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Sample records for human papillomavirus type-16

  1. 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 (...

  2. 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...

  3. 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

  4. 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.

  5. 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.

  6. 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

    2008-10-02

    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.

  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. 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.

  9. 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

    2008-01-01

    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

  10. 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.

  11. 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

  12. 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...

  13. 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

  14. 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....

  15. 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...

  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, 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...

  17. 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.

  18. 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

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

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    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...

  20. 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.

  1. Human Papillomavirus Subtype 16 and the Pathologic Characteristics of Laryngeal Cancer

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    Mohammed Abdel Motaal Gomaa MD

    2017-05-01

    Full Text Available Objective Laryngeal cancer is the most common type of cancer in the head and neck. Human papillomavirus (HPV represents a group of >150 related viruses. Infection with certain types of HPV can cause some types of cancer. This study aimed to evaluate the sociodemographic and histopathologic characters of squamous cell carcinoma of the larynx and its relationship to HPV subtype 16 (HPV-16. Study design Cross-sectional. Setting Tertiary university hospitals at 5 districts in Egypt (Minia, Cairo, Giza, Qaluobia, and Bani Seuif. Subjects and Methods This cross-sectional study was conducted on 50 adult patients with laryngeal cancer who were admitted at 5 tertiary care hospitals in Egypt from January 2014 through December 2014. All patients were subjected to a comprehensive preoperative assessment, histopathologic assessments of tumor biopsies, and immunohistochemical staining for HPV-16. Results HPV-16 immunostaining was positive in 9 patients (18%. A significant correlation between HPV-16 immunoreactivity and tumor grade ( P < .001 was detected, with no significant correlation between HPV-16 immunoreactivity and other clinical and pathologic variables. Conclusion The frequency of HPV-16 in laryngeal carcinoma is 18%, and there is significant correlation between HPV-16 and tumor grade.

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

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

    2010-01-01

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

  3. 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

  4. 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

  5. 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...

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

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    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.

  7. 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.

  8. 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.

  9. Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18

    International Nuclear Information System (INIS)

    Pastrana, Diana V.; Buck, Christopher B.; Pang, Y.-Y. S.; Thompson, Cynthia D.; Castle, Philip E.; FitzGerald, Peter C.; Krueger Kjaer, Susanne; Lowy, Douglas R.; Schiller, John T.

    2004-01-01

    Sensitive high-throughput neutralization assays, based upon pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter gene, were developed and validated for human papillomavirus (HPV)16, HPV18, and bovine papillomavirus 1 (BPV1). SEAP pseudoviruses were produced by transient transfection of codon-modified papillomavirus structural genes into an SV40 T antigen expressing line derived from 293 cells, yielding sufficient pseudovirus from one flask for thousands of titrations. In a 96-well plate format, in this initial characterization, the assay was reproducible and appears to be as sensitive as, but more specific than, a standard papillomavirus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). The neutralization assay detected type-specific HPV16 or HPV18 neutralizing antibodies (titers of 160-10240) in sera of the majority of a group of women infected with the corresponding HPV type, but not in virgin women. Sera from HPV16 VLP vaccinees had high anti-HPV16 neutralizing titers (mean: 45000; range: 5120-163840), but no anti-HPV18 neutralizing activity. The SEAP pseudovirus-based neutralization assay should be a practical method for quantifying potentially protective antibody responses in HPV natural history and prophylactic vaccine studies

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. Seroprevalence of Human Papillomavirus Types 6, 11, 16 and 18 in Chinese Women

    Directory of Open Access Journals (Sweden)

    Ji Jia

    2012-06-01

    Full Text Available Abstract Background Human papillomavirus (HPV seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women. Methods Population-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles. Results A total of 4,731 women (median age 35, age range 14-54 were included, of which 4,211 were sexually active women (median age 37 and 520 virgins (median age 18. Low risk HPV 6 was the most common serotype detected (7.3%, followed by HPV 16 (5.6%, HPV 11 (2.9%, and HPV 18 (1.9%. Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8% than virgins (2.5% (P = 0.005. Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P  = 4 partners versus 1 partner, P  Conclusions HPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.

  13. Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections.

    Science.gov (United States)

    van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J

    2017-10-01

    Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially ( P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is

  14. 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...

  15. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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 ...

  18. 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.

  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. 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

  1. 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.

  2. Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts in HeLa cells

    International Nuclear Information System (INIS)

    Inagaki, Yutaka; Tsunokawa, Youko; Takebe, Naoko; Terada, Masaaki; Sugimura, Takashi; Nawa, Hiroyuki; Nakanishi, Shigetada

    1988-01-01

    HeLa cells expressed 3.4- and 1.6-kilobase (kb) transcripts of the integrated human papillomavirus (HPV) type 18 genome. Two types of cDNA clones representing each size of HPV type 18 transcript were isolated. Sequence analysis of these two types of cDNA clones revealed that the 3.4-kb transcript contained E6, E7, the 5' portion of E1, and human sequence and that the 1.6-kb transcript contained spliced and frameshifted E6 (E6 * ), E7, and human sequence. There was a common human sequence containing a poly(A) addition signal in the 3' end portions of both transcripts, indicating that they were transcribed from the HPV genome at the same integration site with different splicing. Furthermore, the 1.6-kb transcript contained both of the two viral TATA boxes upstream of E6, strongly indicating that a cellular promoter was used for its transcription

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

    Science.gov (United States)

    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. 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

  5. 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

  6. 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

  7. A novel vaccine for cervical cancer: quadrivalent human papillomavirus (types 6, 11, 16 and 18 recombinant vaccine (Gardasil®

    Directory of Open Access Journals (Sweden)

    Vandana A Govan

    2008-03-01

    Full Text Available Vandana A GovanDivision of Medical Virology, Department of Clinical Laboratory Sciences and Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, South AfricaAbstract: Human papillomaviruses (HPVs are one of the most common sexually transmitted infections and remains a public health problem worldwide. There is strong evidence that HPV causes cervical, vulva and vaginal cancers, genital warts and recurrent respiratory papillomatosis. The current treatments for HPV-induced infections are ineffective and recurrence is commonplace. Therefore, to reduce the burden of HPV-induced infections, several studies have investigated the efficacy of different prophylactic vaccines in clinical human trials directed against HPV types 6, 11, 16, or 18. Notably, these HPV types contribute to a significant proportion of disease worldwide. This review will focus on the published results of Merck & Co’s prophylactic quadrivalent recombinant vaccine targeting HPV types 6, 11, 16, and 18 (referred to as Gardasil®. Data from the Phase III trial demonstrated that Gardasil was 100% effi cacious in preventing precancerous lesions of the cervix, vulva, and vagina and effective against genital warts. Due to the success of these human clinical trials, the FDA approved the registration of Gardasil on the 8 June 2006. In addition, since Gardasil has been efficacious for 5 years post vaccination, the longest evaluation of an HPV vaccine, it is expected to reduce the incidence of these type specific HPV-induced diseases in the future.Keywords: Gardasil, HPV, prophylactic vaccine, cervical disease

  8. 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....

  9. 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.

  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. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years

    DEFF Research Database (Denmark)

    Brown, Darron R; Kjaer, Susanne K; Sigurdsson, Kristján

    2009-01-01

    BACKGROUND: Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. METHODS: We enrolled 17......,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV...... types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. RESULTS: Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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...

  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. 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

  16. 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

  17. Human papillomavirus-16 presence and physical status in lung carcinomas from Asia

    Directory of Open Access Journals (Sweden)

    Morewaya Jacob

    2010-11-01

    Full Text Available Abstract Background Although human papillomavirus (HPV genome has been detected in lung cancer, its prevalence is highly variable around the world. Higher frequencies have been reported in far-east Asian countries, when compared with European countries. The present study analysed the HPV-16 presence in 60 lung carcinomas from the Asian countries China, Pakistan and Papua New Guinea. Results HPV-16 was present in 8/59 (13% samples. According to histological type, HPV-16 was detected in 8/18 (44% squamous cell carcinomas (SQCs, which were mainly from Pakistan; 0/38 (0% adenocarcinomas (ACs, which were mainly from China; and in 0/4 (0% small cell carcinomas (SCLCs. The observed histological difference was statistically significant (p Conclusion These results support the notion that HPV-16 infection is highly associated with SQCs in Pakistan. Our results show a frequent HPV-16 integration in SQCs, although the low viral load casts doubt respect a direct etiological role of HPV in lung carcinomas from Asia. Additional HPV-16 characterization is necessary to establish a direct or indirect etiological role of HPV in this malignancy.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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.

  1. 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

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

    Science.gov (United States)

    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

  3. 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

  4. The role of human papillomavirus in p16-positive oral cancers.

    Science.gov (United States)

    Belobrov, Simone; Cornall, Alyssa M; Young, Richard J; Koo, Kendrick; Angel, Christopher; Wiesenfeld, David; Rischin, Danny; Garland, Suzanne M; McCullough, Michael

    2018-01-01

    The aim of this study was to identify the presence and frequency of human papillomavirus (HPV) nucleic acid in p16-positive oral squamous cell carcinomas (OSCCs), to assess whether the virus was transcriptionally active and to assess the utility of p16 overexpression as a surrogate marker for HPV in OSCC. Forty-six OSCC patients treated between 2007 and 2011 with available formalin-fixed paraffin-embedded (FFPE) specimens were included. Twenty-three patients were positive for p16 by immunohistochemistry (IHC) and these were matched with 23 patients with p16-negative tumours. Laser capture microdissection of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA was extracted and tested for high-risk HPV types using a PCR-ELISA method based on the L1 SPF10 consensus primers, and a real-time PCR method targeting HPV-16 and HPV-18 E6 region. Genotyping of HPV-positive cases was performed using a reverse line blot hybridization assay (Inno-LiPA). RNAScope ® (a chromogenic RNA in situ hybridization assay) was utilized to detect E6/E7 mRNA of known high-risk HPV types for detection of transcriptionally active virus. HPV DNA was found in 3 OSCC cases, all of which were p16 IHC-positive. Two cases were genotyped as HPV-16 and one as HPV-33. Only one of the HPV-16 cases was confirmed to harbour transcriptionally active virus via HPV RNA ISH. We have shown that the presence of transcriptionally active HPV rarely occurs in OSCC and that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose that non-viral mechanisms are responsible for the majority of IHC p16 overexpression in OSCC. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. 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

  6. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women.

    Science.gov (United States)

    Perez, Gonzalo; Lazcano-Ponce, Eduardo; Hernandez-Avila, Mauricio; García, Patricia J; Muñoz, Nubia; Villa, Luisa L; Bryan, Janine; Taddeo, Frank J; Lu, Shuang; Esser, Mark T; Vuocolo, Scott; Sattler, Carlos; Barr, Eliav

    2008-03-15

    The prevalence of HPV infection in Latin America is among the highest in the world. A quadrivalent (types 6/11/16/18) human papillomavirus L1 virus-like-particle vaccine has been shown to be 95-100% effective in preventing HPV 6/11/16/18-related cervical and genital disease in women naive to vaccine HPV types. A total of 6,004 female subjects aged 9-24 were recruited from Brazil, Mexico, Colombia, Costa Rica, Guatemala and Peru. Subjects were randomized to immunization with intramuscular (deltoid) injections of HPV vaccine or placebo at enrollment (day 1), month 2 and month 6. Among vaccinated subjects in the per-protocol population from Latin America, quadrivalent HPV vaccine was 92.8 and 100% effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types, respectively. These data support vaccination of adolescents and young adults in the region, which is expected to greatly reduce the burden of cervical and genital cancers, precancers and genital warts. (c) 2007 Wiley-Liss, Inc.

  7. Type-specific human papillomavirus biological features: validated model-based estimates.

    Directory of Open Access Journals (Sweden)

    Iacopo Baussano

    Full Text Available Infection with high-risk (hr human papillomavirus (HPV is considered the necessary cause of cervical cancer. Vaccination against HPV16 and 18 types, which are responsible of about 75% of cervical cancer worldwide, is expected to have a major global impact on cervical cancer occurrence. Valid estimates of the parameters that regulate the natural history of hrHPV infections are crucial to draw reliable projections of the impact of vaccination. We devised a mathematical model to estimate the probability of infection transmission, the rate of clearance, and the patterns of immune response following the clearance of infection of 13 hrHPV types. To test the validity of our estimates, we fitted the same transmission model to two large independent datasets from Italy and Sweden and assessed finding consistency. The two populations, both unvaccinated, differed substantially by sexual behaviour, age distribution, and study setting (screening for cervical cancer or Chlamydia trachomatis infection. Estimated transmission probability of hrHPV types (80% for HPV16, 73%-82% for HPV18, and above 50% for most other types; clearance rates decreasing as a function of time since infection; and partial protection against re-infection with the same hrHPV type (approximately 20% for HPV16 and 50% for the other types were similar in the two countries. The model could accurately predict the HPV16 prevalence observed in Italy among women who were not infected three years before. In conclusion, our models inform on biological parameters that cannot at the moment be measured directly from any empirical data but are essential to forecast the impact of HPV vaccination programmes.

  8. 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,.

  9. 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...

  10. [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.

  11. Prevalence of the integration status for human papillomavirus 16 in esophageal carcinoma samples.

    Science.gov (United States)

    Li, Shuying; Shen, Haie; Li, Ji; Hou, Xiaoli; Zhang, Ke; Li, Jintao

    2018-03-01

    To investigate the etiology of esophageal cancer (EC) related with human papillomavirus (HPV) infection. Fresh surgically resected tissue samples and clinical information were obtained from 189 patients. Genomic DNA was extracted, and HPV was detected using polymerase chain reaction (PCR) with HPV L1 gene primers of MY09/11; HPV16 was detected using HPV16 E6 type-specific primer sets. Copies of HPV16 E2, E6, and the human housekeeping gene β-actin were tested using quantitative PCR to analyze the relationship between HPV16 integration and esophageal squamous cell carcinoma and the relationship between the HPV16 integration status and clinical information of patients. Of the 189 samples, 168 HPV-positive samples were detected, of which 76 were HPV16 positive. Among the HPV16 positive samples, 2 cases (E2/E6 ratio>1) were 2.6% (2/76) purely episomal, 65 (E2/E6 ratio between 0 and 1) were 85.6% (65/76) mixture of integrated and episomal, and 9 (E2/E6 ratio=0) were 11.8% (9/76) purely integrated. The results indicate that integration of HPV16 was more common in the host genome than in the episome genome. The prevalence rate of HPV16 integration is increasing with the pathological stage progression of esophageal carcinoma (EC). A high prevalence of HPV16 suggested that HPV16 has an etiological effect on the progress of EC. Integration of HPV16 is more common than episome genome in the host cells, indicating that continuous HPV infection is the key to esophageal epithelial cell malignant conversion and canceration.

  12. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions

    DEFF Research Database (Denmark)

    Kjaer, Susanne K; Sigurdsson, Kristján; Iversen, Ole-Erik

    2009-01-01

    Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions bas...

  13. [Detection and typing by molecular biology of human papillomavirus in genital samples].

    Science.gov (United States)

    Suárez Moya, A; Esquivias Gómez, J I; Vidart Aragón, J A; Picazo de la Garza, J J

    2006-06-01

    Recently, there has been a marked increase in human papillomavirus (HPV) infection, and the etiological relationship between some HPV genotypes and genital cancer has been confirmed. Therefore, we used current molecular biology techniques to evaluate the prevalence of these viruses and their genotype in genital samples. We processed 401 genital samples from 281 women and 120 men, all with a diagnosis compatible with HPV infection. Virus was detected using PCR, and positive samples were typed using an array technique which enabled us to detect the 35 most common types of mucous-associated HPV. Of the 401 patients studied, 185 (46.1%) were positive, and only one type of HPV was detected in 133 cases. We found that 41.6% of the women and 56.7% of the men were positive. A total of 260 HPVs were typed; 154 were high oncogenic risk. They infected 16 men (23.5%) and 88 women (75.2%). The difference was statistically significant (pHVP 16 in 52 cases. We found a 46% prevalence of HPV infection. More than half of these patients were infected by high-risk HPV. The presence of high-risk HPV was significantly higher in women.

  14. 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

  15. 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.

  16. 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

  17. Detection and analysis of human papillomavirus 16 and 18 homologous DNA sequences in oral lesions.

    Science.gov (United States)

    Wen, S; Tsuji, T; Li, X; Mizugaki, Y; Hayatsu, Y; Shinozaki, F

    1997-01-01

    The prevalence of human papillomavirus (HPV) 16 and 18 was investigated in oral lesions of the population of northeast China including squamous cell carcinomas (SCCs), candida leukoplakias, lichen planuses and papillomas, by southern blot hybridization with polymerase chain reaction (PCR). Amplified HPV16 and 18 E6 DNA was analyzed by cycle sequence. HPV DNA was detected in 14 of 45 SCCs (31.1%). HPV18 E6 DNA and HPV16 E6. DNA were detected in 24.4% and 20.0% of SCCs. respectively. Dual infection of both HPV 16 and HPV 18 was detected in 6 of 45 SCCs (13.3%), but not in other oral lesions. HPV 18 E6 DNA was also detected in 2 of 3 oral candida leukoplakias, but in none of the 5 papillomas. Our study indicated that HPV 18 infection might be more frequent than HPV 16 infection in oral SCCs in northeast Chinese, dual infection of high risk HPV types was restricted in oral SCCs, and that HPV infection might be involved in the pathogenesis of oral candida leukoplakia.

  18. 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.

  19. 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.

  20. Detection of human papillomavirus type 18 E6 and E7-specific CD4+ T-helper 1 immunity in relation to health versus disease

    NARCIS (Netherlands)

    Welters, Marij J. P.; van der Logt, Pauline; van den Eeden, Susan J. F.; Kwappenberg, Kitty M. C.; Drijfhout, Jan Wouter; Fleuren, Gert Jan; Kenter, Gemma G.; Melief, Cornelis J. M.; van der Burg, Sjoerd H.; Offringa, Rienk

    2006-01-01

    The most common high-risk human papillomavirus types, HPV16 and 18, differ markedly with respect to their interaction with the host. Clearance of HPV18 infections generally takes longer and HPV18-positive cancers have a poorer prognosis. We therefore evaluated Th1-type immunity against the E6 and E7

  1. A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16.

    Science.gov (United States)

    Gottschalk, Elinor Y; Meneses, Patricio I

    2015-09-01

    The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the trans-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of

  2. 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

  3. 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

  4. 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...

  5. 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 ...

  6. 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...

  7. 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.

  8. 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

  9. 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

  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. 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.

  12. 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

  13. The Cellular DNA Helicase ChlR1 Regulates Chromatin and Nuclear Matrix Attachment of the Human Papillomavirus 16 E2 Protein and High-Copy-Number Viral Genome Establishment.

    Science.gov (United States)

    Harris, Leanne; McFarlane-Majeed, Laura; Campos-León, Karen; Roberts, Sally; Parish, Joanna L

    2017-01-01

    In papillomavirus infections, the viral genome is established as a double-stranded DNA episome. To segregate the episomes into daughter cells during mitosis, they are tethered to cellular chromatin by the viral E2 protein. We previously demonstrated that the E2 proteins of diverse papillomavirus types, including bovine papillomavirus (BPV) and human papillomavirus 16 (HPV16), associate with the cellular DNA helicase ChlR1. This virus-host interaction is important for the tethering of BPV E2 to mitotic chromatin and the stable maintenance of BPV episomes. The role of the association between E2 and ChlR1 in the HPV16 life cycle is unresolved. Here we show that an HPV16 E2 Y131A mutant (E2 Y131A ) had significantly reduced binding to ChlR1 but retained transcriptional activation and viral origin-dependent replication functions. Subcellular fractionation of keratinocytes expressing E2 Y131A showed a marked change in the localization of the protein. Compared to that of wild-type E2 (E2 WT ), the chromatin-bound pool of E2 Y131A was decreased, concomitant with an increase in nuclear matrix-associated protein. Cell cycle synchronization indicated that the shift in subcellular localization of E2 Y131A occurred in mid-S phase. A similar alteration between the subcellular pools of the E2 WT protein occurred upon ChlR1 silencing. Notably, in an HPV16 life cycle model in primary human keratinocytes, mutant E2 Y131A genomes were established as episomes, but at a markedly lower copy number than that of wild-type HPV16 genomes, and they were not maintained upon cell passage. Our studies indicate that ChlR1 is an important regulator of the chromatin association of E2 and of the establishment and maintenance of HPV16 episomes. Infections with high-risk human papillomaviruses (HPVs) are a major cause of anogenital and oropharyngeal cancers. During infection, the circular DNA genome of HPV persists within the nucleus, independently of the host cell chromatin. Persistence of infection

  14. Isolation of a novel human papillomavirus (type 51) from a cervical condyloma

    International Nuclear Information System (INIS)

    Nuovo, G.J.; Crum, C.P.; Levine, R.U.; Silverstein, S.J.; De Villiers, E.M.

    1988-01-01

    The authors cloned the DNA from a novel human papillomavirus (HPV) present in a cervical condyloma. When DNA from this isolate was hybridized at high stringency with HPV types 1 through 50 (HPV-1 through HPV-50), it showed weak homology with HPV-6 and -16 and stronger homology with HPV-26. A detailed restriction endonuclease map was prepared which showed marked differences from the maps for other HPVs that have been isolated from the female genital tract. Reassociation kinetic analysis revealed that HPV-26 and this new isolate were less than 10% homologous; hence, the new isolate is a noel strain of HPV. The approximate positions of the open reading frames of the new strain were surmised by hybridization with probes derived from individual open reading frames of HPV-16. In an analysis of 175 genital biopsies from patients with abnormal Papanicolaou smears, sequences hybridizing under highly stringent conditions to probes from this novel HPV type were found in 4.2, 6.1, and 2.4% of biopsies containing normal squamous epithelium, condylomata, and intraepithelial neoplasia, respectively. In addition, sequences homologous to probes from this novel isolate were detected in one of five cervical carcinomas examined

  15. 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.

  16. 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

  17. 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.

  18. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

    International Nuclear Information System (INIS)

    Hu Lulin; Plafker, Kendra; Vorozhko, Valeriya; Zuna, Rosemary E.; Hanigan, Marie H.; Gorbsky, Gary J.; Plafker, Scott M.; Angeletti, Peter C.; Ceresa, Brian P.

    2009-01-01

    Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis

  19. 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.

  20. 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.

  1. 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.

  2. Human papillomavirus prevalence and type distribution in 3603 HIV-positive and HIV-negative women in the general population of Tanzania

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Kahesa, Crispin

    2012-01-01

    The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation for a po......The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation...

  3. 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.

  4. 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...

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. Human Papillomavirus types distribution among women with cervical preneoplastic, lesions and cancer in Luanda, Angola.

    Science.gov (United States)

    Damião, Paciência de Almeida; Oliveira-Silva, Michelle; Moreira, Miguel Ângelo; Poliakova, Natalia; de Lima, Maria Emilia Rt; Chiovo, José; Nicol, Alcina Frederica

    2016-01-01

    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. To determine the frequency of HPV among women with squamous intraepithelial lesions from women in Luanda, Angola. Study participants included women diagnosed with cytological abnormalities that voluntarily provided Pap smears (n = 64). Genomic DNA was extracted from the samples for use as templates in the PCR amplification of HPV sequences. PCR products were sequenced to determine HPV type. HPV DNA was detected in 71.9% (46/64) in the samples. A higher diversity of HPV types was found in the cytological lesions, such as ASCUS and LSIL (HPV16, 6, 18, 31, 58, 66, 70 and 82, in order of frequency) than that detected for HSIL and SSC (HPV16, 18, 6 and 33). The most prevalent HPV type were: HPV16, HPV6 and HPV18. This is the first report on HPV type diversity and frequency in woman of Angola. The results suggest that large-scale studies across Africa would improve our understanding of interrelationship between HPV infections and cervical cancer. More directly, the identification of the HPV types most prevalent suggests that women in Angola would benefit from currently available HPV vaccines.

  10. 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.

  11. 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.

  12. 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

  13. [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.

  14. Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

    NARCIS (Netherlands)

    Schmeink, C.E.; Bekkers, R.L.M.; Josefsson, A.; Richardus, J.H.; Berndtsson Blom, K.; David, M.P.; Dobbelaere, K.; Descamps, D.

    2011-01-01

    BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV

  15. A pilot analytic study of a research-level, lower-cost human papillomavirus 16, 18, and 45 test

    OpenAIRE

    Yang, Hannah P.; Walmer, David K.; Merisier, Delson; Gage, Julia C.; Bell, Laura; Rangwala, Sameera; Shrestha, Niwashin; Kobayashi, Lori; Eder, Paul S.; Castle, Philip E.

    2011-01-01

    The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16, HPV18, and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings (“triage test”). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kap...

  16. 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.

  17. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    Science.gov (United States)

    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 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV. Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection. PMID:27331659

  18. 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.

  19. 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.

  20. 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.)

  1. 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.

  2. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

    DEFF Research Database (Denmark)

    Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf

    2013-01-01

    Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination...... on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical...... higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    Directory of Open Access Journals (Sweden)

    Yat Ming Lau

    Full Text Available High-risk human papillomavirus (HPV types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4 years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%, HPV-18 (21.6%, HPV-52 (11.9%, and HPV-58 (9.3%. Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1% patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90, whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79. However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  10. 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.

  11. Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

    Directory of Open Access Journals (Sweden)

    Tommasino Massimo

    2011-06-01

    Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

  12. 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

  13. 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

  14. 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...

  15. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women.

    Science.gov (United States)

    Barr, Eliav; Gause, Christine K; Bautista, Oliver M; Railkar, Radha A; Lupinacci, Lisa C; Insinga, Ralph P; Sings, Heather L; Haupt, Richard M

    2008-03-01

    The purpose of this study was to inform policy regarding human papillomavirus (HPV) vaccination in North America. We measured the clinical impact of HPV-6/-11/-16/-18 vaccination in North American women. The study enrolled 21,954 women, the majority aged 16-25, across 5 studies of a quadrivalent HPV vaccine or its HPV-16 vaccine prototype. The North American subjects (n = 5996) were pooled from these trials, and the prevalence of HPV-6/-11/-16/-18 exposure was measured. The impact of vaccination on the burden of anogenital HPV lesions in an intention-to-treat population (regardless of enrollment HPV status) was calculated. At enrollment, the median age was 20 years; 13% of the women had had a Papanicolaou test abnormality, and 76% of the women had negative tests results for all 4 vaccine HPV types. With approximately 3 years of follow-up evaluations in the intention-to-treat population (regardless of enrollment HPV status), vaccination reduced the rate of HPV-16- and -18-related precancers and HPV-6/-11/-16/-18-related genital lesions by 66.4% (95% CI, 42.7%-81.1%) and 57.7% (95% CI, 27.3%-76.3%), respectively. The administration of HPV vaccine to sexually active North American women reduced the burden of HPV-6/-11/-16/-18-related disease. Catch-up vaccination programs in this population are warranted.

  16. 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

  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. 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

  19. 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.)

  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. 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

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

    Science.gov (United States)

    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.

  3. 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)

  4. 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...

  5. Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV-6/11/16/18 vaccine in Canada

    Directory of Open Access Journals (Sweden)

    Kohli Michele

    2012-10-01

    Full Text Available Background In Canada, two vaccines that have demonstrated high efficacy against infection with human papillomavirus (HPV types16 and −18 are available. The HPV-6/11/16/18 vaccine provides protection against genital warts (GW while the HPV-16/18 vaccine may provide better protection against other oncogenic HPV types. In this analysis, the estimated clinical and economic benefit of each of these vaccines was compared in the Canadian setting. Methods A Markov model of the natural history of HPV infection among women, cervical cancer (CC and GW was used to estimate the impact of vaccinating a cohort of 100,000 12-year-old females on lifetime outcomes and healthcare system costs (no indirect benefit in males included. A budget impact model was used to estimate the impact of each vaccine by province. Results In the base case, vaccination with the HPV-16/18 vaccine was predicted to prevent 48 additional CC cases, and 16 additional CC deaths, while vaccination with the HPV-6/11/16/18 vaccine was predicted to prevent 6,933 additional GW cases. Vaccination with the HPV-16/18 vaccine was estimated to save 1 additional discounted quality adjusted life year (QALY at an overall lower lifetime cost to the healthcare system compared to the HPV-6/11/16/18 vaccine (assuming vaccine price parity. In sensitivity analyses, the HPV-6/11/16/18 vaccine was associated with greater QALYs saved when the cross-protection efficacy of the HPV-16/18 vaccine was reduced, or the burden of GW due to HPV-6/11 was increased. In most scenarios with price parity, the lifetime healthcare cost of the strategy with the HPV-16/18 vaccine was predicted to be lower than the HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analyses, the HPV-16/18 vaccine provided more QALY benefit than the HPV-6/11/16/18 vaccine in 49.2% of scenarios, with lower relative lifetime costs in 83.5% of scenarios. Conclusions Overall, the predicted lifetime healthcare costs and QALYs saved by

  6. 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

  7. 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)

  8. A pilot analytic study of a research-level, lower-cost human papillomavirus 16, 18, and 45 test.

    Science.gov (United States)

    Yang, Hannah P; Walmer, David K; Merisier, Delson; Gage, Julia C; Bell, Laura; Rangwala, Sameera; Shrestha, Niwashin; Kobayashi, Lori; Eder, Paul S; Castle, Philip E

    2011-09-01

    The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16, HPV18, and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings ("triage test"). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kappa = 0.87). DNA sequencing on a subset of 16 HPV16/18/45 positive and 16 HPV16/18/45 negative verified the analytic specificity of the research test. It is concluded that the HPV16/18/45 assay is a promising triage test with a minimum detection of approximately 5000 viral copies, the clinically relevant threshold. Published by Elsevier B.V.

  9. Modulation of microRNA-mRNA Target Pairs by Human Papillomavirus 16 Oncoproteins

    Directory of Open Access Journals (Sweden)

    Mallory E. Harden

    2017-01-01

    Full Text Available The E6 and E7 proteins are the major oncogenic drivers encoded by high-risk human papillomaviruses (HPVs. While many aspects of the transforming activities of these proteins have been extensively studied, there are fewer studies that have investigated how HPV E6/E7 expression affects the expression of cellular noncoding RNAs. The goal of our study was to investigate HPV16 E6/E7 modulation of cellular microRNA (miR levels and to determine the potential consequences for cellular gene expression. We performed deep sequencing of small and large cellular RNAs in primary undifferentiated cultures of human foreskin keratinocytes (HFKs with stable expression of HPV16 E6/E7 or a control vector. After integration of the two data sets, we identified 51 differentially expressed cellular miRs associated with the modulation of 1,456 potential target mRNAs in HPV16 E6/E7-expressing HFKs. We discovered that the degree of differential miR expression in HFKs expressing HPV16 E6/E7 was not necessarily predictive of the number of corresponding mRNA targets or the potential impact on gene expression. Additional analyses of the identified miR-mRNA pairs suggest modulation of specific biological activities and biochemical pathways. Overall, our study supports the model that perturbation of cellular miR expression by HPV16 E6/E7 importantly contributes to the rewiring of cellular regulatory circuits by the high-risk HPV E6 and E7 proteins that contribute to oncogenic transformation.

  10. Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

    DEFF Research Database (Denmark)

    Pedersen, Court; Breindahl, Morten; Aggarwal, Naresh

    2012-01-01

    This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A......, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone....

  11. 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

  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. Long-term Study of a Quadrivalent Human Papillomavirus Vaccine

    DEFF Research Database (Denmark)

    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...

  14. 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

  15. Sonoporation delivery of monoclonal antibodies against human papillomavirus 16 E6 restores p53 expression in transformed cervical keratinocytes.

    Directory of Open Access Journals (Sweden)

    Melissa Togtema

    Full Text Available High-risk types of human papillomavirus (HPV, such as HPV16, have been found in nearly all cases of cervical cancer. Therapies targeted at blocking the HPV16 E6 protein and its deleterious effects on the tumour suppressor pathways of the cell can reverse the malignant phenotype of affected keratinocytes while sparing uninfected cells. Through a strong interdisciplinary collaboration between engineering and biology, a novel, non-invasive intracellular delivery method for the HPV16 E6 antibody, F127-6G6, was developed. The method employs high intensity focused ultrasound (HIFU in combination with microbubbles, in a process known as sonoporation. In this proof of principle study, it was first demonstrated that sonoporation antibody delivery into the HPV16 positive cervical carcinoma derived cell lines CaSki and SiHa was possible, using chemical transfection as a baseline for comparison. Delivery of the E6 antibody using sonoporation significantly restored p53 expression in these cells, indicating the antibody is able to enter the cells and remains active. This delivery method is targeted, non-cytotoxic, and non-invasive, making it more easily translatable for in vivo experiments than other transfection methods.

  16. 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.

  17. A chimeric 18L1-45RG1 virus-like particle vaccine cross-protects against oncogenic alpha-7 human papillomavirus types.

    Directory of Open Access Journals (Sweden)

    Bettina Huber

    Full Text Available Persistent infection with oncogenic human papillomaviruses (HPV types causes all cervical and a subset of other anogenital and oropharyngeal carcinomas. Four high-risk (hr mucosal types HPV16, 18, 45, or 59 cause almost all cervical adenocarcinomas (AC, a subset of cervical cancer (CxC. Although the incidence of cervical squamous cell carcinoma (SCC has dramatically decreased following introduction of Papanicolaou (PAP screening, the proportion of AC has relatively increased. Cervical SCC arise mainly from the ectocervix, whereas AC originate primarily from the endocervical canal, which is less accessible to obtain viable PAP smears. Licensed (bivalent and quadrivalent HPV vaccines comprise virus-like particles (VLP of the most important hr HPV16 and 18, self-assembled from the major capsid protein L1. Due to mainly type-restricted efficacy, both vaccines do not target 13 additional hr mucosal types causing 30% of CxC. The papillomavirus genus alpha species 7 (α7 includes a group of hr types of which HPV18, 45, 59 are proportionally overrepresented in cervical AC and only partially (HPV18 targeted by current vaccines. To target these types, we generated a chimeric vaccine antigen that consists of a cross-neutralizing epitope (homologue of HPV16 RG1 of the L2 minor capsid protein of HPV45 genetically inserted into a surface loop of HPV18 L1 VLP (18L1-45RG1. Vaccination of NZW rabbits with 18L1-45RG1 VLP plus alum-MPL adjuvant induced high-titer neutralizing antibodies against homologous HPV18, that cross-neutralized non-cognate hr α7 types HPV39, 45, 68, but not HPV59, and low risk HPV70 in vitro, and induced a robust L1-specific cellular immune response. Passive immunization protected mice against experimental vaginal challenge with pseudovirions of HPV18, 39, 45 and 68, but not HPV59 or the distantly related α9 type HPV16. 18L1-45RG1 VLP might be combined with our previously described 16L1-16RG1 VLP to develop a second generation bivalent

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Human papillomavirus detection and typing using a nested-PCR-RFLP assay.

    Science.gov (United States)

    Coser, Janaina; Boeira, Thaís da Rocha; Fonseca, André Salvador Kazantzi; Ikuta, Nilo; Lunge, Vagner Ricardo

    2011-01-01

    It is clinically important to detect and type human papillomavirus (HPV) in a sensitive and specific manner. Development of a nested-polymerase chain reaction-restriction fragment length polymorphism (nested-PCR-RFLP) assay to detect and type HPV based on the analysis of L1 gene. Analysis of published DNA sequence of mucosal HPV types to select sequences of new primers. Design of an original nested-PCR assay using the new primers pair selected and classical MY09/11 primers. HPV detection and typing in cervical samples using the nested-PCR-RFLP assay. The nested-PCR-RFLP assay detected and typed HPV in cervical samples. Of the total of 128 clinical samples submitted to simple PCR and nested-PCR for detection of HPV, 37 (28.9%) were positive for the virus by both methods and 25 samples were positive only by nested-PCR (67.5% increase in detection rate compared with single PCR). All HPV positive samples were effectively typed by RFLP assay. The method of nested-PCR proved to be an effective diagnostic tool for HPV detection and typing.

  5. 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

  6. Seroprevalence of Human Papillomavirus (HPV) Type 6, 11, 16, 18, by Anatomic Site of HPV Infection, in Women Aged 16-64 Years living in the Metropolitan Area of San Juan, Puerto Rico.

    Science.gov (United States)

    Pérez-Caraballo, Aixa M; Suarez, Erick; Unger, Elizabeth R; Palefsky, Joel M; Panicker, Gitika; Ortiz, Ana Patricia

    2018-03-01

    It is unknown if human papillomavirus (HPV) serum antibody responses vary by anatomic site of infection. We aimed to assess the seroprevalence for HPV 6, 11, 16 and 18 in association with HPV DNA detection in different anatomic sites among women. This cross sectional population-based study analyzed data from 524 women aged 16-64 years living in the San Juan metropolitan area of Puerto Rico (PR). Questionnaires were used to assess demographic and lifestyle variables, while anogenital and blood samples were collected for HPV analysis. Logistic regression models were used to estimate the adjusted prevalence odds ratio (POR) in order to determine the association between HPV DNA infection status in the cervix and anus and serum antibody status, controlling for different potential confounders. Overall, 46.9% of women had detectable antibodies to one or more types whereas 8.7% had HPV DNA for one or more of these types detected in cervix (4.0%) or anus (6.5%). Women with cervical HPV detection tended to be more HPV seropositive than women without cervical detection (adjusted POR (95%CI): 2.41 (0.90, 6.47), p=0.078); however the type-specific association between cervical DNA and serum antibodies was only significant for HPV 18 (adjusted POR (95% CI): 5.9 (1.03, 33.98)). No significant association was detected between anal HPV and seropositivity (p>0.10). Differences in the anatomic site of infection could influence seroconversion, however, longitudinal studies will be required for further evaluation. This information will be instrumental in advancing knowledge of immune mechanisms involved in anatomic site response.

  7. 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.

  8. Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women

    OpenAIRE

    Kim, Seung Cheol; Song, Yong Sang; Kim, Young-Tae; Kim, Young Tak; Ryu, Ki-Sung; Gunapalaiah, Bhavyashree; Bi, Dan; Bock, Hans L; Park, Jong-Sup

    2011-01-01

    Objective The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years. Methods Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularl...

  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. 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 ...

  11. Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

    Science.gov (United States)

    Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

    2011-09-21

    Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

  12. 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

  13. 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.

  14. 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 ...

  15. 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

  16. Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer

    OpenAIRE

    Clifford, Gary M.; Tully, Stephen; Franceschi, Silvia

    2017-01-01

    Abstract Background. Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. Methods. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undete...

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

    Science.gov (United States)

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

    2018-05-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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....

  2. 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.

  3. 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.

  4. 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.

  5. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Human papillomavirus type-specific prevalence in the cervical cancer screening population of Czech women.

    Directory of Open Access Journals (Sweden)

    Ruth Tachezy

    Full Text Available BACKGROUND: Infection with high-risk human papillomavirus (HPVtypes has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice. OBJECTIVES: The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV. METHODS: Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2 and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB. RESULTS: Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393 of women were positive for any HPV type by BS-RLB, 18.2% (254/1393 by HR HC2, and 22.3% (310/1393 by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%. HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years. CONCLUSIONS: Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.

  11. Analisis Filogenetik Gen L1 Human Papillomavirus 16 pada Penderita Kanker Serviks di Bandung

    Directory of Open Access Journals (Sweden)

    Fitri Rahmi Fadhilah

    2015-09-01

    Full Text Available Chronic infection with high-risk (hr human papillomavirus (HPV can lead to cervical cancer. Various hrHPV genotypes have been identified and HPV genotype 16 is the most common genotypes that infect cervical cancer. HPV L1 fragment can identify the origin of HPV. The purpose of this study was to explore the origins of HPV-16 by making a phylogenetic tree. This study used analytical descriptive method and was was conducted at the Laboratory of Molecular Genetics, Health Research Unit, Faculty of Medicine, Universitas Padjadjaran Bandung in the period of February to August 2013. Biopsy from cervical cancer patient was donated by the Department of Obstetrics, Faculty of Medicine, Universitas Padjadjaran, Bandung. Isolation of DNA was prepared from tissue biopsies of cervical cancer and L1 fragment was amplified with the specific primer. Infection with HPV-16 was confirmed by Linear Array test (Roche design. The sequence then was constructed using the phylogenetic program (MEGA5. Results showed that the isolate from patient with cervical cancer from Bandung was in one subgroup with HPV from Asia and East Asia. In conclusion, cluster HPV of Bandung is in the same strain as the strain in Asia and East Asia

  12. Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population

    OpenAIRE

    Wang, Zhen; Xia, Rong-Hui; Ye, Dong-Xia; Li, Jiang

    2016-01-01

    Objectives To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population. Methods The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples. p53 expression levels and TP...

  13. [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.

  14. 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. ...

  15. Human papillomavirus and its influence on head and neck cancer predisposition

    Directory of Open Access Journals (Sweden)

    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.

  16. Detection of human papillomavirus type 6/11 DNA in conjunctival papillomas by in situ hybridization with radioactive probes

    International Nuclear Information System (INIS)

    McDonnell, P.J.; McDonnell, J.M.; Kessis, T.; Green, W.R.; Shah, K.V.

    1987-01-01

    Twenty-three conjunctival papillomas and 28 conjunctival dysplasias were examined for human papillomavirus (HPV)-DNA sequences by in situ hybridization with nick-translated 35 S-labeled HPV probes. Adjacent paraffin sections were hybridized with HPV type 2, 6, 16, and 18 probes at Tm - 17 degrees C. Fifteen tissues, all papillomas, displayed positive hybridization with the HPV-6 probe. Infection with HPV-6 (or the closely related HPV-11) appeared to be responsible for most of the conjunctival papillomas of children and young adults. The presence of genital tract HPV-6 in these lesions suggests that some of the infections were acquired during passage through an infected birth canal. The lack of hybridization in adult conjunctival dysplasias indicates either that HPVs are not associated with this condition or that the probes and the technique utilized were not adequate for demonstration of this association

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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)

  20. [Human Papilloma virus in Quechua women from Jujuy with high frequency of cervical cancer: viral types and HPV-16 variants].

    Science.gov (United States)

    Picconi, Maria Alejandra; Gronda, Jorge; Alonio, Lidia V; Villa, Luisa L; Sichero, Laura; Miranda, Sergio; Barcena, Martin; Teyssie, Angelica

    2002-01-01

    Human Papillomaviruses (HPVs) are etiologically associated to cervical carcinoma. In order to evaluate HPV infection and its relationship with the high frequency of this neoplasia in Quechua women from Jujuy (Argentina), 271 cervical samples from preneoplastic and neoplastic lesions (biopsies) and normal controls (cytologies) were studied. Detection and typing were performed using PCR-RFLP or PCR-hybridization and the HPV-16 variability in L1 and E6 genes (by PCR-hybridization) was analysed. HPV was detected in 52% of controls, 91% of low-grade lesions, 97% of high-grade lesions and 100% of invasive carcinomas, corresponding 55% to HPV-16. HPV-16 European variants were predominant, most of them being non-prototypic strains. The high frequency of high risk infection types and the raised proportion of HPV-16 non-prototypic variants related to a greater oncogenic potential could explain, in part, the high cervical cancer frequency of this native population. These data may contribute to disease control and vaccinal formulation.

  1. 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.

  2. Specific identification of human papillomavirus type in cervical smears and paraffin sections by in situ hybridization with radioactive probes: a preliminary communication

    International Nuclear Information System (INIS)

    Gupta, J.; Gendelman, H.E.; Naghashfar, Z.; Gupta, P.; Rosenshein, N.; Sawada, E.; Woodruff, J.D.; Shah, K.

    1985-01-01

    Cervical Papanicolaou smears and paraffin sections of biopsy specimens obtained from women attending dysplasia clinics were examined for viral DNA sequences by in situ hybridization technique using 35 S-labeled cloned recombinant DNA probes of human papillomavirus (HPV) types 6, 11, and 16. These and one unrelated DNA probe complementary to measles virus RNA were labeled by nick translation using either one or two 35 S-labeled nucleotides. Paraffin sections and cervical smears were collected on pretreated slides, hybridized with the probes under stringent or nonstringent conditions for 50 h, and autoradiographed. Additional cervical specimens from the same women were examined for the presence of genus-specific papillomavirus capsid antigen by the immunoperoxidase technique. Preliminary results may be summarized as follows. The infecting virus could be identified in smears as well as in sections. Viral DNA sequences were detected only when there were condylomatous cells in the specimen and in only a proportion of the condylomatous cells. Even under stringent conditions, some specimens reacted with both HPV-6 and HPV-11. In some instances, the cells did not hybridize with any of the three probes even when duplicate specimens contained frankly condylomatous, capsid antigen-positive cells. In situ hybridization of Papanicolaou smears or of tissue sections is a practical method for diagnosis and follow-up of specific papillomavirus infection using routinely collected material

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

    Directory of Open Access Journals (Sweden)

    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.

  4. The human papillomavirus type 11 and 16 E6 proteins modulate the cell-cycle regulator and transcription cofactor TRIP-Br1

    International Nuclear Information System (INIS)

    Gupta, Sanjay; Takhar, Param Parkash S; Degenkolbe, Roland; Heng Koh, Choon; Zimmermann, Holger; Maolin Yang, Christopher; Guan Sim, Khe; I-Hong Hsu, Stephen; Bernard, Hans-Ulrich

    2003-01-01

    The genital human papillomaviruses (HPVs) are a taxonomic group including HPV types that preferentially cause genital and laryngeal warts ('low-risk types'), such as HPV-6 and HPV-11, or cancer of the cervix and its precursor lesions ('high-risk types'), such as HPV-16. The transforming processes induced by these viruses depend on the proteins E5, E6, and E7. Among these oncoproteins, the E6 protein stands out because it supports a particularly large number of functions and interactions with cellular proteins, some of which are specific for the carcinogenic HPVs, while others are shared among low- and high-risk HPVs. Here we report yeast two-hybrid screens with HPV-6 and -11 E6 proteins that identified TRIP-Br1 as a novel cellular target. TRIP-Br1 was recently detected by two research groups, which described two separate functions, namely that of a transcriptional integrator of the E2F1/DP1/RB cell-cycle regulatory pathway (and then named TRIP-Br1), and that of an antagonist of the cyclin-dependent kinase suppression of p16INK4a (and then named p34SEI-1). We observed that TRIP-Br1 interacts with low- and high-risk HPV E6 proteins in yeast, in vitro and in mammalian cell cultures. Transcription activation of a complex consisting of E2F1, DP1, and TRIP-Br1 was efficiently stimulated by both E6 proteins. TRIP-Br1 has an LLG E6 interaction motif, which contributed to the binding of E6 proteins. Apparently, E6 does not promote degradation of TRIP-Br1. Our observations imply that the cell-cycle promoting transcription factor E2F1/DP1 is dually targeted by HPV oncoproteins, namely (i) by interference of the E7 protein with repression by RB, and (ii) by the transcriptional cofactor function of the E6 protein. Our data reveal the natural context of the transcription activator function of E6, which has been predicted without knowledge of the E2F1/DP1/TRIP-Br/E6 complex by studying chimeric constructs, and add a function to the limited number of transforming properties shared

  5. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years

    DEFF Research Database (Denmark)

    Huh, Warner K; Joura, Elmar A; Giuliano, Anna R

    2017-01-01

    BACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18...... antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS: We undertook this randomised, double-blind, efficacy, immunogenicity......, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central...

  6. 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...

  7. 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.

  8. High-throughput and automatic typing via human papillomavirus identification map for cervical cancer screening and prognosis.

    Science.gov (United States)

    Yi, Linglu; Xu, Xueqin; Lin, Xuexia; Li, Haifang; Ma, Yuan; Lin, Jin-Ming

    2014-07-07

    A novel human papillomavirus (HPV) typing assay for cervical cancer screening and prognosis was developed by the combination of restriction fragment length polymorphism (RFLP) and microchip electrophoresis (MCE) to achieve higher levels of sensitivity and throughput. The detection limit of 2 × 10(2) copies, high sensitivity and typing accuracy on the account of PCR-RFLP-MCE method guarantee the successful diagnosis results of 4-fold higher infection rate over cytologic tests. From clinical samples, eleven kinds of HPV types were identified with a good compatibility degree of over 90%. The described method showed good reliability in clinical samples and provided a promising alternative for pathological studies at the molecular level.

  9. 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

  10. 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.

  11. 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.

  12. 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

  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. 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.

  15. p16 expression in follicular dendritic cell sarcoma: a potential mimicker of human papillomavirus-related oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Lingxin; Yang, Chen; Lewis, James S; El-Mofty, Samir K; Chernock, Rebecca D

    2017-08-01

    Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm that most commonly occurs in cervical lymph nodes. It has histologic and clinical overlap with the much more common p16-positive human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx, which characteristically has nonkeratinizing morphology and often presents as an isolated neck mass. Not surprisingly, follicular dendritic cell sarcomas are commonly misdiagnosed as squamous cell carcinoma. Immunohistochemistry is helpful in separating the 2 entities. Follicular dendritic cell sarcoma expresses dendritic markers such as CD21 and CD23 and is almost always cytokeratin negative. However, in many cases of HPV-related oropharyngeal carcinoma, only p16 immunohistochemistry as a prognostic and surrogate marker for HPV is performed. p16 expression in follicular dendritic cell sarcoma has not been characterized. Here, we investigate the expression of p16 in follicular dendritic cell sarcoma and correlate it with retinoblastoma protein expression. A pilot study of dendritic marker expression in HPV-related oropharyngeal squamous cell carcinoma was also performed. We found that 4 of 8 sarcomas expressed p16 with strong and diffuse staining in 2 cases. In 2 of the 4 cases, p16 expression corresponded to loss of retinoblastoma protein expression. Dendritic marker expression (CD21 and CD23) was not found in HPV-related oropharyngeal squamous cell carcinomas. As such, positive p16 immunohistochemistry cannot be used as supportive evidence for the diagnosis of squamous cell carcinoma as strong and diffuse p16 expression may also occur in follicular dendritic cell sarcoma. Cytokeratins and dendritic markers are critical in separating the two tumor types. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 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 ...

  17. 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

  18. [Expression, purification and immunogenicity of human papillomavirus type 11 virus-like particles from Escherichia coli].

    Science.gov (United States)

    Yan, Chunyan; Li, Shaowei; Wang, Jin; Wei, Minxi; Huang, Bo; Zhuang, Yudi; Li, Zhongyi; Pan, Huirong; Zhang, Jun; Xia, Ningshao

    2009-11-01

    To produce human papillomavirus type 11 virus-like particles (HPV11 VLPs) from Escherichia coli and to investigate its immunogenicity and type cross neutralization nature. We expressed the major capsid protein of HPV11 (HPV11-L1) in Escherichia coli ER2566 in non fusion fashion and purified by amino sulfate precipitation, ion-exchange chromatography and hydrophobic interaction chromatography, sequentially. Then we removed the reductant DTT to have the purified HPV11-L1 self-assemble into VLPs in vitro. We investigated the morphology of these VLPs with dynamic light scattering and transmission electron microscopy. We assayed the immunogenicity of the resultant HPV11 VLPs by vaccinations on mice and evaluated by HPV6/11/16/18 pseudovirion neutralization cell models. We expressed HPV11 L1 in Escherichia coli with two forms, soluble and inclusion body. The soluble HPV11 L1 with over 95% purity can self assemble to VLPs in high efficiency. Morphologically, these VLPs were globular, homogeneous and with a diameter of - 50 nm, which is quite similar with native HPV11 virions. The half effective dosage (ED50) of HPV11 VLPs is 0.031 microg, and the maximum titer of neutralizing antibody elicited is averaged to 10(6). The cross neutralization activity (against HPV6/16/18) of the anti-HPV11 serum was found to have exact correlation to the inter-type homology in amino acid alignment. We can provide HPV11 VLPs with highly immunogenicity from prokaryote expression system, which may pave a new way for research and development of prophylactic vaccine for HPV11.

  19. [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.

  20. 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....

  1. What drives the number of high-risk human papillomavirus types in the anal canal in HIV-positive men who have sex with men?

    NARCIS (Netherlands)

    del Amo, Julia; González, Cristina; Geskus, Ronald B.; Torres, Montse; del Romero, Jorge; Viciana, Pompeyo; Masiá, Mar; Blanco, Jose R.; Hernández-Novoa, Beatriz; Ortiz, Marta; Peña, Alejandro; García, Federico; Torres, Montserrat; Ocampo, Antonio; Da Silva, Alfredo Rodríguez; Miralles, Celia; Mauricio Iribarren, Gustavo; Madrid, Nadia; Dronda, Fernando; Benito, Amparo; Sanz, Itziar; Vera, Mar; Rodríguez, Carmen; Martín Alegre, Carmen; Carlos Carrió, Juan; Raposo, Montse; Trastoy, Mónica; Fontillón, Maria; Robledano, Catalina; Gutierrez, Félix; Padilla, Sergio; Andrada, Encarna; Cervero, Miguel; Ramón Blanco, José; Pérez, Laura; Portilla, Joaquín; Portilla, Irene; Angel Vonwichmann, Miguel; Antonio Iribarren, José; Camino, Xabier; Sendagorta, Elena; Herranz, Pedro; Rodríguez, Patricia; Luis Gómez, Juan; Rosado, Dacil; Alejos, Belén; Angeles Rodríguez, Maria

    2013-01-01

    We estimated the effect of sexual behavior, age, and immunodeficiency on the number of high-risk human papillomavirus (HR-HPV) types in the anal canal among human immunodeficiency virus-positive men who have sex with men (MSM). Anal samples were genotyped with the Linear Array HPV Genotyping Test,

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

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

    OpenAIRE

    Longuet, M; Beaudenon, S; Orth, G

    1996-01-01

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

  8. 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

  9. 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

  10. 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...

  11. Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kawakami, Hisato; Okamoto, Isamu; Terao, Kyoichi; Sakai, Kazuko; Suzuki, Minoru; Ueda, Shinya; Tanaka, Kaoru; Kuwata, Kiyoko; Morita, Yume; Ono, Koji; Nishio, Kazuto; Nishimura, Yasumasa; Doi, Katsumi; Nakagawa, Kazuhiko

    2013-01-01

    Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074–0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese

  12. Human papillomavirus types distribution in eastern Sicilian females with cervical lesions. A correlation with colposcopic and histological findings.

    Science.gov (United States)

    Le Donne, Maria; Giuffrè, Giuseppe; Caruso, Carmela; Nicotina, Piero Antonio; Alibrandi, Angela; Scalisi, Rosalba; Simone, Angela; Chiofalo, Benito; Triolo, Onofrio

    2013-07-01

    To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17-68 years, with previous cytological abnormalities, were included in this study. HPV-DNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6 %) followed by HPV-31 (26.9 %), -6 (18.6 %), -58 (8.8 %), -18 (6.7 %), -66 (5.7 %), -52 and -53 (4.7 %). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5 % was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P = 0.023; and HPV-53 P = 0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7 %, 31.2 %, 44 % and 37.2 % of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25 %, 8 %, and 13.3 % of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.

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

    OpenAIRE

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

    2011-01-01

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

  14. 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.

  15. [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.

  16. Tumor Cell Anaplasia and Multinucleation Are Predictors of Disease Recurrence in Oropharyngeal Squamous Cell Carcinoma, Including Among Just the Human Papillomavirus-Related Cancers

    OpenAIRE

    Lewis, James S.; Scantlebury, Juliette B.; Luo, Jingqin; Thorstad, Wade L.

    2012-01-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all su...

  17. 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...

  18. In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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.

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

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    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

  2. Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes

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    Shterzer, Naama; Heyman, Dariya; Shapiro, Beny; Yaniv, Abraham; Jackman, Anna [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Serour, Francis [Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon (Israel); Chaouat, Malka [Laboratory of Experimental Surgery, Hadassah University Hospital, Ein Karem, Jerusalem (Israel); Gonen, Pinhas [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Tommasino, Massimo [International Agency for Research on Cancer, World Health Organization, Lyon (France); Sherman, Levana [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-11-15

    In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis. - Highlights: • Primary keratinocytes were used to evaluate transforming and carcinogenic abilities of cutaneous HPVs. • E6E7 of cancer associated β HPV types transform primary human keratinocytes. • E6 proteins of cancer and wart associated HPVs inhibit UVB induced cell death. • E6s of cancer and wart associated HPVs attenuate UVB induced proliferation arrest. • E6s of cancer and wart associated HPVs attenuate UVB induced apoptosis signaling.

  3. Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes

    International Nuclear Information System (INIS)

    Shterzer, Naama; Heyman, Dariya; Shapiro, Beny; Yaniv, Abraham; Jackman, Anna; Serour, Francis; Chaouat, Malka; Gonen, Pinhas; Tommasino, Massimo; Sherman, Levana

    2014-01-01

    In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis. - Highlights: • Primary keratinocytes were used to evaluate transforming and carcinogenic abilities of cutaneous HPVs. • E6E7 of cancer associated β HPV types transform primary human keratinocytes. • E6 proteins of cancer and wart associated HPVs inhibit UVB induced cell death. • E6s of cancer and wart associated HPVs attenuate UVB induced proliferation arrest. • E6s of cancer and wart associated HPVs attenuate UVB induced apoptosis signaling

  4. 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.

  5. 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

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

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    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.

  7. Vaccine-preventable anal human papillomavirus in Australian gay and bisexual men

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    I. Mary Poynten

    2017-06-01

    Full Text Available Objective: HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM. Methods: The Study of the Prevention of Anal Cancer (SPANC is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status. Results: Anal HPV results from 606 (98.2% of 617 participants (median age 49 years, 35.7% HIV-positive showed 525 (86.7% had ≥1 HPV type and 178 (29.4% had HPV16. Over one third of participants (214, 35.3% had no nonavalent vaccine-preventable types detected. Two (0.3% participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p<0.001 and younger participants (p=0.059 were more likely to have more vaccine-preventable HPV types detected. Conclusion: Anal HPV was highly prevalent in this largely community-based GBM cohort. Vaccine-preventable HPV16 was detected in approximately one third of participants. These findings suggest that the potential efficacy of HPV vaccination of older GBM should be explored. Keywords: Human papillomavirus, HPV, Anal, Vaccine, Prevalence, Gay and bisexual men, MSM, HIV

  8. 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.

  9. Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer

    Science.gov (United States)

    Tully, Stephen; Franceschi, Silvia

    2017-01-01

    Abstract Background. Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. Methods. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undetermined significance (ASCUS); 2173 with low-grade and 1282 with high-grade squamous intraepithelial lesions (HSILs) diagnosed cytologically; 1198 with cervical intraepithelial neoplasia grade 1 (CIN1), 456 with CIN2, and 455 with CIN3 diagnosed histologically; and 796 with invasive cervical cancers (ICCs). A large proportion of WHIV, and almost all with ICCs, were from Africa. Results. In Africa, HPV 16 accounted for 13% of HPV-positive WHIV with normal cytological findings, but this proportion increased through ASCUS, low-grade squamous intraepithelial lesions, CIN1, and CIN2 (18%–25%), up to 41%–47% for CIN3 and ICCs. Only HPV 16, HPV 18, and HPV 45 accounted for a greater proportion of HPV infections in ICCs compared with normal cytological findings (ICC:normal ratios, 3.68, 2.47, and 2.55, respectively). Other high-risk types accounted for important proportions of low- and/or high-grade lesions, but their contribution dropped in ICCs, with ICC:normal ratios in Africa ranging from 0.79 for HPV 33 down to 0.38 for HPV 56. Findings for HPV 16 and HPV 18 in Europe/North America, Asia, and Latin America were compatible with those from Africa. Conclusions. HPV 16 and HPV 18 in particular, but also HPV 45, at least in Africa, warrant special attention in WHIV. Broad consistency of findings with those in HIV-uninfected population would suggest that the risk stratification offered by partial HPV genotyping tests also have relevance for HIV-positive women. PMID:28199532

  10. 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....

  11. 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

  12. 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

  13. Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva

    DEFF Research Database (Denmark)

    Faber, Mette T; Sand, Freja Lærke; Albieri, Vanna

    2017-01-01

    In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were...... used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model...... samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions....

  14. 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.

  15. 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...

  16. [Experimental study on carcinogenesis by human papillomavirus type 8 E7 gene].

    Science.gov (United States)

    Nishikawa, T

    1994-05-01

    Human papillomavirus (HPV) 5 and HPV8 are often detected in skin cancers developed in patients suffering from epidermodysplasia verruciformis, as well as in skin cancers developed in immunosuppressed patients. In the present study, in order to examine the transforming activity of the HPV8E7 gene, the HPV8E7 and HPV8E6/E7 genes were cloned into the expression vector (pcD2-Y), under the SV40 enhancer/promoter to construct pcD2-8E7 and pcD2-8E6/E7, respectively. The E7 and E6/E7 genes of genital high-risk HPV16 were also cloned into pcD2-Y to construct pcD2-16E7 and pcD2-16E6/E7, respectively. They were tested for their ability to collaboratively transform primary rat embryo fibroblasts (REFs) with activated H-ras gene. Transfection experiments of REFs having an activated H-ras gene revealed that pcD2-8E7, as well as pcD2-16E7 and pcD2-16E6/E7, induced transformation of cells in G418-resistant colonies at efficiencies of 11.9%, 43.0% and 53.0%, respectively. Transformed cell lines induced by activated H-ras gene and pcD2-8E7 or pcD2-16E7 were named 8RE and 16RE cell lines, respectively. Tumor induction in syngeneic newborn rats by injected the 8RE cells was higher than that of the 16RE cells. In cytological and histological examination, the 8RE cell lines and their induced tumors were different from the 16RE cell lines and their induced tumors. The 8RE cell lines showed the characteristic transformation with efficient growth ability on plastic and colony formation in 0.3% soft agar. These results support the hypothesis that the HPV8E7 gene plays an important role in the carcinogenesis of skin cancers.

  17. 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.

  18. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial.

    Science.gov (United States)

    Muñoz, Nubia; Manalastas, Ricardo; Pitisuttithum, Punee; Tresukosol, Damrong; Monsonego, Joseph; Ault, Kevin; Clavel, Christine; Luna, Joaquin; Myers, Evan; Hood, Sara; Bautista, Oliver; Bryan, Janine; Taddeo, Frank J; Esser, Mark T; Vuocolo, Scott; Haupt, Richard M; Barr, Eliav; Saah, Alfred

    2009-06-06

    Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years. Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220. 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs

  19. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection.

    Science.gov (United States)

    Brotman, Rebecca M; Shardell, Michelle D; Gajer, Pawel; Tracy, J Kathleen; Zenilman, Jonathan M; Ravel, Jacques; Gravitt, Patti E

    2014-12-01

    We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection. Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models. Participants had an average of 29 samples, with HPV point prevalence between 58%-77%. CST was associated with changes in HPV status (PVaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. 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.

  1. Annual disease burden due to human papillomavirus 16 and 18 infections in Finland.

    Science.gov (United States)

    Syrjänen, Kari J

    2009-01-01

    Apart from cancers of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, premalignant and malignant lesions at different anatomic sites in both genders. Malignant tumours and their precursors are usually attributed to the oncogenic (high-risk, HR) HPV types, whereas benign lesions (mostly papillomas) are ascribed to the low-risk (LR) HPV types, most notably HPV6 and HPV11. To date, the main interest has been focused on HR-HPV types and their associated pathology, and much less attention has been paid to the lesions caused by the LR-HPV types. The recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11) has resulted in considerably increased interest in these LR-HPV types as well. This author recently conducted a systematic survey of the annual disease burden due to HPV6/11 infections in Finland. As a rational continuation, the present survey was conducted to estimate the annual disease burden due to HPV16 and HPV18 infections in our country. Together, these 2 documents form the foundation for calculations of the annual costs needed to treat the diseases caused by these 2 most common LR and HR HPV types. Similar to HPV6/11, accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV16/18 vaccines. In the first step, the published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. The GLOBOCAN 2004 (IARC; International Agency for Research on Cancer) database was used to derive the global numbers of incident cases for each of these malignancies in 2002, and the Finnish Cancer Registry (FCR) website was used to obtain these numbers for Finland (y 2005). The evidence linking HPV to each individual tumour category was classified as: (1) established, (2) emerging, and (3) controversial. All published evidence was

  2. Human papillomavirus 16 infection predicts poor outcome in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Xi R

    2015-03-01

    Full Text Available Ruxing Xi,1 Xiaozhi Zhang,1 Xin Chen,1 Shupei Pan,1 Beina Hui,1 Li Zhang,1 Shenbo Fu,1 Xiaolong Li,2 Xuanwei Zhang,1 Tuotuo Gong,1 Jia Guo,1 Shaomin Che1 1Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiao Tong University, 2Department of Radiotherapy, The People’s Liberation Army 323 Hospital, Xi’an, People’s Republic of China Background: Previous studies indicate that human papillomavirus 16 (HPV16 infection plays a pivotal role in the etiology of esophageal squamous cell carcinoma (ESCC. We aim to detect the influence of HPV16 infection on ESCC patient prognosis. Patients and methods: Immunohistochemical staining for HPV16 E6 oncoprotein, the low-affinity p75 neurotrophin receptor (p75NTR, and phosphatidylinositol 3-kinase (PI3K was performed on 103 archived surgical specimens from patients with ESCC and 54 control samples from patients with benign esophageal tumor or inflammatory lesions. All patients were from the Shaan Xi Province, People’s Republic of China. Results: HPV16 E6 expression was significantly higher in the ESCC group (P<0.05. HPV16 E6 expression was significantly higher in men than in women (P<0.05. p75NTR expression was higher in those aged >56 years (P<0.05. PI3K expression was higher in those with a more advanced histopathological grade (P<0.05. There was a positive correlation between HPV16 E6 and p75NTR expression (r=0.547, P<0.001 and between p75NTR and PI3K expression (r=0.364, P<0.001. In 100 evaluable patients, the 5-year overall survival (OS rate was 11%. In patients with ESCC, HPV16 E6 and PI3K expression were negatively correlated with the 3-year OS (P<0.05, 5-year OS (P<0.05, and progression-free survival (P<0.05. Conclusion: HPV16 infection likely contributes to the etiology of ESCC patients in Shaan Xi, People’s Republic of China. HPV16 infection status and PI3K expression levels could be useful for predicting prognosis in patients with ESCC. Keywords: low-affinity p75

  3. 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.

  4. Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

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    Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

    2015-04-15

    High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

  5. Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

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    Gemigniani, Franco; Hernández-Losa, Javier; Ferrer, Berta; García-Patos, Vicente

    2015-12-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine. © 2015 Japanese Dermatological Association.

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

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    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.

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

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    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.

  8. Chimeric L2-Based Virus-Like Particle (VLP Vaccines Targeting Cutaneous Human Papillomaviruses (HPV.

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    Bettina Huber

    Full Text Available Common cutaneous human papillomavirus (HPV types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas, but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa 17-36 on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross- protected against beta HPV5/20/24/38/96/16 (but not type 76, while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target

  9. Prevalence and type distribution of human papillomavirus infection among women with different degrees of cervical cytological abnormalities in Sicily (Italy

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    Concetta Franchina

    2016-06-01

    Full Text Available Human papillomaviruses (HPVs are etiological agents of cervical cancer. In the absence of Pap smear alterations, high-risk HPV DNA can be detected in cervical samples. The prevalence of papillomavirus infection and their genotype distribution varies greatly across populations. The aims of this study were: i to assess the prevalences of HPV genotypes in people living in Eastern Sicily (Italy and the frequency of HPV multiple infections; ii to evaluate the association between HPV genotypes and cervical lesions in order to improve the epidemiological knowledge useful for monitoring or treating infected women. Nested PCR and reverse dot/blot hybridization were used for the detection and typing of HPV DNA in 315 women who had had an abnormal PAP-smear. HPV DNA test was positive in 70.5% cases; the prevalence was 50% in atypical squamous cells of undetermined significance (ASCUS, 80.8% in low grade-, and 76.2% in high grade-squamous intraepithelial lesion (H-SIL. The genotype distribution showed a predominance of HPV-16 (56.7% followed by HPV-18 (12.2%, HPV-31 (9.5% and HPV-6 (9.5%. Multiple infections were detected in 35.1% of the infected patients. High frequency of positive results for HPV was confirmed and, even in case of ASCUS, patients should be taken into account for genotyping. Our data indicate that multiple infections are consistent in women with low-grade lesions while they are less frequent in women with H-SIL. This could reinforce the theory of the multi-stage cancer model, by which one HPV type becomes predominant along with the progression of cervical lesion severity.

  10. Cost-effectiveness of adding vaccination with the AS04-adjuvanted human papillomavirus 16/18 vaccine to cervical cancer screening in Hungary

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    Vokó Zoltán

    2012-10-01

    Full Text Available Abstract Background The cervical cancer screening program implemented in Hungary to date has not been successful. Along with screening, vaccination is an effective intervention to prevent cervical cancer. The aim of this study was to assess the cost-effectiveness of adding vaccination with the human papillomavirus 16/18 vaccine to the current cervical cancer screening program in Hungary. Methods We developed a cohort simulation state-transition Markov model to model the life course of 12-year-old girls. Eighty percent participation in the HPV vaccination program at 12 years of age was assumed. Transitional probabilities were estimated using data from the literature. Local data were used regarding screening participation rates, and the costs were estimated in US $. We applied the purchasing power parity exchange rate of 129 HUF/$ to the cost data. Only direct health care costs were considered. We used a 3.7% discount rate for both the cost and quality-adjusted life years (QALYs. The time horizon was 88 years. Results Inclusion of HPV vaccination at age 12 in the cervical cancer prevention program was predicted to be cost-effective. The incremental cost-effectiveness ratio (ICER of adding HPV vaccination to the current national cancer screening program was estimated to be 27 588 $/QALY. The results were sensitive to the price of the vaccine, the discount rate, the screening participation rate and whether herd immunity was taken into account. Conclusions Our modeling analysis showed that the vaccination of 12-year-old adolescent girls against cervical cancer with the AS04-adjuvanted human papillomavirus 16/18 vaccine would be a cost-effective strategy to prevent cervical cancer in Hungary.

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

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    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.

  12. Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

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    Camara, Geni NL; Cerqueira, Daniela M; Oliveira, Ana PG; Silva, Evandro O; Carvalho, Luciano GS; Martins, Cláudia RF

    2003-01-01

    As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using c...

  13. 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.

  14. Determination of p16 overexpression as an indicator of human papillomavirus infection in oral dysplasia and carcinoma

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    Adrija Pathak

    2017-01-01

    Full Text Available Context: Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. In the past few years, human papillomavirus (HPV infection has been suggested as a risk factor for oral cancer apart from traditional risk factors such as smoking, tobacco, and alcohol consumption. Aims: The aim of this study was to determine HPV status of the tumors using polymerase chain reaction (HPV-DNA PCR and p16 immunostaining and to correlate p16 overexpression as an indicator of HPV-associated oral dysplasia and carcinoma. Settings and Design: A prospective study was conducted in fifty cases of suspected oral cancer. Materials and Methods: PCR Amplification of extracted HPV-DNA was done for HPV-DNA status in fresh tissue of suspected oral cancer cases. Histomorphological features of the cases were analyzed, and p16 immunohistochemistry was performed on the same specimen after making paraffin blocks to study p16 overexpression. Statistical Analysis Used: Chi-square test was used to analyze the differences between discrete variables. Results: 5/6 (83.3% HPV-DNA-positive cases were positive for p16 expression, whereas 26/44 (59.09% p16-positive cases which were negative for HPV-DNA. Sensitivity and specificity of p16 as a surrogate marker for HPV-DNA were found to be 83.3% and 40%, respectively. Conclusions: p16 immunostaining is a good first-line assay for eliminating HPV-negative cases from additional analysis, but other causes of p16 overexpression in oral tumorigenesis related to tobacco consumption in keratinizing squamous cell carcinoma needs to be explored further.

  15. The Subcellular Localisation of the Human Papillomavirus (HPV 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

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    Özlem Cesur

    2015-06-01

    Full Text Available Human papillomavirus (HPV is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2 selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.

  16. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    Science.gov (United States)

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  17. Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

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    Geni NL Camara

    2003-10-01

    Full Text Available As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061 were less frequent (= or < 2.5% each. The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

  18. 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

  19. Clustering self-organizing maps (SOM) method for human papillomavirus (HPV) DNA as the main cause of cervical cancer disease

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    Bustamam, A.; Aldila, D.; Fatimah, Arimbi, M. D.

    2017-07-01

    One of the most widely used clustering method, since it has advantage on its robustness, is Self-Organizing Maps (SOM) method. This paper discusses the application of SOM method on Human Papillomavirus (HPV) DNA which is the main cause of cervical cancer disease, the most dangerous cancer in developing countries. We use 18 types of HPV DNA-based on the newest complete genome. By using open-source-based program R, clustering process can separate 18 types of HPV into two different clusters. There are two types of HPV in the first cluster while 16 others in the second cluster. The analyzing result of 18 types HPV based on the malignancy of the virus (the difficultness to cure). Two of HPV types the first cluster can be classified as tame HPV, while 16 others in the second cluster are classified as vicious HPV.

  20. Molecular cloning and characterisation of a novel type of human papillomavirus 160 isolated from a flat wart of an immunocompetent patient.

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    Tsuyoshi Mitsuishi

    Full Text Available More than 150 types of Human papillomaviruses (HPVs have been isolated from numerous cutaneous and/or mucosal lesions. Flat wart samples on the face from 36 immunocompetent patients were collected and screened for HPV. From one sample, we cloned a putative novel genotype. The novel type consisted of 7779 bp in length with a GC content of 47.1%, containing open reading frames for putative early proteins (E1, E2, E4, E6, and E7 and two late proteins (L1 and L2. Homology searches and phylogenetic analyses indicated that it belonged to Alphapapillomavirus (Alpha-PV species 2 and most closely resembled HPV 3. The virus fulfilled the definition of a novel type, and was named HPV 160 by the Reference Center for Papillomaviruses. The putative E7 protein of HPV 160 as well as HPV 29, 77, and 78 contained the Leu-X-Cys-X-Glu pRB-binding motif but other Alpha-PV species 2 (HPV 3, 10, 28, 94, 117, and 125 did not have this conserved motif.

  1. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

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    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.

  2. 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.

  3. 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.

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

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    Marina Tayla Mesquita Aguiar

    2014-04-01

    desenvolvimento do câncer anal, incluindo idade maior que 50 anos, dieta pobre em fibras, fístulas anais crônicas, tabagismo, múltiplos parceiros, prática de intercurso anal, infecção pelo HIV e imunossupressão. Entretanto, a presença do Papilomavírus Humano (HPV representa o principal fator de risco para o desenvolvimento do câncer anal. O objetivo deste estudo consistiu em avaliar os aspectos clínico-patológicos de uma série de pacientes com carcinomas anais diagnosticados no Hospital Araújo Jorge, Goiânia/GO, bem como a prevalência do genoma do HPV nesses tumores. Dados clínico-patológicos e sóciodemográficos foram colhidos a partir dos respectivos prontuários e blocos de parafina contendo espécimes de carcinomas anais foram usados para extração de DNA e detecção de HPV, por meio da reação em cadeia da polimerase, usando oligonucleotídeos iniciadores SPF. Quarenta e três casos foram selecionados e tiveram os dados clinico-patológicos analisados, enquanto 38 casos foram testados para a detecção do genoma do HPV. Dentre os pacientes avaliados, 62,8% eram mulheres; 53,4% dos tumores eram carcinomas de células escamosas e 46,5% dos pacientes estavam na faixa etária entre os 60 e 75 anos. Fatores de risco, como tabagismo (39,5% e etilismo (20,9% foram registrados no grupo estudado. Metástases linfonodais foram detectadas em 30,2% dos casos e 7,0% apresentaram metástase à distância. A detecção de HPV foi positiva em 76,0% dos casos analisados e este significativamente associado aos carcinomas de células escamosas. O comportamento agressivo e o estágio avançado dos carcinomas anais descritos no presente estudo destacam a necessidade de medidas de prevenção que contemplem esses tumores, incluindo a vacinação contra o HPV. Keywords: Anal cancer, Characteristics, Human papillomavirus, HPV, HPV16, HPV18, Palavras-chave: Câncer anal, Características, Papilomavirus humano, HPV, HPV16, HPV18

  5. 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.

  6. Clinical trial experience with prophylactic human papillomavirus 6/11/16/18 vaccine in young black women.

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    Clark, Liana R; Myers, Evan R; Huh, Warner; Joura, Elmar A; Paavonen, Jorma; Perez, Gonzalo; James, Margaret K; Sings, Heather L; Haupt, Richard M; Saah, Alfred J; Garner, Elizabeth I O

    2013-03-01

    Human papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproportionally diagnosed and have higher mortality from cervical cancer in the United States. Here we describe the prophylactic efficacy and safety of a quadrivalent HPV-6/11/16/18 vaccine in black women. A total of 700 black women from Latin America, Europe, and North America (aged 16-24 years) received the vaccine or placebo in one of two studies. Analyses focused on the efficacy and safety of the vaccine. Baseline rates of Chlamydia trachomatis infection and history of past pregnancy were more than twice as high in black women compared with the non-black women who were enrolled in these trials. HPV-6/11/16 or 18 DNA was detected in 18% of black women versus 14.6% in non-black women at day 1. For black women, vaccine efficacy against disease caused by HPV-6/11/16/18 was 100% for cervical intraepithelial neoplasia (0 vs. 15 cases; 95% confidence interval, 64.5%-100%) and 100% for vulvar and vaginal intraepithelial neoplasia and condylomata acuminata (0 vs. 17 cases; 95% confidence interval, 69.3%-100%). There were no serious vaccine-related adverse experiences. A similar proportion of pregnancies resulted in live births (75.8% vaccine; 72.7% placebo) and fetal loss (24.2% vaccine; 27.3% placebo). Prophylactic quadrivalent HPV-6/11/16/18 vaccination of young black women demonstrated high efficacy, safety, and tolerability. HPV vaccination has the potential to reduce cervical cancer-related health disparities both in the United States and around the world. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  7. Impact of viral E2-gene status on outcome after radiotherapy for patients with human papillomavirus 16-positive cancer of the uterine cervix

    International Nuclear Information System (INIS)

    Lindel, Katja; Villiers, Ethel-Michele de; Burri, Philipp; Studer, Ueli; Altermatt, Hans J.; Greiner, Richard H.; Gruber, Guenther

    2006-01-01

    Purpose: Integration of high-risk papillomavirus DNA has been considered an important step in oncogenic progression to cervical carcinoma. Disruption of the human papillomavirus (HPV) genome within the E2 gene is frequently a consequence. This study investigated the influence of episomal viral DNA on outcome in patients with advanced cervical cancer treated with primary radiotherapy. Methods and Materials: Paraffin-embedded biopsies of 82 women with locally advanced cervical cancer could be analyzed for HPV infection by multiplex polymerase chain reaction (PCR) by use of SPF1/2 primers. E2-gene intactness of HPV-16-positive samples was analyzed in 3 separate amplification reactions by use of the E2A, E2B, E2C primers. Statistical analyses (Kaplan-Meier method; log-rank test) were performed for overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS), and distant metastases-free survival (DMFS). Results: Sixty-one (75%) of 82 carcinomas were HPV positive, 44 of them for HPV-16 (72%). Seventeen of the 44 HPV-16-positive tumors (39%) had an intact E2 gene. Patients with a HPV-16-positive tumor and an intact E2 gene showed a trend for a better DFS (58% vs. 38%, p = 0.06) compared with those with a disrupted E2 gene. A nonsignificant difference occurred regarding OS (87% vs. 66%, p = 0.16) and DMFS (57% vs. 48%, p = 0.15). Conclusion: E2-gene status may be a promising new target, but more studies are required to elucidate the effect of the viral E2 gene on outcome after radiotherapy in HPV-positive tumors

  8. Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

    International Nuclear Information System (INIS)

    Herd, Karen A.; Harvey, Tracey; Khromykh, Alexander A.; Tindle, Robert W.

    2004-01-01

    The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses

  9. Increased p50/p50 NF-κB Activation in Human Papillomavirus Type 6- or Type 11-Induced Laryngeal Papilloma Tissue

    Science.gov (United States)

    Vancurova, Ivana; Wu, Rong; Miskolci, Veronika; Sun, Shishinn

    2002-01-01

    We have observed elevated NF-κB DNA-binding activity in nuclear extracts from human papillomavirus type 6- and 11-infected laryngeal papilloma tissues. The predominant DNA-binding species is the p50/p50 homodimer. The elevated NF-κB activity could be correlated with a reduced level of cytoplasmic IκBβ and could be associated with the overexpression of p21CIP1/WAF1 in papilloma cells. Increased NF-κB activity and cytoplasmic accumulation of p21CIP1/WAF1 might counteract death-promoting effects elicited by overexpressed PTEN and reduced activation of Akt and STAT3 previously noted in these tissues. PMID:11773428

  10. Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine

    DEFF Research Database (Denmark)

    Schwarz, Tino F; Kocken, Mariëlle; Petäjä, Tiina

    2010-01-01

    and CVS samples were collected from a subset of women aged 10-65 years (N=350) at pre-specified time-points from 7 to 36 months post-vaccination. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay. Pearson correlation coefficients between serum and CVS...... in serum were substantially higher at all time-points than those in a control group of women who had cleared a natural HPV infection in another trial. In women with detectable antibodies in both serum and CVS, good correlation was seen between HPV-16/18 antibody levels at all time-points (Pearson......This pooled analysis of data from four Phase III clinical trials was undertaken to assess the correlation between levels of anti-human papillomavirus (HPV)-16/18 antibodies in serum and cervicovaginal secretions (CVS) in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Serum...

  11. 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...

  12. [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.

  13. 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.

  14. 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.

  15. Human papillomavirus detection with genotyping by the cobas and Aptima assays: Significant differences in HPV 16 detection?

    Science.gov (United States)

    Chorny, Joseph A; Frye, Teresa C; Fisher, Beth L; Remmers, Carol L

    2018-03-23

    The primary high-risk human papillomavirus (hrHPV) assays in the United States are the cobas (Roche) and the Aptima (Hologic). The cobas assay detects hrHPV by DNA analysis while the Aptima detects messenger RNA (mRNA) oncogenic transcripts. As the Aptima assay identifies oncogenic expression, it should have a lower rate of hrHPV and genotype detection. The Kaiser Permanente Regional Reference Laboratory in Denver, Colorado changed its hrHPV assay from the cobas to the Aptima assay. The rates of hrHPV detection and genotyping were compared over successive six-month periods. The overall hrHPV detection rates by the two platforms were similar (9.5% versus 9.1%) and not statistically different. For genotyping, the HPV 16 rate by the cobas was 1.6% and by the Aptima it was 1.1%. These differences were statistically different with the Aptima detecting nearly one-third less HPV 16 infections. With the HPV 18 and HPV 18/45, there was a slightly higher detection rate of HPV 18/45 by the Aptima platform (0.5% versus 0.9%) and this was statistically significant. While HPV 16 represents a low percentage of hrHPV infections, it was detected significantly less by the Aptima assay compared to the cobas assay. This has been previously reported, although not highlighted. Given the test methodologies, one would expect the Aptima to detect less HPV 16. This difference appears to be mainly due to a significantly increased number of non-oncogenic HPV 16 infections detected by the cobas test as there were no differences in HPV 16 detection rates in the high-grade squamous intraepithelial lesions indicating that the two tests have similar sensitivities for oncogenic HPV 16. © 2018 Wiley Periodicals, Inc.

  16. Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants

    International Nuclear Information System (INIS)

    Calleja-Macias, Itzel E.; Kalantari, Mina; Huh, John; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto; Gonzalez-Guerrero, Juan F.; Williamson, Anna-Lise; Hagmar, Bjoern; Wiley, Dorothy J.; Villarreal, Luis; Bernard, Hans-Ulrich; Barrera-Saldana, Hugo A.

    2004-01-01

    Cervical cancer, mainly caused by infection with human papillomaviruses (HPVs), is a major public health problem in Mexico. During a study of the prevalence of HPV types in northeastern Mexico, we identified, as expected from worldwide comparisons, HPV-16, 18, 31, and 35 as highly prevalent. It is well known that the genomes of HPV types differ geographically because of evolution linked to ethnic groups separated in prehistoric times. As HPV intra-type variation results in pathogenic differences, we analyzed genomic sequences of Mexican variants of these four HPV types. Among 112 HPV-16 samples, 14 contained European and 98 American Indian (AA) variants. This ratio is unexpected as people of European ethnicity predominate in this part of Mexico. Among 15 HPV-18 samples, 13 contained European and 2 African variants, the latter possibly due to migration of Africans to the Caribbean coast of Mexico. We constructed phylogenetic trees of HPV-31 and 35 variants, which have never been studied. Forty-six HPV-31 isolates from Mexico, Europe, Africa, and the United States (US) contained a total of 35 nucleotide exchanges in a 428-bp segment, with maximal distances between any two variants of 16 bp (3.7%), similar to those between HPV-16 variants. The HPV-31 variants formed two branches, one apparently the European, the other one an African branch. The European branch contained 13 of 29 Mexican isolates, the African branch 16 Mexican isolates. These may represent the HPV-31 variants of American Indians, as a 55% prevalence of African variants in Mexico seems incomprehensible. Twenty-seven HPV-35 samples from Mexico, Europe, Africa, and the US contained 11 mutations in a 893-bp segment with maximal distances between any two variants of only 5 mutations (0.6%), including a characteristic 16-bp insertion/deletion. These HPV-35 variants formed several phylogenetic clusters rather than two- or three-branched trees as HPV-16, 18, and 31. An HPV-35 variant typical for American

  17. 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)

  18. 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

  19. Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus

    Science.gov (United States)

    Zafereo, Mark E.; Xu, Li; Dahlstrom, Kristina R.; Viamonte, Carlo A.; El-Naggar, Adel K.; Wei, Qingyi; Li, Guojun; Sturgis, Erich M.

    2016-01-01

    Objective Human papillomavirus (HPV) is a causal and prognostic factor for oropharyngeal cancer, but its role in squamous cell carcinoma of the oral cavity (SCCOC) is unclear. We sought to clarify HPV's role in SCCOC. Materials and Methods Patients with newly diagnosed SCCOC (N=460) were prospectively recruited, treated, and followed at one institution. p16/HPV status was determined by p16 immunohistochemistry (IHC) (N=210), PCR-based HPV 16/18 E6/7 DNA testing (N=403), and/or HPV in situ hybridization (ISH) (N=178). Kaplan-Meier curves and log-rank tests were used to compare survival by p16/HPV status. Results p16 expression was detected in 30% of tumors (62/210) and HPV 16/18 E6/7 DNA in 28% (114/403), although correlation between these two assays was poor (r=−0.01). Patients with p16-positive tumors were more likely to be younger and have primary tumors of the oral tongue. Only 4% of tumors (7/171) were positive for HPV by ISH. Comparisons of patients with p16-positive and p16-negative tumors, patients with HPV-positive and HPV-negative tumors by PCR, and patients with HPV-positive and HPV-negative tumors by ISH showed no significant differences in disease-specific or disease-free survival by p16/HPV status. When we applied a more stringent definition of HPV positivity based on a combination of assay results, only 10 of 166 tumors were HPV positive, and there were no significant differences in demographic, exposure, clinical, or survival characteristics between these patients and the 156 HPV-negative patients. Conclusions Very few patients with SCCOC have HPV-driven tumors. SCCOC that overexpresses p16 may be a unique subset deserving of further study. PMID:27086486

  20. Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

    Science.gov (United States)

    Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

    2017-08-01

    Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Proteflazid® and local immunity in diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections.

    Science.gov (United States)

    Kaminsky, Vjacheslav; Chernyshov, Viktor; Grynevych, Oleksandr; Benyuk, Vasil; Kornatskaya, Alla; Shalko, Miroslava; Usevich, Igor; Revenko, Oleg; Shepetko, Maxim; Solomakha, Ludmila

    2017-03-21

    Reporting of clinical trials results for Proteflazid® in the drug formulation suppositories and vaginal swabs soaked in the solution of the drug to the local immunity of the female reproductive tract. The aim of study was to examine the state of local immunity in the reproductive tract of women with sexually transmitted diseases caused by human papillomavirus, herpes viruses (Type 1, 2) and mixed infection (herpes viruses + chlamydia). The trials involved 216 women with viral sexually transmitted diseases: Cervical Dysplasia associated with papillomavirus infection (HPV) (Group 1); Herpes genitalis type 1 (HSV- 1) and type 2 (HSV-1) (Group 2); mixed infection - HSV-1, HSV-2 and chlamydia (Group 3). Treatment results have confirmed that Proteflazid® contributes to sustainable performance improvement of basic factors of local immunity - sIgA, lysozyme and complement component C3 in the cervical mucus for all three groups of women. Proteflazid® enhances level of local immunity markers (sIgA, lysozyme, C3 complement component) and improves their ratios. Also it intensifies anticontagious activity of mucosal protection and female reproductive system as whole, during treatment diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections (herpesvirus and chlamydia).

  2. 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.

  3. 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

  4. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

    Science.gov (United States)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

    2007-08-01

    To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

  5. 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.

  6. Human Papillomavirus 16, 18, 31 and 45 viral load, integration and methylation status stratified by cervical disease stage

    International Nuclear Information System (INIS)

    Marongiu, Luigi; Godi, Anna; Parry, John V; Beddows, Simon

    2014-01-01

    Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3’L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2–26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0–6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8–18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. This

  7. 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.

  8. Variantes del Papilomavirus Humano 16 y su asociación con el HLA en cáncer cervical Variants of Human Papillomavirus 16 and its association with HLA in cervical cancer

    Directory of Open Access Journals (Sweden)

    Jehidys Montiel Ramos

    2010-12-01

    Full Text Available El cáncer cervical es el segundo cáncer más común en mujeres en el mundo y es el principal cáncer en mujeres en países en desarrollo. La infección persistente por los genotipos oncogénicos del Virus del Papiloma Humano (VPH es la causa necesaria para el desarrollo del cáncer cervical, siendo el VPH-16 el genotipo responsable del 50-60% de los casos. Las variantes No Europeas del VPH-16 han sido asociadas con infección persistente, lesiones de alto grado y cáncer. Los polimorfismos del Antígeno Leucocitario Humano (HLA están también asociados con la susceptibilidad al cáncer cervical y se ha postulado una relación entre variantes del VPH y ciertos alelos del HLA. La presente revisión hace referencia a la relación entre los polimorfismos de HLA y el desarrollo de cáncer cervical y la evidencia que documenta la interrelación de este factor con la variabilidad del VPH-16. Salud UIS 2010; 42: 272-280Cervical cancer is the second most common cancer in women worldwide and the most frequent cancer in women of the majority of developing countries. Persistent infection with Human Papillomavirus (HPV oncogenic types of HPV is necessary to develop cervical, cancer, with HPV-16 responsible for 50-60% of cases. Non-European variants of HPV-16 have been associated with persistant infection and high degree cervical cancer. Human Leucocyte Antigen (HLA polymorphisms are also associated with susceptibility to cervical cancer. It has been suggested relationship between HPV-16 variability and some HLA Alleles., This revision refers to the relation between HLA polymorphisms and cervical cancer development, and present evidence that may explain its relation with HPV-16 variability. Salud UIS 2010; 42: 272-280

  9. 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.

  10. 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.

  11. 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…

  12. 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

  13. 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.

  14. Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model.

    Science.gov (United States)

    Jit, Mark; Brisson, Marc; Laprise, Jean-François; Choi, Yoon Hong

    2015-01-06

    To investigate the incremental cost effectiveness of two dose human papillomavirus vaccination and of additionally giving a third dose. Cost effectiveness study based on a transmission dynamic model of human papillomavirus vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus vaccines were assumed to provide 10, 20, or 30 years' vaccine type protection and cross protection or lifelong vaccine type protection without cross protection. Three dose schedules were assumed to give lifelong vaccine type and cross protection. United Kingdom. Males and females aged 12-74 years. No, two, or three doses of human papillomavirus vaccine given routinely to 12 year old girls, with an initial catch-up campaign to 18 years. Costs (from the healthcare provider's perspective), health related utilities, and incremental cost effectiveness ratios. Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (€109.23; $136.00) per dose. If two doses give only 10 years' protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17,000, interquartile range £11,700-£25,800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom. Two dose human papillomavirus vaccine schedules are likely to be the most cost effective option provided protection lasts for at least 20 years. As the precise duration of two dose schedules may not be known for decades, cohorts given two doses should be closely

  15. High-throughput pseudovirion-based neutralization assay for analysis of natural and vaccine-induced antibodies against human papillomaviruses.

    Directory of Open Access Journals (Sweden)

    Peter Sehr

    Full Text Available A highly sensitive, automated, purely add-on, high-throughput pseudovirion-based neutralization assay (HT-PBNA with excellent repeatability and run-to-run reproducibility was developed for human papillomavirus types (HPV 16, 18, 31, 45, 52, 58 and bovine papillomavirus type 1. Preparation of 384 well assay plates with serially diluted sera and the actual cell-based assay are separated in time, therefore batches of up to one hundred assay plates can be processed sequentially. A mean coefficient of variation (CV of 13% was obtained for anti-HPV 16 and HPV 18 titers for a standard serum tested in a total of 58 repeats on individual plates in seven independent runs. Natural antibody response was analyzed in 35 sera from patients with HPV 16 DNA positive cervical intraepithelial neoplasia grade 2+ lesions. The new HT-PBNA is based on Gaussia luciferase with increased sensitivity compared to the previously described manual PBNA (manPBNA based on secreted alkaline phosphatase as reporter. Titers obtained with HT-PBNA were generally higher than titers obtained with the manPBNA. A good linear correlation (R(2 = 0.7 was found between HT-PBNA titers and anti-HPV 16 L1 antibody-levels determined by a Luminex bead-based GST-capture assay for these 35 sera and a Kappa-value of 0.72, with only 3 discordant sera in the low titer range. In addition to natural low titer antibody responses the high sensitivity of the HT-PBNA also allows detection of cross-neutralizing antibodies induced by commercial HPV L1-vaccines and experimental L2-vaccines. When analyzing the WHO international standards for HPV 16 and 18 we determined an analytical sensitivity of 0.864 and 1.105 mIU, respectively.

  16. Transcriptional regulatory elements in the noncoding region of human papillomavirus type 6

    International Nuclear Information System (INIS)

    Wu, Tzyy-Choou.

    1989-01-01

    The structure and function of the transcriptional regulatory region of human papillomavirus type 6 (HPV-6) has been investigated. To investigate tissue specific gene expression, a sensitive method to detect and localize HPV-6 viral DNA, mRNA and protein in plastic-embedded tissue sections of genital and respiratory tract papillomata by using in situ hybridization and immunoperoxidase assays has been developed. This method, using ultrathin sections and strand-specific 3 H labeled riboprobes, offers the advantages of superior morphological preservation and detection of viral genomes at low copy number with good resolution, and the modified immunocytochemistry provides better sensitivity. The results suggest that genital tract epithelium is more permissive for HPV-6 replication than respiratory tract epithelium. To study the tissue tropism of HPV-6 at the level of regulation of viral gene expression, the polymerase chain reaction was used to isolate the noncoding region (NCR) of HPV-6 in independent isolates. Nucleotide sequence analysis of molecularly cloned DNA identified base substitutions, deletions/insertions and tandem duplications. Transcriptional regulatory elements in the NCR were assayed in recombinant plasmids containing the bacterial gene for chloramphenicol acetyl transferase

  17. 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 ...

  18. High Prevalence and Genotypic Diversity of the Human Papillomavirus in Amazonian Women, Brazil

    Directory of Open Access Journals (Sweden)

    Danielle Albuquerque Pires Rocha

    2013-01-01

    Full Text Available The aim of this study was to determine the prevalence of human papillomavirus (HPV in a women population living within the state of Amazonas, Brazil, and to determine the viral genotypes found. The study included 361 sexually active women over 18 years of age. We performed the Pap test and the molecular diagnosis for HPV DNA using polymerase chain reaction (PCR. The amplicons obtained were sequenced in automatic sequencer for genotyping. The presence of HPV DNA was found in 29.1% (105 of the women. Only 321 women presented satisfactory slides for cytological diagnosis, 97.9% (314 had normal cytology (negative for cancer, and 2.1% (7 had abnormal cytology (4 ASCUS, 1 LSIL, and 2 HSIL. The types more frequently found were HPV 16 (58.1% and HPV 58 (20.0%. Additionally, we found more 13 types of HPV. Compared with previous studies in Brazil, our data confirmed a high prevalence and genotypic diversity of HPV in Brazilian women.

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

    Science.gov (United States)

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

    2016-07-01

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

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

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

  1. 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 ...

  2. Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

    Science.gov (United States)

    Daher, Tamas; Tur, Mehmet Kemal; Brobeil, Alexander; Etschmann, Benjamin; Witte, Biruta; Engenhart-Cabillic, Rita; Krombach, Gabriele; Blau, Wolfgang; Grimminger, Friedrich; Seeger, Werner; Klussmann, Jens Peter; Bräuninger, Andreas; Gattenlöhner, Stefan

    2018-06-01

    In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment. © 2018 Wiley Periodicals, Inc.

  3. 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.

  4. 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.

  5. 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

  6. [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.

  7. Low prevalence of human papillomavirus in oral cavity squamous cell carcinoma in Queensland, Australia.

    Science.gov (United States)

    Emmett, Sarah; Jenkins, Glenn; Boros, Samuel; Whiteman, David C; Panizza, Benedict; Antonsson, Annika

    2017-09-01

    While human papillomavirus (HPV) is an accepted risk factor for oropharyngeal squamous cell carcinoma (SCC), its aetiological role in oral cavity SCC remains unclear. This study aimed to determine the HPV prevalence in an Australian population. DNA was extracted from 63 formalin-fixed paraffin-embedded tumour specimens histologically confirmed as SCC of the oral cavity, diagnosed during 2006-2012. Clinical data were extracted from medical records. HPV presence was determined by polymerase chain reaction. Positive samples were typed by sequencing. Immunohistochemistry was used to assess p16 INK4A , p53, pRB, Ki67, Cyclin D1 and p21 WAF1 expression. Five of the 63 tumours (8%) were positive for HPV DNA (three HPV-16 positive and two HPV-18 positive). Two tumours overexpressed p16 INK4A (3%) and one of these was also HPV positive. Overexpression of Cyclin D1 correlated significantly with tumour recurrence (P = 0.029) and death (P = 0.002). This study has identified a low prevalence of high-risk HPV in Queensland, Australia. © 2016 Royal Australasian College of Surgeons.

  8. Identification of a novel human papillomavirus by metagenomic analysis of samples from patients with febrile respiratory illness.

    Directory of Open Access Journals (Sweden)

    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.

  9. 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...

  10. Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes.

    Science.gov (United States)

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

    2017-05-01

    Human papillomaviruses (HPVs) target promyelocytic leukemia (PML) nuclear bodies (NBs) during infectious entry and PML protein is important for efficient transcription of incoming viral genome. However, the transcriptional down regulation was shown to be promoter-independent in that heterologous promoters delivered by papillomavirus particles were also affected. To further investigate the role of PML protein in HPV entry, we used small hairpin RNA to knockdown PML protein in HaCaT keratinocytes. Confirming previous findings, PML knockdown in HaCaT cells reduced HPV16 transcript levels significantly following infectious entry without impairing binding and trafficking. However, when we quantified steady-state levels of pseudogenomes in interphase cells, we found strongly reduced genome levels compared with parental HaCaT cells. Because nuclear delivery was comparable in both cell lines, we conclude that viral pseudogenome must be removed after successful nuclear delivery. Transcriptome analysis by gene array revealed that PML knockdown in clonal HaCaT cells was associated with a constitutive interferon response. Abrogation of JAK1/2 signaling prevented genome loss, however, did not restore viral transcription. In contrast, knockdown of PML protein in HeLa cells did not affect HPV genome delivery and transcription. HeLa cells are transformed by HPV18 oncogenes E6 and E7, which have been shown to interfere with the JAK/Stat signaling pathway. Our data imply that PML NBs protect incoming HPV genomes. Furthermore, they provide evidence that PML NBs are key regulators of the innate immune response in keratinocytes. Promyelocytic leukemia nuclear bodies (PML NBs) are important for antiviral defense. Many DNA viruses target these subnuclear structures and reorganize them. Reorganization of PML NBs by viral proteins is important for establishment of infection. In contrast, HPVs require the presence of PML protein for efficient transcription of incoming viral genome. Our

  11. Human papillomavirus genotype distribution in cervical cancer cases in Spain. Implications for prevention.

    Science.gov (United States)

    Alemany, Laia; Pérez, Cristina; Tous, Sara; Llombart-Bosch, Antonio; Lloveras, Belen; Lerma, Enrique; Guarch, Rosa; Andújar, Miguel; Pelayo, Adela; Alejo, Maria; Ordi, Jaume; Klaustermeier, Joellen; Velasco, Julio; Guimerà, Nuria; Clavero, Omar; Castellsagué, Xavier; Quint, Wim; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia

    2012-03-01

    Human papillomavirus (HPV) genotype distribution in invasive cervical cancer (ICC) is critical to guide the introduction and to assess the impact of HPV prophylactic vaccines. This study aims to provide specific information for Spain. 1043 histological confirmed ICC cases diagnosed from 1940 to 2007 from six Spanish regions were assembled. HPV DNA detection was performed by SPF(10) broad-spectrum PCR followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA(25)) (version 1). Of 1043 ICC cases, 904 were HPV DNA positive (adjusted prevalence: 89.1%). The eight most common types, in decreasing order, were HPV 16, 18, 33, 31, 45, 35, 52 and 56, accounting for more than 90% of cases. HPV 16 and 18 contributed to 72.4% of all HPV positive ICC cases. In cervical adenocarcinomas, this contribution increased up to 94%. HPV 16 and 18 relative contributions showed a stable pattern over the 60 year study period. HPV 45, 18 and 16-positive ICC cases presented at younger ages than cases with other HPV types (adjusted mean age: 43.8, 45.2, 52.6 and 57.7 years, respectively). HPV 16 and 18 accounted together for a 72.4% of positive cases, with no statistically significant changes in their relative contributions over the last decades. In 94% of cervical adenocarcinomas we identified at least one of the two HPV types included in the current vaccines (HPV 16/18). Results suggest a major impact of HPV vaccines on reduction of ICC burden in Spain in the HPV vaccinated cohorts. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. 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

  13. 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

  14. 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.

  15. [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.

  16. Prevalence of oncogenic human papillomavirus genotypes in patients diagnosed with anogenital malignancies in Botswana

    Directory of Open Access Journals (Sweden)

    Patricia S. Rantshabeng

    2017-11-01

    Full Text Available Abstract Background Human papillomavirus (HPV associated malignancies are the leading cause of cancer death in Botswana. We sought to determine causative HPV types in patients with anogenital malignancies in Botswana to inform vaccine strategy. Methods We used formalin-fixed and paraffin-embedded (FFPE tissue blocks from patients diagnosed with anal, penile and vulvar squamous cell carcinomas between the years, 2014 and 2016. Presence of HPV 16, 18, or other high-risk (HR types was detected using Abbott m2000 real-time PCR platform. Tissues with other high-risk types were subsequently analysed using a multiplex qPCR assay that includes 15 validated fluorophore probes. Results A total of 126 tissue specimens, comprising of 21 anal (9 males, 12 females, 31 penile and 74 vulvar were studied. Ninety-three (73.8% patients had their HIV status documented in the records while the rest did not. Eighty-three (83 out of 93 were HIV positive, a prevalence of 89.4% (95% CI: 81–94. HPV was detected in 68/126 (54% tissues, of which 69% (95% CI: 54–79 had HPV 16 only, 28% (95% CI: 19–40 had other hr.-HPV types and 2.9% (95% CI, 3.5–10.1 were co-infected with HPV 16 and other hr.-types. Other high-risk types detected included HPV 26, 31, 33, 35, 39, 45, 51, 52, 66 and 68. HPV 18 was not detected. Multiple-type HPV infection was detected in 44 of 47 (93.6% HIV positive participants co-infected with HPV. In HIV-negative individuals, only HPV 16 was detected. Conclusion In our study, anogenital carcinomas were associated with HPV 16 and other hr.-HPV types besides HPV 16 and 18. HIV co-infected patients had multiple hr.-HPV types detected whereas in HIV-negative patients only HPV 16 was detected. Our study suggests that multivalent vaccines may be more suitable in this setting, especially for HIV-infected individuals.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  18. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal

    DEFF Research Database (Denmark)

    Serup-Hansen, Eva; Linnemann, Dorte; Skovrider-Ruminski, Wojciech

    2014-01-01

    -specific survival (DSS) in patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to III carcinoma of the anal canal. PATIENTS AND METHODS: HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed......PURPOSE: Carcinomas of the anal canal are strongly associated with the human papillomavirus (HPV). Expression of p16 is used as a surrogate marker of HPV infection. In a retrospective study, we evaluated HPV genotyping and p16 expression as prognostic markers of overall survival (OS) and disease...... by using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone. RESULTS: HPV16 was detected in 81.0% of the tumors, followed by HPV33 (5.1%), HPV18 (2.2%), and HPV58 (0.7%). p16 positivity was found in 92.9% of the tumors...

  19. 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.

  20. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    International Nuclear Information System (INIS)

    García-Espinosa, Benjamín; Moro-Rodríguez, Ernesto; Álvarez-Fernández, Emilio

    2012-01-01

    Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited

  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. 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...

  3. Quadrivalent human papillomavirus recombinant vaccine: The first vaccine for cervical cancers

    Directory of Open Access Journals (Sweden)

    Sharma Rashmi

    2007-01-01

    Full Text Available Gardasil ® is the first quadrivalent human papillomavirus (HPV- types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 years old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.

  4. 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

  5. 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.

  6. 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.

  7. Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples.

    Science.gov (United States)

    Alemany, L; Saunier, M; Tinoco, L; Quirós, B; Alvarado-Cabrero, I; Alejo, M; Joura, E A; Maldonado, P; Klaustermeier, J; Salmerón, J; Bergeron, C; Petry, K U; Guimerà, N; Clavero, O; Murillo, R; Clavel, C; Wain, V; Geraets, D T; Jach, R; Cross, P; Carrilho, C; Molina, C; Shin, H R; Mandys, V; Nowakowski, A M; Vidal, A; Lombardi, L; Kitchener, H; Sica, A R; Magaña-León, C; Pawlita, M; Quint, W; Bravo, I G; Muñoz, N; de Sanjosé, S; Bosch, F X

    2014-11-01

    This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Role of Ultraviolet Radiation in Papillomavirus-Induced Disease

    Science.gov (United States)

    Uberoi, Aayushi; Yoshida, Satoshi; Frazer, Ian H.; Pitot, Henry C.; Lambert, Paul F.

    2016-01-01

    Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans. PMID:27244228

  10. 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.

  11. 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

  12. 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.

  13. The prevalence of human papillomavirus infection in Iranian patients with sinonasal inverted papilloma.

    Science.gov (United States)

    Jalilvand, Somayeh; Saidi, Masoumeh; Shoja, Zabihollah; Ghavami, Nastaran; Hamkar, Rasool

    2016-03-01

    Inverted papilloma (IP) is an uncommon disease which arises in the mucosal membrane of the nasal cavity and paranasal sinus. It has been proposed that human papillomavirus (HPV) is the causal agent in the pathogenesis of IP and plays a key role in the progression from benign IP to malignancy. As there are no prior studies that focus on an Iranian population, this study intended to characterize the prevalence of HPV types in benign and malignant forms of IP. In this retrospective study, we included a total of 40 IP patients [37 benign IP and 3 IP/squamous cell carcinoma (SCC)] who were referred to Amiralam Hospital in Tehran from 2004-2006. HPV was detected in 18.9% and 100% of IP and IP/SCC cases, respectively. In all HPV positive cases of IP and IP/SCC cases, HPV6/11 and HPV16/18 were detected, respectively. Therefore, HPV types were different between the IP and IP/SCC patients, and this difference was statistically significant (p = 0.002). This study suggests that HPV6 and 11 may be involved in the development of IP, but HPV16 and 18 likely play an important role in the progression from benign to malignant form of IP. Copyright © 2015. Published by Elsevier Taiwan LLC.

  14. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

    Directory of Open Access Journals (Sweden)

    Ángela María Ruiz-Sternberg

    2018-06-01

    Full Text Available Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312 received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6. Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99% 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV

  15. 4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years.

    Science.gov (United States)

    Ferris, Daron G; Samakoses, Rudiwilai; Block, Stanley L; Lazcano-Ponce, Eduardo; Restrepo, Jaime Alberto; Mehlsen, Jesper; Chatterjee, Archana; Iversen, Ole-Erik; Joshi, Amita; Chu, Jian-Li; Krick, Andrea Likos; Saah, Alfred; Das, Rituparna

    2017-12-01

    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. In the base study (V501-018), 1661 sexually inactive boys and girls received the 4vHPV vaccine (early vaccination group [EVG], managed for 9.9 years) or a placebo at day 1, month 2, and month 6. Thereafter, at month 30, the placebo group (catch-up vaccination group [CVG], managed for 7.4 years) received the 4vHPV vaccine by using the same dosing schedule. Long-term anti-HPV type 6, 11, 16, and 18 immune responses were 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). 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 persistent infection for ≥12 months. No new serious adverse events were reported through 10 years. A 3-dose regimen of the 4vHPV vaccine was immunogenic, clinically effective, and generally well tolerated in preadolescents and adolescents during 10 years of follow-up. These long-term findings support efforts to vaccinate this population against HPV before exposure. Copyright © 2017 by the American Academy of Pediatrics.

  16. 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 ...

  17. 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.

  18. Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    S. M. B. Cavalcanti

    1994-12-01

    Full Text Available A hundred-sixty paraffin-embedded specimens from female cervical lesions were examined for human papillomavirus (HPV types 6, 11, 16 and 18 infections by non-isotopic in situ hybridization. The data were compared with histologic diagnosis. Eighty-eight (55 biopsies contained HPV DNA sequences. In low grade cervical intraepithelial neoplasias (CIN I, HPV infection was detected in 78.7 of the cases, the benign HPV 6 was the most prevalent type. HPV DNA was detected in 58 of CIN II and CIN III cases and in 41.8 of squamous cell carcinomas (SCC. Histologically normal women presented 20 of HPV infection. Oncogenic HPV was found in 10 of these cases, what may indicate a higher risk of developing CINs and cancer. Twenty-five percent of the infected tissues contained mixed infections. HPV 16 was the most common type infecting the cervix and its prevalence raised significantly with the severity of the lesions, pointing its role in cancer pathogenesis. White women presented twice the cervical lesions of mulatto and African origin women, although HPV infection rates were nearly the same for the three groups (approximately 50. Our results showed that HPV typing by in situ hybridization is a useful tool for distinguishing between low and high risk cervical lesions. Further studies are required to elucidate risk factors associated with HPV infection and progression to malignancy in Brazilian population.

  19. 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

  20. 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.

  1. Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge.

    Science.gov (United States)

    Gustavsson, Inger; Sanner, Karin; Lindell, Monica; Strand, Anders; Olovsson, Matts; Wikström, Ingrid; Wilander, Erik; Gyllensten, Ulf

    2011-08-01

    Most procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media. To evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA Elute Micro card and biopsy analysis. A total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays. All samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2-3 (CIN 2-3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis. The Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Human papillomavirus genomes in squamous cell carcinomas of the uterine cervix

    International Nuclear Information System (INIS)

    Matsukura, Toshihiko; Sugase, Motoyasu

    2004-01-01

    The association between invasive cervical carcinoma and human papillomavirus (HPV) has now been established beyond doubt, but this is not necessarily a direct-and-effect association. To assess the causality of HPV, we analyzed HPV genomes in squamous cell carcinomas (SCCS) of the uterine cervix by both blot hybridization and PCR. Genital HPV sequences were found in 231 (79%) of 294 SCCs by blot hybridization with more than five copies of entire HPV genomes identified in some cases including HPV 16 (92 cases), HPV 58 (32 cases), and HPV 52 (24 cases). By PCR-direct sequence analysis in 250 of 294 SCCs, genital HPV sequences were found in 240 samples (96%). The partial L1 sequences of HPV 16 were identified in 123 cases, and those of HPVs 18 and 31 were found in 24 and 20 cases, respectively. In addition, multiple HPV types were identified in 29 (12%) of 250 SCCs, and the HPV copy number, detected by PCR only, was less than 0.05. Marked discrepancies were therefore evident between the two analytical techniques. In this report, we discuss the causality of HPV for SCC with regard to the length of the viral genome, the amount of viral DNA, and multiple HPVs in single SCCs

  3. 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...

  4. 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...

  5. Human papillomavirus infection and the malignant transformation of sinonasal inverted papilloma: A meta-analysis.

    Science.gov (United States)

    Zhao, Ren-Wu; Guo, Zhi-Qiang; Zhang, Ru-Xin

    2016-06-01

    A growing number of molecular epidemiological studies have been conducted to evaluate the association between human papillomavirus (HPV) infection and the malignancy of sinonasal inverted papilloma (SNIP). However, the results remain inconclusive. Here, a meta-analysis was conducted to quantitatively assess this association. Case-control studies investigating SNIP tissues for presence of HPV DNA were identified. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method. An assessment of publication bias and sensitivity analysis were also performed. We calculated a pooled OR of 2.16 (95% CI=1.46-3.21, P<0.001) without statistically significant heterogeneity or publication bias. Stratification by HPV type showed a stronger association for patients with high-risk HPV (hrHPV) types, HPV-16, HPV-18, and HPV-16/18 infection (OR=8.8 [95% CI: 4.73-16.38], 8.04 [95% CI: 3.34-19.39], 18.57 [95% CI: 4.56-75.70], and 26.24 [4.35-158.47], respectively). When only using PCR studies, pooled ORs for patients with hrHPV, HPV-16, and HPV18 infection still reached statistical significance. However, Egger's test reflected significant publication bias in the HPV-16 sub-analysis (P=0.06), and the adjusted OR was no longer statistically significant (OR=1.65, 95%CI: 0.58-4.63). These results suggest that HPV infection, especially hrHPV (HPV-18), is significantly associated with malignant SNIP. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. High-risk and multiple human papillomavirus infections among married women in Can Tho, Viet Nam.

    Science.gov (United States)

    Vu, Lan Thi Hoang

    2012-07-01

    The two currently licensed human papillomavirus (HPV) vaccines are highly efficacious in preventing cervical pre-cancers related to HPV 6, 11, 16 and 18. Before implementing a large-scale HPV vaccine campaign in Viet Nam, information about the prevalence of infection with the HPV vaccine types is required. This study was done in Can Tho, the province with the highest prevalence of cervical cancer in the south of Viet Nam, to explore the distribution of other high-risk types of HPV among married women in this province. The study employed a cross-sectional design with multistage sampling. A total of 1000 participants were randomly selected, interviewed and given gynaecological examinations. HPV infection status and HPV genotyping test were completed for all participants. A broad spectrum of HPV types was reported in this study. The prevalence of cases infected with HPV 16 and/or 18 was 7%; the prevalence of cases infected with other high-risk HPV types was 6%. The highest prevalence for single and multiple infections, as well as for high-risk infections, was reported for the youngest age group (less than 30 years). While it is relevant to implement an HPV vaccine campaign in Viet Nam due to the high prevalence of infection with HPV 16 and/or 18, it is important to note that one can be infected with multiple types of HPV. Vaccination does not protect against all types of high-risk HPV. Future vaccine campaigns should openly disclose this information to women receiving vaccines.

  7. Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Nulton, Tara J; Olex, Amy L; Dozmorov, Mikhail; Morgan, Iain M; Windle, Brad

    2017-03-14

    Human papillomavirus (HPV) DNA is detected in up to 80% of oropharyngeal carcinomas (OPC) and this HPV positive disease has reached epidemic proportions. To increase our understanding of the disease, we investigated the status of the HPV16 genome in HPV-positive head and neck cancers (HNC). Raw RNA-Seq and Whole Genome Sequence data from The Cancer Genome Atlas HNC samples were analyzed to gain a full understanding of the HPV genome status for these tumors. Several remarkable and novel observations were made following this analysis. Firstly, there are three main HPV genome states in these tumors that are split relatively evenly: An episomal only state, an integrated state, and a state in which the viral genome exists as a hybrid episome with human DNA. Secondly, none of the tumors expressed high levels of E6; E6*I is the dominant variant expressed in all tumors. The most striking conclusion from this study is that around three quarters of HPV16 positive HNC contain episomal versions of the viral genome that are likely replicating in an E1-E2 dependent manner. The clinical and therapeutic implications of these observations are discussed.

  8. Role of Ultraviolet Radiation in Papillomavirus-Induced Disease.

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    Aayushi Uberoi

    2016-05-01

    Full Text Available Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1 that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR, specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans.

  9. Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

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    Angela RI Meyrelles

    2016-02-01

    Full Text Available This study investigated the rate of human papillomavirus (HPV persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample, re-infection (detection of different types of HPV in the 2 samples, and type-specific HPV persistence (the same HPV type found in both samples. An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30% or re-infection (20%. A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79. Our findings show that bonafide (type-specific HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

  10. High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men.

    Science.gov (United States)

    Glick, Sara Nelson; Feng, Qinghua; Popov, Viorica; Koutsky, Laura A; Golden, Matthew R

    2014-02-01

    There are few published estimates of anal human papillomavirus (HPV) infection rates among young men who have sex with men (YMSM). We estimated incidence and prevalence of type-specific anal HPV infection using clinician-collected anal swabs for HPV DNA testing obtained during a 1-year prospective study of 94 YMSM (mean age, 21 years) in Seattle. Seventy percent of YMSM had any HPV infection detected during the study, and HPV-16 and/or -18 were detected in 37%. The incidence rate for any new HPV infection was 38.5 per 1000 person-months and 15.3 per 1000 person-months for HPV-16/18; 19% had persistent HPV-16/18 infection. No participant tested positive for all 4 HPV types in the quadrivalent vaccine. The number of lifetime male receptive anal sex partners was significantly associated with HPV infection. The prevalence of HPV-16/18 was 6% among YMSM with a history of 1 receptive anal sex partner and 31% among YMSM with ≥ 2 partners. Although the high prevalence of HPV among YMSM highlights the desirability of vaccinating all boys as a strategy to avert the morbidity of HPV infection, most YMSM appear to remain naive to either HPV-16 or -18 well into their sexual lives and would benefit from HPV immunization.

  11. Vaccines against papillomavirus infections and disease

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    Villa Luisa Lina

    2003-01-01

    Full Text Available Squamous cell carcinoma of the uterine cervix is the second cause of cancer-related deaths in women, the higher incidence being observed in developing countries. Infection with oncogenic types of human papillomavirus (HPV is considered the major risk factor for the development of malignancies in the uterine cervix. However, HPV is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenic process, both present in the environment and from the host. Studies performed in animals, and more recently in humans, indicate that vaccination against the capsid proteins of the virus can prevent efficiently from infection. Furthermore, therapeutic vaccines are under investigation aiming the regression of papillomavirus induced tumors. The scientific basis for the development of papillomavirus vaccines and present status of clinical trials will be addressed in this chapter.

  12. 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.

  13. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Rijkee, Laurie K; Skeate, Joseph G; Taylor, Julia R; Koopman, Maaike E; Brand, Heike E; Wong, Michael K; McKee, Greg M; Salazar, Andres M; Kast, W Martin

    2015-12-01

    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.

  14. 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.

  15. 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

  16. Prevalence of and risk factors for oral human papillomavirus among young women in Costa Rica.

    Science.gov (United States)

    Lang Kuhs, Krystle A; Gonzalez, Paula; Struijk, Linda; Castro, Felipe; Hildesheim, Allan; van Doorn, Leen-Jan; Rodriguez, Ana Cecilia; Schiffman, Mark; Quint, Wim; Lowy, Douglas R; Porras, Carolina; Delvecchio, Corey; Katki, Hormuzd A; Jimenez, Silvia; Safaeian, Mahboobeh; Schiller, John; Solomon, Diane; Wacholder, Sholom; Herrero, Rolando; Kreimer, Aimée R

    2013-11-15

    Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America. Women (N = 5838) aged 22-29 in the control and vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8-5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0-6.1 for ≥4 partners compared to 0-1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior. Clinical Trials Registration. NCT00128661.

  17. 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.

  18. Association of High-Risk Human Papillomavirus with Genital Tract Mucosal Immune Factors In HIV-Infected Women

    Science.gov (United States)

    Buckley, Niall; Huber, Ashley; Lo, Yungtai; Castle, Philip E.; Kemal, Kimdar; Burk, Robert D.; Strickler, Howard D.; Einstein, Mark H.; Young, Mary; Anastos, Kathryn; Herold, Betsy C.

    2015-01-01

    Problem High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication. Method of Study Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n=8), other HR-HPV (n=41), and non-HR-HPV controls (n=79). Results Compared to controls, HR-HPV groups had higher plasma viral loads (p=0.004), lower CD4 cells (p=0.02), more genital tract HIV RNA (p=0.03), greater number of different HPV types (p<0.001), higher cervicovaginal lavage (CVL) IL-1α (p=0.03) and human beta defensin 2 (HBD2) (p=0.049), and less anti-HIVBal activity (p=0.03). HPV-16 remained significantly associated with higher HBD2 (p=0.03), higher IL-1α (p=0.009), and lower anti-HIVBaL activity (p=0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count. Conclusion HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health. PMID:26685115

  19. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9

    International Nuclear Information System (INIS)

    Zhen, Shuai; Hua, Ling; Takahashi, Y.; Narita, S.; Liu, Yun-Hui; Li, Yan

    2014-01-01

    Highlights: • Established CRISPR/Cas9 targeting promoter of HPV 16 and targeting E6, E7 transcript. • CRISPR/Cas9 resulted in accumulation of p53 and p21, reduced the proliferation of cervical cancer cells. • Finding inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9. • CRISPR/Cas9 will be a new treatment strategy, in cervical and other HPV-associated cancer therapy. - Abstract: Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. In the hope of developing a gene-specific therapy for HPV-related cancer, we established CRISPR/Cas9 targeting promoter of HPV 16 E6/E7 and targeting E6, E7 transcript, transduced the CRISPR/Cas9 into cervical HPV-16-positive cell line SiHa. The results showed that CRISPR/Cas9 targeting promoter, as well as targeting E6 and E7 resulted in accumulation of p53 and p21 protein, and consequently remarkably reduced the abilities of proliferation of cervical cancer cells in vitro. Then we inoculated subcutaneously cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9 targeting (promoter+E6+E7)-transcript. Our results may provide evidence for application of CRISPR/Cas9 targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy

  20. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9

    Energy Technology Data Exchange (ETDEWEB)

    Zhen, Shuai [Baoji Maternal and Child Health Hospital, 2 Xinjian Road East, WeiBin District, Baoji City, 721000, Shanxi Province (China); Xijing Hospital, Fourth Military Medical University, Xi’an (China); Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Kyoto University, Kyoto 606-8507 (Japan); Hua, Ling [Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Takahashi, Y.; Narita, S. [Kyoto University, Kyoto 606-8507 (Japan); Liu, Yun-Hui [Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Li, Yan [Baoji Hospital of Traditional Chinese Medicine, No 43, BaoFu Road, Baoji City, Shanxi Province (China)

    2014-08-08

    Highlights: • Established CRISPR/Cas9 targeting promoter of HPV 16 and targeting E6, E7 transcript. • CRISPR/Cas9 resulted in accumulation of p53 and p21, reduced the proliferation of cervical cancer cells. • Finding inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9. • CRISPR/Cas9 will be a new treatment strategy, in cervical and other HPV-associated cancer therapy. - Abstract: Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. In the hope of developing a gene-specific therapy for HPV-related cancer, we established CRISPR/Cas9 targeting promoter of HPV 16 E6/E7 and targeting E6, E7 transcript, transduced the CRISPR/Cas9 into cervical HPV-16-positive cell line SiHa. The results showed that CRISPR/Cas9 targeting promoter, as well as targeting E6 and E7 resulted in accumulation of p53 and p21 protein, and consequently remarkably reduced the abilities of proliferation of cervical cancer cells in vitro. Then we inoculated subcutaneously cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9 targeting (promoter+E6+E7)-transcript. Our results may provide evidence for application of CRISPR/Cas9 targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy.

  1. Human papillomavirus genotyping using an automated film-based chip array.

    Science.gov (United States)

    Erali, Maria; Pattison, David C; Wittwer, Carl T; Petti, Cathy A

    2009-09-01

    The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (-) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (-) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping.

  2. 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 ...

  3. 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 ...

  4. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

    OpenAIRE

    Ángela María Ruiz-Sternberg; Edson D. Moreira, Jr; Jaime A. Restrepo; Eduardo Lazcano-Ponce; Robinson Cabello; Arnaldo Silva; Rosires Andrade; Francisco Revollo; Santos Uscanga; Alejandro Victoria; Ana María Guevara; Joaquín Luna; Manuel Plata; Claudia Nossa Dominguez; Edison Fedrizzi

    2018-01-01

    Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years...

  5. Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience.

    Science.gov (United States)

    Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

    2014-05-01

    To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010). Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  6. Burden and trends of type-specific human papillomavirus infections and related diseases in the latin america and Caribbean region.

    Science.gov (United States)

    Parkin, D Maxwell; Almonte, Maribel; Bruni, Laia; Clifford, Gary; Curado, Maria-Paula; Piñeros, Marion

    2008-08-19

    We present the burden of human papillomavirus (HPV)-related cancers (cancers of the cervix, anogenital region, oral cavity and pharynx) in terms of incidence and mortality, for the countries of the Latin America and Caribbean region. The region is a high-risk area for cancer of the cervix and, although incidence has declined since the 1960s, projected demographic changes imply that the actual burden of new cases will increase by more than 75% in the next 20 years, while the average and at diagnosis will increase. Approximately 65% of cervical cancer cases and 50% of the high risk lesions are associated with HPV-16 and 18. Incidence rates of other HPV-related cancers are significantly lower. The paper also describes the estimated impact of genital warts and the limited data available on the occurrence of HPV infections of the upper aerodigestive tract in the region.

  7. 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

  8. Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication.

    Science.gov (United States)

    Gauson, Elaine J; Donaldson, Mary M; Dornan, Edward S; Wang, Xu; Bristol, Molly; Bodily, Jason M; Morgan, Iain M

    2015-05-01

    To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination. Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease

  9. 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....

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Seroprevalence and Associated Factors of 9-Valent Human Papillomavirus (HPV) Types among Men in the Multinational HIM Study.

    Science.gov (United States)

    Rahman, Shams; Pierce Campbell, Christine M; Rollison, Dana E; Wang, Wei; Waterboer, Tim; Michel, Angelika; Pawlita, Michael; Villa, Luisa L; Lazcano Ponce, Eduardo; Borenstein, Amy R; Giuliano, Anna R

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Recently a 9-valent HPV (9vHPV) prophylactic vaccine was licensed. Seroprevalence prior to vaccine dissemination is needed for monitoring vaccine effectiveness over time. Few studies have assessed the seroprevalence of 9vHPV types in men. To investigate the seroprevalence of 9vHPV vaccine types and associated risk factors among men residing in Brazil, Mexico, and the United States. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens collected at enrollment were tested for antibodies against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58) using a glutathione S-transferase (GST) L1-based multiplex serologic assay. Socio-demographic, lifestyle and sexual behavior data at enrollment were collected through a questionnaire. Binomial proportions were used to estimate seroprevalence and logistic regression was used to examine factors associated with seropositivity of type-specific and grouped (i.e. 9vHPV, high-risk 9vHPV, low risk 9vHPV, and five-additional) HPV types. Overall, 28.3% of men were seropositive for at least one of the 9vHPV vaccine types, 14.0% for at least one of the seven high-risk types (16, 18, 31, 33, 45, 52 and 58) and 11.2% for at least one of the five high-risk types (31, 33, 45, 52 and 58) not included in the quadrivalent HPV vaccine, and 17.4% for at least one of the low-risk types (6/11). In multivariate analyses, odds ratios adjusted (AOR) for country of residence, age, marital status, smoking, number of anal sex lifetime partners, compared to men with no anal sex lifetime partners, men with ≥2 partners were more likely to be seropositive for grouped HPV [(9vHPV: AOR 2.52; 95% confidence interval (CI) 1.40-4.54), (high-risk 9vHPV: AOR 2.18; 95%CI: 1.05-4.50) and (low-risk 9vHPV: AOR 2.12; 95%CI: 1.12-4.03)], and individual HPV types 6, 16, 33 and 58 with AORs ranging from 2.19 to 7

  15. Single-tube multiplex PCR using type-specific E6/E7 primers and capillary electrophoresis genotypes 21 human papillomaviruses in neoplasia

    Directory of Open Access Journals (Sweden)

    Warenholt Janina

    2011-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV E6/E7 type-specific oncogenes are required for cervical carcinogenesis. Current PCR protocols for genotyping high-risk HPV in cervical screening are not standardized and usually use consensus primers targeting HPV capsid genes, which are often deleted in neoplasia. PCR fragments are detected using specialized equipment and extra steps, including probe hybridization or primer extension. In published papers, analytical sensitivity is typically compared with a different protocol on the same sample set. A single-tube multiplex PCR containing type-specific primers was developed to target the E6/E7 genes of two low-risk and 19 high-risk genotypes (HPV6, 11 and 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82 and the resulting short fragments were directly genotyped by high-resolution fluorescence capillary electrophoresis. Results The method was validated using long oligonucleotide templates, plasmid clones and 207 clinical samples of DNA from liquid-based cytology, fresh and formalin-fixed specimens and FTA Microcards® imprinted with cut tumor surfaces, swabbed cervical cancers or ejected aspirates from nodal metastases of head and neck carcinomas. Between one and five long oligonucleotide targets per sample were detected without false calls. Each of the 21 genotypes was detected in the clinical sample set with up to five types simultaneously detected in individual specimens. All 101 significant cervical neoplasias (CIN 2 and above, except one adenocarcinoma, contained E6/E7 genes. The resulting genotype distribution accorded with the national pattern with HPV16 and 18 accounting for 69% of tumors. Rare HPV types 70 and 73 were present as the sole genotype in one carcinoma each. One cervical SCC contained DNA from HPV6 and 11 only. Six of twelve oropharyngeal cancer metastases and three neck metastases of unknown origin bore E6/E7 DNA; all but one were HPV16. One neck

  16. Aggregation and competitive exclusion: explaining the coexistence of human Papillomavirus types and the effectiveness of limited vaccine conferred cross-immunity.

    Science.gov (United States)

    Waters, E K

    2012-12-01

    Human Papillomavirus (HPV) types are sexually transmitted infections that cause a number of human cancers. According to the competitive exclusion principle in ecology, HPV types that have lower transmission probabilities and shorter durations of infection should be outcompeted by more virulent types. This, however, is not the case, as numerous HPV types co-exist, some which are less transmissible and more easily cleared than others. This paper examines whether this exception to the competitive exclusion principle can be explained by the aggregation of infection with HPV types, which results in patchy spatial distributions of infection, and what implications this has for the effect of vaccination on multiple HPV types. A deterministic transmission model is presented that models the patchy distribution of infected individuals using Lloyd's mean crowding. It is first shown that higher aggregation can result in a reduced capacity for onward transmission and reduce the required efficacy of vaccination. It is shown that greater patchiness in the distribution of lower prevalence HPV types permits co-existence. This affirms the hypothesis that the aggregation of HPV types provides an explanation for the violation of the competitive exclusion principle. Greater aggregation of lower prevalence types has important implications where type-specific HPV vaccines also offer cross-protection against non-target types. It is demonstrated that the degree of cross-protection can be less than the degree of vaccine protection conferred against directly targeted types and still result in the elimination of non-target types when these non-target types are patchily distributed.

  17. 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

  18. 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.

  19. Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors.

    Directory of Open Access Journals (Sweden)

    Sara Soto-De Leon

    Full Text Available BACKGROUND: Infection with multiple types of human papillomavirus (HPV is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. PRINCIPAL FINDINGS: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%, while this risk decreased in women who had given birth more than 4 times (-31.1%, or were of mestizo (-24.6% or black (-40.9% ethnicity. CONCLUSIONS: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

  20. 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...

  1. 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...

  2. Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study

    Directory of Open Access Journals (Sweden)

    Golubović Mileta

    2017-01-01

    Full Text Available Background/Aim. In patients with premalignant cervical lesions, human papillomavirus (HPV infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. Methods. This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. Results. In the group of 80 (3.1%; n = 80/2,578 of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70% of them had cervicitis, and 1/3 or 24 (30% had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions. Conclusion. Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure.

  3. 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.

  4. 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

  5. Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

    International Nuclear Information System (INIS)

    Zhang, Donghong; Zhang, Qingying; Zhou, Li; Huo, Leijun; Zhang, Yi; Shen, Zhongying; Zhu, Yi

    2010-01-01

    Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027). High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC

  6. 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...

  7. 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...

  8. Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses

    NARCIS (Netherlands)

    Welters, Marij J. P.; Kenter, Gemma G.; de Vos van Steenwijk, Peggy J.; Löwik, Margriet J. G.; Berends-van der Meer, Dorien M. A.; Essahsah, Farah; Stynenbosch, Linda F. M.; Vloon, Annelies P. G.; Ramwadhdoebe, Tamara H.; Piersma, Sytse J.; van der Hulst, Jeanette M.; Valentijn, A. Rob P. M.; Fathers, Lorraine M.; Drijfhout, Jan W.; Franken, Kees L. M. C.; Oostendorp, Jaap; Fleuren, Gert Jan; Melief, Cornelis J. M.; van der Burg, Sjoerd H.

    2010-01-01

    One half of a group of 20 patients with human papillomavirus type 16 (HPV16)-induced vulvar intraepithelial neoplasia grade 3 displayed a complete regression (CR) after therapeutic vaccination with HPV16 E6/E7 synthetic long peptides. Patients with relatively larger lesions generally did not display

  9. 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

  10. Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions.

    Science.gov (United States)

    Chuerduangphui, Jureeporn; Pientong, Chamsai; Swangphon, Piyawut; Luanratanakorn, Sanguanchoke; Sangkomkamhang, Ussanee; Tungsiriwattana, Thumwadee; Kleebkaow, Pilaiwan; Burassakarn, Ati; Ekalaksananan, Tipaya

    2018-05-09

    Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16 INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16 INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16 INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16 INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16 INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203-24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604-16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16 INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228-1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

  11. The role of human papillomavirus in head and neck cancer in Senegal.

    Science.gov (United States)

    Ndiaye, Cathy; Alemany, Laia; Diop, Yankhoba; Ndiaye, Nafissatou; Diémé, Marie-Joseph; Tous, Sara; Klaustermeier, Jo Ellen; Alejo, Maria; Castellsagué, Xavier; Bosch, F Xavier; Trottier, Helen; Sanjosé, Silvia de

    2013-04-17

    Exploring the presence and role of human papillomavirus (HPV) in head and neck cancer (HNC) is a necessary step to evaluate the potential impact of HPV prophylactic vaccines. To assess the prevalence and oncogenic role of HPV in HNC in Senegal. This is a multicenter cross-sectional study. Paraffin-embedded blocks of cases diagnosed with invasive HNC between 2002 and 2010 were collected from 4 pathology laboratories in Senegal. Presence of HPV DNA was determined by PCR and DEIA, and genotyping performed with LiPA25. Tubulin analysis was performed to assess DNA quality. HPV DNA-positive cases were tested for p16INK4a expression. A total of 117 cases were included in the analysis: 71% were men, mean age was 52 years old (SD ±18.3), and 96% of cases were squamous cell carcinoma. Analysis was performed on 41 oral cavity tumors, 64 laryngeal tumors, 5 oropharyngeal tumors and 7 pharyngeal tumors. Only four cases (3.4%; 95% CI = 0.9%-8.5%) harbored HPV DNA. HPV types detected were HPV16, HPV35 and HPV45. However, among HPV-positive cases, none showed p16INK4a overexpression. Our findings indicate that HPV DNA prevalence in HNC in Senegal is very low, suggesting that HPV is not a strong risk factor for these cancers. Additional larger studies are needed to confirm these findings and explore other potential risk factors specific to the region.

  12. Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

    International Nuclear Information System (INIS)

    Hufbauer, M.; Lazic, D.; Akguel, B.; Brandsma, J.L.; Pfister, H.; Weissenborn, S.J.

    2010-01-01

    Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

  13. Human papillomavirus genotype distribution in Madrid and correlation with cytological data.

    Science.gov (United States)

    Martín, Paloma; Kilany, Linah; García, Diego; López-García, Ana M; Martín-Azaña, Ma José; Abraira, Victor; Bellas, Carmen

    2011-11-15

    Cervical cancer is the second most common cancer in women worldwide. Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor associated with cervical cancer. This study analysed the distribution of type-specific HPV infection among women with normal and abnormal cytology, to assess the potential benefit of prophylaxis with anti-HPV vaccines. Cervical samples of 2,461 women (median age 34 years; range 15-75) from the centre of Spain were tested for HPV DNA. These included 1,656 samples with normal cytology (NC), 336 with atypical squamous cells of undetermined significance (ASCUS), 387 low-grade squamous intraepithelial lesions (LSILs), and 82 high-grade squamous intraepithelial lesions (HSILs). HPV detection and genotyping were performed by PCR using 5'-biotinylated MY09/11 consensus primers, and reverse dot blot hybridisation. HPV infection was detected in 1,062 women (43.2%). Out of these, 334 (31%) samples had normal cytology and 728 (69%) showed some cytological abnormality: 284 (27%) ASCUS, 365 (34%) LSILs, and 79 (8%) HSILs. The most common genotype found was HPV 16 (28%) with the following distribution: 21% in NC samples, 31% in ASCUS, 26% in LSILs, and 51% in HSILs. HPV 53 was the second most frequent (16%): 16% in NC, 16% in ASCUS, 19% in LSILs, and 5% in HSILs. The third genotype was HPV 31 (12%): 10% in NC, 11% in ASCUS, 14% in LSILs, and 11% in HSILs. Co-infections were found in 366 samples (34%). In 25%, 36%, 45% and 20% of samples with NC, ASCUS, LSIL and HSIL, respectively, more than one genotype was found. HPV 16 was the most frequent genotype in our area, followed by HPV 53 and 31, with a low prevalence of HPV 18 even in HSILs. The frequency of genotypes 16, 52 and 58 increased significantly from ASCUS to HSILs. Although a vaccine against HPV 16 and 18 could theoretically prevent approximately 50% of HSILs, genotypes not covered by the vaccine are frequent in our population. Knowledge of the epidemiological

  14. Human papillomavirus genotype distribution in Madrid and correlation with cytological data

    Directory of Open Access Journals (Sweden)

    Martín Paloma

    2011-11-01

    Full Text Available Abstract Background Cervical cancer is the second most common cancer in women worldwide. Infection with certain human papillomavirus (HPV genotypes is the most important risk factor associated with cervical cancer. This study analysed the distribution of type-specific HPV infection among women with normal and abnormal cytology, to assess the potential benefit of prophylaxis with anti-HPV vaccines. Methods Cervical samples of 2,461 women (median age 34 years; range 15-75 from the centre of Spain were tested for HPV DNA. These included 1,656 samples with normal cytology (NC, 336 with atypical squamous cells of undetermined significance (ASCUS, 387 low-grade squamous intraepithelial lesions (LSILs, and 82 high-grade squamous intraepithelial lesions (HSILs. HPV detection and genotyping were performed by PCR using 5'-biotinylated MY09/11 consensus primers, and reverse dot blot hybridisation. Results HPV infection was detected in 1,062 women (43.2%. Out of these, 334 (31% samples had normal cytology and 728 (69% showed some cytological abnormality: 284 (27% ASCUS, 365 (34% LSILs, and 79 (8% HSILs. The most common genotype found was HPV 16 (28% with the following distribution: 21% in NC samples, 31% in ASCUS, 26% in LSILs, and 51% in HSILs. HPV 53 was the second most frequent (16%: 16% in NC, 16% in ASCUS, 19% in LSILs, and 5% in HSILs. The third genotype was HPV 31 (12%: 10% in NC, 11% in ASCUS, 14% in LSILs, and 11% in HSILs. Co-infections were found in 366 samples (34%. In 25%, 36%, 45% and 20% of samples with NC, ASCUS, LSIL and HSIL, respectively, more than one genotype was found. Conclusions HPV 16 was the most frequent genotype in our area, followed by HPV 53 and 31, with a low prevalence of HPV 18 even in HSILs. The frequency of genotypes 16, 52 and 58 increased significantly from ASCUS to HSILs. Although a vaccine against HPV 16 and 18 could theoretically prevent approximately 50% of HSILs, genotypes not covered by the vaccine are frequent in

  15. Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice

    Science.gov (United States)

    Park, Soyeong; Park, Jung Wook; Pitot, Henry C.

    2016-01-01

    ABSTRACT   Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. Importance   Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an

  16. Measurement of neutralizing serum antibodies of patients vaccinated with human papillomavirus L1 or L2-based immunogens using furin-cleaved HPV Pseudovirions.

    Directory of Open Access Journals (Sweden)

    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

  17. 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.

  18. 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 ...

  19. 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 ...

  20. 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.

  1. Human papillomavirus in tonsillar squamous cell carcinomas from Guatemala and Brazil.

    Science.gov (United States)

    Piña, Alicia Rumayor; Jimenez, Laísa Simakawa; Mariano, Fernanda Viviane; de Andrade, Bruno Augusto Benevenuto; Carlos, Román; Altemani, Albina; de Almeida, Oslei Paes

    2016-04-01

    A subgroup of tonsillar squamous cell carcinoma (SCC) is associated with human papillomavirus (HPV). Nevertheless, the prevalence of HPV seems to be variable in different regions and ethnic groups. There are no reports of HPV in tonsillar carcinomas in Guatemala, and data from Brazil are scarce. The aim of this study is to analyze and compare HPV presence in samples of tonsillar SCC from these countries. This study describes the histologic features, expression of p16 by immunohistochemistry (IHC), and HPV by in situ hybridization (ISH) in 13 Guatemalan and 13 Brazilian patients. All cases of tonsillar SCC from Guatemala were positive for p16, 92% expressed HPV by ISH, and 75% corresponded to the high-risk genotype 16/18. From the Brazilian patients, only four expressed p16, and all were negative for HPV. Cases from Guatemala, which were mostly nonkeratinizing SCC and originated from the crypt/reticular epithelium of the tonsil, had high-risk integrated HPV, whereas in Brazilian cases, which were mostly keratinizing SCC that originated from the surface epithelium, there was no association with HPV. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [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.

  3. 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

  4. 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...

  5. 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.

  6. Infection with the oncogenic human papillomavirus type 59 alters protein components of the cornified cell envelope

    International Nuclear Information System (INIS)

    Lehr, Elizabeth; Brown, Darron R.

    2003-01-01

    Infection of the genital tract with human papillomaviruses (HPVs) leads to proliferative and dysplastic epithelial lesions. The mechanisms used by the virus to escape the infected keratinocyte are not well understood. Infection of keratinocytes with HPV does not cause lysis, the mechanism used by many viruses to release newly formed virions. For HPV 11, a type associated with a low risk of neoplastic disease, the cornified cell envelope (CCE) of infected keratinocytes is thin and fragile, and transcription of loricrin, the major CCE protein, is reduced. The effects of high-risk HPV infection on components of the CCE have not been previously reported. HPV 59, an oncogenic genital type related to HPV types 18 and 45 was identified in a condylomata acuminata lesion. An extract of this lesion was used to infect human foreskin fragments, which were grown in athymic mice as xenografts. Continued propagation using extracts of xenografts permitted growth of additional HPV 59-infected xenografts. CCEs purified from HPV 59-infected xenografts displayed subtle morphologic abnormalities compared to those derived from uninfected xenografts. HPV 59-infected xenografts revealed dysplastic-appearing cells with mitotic figures. Detection of loricrin, involucrin, and cytokeratin 10 was reduced in HPV 59-infected epithelium, while small proline-rich protein 3 (SPR3) was increased. Reduction in loricrin was most apparent in regions of epithelium containing abundant HPV 59 DNA. Compared to uninfected epithelium, loricrin transcription was decreased in HPV 59-infected epithelium. We conclude that HPV 59 shares with HPV 11 the ability to alter CCE components and to specifically reduce transcription of the loricrin gene. Because loricrin is the major CCE protein, a reduction in this component could alter the physical properties of the CCE, thus facilitating virion release

  7. 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...

  8. Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women.

    Science.gov (United States)

    Kim, Seung Cheol; Song, Yong Sang; Kim, Young-Tae; Kim, Young Tak; Ryu, Ki-Sung; Gunapalaiah, Bhavyashree; Bi, Dan; Bock, Hans L; Park, Jong-Sup

    2011-06-30

    The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years. Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout. In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered. The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.).

  9. 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

  10. 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.

  11. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

    Directory of Open Access Journals (Sweden)

    Chang Hun Lee

    Full Text Available Little is known about the epidemiology on human papillomavirus (HPV infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea.A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour.A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM and 68 from men who have sex with women (MSW. Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001. High-risk HPV (HR-HPV prevalence was higher among MSM (47.4% than MSW (25.0%; P = 0.002. The HR-HPV types identified most frequently were HPV 16 (11%, HPV 18 (9.9%, and HPV 58 (5% in MSM, and HPV 58(11% and HPV 16 (8.9% in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001. Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001. In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection.Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

  12. 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 ...

  13. 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.

  14. 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

  15. 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® ...

  16. Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

    International Nuclear Information System (INIS)

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Huei-Jean; Chao, Angel; Chang, Chee-Jen; Chang, Ting-Chang; Chou, Hung-Hsueh; Hong, Ji-Hong

    2010-01-01

    Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy. Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method. Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group. Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration.

  17. 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 ...

  18. Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Naylor, Paul H; Egan, James E; Berinstein, Neil L; Kast, W Martin

    2016-05-01

    Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

  19. Etiological role of human papillomavirus infection for inverted papilloma of the bladder.

    Science.gov (United States)

    Shigehara, Kazuyoshi; Sasagawa, Toshiyuki; Doorbar, John; Kawaguchi, Shohei; Kobori, Yoshitomo; Nakashima, Takao; Shimamura, Masayoshi; Maeda, Yuji; Miyagi, Tohru; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Koh, Eitetsu; Namiki, Mikio

    2011-02-01

    The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. 2010 Wiley-Liss, Inc.

  20. Genotype-Specific Clearance of Genital Human Papillomavirus (HPV) Infections among Mothers in the Finnish Family HPV Study▿

    OpenAIRE

    Louvanto, Karolina; Syrjänen, Kari J.; Rintala, Marjut A. M.; Grénman, Seija E.; Syrjänen, Stina M.

    2010-01-01

    The majority of cervical human papillomavirus (HPV) infections in young women are transient, but whether the clearance differs among different HPV genotypes and the different factors predicting genotype-specific clearance are partly unknown. In the Finnish Family HPV Study, 131 of 252 women (mean age, 25.5 years) cleared their infection during the prospective follow-up of 6 years (median, 62.4 months; range, 1.6 to 94.5 months). Cervical scrapings collected at each visit were tested for 24 lo...

  1. Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

    International Nuclear Information System (INIS)

    Oliveira, Cristina Mendes de; Fregnani, José Humberto Tavares Guerreiro; Carvalho, Jesus Paula; Longatto-Filho, Adhemar; Levi, José Eduardo

    2013-01-01

    Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted

  2. Molecular epidemiology and phylogenetic analysis of human papillomavirus infection in women with cervical lesions and cancer from the coastal region of Ecuador.

    Science.gov (United States)

    Bedoya-Pilozo, Cesar H; Medina Magües, Lex G; Espinosa-García, Maylen; Sánchez, Martha; Parrales Valdiviezo, Johanna V; Molina, Denisse; Ibarra, María A; Quimis-Ponce, María; España, Karool; Párraga Macias, Karla E; Cajas Flores, Nancy V; Orlando, Solon A; Robalino Penaherrera, Jorge A; Chedraui, Peter; Escobar, Saul; Loja Chango, Rita D; Ramirez-Morán, Cecibel; Espinoza-Caicedo, Jasson; Sánchez-Giler, Sunny; Limia, Celia M; Alemán, Yoan; Soto, Yudira; Kouri, Vivian; Culasso, Andrés C A; Badano, Inés

    The aim of the present study was to gather information regarding the molecular epidemiology of Human papillomavirus (HPV) and related risk factors in a group of women with low- and high-grade cervical lesions and cancer from the coastal region of Ecuador. In addition, we studied the evolution of HPV variants from the most prevalent types and provided a temporal framework for their emergence, which may help to trace the source of dissemination within the region. We analyzed 166 samples, including 57 CIN1, 95 CIN2/3 and 14 cancer cases. HPV detection and typing was done by PCR-sequencing (MY09/MY11). HPV variants and estimation of the time to most recent common ancestor (tMRCA) was assessed through phylogeny and coalescence analysis. HPV DNA was found in 54.4% of CIN1, 74.7% of CIN2/3 and 78.6% of cancer samples. HPV16 (38.9%) and HPV58 (19.5%) were the most prevalent types. Risk factors for the development of cervical lesions/cancer were the following: three or more pregnancies (OR=4.3), HPV infection (OR=3.7 for high-risk types; OR=3.5 for HPV16), among others. With regard to HPV evolution, HPV16 isolates belonged to lineages A (69%) and D (31%) whereas HPV58 isolates belonged only to lineage A. The period of emergence of HPV16 was in association with human populations (tMRCA=91052 years for HPV16A and 27000 years for HPV16D), whereas HPV58A preceded Homo sapiens evolution (322257 years). This study provides novel data on HPV epidemiology and evolution in Ecuador, which will be fundamental in the vaccine era. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    DEFF Research Database (Denmark)

    Dreher, Anita; Rossing, Maria; Kaczkowski, Bogumil

    2011-01-01

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

  4. Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme

    Science.gov (United States)

    Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

    2014-01-01

    Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and

  5. Human papillomavirus distribution in invasive cervical carcinoma in sub-Saharan Africa: could HIV explain the differences?

    Science.gov (United States)

    Ndiaye, Cathy; Alemany, Laia; Ndiaye, Nafissatou; Kamaté, Bakarou; Diop, Yankhoba; Odida, Michael; Banjo, Kunbi; Tous, Sara; Klaustermeier, Jo Ellen; Clavero, Omar; Castellsagué, Xavier; Bosch, F Xavier; Trottier, Helen; de Sanjosé, Silvia

    2012-12-01

    To describe human papillomavirus (HPV) distribution in invasive cervical carcinoma (ICC) from Mali and Senegal and to compare type-specific relative contribution among sub-Saharan African (SSA) countries. A multicentric study was conducted to collect paraffin-embedded blocks of ICC. Polymerase chain reaction, DNA enzyme immunoassay and line probe assay were performed for HPV detection and genotyping. Data from SSA (Mozambique, Nigeria and Uganda) and 35 other countries were compared. One hundred and sixty-four ICC cases from Mali and Senegal were tested from which 138 were positive (adjusted prevalence = 86.8%; 95% CI = 79.7-91.7%). HPV16 and HPV18 accounted for 57.2% of infections and HPV45 for 16.7%. In SSA countries, HPV16 was less frequent than in the rest of the world (49.4%vs. 62.6%; P < 0.0001) but HPV18 and HPV45 were two times more frequent (19.3%vs. 9.4%; P < 0.0001 and 10.3%vs. 5.6%; P < 0.0001, respectively). There was an ecological correlation between HIV prevalence and the increase of HPV18 and the decrease of HPV45 in ICC in SSA (P = 0.037 for both). HPV16/18/45 accounted for two-thirds of the HPV types found in invasive cervical cancer in Mali and Senegal. Our results suggest that HIV may play a role in the underlying HPV18 and HPV45 contribution to cervical cancer, but further studies are needed to confirm this correlation. © 2012 Blackwell Publishing Ltd.

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

    Directory of Open Access Journals (Sweden)

    Ferenczy Alex

    2010-11-01

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

  7. The Tetraspanin CD151 in Papillomavirus Infection

    Directory of Open Access Journals (Sweden)

    Konstanze D. Scheffer

    2014-02-01

    Full Text Available Human papillomaviruses (HPV are non-enveloped DNA tumor viruses that infect skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers. During the multistep process of infection, numerous host proteins are required for the delivery of virus genetic information into the nucleus of target cells. Over the last two decades, many host-cell proteins such as heparan sulfate proteoglycans, integrins, growth factor receptors, actin and the tetraspanin CD151 have been described to be involved in the process of infectious entry of HPV16. Tetraspanins have the ability to organize membrane microdomains and to directly influence the function of associated molecules, including binding of receptors to their ligands, receptor oligomerization and signal transduction. Here, we summarize the current knowledge on CD151, and CD151-associated partners during HPV infection and discuss the underlying mechanisms.

  8. 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® ...

  9. Long-Term Stability of Human Genomic and Human Papillomavirus DNA Stored in BD SurePath and Hologic PreservCyt Liquid-Based Cytology Media

    Science.gov (United States)

    Agreda, Patricia M.; Beitman, Gerard H.; Gutierrez, Erin C.; Harris, James M.; Koch, Kristopher R.; LaViers, William D.; Leitch, Sharon V.; Maus, Courtney E.; McMillian, Ray A.; Nussbaumer, William A.; Palmer, Marcus L. R.; Porter, Michael J.; Richart, Gregory A.; Schwab, Ryan J.

    2013-01-01

    We evaluated the effect of storage at 2 to 8°C on the stability of human genomic and human papillomavirus (HPV) DNA stored in BD SurePath and Hologic PreservCyt liquid-based cytology media. DNA retained the ability to be extracted and PCR amplified for more than 2.5 years in both medium types. Prior inability to detect DNA in archived specimens may have been due to failure of the extraction method to isolate DNA from fixed cells. PMID:23678069

  10. 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.

  11. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

    Directory of Open Access Journals (Sweden)

    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

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

    African Journals Online (AJOL)

    Chicago Il, USA). Results: Overall HPV prevalence was 65.2% (277/425), with 85.9% (238/277) single and 14.1% (39/277) multiple infection. The most prevalent HPV types were HPVs 16, 58, 18, 31, and 45. HPV 16 was the most prevalent ...

  13. 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

  14. α-Defensin HD5 Inhibits Human Papillomavirus 16 Infection via Capsid Stabilization and Redirection to the Lysosome

    Directory of Open Access Journals (Sweden)

    Mayim E. Wiens

    2017-01-01

    Full Text Available α-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5 blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition. Instead, HD5 altered HPV trafficking in the cell. In the presence of an inhibitory concentration of HD5, HPV was internalized and reached the early endosome. The internalized capsid became permeable to antibodies and proteases; however, HD5 prevented dissociation of the viral capsid from the genome, reduced viral trafficking to the trans-Golgi network, redirected the incoming viral particle to the lysosome, and accelerated the degradation of internalized capsid proteins. This mechanism is equivalent to the mechanism by which HD5 inhibits human adenovirus. Thus, our data support capsid stabilization and redirection to the lysosome during infection as a general antiviral mechanism of α-defensins against nonenveloped viruses.

  15. 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 ...

  16. 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)

  17. 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

  18. Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population.

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    Full Text Available To investigate the clinicopathological characteristics, human papillomavirus (HPV infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC and determine their utility as prognostic predictors in a primarily eastern Chinese population.The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH in 188 OPSCC samples. p53 expression levels and TP53 gene mutations were assessed through immunohistochemistry and sequencing, respectively. Clinicopathological characteristics and follow-up information were collected. Overall survival was estimated using the Log-rank test.Overall, 22 of the 188 OPSCC samples were associated with HPV infection. HPV16 was identified in all 22 samples, whereas no samples were positive for HPV18. All 22 HPV-associated OPSCC samples were p53 negative and lacked TP53 mutations. HPV16 positivity, female patients, non-smokers, and patients with histological grade I and stage N0 diseases showed better overall survival (p = 0.009, 0.003, 0.048, 0.009, and 0.004, respectively. No significant differences in overall survival between smoking and non-smoking patients were observed in the HPV-associated OPSCC group. Patients without mutations in TP53 exons 5-8 had better prognoses (p = 0.031 among the 43 sequenced specimens. Multivariate analysis indicated that HPV16 infection status (p = 0.011, histological grade (p = 0.017, and N stage (p = 0.019 were independent prognostic factors for patients with OPSCC.Distinct from the situation in Europe and America, for the patients with OPSCC in this study, HPV16 infection was relatively low, although it was still the most important independent prognostic predictor for the disease. In addition to the high smoking and drinking rate in this population, HPV16 infection and TP53 dysfunction appear to be two distinct pathogens for OPSCC patients in the eastern Chinese

  19. Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population.

    Science.gov (United States)

    Wang, Zhen; Xia, Rong-Hui; Ye, Dong-Xia; Li, Jiang

    2016-01-01

    To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population. The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples. p53 expression levels and TP53 gene mutations were assessed through immunohistochemistry and sequencing, respectively. Clinicopathological characteristics and follow-up information were collected. Overall survival was estimated using the Log-rank test. Overall, 22 of the 188 OPSCC samples were associated with HPV infection. HPV16 was identified in all 22 samples, whereas no samples were positive for HPV18. All 22 HPV-associated OPSCC samples were p53 negative and lacked TP53 mutations. HPV16 positivity, female patients, non-smokers, and patients with histological grade I and stage N0 diseases showed better overall survival (p = 0.009, 0.003, 0.048, 0.009, and 0.004, respectively). No significant differences in overall survival between smoking and non-smoking patients were observed in the HPV-associated OPSCC group. Patients without mutations in TP53 exons 5-8 had better prognoses (p = 0.031) among the 43 sequenced specimens. Multivariate analysis indicated that HPV16 infection status (p = 0.011), histological grade (p = 0.017), and N stage (p = 0.019) were independent prognostic factors for patients with OPSCC. Distinct from the situation in Europe and America, for the patients with OPSCC in this study, HPV16 infection was relatively low, although it was still the most important independent prognostic predictor for the disease. In addition to the high smoking and drinking rate in this population, HPV16 infection and TP53 dysfunction appear to be two distinct pathogens for OPSCC patients in the eastern Chinese population.

  20. Expression of Human papillomavirus 16 E7ggg oncoprotein on N- and C-terminus of Potato virus X coat protein in bacterial and plant cells

    Czech Academy of Sciences Publication Activity Database

    Plchová, Helena; Moravec, Tomáš; Hoffmeisterová, Hana; Folwarczna, Jitka; Čeřovská, Noemi

    2011-01-01

    Roč. 77, č. 2 (2011), s. 146-152 ISSN 1046-5928 R&D Projects: GA ČR GA521/09/1525 Institutional research plan: CEZ:AV0Z50380511 Keywords : Bacterial expression * Human papillomavirus * Oncoprotein E7 Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.587, year: 2011

  1. 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.

  2. High prevalence of human papillomavirus infection in American Indian women of the Northern Plains

    Science.gov (United States)

    Bell, Maria C.; Schmidt-Grimminger, Delf; Patrick, Sarah; Ryschon, Tim; Linz, Laurie; Chauhan, Subhash C.

    2008-01-01

    Objectives Cervical cancer is the leading gynecological malignancy worldwide, and the incidence of this disease is very high in American Indian women. Infection with the Human Papillomavirus (HPV) is responsible for more than 95% of cervical squamous carcinomas. Therefore, the main objective of this study was to analyze oncogenic HPV infections in American Indian women residing in the Northern Plains. Methods Cervical samples were collected from 287 women attending a Northern Plains American Indian reservation outpatient clinic. DNA was extracted from the cervical samples and HPV specific DNA were amplified by polymerase chain reaction (PCR) using the L1 consensus primer sets. The PCR products were hybridized with the Roche HPV Line Blot assay for HPV genotyping to detect 27 different low and high-risk HPV genotypes. The chi-square test was performed for statistical analysis of the HPV infection and cytology diagnosis data. Results Of the total 287 patients, 61 women (21.25%) tested positive for HPV infection. Among all HPV-positive women, 41 (67.2%) were infected with high-risk HPV types. Of the HPV infected women, 41% presented with multiple HPV genotypes. Additionally, of the women infected with oncogenic HPV types, 20 (48.7%) were infected with HPV 16 and 18 and the remaining 21 (51.3%) were infected with other oncogenic types (i.e., HPV59, 39, 73). Women infected with oncogenic HPV types had significantly higher (p=0.001) abnormal Papanicolaou smear tests (Pap test) compared to women who were either HPV negative or positive for non-oncogenic HPV types. The incidence of HPV infection was inversely correlated (pIndian women residing on Northern Plains Reservations. In addition, a significant proportion of the oncogenic HPV infections were other than HPV16 and 18. PMID:17659767

  3. 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 recei