo, César; García, Patricia J; Pérez, Gonzalo

    2008-08-19

    The incidence of cervical cancer in Latin America and the Caribbean (LAC) is among the highest in the world. Because there are major demographic shifts happening in LAC countries (population growth, urbanization and ageing) cervical cancer incidence and mortality will likely continue to be a significant public health problem. Overall human papillomavirus (HPV) prevalence in the LAC general population has been found to be 2-fold higher than the average worldwide prevalence. The large HPV and cancer burden may be explained by the highly prevalent HPV variants of HPV types -16 and 18, which have an increased oncogenic potential. Given the major mode of transmission of genital HPV is sexual, certain, patterns of sexual behaviour (early age at first sexual intercourse, number of sexual partners and sexual behaviour of the partner) are associated with an increased risk of HPV genital acquisition. Although HPV infection is necessary for carcinogenesis, certain co-factors (high parity, long term use of oral contraceptives, smoking and co-infection with the human immunodeficiency virus (HIV)) help in the progression from infection to cancer. Many studies that have contributed to this evidence have been carried out in LAC and are reviewed and summarised in this article. Since HPV vaccines will likely take years to implement, and many more years to show impact on disease, cervical cancer screening programmes remain as the key intervention to control disease in LAC in the years to come.

  4. Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells

    International Nuclear Information System (INIS)

    Lagrange, Magali; Boulade-Ladame, Charlotte; Mailly, Laurent; Weiss, Etienne; Orfanoudakis, Georges; Deryckere, Francois

    2007-01-01

    The E6 protein of human papillomavirus type 16 (16E6) is involved in the tumorigenesis of human cervical cells by targeting numerous cellular proteins. We have designed a strategy for neutralizing 16E6 based on the intracellular expression of single-chain Fv antibodies (scFvs) specific to 16E6. Recombinant adenovirus vectors were constructed to allow expression of two 16E6-binding scFvs and one 16E6-non-binding scFv in HPV16-positive and -negative cells. Expression of the scFvs provoked two types of effects: (i) inhibition of proliferation of all cell lines tested, this aspecific toxicity being likely due to the aggregation of unfolded scFvs; and (ii) apoptosis observed only in HPV16-positive cervical cancer cell lines after expression of 16E6-binding scFvs, this specific effect being proportional to the intracellular solubility of the scFvs. These data demonstrate the feasibility of intracellular immunization with anti-16E6 scFvs and highlight the importance of the solubility of the intracellular antibodies

  5. Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

    Science.gov (United States)

    Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

    2013-05-01

    Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

  6. Population-level impact, herd immunity, and elimination after human papillomavirus vaccination

    DEFF Research Database (Denmark)

    Brisson, Marc; Bénard, Élodie; Drolet, Mélanie

    2016-01-01

    BackgroundModelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-a...

  7. Frequent detection of human papillomavirus 16 E2-specific T-helper immunity in healthy subjects

    NARCIS (Netherlands)

    de Jong, Annemieke; van der Burg, Sjoerd H.; Kwappenberg, Kitty M. C.; van der Hulst, Jeanette M.; Franken, Kees L. M. C.; Geluk, Annemieke; van Meijgaarden, Krista E.; Drijfhout, Jan Wouter; Kenter, Gemma; Vermeij, Pieter; Melief, Cornelis J. M.; Offringa, Rienk

    2002-01-01

    The incidence of genital human papillomavirus (HPV) infections is high in young, sexually active individuals. Most infections are cleared within 1 year after infection. The targets for the cellular immune response in this process of viral clearance remain to be identified, but the expression pattern

  8. Determinants of Human Papillomavirus Vaccination Intention Among Female Sex Workers in Amsterdam, the Netherlands

    NARCIS (Netherlands)

    Marra, E.; Dam, L. van; Kroone, N.; Alberts, C.J.; Craanen, M.; Zimet, G.D.; Heijmam, T.; Hogewoning, A.A.; Sonder, G.J.B.; Vries, H.J.C. de; Alberts, C.J.; Paulussen, T.G.W.M.; Schim van der Loeff, M.F.

    2017-01-01

    Introduction: Female sex workers (FSWs) are at risk for human papillomavirus (HPV)-induced diseases but are currently not targeted by the HPV vaccination program in the Netherlands. We explored determinants of their intention to get vaccinated against HPV in case vaccination would be offered to

  9. 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

  10. Knowledge about Human Papillomavirus and Cervical Cancer: Predictors of HPV Vaccination among Dental Students

    Science.gov (United States)

    Rajiah, Kingston; Maharajan, Mari Kannan; Fang Num, Kelly Sze; How Koh, Raymond Chee

    2017-06-25

    Background: The objective of this study is to determine the influence of dental students’ knowledge and attitude regarding human papillomavirus infection of cervical cancer on willingness to pay for vaccination. Basic research design: A convenience sampling method was used. The minimal sample size of 136 was calculated using the Raosoft calculator with a 5 % margin of error and 95% confidence level. Participants: The study population were all final year dental students from the School of Dentistry. Methods: A self-administered questionnaire was used to measure knowledge levels and attitudes regarding human papillomavirus vaccination. Contingent valuation was conducted for willingness to pay for vaccination. Main outcome measures: The Center for Disease Control and Prevention has stated that human papillomavirus are associated with oropharynx cancer and the American Dental Association insist on expanding public awareness of the oncogenic potential of some HPV infections. Thus, as future dental practitioners, dental students should be aware of human papillomavirus and their links with cancer and the benefits of vaccination. Results: Knowledge on HPV and cervical cancer did not impact on attitudes towards vaccines. However, significant correlation existed between knowledge and willingness to pay for vaccination. Conclusions: Dental students’ knowledge on HPV and cervical cancer has no influence on their attitude towards HPV vaccines. However, their willingness to pay for HPV vaccination is influenced by their knowledge of cervical cancer and HPV vaccination. Creative Commons Attribution License

  11. Investigating Stakeholder Attitudes and Opinions on School-Based Human Papillomavirus Vaccination Programs

    Science.gov (United States)

    Nodulman, Jessica A.; Starling, Randall; Kong, Alberta S.; Buller, David B.; Wheeler, Cosette M.; Woodall, W. Gill

    2015-01-01

    Background: In several countries worldwide, school-based human papillomavirus (HPV) vaccination programs have been successful; however, little research has explored US stakeholders' acceptance toward school-based HPV vaccination programs. Methods: A total of 13 focus groups and 12 key informant interviews (N?=?117; 85% females; 66% racial/ethnic…

  12. Human papillomavirus testing as a cytology gold standard : comparing Surinam with the Netherlands

    NARCIS (Netherlands)

    Wachtel, MS; Boon, ME; Korporaal, H; Kok, LP

    Polymerase chain reaction to detect high- risk human papillomavirus has been suggested as a gold standard for cytology. The Netherlands and Surinam were prospectively compared in regard to the proportions of Negative, Atypical Squamous Cells of Undetermined Significance, and Squamous Intraepithelial

  13. Opportunities for Increasing Human Papillomavirus Vaccine Provision in School Health Centers

    Science.gov (United States)

    Moss, Jennifer L.; Feld, Ashley L.; O'Malley, Brittany; Entzel, Pamela; Smith, Jennifer S.; Gilkey, Melissa B.; Brewer, Noel T.

    2014-01-01

    Background: Uptake of human papillomavirus (HPV) vaccine remains low among adolescents in the United States. We sought to assess barriers to HPV vaccine provision in school health centers to inform subsequent interventions. Methods: We conducted structured interviews in the fall of 2010 with staff from all 33 school health centers in North…

  14. Persistence and reappearance of high-risk human papillomavirus after conization

    DEFF Research Database (Denmark)

    Gosvig, Camilla Flarup; Huusom, Lene Drasbek; Andersen, Klaus Kaae

    2013-01-01

    Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development...

  15. Attribution of 12 High-Risk Human Papillomavirus Genotypes to Infection and Cervical Disease

    DEFF Research Database (Denmark)

    Joura, Elmar A.; Ault, Kevin A.; Bosch, F. Xavier

    2014-01-01

    BACKGROUND: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined...

  16. Restriction of human papillomavirus DNA testing in primary cervical screening to women above age 30

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Njor, Sisse H; Lynge, Elsebeth

    2012-01-01

    Cervical screening with human papillomavirus (HPV) testing is less specific for high-grade cervical intraepithelial neoplasia (=CIN3) than cytology. The aim of this systematic review was to determine whether a restriction of HPV testing to women aged at least 30 years would eliminate the problem...

  17. Type-specific human papillomavirus infections among young heterosexual male and female STI clinic attendees

    NARCIS (Netherlands)

    Vriend, Henrike J; Boot, Hein J; van der Sande, Marianne A B; Rossen, John

    BACKGROUND: Baseline genotype-specific human papillomavirus (HPV) prevalence rates and associated risk factors per gender enable future assessment of the impact of vaccination on HPV dynamics. METHODS: Before the start of national HPV vaccination for girls, data were collected cross-sectionally in

  18. Knowledge, Attitudes, and Informational Behaviors of College Students in Regard to the Human Papillomavirus

    Science.gov (United States)

    Sandfort, Jessica R.; Pleasant, Andrew

    2009-01-01

    Objective: To assess students' human papillomavirus (HPV) knowledge, attitudes, and behaviors. Participants/ Methods: Students (N = 1,282) at a large, public university in the Northeast United States completed a questionnaire during February 2008 assessing HPV knowledge, prevalence, transmission, cervical cancer risk and stigma; sexual behavior,…

  19. Attitudes towards human papillomavirus vaccination among Arab ethnic minority in Denmark

    DEFF Research Database (Denmark)

    Zeraiq, Lina; Nielsen, Dorthe; Sodemann, Morten

    2015-01-01

    Background: Knowledge regarding the human papillomavirus (HPV) and HPV vaccine uptake among ethnic minorities is poorly explored in Denmark. The objective of this study was to explore attitudes and knowledge towards HPV vaccination among Arab mothers and their daughters. Methods: Five Arabic-speaking...

  20. Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours

    DEFF Research Database (Denmark)

    Grønhøj Larsen, C; Gyldenløve, M; Jensen, D H

    2014-01-01

    A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diag...

  1. Prevalence of Human Papillomavirus in Anal and Oral Sites Among Patients with Genital Warts

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Sand, Carsten; Forslund, Ola

    2014-01-01

    Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant...

  2. Concordant testing results between various Human Papillomavirus assays in primary cervical cancer screening

    DEFF Research Database (Denmark)

    de Thurah, Lena; Bonde, Jesper; Hoa Lam, Janni Uyen

    2018-01-01

    OBJECTIVES: Human Papillomavirus (HPV) assays are increasingly used for primary cervical screening and HPV vaccination effect monitoring. We undertook a systematic literature review to determine the concordance in positive test results (i.e., detection of HPV infections) between Hybrid Capture 2 ...

  3. Chlamydia trachomatis and genital human papillomavirus infections in female university students in Honduras.

    NARCIS (Netherlands)

    Tabora, N.; Zelaya, A.; Bakkers, J.; Melchers, W.J.; Ferrera, A.

    2005-01-01

    Sexually transmitted infections are a serious health problem in Honduras. Human papillomavirus (HPV) and Chlamydia trachomatis are major causes of sexually transmitted diseases. To determine the prevalence of C. trachomatis and HPV in young women, 100 female university students in Honduras were

  4. 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 ...

  5. Global burden of human papillomavirus and related diseases.

    Science.gov (United States)

    Forman, David; de Martel, Catherine; Lacey, Charles J; Soerjomataram, Isabelle; Lortet-Tieulent, Joannie; Bruni, Laia; Vignat, Jerome; Ferlay, Jacques; Bray, Freddie; Plummer, Martyn; Franceschi, Silvia

    2012-11-20

    The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be

  6. Epidemiological studies on viral infections and co-infections : Human immunodeficiency virus, hepatitis C virus and human papillomavirus

    NARCIS (Netherlands)

    van Santen, D.K.

    2018-01-01

    The research described in this thesis aimed to increase our understanding of the incidence, disease progression and treatment of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and human papillomavirus (HPV) infections and co-infections in key populations. Chapter 1 contains an overview

  7. Sentimentos vivenciados por mulheres submetidas a tratamento para Papillomavirus Humano Sentimientos vivenciados por mujeres sometidas a Tratamiento para el Papillomavirus Humano Feelings experienced by women submitted to a treatment for Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Ana Luiza Santos de Carvalho

    2007-06-01

    Full Text Available A carência de informações sobre o papillomavirus humano pode gerar idéias errôneas sobre o tratamento, o que interfere no contexto sócio-familiar da mulher. Com o objetivo de conhecer os sentimentos vivenciados por mulheres submetidas a tratamento de lesões por papillomavirus humano, foi realizada uma pesquisa qualitativa de natureza exploratória com 12 mulheres, baseada na obtenção e análise de depoimentos por meio de entrevista semi-estruturada. As informações foram analisadas de acordo com a literatura e dispostas em duas temáticas: Reações emocionais e Repercussões no relacionamento. Conclui-se que a mulher que está sendo submetida a tratamento de lesões por papillomavirus humano necessita de cuidados, por parte dos enfermeiros, como forma de melhor enfrentar esse período a qual está vivenciando.La carencia de informaciones sobre el papillomavirus humano puede generar ideas erradas sobre el tratamiento, lo que interfiere en el contexto social y familiar de la mujer. Con el objetivo de conocer los sentimientos vividos por mujeres sometidas a tratamiento de lesiones por papillomavirus humanos, fue realizada una investigación cualitativa de naturaleza exploratoria con 12 mujeres, basada en la obtención y análisis de deposiciones por medio de entrevistas medio-estructurada. Las informaciones fueran analizadas conforme con la literatura y dispuestas en dos temáticas: Reacciones emocionales y Repercusiones en el reracionamiento. Concluyese que la mujer que esta siendo sometida al tratamiento de lesiones por papillomavirus humano necesita de cuidados, por parte de los enfermeros, como forma de mejor enfrentar ese periodo el cual esta viviendo.The lack of information on the papillomavirus human can generate misconception on the treatment interfering in the familiar and social context of the woman. With the purpose to know the feelings experienced by women submitted to treatment of lesions by human papillomavirus, was carried

  8. Prevalence of and risk factors for anal human papillomavirus infection in men who have sex with women: a cross-national study.

    Science.gov (United States)

    Nyitray, Alan G; Smith, Dan'elle; Villa, Luisa; Lazcano-Ponce, Eduardo; Abrahamsen, Martha; Papenfuss, Mary; Giuliano, Anna R

    2010-05-15

    Although the primary cause of anal cancer is human papillomavirus (HPV) infection in the anal canal, little attention has been paid to the epidemiology of anal HPV infection in men who have sex with women (MSW). Exfoliated cells from the anal canal of 902 MSW in Brazil (São Paulo), Mexico (Cuernavaca), and the United States (Tampa) were tested for HPV DNA. The prevalence of HPV infection in the anal canal (12.0%) was similar among MSW in each city (P=.77), whereas 7.0% had infection with oncogenic types. Men in Tampa had a 4-fold higher prevalence of infection with HPV type 16 (HPV-16) than that among men in São Paulo or Cuernavaca (PMen who have a larger lifetime number of female sex partners, who are in a sexual relationship of men were most likely to have an anal HPV infection.

  9. Reevaluation of epidemiological data demonstrates that it is consistent with cross-immunity among human papillomavirus types.

    Science.gov (United States)

    Durham, David P; Poolman, Eric M; Ibuka, Yoko; Townsend, Jeffrey P; Galvani, Alison P

    2012-10-01

    The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity. We reevaluate the epidemiological data using a model to determine the odds ratios of multiple to single infections expected in the presence or absence of cross-immunity. We simulate a virtual longitudinal survey to determine the effect cross-immunity has on the prevalence of multiple infections. We calibrate our model to epidemiological data and estimate the extent of type replacement following vaccination against specific HPV types. We find that cross-immunity can produce odds ratios of infection comparable with epidemiological observations. We show that the sample sizes underlying existing surveys have been insufficient to identify even intense cross-immunity. We also find that the removal of HPV type 16, type 18, and types 6 and 11 would increase the prevalence of nontargeted types by 50%, 29%, and 183%, respectively. Cross-immunity between HPV types is consistent with epidemiological data, contrary to previous interpretations. Cross-immunity may cause significant type replacement following vaccination, and therefore should be considered in future vaccine studies and epidemiological models.

  10. Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection

    International Nuclear Information System (INIS)

    Fang, L.; Ward, M.G.; Welsh, P.A.; Budgeon, L.R.; Neely, E.B.; Howett, M.K.

    2003-01-01

    Recent epidemiological studies have found that women infected with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) type 16 or HPV-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. However, it remains unclear if HSV-2 is a cofactor for cervical cancer or if HPV and HSV-2 interact in any way. We have studied the effect of HSV-2 infection on HPV-11 gene expression in an in vitro double-infection assay. HPV transcripts were down-regulated in response to HSV-2 infection. Two HSV-2 vhs mutants failed to reduce HPV-16 E1-circumflexE4 transcripts. We also studied the effect of HSV-2 infection on preexisting experimental papillomas in a vaginal epithelial xenograft model. Doubly infected grafts demonstrated papillomatous transformation and the classical cytopathic effect from HSV-2 infection. HPV and HSV DNA signals were mutually exclusive. These studies may have therapeutic applications for HPV infections and related neoplasms

  11. Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination

    International Nuclear Information System (INIS)

    Pimenta, Jeanne M; Galindo, Claudia; Jenkins, David; Taylor, Sylvia M

    2013-01-01

    Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines. We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature. ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80–85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually). It is predicted that the currently available HPV vaccines will be highly effective in preventing HPV-related cervical

  12. Within-Host Variations of Human Papillomavirus Reveal APOBEC-Signature Mutagenesis in the Viral Genome.

    Science.gov (United States)

    Hirose, Yusuke; Onuki, Mamiko; Tenjimbayashi, Yuri; Mori, Seiichiro; Ishii, Yoshiyuki; Takeuchi, Takamasa; Tasaka, Nobutaka; Satoh, Toyomi; Morisada, Tohru; Iwata, Takashi; Miyamoto, Shingo; Matsumoto, Koji; Sekizawa, Akihiko; Kukimoto, Iwao

    2018-03-28

    Persistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied with the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here we explored within-host genetic diversity of HPV by performing deep sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52 and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), and were deep-sequenced. After constructing a reference vial genome sequence for each specimen, nucleotide positions showing changes with > 0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1, n = 56; CIN2/3, n = 68; ICC, n = 27), with varying numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the tri-nucleotides context encompassing substituted bases revealed that Tp C pN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions. IMPORTANCE HPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep sequencing analyses, we show for the first time a comprehensive snapshot of the "within

  13. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Directory of Open Access Journals (Sweden)

    Nagayasu Egawa

    2015-07-01

    Full Text Available Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

  14. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Science.gov (United States)

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-01-01

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

  15. T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation

    Directory of Open Access Journals (Sweden)

    Andrew W. Woodham

    2016-12-01

    Full Text Available Human papillomavirus type 16 (HPV16 infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs, the resident epithelial antigen-presenting cells (APCs. The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1, but without costimulation (signal 2. We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8+ T cells receiving signal 1+2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals. Keywords: T cell anergy, T cell ignorance, Immune tolerance, Human papillomavirus, HPV16, Langerhans cells

  16. Inverted papilloma of the cervix and vagina: report of 2 cases of a rare lesion associated with human papillomavirus 42.

    Science.gov (United States)

    Hennell, Claire; Jamison, Jackie; Wells, Michael; McCluggage, W Glenn

    2012-03-01

    We report 2 cases of a lesion that we term inverted papilloma of the lower female genital tract, occurring in the cervix and upper vagina of 60- and 50-year-old women, respectively. Microscopically, the features were similar to those of inverted transitional papilloma of the urinary bladder with interconnecting islands, trabeculae, and solid sheets of bland transitional epithelium with an inverted growth pattern. There were small foci of squamous and glandular differentiation in the cervical case. Linear array human papillomavirus genotyping revealed human papillomavirus type 42 in both cases. Inverted papilloma in the lower female genital tract is extremely rare with, as far as we are aware, only 3 previously reported similar cases in the cervix and none in the vagina. Our results suggest that these neoplasms when occurring in the lower female genital tract may be associated with low-risk human papillomavirus, perhaps specifically human papillomavirus 42. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Risk Factors for High-Risk Human Papillomavirus Detection Among HIV-Negative and HIV-Positive Women From Tanzania

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Munk, Christian

    2013-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny....

  18. Human Papillomavirus Cervical Infection and Associated Risk Factors in a Region of Argentina With a High Incidence of Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    S. A. Tonon

    1999-01-01

    Full Text Available Objective: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer.

  19. Using organotypic (raft) epithelial tissue cultures for the biosynthesis and isolation of infectious human papillomaviruses.

    Science.gov (United States)

    Ozbun, Michelle A; Patterson, Nicole A

    2014-08-01

    Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection. Copyright © 2014 John Wiley

  20. VACCINATION AGAINST HUMAN PAPILLOMAVIRUS INFECTION: A SAFE SOLUTION TO THE GLOBAL PROBLEM

    Directory of Open Access Journals (Sweden)

    M.G. Galitskaya

    2011-01-01

    Full Text Available The problem of diagnosis, prevention and treatment of diseases caused by human papilloma virus (HPV, in recent years has become more urgent, not only for physicians, scientists, but also for patients. This is due to the high contagiousness of HPV, its prevalence and, of course, proved oncogenicity. Creation and introduction of preventive vaccines against the most common HPV types played a definite role in the global health, and, of course, raised the attention of doctors and the public to human papillomavirus infection and associated diseases. At the same time propaganda against vaccination blocks the widespread adoption of this disease prevention in our country. In this paper, we introduce the American experience of monitoring vaccination adverse events.Key words: human papillomavirus infection, prevention, vaccination, adverse events, monitoring, children.

  1. The most effective and promising population health strategies to advance human papillomavirus vaccination.

    Science.gov (United States)

    Jacobson, Robert M; Agunwamba, Amenah A; St Sauver, Jennifer L; Finney Rutten, Lila J

    2016-01-01

    The US is failing to make substantive progress toward improving rates of human papillomavirus vaccine uptake. While the Healthy People 2020 goal for human papillomavirus (HPV) vaccination is 80%, the three-dose completion rate in the US in 2014 for 13- to 17-year-old females is less than 40%, and the rate for males is just above 20%. Experts point to a number of reasons for the poor HPV vaccination rates including parental concerns about safety, necessity, and timing. However, the evidence refuting these concerns is substantial. Efforts focusing on education and communication have not shown promise, but several population health strategies have reminder/recall systems; practice-focused strategies targeting staff, clinicians, and parents; assessment and feedback activities; and school-based HPV vaccination programs.

  2. Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: a systematic review.

    Science.gov (United States)

    Fesenfeld, Michaela; Hutubessy, Raymond; Jit, Mark

    2013-08-20

    The World Health Organization recommends establishing that human papillomavirus vaccination is cost-effective before vaccine introduction. We searched Pubmed, Embase and the Cochrane Library to 1 April 2012 for economic evaluations of human papillomavirus vaccination in low and middle income countries. We found 25 articles, but almost all low income countries and many middle income countries lacked country-specific studies. Methods, assumptions and consequently results varied widely, even for studies conducted for the same country. Despite the heterogeneity, most studies conclude that vaccination is likely to be cost-effective and possibly even cost saving, particularly in settings without organized cervical screening programmes. However, study uncertainty could be reduced by clarity about vaccine prices and vaccine delivery costs. The review supports extending vaccination to low income settings where vaccine prices are competitive, donor funding is available, cervical cancer burden is high and screening options are limited. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. An optimized formulation of a thermostable spray dried virus-like particles vaccine against human papillomavirus

    Science.gov (United States)

    Saboo, Sugandha; Tumban, Ebenezer; Peabody, Julianne; Wafula, Denis; Peabody, David S.; Chackerian, Bryce; Muttil, Pavan

    2016-01-01

    Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP) based vaccine for Human Papillomavirus (HPV) infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multi-component excipient system and by optimizing the spray drying parameters using a half-factorial design approach. Dry powder VLPs were stable after spray drying and after long-term storage at elevated temperatures. Immunization of mice with a single dose of reconstituted dry powder VLPs that were stored at 37°C for more than a year elicited high anti-L2 IgG antibody titers. Spray dried thermostable, broadly protective L2 bacteriophage VLPs vaccine could be accessible to remote regions of the world (where ~84% of cervical cancer patients reside) by eliminating the cold-chain requirement during transportation and storage. PMID:27019231

  4. Superior therapeutic efficacy of alphavirus-mediated immunization against human papilloma virus type 16 antigens in a murine tumour model : effects of the route of immunization

    NARCIS (Netherlands)

    Daemen, T; Riezebos-Brilman, A; Regts, J; Dontje, B; van der Zee, A; Wilschut, J

    2004-01-01

    In our efforts to develop a strong, effective immune response against cervical carcinoma and premalignant disease, we study the use of recombinant Semliki Forest virus (SFV) encoding the oncoproteins E6 and E7 from high-risk human papilloma viruses (HPVs). Optimal immunization conditions are

  5. Role of high-risk human papillomavirus in the etiology of oral and oropharyngeal cancers in Thailand: A case-control study.

    Science.gov (United States)

    Chotipanich, Adit; Siriarechakul, Surattaya; Mungkung, On-Ong

    2018-01-01

    Among developing countries, Thailand shows no increase in the incidence of human papillomavirus-driven oropharyngeal cancer. The causal role of human papillomavirus infection in this pathology has not been researched thoroughly. A hospital-based, case-control study was performed which included 104 patients with newly diagnosed oral and oropharyngeal squamous cell carcinomas and 104 individuals without cancer. The Cervista high-risk human papillomavirus and 16/18 assays were used to detect human papillomavirus. Odds ratios were used to assess the association between high-risk genotypes of human papillomavirus and the cancers. High-risk human papillomavirus was detected in 4 of 52 (7.7%) oral cancer cases, 6 of 52 (11.5%) oropharyngeal cancer cases, and 1 of 104 (0.96%) control subjects. Of 104 cancer patients in the study, 83 were smokers. High-risk human papillomavirus was significantly associated with oropharyngeal cancer (odds ratio = 13.44, 95% confidence interval = 1.6-114.8) but was nonsignificantly associated with oral cancer (odds ratio = 8.58, 95% confidence interval = 0.9-78.9). However, after adjustment for smoking, high-risk human papillomavirus was determined to be nonsignificantly associated with oropharyngeal cancer (adjusted odds ratio = 5.83, 95% confidence interval = 0.8-43.5). Although low human papillomavirus prevalence was observed, the rate of high-risk human papillomavirus infection in the cancer group was still higher than that in the control group. Smoking may have an influence on the etiology of human papillomavirus-related cancers. However, the study is underpowered to clarify the role of human papillomavirus as the independent risk factor for oral and oropharyngeal cancers in the Thai population.

  6. Pain in adolescent girls receiving human papillomavirus vaccine with concomitantly administered vaccines.

    Science.gov (United States)

    Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

    2015-02-01

    Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

  7. The human papillomavirus vaccine: A powerful tool for the primary prevention of cervical cancer.

    OpenAIRE

    Nubia Muñoz; Julio César Reina; Gloria Inés Sánchez

    2009-01-01

    Prophylactic human papillomavirus (HPV) vaccine is the most promissory public health tool for primary prevention of cervical cancer. Immunization of females before the acquisition of HPV infection has the greatest impact in preventing pre-neoplasic lesions and cervical cancer. Current HPV vaccines do not eliminate cervical cancer risk, therefore, screening should continue covering vaccinated as well as women that do not get the vaccine. The strategies that include combination of high-coverage...

  8. Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells

    OpenAIRE

    Kinjo, T; Kamiyama, K; Chinen, K; Iwamasa, T; Kurihara, K; Hamada, T

    2003-01-01

    Background/Aim: It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, ...

  9. Epidemiological study in Okinawa, Japan, of human papillomavirus infection of the uterine cervix.

    OpenAIRE

    Maehama, Toshiyuki

    2005-01-01

    OBJECTIVE: To investigate the prevalence and type distribution of human papillomavirus (HPV) in women with normal cervical cytology and with cervical intraepithelial neoplasia I to III(CIN) or carcinoma of the cervix in Okinawa, Japan. METHODS: We investigated HPV DNA in 4,078 subjects with cytologically normal cervices, 279 subjects with CIN, and 383 subjects with cervical cancer in Okinawa Prefecture in Japan. The presence of HPV DNA was also compared among generations. HPV DNA was both det...

  10. Characterization of human papillomavirus type 66 from an invasive carcinoma of the uterine cervix.

    OpenAIRE

    Tawheed, A R; Beaudenon, S; Favre, M; Orth, G

    1991-01-01

    Human papillomavirus (HPV) DNA sequences coexisting with HPV16 and HPV45 were cloned from an invasive cervical carcinoma. The cloned HPV was shown to be a novel type, named HPV66, and is related to HPV56 (an HPV detected in cervical cancer). After screening 160 anogenital biopsies, four specimens exhibited histological features of intraepithelial neoplasia and contained HPV66 sequences. Of these, three were found to be associated with another HPV type.

  11. Exploring human papillomavirus vaccination refusal among ethnic minorities in England: A comparative qualitative study

    OpenAIRE

    Forster, Alice S.; Rockliffe, Lauren; Marlow, Laura A.V.; Bedford, Helen; McBride, Emily; Waller, Jo

    2017-01-01

    Abstract Objectives In England, uptake of human papillomavirus (HPV) vaccination to prevent HPV‐related cancer is lower among girls from ethnic minority backgrounds. We aimed to explore the factors that prevented ethnic minority parents from vaccinating, compared to White British nonvaccinating parents and vaccinating ethnic minority parents. Methods Interviews with 33 parents (n = 14 ethnic minority non‐vaccinating, n = 10 White British nonvaccinating, and n = 9 ethnic minority vaccinating) ...

  12. Human Papillomavirus infection in men residing in Brazil, Mexico, and the USA

    OpenAIRE

    2008-01-01

    OBJECTIVE: To assess Human Papillomavirus (HPV) type distribution among men ages 18 years and older recruited from three different countries utilizing a common protocol for sampling HPV detection, and to evaluate whether HPV detection differs by age and country. MATERIAL AD METHODS: The study protocol includes a pre-enrollment run-in visit, a baseline (enrollment) visit, and nine additional visits after enrollment scheduled six months apart. For this analysis, the first 1160 men who completed...

  13. 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...

  14. Using Facebook to Recruit Young Australian Men Into a Cross-Sectional Human Papillomavirus Study

    OpenAIRE

    Das, Roopa; Machalek, Dorothy A; Molesworth, Edmund G; Garland, Suzanne M

    2017-01-01

    Background Young men can be difficult to engage in health research using traditional methods of recruitment. Social networking sites are increasingly being used to recruit participants into health research, due to their cost effectiveness, overall generalizability, and wide reach. Objective The aim of this study was to determine the feasibility of using Facebook to recruit young Australian men into a human papillomavirus (HPV) prevalence study. Methods We recruited male permanent residents of...

  15. Human papillomavirus in oral lesions Virus papiloma humano en lesiones orales

    OpenAIRE

    Joaquín V. Gónzalez; Rafael A. Gutiérrez; Alicia Keszler; Maria Del Carmen Colacino; Lidia V. Alonio; Angélica R. Teyssie; Maria Alejandra Picconi

    2007-01-01

    Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell ...

  16. [Human papillomavirus and cervical cancer in México: a constant struggle].

    Science.gov (United States)

    Torres-Poveda, Kirvis; Madrid-Marina, Vicente

    2015-01-01

    Given that human papillomavirus and cervical cancer are a health problem in México, since they affect women of reproductive age and have a negative impact on our society, it is crucial to prevent those diseases and to raise awareness among physicians who deal with their clinical and therapeutic management. That is the reason why we show three Original contributions and 13 Current themes in this supplement of the Revista Médica del Instituto Mexicano del Seguro Social.

  17. DNA damage response is hijacked by human papillomaviruses to complete their life cycle

    OpenAIRE

    Hong, Shi-yuan

    2017-01-01

    The DNA damage response (DDR) is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses (HPVs) are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identifi...

  18. Cutaneous Human Papillomavirus Infection and Development of Subsequent Squamous Cell Carcinoma of the Skin

    OpenAIRE

    Hampras, Shalaka S.; Reed, Rhianna A.; Bezalel, Spencer; Cameron, Michael; Cherpelis, Basil; Fenske, Neil; Sondak, Vernon K.; Messina, Jane; Tommasino, Massimo; Gheit, Tarik; Rollison, Dana E.

    2016-01-01

    The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC (n = 150) enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available...

  19. Human papillomavirus infection in Beijing, People's Republic of China: a population-based study

    Science.gov (United States)

    Zhao, R; Zhang, W Y; Wu, M H; Zhang, S W; Pan, J; Zhu, L; Zhang, Y P; Li, H; Gu, Y S; Liu, X Z

    2009-01-01

    Background: No recent data exist on human papillomavirus (HPV) infection in Beijing, People's Republic of China. Materials and method We interviewed and examined a representative, randomly selected sample of 5552 sexually active women aged 25–54 years. Cervical cell samples were analysed for HPV DNA by a MY09/11-based PCR assay. Results: Human papillomavirus prevalence was 6.7% overall and 4.8% among women without cervical abnormalities. Of the 21 subtypes identified, HPV16 was the commonest type (2.6% overall; 39.1% of HPV-positive women), followed by HPV 58 (1.0%), 33 (0.8%), 43 (0.7%) and 56 (0.7%). High-risk HPV types predominated in all age groups. Human papillomavirus prevalence was highest in young to middle-aged women. Marital status, number of husband's sexual partners, age at sexual debut and nulligravidity were all associated with being HPV positive. Conclusions: In our survey, HPV 16, HPV 58 and HPV 33 were the most prevalent HPV types in Beijing, indicating the potential for the prophylactic HPV 16/18 vaccine in China. PMID:19862002

  20. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

    DEFF Research Database (Denmark)

    Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

    2010-01-01

    To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

  1. Trivalent Human Papillomavirus (HPV) VLP vaccine covering HPV type 58 can elicit high level of humoral immunity but also induce immune interference among component types.

    Science.gov (United States)

    Zhang, Ting; Xu, Yufei; Qiao, Liang; Wang, Youchun; Wu, Xueling; Fan, Dongsheng; Peng, Qinglin; Xu, Xuemei

    2010-04-26

    Both Human Papillomavirus (HPV) type 16/18 bivalent vaccine and type 16/18/6/11 quadrivalent vaccine have been proved to be safe and effective, and licensed for public use. However, these two vaccines do not quite match the distribution of HPV types in China, Southeast Asia and Latin America, where HPV 58 is highly prevalent. Here we produced three types of virus-like particles (VLPs) in baculovirus expression system, formulated a trivalent vaccine containing HPV 16, 18, and 58 L1 VLPs and examined its in vitro neutralizing titers. This vaccine could induce high level and long-term humoral immunity against the component types. But immune interference was observed when comparing type specific neutralizing antibody levels induced by trivalent vaccine to those by corresponding monovalent vaccines. This kind of interference would become more obvious when formulating more types of VLPs into multivalent vaccines, but could be greatly overcome by decreasing the antigen dosage and adding a proper adjuvant. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. No increased sperm DNA fragmentation index in semen containing human papillomavirus or herpesvirus

    DEFF Research Database (Denmark)

    Kaspersen, Maja Døvling; Bungum, Mona; Fedder, Jens

    2013-01-01

    It remains unknown whether human papillomaviruses (HPVs) or human herpesviruses (HHVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen from 76 sperm donors was examined by a PCR......-based hybridization array that identifies all HHVs and 35 of the most common HPVs. Sperm DNA integrity was determined by the sperm chromatin structure assay. HPVs or HHVs, or both, were found in 57% of semen samples; however, sperm DNA fragmentation index was not increased in semen containing these viruses....

  3. Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus.

    Directory of Open Access Journals (Sweden)

    Linda L Theisen

    Full Text Available Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and

  4. Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Joseph G Skeate

    Full Text Available Nano-Pulse Stimulation (NPS is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

  5. Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

    Science.gov (United States)

    Skeate, Joseph G; Da Silva, Diane M; Chavez-Juan, Elena; Anand, Snjezana; Nuccitelli, Richard; Kast, W Martin

    2018-01-01

    Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s) associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

  6. Design and statistical considerations for studies evaluating the efficacy of a single dose of the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Sampson, Joshua N; Hildesheim, Allan; Herrero, Rolando; Gonzalez, Paula; Kreimer, Aimee R; Gail, Mitchell H

    2018-05-01

    Cervical cancer is a leading cause of cancer mortality in women worldwide. Human papillomavirus (HPV) types 16 and 18 cause about 70% of all cervical cancers. Clinical trials have demonstrated that three doses of either commercially available HPV vaccine, Cervarix ® or Gardasil ®, prevent most new HPV 16/18 infections and associated precancerous lesions. Based on evidence of immunological non-inferiority, 2-dose regimens have been licensed for adolescents in the United States, European Union, and elsewhere. However, if a single dose were effective, vaccine costs would be reduced substantially and the logistics of vaccination would be greatly simplified, enabling vaccination programs in developing countries. The National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomédicas (ACIB) are conducting, with support from the Bill & Melinda Gates Foundation and the International Agency for Research on Cancer (IARC), a large 24,000 girl study to evaluate the efficacy of a 1-dose regimen. The first component of the study is a four-year non-inferiority trial comparing 1- to 2-dose regimens of the two licensed vaccines. The second component is an observational study that estimates the vaccine efficacy (VE) of each regimen by comparing the HPV infection rates in the trial arms to those in a contemporaneous survey group of unvaccinated girls. In this paper, we describe the design and statistical analysis for this study. We explain the advantage of defining non-inferiority on the absolute risk scale when the expected event rate is near 0 and, given this definition, suggest an approach to account for missing clinic visits. We then describe the problem of estimating VE in the absence of a randomized placebo arm and offer our solution. Copyright © 2018. Published by Elsevier Inc.

  7. Reported changes in sexual behaviour and human papillomavirus knowledge in Peruvian female sex workers following participation in a human papillomavirus vaccine trial.

    Science.gov (United States)

    Brown, B; Blas, M M; Heidari, O; Carcamo, C; Halsey, N A

    2013-07-01

    Limited data exist on the effect of clinical trial participation on sexual behavioural change. Two hundred female sex workers working in Lima, Peru received human papillomavirus (HPV) vaccine in either the standard (0, 2, 6 months) or modified (0, 3, 6 months) schedule. Participants received comprehensive screening and treatment for sexually transmitted infections (STIs), counselling on safe sex practices, education about HPV and the HPV vaccine, contraceptives (oral and condoms) and family planning at each visit. We assessed vaccine completion rates, change in sexual practices, and changes in HPV knowledge before and after participation in the vaccine trial. There were high rates of vaccine completion, 91% overall. The estimated number of reported new and total clients over a 30-day period decreased significantly (P Knowledge about HPV and HPV-related disease increased among all participants. In addition, all participants listed at least one preventive strategy during the month 7 follow-up survey.

  8. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

    DEFF Research Database (Denmark)

    Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

    2010-01-01

    To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).......To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

  9. A vaccine of L2 epitope repeats fused with a modified IgG1 Fc induced cross-neutralizing antibodies and protective immunity against divergent human papillomavirus types.

    Science.gov (United States)

    Chen, Xue; Liu, Hongyang; Zhang, Ting; Liu, Yanchun; Xie, Xixiu; Wang, Zhirong; Xu, Xuemei

    2014-01-01

    Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17-36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%. Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization. Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits. Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development.

  10. [Low rate of oropharyngeal human papillomavirus infection among women with cervical lesion. Preliminary results from the South-Eastern Hungarian population].

    Science.gov (United States)

    Vanya, Melinda; Jakó, Mária; Terhes, Gabriella; Szakács, László; Kaiser, László; Deák, Judit; Bártfai, György

    2016-01-10

    Although the natural history of cervical and oral human papillomavirus infection has been intensively investigated in the past years, the ability of this virus to infect oral and genital mucosae in the same individual and its potential to co-infect both cervical and oral mucosa are still unclear. The aim of the authors was to assess the presence of oropharyngeal human papillomavirus infection in women with cervical lesions in the South-Eastern Hungarian population. The total of 103 women have been included in the study between March 1, 2013 and January 1, 2015. Brushing was used to collect cells from the oropharyngeal mucosa. Human papillomavirus DNA was detected using polymerase chain reaction, and Amplicor line blot test was used for genotyping. Oropharyngeal human papillomavirus infection was detected in 2 cases (3%). The detected genotypes were 31, 40/61 and 73 in the oropharyngeal region. The results indicate that in women with cervical lesions oropharyngeal human papillomavirus infection rarely occurs.

  11. Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

    International Nuclear Information System (INIS)

    Kitkumthorn, Nakarin; Mutirangura, Apiwat; Yanatatsanajit, Pattamawadee; Kiatpongsan, Sorapop; Phokaew, Chureerat; Triratanachat, Surang; Trivijitsilp, Prasert; Termrungruanglert, Wichai; Tresukosol, Damrong; Niruthisard, Somchai

    2006-01-01

    The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer

  12. Early experience with human papillomavirus vaccine introduction in the United States, Canada and Australia.

    Science.gov (United States)

    Shefer, Abigail; Markowitz, Lauri; Deeks, Shelley; Tam, Theresa; Irwin, Kathleen; Garland, Suzanne M; Schuchat, Anne

    2008-08-19

    Successful incorporation of a new vaccine into a nation's vaccination program requires addressing a number of issues, including: 1) establishing national recommendations; 2) assuring education of and acceptance by the public and medical community; 3) establishing and maintaining an appropriate infrastructure for vaccine delivery; 4) financing the vaccine and the program, in addition to political will. This article reviews the early experience with implementation of human papillomavirus (HPV) vaccination programs. It focuses on the United States of America and Canada and provides a brief report on Australia, where introduction is underway.

  13. 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....

  14. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

    Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

  15. 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...

  16. A systematic review of factors influencing human papillomavirus vaccination among immigrant parents in the United States.

    Science.gov (United States)

    Kim, Kyounghae; LeClaire, Anna-Rae

    2017-11-21

    To critically appraise factors influencing human papillomavirus (HPV) vaccination among immigrant parents in the United States, a comprehensive search of electronic databases and reference lists was conducted. The findings from 22 articles were ordered based on a socioecological model. About 30% of children initiated and 14% completed a three-dose series. Correlates of HPV vaccine initiation rates included lack of information, concerns about vaccine safety and promiscuity, providers' recommendations, school mandates, financial issues, immigration laws, and living in disadvantaged neighborhoods. Upstream initiatives embracing cultural descriptors could facilitate HPV vaccination, reducing HPV-related disparities in cancer among immigrants in the US.

  17. The role of Human papillomavirus in head and neck cancer and the impact on radiotherapy outcome

    International Nuclear Information System (INIS)

    Lassen, Pernille

    2010-01-01

    The profound influence of Human papillomavirus (HPV) on the epidemiological pattern and clinical course of head and neck cancer (HNSCC) has led to a change in the traditional understanding of this disease entity. Separate therapeutic strategies based on tumour HPV status are under consideration and in this light provision of knowledge concerning the influence of tumour HPV on the radiation response in HNSCC appears highly relevant. This review provides a summary of the current understanding of the role of HPV in head and neck cancer with specific focus on the viral impact on radiotherapy outcome of HNSCC.

  18. The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment.

    Science.gov (United States)

    Bogani, Giorgio; Leone Roberti Maggiore, Umberto; Signorelli, Mauro; Martinelli, Fabio; Ditto, Antonino; Sabatucci, Ilaria; Mosca, Lavinia; Lorusso, Domenica; Raspagliesi, Francesco

    2018-02-01

    Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The problem of false-positive human papillomavirus DNA tests in cervical screening

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Pribac, Igor; Frederiksen, Maria Eiholm

    2013-01-01

    Human Papillomavirus (HPV) testing has been extensively studied in randomized controlled trials of primary cervical screening. Based on encouraging results concerning its high detection rates and a high negative predictive value for high-grade cervical intraepithelial neoplasia (CIN), HPV testing...... will probably replace cytology in future primary cervical screening. However, HPV testing is associated with more frequent false-positive tests compared to cytology. False-positive tests are defined as positive screening tests which are not subsequently confirmed with high-grade CIN. Several authors have...

  20. Discrete-time semi-Markov modeling of human papillomavirus persistence

    Science.gov (United States)

    Mitchell, C. E.; Hudgens, M. G.; King, C. C.; Cu-Uvin, S.; Lo, Y.; Rompalo, A.; Sobel, J.; Smith, J. S.

    2011-01-01

    Multi-state modeling is often employed to describe the progression of a disease process. In epidemiological studies of certain diseases, the disease state is typically only observed at periodic clinical visits, producing incomplete longitudinal data. In this paper we consider fitting semi-Markov models to estimate the persistence of human papillomavirus (HPV) type-specific infection in studies where the status of HPV type(s) is assessed periodically. Simulation study results are presented indicating the semi-Markov estimator is more accurate than an estimator currently used in the HPV literature. The methods are illustrated using data from the HIV Epidemiology Research Study (HERS). PMID:21538985

  1. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    OpenAIRE

    Clifford, Gary M.; de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

    2016-01-01

    Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 384...

  2. Prevalence of Human Papillomavirus in Self-Taken Samples from Screening Nonattenders

    DEFF Research Database (Denmark)

    Lam, J U H; Rebolj, M; Ejegod, D M

    2017-01-01

    The Copenhagen Self-Sampling Initiative (CSi) has shown how human papillomavirus (HPV)-based self-sampling can be used to increase screening participation among 23,632 nonattenders in the Capital Region of Denmark. In this study, we describe HPV prevalence and genotype frequency in 4,824 self...... study, which had been undertaken in the same screening laboratory. Nonattenders had an HPV prevalence of 11.3% as determined by the CLART assay, which was lower than that for women from the Horizon study (18.5%). One-third of the CSi women who tested HPV positive by self-sampling tested HPV negative...

  3. Vacinas contra o Papilomavirus humano Vaccines against human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Sidney Roberto Nadal

    2006-09-01

    outras doenças anogenitais associadas à infecção pelo HPV.Papillomavirus infection is more common in young sexually active people. It is so prevalent that from 75% to 80% of this population will be infected in their lifetime. Most lesions will be eradicated spontaneously at the point of not being detected even with the most sensible methods. Persistent infections with oncogenic HPV increase intraepithelial neoplasia and cancer risks. Two ways of prevention may be proposed: screening for precursor lesions and immunization against HPV, to avoid them. Although anogenital cancer incidence is decreasing with screening methods, costs are high and emotional disturbance may be caused by an abnormal result. So, vaccines to prevent diseases associated to HPV must be available. In the last decade, clinical tests began with several vaccines targeting the most frequent HPV types. The goal of prophylactic vaccines is to prevent primary or persistent HPV infections, and thus prevent cervical cancer and/or genital warts and the aim of the therapeutic types is to prevent progression of HPV infection, induce regression of intraepithelial neoplasia or condylomata, or eradicate residual cervical cancer. Prophylactic HPV vaccines in late stages of clinical testing are composed of HPV L1 capsid protein that self-assemble into virus-like particles (VLPs when expressed in recombinant systems, resulting in strong adaptive immune responses that are capable of neutralizing subsequent natural infections. Some studies observed 100% efficacy in preventing clinical disease for specific HPV types at least 5 years after immunization. Vaccines that target E6 and E7 proteins also represent an important strategy to control HPV-associated lesions and are in test in animal models. HPV vaccines seem to be more effective when administered prior to initiation of sexual activity, and vaccination campaigns should target preadolescent and adolescent populations. It is expected that with good coverage of the

  4. Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection

    DEFF Research Database (Denmark)

    Jensen, Kirsten E; Thomsen, Louise T; Schmiedel, Sven

    2014-01-01

    Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithel...... intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection.......Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical...

  5. Original Research Human papillomavirus in head and neck ...

    African Journals Online (AJOL)

    2017 The College of Medicine and the Medical Association of Malawi. This work is ... Original Research. Human ... simultaneous evaluation of other risk factors including HIV ..... increased HNSCC compared to HIV-negative people.18,19.

  6. Human Papillomavirus Detection from Human Immunodeficiency Virus-Infected Colombian Women's Paired Urine and Cervical Samples

    Science.gov (United States)

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C.; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C.; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E.; Patarroyo, Manuel A.

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance. PMID:23418581

  7. Is routine human papillomavirus vaccination an option for Ghana ...

    African Journals Online (AJOL)

    Cervical cancer remains an important public health problem in developing countries where over 80% of the global burden occurs annually but screening has been ineffective. In a polygamous country like Ghana with a high incidence of cervical cancer but no national screening program, the Human Papilloma Virus (HPV) ...

  8. Absence of an association of human polyomavirus and papillomavirus infection with lung cancer in China: a nested case–control study

    International Nuclear Information System (INIS)

    Colombara, Danny V.; Manhart, Lisa E.; Carter, Joseph J.; Hawes, Stephen E.; Weiss, Noel S.; Hughes, James P.; Qiao, You-Lin; Taylor, Philip R.; Smith, Jennifer S.; Galloway, Denise A.

    2016-01-01

    Studies of human polyomavirus (HPyV) infection and lung cancer are limited and those regarding the association of human papillomavirus (HPV) infection and lung cancer have produced inconsistent results. We conducted a nested case–control study to assess the association between incident lung cancer of various histologies and evidence of prior infection with HPyVs and HPVs. We selected serum from 183 cases and 217 frequency matched controls from the Yunnan Tin Miner’s Cohort study, which was designed to identify biomarkers for early detection of lung cancer. Using multiplex liquid bead microarray (LBMA) antibody assays, we tested for antibodies to the VP1 structural protein and small T antigen (ST-Ag) of Merkel cell, KI, and WU HPyVs. We also tested for antibodies against HPV L1 structural proteins (high-risk types 16, 18, 31, 33, 52, and 58 and low-risk types 6 and 11) and E6 and E7 oncoproteins (high risk types 16 and 18). Measures of antibody reactivity were log transformed and analyzed using logistic regression. We found no association between KIV, WUV, and MCV antibody levels and incident lung cancer (P-corrected for multiple comparisons >0.10 for all trend tests). We also found no association with HPV-16, 18, 31, 33, 52, and 58 seropositivity (P-corrected for multiple comparisons >0.05 for all). Future studies of infectious etiologies of lung cancer should look beyond HPyVs and HPVs as candidate infectious agents. The online version of this article (doi:10.1186/s12885-016-2381-3) contains supplementary material, which is available to authorized users

  9. [Genetics and susceptibility to human papillomaviruses: epidermodysplasia verruciformis, a disease model].

    Science.gov (United States)

    Orth, Gérard

    2010-06-01

    The outcomes of infection by human papillomaviruses (HPV), both oncogenic and non oncogenic, show major interindividual variability The underlying genetic factors and mechanisms are poorly known, but their complexity is illustrated by epidermodysplasia verruciformis (EV), a rare autosomal recessive genodermatosis associated with a high risk of non melanoma skin cancer. This model disease is characterized by abnormal susceptibility to widespread betapapillomaviruses, including HPV-5, a virus associated with EV cancers. Most cases of EV are caused by a mutation that inactivates either of two related genes, EVER1 and EVER2. This inactivation likely compensates for the absence of a viral gene (E5 or E8) essential for HPV pathogenicity. Proteins E5 and E8 interfere with the interaction between EVER proteins and ZnT1, a zinc transporter EV is thus likely to represent a primary defect of intrinsic (constitutive) immunity or innate immunity to betapapillomaviruses, involving modulation of zinc homeostasis upon keratinocyte infection. It remains to be established which cellular genes are involved in intrinsic, innate or acquired immune responses to other human papillomaviruses, including oncogenic genital types.

  10. HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

    Science.gov (United States)

    De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

    2008-11-01

    The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

  11. Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso

    Directory of Open Access Journals (Sweden)

    Ina Marie Angèle Traore

    2016-01-01

    Full Text Available High-risk human papillomavirus (HPV is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3±8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181. The most common high-risk HPV genotypes were HPV 39 (18.5%, HPV 52 (16.7%, HPV 18 (14.8%, and HPV 35 (13.0%. HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine.

  12. Prevalence of mucosal and cutaneous human papillomavirus in Moroccan breast cancer

    Directory of Open Access Journals (Sweden)

    Amal ElAmrani

    2018-06-01

    Full Text Available Background: Due to recent technical improvements and some encouraging new results, there has been a resurgence of interest in the possibility that a substantial proportion of breast cancers (BCs may be caused by viral infections, including Human papillomavirus (HPV. The aim of this study was to determine the prevalence of mucosal and cutaneous HPV in tumours from Moroccan BC patients. Materials and methods: Frozen tumours from 76 BC cases and 12 controls were evaluated for the presence of 62 HPV-types using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. Results: HPV DNA was found in 25.0% of BC tumours and only 8.3% of controls. Beta and gamma HPV types were found in 10.5% and 6.6% of BC tumours, respectively. High-risk mucosal types HPV16 and 18 were not detected in the subjects, but other probable/possible high-risk or high-risk -HPV types (HPV51, 52, 58, 59, and 66 were found in 5.3% of BC tumours. Statistical analysis showed no significant difference between, controls, BC cases and the inflammatory status (p > 0.05. Conclusion: HPV DNA was found 3 times as frequently in the BC tumours as in the controls. However, this difference requires confirmation in a larger sample. Keywords: Breast cancer, Human papillomavirus, Inflammatory breast cancer, Type-specific multiplex genotyping, Morocco

  13. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C

    Directory of Open Access Journals (Sweden)

    Diane M. Da Silva

    2015-12-01

    Full Text Available Human papillomaviruses (HPV establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC, the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C, and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8+ T cells in vitro. Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8+ T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection. Keywords: Papillomavirus, HPV16, Langerhans cells, Immune escape

  14. Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso.

    Science.gov (United States)

    Traore, Ina Marie Angèle; Zohoncon, Théodora Mahoukèdè; Dembele, Adama; Djigma, Florencia W; Obiri-Yeboah, Dorcas; Traore, Germain; Bambara, Moussa; Ouedraogo, Charlemagne; Traore, Yves; Simpore, Jacques

    2016-01-01

    High-risk human papillomavirus (HPV) is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3 ± 8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181). The most common high-risk HPV genotypes were HPV 39 (18.5%), HPV 52 (16.7%), HPV 18 (14.8%), and HPV 35 (13.0%). HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine.

  15. Are 20 human papillomavirus types causing cervical cancer?

    OpenAIRE

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim

    2014-01-01

    Abstract: In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the -Papillomaviridae, in particular to the species 5 (HPV51), 6 (HPV56), 7 (H...

  16. E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway

    International Nuclear Information System (INIS)

    Contreras-Paredes, Adriana; Cruz-Hernandez, Erick de la; Martinez-Ramirez, Imelda; Duenas-Gonzalez, Alfonso; Lizano, Marcela

    2009-01-01

    Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation

  17. Serology for human papillomavirus Serología para el virus del papiloma humano

    Directory of Open Access Journals (Sweden)

    Pierre Coursaget

    2003-01-01

    Full Text Available Difficulties with serology for papillomavirus are associated with the large number of human papillomavirus, cross-reactions between papillomavirus, and to the diversity of lesions and target sites for infection. In addition, the expression of the papillomavirus in the superficial layers of the epithelium gives rise to the weak presentation to immunocompetent cells of viral antigens, which in turn gives rise to a weak serological response. Distinct efforts have been made in previous decades to develop more specific and sensitive serological assays. These former studies use fusion proteins and synthetic peptides, although they remain on the whole uninteresting, due to their lack of sensitivity and specificity. Only in the last few years, and principally due to the advent of various virus-like particles (VLP, have more sensitive and specific assays become available.Las limitaciones para la utilización de la serología para el estudio del virus del papiloma humano con fines clínicos están asociadas con la gran variedad de subtipos humanos, con las reacciones cruzadas que existen entre diversos genotipos, la diversidad de lesiones precursoras de cáncer y con los sitios blancos de infección. Asimismo, la expresión del virus del papiloma humano en las capas superficiales del epitelio dan origen a una débil presentación de células inmunocompetentes de antígenos virales, lo cual origina una elevación de la respuesta serológica. Distintos esfuerzos se han realizado en décadas previas para desarrollar ensayos serológicos más específicos y sensibles. En muchas investigaciones se ha utilizado una fusión de proteínas y péptidos sintéticos que tienen como principal limitación su escasa sensibilidad y especificidad. Sólo en los últimos años, y principalmente debido al arribo de partículas parecidas a este virus, tenemos disponibles ensayos más sensibles y específicos, ampliamente descritos en este artículo.

  18. 78 FR 42530 - Prospective Grant of an Exclusive License: Human Papillomavirus 16 E2 and E6 Peptides for...

    Science.gov (United States)

    2013-07-16

    ... peptide from HPV 16. E6 peptide vaccines are potentially prophylactic or therapeutic for cervical cancer... Exclusive License: Human Papillomavirus 16 E2 and E6 Peptides for Cervical Cancer Vaccine Development AGENCY... principal place of business in Augusta, Georgia. The United States of America is an assignee to the patent...

  19. Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin

    NARCIS (Netherlands)

    Kagie, M. J.; Kenter, G. G.; Zomerdijk-Nooijen, Y.; Hermans, J.; Schuuring, E.; Timmers, P. J.; Trimbos, J. B.; Fleuren, G. J.

    1997-01-01

    OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) infection in various vulvar lesions. METHODS: HPV infection using consensus primer-PCR was studied in 66 patients with vulvar carcinoma and in the synchronous epithelial lesions. RESULTS: HPV infection was present in 13/66

  20. Reevaluation of Epidemiological Data Demonstrates That It Is Consistent With Cross-Immunity Among Human Papillomavirus Types

    OpenAIRE

    Durham, David P.; Poolman, Eric M.; Ibuka, Yoko; Townsend, Jeffrey P.; Galvani , Alison P.

    2012-01-01

    Background. The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity.

  1. 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…

  2. Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers

    NARCIS (Netherlands)

    RESNICK, R. M.; Cornelissen, M. T.; WRIGHT, D. K.; EICHINGER, G. H.; FOX, H. S.; ter Schegget, J.; MANOS, M. M.

    1990-01-01

    We developed a polymerase chain reaction DNA amplification system using two distinct consensus oligonucleotide primer sets for the improved detection and typing of a broad spectrum of human genital papillomavirus (HPV) sequences, including those of novel viruses. The system incorporates one primer

  3. Prevalence and Type Distribution of Human Papillomavirus Among 1813 Men in Tanzania and the Relationship to HIV Status

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Iftner, Thomas; Mwaiselage, Julius

    2013-01-01

    Infection with high-risk (HR) human papillomavirus (HPV) is associated with penile cancer in men, cervical cancer in women, and anal cancer and certain types of head and neck cancers in both sexes. Few studies have assessed the prevalence and type distribution of HPV among men in sub-Saharan Africa......, where the rates of HIV and penile and cervical cancer are high....

  4. Anal and penile high-risk human papillomavirus prevalence in HIV-negative and HIV-infected MSM

    NARCIS (Netherlands)

    van Aar, Fleur; Mooij, Sofie H.; van der Sande, Marianne A. B.; Speksnijder, Arjen G. C. L.; Stolte, Ineke G.; Meijer, Chris J. L. M.; Verhagen, Dominique W. M.; King, Audrey J.; de Vries, Henry J. C.; Schim van der Loeff, Maarten F.

    2013-01-01

    Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in MSM. Analysis of baseline data from a prospective cohort study. MSM aged 18 years or older were

  5. Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries : a meta-analysis

    NARCIS (Netherlands)

    Setiawan, Didik; Luttjeboer, Jos; Pouwels, Koen B.; Wilschut, Jan C.; Postma, Maarten J.

    Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information

  6. 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,…

  7. Human Papillomavirus (HPV) Risk Factors, Vaccination Patterns, and Vaccine Perceptions among a Sample of Male College Students

    Science.gov (United States)

    Fontenot, Holly B.; Collins Fantasia, Heidi; Charyk, Anna; Sutherland, Melissa A.

    2014-01-01

    Objective: To examine human papillomavirus (HPV) vaccination rates, including initiation and completion of the vaccine series, and barriers to vaccination in a sample of male college students. Participants: Male students between the ages of 18 and 25 who reported being currently or previously sexually active (N = 735). Methods: A cross-sectional…

  8. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, MPM; VanLeeuwen, AM; Hollema, H; Quint, WGV; Pieters, WJLM

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  9. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, M. P.; van Leeuwen, A. M.; Hollema, H.; Quint, W. G.; Pieters, W. J.

    1997-01-01

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  10. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence

    DEFF Research Database (Denmark)

    Kjær, Susanne K; Frederiksen, Kirsten; Plum, Christian Edinger Munk

    2010-01-01

    Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection...

  11. Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer

    NARCIS (Netherlands)

    Gaarenstroom, K. N.; Kenter, G. G.; Bonfrer, J. M.; Korse, C. M.; Gallee, M. P.; Hart, A. A.; Müller, M.; Trimbos, J. B.; Helmerhorst, T. J.

    1994-01-01

    BACKGROUND: The objective of this study was to investigate the prognostic significance of serum antibodies to human papillomavirus (HPV)-16 peptides in patients with squamous cell cervical cancer. METHODS: Pretreatment sera from 78 patients and 198 control women were tested by an enzyme-linked

  12. Correlates to Human Papillomavirus Vaccination Status and Willingness to Vaccinate in Low-Income Philadelphia High School Students

    Science.gov (United States)

    Bass, Sarah B.; Leader, Amy; Shwarz, Michelle; Greener, Judith; Patterson, Freda

    2015-01-01

    Background: Little is known about the correlates of human papillomavirus (HPV) vaccination or willingness to be vaccinated in urban, minority adolescents. Methods: Using responses to the 2013 Youth Risk Behavior Survey in Philadelphia, a random sample of high schools provided weighted data representing 20,941 9th to 12th graders. Stratified by…

  13. Does Mother Know Best? An Actor-Partner Model of College-Age Women's Human Papillomavirus Vaccination Behavior

    Science.gov (United States)

    Krieger, Janice L.; Kam, Jennifer A.; Katz, Mira L.; Roberto, Anthony J.

    2011-01-01

    This study examined the associations of perceived threat, perceived efficacy, and parent-child communication with the extent to which college-age women received the human papillomavirus (HPV) vaccine. Daughters and their mothers completed a survey about the HPV vaccine (N = 182 dyads). The results showed that mothers' perceived self-efficacy to…

  14. Improvement of Gynecological Screening of Female Renal Transplant Recipients by Self-Sampling for Human Papillomavirus Detection

    NARCIS (Netherlands)

    Hinten, F.; Hilbrands, L.B.; Meeuwis, K.A.P.; Bergen-Verkuyten, M.C. van; Slangen, B.F.; Rossum, M.M. van; Rahamat-Langendoen, J.C.; Massuger, L.F.A.G.; Hullu, J.A. de; Melchers, W.J.G.

    2017-01-01

    OBJECTIVES: Female renal transplant recipients (RTRs) have increased risk for developing human papillomavirus (HPV)-related (pre)malignancies of the lower genital tract. Annual cervical screening is advised for RTRs, but the participation rate is low. The aim of this study is to investigate whether

  15. Presence of human papillomavirus in semen of healthy men is firmly associated with HPV infections of the penile epithelium

    NARCIS (Netherlands)

    Luttmer, Roosmarijn; Dijkstra, Maaike G.; Snijders, Peter J. F.; Jordanova, Ekaterina S.; King, Audrey J.; Pronk, Divera T. M.; Foresta, Carlo; Garolla, Andrea; Hompes, Peter G. A.; Berkhof, Johannes; Bleeker, Maaike C. G.; Doorbar, John; Heideman, Daniëlle A. M.; Meijer, Chris J. L. M.

    2015-01-01

    To study the source of human papillomavirus (HPV) in semen. Observational study (CCMO-NL3248800010). Academic hospital-based laboratory. Healthy male volunteers (n = 213). One penile scrape and three semen samples were obtained per participant for HPV-DNA testing by both GP5+/6+ polymerase chain

  16. Seroepidemiological Evaluation of High-Risk Human Papillomavirus Types Among Married and Unmarried Iranian Women in Tehran, Iran

    OpenAIRE

    Abedini; Karimi; Shamsy; Mansour Ghanaie; Gholinejad

    2016-01-01

    Background Human papillomavirus (HPV) is a DNA virus that establishes productive infections only in keratinocytes of the skin or mucous membranes. Objectives This study aimed to determine the frequency of two high-risk genotypes of HPV among married and unmarried Iranian women. Materials and Methods This cross-sectional population-based study consisted of two groups of women: non-m...

  17. A novel strategy for human papillomavirus detection and genotyping with SybrGreen and molecular beacon polymerase chain reaction

    NARCIS (Netherlands)

    Szuhai, K; Sandhaus, E; Kolkman-Uljee, SM; Lemaitre, M; Truffert, JC; Dirks, RW; Tanke, HJ; Fleuren, GJ; Schuuring, E; Raap, AK

    2001-01-01

    Human papillomaviruses (HPVs) play an important role in the pathogenesis of cervical cancer. For identification of the large number of different HPV types found in (pre)malignant lesions, a robust methodology is needed that combines general HPV detection with HPV genotyping. We have developed for

  18. Applying a gender lens on human papillomavirus infection: cervical cancer screening, HPV DNA testing, and HPV vaccination

    NARCIS (Netherlands)

    Brankovic, I; Verdonk, P.; Klinge, I.

    2013-01-01

    Background: 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

  19. Periodontitis and oral human papillomavirus infection among Hispanic adults

    Directory of Open Access Journals (Sweden)

    Ana Patricia Ortiz

    2018-06-01

    Full Text Available Introduction: Research on the association between periodontitis and oral human papilloma virus (HPV infection is inconsistent. The cross-sectional association of severe periodontitis with oral HPV infection was investigated in a sample of Hispanic adults. Methods: Data from the 2014–2016 San Juan Overweight Adults Longitudinal Study (n = 740 was analyzed. Periodontitis assessment and self-collection of oral HPV samples followed the National Health and Nutrition Examination Survey methodology. Periodontitis was defined using the Centers of Disease Control and Prevention/American Academy of Periodontology definition. HPV typing was performed using polymerase chain reaction. Multivariate logistic regression models were used to calculate odds ratios (ORs and 95% confidence intervals (CIs. Results: 5.7% of participants had oral HPV infection and 20.3% had severe periodontitis. Adults with severe periodontitis had higher odds of oral HPV infection than those with none/mild disease (OR=2.9, 95% CI: 1.0–8.4, p < 0.05 in multivariable analysis. Adults with clinical attachment loss≥ 7 mm and pocket depth PD≥ 6 mm had 2- to 3-fold higher odds of HPV infection. Conclusions: Severe periodontitis was positively associated to oral HPV infection. Longitudinal evaluation of periodontal inflammation's role in acquisition and persistence of oral HPV infection is needed, as periodontitis screening could identify individuals at increased risk of HPV-related oral malignancies. Keywords: Periodontitis, Oral HPV, Hispanics, Adults, Oral health, Puerto Rico

  20. Economic Burden of Human Papillomavirus-Related Diseases in Italy

    Science.gov (United States)

    Baio, Gianluca; Capone, Alessandro; Marcellusi, Andrea; Mennini, Francesco Saverio; Favato, Giampiero

    2012-01-01

    Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention. PMID:23185412

  1. The distribution of sexually-transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa

    Directory of Open Access Journals (Sweden)

    Hause Lara

    2007-07-01

    Full Text Available Abstract Background Human Papillomaviruses (HPV are double-stranded DNA viruses, considered to be the primary etiological agents in cervical intraepithelial neoplasias and cancers. Approximately 15–20 of the 40 mucosal HPVs confer a high-risk of progression of lesions to invasive cancer. In this study, we investigated the prevalence of sexually transmitted HPVs in Human Immunodeficiency Virus (HIV positive and negative patients in Zambia, Africa. The rate of high-risk HPV genotypes worldwide varies within each country. Thus, we sought to investigate the rates of HPV infection in sub-Saharan Africa and the potential role of HIV in affecting the HPV genotype distribution. Methods This retrospective cross-sectional study reports findings on the association and effects of HIV on HPV infections in an existing cohort of patients at University Teaching Hospital (UTH Lusaka, Zambia. The objective of this study was to assess HPV prevalence, genotype distribution and to identify co-factors that influence HPV infection. Polymerase chain reaction (PCR with two standard consensus primer sets (CpI/II and GP5+/6+ was used to test for the presence of HPV DNA. Primers specific for β-actin were used to monitor DNA quality. Vaginal lavage samples, collected between 1998-1999 from a total of 70 women, were part of a larger cohort that was also analyzed for HIV and human herpesvirus infection. Seventy of the samples yielded usable DNA. HIV status was determined by two rapid assays, Capillus and Determine. The incidence of HIV and HPV infections and HPV genotype distributions were calculated and statistical significance was determined by Chi-Squared test. Results We determined that most common HPV genotypes detected among these Zambian patients were types 16 and 18 (21.6% each, which is approximately three-fold greater than the rates for HPV16, and ten-fold greater than the rates for HPV18 in the United States. The worldwide prevalence of HPV16 is approximately 14

  2. Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.

    Science.gov (United States)

    Correnti, Maria; Medina, Francisco; Cavazza, María Eugenia; Rennola, Antonieta; Avila, Maira; Fernándes, Andreína

    2011-06-01

    Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women. Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections. HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31. Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Low Rate of Detection of Mucosal High-Risk-Type Human Papillomavirus in Korean Patients with Extragenital Bowen's Disease and Squamous Cell Carcinoma, Especially in Digital Cases

    Directory of Open Access Journals (Sweden)

    Hye-Rim Park

    2013-01-01

    Full Text Available Human papillomavirus (HPV infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (, squamous cell carcinoma (, bowenoid papulosis (, verrucous carcinoma (, actinic keratosis (, and basal cell carcinoma (. We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease ( nor those with squamous cell carcinoma ( showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6% of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (, while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7% of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.

  4. Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X.

    Science.gov (United States)

    Illiano, Elena; Bissa, Massimiliano; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo

    2016-10-02

    The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6 F47R ) and E7 (E7 GGG ) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6 F47R CP and E7 GGG CP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6 F47R CP and DNAE7 GGG CP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6 F47R CP and in particular E7 GGG CP were administered alone. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Human papillomavirus and its influence on head and neck cancer predisposition

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    Kamil H. Nelke

    2013-07-01

    Full Text Available Human papillomavirus (HPV is a virus often infecting humans. It is often present on skin or mucousmembranes. These diverse DNA viruses are often linked to many various benign and malignant neoplasticlesions. Over 40 types of HPV are transmitted through sexual contact and infect the anogenital regionwhich might be secondly transmitted to the oral mucous. Over 150 HPV viruses are defined according tothe invaded site. Oral papillomas are marked with numbers 6, 7, 11, 16 and 32. Squamous cell papillomais often found in laryngeal epithelial tumor associated with HPV-6 and HPV-11 and also HPV-16 in oralsquamous cell carcinoma (OSCC. In the last 15 years OSCC has become more common in children andyoung adults. The role of HPV virus causing oral squamous cell carcinomas is more often realized, butpeople’s lack of knowledge and risky sexual behavior is still the main factor in growing HPV infections.

  6. Comparative transforming potential of different human papillomaviruses associated with non-melanoma skin cancer

    International Nuclear Information System (INIS)

    Massimi, Paola; Thomas, Miranda; Bouvard, Veronique; Ruberto, Irene; Campo, M. Saveria; Tommasino, Massimo; Banks, Lawrence

    2008-01-01

    It is well established that high-risk human papillomaviruses (HPVs) that infect mucosal epithelia are the causative agents of cervical cancer. In contrast, the association of cutaneo-tropic HPV types with the development of non-melanoma skin cancer (NMSC) is less well defined. In this study, we have analysed the in vitro transforming potential of various cutaneous HPV types. Using oncogene cooperation assays with activated ras, we have shown that diverse cutaneous types, including 12, 14, 15, 24, 36 and 49, have significant transforming potential. Interestingly, most of this activity appears to be encoded by the E6 gene product. In contrast, the common HPV-10 exhibits no significant transforming potential in these assays. This difference may be a reflection of different patterns of cellular localization, with transforming E6s being nuclear and non-transforming being cytoplasmic. These results provide molecular support for a role of these viruses in the development of certain human malignancies

  7. Detection of human papillomavirus in laryngeal lesions by in situ hybridization

    DEFF Research Database (Denmark)

    Multhaupt, H A; Fessler, J N; Warhol, M J

    1994-01-01

    Human papillomavirus (HPV) is associated with human neoplasms of squamous epithelium. Squamous papillomas and verrucous carcinomas are two types of squamous neoplasms of the larynx that present difficult problems in differential diagnosis. Using in situ hybridization with biotinylated DNA probes......, we examined benign squamous papillomas and verrucous squamous carcinomas of the larynx for the presence of HPV. Forty-two biopsy specimens from 18 patients with laryngeal papillomas and 11 biopsy specimens from seven patients with verrucous carcinomas were obtained from the files of Pennsylvania...... Hospital, Philadelphia, PA. Tissue sections were hybridized with an HPV DNA cocktail. The HPV-positive cases then were subtyped further with DNA probes specific for HPV subtypes 6/11, 16/18, and 31/33/35. All benign squamous papillomas (42 of 42) were positive for HPV subtype 6/11. None of the verrucous...

  8. Molecular analysis of human papillomavirus virus-like particle activated Langerhans cells in vitro.

    Science.gov (United States)

    Woodham, Andrew W; Raff, Adam B; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LC) are the resident antigen-presenting cells in human epithelium, and are therefore responsible for initiating immune responses against human papillomaviruses (HPV) entering the epithelial and mucosal layers in vivo. Upon proper pathogenic stimulation, LC become activated causing an internal signaling cascade that results in the up-regulation of co-stimulatory molecules and the release of inflammatory cytokines. Activated LC then migrate to lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response. However, HPV manipulates LC in a suppressive manner that alters these normal maturation responses. Here, in vitro LC activation assays for the detection of phosphorylated signaling intermediates, the up-regulation of activation-associated surface markers, and the release of inflammatory cytokines in response to HPV particles are described.

  9. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    2010-01-01

    Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

  10. Knowledge, attitudes, and perception towards human papillomavirus among university students in Pakistan

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    Tahir Mehmood Khan

    2016-12-01

    Full Text Available This cross-sectional study comprises a questionnaire-based survey regarding knowledge about human papillomavirus and its vaccine among students in different educational fields at public and private universities in the city of Lahore in Pakistan. A 26-item questionnaire was used to attain the objective of this study. The reliability of this tool was assessed using Cronbach's alpha (0.79 and the Kaiser-Meyer-Olkin value was 0.827. The response rate to the survey was 78.0%, of whom the majority (74.9% were females and 308 (79% were single (median age=23 years. While assessing the respondents' knowledge about HPV, 223(57% students reported that they had already heard of HPV (human papillomavirus and nearly 215 (55% reported that HPV causes cervical cancer and can infect both men and women. Gender and field of study were two main factors found influencing the respondents' knowledge about HPV. Moreover, students' understanding about the mode of transmission of HPV was cursory: 40.51% said they did not know how HPV is transmitted, 133 (34.10% stated that HPV spreads through the exchange of bodily fluids, and 22 (5.64% selected cough/sneezing. In terms of prevention, 175 (44.87% students stated that HPV can be prevented by vaccination, 30.0% reported sexual abstinence, 21.54% using condoms, and nearly 5.38% disclosed use of antibiotics. Addressing the knowledge of students regarding HPV vaccine, nearly 53% stated there is no vaccine against HPV and almost 64% rejected the statement that HPV vaccine prevents cervical cancer. In addition, students reported that they will be more than willing to get vaccinated for HPV if their physician recommend them (RII=0.74 followed by parents (RII=0.69. The results of this study revealed a poor understanding among respondents about the health problems associated with HPV, its prevention, modes of transmission and arability of HPV vaccine in Pakistan. Keywords: Human papillomavirus, Vaccine, Knowledge, Attitude

  11. Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses.

    Science.gov (United States)

    Pouyanfard, Somayeh; Spagnoli, Gloria; Bulli, Lorenzo; Balz, Kathrin; Yang, Fan; Odenwald, Caroline; Seitz, Hanna; Mariz, Filipe C; Bolchi, Angelo; Ottonello, Simone; Müller, Martin

    2018-02-15

    The amino terminus of the human papillomavirus (HPV) minor capsid protein L2 contains a major cross-neutralization epitope which provides the basis for the development of a broadly protecting HPV vaccine. A wide range of protection against different HPV types would eliminate one of the major drawbacks of the commercial, L1-based prophylactic vaccines. Previously, we have reported that insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin protein generates a potent antigen inducing comprehensive protection against different animal and human papillomaviruses. We also reported, however, that although protection is broad, some oncogenic HPV types escape the neutralizing antibody response, if L2 epitopes from single HPV types are used as immunogen. We were able to compensate for this by applying a mix of thioredoxin proteins carrying L2 epitopes from HPV16, -31, and -51. As the development of a cost-efficient HPV prophylactic vaccines is one of our objectives, this approach is not feasible as it requires the development of multiple good manufacturing production processes in combination with a complex vaccine formulation. Here, we report the development of a thermostable thioredoxin-based single-peptide vaccine carrying an L2 polytope of up to 11 different HPV types. The L2 polytope antigens have excellent abilities in respect to broadness of protection and robustness of induced immune responses. To further increase immunogenicity, we fused the thioredoxin L2 polytope antigen with a heptamerization domain. In the final vaccine design, we achieve protective responses against all 14 oncogenic HPV types that we have analyzed plus the low-risk HPVs 6 and 11 and a number of cutaneous HPVs. IMPORTANCE Infections by a large number of human papillomaviruses lead to malignant and nonmalignant disease. Current commercial vaccines based on virus-like particles (VLPs) effectively protect against some HPV types but fail to do so for most others. Further, only

  12. Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

    Science.gov (United States)

    Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

    2014-12-01

    This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  13. In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line

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    Shuai Zhen

    2016-12-01

    Full Text Available PURPOSE: Human papillomavirus (HPV type 16 is one of the major etiologic factors of cervical cancer. Our study aims to investigate the potentiality of the antiviral clustered regularly interspaced short palindromic repeat (CRISPR/CRISPR-associated Cas9 system (CRISPR/Cas9 targeting the E6 and E7 oncogenes of HPV16 as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP for cervical cancer. METHODS: Specifically, the therapeutic efficacy of combination of CDDP and HPV16 E6 + E7-CRISPR/Cas9 was assessed in cervical cancer cells and cervical cancer xenograft models. RESULTS: In vitro experiments showed that long-term exposure of SiHa cells to the HPV16 E6 + E7-CRISPR/Cas9 induced apoptosis, and its pro-apoptosis effect became more obvious when combined with CDDP. In vivo study found the efficacy of the combination of HPV16 E6 + E7-CRISPR/Cas9 and CDDP were superior to either of the treatments in term of apoptosis induction and metastasis inhibition. CONCLUSION: Collectively, our results suggested that HPV16 E6 + E7-CRISPR/Cas9 could be an effective sensitizer of CDDP chemotherapy in cervical cancer.

  14. The agmatine-containing poly(amidoamine) polymer AGMA1 binds cell surface heparan sulfates and prevents attachment of mucosal human papillomaviruses.

    Science.gov (United States)

    Cagno, Valeria; Donalisio, Manuela; Bugatti, Antonella; Civra, Andrea; Cavalli, Roberta; Ranucci, Elisabetta; Ferruti, Paolo; Rusnati, Marco; Lembo, David

    2015-09-01

    The agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Detection of human papillomavirus among women in Laos: feasibility of using filter paper card and prevalence of high-risk types.

    Science.gov (United States)

    Phongsavan, Keokedthong; Gustavsson, Inger; Marions, Lena; Phengsavanh, Alongkone; Wahlström, Rolf; Gyllensten, Ulf

    2012-10-01

    Persistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate. This is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay. Overall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction-based analysis. The prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.

  16. Cost-Effectiveness of Cervical Cancer Screening With Human Papillomavirus DNA Testing and HPV-16,18 Vaccination

    Science.gov (United States)

    Goldhaber-Fiebert, Jeremy D.; Stout, Natasha K.; Salomon, Joshua A.; Kuntz, Karen M.; Goldie, Sue J.

    2011-01-01

    Background The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination. Methods An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years. Results For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78 000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41 000 per QALY with screening every 5 years and $188 000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially. Conclusions For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more

  17. Identification of a novel human papillomavirus by metagenomic analysis of samples from patients with febrile respiratory illness.

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    John L Mokili

    Full Text Available As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome and 63.1% (L1 sequence identity with its closest relative in the Papillomavirus episteme (PAVE database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4 and a non-coding long control region (LCR between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses.

  18. Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.

    Science.gov (United States)

    Da Silva, Diane M; Movius, Carly A; Raff, Adam B; Brand, Heike E; Skeate, Joseph G; Wong, Michael K; Kast, W Martin

    2014-03-01

    Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Measurement of neutralizing serum antibodies of patients vaccinated with human papillomavirus L1 or L2-based immunogens using furin-cleaved HPV Pseudovirions.

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    Joshua W Wang

    Full Text Available Antibodies specific for neutralizing epitopes in either Human papillomavirus (HPV capsid protein L1 or L2 can mediate protection from viral challenge and thus their accurate and sensitive measurement at high throughput is likely informative for monitoring response to prophylactic vaccination. Here we compare measurement of L1 and L2-specific neutralizing antibodies in human sera using the standard Pseudovirion-Based Neutralization Assay (L1-PBNA with the newer Furin-Cleaved Pseudovirion-Based Neutralization Assay (FC-PBNA, a modification of the L1-PBNA intended to improve sensitivity towards L2-specific neutralizing antibodies without compromising assay of L1-specific responses. For detection of L1-specific neutralizing antibodies in human sera, the FC- PBNA and L1-PBNA assays showed similar sensitivity and a high level of correlation using WHO standard sera (n = 2, and sera from patients vaccinated with Gardasil (n = 30 or an experimental human papillomavirus type 16 (HPV16 L1 VLP vaccine (n = 70. The detection of L1-specific cross-neutralizing antibodies in these sera using pseudovirions of types phylogenetically-related to those targeted by the L1 virus-like particle (VLP vaccines was also consistent between the two assays. However, for sera from patients (n = 17 vaccinated with an L2-based immunogen (TA-CIN, the FC-PBNA was more sensitive than the L1-PBNA in detecting L2-specific neutralizing antibodies. Further, the neutralizing antibody titers measured with the FC-PBNA correlated with those determined with the L2-PBNA, another modification of the L1-PBNA that spacio-temporally separates primary and secondary receptor engagement, as well as the protective titers measured using passive transfer studies in the murine genital-challenge model. In sum, the FC-PBNA provided sensitive measurement for both L1 VLP and L2-specific neutralizing antibody in human sera. Vaccination with TA-CIN elicits weak cross-protective antibody in a

  20. Determinants of human papillomavirus vaccine acceptability in Latin America and the Caribbean.

    Science.gov (United States)

    Winkler, Jennifer L; Wittet, Scott; Bartolini, Rosario M; Creed-Kanashiro, Hilary M; Lazcano-Ponce, Eduardo; Lewis-Bell, Karen; Lewis, Merle J; Penny, Mary E

    2008-08-19

    Prophylactic human papillomavirus (HPV) vaccines provide promise as a key component of future cervical cancer prevention programs in the Latin America and the Caribbean region. The successful introduction and acceptance of these vaccines will depend on a range of factors including awareness of cervical cancer as a problem, affordability of the vaccine, political will, competition with other vaccines, feasibility of vaccine delivery and acceptability of the vaccine among the range of groups who will influence uptake. While existing data about acceptability from Latin America and the Caribbean is scarce, it is clear that health policymakers, providers and the general public lack knowledge about HPV and cervical cancer. Furthermore, they would value more local epidemiologic data related to cervical cancer. Price is currently a major barrier to vaccine acceptability and a priority for advocacy. More research is required in Latin America and the Caribbean to determine what messages and strategies will work in these communities.

  1. Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts

    DEFF Research Database (Denmark)

    Blomberg, Maria; Dehlendorff, Christian; Sand, Carsten

    2015-01-01

    BACKGROUND: Reducing the number of doses in the human papillomavirus (HPV) vaccination regimen from 3 to 2 could increase coverage rates. In this cohort study, we assessed the risk of genital warts (GWs) according to timing and number of doses of quadrivalent HPV vaccine. METHODS: From population......-based registries, we identified all girls in Denmark born during 1985-1999, for whom information on HPV vaccinations was retrieved. The cohort was followed for GW occurrence during 2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to determine differences in GW rates by number...... of vaccine doses. RESULTS: Of the 550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly with each additional dose of vaccine. For girls who received 2 doses, extension of the interval between doses...

  2. Oral focal epithelial hyperplasia: report of 3 cases with human papillomavirus DNA sequencing analysis.

    Science.gov (United States)

    Gültekin, S E; Tokman Yildirim, Benay; Sarisoy, S

    2011-01-01

    Focal epithelial hyperplasia (FEH), or Heck's disease, is a benign proliferative viral infection of the oral mucosa that is related to Human Papil-lomavirus (HPV), mainly subtypes 13 and 32. Although this condition is known to exist in numerous populations and ethnic groups, the reported cases among Caucasians are relatively rare. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. Histopathologically, it is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, fusion, and horizontal outgrowth of epithelial ridges and the cells named mitozoids. The purpose of this case report was to present 3 cases of focal epithelial hyperplasia in a pediatric age group. Histopathological and clinical features of cases are discussed and DNA sequencing analysis is reported in which HPV 13, HPV 32, and HPV 11 genomes are detected.

  3. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    José E. Levi

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  4. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Levi José E.

    2002-01-01

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  5. 4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years

    DEFF Research Database (Denmark)

    Ferris, Daron G; Samakoses, Rudiwilai; Block, Stanley L

    2017-01-01

    OBJECTIVES: We describe the final 10-year data for the long-term follow-up study of the 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and adolescents. METHODS: In the base study (V501-018), 1661 sexually inactive boys and girls received the 4vHPV vaccine (early vaccination group...... assessed. Effectiveness was estimated by calculating the incidence rate of the primary endpoints (HPV types 6, 11, 16, and 18-related disease or persistent infection). RESULTS: For HPV types 6, 11, and 16, 89% to 96% of subjects remained seropositive through 10-years postvaccination. The preadolescents had...... 38% to 65% higher geometric mean titers at month 7, which remained 16% to 42% higher at 10 years compared with adolescents. No cases of HPV type 6, 11, 16, and 18-related diseases were observed. Ten subjects had a persistent infection of ≥6 months duration with vaccine-type HPV and 2 subjects had...

  6. Delay and refusal of human papillomavirus vaccine for girls, national immunization survey-teen, 2010.

    Science.gov (United States)

    Dorell, Christina; Yankey, David; Jeyarajah, Jenny; Stokley, Shannon; Fisher, Allison; Markowitz, Lauri; Smith, Philip J

    2014-03-01

    Human papillomavirus (HPV) vaccine coverage among girls is low. We used data reported by parents of 4103 girls, 13 to 17 years old, to assess associations with, and reasons for, delaying or refusing HPV vaccination. Sixty-nine percent of parents neither delayed nor refused vaccination, 11% delayed only, 17% refused only, and 3% both delayed and refused. Eighty-three percent of girls who delayed only, 19% who refused only, and 46% who both delayed and refused went on to initiate the vaccine series or intended to initiate it within the next 12 months. A significantly higher proportion of parents of girls who were non-Hispanic white, lived in households with higher incomes, and had mothers with higher education levels, delayed and/or refused vaccination. The most common reasons for nonvaccination were concerns about lasting health problems from the vaccine, wondering about the vaccine's effectiveness, and believing the vaccine is not needed.

  7. Human papillomavirus vaccine and sexual behavior among adolescent and young women.

    Science.gov (United States)

    Liddon, Nicole C; Leichliter, Jami S; Markowitz, Lauri E

    2012-01-01

    Vaccines to prevent certain types of human papillomavirus (HPV) and associated cancers are recommended for routine use among young women. Nationally representative reports of vaccine uptake have not explored the relationship between HPV vaccine initiation and various sexual behaviors. Explore sexual behavior and demographic correlates of HPV vaccine initiation from a nationally representative survey of adolescent and young adult women. In 2007-2008, a total of 1243 girls/women aged 15-24 years responded to questions about receiving HPV vaccine in the National Survey of Family Growth (NSFG). In 2010, demographic and sexual behavior correlates were evaluated in bivariate and multivariate analyses by age. HPV vaccine initiation was higher among those aged 15-19 years than those aged 20-24 years (30.3% vs 15.9%, p19 years. No association was found between HPV vaccination and risky sexual behavior. Published by Elsevier Inc.

  8. Detection of human papillomavirus DNA in urine. A review of the literature.

    Science.gov (United States)

    Vorsters, A; Micalessi, I; Bilcke, J; Ieven, M; Bogers, J; Van Damme, P

    2012-05-01

    The detection of human papillomavirus (HPV) DNA in urine, a specimen easily obtained by a non-invasive self-sampling method, has been the subject of a considerable number of studies. This review provides an overview of 41 published studies; assesses how different methods and settings may contribute to the sometimes contradictory outcomes; and discusses the potential relevance of using urine samples in vaccine trials, disease surveillance, epidemiological studies, and specific settings of cervical cancer screening. Urine sampling, storage conditions, sample preparation, DNA extraction, and DNA amplification may all have an important impact on HPV DNA detection and the form of viral DNA that is detected. Possible trends in HPV DNA prevalence in urine could be inferred from the presence of risk factors or the diagnosis of cervical lesions. HPV DNA detection in urine is feasible and may become a useful tool but necessitates further improvement and standardization.

  9. CURRENT ISSUES FACING THE INTRODUCTION OF HUMAN PAPILLOMAVIRUS VACCINE IN MALAYSIA

    Directory of Open Access Journals (Sweden)

    I-Ching Sam

    2007-01-01

    Full Text Available Certain human papillomavirus (HPV types are strongly associated with cervical cancer. Recently-described effective vaccines against these HPV types represent a great medical breakthrough in preventing cervical cancer. In Malaysia, the vaccine has just received regulatory approval. We are likely to face similar barriers to implementing HPV vaccination as reported by countries where vaccination has been introduced. Most women have poor understanding of HPV and its link to cervical cancer. Physicians who will be recommending HPV vaccines may not have extensive knowledge or experience with HPV-related disease. Furthermore, a vaccine against a sexually-transmitted infection may elicit negative reactions from potential recipients or their carers, particularly in a conservative society. Given the high cost of the vaccine, reaching the most vulnerable women is a concern. To foster broad acceptance of HPV vaccine, education must be provided to health care providers, parents and young women about the risks of HPV infection and the benefits of vaccination.

  10. Human papillomavirus immunization uptake among girls with a refugee background compared with Danish-born girls

    DEFF Research Database (Denmark)

    P. Møller, Sanne; Kristiansen, Maria; Norredam, Marie

    2018-01-01

    Refugee children and their families may experience impaired access to healthcare; therefore, we aimed to uncover human papillomavirus (HPV) immunization patterns among a large group of refugee girls compared with Danish-born girls. We also examined possible predictors of uptake among refugee girls....... We used aregister-based cohort design where refugee girls (n = 3264) who, between 1 January 1994 and 31 December 2010, obtained residency permits in Denmark, were included and matched on age and sex with Danish-born girls (n = 19 584). Personal identification numbers were cross-linked to the National...... Danish Health Service Register, identifying all contacts for HPV-immunization in both the ordinary HPV-immunization program and in a catch-up program. We applied logistic regression to estimate the odds ratios (OR) of uptake. We found that refugee girls had significantly lower HPV-immunization uptake...

  11. Physician communication about adolescent vaccination: How is human papillomavirus vaccine different?

    Science.gov (United States)

    Gilkey, Melissa B; Moss, Jennifer L; Coyne-Beasley, Tamera; Hall, Megan E; Shah, Parth D; Brewer, Noel T

    2015-08-01

    Low human papillomavirus (HPV) vaccination coverage stands in stark contrast to our success in delivering other adolescent vaccines. To identify opportunities for improving physicians' recommendations for HPV vaccination, we sought to understand how the communication context surrounding adolescent vaccination varies by vaccine type. A national sample of 776 U.S. physicians (53% pediatricians, 47% family medicine physicians) completed our online survey in 2014. We assessed physicians' perceptions and communication practices related to recommending adolescent vaccines for 11- and 12-year-old patients. About three-quarters of physicians (73%) reported recommending HPV vaccine as highly important for patients, ages 11-12. More physicians recommended tetanus, diphtheria, and acellular pertussis (Tdap) (95%) and meningococcal vaccines (87%, both pCommunication strategies are needed to support physicians in recommending HPV vaccine with greater confidence and efficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Barriers for Hispanic women in receiving the human papillomavirus vaccine: a nursing challenge.

    Science.gov (United States)

    Wagner, Janelle

    2009-12-01

    Cervical cancer affects more Hispanic women than non-Hispanic women in the United States. A vaccination exists to aid in the prevention of cervical cancer; an estimated 70% of cases could be avoided with the human papillomavirus (HPV) vaccine. However, women of Hispanic descent have many access barriers. By identifying and addressing such barriers, nurses can play a significant role in educating Hispanic women about the benefits of vaccination before HPV exposure occurs. Theoretical integration with Leininger's Culture Care Theory of Diversity and Universality provides a framework to address cultural differences and awareness when educating Hispanic women about this health issue. Additional nursing research into effective communication and educational programs to help reach the Hispanic population continues to be a priority in this vulnerable community.

  13. Human Papillomavirus Assays and Cytology in Primary Cervical Screening of Women Aged 30 Years and Above

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah

    2016-01-01

    In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30-65 years in Copenhagen, Denmark....... Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected...... more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results...

  14. A brief history of economic evaluation for human papillomavirus vaccination policy.

    Science.gov (United States)

    Beutels, Philippe; Jit, Mark

    2010-09-01

    This commentary discusses key issues for health economic evaluation and modelling, applied to human papillomavirus (HPV) vaccine programs. We outline some of the specific features of HPV disease and vaccination, and associated policy questions in light of a literature search for economic evaluations on HPV vaccination. We observe that some policy questions could not be reliably addressed by many of the 43 published economic evaluations we found. Despite this, policy making on universal HPV vaccination followed shortly after vaccine licensure in many developed countries, so the role economic evaluation played in informing these decisions (pre-dating 2008) seems to have been fairly limited. For more recent decisions, however, economic evaluation is likely to have been used more widely and more intensively. We expect future cost-effectiveness analyses to be more instrumental in policy making regarding vaccines covering more HPV types, therapeutic HPV vaccines, and novel diagnostic tests for biomarkers of HPV infection and disease integrated with cervical screening programs.

  15. Awareness of human papillomavirus in 23 000 Danish men from the general male population

    DEFF Research Database (Denmark)

    Nielsen, Ann; Munk, Christian; Liaw, Kai-Li

    2009-01-01

    Men play an important role in transmission of human papillomavirus (HPV). Both in men and in women HPV causes great morbidity, such as cervical cancer, penile and anal cancer, and genital warts. The awareness of HPV and its consequences is essential to a successful vaccination program against HPV....... In this study, we assessed awareness of HPV in Danish men. A random sample of men aged 18-45 years from the general male population was invited to participate in the study. The participants filled in a self-administered questionnaire with questions concerning awareness of HPV, lifestyle, and sexual habits....... In the period from November 2006 to June 2007, more than 23 000 men were included in the study (participation rate approximately 71%). Overall, 10% of the participants reported to have heard of HPV. Comparison with an earlier study in Danish women showed lower awareness in men than in women (25%). Higher...

  16. Human papillomavirus-associated cancers as acquired immunodeficiency syndrome defining illnesses

    Directory of Open Access Journals (Sweden)

    Shohreh Shahabi

    2013-04-01

    Full Text Available The Centers for Disease Control currently report cervical, vulvar, vaginal, anal and some head and neck cancers as human papillomavirus (HPV-associated cancers. Only cervical cancer is listed amongst acquired immunodeficiency syndrome (AIDS defining illnesses. All of these cancers may represent progression of the immunocompromised state with the inability to eradicate viral infection. This study reports the case of a 27-year old HIV positive female presenting with a persistent right vulvar exophytic lesion. High-risk HPV analysis and immunostaining for P16 were both positive. A biopsy of the lesion revealed invasive squamous cell carcinoma. The patient underwent neoadjuvant radiation and chemotherapy followed by a radical vulvectomy. During treatment, her CD4 T-lymphocyte count decreased to 120 advancing her condition from HIV to AIDS. This case suggests that all HPV-associated cancers should be included as AIDS defining illnesses.

  17. Detection of Human Papillomavirus Type 2 Related Sequence in Oral Papilloma

    Science.gov (United States)

    Yamaguchi, Taihei; Shindoh, Masanobu; Amemiya, Akira; Inoue, Nobuo; Kawamura, Masaaki; Sakaoka, Hiroshi; Inoue, Masakazu; Fujinaga, Kei

    1998-01-01

    Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma. PMID:9699941

  18. Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias

    DEFF Research Database (Denmark)

    Holl, Katsiaryna; Nowakowski, Andrzej M; Powell, Ned

    2015-01-01

    Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providing...... uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type-distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461...... of CGN are HPV16/18/45-positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV....

  19. Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah

    2016-01-01

    intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women......Laboratories can nowadays choose from >100 Human Papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART and APTIMA, frequently do not detect...... the same HPV infections. Here, we determined the characteristics of the concordant (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30-65 years (n=2859) and in a concurrent referral population from the same...

  20. Role of human papillomavirus testing and cytology in follow-up after conization

    DEFF Research Database (Denmark)

    Gosvig, Camilla F; Huusom, Lene D; Deltour, Isabelle

    2015-01-01

    intraepithelial neoplasia grade 2 or worse (CIN2+) after conization. DESIGN: Prospective cohort study. SETTING: Denmark. POPULATION: 667 women attending for conization. METHODS: Cervical specimens were collected during 2002-2006 at first visit after conization for cytological examination and Hybrid Capture 2......OBJECTIVE: Adequate follow-up of women who have undergone conization for high-grade cervical lesions is crucial in cervical cancer screening programs. We evaluated the performance of testing for high-risk human papillomavirus (HPV) types, cytology alone, and combined testing in predicting cervical...... detection of high-risk HPV. The women were passively followed until 2 years after first follow-up visit by linkage to the nationwide Pathology Data Bank. RESULTS: At first visit after conization (median time, 3.4 months), 20.4% were HPV-positive and 17.2% had atypical squamous intraepithelial lesions...

  1. [News items on human papillomavirus and its vaccine in the Valencian press (2006-2011)].

    Science.gov (United States)

    Tuells, José; Duro Torrijos, José Luis; Chilet Rosell, Elisa; Pastor Villalba, Eliseo; Portero Alonso, Antonio; Navarro Ortiz, Carmen; Galiana de la Villa, Eva María

    2013-01-01

    The process of introducing the human papillomavirus (HPV) vaccine aimed at teenage girls has not been entirely without controversy in Spain. This vaccine was originally hyped as a preventive measure in the fight against cervical cancer but the resulting euphoria was tempered by a message calling for evidence. During administration of the second dose of the vaccine in February 2009, an unexpected turn of events attracted vast media coverage when two teenagers experienced adverse effects after immunization in Valencia (Spain). This study analyzes the scope and content of news items on HPV, immunization and cervical cancer published between 2006 and 2011 in two widely disseminated regional newspapers in Valencia. We also discuss the extent to which the messages transmitted may have influenced acceptability of the vaccine. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

  2. Possible adverse effects of the quadrivalent human papillomavirus vaccine in the Region of Southern Denmark

    DEFF Research Database (Denmark)

    Cramon, Cecilie; Lindegaard Poulsen, Christina; Hartling, Ulla Birgitte

    2017-01-01

    INTRODUCTION: Since the introduction of the quadrivalent human papillomavirus vaccine, young girls and women have reported a broad range of symptoms. These have been described as possible adverse effects of the vaccine. In this study, we describe demographic characteristics, symptomatology......, clinical and laboratory test results in patients referred with suspected adverse effects in the Region of Southern Denmark. METHODS: We conducted a retrospective, descriptive study. The patients filled out a questionnaire, were interviewed by a doctor and received a standard physical examination...... still in diagnostic workup when the present study concluded. CONCLUSIONS: The patients reported a wide range of symptoms. We found an overall low prevalence of POTS. It should be further investigated whether these patients might suffer from a functional disorder rather than from adverse effects...

  3. RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

    Science.gov (United States)

    Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

    2016-01-01

    Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

  4. Lack of detection of human papillomavirus infection by hybridization test in prostatic biopsies

    International Nuclear Information System (INIS)

    Gazzaz, Faten S; Mosli, Hisham A

    2009-01-01

    To explore the possibility of finding human papillomavirus (HPV) infection in the prostate tissue of a cohort of Saudi men presenting with benign prostatic hyperplasia (BPH) or prostate cancer. A cohort study on prospectively collected tissue samples was conducted at King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia from March 2007 to December 2008 on a total of 56 male patients, age range 50-93 years (average 68), diagnosed as having BPH or prostate cancer. The HPV DNA hybridization by hybrid capture 2 technology was performed on prostate biopsies of these patients to detect 18 types of HPV infection, and differentiate between 2 HPV DNA groups, the low-risk types, and the high/intermediate risk types.The tissues of all the prostatic biopsies were negative for HPV DNA. Our results, using the hybridization test, indicate that it is unlikely that HPV-16 or HPV-18, or the other tested subtypes, enhance the risk of prostate cancer. (author)

  5. The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination.

    Science.gov (United States)

    Chesson, Harrell W; Forhan, Sara E; Gottlieb, Sami L; Markowitz, Lauri E

    2008-08-18

    We estimated the health and economic benefits of preventing recurrent respiratory papillomatosis (RRP) through quadrivalent human papillomavirus (HPV) vaccination. We applied a simple mathematical model to estimate the averted costs and quality-adjusted life years (QALYs) saved by preventing RRP in children whose mothers had been vaccinated at age 12 years. Under base case assumptions, the prevention of RRP would avert an estimated USD 31 (range: USD 2-178) in medical costs (2006 US dollars) and save 0.00016 QALYs (range: 0.00001-0.00152) per 12-year-old girl vaccinated. Including the benefits of RRP reduced the estimated cost per QALY gained by HPV vaccination by roughly 14-21% in the base case and by 100% in the sensitivity analyses. More precise estimates of the incidence of RRP are needed, however, to quantify this impact more reliably.

  6. Cost-effectiveness of human papillomavirus vaccination in the United States.

    Science.gov (United States)

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

    2008-02-01

    We describe a simplified model, based on the current economic and health effects of human papillomavirus (HPV), to estimate the cost-effectiveness of HPV vaccination of 12-year-old girls in the United States. Under base-case parameter values, the estimated cost per quality-adjusted life year gained by vaccination in the context of current cervical cancer screening practices in the United States ranged from $3,906 to $14,723 (2005 US dollars), depending on factors such as whether herd immunity effects were assumed; the types of HPV targeted by the vaccine; and whether the benefits of preventing anal, vaginal, vulvar, and oropharyngeal cancers were included. The results of our simplified model were consistent with published studies based on more complex models when key assumptions were similar. This consistency is reassuring because models of varying complexity will be essential tools for policy makers in the development of optimal HPV vaccination strategies.

  7. What works for human papillomavirus vaccine introduction in low and middle-income countries?

    Directory of Open Access Journals (Sweden)

    Natasha Howard

    2017-12-01

    Full Text Available Since 2007, low and middle-income countries (LMICs have gained experience delivering HPV vaccines through HPV vaccination pilots, demonstration projects and national programmes. This commentary summarises lessons from HPV vaccination experiences in 45 LMICs and what works for HPV vaccination introduction. Methods included a systematic literature review, unpublished document review, and key informant interviews. Data were extracted from 61 peer-reviewed articles, 11 conference abstracts, 188 technical reports, and 56 interviews, with quantitative data analysed descriptively and qualitative data analysed thematically. Key lessons are described under five themes of preparation, communications, delivery, coverage achievements, and sustainability. Lessons learnt were generally consistent across countries and projects and sufficient lessons have been learnt for countries to deliver HPV vaccine through phased national rollout rather than demonstration projects. However, challenges remain in securing the political will and financial resources necessary to implement successful national programmes. Keywords: Cervical cancer prevention, Human papillomavirus, Vaccination, Low and middle-income countries, Demonstration projects

  8. Detection of human papillomavirus in dental biofilm and the uterine cervix of a pregnant adolescent.

    Science.gov (United States)

    Cavalcanti, Édila Figuerêdo Feitosa; Silva, Célia Regina; Ferreira, Dennis Carvalho; Ferreira, Mariana Vasconcellos Martins; Vanderborght, Patrícia Rosa; Torres, Maria Cynésia Medeiros Barros; Torres, Sandra Regina

    2016-01-01

    Adolescence and pregnancy are considered to be risk factors for human papillomavirus (HPV) infection. The relationship between this infection in the uterine cervix and oral HPV infection is controversial. This report describes a case of a pregnant 16-year-old adolescent who presented HPV infection in the uterine cervix and the mouth. Smears were collected from the cervix and the tongue/palate. Dental biofilm samples were also collected. The microarray technique was used to detect HPV. The HPV 56 subtype was observed in the cervical smear and HPV 6 in dental biofilm. In this pregnant adolescent, HPV infection was present in both the cervix and the mouth, but the HPV subtypes infecting these two areas were different.

  9. Young Asian Americans' knowledge and perceptions of cervical cancer and the human papillomavirus.

    Science.gov (United States)

    Gor, Beverly J; Chilton, Janice A; Camingue, Pamela T; Hajek, Richard A

    2011-02-01

    Cervical cancer is a major health disparity among Asian Americans, with cervical cancer rates of Vietnamese women being significantly higher than for the general US female population and low screening rates reported for Asian American females. Focus groups and interviews were conducted with young Vietnamese, Filipino, and Korean adults (ages 18-29) to collect information on knowledge, perceptions and sources of information regarding cervical cancer, Pap tests and the human papillomavirus. 16 Korean, 18 Vietnamese, and 18 Filipino (50% female) adults participated in the study. Many participants had never heard of HPV, cervical cancer and Pap testing. Cervical cancer screening rates were low for Korean and Vietnamese females and were influenced by moral beliefs and lack of awareness. Culturally relevant education materials that consider specific Asian ethnicity and language are needed to increase awareness of cervical cancer, Pap testing, and HPV among Asian American young adults.

  10. Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation.

    Science.gov (United States)

    Fisher, Chris

    2015-01-01

    Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR) and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.

  11. Traditional Chinese medicine for human papillomavirus (HPV) infections: A systematic review.

    Science.gov (United States)

    Lin, Jing; Chen, Lanting; Qiu, Xuemin; Zhang, Na; Guo, Qiting; Wang, Yan; Wang, Mingyan; Gober, Hans-Jürgen; Li, Dajin; Wang, Ling

    2017-07-24

    Human papillomavirus (HPV) infections are common and generally harmless, but persistent infections can bring health problems like cancer and genital warts. For the uninfected group, HPV vaccines provide safe and effective protection, but they're type-restricted and expensive. For those infected, so far there have been a handful of treatments for HPV-associated benign or malignant diseases, traditional Chinese medicine being one of them. This systematic review focuses on the application of traditional Chinese medicine in HPV infection and related diseases on the basis of clinical findings. Moreover it covers compositions and mechanisms based on in vitro laboratory methods and animal models. Traditional Chinese medicine improves clinical index in the treatment of cervical cancer and genital warts; the mechanisms behind the effectiveness might be the regulation of cell apoptosis, viral gene transcription and translation, cell signal transduction pathways, and immune function.

  12. Burden and incidence of human papillomavirus-associated cancers and precancerous lesions in Denmark

    DEFF Research Database (Denmark)

    Svahn, Malene F; Munk, Christian; von Buchwald, Christian

    2016-01-01

    the study period, and almost identical incidence rates were seen for women and men in the youngest birth cohorts. The current burden of HPV-associated lesions amounted to more than 5000 cases, the vast majority (85%) being severe precancerous lesions. The highest risk for HPV-associated cancers......AIM: The aim of the study was to investigate the incidence of human papillomavirus (HPV)-associated cancers in Denmark between 1978 and 2011, estimate the current absolute annual number (burden) of HPV-associated cancers (HPVaCa) and their precancerous lesions, and assess whether...... there is socioeconomic inequality in the risk of HPV-associated cancers. METHODS: From four nationwide population-based registries, information was collected on HPVaCa diagnosed during 1978-2011 and age-standardised incidence rate for each site by calendar year and birth cohort was calculated. Furthermore, the current...

  13. Awareness of human papillomavirus among women attending a well woman clinic.

    Science.gov (United States)

    Waller, J; McCaffery, K; Forrest, S; Szarewski, A; Cadman, L; Wardle, J

    2003-08-01

    To assess the level and accuracy of public understanding of human papillomavirus (HPV) in the United Kingdom. Women attending a well woman clinic were asked to complete a questionnaire assessing HPV awareness and specific knowledge about the virus. Questionnaires were completed by 1032 women, of whom 30% had heard of HPV. Older women, non-smokers, and those with a history of candida, genital warts, or an abnormal smear result were more likely to have heard of HPV. Even among those who had heard of HPV, knowledge was generally poor, and fewer than half were aware of the link with cervical cancer. There was also confusion about whether condoms or oral contraceptives could protect against HPV infection. In this relatively well educated sample, awareness and knowledge of HPV were poor. Public education is urgently needed so that women participating in cervical cancer screening are fully informed about the meaning of their results, especially if HPV testing is soon to be introduced.

  14. Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

    Science.gov (United States)

    Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

    2013-02-01

    To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

  15. Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

    Science.gov (United States)

    Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William J; Messina, Jane L; Stoler, Mark H; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2016-01-01

    Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  16. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis

    Science.gov (United States)

    Drolet, Mélanie; Bénard, Élodie; Boily, Marie-Claude; Ali, Hammad; Baandrup, Louise; Bauer, Heidi; Beddows, Simon; Brisson, Jacques; Brotherton, Julia M L; Cummings, Teresa; Donovan, Basil; Fairley, Christopher K; Flagg, Elaine W; Johnson, Anne M; Kahn, Jessica A; Kavanagh, Kimberley; Kjaer, Susanne K; Kliewer, Erich V; Lemieux-Mellouki, Philippe; Markowitz, Lauri; Mboup, Aminata; Mesher, David; Niccolai, Linda; Oliphant, Jeannie; Pollock, Kevin G; Soldan, Kate; Sonnenberg, Pam; Tabrizi, Sepehr N; Tanton, Clare; Brisson, Marc

    2016-01-01

    Summary Background Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. Methods We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I2 and χ2 statistics and we did trends analysis to examine the dose–response association between HPV vaccination coverage and each study effect measure. Findings We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19–0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22–0·71) in girls 13–19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54–0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20

  17. First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

    Science.gov (United States)

    Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

    2017-09-01

    Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

  18. Association of Chlamydia trachomatis Infection and Herpes Simplex Virus Type 2 Serostatus With Genital Human Papillomavirus Infection in Men: The HPV in Men Study

    NARCIS (Netherlands)

    Alberts, Catharina Johanna; Schim van der Loeff, Maarten F.; Papenfuss, Mary R.; da Silva, Roberto José Carvalho; Villa, Luisa Lina; Lazcano-Ponce, Eduardo; Nyitray, Alan G.; Giuliano, Anna R.

    2013-01-01

    Background: Studies in women indicate that some sexually transmitted infections promote human papillomavirus (HPV) persistence and carcinogenesis. Little is known about this association in men; therefore, we assessed whether Chlamydia trachomatis (CT) infection and herpes simplex virus type 2

  19. Differences in incidence and co-occurrence of vaccine and nonvaccine human papillomavirus types in Finnish population before human papillomavirus mass vaccination suggest competitive advantage for HPV33.

    Science.gov (United States)

    Merikukka, Marko; Kaasila, Marjo; Namujju, Proscovia B; Palmroth, Johanna; Kirnbauer, Reinhard; Paavonen, Jorma; Surcel, Heljä-Marja; Lehtinen, Matti

    2011-03-01

    To understand likelihood of type replacement after vaccination against the high-risk human papillomavirus (HPV) types, we evaluated competition of the seven most common genital HPV types in a population sample of unvaccinated, fertile-aged Finnish women. First trimester sera from two consecutive pregnancies were retrieved from 3,183 Finnish women (mean age, 23.1 years) of whom 42.3% had antibodies to at least one HPV type (6/11/16/18/31/33/45) at the baseline. Antibody positivity to more than one HPV types by the second pregnancy was common among the baseline HPV seropositives. However, compared to baseline HPV-seronegative women, significantly increased incidence rate ratios (IRRs), indicating an increased risk to seroconvert for another HPV type, were consistently noted only for HPV33 among baseline HPV16 or HPV18 antibody (ab)-positive women: HPV(16ab only) (→) (16&33ab) IRR 2.9 [95% confidence interval (CI) 1.6-5.4] and HPV(18ab only) (→) (18&33ab) IRR 2.5 (95% CI 1.1-6.0), irrespectively of the presence of antibodies to other HPV types at baseline: HPV(16ab) (→) (16&33ab) IRR 3.2 (95% CI 2.0-5.2) and HPV(18ab) (→) (18&33ab) IRR 3.6 (95% CI 2.1-5.9). Our findings suggest a possible competitive advantage for HPV33 over other genital HPV types in the unvaccinated population. HPV33 should be monitored for type replacement after HPV mass vaccination. Copyright © 2010 UICC.

  20. Racial and ethnic disparities in human papillomavirus-associated cancer burden with first-generation and second-generation human papillomavirus vaccines.

    Science.gov (United States)

    Burger, Emily A; Lee, Kyueun; Saraiya, Mona; Thompson, Trevor D; Chesson, Harrell W; Markowitz, Lauri E; Kim, Jane J

    2016-07-01

    In the United States, the burden of human papillomavirus (HPV)-associated cancers varies by racial/ethnic group. HPV vaccination may provide opportunities for primary prevention of these cancers. Herein, the authors projected changes in HPV-associated cancer burden among racial/ethnic groups under various coverage assumptions with the available first-generation and second-generation HPV vaccines to evaluate changes in racial/ethnic disparities. Cancer-specific mathematical models simulated the burden of 6 HPV-associated cancers. Model parameters, informed using national registries and epidemiological studies, reflected sex-specific, age-specific, and racial/ethnic-specific heterogeneities in HPV type distribution, cancer incidence, stage of disease at detection, and mortality. Model outcomes included the cumulative lifetime risks of developing and dying of 6 HPV-associated cancers. The level of racial/ethnic disparities was evaluated under each alternative HPV vaccine scenario using several metrics of social group disparity. HPV vaccination is expected to reduce the risks of developing and dying of HPV-associated cancers in all racial/ethnic groups as well as reduce the absolute degree of disparities. However, alternative metrics suggested that relative disparities would persist and in some scenarios worsen. For example, when assuming high uptake with the second-generation HPV vaccine, the lifetime risk of dying of an HPV-associated cancer for males decreased by approximately 60%, yet the relative disparity increased from 3.0 to 3.9. HPV vaccines are expected to reduce the overall burden of HPV-associated cancers for all racial/ethnic groups and to reduce the absolute disparity gap. However, even with the second-generation vaccine, relative disparities will likely still exist and may widen if the underlying causes of these disparities remain unaddressed. Cancer 2016;122:2057-66. © 2016 American Cancer Society. © 2016 American Cancer Society.

  1. Prevalence of human papillomavirus types 11, 16 and 18 in cervical swabs. A study of 1362 pregnant women

    DEFF Research Database (Denmark)

    Hørding, U.; Iversen, A.K.N.; Sebbelov, A.

    1990-01-01

    Med. mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation......Med. mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation...

  2. Parents willingness to pay for a human papillomavirus vaccine to protect their adolescent daughters. Maule Region, Chile.

    Directory of Open Access Journals (Sweden)

    Arcadio A Cerda

    2014-01-01

    Full Text Available Objective. To determine the willingness to pay of parents of teenage daughters for a vaccine against human papillomavirus in the Maule Region, Chile. Materials and methods. A sample of 386 parents with daughters between 12 and 18 years old, representing the five largest cities of the Region of Maule, socioeconomically stratified. WTP was obtained using the contingent valuation method in double bounded format. Results. Parents are willing to pay an average of US$ 252.71 to vaccinate their daughters against virus, where the price and number of daughters negatively affects the probability of willingness to pay, and family income positively affects the probability. Conclusion. There is a possibility of using shared funding between the government and the parents of potential daughter to be affected by the human papillomavirus to reduce cervical cancer events.

  3. IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

    Science.gov (United States)

    Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

    2014-09-01

    Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

  4. Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

    Science.gov (United States)

    Khoury, Ruby; Sauter, Sharon; Butsch Kovacic, Melinda; Nelson, Adam S.; Myers, Kasiani C.; Mehta, Parinda A.; Davies, Stella M.; Wells, Susanne I.

    2018-01-01

    Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. HPV oncogene activities and the biology of SCCs have been intensely studied in laboratory models and humans. What remains largely unknown are host tissue and immune-related factors that determine an individual’s susceptibility to infection and/or carcinogenesis. Such susceptibility factors could serve to identify those at greatest risk and spark individually tailored HPV and SCC prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that is in part characterized by extreme susceptibility to SCCs. An increased prevalence of HPV has been reported in affected individuals, and molecular and functional connections between FA, SCC, and HPV were established in laboratory models. However, the presence of HPV in some human FA tumors is controversial, and the extent of the etiological connections remains to be established. Herein, we discuss cellular, immunological, and phenotypic features of FA, placed into the context of HPV pathogenesis. The goal is to highlight this orphan disease as a unique model system to uncover host genetic and molecular HPV features, as well as SCC susceptibility factors. PMID:29361695

  5. Suppression of Antitumor Immune Responses by Human Papillomavirus through Epigenetic Downregulation of CXCL14

    Directory of Open Access Journals (Sweden)

    Louis Cicchini

    2016-05-01

    Full Text Available High-risk human papillomaviruses (HPVs are causally associated with multiple human cancers. Previous studies have shown that the HPV oncoprotein E7 induces immune suppression; however, the underlying mechanisms remain unknown. To understand the mechanisms by which HPV deregulates host immune responses in the tumor microenvironment, we analyzed gene expression changes of all known chemokines and their receptors using our global gene expression data sets from human HPV-positive and -negative head/neck cancer and cervical tissue specimens in different disease stages. We report that, while many proinflammatory chemokines increase expression throughout cancer progression, CXCL14 is dramatically downregulated in HPV-positive cancers. HPV suppression of CXCL14 is dependent on E7 and associated with DNA hypermethylation in the CXCL14 promoter. Using in vivo mouse models, we revealed that restoration of Cxcl14 expression in HPV-positive mouse oropharyngeal carcinoma cells clears tumors in immunocompetent syngeneic mice, but not in Rag1-deficient mice. Further, Cxcl14 reexpression significantly increases natural killer (NK, CD4+ T, and CD8+ T cell infiltration into the tumor-draining lymph nodes in vivo. In vitro transwell migration assays show that Cxcl14 reexpression induces chemotaxis of NK, CD4+ T, and CD8+ T cells. These results suggest that CXCL14 downregulation by HPV plays an important role in suppression of antitumor immune responses. Our findings provide a new mechanistic understanding of virus-induced immune evasion that contributes to cancer progression.

  6. Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort.

    Science.gov (United States)

    Lee, Jung Eun; Lee, Sunghee; Lee, Heetae; Song, Yun-Mi; Lee, Kayoung; Han, Min Ji; Sung, Joohon; Ko, GwangPyo

    2013-01-01

    Human papillomavirus (HPV) is the most important causative agent of cervical cancers worldwide. However, our understanding of how the vaginal microbiota might be associated with HPV infection is limited. In addition, the influence of human genetic and physiological factors on the vaginal microbiota is unclear. Studies on twins and their families provide the ideal settings to investigate the complicated nature of human microbiota. This study investigated the vaginal microbiota of 68 HPV-infected or uninfected female twins and their families using 454-pyrosequencing analysis targeting the variable region (V2-V3) of the bacterial 16S rRNA gene. Analysis of the vaginal microbiota from both premenopausal women and HPV-discordant twins indicated that HPV-positive women had significantly higher microbial diversity with a lower proportion of Lactobacillus spp. than HPV-negative women. Fusobacteria, including Sneathia spp., were identified as a possible microbiological marker associated with HPV infection. The vaginal microbiotas of twin pairs were significantly more similar to each other than to those from unrelated individuals. In addition, there were marked significant differences from those of their mother, possibly due to differences in menopausal status. Postmenopausal women had a lower proportion of Lactobacillus spp. and a significantly higher microbiota diversity. This study indicated that HPV infection was associated with the composition of the vaginal microbiota, which is influenced by multiple host factors such as genetics and menopause. The potential biological markers identified in this study could provide insight into HPV pathogenesis and may represent biological targets for diagnostics.

  7. Replication and interaction of herpes simplex virus and human papillomavirus in differentiating host epithelial tissue

    International Nuclear Information System (INIS)

    Meyers, Craig; Andreansky, Samita S.; Courtney, Richard J.

    2003-01-01

    We have investigated the interactions and consequences of superinfecting and coreplication of human papillomavirus (HPV) and herpes simplex virus (HSV) in human epithelial organotypic (raft) culture tissues. In HPV-positive tissues, HSV infection and replication induced significant cytopathic effects (CPE), but the tissues were able to recover and maintain a certain degree of tissue integrity and architecture. HPV31b not only maintained the episomal state of its genomic DNA but also maintained its genomic copy number even during times of extensive HSV-induced CPE. E2 transcripts encoded by HPV31b were undetectable even though HPV31b replication was maintained in HSV- infected raft tissues. Expression of HPV31b oncogenes (E6 and E7) was also repressed but to a lesser degree than was E2 expression. The extent of CPE induced by HSV is dependent on the magnitude of HPV replication and gene expression at the time of HSV infection. During active HSV infection, HPV maintains its genomic copy number even though genes required for its replication were repressed. These studies provide new insight into the complex interaction between two common human sexually transmitted viruses in an in vitro system, modeling their natural host tissue in vivo

  8. Randomized Comparison of Two Vaginal Self-Sampling Methods for Human Papillomavirus Detection: Dry Swab versus FTA Cartridge

    OpenAIRE

    Catarino, Rosa; Vassilakos, Pierre; Bilancioni, Aline; Vanden Eynde, Mathieu; Meyer-Hamme, Ulrike; Menoud, Pierre-Alain; Guerry, Fr?d?ric; Petignat, Patrick

    2015-01-01

    Background Human papillomavirus (HPV) self-sampling (self-HPV) is valuable in cervical cancer screening. HPV testing is usually performed on physician-collected cervical smears stored in liquid-based medium. Dry filters and swabs are an alternative. We evaluated the adequacy of self-HPV using two dry storage and transport devices, the FTA cartridge and swab. Methods A total of 130 women performed two consecutive self-HPV samples. Randomization determined which of the two tests was performed f...

  9. Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum ▿

    OpenAIRE

    Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

    2010-01-01

    The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CI...

  10. Giving It Our Best Shot? Human Papillomavirus and Hepatitis B Virus Immunization Among Refugees, Massachusetts, 2011-2013.

    Science.gov (United States)

    Berman, Rachel Stein; Smock, Laura; Bair-Merritt, Megan H; Cochran, Jennifer; Geltman, Paul L

    2017-06-22

    The receipt rate of hepatitis B virus vaccine among adolescents in the United States is high, while the receipt rate of human papillomavirus vaccine is low. Rates have not been closely studied among refugees, whose home countries have high rates of disease caused by these viruses. We examined human papillomavirus and hepatitis B virus immunization rates among 2,269 refugees aged 9 to 26 years who resettled in Massachusetts from 2011 through 2013. This was a secondary analysis of data from their medical screenings. We used binary logistic regression to assess characteristics associated with immunization and bivariate analyses to compare refugee immunization rates with those of the general US population. Forty-five percent of US adolescents aged 13 to 17 years received 1 dose of human papillomavirus vaccine, compared with 68% of similarly aged refugees. Males (adjusted odds ratio [aOR], 0.62; 95% confidence interval [CI], 0.52-0.74), refugees older than 13 years (aOR, 0.74; 95% CI, 0.60-0.93), and refugees not from Sub-Saharan Africa (aOR, 0.74; 95% CI, 0.59-0.92) were less likely to receive human papillomavirus vaccine, while arrivals in 2012 through 2013 were more likely (aOR, 1.6; 95% CI, 1.3-1.9) than those arriving in 2011. Refugees older than 13 years were less likely to receive 2 doses of hepatitis B virus vaccine (aOR, 0.49; 95% CI, 0.37-0.63) than older refugees. Specialized post-arrival health assessment may improve refugees' immunization rates.

  11. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening

    OpenAIRE

    Katki, Hormuzd A.; Cheung, Li C.; Fetterman, Barbara; Castle, Philip E.; Sundaram, Rajeshwari

    2015-01-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interv...

  12. 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...

  13. Development of electrochemical biosensors and solid-phase amplification methods for the detection of human papillomavirus genes

    OpenAIRE

    Civit Pitarch, Laia

    2012-01-01

    A rapid, accurate and reliable diagnosis is crucial for the identification of a disease, like cancer, where an early detection can improve patient survival outcomes. Cervical cancer is the third most commonly diagnosed and the fourth leading cause of cancer death in women. It is well known that persistent infections with high-risk human papillomaviruses (HPV) are the primary cause of cervical cancer. Electrochemical DNA biosensors have received important attention owing to their characterist...

  14. Conjunctival papilloma caused by human papillomavirus type 11 treated with systemic interferon in a five-year-old boy.

    Science.gov (United States)

    Okan, Gökhan; Ayan, Inci; Karslioğlu, Safak; Altiok, Ender; Yenmiş, Güven; Vural, Gürcan

    2010-01-01

    Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma represents 7-10% of conjunctival tumors. Human papillomavirus (HPV)-6 and HPV-11 are the major HPV types responsible for conjunctival lesions. A five-year-old boy with a two-year history of conjunctival papilloma caused by HPV type 11 treated with systemic interferon alpha is reported and the literature is reviewed.

  15. Feasibility and implementation of a literature information management system for human papillomavirus in head and neck cancers with imaging.

    Science.gov (United States)

    Wu, Dee H; Matthiesen, Chance L; Alleman, Anthony M; Fournier, Aaron L; Gunter, Tyler C

    2014-01-01

    This work examines the feasibility and implementation of information service-orientated architecture (ISOA) on an emergent literature domain of human papillomavirus, head and neck cancer, and imaging. From this work, we examine the impact of cancer informatics and generate a full set of summarizing clinical pearls. Additionally, we describe how such an ISOA creates potential benefits in informatics education, enhancing utility for creating enduring digital content in this clinical domain.

  16. Targeted Facebook Advertising is a Novel and Effective Method of Recruiting Participants into a Human Papillomavirus Vaccine Effectiveness Study

    OpenAIRE

    Subasinghe, Asvini K; Nguyen, Margaret; Wark, John D; Tabrizi, Sepehr N; Garland, Suzanne M

    2016-01-01

    Background Targeted advertising using social networking sites (SNS) as a recruitment strategy in health research is in its infancy. Objective The aim of this study was to determine the feasibility of targeted Facebook advertisements to increase recruitment of unvaccinated women into a human papillomavirus (HPV) vaccine effectiveness study. Methods Between September 2011 and November 2013, females aged 18 to 25 years, residing in Victoria, Australia, were recruited through Facebook advertiseme...

  17. Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils

    OpenAIRE

    Alvarez, Karla Lucia Fernandez; Beldi, Mariana Carmezim; Sarmanho, Fabiane; Rossetti, Renata Ariza Marques; Silveira, Caio Raony Farina; Mota, Giana Rabello; Andreoli, Maria Antonieta; Caruso, Eliana Dias de Carvalho; Kamillos, Marcia Ferreira; Souza, Ana Marta; Mastrocalla, Haydee; Clavijo-Salomon, Maria Alejandra; Barbuto, José Alexandre Marzagão; Lorenzi, Noely Paula; Longatto Filho, Adhemar

    2017-01-01

    Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by...

  18. Communication and US-Somali Immigrant Human Papillomavirus (HPV) Vaccine Decision-Making.

    Science.gov (United States)

    Dailey, Phokeng M; Krieger, Janice L

    2017-09-01

    The current study uses a multiple goal theoretical perspective to explore how Somali immigrant families living in Ohio, USA, make decisions regarding whether to vaccinate their children against human papillomavirus (HPV)-a leading cause of cervical cancer. A focus was placed on the communication goals of parents in HPV vaccine discussions with their child and health care provider. Semi-structured interviews were audiotaped, transcribed, and analyzed using a grounded theory approach. Key themes are the implications of the vaccine for early sexual activity, confusion between HPV and HIV (human immunodeficiency virus), the perception that the HPV vaccine is unnecessary, uncertainty about the vaccine's efficacy and side effects, avoidance of parent-child communication about the vaccine, and a preference for framing the vaccine as a health promotion behavior. Framing the threat of HPV in the context of initiation of sexual activity, uncertainty regarding vaccine efficacy, and anticipated regret account for the inconsistency in HPV vaccine uptake among Somali parents. Clinicians should consider talking about HPV as a distal versus an immediate threat and HPV vaccine uptake as a health-promotion behavior rather than a sexually transmitted infection prevention behavior.

  19. Clinical cancer chemoprevention: From the hepatitis B virus (HBV vaccine to the human papillomavirus (HPV vaccine

    Directory of Open Access Journals (Sweden)

    Horng-Jyh Tsai

    2015-04-01

    Full Text Available Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV, a risk factor of hepatocellular cancer, and human papillomavirus (HPV, a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population, and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

  20. DEFB1 polymorphisms are involved in susceptibility to human papillomavirus infection in Brazilian gynaecological patients

    Directory of Open Access Journals (Sweden)

    Ludovica Segat

    2014-11-01

    Full Text Available The human beta defensin 1 (hBD-1 antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV. In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5’UTR and c.*5G>A and c.*87A>G in the 3’UTR in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.