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Sample records for human papillomavirus l2

  1. Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies

    PubMed Central

    Wang, Joshua W.; Jagu, Subhashini; Wu, Wai-Hong; Viscidi, Raphael P.; Macgregor-Das, Anne; Fogel, Jessica M.; Kwak, Kihyuck; Daayana, Sai; Kitchener, Henry; Stern, Peter L.; Gravitt, Patti E.; Trimble, Cornelia L.

    2015-01-01

    Presently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen L2-reactive antibody is not well understood, and no serologic standard exists for L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078 serum samples for HPV16 L2 reactivity, and these were obtained from four prior clinical studies: a population-based (n = 880) surveillance study with a high-risk HPV DNA prevalence of 10.8%, a cohort study of women (n = 160) with high-grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod therapy combined with either photodynamic therapy (PDT) (n = 19) or vaccination with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n = 19). Sera were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA) and then Western blot. Seven of the 1,078 serum samples tested had L2-specific antibodies, but none were detectably neutralizing for HPV16. To develop a standard, we substituted human IgG1 sequences into conserved regions of two rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16 L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These chimeric MAbs retained neutralizing activity and together reacted with 33/34 clinically relevant HPV types tested. In conclusion, our inability to identify an HPV16 L2-specific neutralizing antibody response even in the sera of patients with active genital HPV disease suggests the subdominance of L2 protective epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for immunoassays to measure L2-specific human antibodies. PMID:25972404

  2. A protective and broadly cross-neutralizing epitope of human papillomavirus L2.

    PubMed

    Gambhira, Ratish; Karanam, Balasubramanyam; Jagu, Subhashini; Roberts, Jeffrey N; Buck, Christopher B; Bossis, Ioannis; Alphs, Hannah; Culp, Timothy; Christensen, Neil D; Roden, Richard B S

    2007-12-01

    We generated a monoclonal antibody, RG-1, that binds to highly conserved L2 residues 17 to 36 and neutralizes human papillomavirus 16 (HPV16) and HPV18. Passive immunotherapy with RG-1 was protective in mice. Antiserum to the HPV16 L2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses HPV5, HPV6, HPV16, HPV 18, HPV31, HPV 45, HPV 52, HPV 58, bovine papillomavirus 1, and HPV11 native virions. Depletion of HPV16 L2 peptide 17-36-reactive antibodies from cross-neutralizing rabbit and human L2-specific sera abolished cross-neutralization and drastically reduced neutralization of the cognate type. This cross-neutralization of diverse HPVs associated with cervical cancer, genital warts, and epidermodysplasia verruciformis suggests the possibility of a broadly protective, peptide-based vaccine.

  3. Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry.

    PubMed

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

    2015-10-01

    The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the trans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking. In order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

    PubMed Central

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

    2015-01-01

    ABSTRACT The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the trans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking. IMPORTANCE In order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors. PMID:26246568

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

    PubMed Central

    Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil

    2017-01-01

    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 cutaneous

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

    PubMed

    Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil; Kirnbauer, Reinhard

    2017-01-01

    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 cutaneous HPV

  7. Protection of rabbits against challenge with rabbit papillomaviruses by immunization with the N terminus of human papillomavirus type 16 minor capsid antigen L2.

    PubMed

    Gambhira, Ratish; Jagu, Subhashini; Karanam, Balasubramanyam; Gravitt, Patti E; Culp, Timothy D; Christensen, Neil D; Roden, Richard B S

    2007-11-01

    Current L1 virus-like particle (VLP) vaccines provide type-restricted protection against a small subset of the human papillomavirus (HPV) genotypes associated with cervical cancer, necessitating continued cytologic screening of vaccinees. Cervical cancer is most problematic in countries that lack the resources for screening or highly multivalent HPV VLP vaccines, suggesting the need for a low-cost, broadly protective vaccinogen. Here, N-terminal L2 polypeptides comprising residues 1 to 88 or 11 to 200 derived from HPV16, bovine papillomavirus type 1 (BPV1), or cottontail rabbit papillomavirus (CRPV) were produced in bacteria. Rabbits were immunized with these N-terminal L2 polypeptides and concurrently challenged with CRPV and rabbit oral papillomavirus (ROPV). Vaccination with either N-terminal L2 polypeptides of CRPV effectively protected rabbits from CRPV challenge but not from papillomas induced by cutaneous challenge with CRPV genomic DNA. Furthermore, papillomas induced by CRPV genomic DNA deficient for L2 expression grew at the same rate as those induced by wild-type CRPV genomic DNA, further suggesting that the L2 polypeptide vaccines lack therapeutic activity. Neutralizing serum antibody titers of >15 correlated with protection (P < 0.001), a finding consistent with neutralizing antibody-mediated protection. Surprisingly, a remarkable degree of protection against heterologous papillomavirus types was observed after vaccination with N-terminal L2 polypeptides. Notably, vaccination with HPV16 L2 11-200 protected against cutaneous and mucosal challenge with CRPV and ROPV, respectively, papillomaviruses that are evolutionarily divergent from HPV16. Further, vaccination with HPV16 L2 11-200 generates broadly cross-neutralizing serum antibody, suggesting the potential of L2 as a second-generation preventive HPV vaccine antigen.

  8. Factors influencing subcellular localization of the human papillomavirus L2 minor structural protein

    SciTech Connect

    Kieback, Elisa; Mueller, Martin . E-mail: Martin.Mueller@dkfz.de

    2006-02-05

    Two structural proteins form the capsids of papillomaviruses. The major structural protein L1 is the structural determinant of the capsids and is present in 360 copies arranged in 72 pentamers. The minor structural protein L2 is estimated to be present in twelve copies per capsid. Possible roles for L2 in interaction with cell surface receptors and in virion uptake have been suggested. As previously reported, L2 localizes in subnuclear domains identified as nuclear domain 10 (ND10). As it was demonstrated that L2 is able to recruit viral and cellular proteins to ND10, a possible role for L2 as a mediator in viral assembly has been proposed. In this study, we determined factors influencing the localization of L2 at ND10. Under conditions of moderate L2 expression level and in the absence of heterologous viral components, we observed that, in contrast to previous reports, L2 is mainly distributed homogeneously throughout the nucleus. L2, however, is recruited to ND10 at a higher expression level or in the presence of viral components derived from vaccinia virus or from Semliki Forest virus. We observed that translocation of L2 to ND10 is not a concentration-dependent accumulation but rather seems to be triggered by yet unidentified cellular factors. In contrast to HPV 11 and 16 L2, the HPV 18 L2 protein seems to require L1 for efficient nuclear accumulation.

  9. The S100A10 Subunit of the Annexin A2 Heterotetramer Facilitates L2-Mediated Human Papillomavirus Infection

    PubMed Central

    Woodham, Andrew W.; Da Silva, Diane M.; Skeate, Joseph G.; Raff, Adam B.; Ambroso, Mark R.; Brand, Heike E.; Isas, J. Mario; Langen, Ralf; Kast, W. Martin

    2012-01-01

    Mucosotropic, high-risk human papillomaviruses (HPV) are sexually transmitted viruses that are causally associated with the development of cervical cancer. The most common high-risk genotype, HPV16, is an obligatory intracellular virus that must gain entry into host epithelial cells and deliver its double stranded DNA to the nucleus. HPV capsid proteins play a vital role in these steps. Despite the critical nature of these capsid protein-host cell interactions, the precise cellular components necessary for HPV16 infection of epithelial cells remains unknown. Several neutralizing epitopes have been identified for the HPV16 L2 minor capsid protein that can inhibit infection after initial attachment of the virus to the cell surface, which suggests an L2-specific secondary receptor or cofactor is required for infection, but so far no specific L2-receptor has been identified. Here, we demonstrate that the annexin A2 heterotetramer (A2t) contributes to HPV16 infection and co-immunoprecipitates with HPV16 particles on the surface of epithelial cells in an L2-dependent manner. Inhibiting A2t with an endogenous annexin A2 ligand, secretory leukocyte protease inhibitor (SLPI), or with an annexin A2 antibody significantly reduces HPV16 infection. With electron paramagnetic resonance, we demonstrate that a previously identified neutralizing epitope of L2 (aa 108–120) specifically interacts with the S100A10 subunit of A2t. Additionally, mutation of this L2 region significantly reduces binding to A2t and HPV16 pseudovirus infection. Furthermore, downregulation of A2t with shRNA significantly decreases capsid internalization and infection by HPV16. Taken together, these findings indicate that A2t contributes to HPV16 internalization and infection of epithelial cells and this interaction is dependent on the presence of the L2 minor capsid protein. PMID:22927980

  10. Overlapping and Independent Structural Roles for Human Papillomavirus Type 16 L2 Conserved Cysteines

    PubMed Central

    Conway, Michael J.; Alam, Samina; Christensen, Neil D.; Meyers, Craig

    2009-01-01

    Cryoelectron microscopy images of HPV16 pseudovirions (PsV) depict that each pentamer of L1 can be occluded with a monomer of L2. Further research suggests that an N-terminal external loop of L2 exists which is the target of neutralizing and cross-neutralizing antibodies. Here we show that N-terminal L2 cysteine residues, Cys22 and Cys28, have overlapping and independent structural roles which affect both early and late-stage assembly events. Substitution of either cysteine residue enhances infectivity markedly in comparison to wild-type HPV16. However, only Cys22Ser 20-day virions become nearly as stable as wild-type. In addition, Cys22Ser, and Cys22,28Ser 20-day virions have lost their susceptibility to neutralization by anti-L2 antibodies whereas Cys28Ser 20-day virions remain partially susceptible. These results suggest that Cys28 is necessary for late-stage stabilization of capsids while Cys22 is necessary for proper display of L2 neutralizing epitopes. PMID:19733888

  11. In Silico Analysis of L1/L2 Sequences of Human Papillomaviruses: Implication for Universal Vaccine Design.

    PubMed

    Ghorban Hosseini, Nazila; Tebianian, Majid; Farhadi, Ayoub; Hossein Khani, Ali; Rahimi, Arian; Mortazavi, Mojtaba; Hosseini, Seyed Younes; Taghizadeh, Morteza; Rezaei, Mahsa; Mahdavi, Mehdi

    2017-04-01

    The aim of this study was to design a multiepitope universal vaccine for major human papillomavirus (HPV) structural proteins, L1/L2, by bioinformatics models. For this purpose, we predicted the most probable immunogenic epitopes of L1 and L2 from common high-risk HPV 16, 18, 31, and 45 beside high prevalent type 6 and 11 based on BCPREDS defaulted model, while solvent accessibility of structure was extrapolated. The three-dimensional molecular model of L1 protein was constructed by Swiss Model server, whereas sequence alignment provided model for prediction of L2 protein epitopes. After that, N-glycosylation sites were excluded from estimated epitope regions. Then, by other bioinformatics analyses, 20 epitopes were selected and fused in tandem repeats, reverse translated, and codon optimized to relevant sequence. The final protein parameters such as antigenicity were analyzed by protean program. Evaluation of new recombinant protein sequence indicated a molecular weight of 41.8 kDa with 400 amino acids beside positive charge. The computed isoelectric point (pI) value indicated the acidic nature of final product. The aliphatic index showed low thermal stability of this construct and the Grand Average Hydropathicity value was negative (-0.494). Analyzed plot showed that major parts of new protein construct had hydrophilic property, thus harboring antigenic potency. After all, sequence of final construct reverse translated to DNA and this codon-optimized sequence showed Codon Adaptation Index (CAI) of >0.8 for expression in Escherichia coli. Finally, this sequence ligated into pET28a bacterial expression vector. The new recombinant proteins harboring 20 B cell epitope seem to be suitable antigens based on computational methods as a universal vaccine candidate for HPVs.

  12. Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with cervical disease grade in young women.

    PubMed

    Bryant, Dean; Hibbitts, Samantha; Almonte, Maribel; Tristram, Amanda; Fiander, Alison; Powell, Ned

    2015-05-01

    Persistent infection with human papillomavirus (HPV) type 16 causes the majority of cervical cancers. Genital HPV infection is very common, but neoplastic progression is uncommon. There is an urgent need for biomarkers associated with cervical neoplasia, to enable triage of women who test positive for HPV. To assess the ability of quantitative measurement of HPV16 DNA methylation to separate samples of different cytological and histological grades from young women, among whom rates of HPV infection are high. DNA methylation was quantified by pyrosequencing of bisulphite converted DNA from liquid based cytology samples from 234 women (mean age 20.6 years) who tested positive for HPV16 and showed varying degrees of neoplasia. Methylation was assessed at CpGs in the HPV E2 and L1/L2 regions. The performance of methylation-based classifiers was assessed by ROC curve analyses. The best combination of CpGs (5600 and 5609) achieved AUCs of 0.656 (95% CI=0.520-0.792) for separation of cytologically normal and severely dyskaryotic samples, and 0.639 (95% CI=0.547-0.731) for separation of samples with or without high-grade neoplasia (CIN2+/-). The data are consistent with HPV L1/L2 methylation being a marker of the duration of infection in a specific host. Assessment of HPV DNA methylation is hence a promising biomarker to triage HPV-positive cytology samples, but may have limited utility in young women. Future studies assessing the likely utility of HPV DNA methylation as a potential triage biomarker must take account of women's age. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development.

    PubMed

    Khanal, Sujita; Ferraris, Eric Daniel; Zahin, Maryam; Joh, Joongho; Ghim, Shin-je; Jenson, Alfred Bennett

    2015-10-01

    Current vaccines against Human Papillomavirus (HPV) are highly effective and based on recombinant virus-like particles (VLPs) of the major capsid protein L1. Since these vaccines are HPV type-specific and expensive for global implementation, an alternative, broader-spectrum immunogen would be the N-terminus of the minor capsid protein L2 that induces low titered broadly cross-neutralizing antibodies. Here we analyzed the reactivity of different synthetic L2 peptides containing N-terminus amino acids 17-36 in order to test their antigenicity. Different synthetic peptides were designed to target the 17-36 amino acid sequences, present in highly antigenic amino-terminus of L2 protein. Six different peptides including Cys22-Cys28 disulfide bonded cyclized L2 peptide were examined for their antigenicity against mouse monoclonal antibody RG-1 and rabbit polyclonal antisera to HPV L2 by enzyme-linked immunosorbent assay (ELISA). Here we report that the cyclized form of synthetic L2 peptide, which is formed through Cys22-Cys28 disulfide bridges, has the highest reactivity to antibodies than other synthetic L2 peptides. A cyclized L2 peptide has potential to be an excellent candidate to formulate a low-cost, broadly protective pan-oncogenic HPV vaccine. Copyright © 2015. Published by Elsevier Inc.

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

    PubMed

    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.

  15. Cyclophilins Facilitate Dissociation of the Human Papillomavirus Type 16 Capsid Protein L1 from the L2/DNA Complex following Virus Entry

    PubMed Central

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

    2012-01-01

    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. PMID:22761365

  16. Broad Cross-Protection Is Induced in Preclinical Models by a Human Papillomavirus Vaccine Composed of L1/L2 Chimeric Virus-Like Particles.

    PubMed

    Boxus, Mathieu; Fochesato, Michel; Miseur, Agnès; Mertens, Emmanuel; Dendouga, Najoua; Brendle, Sarah; Balogh, Karla K; Christensen, Neil D; Giannini, Sandra L

    2016-07-15

    At least 15 high-risk human papillomaviruses (HPVs) are linked to anogenital preneoplastic lesions and cancer. Currently, there are three licensed prophylactic HPV vaccines based on virus-like particles (VLPs) of the L1 major capsid protein from HPV-2, -4, or -9, including the AS04-adjuvanted HPV-16/18 L1 vaccine. The L2 minor capsid protein contains HPV-neutralizing epitopes that are well conserved across numerous high-risk HPVs. Therefore, the objective of our study was to assess the capacity to broaden vaccine-mediated protection using AS04-adjuvanted vaccines based on VLP chimeras of L1 with one or two L2 epitopes. Several chimeric VLPs were constructed by inserting L2 epitopes within the DE loop and/or C terminus of L1. Based on the shape, yield, size, and immunogenicity, one of seven chimeras was selected for further evaluation in mouse and rabbit challenge models. The chimeric VLP consisted of HPV-18 L1 with insertions of HPV-33 L2 (amino acid residues 17 to 36; L1 DE loop) and HPV-58 L2 (amino acid residues 56 to 75; L1 C terminus). This chimeric L1/L2 VLP vaccine induced persistent immune responses and protected against all of the different HPVs evaluated (HPV-6, -11, -16, -31, -35, -39, -45, -58, and -59 as pseudovirions or quasivirions) in both mouse and rabbit challenge models. The degree and breadth of protection in the rabbit were further enhanced when the chimeric L1/L2 VLP was formulated with the L1 VLPs from the HPV-16/18 L1 vaccine. Therefore, the novel HPV-18 L1/L2 chimeric VLP (alone or in combination with HPV-16 and HPV-18 L1 VLPs) formulated with AS04 has the potential to provide broad protective efficacy in human subjects. From evaluations in human papillomavirus (HPV) protection models in rabbits and mice, our study has identified a prophylactic vaccine with the potential to target a wide range of HPVs linked to anogenital cancer. The three currently licensed vaccines contain virus-like particles (VLPs) of the L1 major capsid protein from

  17. Broad Cross-Protection Is Induced in Preclinical Models by a Human Papillomavirus Vaccine Composed of L1/L2 Chimeric Virus-Like Particles

    PubMed Central

    Boxus, Mathieu; Fochesato, Michel; Miseur, Agnès; Mertens, Emmanuel; Dendouga, Najoua; Brendle, Sarah; Balogh, Karla K.; Christensen, Neil D.

    2016-01-01

    ABSTRACT At least 15 high-risk human papillomaviruses (HPVs) are linked to anogenital preneoplastic lesions and cancer. Currently, there are three licensed prophylactic HPV vaccines based on virus-like particles (VLPs) of the L1 major capsid protein from HPV-2, -4, or -9, including the AS04-adjuvanted HPV-16/18 L1 vaccine. The L2 minor capsid protein contains HPV-neutralizing epitopes that are well conserved across numerous high-risk HPVs. Therefore, the objective of our study was to assess the capacity to broaden vaccine-mediated protection using AS04-adjuvanted vaccines based on VLP chimeras of L1 with one or two L2 epitopes. Several chimeric VLPs were constructed by inserting L2 epitopes within the DE loop and/or C terminus of L1. Based on the shape, yield, size, and immunogenicity, one of seven chimeras was selected for further evaluation in mouse and rabbit challenge models. The chimeric VLP consisted of HPV-18 L1 with insertions of HPV-33 L2 (amino acid residues 17 to 36; L1 DE loop) and HPV-58 L2 (amino acid residues 56 to 75; L1 C terminus). This chimeric L1/L2 VLP vaccine induced persistent immune responses and protected against all of the different HPVs evaluated (HPV-6, -11, -16, -31, -35, -39, -45, -58, and -59 as pseudovirions or quasivirions) in both mouse and rabbit challenge models. The degree and breadth of protection in the rabbit were further enhanced when the chimeric L1/L2 VLP was formulated with the L1 VLPs from the HPV-16/18 L1 vaccine. Therefore, the novel HPV-18 L1/L2 chimeric VLP (alone or in combination with HPV-16 and HPV-18 L1 VLPs) formulated with AS04 has the potential to provide broad protective efficacy in human subjects. IMPORTANCE From evaluations in human papillomavirus (HPV) protection models in rabbits and mice, our study has identified a prophylactic vaccine with the potential to target a wide range of HPVs linked to anogenital cancer. The three currently licensed vaccines contain virus-like particles (VLPs) of the L1 major

  18. A Novel PDZ Domain Interaction Mediates the Binding between Human Papillomavirus 16 L2 and Sorting Nexin 27 and Modulates Virion Trafficking

    PubMed Central

    Broniarczyk, Justyna; Bergant, Martina; Playford, Martin P.; Banks, Lawrence

    2015-01-01

    ABSTRACT Previous studies have demonstrated an interaction between sorting nexin 17 and the L2 capsid proteins from a variety of papillomavirus types. This interaction is required for late endosomal trafficking of the L2 protein and entry of the L2/DNA complex into the nucleus during infection. Here we show an interaction between papillomavirus L2 proteins and the related PX-FERM family member sorting nexin 27 (SNX27), which is mediated in part by a novel interaction between the PDZ domain of SNX27 and sequences in a central portion of L2. The interaction is direct and, unlike that with SNX17, is variable in strength depending on the papillomavirus type. We show that small interfering RNA (siRNA)-mediated knockdown of SNX27 alone leads to a marginal reduction in the efficiency of viral infection but that double knockdown of both sorting nexins results in a striking reduction in infection, greater than that observed for the knockdown of either sorting nexin alone. These results suggest that the HPV L2 proteins can interact through distinct mechanisms with multiple components of the cellular cargo-sorting machinery. IMPORTANCE The trafficking of papillomaviruses to the host cell nucleus during their natural infectious life cycle is an incompletely understood process. Studies have suggested that the virus minor capsid protein L2 can interact with the endosomal recycling pathway, in part by association with sorting nexin 17, to ensure that virus DNA bound to L2 is recycled through the trans-Golgi network rather than back to the plasma membrane. In this study, we characterize the interaction between L2 and a second sorting nexin, SNX27, which is also part of the retromer complex. The study furthers our understanding of papillomavirus infection dynamics and provides potential tools for the further dissection of endosomal structure and function. PMID:26202251

  19. L2, the minor capsid protein of papillomavirus

    SciTech Connect

    Wang, Joshua W.; Roden, Richard B.S.

    2013-10-15

    The capsid protein L2 plays major roles in both papillomavirus assembly and the infectious process. While L1 forms the majority of the capsid and can self-assemble into empty virus-like particles (VLPs), L2 is a minor capsid component and lacks the capacity to form VLPs. However, L2 co-assembles with L1 into VLPs, enhancing their assembly. L2 also facilitates encapsidation of the ∼8 kbp circular and nucleosome-bound viral genome during assembly of the non-enveloped T=7d virions in the nucleus of terminally differentiated epithelial cells, although, like L1, L2 is not detectably expressed in infected basal cells. With respect to infection, L2 is not required for particles to bind to and enter cells. However L2 must be cleaved by furin for endosome escape. L2 then travels with the viral genome to the nucleus, wherein it accumulates at ND-10 domains. Here, we provide an overview of the biology of L2. - Highlights: • L2 is the minor antigen of the non-enveloped T=7d icosahedral Papillomavirus capsid. • L2 is a nuclear protein that can traffic to ND-10 and facilitate genome encapsidation. • L2 is critical for infection and must be cleaved by furin. • L2 is a broadly protective vaccine antigen recognized by neutralizing antibodies.

  20. Human Papillomavirus (HPV) Vaccine

    MedlinePlus

    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 ...

  1. HPV (Human Papillomavirus)

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More ... outside of the body. To Learn More About HPV Human Papillomavirus Vaccine More in For Women Medication ...

  2. [Human papillomaviruses].

    PubMed

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  3. L2, the minor capsid protein of papillomavirus

    PubMed Central

    Wang, Joshua W.; Roden, Richard B.S.

    2013-01-01

    The capsid protein L2 plays major roles in both papillomavirus assembly and the infectious process. While L1 forms the majority of the capsid and can self-assemble into empty virus-like particles (VLPs), L2 is a minor capsid component and lacks the capacity to form VLPs. However, L2 co-assembles with L1 into VLPs, enhancing their assembly. L2 also facilitates encapsidation of the ~8kbp circular and nucleosome-bound viral genome during assembly of the non-enveloped T=7d virions in the nucleus of terminally differentiated epithelial cells, although, like L1, L2 is not detectably expressed in infected basal cells. With respect to infection, L2 is not required for particles to bind to and enter cells. However L2 must be cleaved by furin for endosome escape. L2 then travels with the viral genome to the nucleus, wherein it accumulates at ND-10 domains. Here, we provide an overview of the biology of L2. PMID:23689062

  4. Human papillomavirus molecular biology.

    PubMed

    Harden, Mallory E; Munger, Karl

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

  5. Vaccination against human papillomavirus

    PubMed Central

    Mello, Claudia Figueiredo

    2013-01-01

    ABSTRACT Human papillomavirus infection is common and causes different manifestations. This infection is a public health concern because it has been associated with genital tract malignant diseases among men and women. Currently two vaccines are available to prevent the human papillomavirus infection and its associated diseases. PMID:24488402

  6. Human Papillomavirus (HPV) Vaccines

    MedlinePlus

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV ...

  7. Emerging human papillomavirus vaccines

    PubMed Central

    Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.

    2013-01-01

    Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511

  8. Furin Cleavage of L2 during Papillomavirus Infection: Minimal Dependence on Cyclophilins.

    PubMed

    Bronnimann, Matthew P; Calton, Christine M; Chiquette, Samantha F; Li, Shuaizhi; Lu, Mingfeng; Chapman, Janice A; Bratton, Kristin N; Schlegel, Angela M; Campos, Samuel K

    2016-07-15

    Despite an abundance of evidence supporting an important role for the cleavage of minor capsid protein L2 by cellular furin, direct cleavage of capsid-associated L2 during human papillomavirus 16 (HPV16) infection remains poorly characterized. The conserved cleavage site, close to the L2 N terminus, confounds observation and quantification of the small cleavage product by SDS-PAGE. To overcome this difficulty, we increased the size shift by fusing a compact protein domain, the Propionibacterium shermanii transcarboxylase domain (PSTCD), to the N terminus of L2. The infectious PSTCD-L2 virus displayed an appreciable L2 size shift during infection of HaCaT keratinocytes. Cleavage under standard cell culture conditions rarely exceeded 35% of total L2. Cleavage levels were enhanced by the addition of exogenous furin, and the absolute levels of infection correlated to the level of L2 cleavage. Cleavage occurred on both the HaCaT cell surface and extracellular matrix (ECM). Contrary to current models, experiments on the involvement of cyclophilins revealed little, if any, role for these cellular enzymes in the modulation of furin cleavage. HPV16 L2 contains two consensus cleavage sites, Arg5 (2RHKR5) and Arg12 (9RTKR12). Mutant PSTCD-L2 viruses demonstrated that although furin can cleave either site, cleavage must occur at Arg12, as cleavage at Arg5 alone is insufficient for successful infection. Mutation of the conserved cysteine residues revealed that the Cys22-Cys28 disulfide bridge is not required for cleavage. The PSTCD-L2 virus or similar N-terminal fusions will be valuable tools to study additional cellular and viral determinants of furin cleavage. Furin cleavage of minor capsid protein L2 during papillomavirus infection has been difficult to directly visualize and quantify, confounding efforts to study this important step of HPV infection. Fusion of a small protein domain to the N terminus greatly facilitates direct visualization of the cleavage product

  9. Furin Cleavage of L2 during Papillomavirus Infection: Minimal Dependence on Cyclophilins

    PubMed Central

    Bronnimann, Matthew P.; Calton, Christine M.; Chiquette, Samantha F.; Li, Shuaizhi; Lu, Mingfeng; Chapman, Janice A.; Bratton, Kristin N.; Schlegel, Angela M.

    2016-01-01

    ABSTRACT Despite an abundance of evidence supporting an important role for the cleavage of minor capsid protein L2 by cellular furin, direct cleavage of capsid-associated L2 during human papillomavirus 16 (HPV16) infection remains poorly characterized. The conserved cleavage site, close to the L2 N terminus, confounds observation and quantification of the small cleavage product by SDS-PAGE. To overcome this difficulty, we increased the size shift by fusing a compact protein domain, the Propionibacterium shermanii transcarboxylase domain (PSTCD), to the N terminus of L2. The infectious PSTCD-L2 virus displayed an appreciable L2 size shift during infection of HaCaT keratinocytes. Cleavage under standard cell culture conditions rarely exceeded 35% of total L2. Cleavage levels were enhanced by the addition of exogenous furin, and the absolute levels of infection correlated to the level of L2 cleavage. Cleavage occurred on both the HaCaT cell surface and extracellular matrix (ECM). Contrary to current models, experiments on the involvement of cyclophilins revealed little, if any, role for these cellular enzymes in the modulation of furin cleavage. HPV16 L2 contains two consensus cleavage sites, Arg5 (2RHKR5) and Arg12 (9RTKR12). Mutant PSTCD-L2 viruses demonstrated that although furin can cleave either site, cleavage must occur at Arg12, as cleavage at Arg5 alone is insufficient for successful infection. Mutation of the conserved cysteine residues revealed that the Cys22-Cys28 disulfide bridge is not required for cleavage. The PSTCD-L2 virus or similar N-terminal fusions will be valuable tools to study additional cellular and viral determinants of furin cleavage. IMPORTANCE Furin cleavage of minor capsid protein L2 during papillomavirus infection has been difficult to directly visualize and quantify, confounding efforts to study this important step of HPV infection. Fusion of a small protein domain to the N terminus greatly facilitates direct visualization of the

  10. The human papillomaviruses.

    PubMed

    Orth, G; Jablonska, S; Breitburd, F; Favre, M; Croissant, O

    1978-01-01

    Recent biochemical and serological studies have shown the existence of at least four distinct types of human papillomaviruses (HPVs) causing benign skin lesions. These viruses show hardly no antigenic relationships; their DNAs differ by their sensitivity to restriction endonucleases, and show little, if any, sequence homology, as detected by molecular hybridization using complementary RNAs transcribed in vitro. Data on the pathogenicity of HPVs are still incomplete but indicate that some types of benign skin lesions (plantar warts, common warts, flat warts) may be preferentially associated with some types of HPV. Most interesting is that epidermodysplasia verruciformis has been found associated with two types of virus, and that malignant conversion of some lesions has been observed in all the patients infected with one of them. This suggests that at least a HPV may have a higher oncogenic potential, as do rabbit (Shope) papillomavirus and bovine alimentary tract papillomavirus. Much remains to be known on human papilloma-viruses and further studies may lead to the characterization of additional types of HPVs, especially in genital condylomata acuminata and laryngeal papillomas whose malignant conversion, although rare, may be observed. Progress in this field has been and remains hampered by the lack of cell culture systems allowing replication of these highly host and tissue specific viruses, and by the widely variable virus content of the different human lesions known to be associated with a papillomavirus. Further studies are warranted by the possible role of these widespread and epitheliotropic viruses in the origin of some carcinomas in man.

  11. Papillomaviruses and human disease

    SciTech Connect

    Syrjanen, K.; Gissman, L.; Koss, L.G.

    1987-01-01

    This book contains 17 selections. Some of the titles are: Papillomaviruses: particles, genome organization and proteins; Physical state of papillomavirus DNA in tumors; Transforming and regulatory functions of bovine papillomavirus Type 1; and Transcription of papillomavirus genomes.

  12. Methylation of human papillomavirus 16, 18, 31, and 45 L2 and L1 genes and the cellular DAPK gene: Considerations for use as biomarkers of the progression of cervical neoplasia.

    PubMed

    Kalantari, Mina; Osann, Kathryn; Calleja-Macias, Itzel E; Kim, Seong; Yan, Bing; Jordan, Sara; Chase, Dana M; Tewari, Krishnansu S; Bernard, Hans-Ulrich

    2014-01-05

    During progression of cervical cancer, human papillomavirus genomes and cellular tumor suppressor genes can become methylated. Toward a better understanding of these biomarkers, we studied 104 samples with HPV16, 18, 31, and 45 representing five pathological categories from asymptomatic infection to cancer. We grouped all samples by HPV type and pathology and measured the overall methylation of informative amplicons of HPV late genes and the cellular DAPK gene. Methylation of all four HPV types as well as of the DAPK gene is lowest in asymptomatic infection and increases successively in all four pathological categories during progression to cancer. 27 out of 28 cancer samples showed methylation both in the L2/L1 genes as well as in DAPK, but a much lower fraction in all other pathological categories. We discuss the problem to develop diagnostic tests based on complex methylation patterns that make it difficult to classify amplicons as "methylated" or "unmethylated".

  13. A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types

    PubMed Central

    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. PMID:24802101

  14. Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes.

    PubMed

    Kalnin, Kirill; Tibbitts, Timothy; Yan, Yanhua; Stegalkina, Svetlana; Shen, Lihua; Costa, Victor; Sabharwal, Robert; Anderson, Stephen F; Day, Patricia M; Christensen, Neil; Schiller, John T; Jagu, Subhashini; Roden, Richard B S; Almond, Jeffrey; Kleanthous, Harold

    2014-06-12

    Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV 'pseudovirions' encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a. 11(×11-200) or oligomeric L2 comprising a fusion of the a.a. 11-88 peptides of five (Fla∼5×11-88) or eight (Fla∼8×11-88) genital HPV types. Immunogenicity and bioactivity of Fla-L2 constructs were assessed using an in vitro neutralization and cell-based TLR-5 binding assay, respectively. Efficacy was evaluated following active immunization of rabbits or mice administered 3 intramuscular doses of Fla-L2 recombinants without exogenous adjuvant, followed by challenge. In addition, passive immunization studies of naïve rabbits with serial dilutions of pooled immune sera were used to determine End-Point Protection Titers (EPPT) for each formulation against a broader spectrum of HPV quasivirions. Efficacy was assessed for up to 10 weeks on the basis of wart volume induced following challenge and results compared to licensed L1-VLP vaccines (Gardasil and Cervarix). Following active immunization at doses as low as 1 μg, Fla-L2 fusions afforded complete protection against infection (mice) and disease (rabbits) following either homologous or heterologous HPV challenge. Passive immunization with anti-L2 immune sera discriminated between the different vaccine candidates under evaluation, demonstrated the protective role of antibody and suggested the superiority of this oligomeric L2-TLR5 agonist fusion approach compared to L1-based

  15. Oncogenic human papillomaviruses.

    PubMed

    McBride, Alison A

    2017-10-19

    Human papillomaviruses (HPVs) are an ancient group of viruses with small, double-stranded DNA circular genomes. They are species-specific and have a strict tropism for mucosal and cutaneous stratified squamous epithelial surfaces of the host. A subset of these viruses has been demonstrated to be the causative agent of several human cancers. Here, we review the biology, natural history, evolution and cancer association of the oncogenic HPVs.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  16. Oncogenic human papillomaviruses

    PubMed Central

    2017-01-01

    Human papillomaviruses (HPVs) are an ancient group of viruses with small, double-stranded DNA circular genomes. They are species-specific and have a strict tropism for mucosal and cutaneous stratified squamous epithelial surfaces of the host. A subset of these viruses has been demonstrated to be the causative agent of several human cancers. Here, we review the biology, natural history, evolution and cancer association of the oncogenic HPVs. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893940

  17. Immunohistochemical detection of Human Papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: Potential utility in diagnosis and management

    PubMed Central

    Yemelyanova, A; Gravitt, PE; Ronnett, BM; Rositch, AF; Ogurtsova, A; Seidman, JD; Roden, RBS

    2012-01-01

    While cervical cancer screening relies on cervical cytology and high-risk HPV detection, histologic diagnosis, and specifically lesion grade, is the main parameter that drives clinical management of screen-positive women. Morphologically diagnosed squamous intraepithelial lesions (SIL/CIN) regress spontaneously in more than half of the cases, but identifying those likely to persist and progress is not currently possible based upon morphology. Lack of major capsid protein L1 expression has been suggested as a feature in progressive lesions, while expression of the minor capsid protein L2 has not been extensively evaluated. The goal of this study is to evaluate immunohistochemical expression of L1 and L2 in SILs in correlation with lesion grade. One hundred fifty cervical specimens with SILs were selected based on HPV 16 or HPV 18 detection by Q-PCR. These included 89 low-grade SILs (LSIL/CIN1) and 123 high-grade SILs (75 HSIL/CIN2 and 48 HSIL/CIN3). More than one lesion/grade was identified in 53 specimens. The presence and grade of SIL was determined by a panel of pathologists. Capsid protein expression was assessed by immunohistochemistry using MAB 837 for L1 and RG-1 for L2. Lesions of different grades in the same specimen were scored separately. Expression of capsid proteins was detected in 34/89 (40%) LSIL/CIN1, 5/75 (6%) HSIL/CIN2 and none of 48 HSIL/CIN3. L1 and L2 were co-expressed in the same area of the lesion in 22 cases. In addition, L1 alone was expressed in 6 lesions and L2 alone in 11 lesions. Among the cases with multiple lesion grades in the same specimen, none with HSIL/CIN 3 expressed capsid proteins in any portion/grade of the lesion. HPV capsid proteins are expressed almost exclusively in LSIL/CIN1 and rarely in HSIL/CIN 2. Additional studies are warranted to examine lack of L1 and L2 expression in LSIL/CIN1 as a predictor of persistence or progression to HSIL/CIN 3, the precursor of cervical cancer. PMID:22996373

  18. Human papillomavirus and cervical cancer.

    PubMed

    Crosbie, Emma J; Einstein, Mark H; Franceschi, Silvia; Kitchener, Henry C

    2013-09-07

    Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

  19. [Network Research on Human Papillomavirus].

    PubMed

    Almeida-Gutiérrez, Eduardo; Paniagua, Ramón; Furuya, María ElenaYuriko

    2015-01-01

    In order to increase the research in important health questions at a national and institutional levels, the Human Papillomavirus Research Network of the Health Research Coordination of the Instituto Mexicano del Seguro Social offers this supplement with the purpose of assisting patients that daily look for attention due to the human papillomavirus or to cervical cancer.

  20. Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection.

    PubMed

    Karanam, Balasubramanyam; Jagu, Subhashini; Huh, Warner K; Roden, Richard B S

    2009-01-01

    A subset of human papillomavirus (HPV) genotypes is responsible for approximately 5% of all cancer deaths globally, and uterine cervical carcinoma accounts for the majority of these cases. The impact of HPV is greatest for women who do not have access to effective secondary preventive measures, and consequently over 80% of cervical cancer deaths worldwide occur in developing nations. The understanding that persistent infection by this 'oncogenic' subset of HPV genotypes is necessary for the development of cervical carcinoma has driven the development of preventive vaccines. Two preventive vaccines comprising recombinant HPV L1 virus-like particles (VLPs) have been licensed. However, the current cost of these vaccines precludes sustained global delivery, and they target only two of the approximately 15 known oncogenic HPV types, although approximately 70% of cervical cancer cases are attributed to these two types and there is evidence for some degree of cross-protection against other closely related types. A possible approach to broader immunity at lower cost is to consider vaccination against L2. L2 vaccines can be produced inexpensively and they also have the promise of conferring much broader cross-type protective immunity than that observed with L1 VLP immunization. However, L2 vaccine development lags behind L1 VLP vaccines and several technical hurdles remain.

  1. Serum antibody response to Human papillomavirus (HPV) infections detected by a novel ELISA technique based on denatured recombinant HPV16 L1, L2, E4, E6 and E7 proteins

    PubMed Central

    Di Bonito, Paola; Grasso, Felicia; Mochi, Stefania; Accardi, Luisa; Donà, Maria Gabriella; Branca, Margherita; Costa, Silvano; Mariani, Luciano; Agarossi, Alberto; Ciotti, Marco; Syrjänen, Kari; Giorgi, Colomba

    2006-01-01

    Background Human papillomaviruses (HPVs) are the primary etiological agents of cervical cancer and are also involved in the development of other tumours (skin, head and neck). Serological survey of the HPV infections is important to better elucidate their natural history and to disclose antigen determinants useful for vaccine development. At present, the analysis of the HPV-specific antibodies has not diagnostic value for the viral infections, and new approaches are needed to correlate the antibody response to the disease outcome. The aim of this study is to develop a novel ELISA, based on five denatured recombinant HPV16 proteins, to be used for detection HPV-specific antibodies. Methods The HPV16 L1, L2, E4, E6 and E7 genes were cloned in a prokaryotic expression vector and expressed as histidine-tagged proteins. These proteins, in a denatured form, were used in ELISA as coating antigens. Human sera were collected from women with abnormal PAP smear enrolled during an ongoing multicenter HPV-PathogenISS study in Italy, assessing the HPV-related pathogenetic mechanisms of progression of cervical cancer precursor lesions. Negative human sera were collected from patients affected by other infectious agents. All the HPV-positive sera were also subjected to an avidity test to assess the binding strength in the antigen-antibody complexes. Results Most of the sera showed a positive reactivity to the denatured HPV16 proteins: 82% of the sera from HPV16 infected women and 89% of the sera from women infected by other HPV genotypes recognised at least one of the HPV16 proteins. The percentages of samples showing reactivity to L1, L2 and E7 were similar, but only a few serum samples reacted to E6 and E4. Most sera bound the antigens with medium and high avidity index, suggesting specific antigen-antibody reactions. Conclusion This novel ELISA, based on multiple denatured HPV16 antigens, is able to detect antibodies in women infected by HPV16 and it is not genotype

  2. [Papillomaviruses and human tumors].

    PubMed

    Vonka, V; Hamsíková, E; Sobotková, E; Smahel, M; Kitasato, H; Sainerová, H; Ludvíková, V; Zák, R; Kanka, J; Kolár, Z; Kovarík, J

    2000-12-01

    The report summarizes the main results obtained in the course of our research project. The results of immunological and epidemiological studies provide further proofs that human papillomaviruses (HPV) are the etiological agents in cervical neoplasia. In addition, they raise hopes that immunological methods may be utilized in diagnostics of cervical cancer and for monitoring the clinical course of this disease in the near future. Since the etiological relationship between HPV and cervical carcinoma seems to be proven beyond reasonable doubt, the development of prophylactic and therapeutic vaccines has become the dominant of the contemporary HPV reseach. For studying immune reactions against HPV-induced tumours we developed a model of HPV16-transformed rodent cells.

  3. Protective immunity to rabbit oral and cutaneous papillomaviruses by immunization with short peptides of L2, the minor capsid protein.

    PubMed

    Embers, Monica E; Budgeon, Lynn R; Pickel, Martin; Christensen, Neil D

    2002-10-01

    The papillomavirus minor capsid protein, L2, has been shown to exhibit immunogenicity, whereby a variety of B-cell epitopes, predominantly in the amino terminus of L2, have been deduced. However, immunity to L2 in vivo has not been examined extensively. Notably, a common neutralization epitope for human papillomavirus (HPV) types 6 and 16 was mapped to amino acids (aa) 108 to 120. The objectives of this study were to derive antisera from rabbits using the corresponding sequences from rabbit viruses and to assess the ability of these peptides to protect against infection. Synthetic peptides consisting of two overlapping sequences each in the region of aa 94 to 122 of the rabbit oral (ROPV) and cottontail rabbit (CRPV) papillomaviruses were used to immunize rabbits. Rabbits were then infected with both ROPV and CRPV and monitored for the development of oral and cutaneous papillomas, respectively. Serum derived from rabbits immunized with either of the two peptides was shown to (i) react to purified L2 from the cognate virus, (ii) specifically recognize L2 within virus-infected cells, and (iii) neutralize virus in vitro. Following viral challenge, cutaneous papilloma growth was completely absent in rabbits immunized with either CRPV peptide. Likewise, ROPV peptide-immunized rabbits were protected from oral papillomatosis. Challenge of CRPV peptide-immune rabbits with the viral genome resulted in efficient papilloma growth, suggesting a neutralizing antibody-mediated mechanism of protection. These results afford in vivo evidence for the immunogenicity provided by a distinct region of L2 and further support previous evidence for the ability of this region to elicit antiviral immunity.

  4. Replication and Assembly of Human Papillomaviruses

    PubMed Central

    Conway, M.J.; Meyers, C.

    2009-01-01

    Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the major capsid protein, L1. The minor capsid protein L2 associates with L1 pentamers, although it is not known if each L1 pentamer contains a single L2 protein. The HPV life cycle strictly adheres to the host cell differentiation program, and as such, native HPV virions are only produced in vivo or in organotypic “raft” culture. Research producing synthetic papillomavirus particles—such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors, known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions (QV)—has bypassed the need for stratifying and differentiating host tissue in viral assembly and has allowed for the rapid analysis of HPV infectivity pathways, transmission, immunogenicity, and viral structure. PMID:19407149

  5. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    MedlinePlus

    ... Search Form Controls Cancel Submit Search the CDC Human Papillomavirus (HPV) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Human Papillomavirus (HPV) Facts & Brochures HPV Fact Sheet HPV & ...

  6. Carcinogenic human papillomavirus infection.

    PubMed

    Schiffman, Mark; Doorbar, John; Wentzensen, Nicolas; de Sanjosé, Silvia; Fakhry, Carole; Monk, Bradley J; Stanley, Margaret A; Franceschi, Silvia

    2016-12-01

    Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge.

  7. [Human papillomavirus prophylactic vaccine].

    PubMed

    Kawana, Kei

    2012-06-01

    Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.

  8. Human papillomavirus vaccine development.

    PubMed

    Fife, K H

    1998-11-01

    The greatest successes in combating important viral infections have been achieved using vaccines. A vaccine to prevent genital tract human papillomavirus (HPV) infections, especially those types associated with genital tract malignancy, could significantly reduce morbidity and mortality from cervical and other genital tract cancers. However, several barriers currently stand in the way of HPV vaccine development. The immunological response to natural HPV infection is incompletely understood and there is uncertainty about which viral antigen(s) should be included in a candidate vaccine. It is clear that immunization of several animal species with the L1 major capsid protein (usually in the form of virus-like particles) spurs the production of anti-HPV antibodies that are neutralizing in several assay systems. However, it is not clear if neutralizing antibody will be present in the genital tract in sufficient quantities to block infection. A second problem is the lack of a reliable serological assay for HPV. This is a major problem for clinical trials in which the identification of susceptible individuals, and incident infections, usually relies on serological diagnosis. Finally, there is also interest in the development of a vaccine that is used to treat individuals who are already infected--a therapeutic vaccine. It is likely that a therapeutic vaccine will need to target different or additional antigens to those comprising a prophylactic vaccine.

  9. Genital human papillomavirus infection.

    PubMed Central

    Lowy, D R; Kirnbauer, R; Schiller, J T

    1994-01-01

    Genital human papillomavirus (HPV) infection is a common sexually transmitted disease that at the present time is not effectively controlled or treated. Many infections are inapparent and transient. However, some HPV infections result in persistent lesions that in some cases undergo carcinogenic progression. A subset of genital HPVs, designated high-risk types, are preferentially associated with high-grade dysplasias and carcinomas. About 90% of cervical cancers contain high-risk HPV DNA, most often HPV16. Development of a subunit vaccine against high-risk genital HPVs is a desirable and, it appears, an increasingly feasible long-term goal. The viral E6 and E7 oncoproteins are selectively maintained and expressed in progressed HPV tumors and could potentially be targets for therapeutic vaccines. The L1 major virion structural proteins have recently been shown to self-assemble into virus-like particles when expressed in insect cells. These particles might serve as the basis for a prophylactic vaccine to prevent genital HPV infection. Images PMID:8146136

  10. Human papillomaviruses and cancer.

    PubMed

    Haedicke, Juliane; Iftner, Thomas

    2013-09-01

    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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Human Papillomavirus Vaccine

    PubMed Central

    Savas, Lara S.; Fernández, Maria E.; Jobe, David; Carmack, Chakema C.

    2012-01-01

    Background Research is needed to understand parental factors influencing human papillomavirus (HPV) vaccination, particularly in groups with a higher burden of cervical cancer. Purpose To determine correlates of HPV vaccination among a sample of low-income parents of age-eligible daughters (aged 9–17 years) who called the 2-1-1 Helpline. Secondary analyses describe potential differences in HPV vaccination correlates by Hispanic and black parent groups, specifically. Methods This 2009 cross-sectional feasibility survey of cancer prevention needs was conducted in Houston at the 2-1-1 Texas/United Way Helpline. In 2012, to examine the association between parental psychosocial, cognitive, and decisional factors and HPV vaccination uptake (one or two doses), bivariate and multivariable logistic regression analyses were conducted for minority parents and for Hispanic and black parent groups, separately. Results Lower rates of HPV vaccination uptake were reported among minority daughters of 2-1-1 callers (29% overall) compared with national and Texas rates. In final adjusted analysis, factors positively associated with HPV vaccination uptake included being offered the vaccination by a doctor or nurse, belief that the vaccine would prevent cervical cancer, and Hispanic ethnicity. Secondary analyses detected differences in factors associated with vaccination in Hispanic and black groups. Conclusions Findings indicate low levels of vaccination among 2-1-1 callers. Increased understanding of determinants of HPV vaccination in low-income minority groups can guide interventions to increase coverage. Because 2-1-1 informational and referral services networks reach populations considered medically underserved, 2-1-1 can serve as a community hub for informing development of and implementing approaches aimed at hard-to-reach groups. PMID:23157770

  12. Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

    PubMed

    Calton, Christine M; Bronnimann, Matthew P; Manson, Ariana R; Li, Shuaizhi; Chapman, Janice A; Suarez-Berumen, Marcela; Williamson, Tatum R; Molugu, Sudheer K; Bernal, Ricardo A; Campos, Samuel K

    2017-05-01

    The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.

  13. Effective vaccination against papilloma development by immunization with L1 or L2 structural protein of cottontail rabbit papillomavirus.

    PubMed

    Lin, Y L; Borenstein, L A; Selvakumar, R; Ahmed, R; Wettstein, F O

    1992-04-01

    Immunization of rabbits with either L1, the major structural protein, or L2, a minor structural protein of cottontail rabbit papillomavirus (CRPV), protected against challenge with the virus. Neutralizing antibodies were elicited by both the L1 and L2 trpE fusion proteins. Neutralization with anti-L1 serum, however, was more efficient than with anti-L2 serum. In contrast, when tested on Western blots the immune response to L2 was stronger than to L1. Rabbits were also protected against CRPV infection by immunization with L1 expressing recombinant vaccinia virus. Sera from two of three rabbits immunized with recombinant vaccinia virus were negative on Western blots but all three were positive in ELISA's with nondenatured fusion protein or in immunoprecipitations. The results suggest that both the viral structural proteins, L1 and L2, merit consideration in the development of a vaccine against papillomavirus.

  14. Oral Human Papillomavirus Infection in Children.

    PubMed

    Ilea, Aranka; Boşca, Bianca; Miclăuş, Viorel; Rus, Vasile; Băbţan, Anida Maria; Mesaros, Anca; Crişan, Bogdan; Câmpian, Radu Septimiu

    2016-02-01

    Oral human papillomavirus infection is rare in children, but the presence of a villous lesion with slow but continuous growth concerns parents, who need information and therapeutic solutions from the physician. All these aspects are discussed based on a case report of a 9-year-old child with an oral human papillomavirus infection.

  15. Human papillomaviruses in epigenetic regulations.

    PubMed

    Durzynska, Julia; Lesniewicz, Krzysztof; Poreba, Elzbieta

    Human Papillomaviruses (HPVs) are double-stranded DNA viruses, that infect epithelial cells and are etiologically involved in the development of human cancer. Today, over 200 types of human papillomaviruses are known. They are divided into low-risk and high-risk HPVs depending on their potential to induce carcinogenesis, driven by two major viral oncoproteins, E6 and E7. By interacting with cellular partners, these proteins are involved in interdependent viral and cell cycles in stratified differentiating epithelium, and concomitantly induce epigenetic changes in infected cells and those undergoing malignant transformation. E6 and E7 oncoproteins interact with and/or modulate expression of many proteins involved in epigenetic regulation, including DNA methyltransferases, histone-modifying enzymes and subunits of chromatin remodeling complexes, thereby influencing host cell transcription program. Furthermore, HPV oncoproteins modulate expression of cellular micro RNAs. Most of these epigenetic actions in a complex dynamic interplay participate in the maintenance of persistent infection, cell transformation, and development of invasive cancer by a considerable deregulation of tumor suppressor and oncogenes. In this study, we have undertaken to discuss a number of studies concerning epigenetic regulations in HPV-dependent cells and to focus on those that have biological relevance to cancer progression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Epigenetics of human papillomaviruses

    SciTech Connect

    Johannsen, Eric; Lambert, Paul F.

    2013-10-15

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

  17. [Apoptosis modulation by human papillomavirus].

    PubMed

    Jave-Suárez, Luis Felipe; Ratkovich-González, Sarah; Olimón-Andalón, Vicente; Aguilar-Lemarroy, Adriana

    2015-01-01

    One of the most important processes to keep the homeostasis in organisms is the apoptosis, also called programmed cell death. This mechanism works through two pathways: The intrinsic or mitochondrial, which responds to DNA damage and extern agents like UV radiation; and the extrinsic or receptor-mediated, which binds to their ligands to initiate the apoptotic trail. The evasion of apoptosis is one of the main causes of cellular transformation to malignity. Many viruses had shown capacity to modify the apoptotic process; among them is the human papillomavirus, which, by means of its oncoproteins, interferes in pathways, reacting with the receptors and molecules and participating in the death mechanism. This creates ideal conditions for cancer development.

  18. Monitoring of human papillomavirus vaccination.

    PubMed

    Dillner, J; Arbyn, M; Unger, E; Dillner, L

    2011-01-01

    Persistent infection with oncogenic human papillomavirus (HPV) is a necessary causal factor in the development of cervical cancer. Moreover, HPV, predominately type 16 and to a lesser degree type 18, is linked causally to varying proportions of other anogenital cancers (vulva, vagina, penis, anus) as well as cancers elsewhere in the body (oropharynx, larynx, conjunctiva). HPV types 6 and 11 cause most of genital warts and recurrent respiratory papillomatosis. Effective prophylactic vaccines have been developed. In this review, we address briefly the immunological aspects of HPV infection and the results of HPV vaccination trials. Internationally standardized monitoring and evaluation of prophylactic HPV vaccination programmes will be essential for arriving at the most cost-effective strategies for cancer control. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

  19. Monitoring of human papillomavirus vaccination

    PubMed Central

    Dillner, J; Arbyn, M; Unger, E; Dillner, L

    2011-01-01

    Persistent infection with oncogenic human papillomavirus (HPV) is a necessary causal factor in the development of cervical cancer. Moreover, HPV, predominately type 16 and to a lesser degree type 18, is linked causally to varying proportions of other anogenital cancers (vulva, vagina, penis, anus) as well as cancers elsewhere in the body (oropharynx, larynx, conjunctiva). HPV types 6 and 11 cause most of genital warts and recurrent respiratory papillomatosis. Effective prophylactic vaccines have been developed. In this review, we address briefly the immunological aspects of HPV infection and the results of HPV vaccination trials. Internationally standardized monitoring and evaluation of prophylactic HPV vaccination programmes will be essential for arriving at the most cost-effective strategies for cancer control. PMID:21062269

  20. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Cancer.gov

    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.

  1. Identification of human papillomavirus in pterygium.

    PubMed

    Hamed-Azzam, Shirin; Edison, Natalia; Briscoe, Daniel; Mukari, Abed; Elmalah, Irit

    2016-05-01

    The purpose of this study was to evaluate the involvement of human papillomavirus in the pathogenesis of primary and recurrent pterygium in northern Israel. A retrospective study examined 100 randomly chosen pterygium specimens with solar elastosis, from 100 patients who underwent pterygium surgery during 2012-2013 at the Emek Medical Center. All the specimens were analysed for evidence of human papillomavirus infection by immunohistochemistry. Human papillomavirus was not detected in any of the 100 pterygia samples by immunohistochemistry. These used samples were taken from 100 patients with mean age of 51.5 years and a primary: recurrent ratio of 8.09:1. We conclude from our study that human papillomavirus infection does not appear to be an important pathogenic factor of pterygium in Israel. © 2015 Emek Medical Center.

  2. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    Cancer.gov

    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

    Cancer.gov

    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. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    Cancer.gov

    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.

  5. Human papillomaviruses-related cancers

    PubMed Central

    Al Moustafa, Ala-Eddin; Al-Awadhi, Rana; Missaoui, Nabiha; Adam, Ishag; Durusoy, Raika; Ghabreau, Lina; Akil, Nizar; Ahmed, Hussain Gadelkarim; Yasmeen, Amber; Alsbeih, Ghazi

    2014-01-01

    Human papillomavirus (HPV) infections are estimated to be the most common sexually transmitted infections worldwide. Meanwhile, it is well established that infection by high-risk HPVs is considered the major cause of cervical cancer since more than 96% of these cancers are positive for high-risk HPVs, especially types 16 and 18. Moreover, during the last 2 decades, numerous studies pointed-out the possible involvement of high-risk HPV in several human carcinomas including head and neck, colorectal and breast cancers. The association between high-risk HPVs and cervical cancer and potentially other human malignancies would necessitate the introduction of vaccines which were generated against the 2 most frequent high-risk HPVs (types 16 and 18) worldwide, including the Middle East (ME) as well as North African countries. The presence of high-risk HPVs in the pathogenesis of human cancers in the ME, which is essential in order to evaluate the importance of vaccination against HPVs, has not been fully investigated yet. In this review, we present an overview of the existing epidemiological evidence regarding the presence of HPV in human cancers in the ME and the potential impact of vaccination against HPV infections and its outcome on human health in this region. PMID:25424787

  6. Evidence and Impact of Human Papillomavirus Latency

    PubMed Central

    Gravitt, Patti E

    2012-01-01

    At present, there is no consensus in the scientific community regarding the ability for human papillomavirus (HPV) infections to establish latency. Based on animal studies, a model of papillomavirus latency has been proposed in which papillomaviruses can be retained in the basal epithelial stem cell pool as latent infections and periodically induced to reactivate when the stem cell divides and one daughter cell is committed to terminal differentiation and induction of the viral life cycle. Tissue resident memory T-cells are hypothesized to control these periodic reactivation episodes and thus limit their duration. In this paper, evidence from human studies consistent with this model of papillomavirus latency is reviewed. Given the strong circumstantial evidence supporting a natural history of HPV infection which includes a immunologically controlled latent state, the longer term implications of HPV latency on a highly infected and aging population may warrant a more serious evaluation. PMID:23341855

  7. Bovine and human papillomaviruses: a comparative review.

    PubMed

    Munday, J S

    2014-11-01

    Fifty years ago, inoculation with bovine papillomavirus (BPV) was found to cause mesenchymal tumors of the skin in cattle and horses, as well as tumors of the bladder in cattle. Subsequent to these studies of BPVs, human papillomaviruses (HPVs) were found to cause cervical cancer resulting in intense research into papillomaviruses. During the past 50 years, the ways that HPVs and BPVs cause disease have been investigated, and both HPVs and BPVs have been associated with an increasingly diverse range of diseases. Herein, the biology, oncogenic mechanisms, and diseases associated with BPVs are compared with those of HPVs. As reviewed, there are currently significant differences between BPVs and HPVs. However, research 50 years ago into BPVs formed a prologue for the recognition that papillomaviruses have a significant role in human disease, and it is possible that future research may similarly reveal that BPVs are less different from HPVs than is currently recognized. © The Author(s) 2014.

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

    MedlinePlus

    ... taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/ ... statements/hpv.html . CDC review information for HPV (Human Papillomavirus) VIS: Page last reviewed: December 2, 2016 ...

  9. Evolutionary and structural analyses of alpha-papillomavirus capsid proteins yields novel insights into L2 structure and interaction with L1

    PubMed Central

    Lowe, John; Panda, Debasis; Rose, Suzanne; Jensen, Ty; Hughes, Willie A; Tso, For Yue; Angeletti, Peter C

    2008-01-01

    Background PVs (PV) are small, non-enveloped, double-stranded DNA viruses that have been identified as the primary etiological agent for cervical cancer and their potential for malignant transformation in mucosal tissue has a large impact on public health. The PV family Papillomaviridae is organized into multiple genus based on sequential parsimony, host range, tissue tropism, and histology. We focused this analysis on the late gene products, major (L1) and minor (L2) capsid proteins from the family Papillomaviridae genus Alpha-papillomavirus. Alpha-PVs preferentially infect oral and anogenital mucosa of humans and primates with varied risk of oncogenic transformation. Development of evolutionary associations between PVs will likely provide novel information to assist in clarifying the currently elusive relationship between PV and its microenvironment (i.e., the single infected cell) and macro environment (i.e., the skin tissue). We attempt to identify the regions of the major capsid proteins as well as minor capsid proteins of alpha-papillomavirus that have been evolutionarily conserved, and define regions that are under constant selective pressure with respect to the entire family of viruses. Results This analysis shows the loops of L1 are in fact the most variable regions among the alpha-PVs. We also identify regions of L2, involved in interaction with L1, as evolutionarily conserved among the members of alpha- PVs. Finally, a predicted three-dimensional model was generated to further elucidate probable aspects of the L1 and L2 interaction. PMID:19087355

  10. Human papillomaviruses and skin cancer.

    PubMed

    Smola, Sigrun

    2014-01-01

    Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

  11. Human Papillomavirus and Cervical Cancer

    PubMed Central

    Burd, Eileen M.

    2003-01-01

    Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results. PMID:12525422

  12. Human papillomavirus in oral lesions.

    PubMed

    González, Joaquín V; Gutiérrez, Rafael A; Keszler, Alicia; Colacino, Maria del Carmen; Alonio, Lidia V; Teyssie, Angelica R; Picconi, Maria Alejandra

    2007-01-01

    Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR) using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.

  13. Human Papillomaviruses: Genetic Basis of Carcinogenicity

    PubMed Central

    Burk, Robert D.; Chen, Zigui; Van Doorslaer, Koenraad

    2009-01-01

    Persistent infection by specific oncogenic human papillomaviruses (HPVs) is established as the necessary cause of cervix cancer. DNA sequence differences between HPV genomes determine whether an HPV has the potential to cause cancer. Of the more than 100 HPV genotypes characterized at the genetic level, at least 15 are associated, to varying degrees, with cervical cancer. Classification based on nucleotide similarity places nearly all HPVs that infect the cervicovaginal area within the α-PV genus. Within this genus, phylogenetic trees inferred from the entire viral genome cluster all cancer-causing types together, suggesting the existence of a common ancestor for the oncogenic HPVs. However, in separate trees built from the early open reading frames (ORFs; i.e. E1, E2, E6, E7) or the late ORFs (i.e. L1, L2), the carcinogenic potential sorts with the early region of the genome, but not the late region. Thus, genetic differences within the early region specify the pathogenic potential of α-HPV infections. Since the HPV genomes are monophyletic and sites are highly correlated across the genome, diagnosis of oncogenic types and non-oncogenic types can be accomplished using any region across the genome. Here we review our current understanding of the evolutionary history of the oncogenic HPVs, in particular, we focus on the importance of viral genome heterogeneity and discuss the genetic basis for the oncogenic phenotype in some but not all α-PVs. PMID:19684441

  14. Global challenges of implementing human papillomavirus vaccines.

    PubMed

    Graham, Janice E; Mishra, Amrita

    2011-06-30

    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. Global challenges of implementing human papillomavirus vaccines

    PubMed Central

    2011-01-01

    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. PMID:21718495

  16. Production of Furin-Cleaved Papillomavirus Pseudovirions and Their Use for In Vitro Neutralization Assays of L1- or L2-Specific Antibodies.

    PubMed

    Wang, Joshua W; Matsui, Ken; Pan, Yuanji; Kwak, Kihyuck; Peng, Shiwen; Kemp, Troy; Pinto, Ligia; Roden, Richard B S

    2015-08-03

    Immunization with Human Papillomavirus (HPV) L1 virus-like particles or L2 capsid protein elicits neutralizing antibodies that mediate protection. A high-throughput and sensitive in vitro neutralization assay is therefore valuable for prophylactic HPV vaccine studies. Over several hours during infection of the genital tract, virions take on a distinct intermediate conformation, including a required furin cleavage of L2 at its N-terminus. This intermediate is an important target for neutralization by L2-specific antibody, but it is very transiently exposed during in vitro infection of most cell lines resulting in insensitive measurement for L2, but not L1-specific neutralizing antibodies. To model this intermediate, we describe a protocol to generate furin-cleaved HPV pseudovirions (fc-PsV), which deliver an encapsidated reporter plasmid to facilitate infectivity measurements. We also describe a protocol for use of fc-PsV in a high-throughput in vitro neutralization assay for the sensitive measurement of both L1 and L2-specific neutralizing antibodies.

  17. Production of Furin-cleaved Papillomavirus Pseudovirions and their use for in vitro neutralization assays of L1 or L2-specific antibodies

    PubMed Central

    Wang, Joshua W; Matsui, Ken; Pan, Yuanji; Kwak, Kihyuck; Peng, Shiwen; Kemp, Troy; Pinto, Ligia; Roden, Richard B.S

    2015-01-01

    Immunization with Human Papillomavirus (HPV) L1 virus-like particles or L2 capsid protein elicits neutralizing antibodies that mediate protection. A high throughput and sensitive in vitro neutralization assay is therefore valuable for prophylactic HPV vaccine studies. Over several hours during infection of the genital tract, virions take on a distinct intermediate conformation, including a required furin cleavage of L2 at its N-terminus. This intermediate is an important target for neutralization by L2-specific antibody, but it is very transiently exposed during in vitro infection of most cell lines resulting in insensitive measurement for L2, but not L1-specific neutralizing antibodies. To model this intermediate, we describe a protocol to generate furin-cleaved HPV pseudovirions (fc-PsV) which deliver an encapsidated reporter plasmid to facilitate infectivity measurements. We also describe a protocol for use of fc-PsV in a high throughput in vitro neutralization assay for the sensitive measurement of both L1 and L2-specific neutralizing antibodies. PMID:26237105

  18. Genetic alterations by human papillomaviruses in oncogenesis.

    PubMed

    Lazo, P A; Gallego, M I; Ballester, S; Feduchi, E

    1992-03-30

    The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.

  19. Lichenoid drug eruption after human papillomavirus vaccination.

    PubMed

    Laschinger, Mary E; Schleichert, Rachel A; Green, Brian

    2015-01-01

    Lichenoid drug reactions have been linked to a long and growing list of medications, most of which are used mainly in adults, making these reactions exceedingly rare in children. To the best of our knowledge, this case report is the first of a lichenoid drug eruption in a child after human papillomavirus vaccination.

  20. Four historic legends in human papillomaviruses research.

    PubMed

    Mammas, Ioannis N; Spandidos, Demetrios A

    2015-01-01

    Human papillomaviruses (HPVs) infection and HPVs-associated lesions, including skin warts in children and adults and cervical neoplasia in women, have been excessively studied since ancient years. In our article, we present briefly four major researchers from the HPVs pre-vaccination historic period: Hippokrates the Asclepiad, Domenico Antonio Rigoni-Stern, George N. Papanicolaou and Harald zur Hausen.

  1. Human Papillomavirus: A Catalyst to a Killer

    ERIC Educational Resources Information Center

    Richman, Alice

    2005-01-01

    Genital human papillomavirus (HPV) is the most prevalent and widespread sexually transmitted disease and is responsible for almost all cases of cervical cancer worldwide. However, HPV has received little public health attention, is not a reportable STD, and often is absent from the repertoire of STDs. In addition, there is pervasive misinformation…

  2. In vitro generation and type-specific neutralization of a human papillomavirus type 16 virion pseudotype.

    PubMed Central

    Roden, R B; Greenstone, H L; Kirnbauer, R; Booy, F P; Jessie, J; Lowy, D R; Schiller, J T

    1996-01-01

    We report a system for generating infectious papillomaviruses in vitro that facilitates the analysis of papillomavirus assembly, infectivity, and serologic relatedness. Cultured hamster BPHE-1 cells harboring autonomously replicating bovine papillomavirus type 1 (BPV1) genomes were infected with recombinant Semliki Forest viruses that express the structural proteins of BPV1. When plated on C127 cells, extracts from cells expressing L1 and L2 together induced numerous transformed foci that could be specifically prevented by BPV neutralizing antibodies, demonstrating that BPV infection was responsible for the focal transformation. Extracts from BPHE-1 cells expressing L1 or L2 separately were not infectious. Although Semliki Forest virus-expressed L1 self-assembled into virus-like particles (VLPs), viral DNA was detected in particles only when L2 was coexpressed with L1, indicating that genome encapsidation requires L2. Expression of human papillomavirus type 16 (HPV16) L1 and L2 together in BPHE-1 cells also yielded infectious virus. These pseudotyped virions were neutralized by antiserum to HPV16 VLPs derived from European (114/K) or African (Z-1194) HPV16 variants but not by antisera to BPV VLPs, to a poorly assembling mutant HPV16 L1 protein, or to VLPs of closely related genital HPV types. Extracts from BPHE-1 cells coexpressing BPV L1 and HPV16 L2 or HPV16 L1 and BPV L2 were not infectious. We conclude that (i) mouse C127 cells express the cell surface receptor for HPV16 and are able to uncoat HPV16 capsids; (ii) if a papillomavirus DNA packaging signal exists, then it is conserved between the BPV and HPV16 genomes; (iii) functional L1-L2 interaction exhibits type specificity; and (iv) protection by HPV virus-like particle vaccines is likely to be type specific. PMID:8709207

  3. Human Alpha and Beta Papillomaviruses Use Different Synonymous Codon Profiles

    PubMed Central

    Cladel, Nancy M.; Bertotto, Alex; Christensen, Neil D.

    2013-01-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field. PMID:20157772

  4. Human alpha and beta papillomaviruses use different synonymous codon profiles.

    PubMed

    Cladel, Nancy M; Bertotto, Alex; Christensen, Neil D

    2010-06-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study, we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field.

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

    PubMed

    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.

  6. Target Cell Cyclophilins Facilitate Human Papillomavirus Type 16 Infection

    PubMed Central

    Sapp, Martin

    2009-01-01

    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. PMID:19629175

  7. Epidemiology of oral human papillomavirus infection

    PubMed Central

    Chung, Christine H.; Bagheri, Ashley; D'Souza, Gypsyamber

    2013-01-01

    Human papillomavirus (HPV) infection is known to cause a subset of oropharyngeal cancers. Data regarding oral HPV infection is limited but emerging. HPV infection of the genital tract has been more thoroughly researched and helps inform our understanding of oral HPV infection. In this article we review current data on HPV prevalence, natural history, mode of acquisition, and risk factors for oral HPV infection. PMID:24080455

  8. Human Papillomavirus in Head and Neck Cancer

    PubMed Central

    Garbuglia, Anna Rosa

    2014-01-01

    Human papillomavirus (HPV) is currently considered to be a major etiologic factor, in addition to tobacco and alcohol, for oropharyngeal cancer (OPC) development. HPV positive OPCs are epidemiologically distinct from HPV negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. HPV16 is the most prevalent types in oral cavity cancer (OCC), moreover the prevalence of beta, and gamma HPV types is higher than that of alpha HPV in oral cavity. PMID:25256828

  9. Animal papillomaviruses.

    PubMed

    Rector, Annabel; Van Ranst, Marc

    2013-10-01

    We provide an overview of the host range, taxonomic classification and genomic diversity of animal papillomaviruses. The complete genomes of 112 non-human papillomavirus types, recovered from 54 different host species, are currently available in GenBank. The recent characterizations of reptilian papillomaviruses extend the host range of the Papillomaviridae to include all amniotes. Although the genetically diverse papillomaviruses have a highly conserved genomic lay-out, deviations from this prototypic genome organization are observed in several animal papillomaviruses, and only the core ORFs E1, E2, L2 and L1 are present in all characterized papillomavirus genomes. The discovery of papilloma-polyoma hybrids BPCV1 and BPCV2, containing a papillomaviral late region but an early region encoding typical polyomaviral nonstructural proteins, and the detection of recombination breakpoints between the early and late coding regions of cetacean papillomaviruses, could indicate that early and late gene cassettes of papillomaviruses are relatively independent entities that can be interchanged by recombination. © 2013 Elsevier Inc. All rights reserved.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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. Characterization of human antibody-reactive epitopes encoded by human papillomavirus types 16 and 18.

    PubMed Central

    Jenison, S A; Yu, X P; Valentine, J M; Galloway, D A

    1991-01-01

    We have previously reported that the most common human serum immunoglobulin G antibody reactivities to human papillomavirus type 16 and type 18 (HPV16 and HPV18)-encoded proteins are directed against the minor capsid proteins (HPV16 L2 and HPV18 L2) and to the E7 protein of HPV16 (S. A. Jenison, X.-P. Yu, J. M. Valentine, L. A. Koutsky, A. E. Christiansen, A. M. Beckmann, and D. A. Galloway, J. Infect. Dis. 162:60-69, 1990). In this study, the antibody-reactive segments of the HPV16 E7, HPV16 L2, and HPV18 L2 polypeptides were mapped by using nested sets of deleted recombinant proteins. A single major immunoreactive region was identified in the HPV16 E7 polypeptide between amino acids (aa) 21 and 34 (DLYCYE-QLNDSSEE). In contrast, three distinct immunoreactive regions of the HPV16 L2 polypeptide were present in the segment between aa149 and aa204, and three distinct immunoreactive regions of the HPV18 L2 polypeptide were present in the segment between aa110 and aa211. With the exception of one serum sample, serum immunoglobulin G antibodies which reacted with HPV16 L2 polypeptides or with HPV18 L2 polypeptides were not cross-reactive. Images PMID:1704924

  13. Evidence of Human Papillomavirus in the Placenta

    PubMed Central

    Weyn, Christine; Thomas, Dominique; Jani, Jacques; Guizani, Meriem; Donner, Cathérine; Van Rysselberge, Michel; Hans, Christine; Bossens, Michel; Englert, Yvon

    2011-01-01

    Human papillomavirus (HPV) is an epitheliotropic virus typically infecting keratinocytes but also possibly epithelial trophoblastic placental cells. In the present study, we set out to investigate whether HPV can be recovered from transabdominally obtained placental cells to avoid any confounding contamination by HPV-infected cervical cells. Thirty-five placental samples from women undergoing transabdominal chorionic villous sampling were analyzed, and we detected HPV-16 and HPV-62 in 2 placentas. This study suggests that HPV infection of the placenta can occur early in pregnancy. The overall clinical implication of these results remains to be elucidated. PMID:21208925

  14. Clinical significance of human papillomavirus genotyping.

    PubMed

    Choi, Youn Jin; Park, Jong Sup

    2016-03-01

    Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV's significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping.

  15. Human Papillomavirus Entry: Hiding in a Bubble.

    PubMed

    DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Sapp, Martin

    2016-09-15

    Incoming human papillomavirus (HPV) utilize vesicular transport to traffic from the plasma membrane to the trans-Golgi network. Following nuclear envelope breakdown during mitosis, the viral DNA associates with condensed chromosomes utilizing spindle microtubules for delivery. Most intriguingly, the viral DNA resides in a transport vesicle until mitosis is completed and the nuclear envelope has reformed. This finding provides support for the transient existence of nuclear membrane-bound vesicles. Due to their transient nature, it also points to the existence of a cell pathway for the disposal of vesicles ending up fortuitously or purposefully in the nucleus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Human Papillomavirus Entry: Hiding in a Bubble

    PubMed Central

    DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata

    2016-01-01

    Incoming human papillomavirus (HPV) utilize vesicular transport to traffic from the plasma membrane to the trans-Golgi network. Following nuclear envelope breakdown during mitosis, the viral DNA associates with condensed chromosomes utilizing spindle microtubules for delivery. Most intriguingly, the viral DNA resides in a transport vesicle until mitosis is completed and the nuclear envelope has reformed. This finding provides support for the transient existence of nuclear membrane-bound vesicles. Due to their transient nature, it also points to the existence of a cell pathway for the disposal of vesicles ending up fortuitously or purposefully in the nucleus. PMID:27412595

  17. The human papillomavirus E7 oncoprotein

    SciTech Connect

    McLaughlin-Drubin, Margaret E. Muenger, Karl

    2009-02-20

    The human papillomavirus (HPV) E7 oncoprotein shares functional similarities with such proteins as adenovirus E1A and SV40 large tumor antigen. As one of only two viral proteins always expressed in HPV-associated cancers, E7 plays a central role in both the viral life cycle and carcinogenic transformation. In the HPV viral life cycle, E7 disrupts the intimate association between cellular differentiation and proliferation in normal epithelium, allowing for viral replication in cells that would no longer be in the dividing population. This function is directly reflected in the transforming activities of E7, including tumor initiation and induction of genomic instability.

  18. Human Papillomavirus: What Every Provider Should Know

    PubMed Central

    Erickson, Britt K.; Alvarez, Ronald D.; Huh, Warner K.

    2012-01-01

    Persistence of Human Papillomavirus (HPV) infection is necessary for the development of cervical cancer. Additionally, infection with HPV is implicated in the majority of cases of other genital tract malignancies including vulvar, penile, and vaginal cancer. HPV testing and vaccination are a routine part of OB/GYN clinical practice. With an enhanced public awareness of HPV infections, many patients turn to their OB/GYN with questions about transmission, testing and prevention. In this review, we will discuss the biology of HPV, epidemiology of disease, methods and indications for testing, and vaccination strategies. PMID:23021131

  19. [Infection therapeutic modalities in human papillomavirus].

    PubMed

    Carrillo Pacheco, Adia; Hernández Valencia, Marcelino; Hernández Quijano, Tomás; Zárate, Arturo

    2012-11-01

    Human papillomavirus (HPV) genital it can infect any mucous of the body and to cause cancer of the uterine cervix. Until recently specific treatments did not exist on this infection, for what had to destroy or to remove the injured tissue by diverse procedures, what could have obstetric repercussions in young women. Recently some surgical modalities and topical drugs have arisen, as well as of systemic employment that allow to arrive to the lesions difficult to approach, and have demonstrated good effectiveness to cure the infection for HPV, for what an analysis of the medical treatment of this infection type is made.

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

    PubMed Central

    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

  1. Human papillomavirus types and recurrent cervical warts

    SciTech Connect

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

    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.

  2. Improving Human Papillomavirus Vaccinations in Military Women.

    PubMed

    Wedel, Sarah; Navarrete, Rebecca; Burkard, Joseph F; Clark, Mary Jo

    2016-10-01

    The purpose of this evidence-based project was to provide patient education to increase human papillomavirus (HPV) vaccination rates in military women. Despite the availability of a vaccine, HPV continues to be the most common sexually transmitted infection in the United States. The goal of this program was to increase patient knowledge and HPV vaccination rates by providing education and a verbal recommendation for vaccination during regularly scheduled well-woman exams. The project resulted in a 65% increase in vaccination rates, raising the preprogram vaccination rate of 55% to a postintervention vaccine percentage of 91%. The results demonstrate the importance of patient education and provider recommendation in vaccine acceptance. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  3. Human papillomavirus oncoproteins and apoptosis (Review)

    PubMed Central

    JIANG, PEIYUE; YUE, YING

    2014-01-01

    The aim of this study was to review the literature and identify the association between human papillomavirus (HPV) oncoproteins and apoptosis. HPV-associated apoptosis may be primarily blocked by a number of oncoproteins, including E5, E6 and E7. E5 protein protects cells from tumor necrosis factor-associated apoptosis; the oncoprotein E6 predominantly inhibits apoptosis through the p53 pathway; and oncoprotein E7 is involved in apoptosis activation and inhibition. In addition, HPV oncoproteins are involved in activating or repressing the transcription of E6/E7. In conclusion, HPV oncoproteins, including E5, E6 and E7 protein, may interfere with apoptosis via certain regulatory principles. PMID:24348754

  4. Oral contraceptives, human papillomavirus and cervical cancer.

    PubMed

    La Vecchia, Carlo; Boccia, Stefania

    2014-03-01

    Oncogenic human papillomavirus is the key determinant of cervical cancer, but other risk factors interact with it to define individual risk. Among these, there is oral contraceptive (OC) use. A quantitative review of the link between OCs and cervical cancer was performed. Long-term (>5 year) current or recent OC use has been related to an about two-fold excess risk of cervical cancer. Such an excess risk, however, levels off after stopping use, and approaches unity 10 or more years after stopping. The public health implications of OC use for cervical cancer are limited. In any case, such implications are greater in middle-income and low-income countries, as well as in central and eastern Europe and Latin America, where cervical cancer screening and control remain inadequate.

  5. Duty to Advocate: Human Papillomavirus Vaccination

    PubMed Central

    Nichols, Kristen; Girotto, Jennifer; Steele, Amy Mitchell-Van; Stoffella, Sylvia

    2017-01-01

    Despite the excellent benefit-to-risk ratio for human papillomavirus (HPV) vaccination and recommendations for its routine use from the Advisory Committee on Immunization Practices (ACIP), significant controversy surrounding HPV vaccination continues to exist. In light of this controversy and continued low rates of vaccination among U.S. adolescents, the Pediatric Pharmacy Advocacy Group (PPAG) endorses the safety and efficacy of HPV vaccination and agrees with ACIP recommendations for protection of the U.S. population against the potentially severe consequences of HPV. The PPAG recommends that all eligible individuals undergo vaccination. We further recommend that pediatric pharmacists participate in the education of patients and their families and serve as advocates for HPV vaccination. This document serves as an update to the 2008 PPAG position statement.1 PMID:28337085

  6. Human papillomavirus and gastrointestinal cancer: A review

    PubMed Central

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  7. Therapy of cutaneous human Papillomavirus infections.

    PubMed

    Rivera, Allison; Tyring, Stephen K

    2004-01-01

    Human Papillomaviruses (HPV) are double-stranded DNA viruses, which result in a variety of clinical manifestations according to type. The most common cutaneous lesions include warts located on the skin and genitalia. Because there is currently no cure for HPV infection, treatment focuses on the alleviation of signs and symptoms. Unfortunately, therapy has not been proved to affect transmissibility. Traditional treatment modalities have focused on the destruction of infected tissue through a variety of techniques. These include podophyllin resin, podophyllotoxin, salicylic acid, trichloroacetic acid, bichloroacetic acid, cryotherapy, laser, and surgical techniques. None of these modalities have been proved to be superior. More recently, immunomodulatory compounds with antiviral properties have demonstrated superior efficacy with clearance rates up to 77% and low recurrence rates. Most importantly, clinical trials of vaccines to prevent acquisition of oncogenic HPV are demonstrating marked safety and efficacy.

  8. New treatments for human papillomavirus infection.

    PubMed

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

    2013-12-01

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

  9. Duty to Advocate: Human Papillomavirus Vaccination.

    PubMed

    Nichols, Kristen; Girotto, Jennifer; Steele, Amy Mitchell-Van; Stoffella, Sylvia

    2017-01-01

    Despite the excellent benefit-to-risk ratio for human papillomavirus (HPV) vaccination and recommendations for its routine use from the Advisory Committee on Immunization Practices (ACIP), significant controversy surrounding HPV vaccination continues to exist. In light of this controversy and continued low rates of vaccination among U.S. adolescents, the Pediatric Pharmacy Advocacy Group (PPAG) endorses the safety and efficacy of HPV vaccination and agrees with ACIP recommendations for protection of the U.S. population against the potentially severe consequences of HPV. The PPAG recommends that all eligible individuals undergo vaccination. We further recommend that pediatric pharmacists participate in the education of patients and their families and serve as advocates for HPV vaccination. This document serves as an update to the 2008 PPAG position statement.1.

  10. Systematic review of human papillomavirus vaccine coadministration.

    PubMed

    Noronha, Alinea S; Markowitz, Lauri E; Dunne, Eileen F

    2014-05-13

    Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

  11. [Human papillomavirus prophylactic vaccines: stakes and perspectives].

    PubMed

    Hantz, S; Alain, S; Denis, F

    2006-01-01

    Human Papillomavirus (HPV) infection is established as the necessary cause of cervical precancers and cancers. To date, more than 120 genotypes are known, but only high risk oncogen genotypes could induce a cancer. HPV 16 and 18 are implied in nearly 70% of cervical cancer around the world. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections providing an opportunity for cervical cancer prevention through vaccination. Candidate prophylactic vaccines based on papillomavirus L1 virus-like particles (VLPs) are currently on human clinical trials: one targeting cervical cancer with a bivalent VLP L1 vaccine containing the two genotypes most frequently involved in cervical cancer (type 16 and 18) and the other, protecting against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine containing genotypes 6, 11, 16 and 18. The first clinical trials revealed the satisfactory tolerance and excellent immunogenicity of these vaccines inducing high serum antibody titers with minimal side effects. After more than three years, both clinical trials on women 15 to 25 years old have shown that vaccines are able to type specifically protect against nearly 90% of infection and all cervical intra-epithelial neoplasia. The vaccinal strategy defined to date targets preadolescents and adolescent young females (11-13 years) before the first sexual course but some questions are still not resolved concerning the prescriber, the actors of the vaccination and the duration of the protection. Nevertheless cervical cancer screening should be carried on for many years, even if a large vaccinal strategy is decided. Such a vaccine would save lives and reduce the need for costly medical procedures and the psychological stress induced by this cancer.

  12. Human papillomavirus molecular biology and disease association

    PubMed Central

    Egawa, Nagayasu; Griffin, Heather; Kranjec, Christian; Murakami, Isao

    2015-01-01

    Summary Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co‐evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High‐risk E6 and E7 proteins differ from their low‐risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high‐risk HPV infection. Most work to date has focused on the study of high‐risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low‐risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25752814

  13. Nuclear Localization but Not PML Protein Is Required for Incorporation of the Papillomavirus Minor Capsid Protein L2 into Virus-Like Particles

    PubMed Central

    Becker, Katrin A.; Florin, Luise; Sapp, Cornelia; Maul, Gerd G.; Sapp, Martin

    2004-01-01

    Recent reports suggest that nuclear domain(s) 10 (ND10) is the site of papillomavirus morphogenesis. The viral genome replicates in or close to ND10. In addition, the minor capsid protein, L2, accumulates in these subnuclear structures and recruits the major capsid protein, L1. We have now used cell lines deficient for promyelocytic leukemia (PML) protein, the main structural component of ND10, to study the role of this nuclear protein for L2 incorporation into virus-like particles (VLPs). L2 expressed in PML protein knockout (PML−/−) cells accumulated in nuclear dots, which resemble L2 aggregates forming at ND10 in PML protein-containing cells. These L2 assemblies also attracted L1 and the transcriptional repressor Daxx, suggesting that they are functional in the absence of PML protein. In addition, L2-containing VLPs assembled in PML−/− cells. In order to analyze whether incorporation of L2 into VLPs requires any specific subcellular localization, an L1 mutant defective for nuclear transport and L2 mutants deficient in nuclear translocation and/or ND10 localization were constructed. Using this approach, we identified two independent L2 domains interacting with L1. Mutant L2 proteins not accumulating in ND10 were incorporated into VLPs. Mutant L1 protein, which assembled into VLPs in the cytoplasm, did not incorporate L2 defective for nuclear translocation. The same mutant L2 protein, which passively diffuses into the nucleus, is incorporated into wild-type L1-VLPs in the nucleus. Our data demonstrate that the incorporation of L2 into VLPs requires nuclear but not ND10 localization. PMID:14722267

  14. Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma.

    PubMed

    Saito, Yuki; Yoshida, Masafumi; Omura, Go; Kobayashi, Kenya; Fujimoto, Chisato; Ando, Mizuo; Sakamoto, Takashi; Asakage, Takahiro; Yamasoba, Tatsuya

    2015-09-01

    In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan. Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus. In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status. p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status. © The Author 2015. Published by Oxford University Press. All rights reserved

  15. Site of infections associated with human papillomavirus.

    PubMed

    Beltrão, Monique; Wanderley, Marcela Silvestre Outtes; de Santana, Nataly Amorim; Bruneska, Danyelly; de Lima Filho, José Luiz

    2015-03-01

    Human papillomavirus (HPV) is the most clinically common sexually transmitted infection due to its carcinogenic power and the high number of lesions that it causes at different sites of the human body. Genital tract organs are the most common sites where the virus can be found, but by increasing the sensitivity of diagnostic technique, it is possible to identify viral presence in different regions of the body such as the stomach, the lung, and the urinary tract. These findings break with the traditional HPV skin/genital tropic profile and demonstrate that the virus is capable of infecting a wide variety of cells, tissues, and organs or can, at least, survive in these areas. The widespread presence of the HPV in the human body, often in latent form, led us to consider the hypothesis that HPV latency may be associated with no disease. This observation raises further questions about the possibility of the virus not causing disease in specific sites of the human body, but rather, behaving like a commensal/opportunistic microorganism.

  16. Negative emotions and stigma associated with a human papillomavirus test result: A comparison between human papillomavirus-positive men and women.

    PubMed

    Daley, Ellen M; Vamos, Cheryl A; Wheldon, Christopher W; Kolar, Stephanie K; Baker, Elizabeth A

    2015-08-01

    Human papillomavirus has largely been framed as a women's health issue, and the psychosocial impact of human papillomavirus among men remains unclear. In this study, we found that women infected with human papillomavirus (n = 154) experienced a greater degree of negative emotions and stigma than human papillomavirus-infected men (n = 190). Among women, younger age and less education were associated with greater expression of negative emotions and stigma. Conversely, being single was significantly associated with a greater degree of negative emotions and stigma beliefs among men. These findings suggest the need to re-frame messages that both men and women receive regarding human papillomavirus. © The Author(s) 2013.

  17. [General aspects of structure, classification and replication of human papillomavirus].

    PubMed

    Santos-López, Gerardo; Márquez-Domínguez, Luis; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2015-01-01

    Human papillomavirus (HPV) refers to a group of viruses which belongs to a larger group, commonly referred to as papillomaviruses. These viruses are taxonomically located in the Papillomaviridae family. Papillomaviruses are small, non-enveloped with a genome of double-stranded DNA and they have affinity for epithelial tissue. Many of them are associated with human infection; they induce benign lesions of the skin (warts) and mucous membranes (condylomas), but they are also associated with some epithelial malignancies, such as cervical cancer and other tumors of the urogenital tract. Papillomaviridae contains 16 genera, which are named with a Greek letter prefix and the termination papillomavirus, e.g., Alphapapillomavirus, Betapapillomavirus, etcetera. From the clinical point of view, human papillomaviruses infecting the genital tract (which are located in the genus Alphapapilomavirus) have been divided into two groups: those of low risk, associated with benign genital warts, and those of high risk, with oncogenic potential, which are the etiological agents of cervical cancer. In this paper we review some relevant aspects of the structure, replication cycle and classification of human papillomaviruses.

  18. Oropharyngeal perinatal colonization by human papillomavirus.

    PubMed

    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.

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

    PubMed

    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.

  20. The natural history of human papillomavirus infection.

    PubMed

    de Sanjosé, Silvia; Brotons, Maria; Pavón, Miguel Angel

    2017-09-06

    Human papillomavirus (HPV) is a small double-stranded DNA virus that commonly infects humans. The oncogenic characteristics of HPV derive from the oncoproteins E6 and E7 that act inhibiting p53 and pRB tumor suppressors. About 5% of all cancers worldwide are attributable mainly to those known as high-risk, including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Infection with HPV is common after sexual initiation, but the majority of HPV infections do not cause symptoms or disease and are cleared within 12-24 months post-infection. Only a small fraction of those infections that persist or progress to a preneoplastic lesion result in cancer. Persistence of HPV infection is needed to start the oncogenic process. Clearance of infection is common in young adults. Viral load and viral type are the main cofactors for progression from infection to cervical intraepithelial lesions and cancer. Smoking, hormonal exposure, and HIV are additional exposures that increase the risk of progression to cancer. The adverse health effects of HPV infections can be largely controlled through vaccination and screening. Copyright © 2017. Published by Elsevier Ltd.

  1. Immunoprevention of human papillomavirus-associated malignancies

    PubMed Central

    Wang1, Joshua W.; Hung, Chein-fu; Huh, Warner K.; Trimble, Cornelia L.; Roden, Richard B.S.

    2014-01-01

    Persistent infection by one of fifteen high risk human papillomavirus (hrHPV) types is a necessary but not sufficient cause of 5% of all human cancers. This provides a remarkable opportunity for cancer prevention via immunization. Since Harald zur Hausen’s pioneering identification of hrHPV types 16 and 18, found in ~50% and ~20% of cervical cancers respectively, two prophylactic HPV vaccines containing virus-like particles (VLP) of each genotype have been widely licensed. These vaccines are beginning to impact infection and HPV-associated neoplasia rates after immunization campaigns in adolescents. Here we review recent progress and opportunities to better prevent HPV-associated cancers, including: broadening immune-protection to cover all hrHPV types, reducing the cost of HPV vaccines especially for developing countries that have the highest rates of cervical cancer, and immune-based treatment of established HPV infections. Screening based upon George Papanicolaou’s cervical cytology testing, and more recently detection of hrHPV DNA/RNA, followed by ablative treatment of high grade cervical intraepithelial neoplasia (CIN2/3) have substantially reduced cervical cancer rates, and we examine their interplay with immune-based modalities for the prevention and eventual elimination of cervical cancer and other HPV-related malignancies. PMID:25488410

  2. Role of human papillomaviruses in carcinogenesis

    PubMed Central

    Ghittoni, Raffaella; Accardi, Rosita; Chiocca, Susanna; Tommasino, Massimo

    2015-01-01

    The human papillomavirus (HPV) family comprises more than 170 different types that preferentially infect the mucosa of the genitals, upper-respiratory tract, or the skin. The ‘high-risk HPV type’, a sub-group of mucosal HPVs, is the cause of approximately 5% of all human cancers, which corresponds to one-third of all virus-induced tumours. Within the high-risk group, HPV16 is the most oncogenic type, being responsible for approximatively 50% of all worldwide cervical cancers. Many studies suggest that, in addition to the high-risk mucosal HPV types, certain cutaneous HPVs also have a role in the development of non-melanoma skin cancer (NMSC). Functional studies on the HPV early gene products showed that E6 and E7 play a key role in carcinogenesis. These two proteins use multiple mechanisms to evade host immune surveillance, allowing viral persistence, and to deregulate cell cycle and apoptosis control, thus facilitating the accumulation of DNA damage and ultimately cellular transformation. The demonstration that high-risk HPV types are the etiological agents of cervical cancer allowed the implementation in the clinical routine of novel screening strategies for cervical lesions, as well as the development of a very efficient prophylactic vaccine. Because of these remarkable achievements, there is no doubt that in the coming decades we will witness a dramatic reduction of cervical cancer incidence worldwide. PMID:25987895

  3. Committee Opinion No. 704: Human Papillomavirus Vaccination.

    PubMed

    2017-06-01

    Human papillomavirus (HPV) is associated with anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. The HPV vaccination significantly reduces the incidence of anogenital cancer and genital warts. Despite the benefits of HPV vaccines, only 41.9% of girls in the recommended age group, and only 28.1% of males in the recommended age group have received all recom-mended doses. Compared with many other countries, HPV vaccination rates in the United States are unacceptably low. The U.S. Food and Drug Administration has approved three vaccines that are effective at preventing HPV infection. These vaccines cover 2, 4, or 9 HPV serotypes, respectively. Safety data for all three HPV vaccines are reassuring. The HPV vaccines are recommended for girls and boys aged 11-12 years and can be given to females and males up to age 26 years. The Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists recommend routine HPV vaccination for girls and boys at the target age of 11-12 years (but it may be given from the age of 9 years) as part of the adolescent immunization platform in order to help reduce the incidence of anogenital cancer and genital warts associated with HPV infection. Obstetrician-gynecologists and other health care providers should stress to parents and patients the benefits and safety of HPV vaccination and offer HPV vaccines in their offices.

  4. Molecular detection methods of human papillomavirus (HPV).

    PubMed

    Zaravinos, Apostolos; Mammas, Ioannis N; Sourvinos, George; Spandidos, Demetrios A

    2009-01-01

    Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, molecular detection methods are the gold standard for identification of HPV. The three categories of molecular assays that are available are based on the detection of HPV DNA and include (1) non-amplified hybridization assays, such as Southern transfer hybridization (STH), dot blot hybridization (DB) and in situ hybridization (ISH); (2) signal amplified hybridization assays, such as hybrid capture assays (HC2); (3) target amplification assays, such as polymerase chain reaction (PCR) and in situ PCR. STH requires large amounts of DNA, is laborious and not reproducible, while ISH has only moderate sensitivity for HPV. The sensitivity of the HC2 assay is similar to that of PCR-based assays, with high sensitivity being achieved by signal rather than target amplification. PCR-based detection is both highly sensitive and specific. Since PCR can be performed on very small amounts of DNA, it is ideal for use on specimens with low DNA content. In the future, with the advance of technology, viral DNA extraction and amplification systems will become more rapid, more sensitive, and more automated.

  5. Human papillomavirus type 56-associated Bowen disease.

    PubMed

    Shimizu, A; Tamura, A; Abe, M; Amano, H; Motegi, S; Nakatani, Y; Hoshino, H; Ishikawa, O

    2012-11-01

    Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear. To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations. Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease. Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types. This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  6. Human papillomavirus and lung cancinogenesis: an overview.

    PubMed

    de Freitas, Antonio Carlos; Gurgel, Ana Pavla; de Lima, Elyda Golçalves; de França São Marcos, Bianca; do Amaral, Carolina Maria Medeiros

    2016-12-01

    Lung cancer is the most common cause of cancer deaths worldwide. Although tobacco smoking is considered to be the main risk factor and the most well-established risk factor for lung cancer, a number of patients who do not smoke have developed this disease. This number varies between 15 % to over one-half of lung cancer cases, and the deaths from lung cancer in non-smokers are increasing every year. There are many other agents that are thought to be etiological, including diesel exhaust exposure, metals, radiation, radon, hormonal factors, cooking oil, air pollution and infectious diseases, such as human papillomavirus (HPV). Studies in various parts of the world have detected HPV DNA at different rates in lung tumors. However, the role of HPV in lung cancer is still unclear. Thus, in this review, we investigated some molecular mechanisms of HPV protein activity in host cells, the entry of HPV into lung tissue and the possible route used by the virus to reach the lung cells.

  7. Requiring human papillomavirus vaccine for immigrant women.

    PubMed

    Hachey, Krista J; Allen, Rebecca H; Nothnagle, Melissa; Boardman, Lori A

    2009-11-01

    The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends human papillomavirus (HPV) vaccination of 11- to 12-year-old girls, with catch-up vaccination for girls and women aged 13 to 26 years. Although compulsory HPV vaccination is not currently mandated for any U.S. population, immigrant women aged 11-26 years are now required to receive the first injection of the vaccine (the full series consists of three doses) as a result of the 1996 Illegal Immigration Reform and Immigrant Responsibility Act. According to this law, immigrants applying for visas to enter the United States or to adjust their immigration status must receive the inoculations that the Advisory Committee on Immunization Practices recommends for U.S. residents. In the case of HPV, this law represents not only an undue burden on immigrant women, but also raises scientific and ethical questions regarding the benefit of vaccination in this population. Given these issues, immigrant women should not be required to provide documentation of HPV vaccination at the time of visa application or adjustment of immigration status.

  8. Human papillomavirus-related esophageal cancer survival

    PubMed Central

    Guo, Lanwei; Liu, Shuzheng; Zhang, Shaokai; Chen, Qiong; Zhang, Meng; Quan, Peiliang; Sun, Xi-Bin

    2016-01-01

    Abstract Background: Human papillomavirus (HPV) has been identified to be related to progression of esophageal cancer. However, the results remain controversial. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Methods: The electronic databases of MEDLINE and Excerpta Medica database were searched till April 30, 2016. Study-specific risk estimates were pooled using a random-effects model. Results: Ten studies involving a total of 1184 esophageal cancer cases were included in this meta-analysis. The pooled hazard ratio comparing HPV-positive to HPV-negative esophageal cancers was 1.03 (95% confidence interval 0.78–1.37), which was not significantly correlated with improved survival. However, HPV-16-positive patients might have a significantly favorable survival (hazard ratio 0.73, 95% confidence interval 0.44–1.21). Conclusion: The meta-analysis indicated that HPV infection may not be of prognostic utility in the evaluation of factors contributing to esophageal cancer. Further large prospective studies are encouraged to stratify survival analysis by HPV type. PMID:27861358

  9. Human papillomavirus related diseases in Malaysians.

    PubMed

    Cheah, P L

    1994-06-01

    The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.

  10. [Human papillomavirus detection in cervical cancer prevention].

    PubMed

    Picconi, María Alejandra

    2013-01-01

    Cervical cancer (CC), which is strongly associated to high-risk human papillomavirus (hr-HPV) infection, continues being a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had no major impact on reducing CC incidence and mortality rates, which are still high in the region. New screening tools to detect precancerous lesions became available, which provide great opportunities for CC prevention, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. Currently, hr-HPV testing represents an invaluable component of clinical guidelines for screening, management and treatment of CC and their precursor lesions. Many testing strategies have been developed that can detect a broad spectrum of hr-HPV types in a single assay; however, only a small subset of them has documented clinical performance for any of the standard HPV testing indications. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated into the lab, it is essential to submit the whole procedure of HPV testing to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Recent progress and current status of these methods are discussed in this article.

  11. Anaphylaxis following quadrivalent human papillomavirus vaccination.

    PubMed

    Brotherton, Julia M L; Gold, Mike S; Kemp, Andrew S; McIntyre, Peter B; Burgess, Margaret A; Campbell-Lloyd, Sue

    2008-09-09

    In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.

  12. The paediatric story of human papillomavirus (Review)

    PubMed Central

    MAMMAS, IOANNIS N.; SOURVINOS, GEORGE; SPANDIDOS, DEMETRIOS A.

    2014-01-01

    Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, which has gained much attention in recent years due to the discoveries of Professor Harald zur Hausen, who first identified a connection between HPV and cervical cancer. Professor Harald zur Hausen, the ‘Father of HPV Virology’, was the recipient of the 2008 Nobel Prize. HPV can be transmitted through physical contact via autoinoculation or fomites, sexual contact, as well as vertically from the HPV-positive mother to her newborn, causing subclinical or clinical infections. In infancy and childhood, HPV-associated clinical infections include skin warts, genital warts and juvenile recurrent respiratory papillomatosis, while cervical squamous intraepithelial lesions have also been reported among adolescent girls. To date, several research teams, worldwide, have extensively investigated HPV from the paediatric point of view. This primitive effort has been performed before the recent great expansion of paediatric HPV research due to the vaccination programmes against HPV, which were introduced into clinical practice in 2006. In this review article, we present a brief overview of paediatric HPV research after the first report in 1978 involving children in the research of HPV until the time point of this great expansion. In the future, it is expected that further unresolved issues will be addressed and clarified, as the paediatric story of HPV remains a challenging research target. PMID:25013461

  13. Human papillomavirus DNA in oral mucosal lesions.

    PubMed

    Giovannelli, Lucia; Campisi, Giuseppina; Lama, Anna; Giambalvo, Ornella; Osborn, John; Margiotta, Valerio; Ammatuna, Pietro

    2002-03-15

    This study determined the presence of human papillomavirus (HPV) DNA in oral mucosa cells from 121 patients with different types of oral mucosal lesions (13 squamous cell carcinomas, 59 potentially malignant lesions, 49 benign erosive ulcerative lesions) and from 90 control subjects. HPV DNA was detected by nested polymerase chain reaction, and genotype was determined by DNA sequencing. HPV prevalence was 61.5% in carcinomas, 27.1% in potentially malignant lesions, 26.5% in erosive ulcerative lesions, and 5.5% in control subjects. The risk of malignant or potentially malignant lesions was associated with HPV and was statistically significant. HPV-18 was found in 86.5% of HPV-positive lesions but was not associated with a particular type of lesion and was found in 80% of the HPV-positive control subjects. HPV infection was related to older age but not to sex, smoking, or alcohol use; the presence of lesions in the oral cavity increased the risk of HPV infection.

  14. Human papillomavirus vaccines and vaccine implementation.

    PubMed

    de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

    2008-11-01

    Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

  15. An update on oral human papillomavirus infection

    PubMed Central

    Bharti, Ankit H.; Chotaliya, Kiran; Marfatia, Y. S.

    2013-01-01

    Human papillomavirus (HPV) constitutes the majority of newly acquired sexually transmitted infections (STIs) in United States as per the centers for disease control factsheet 2013. Genital HPV is the most common STI with incidence of about 5.5 million world-wide, nearly 75% of sexually active men and women have been exposed to HPV at some point in their lives. Oral Sexual behavior is an important contributor to infection of HPV in the oral mucosa especially in cases known to practice high risk behavior and initiating the same at an early age. HPV infection of the oral mucosa currents is believed to affect 1-50% of the general population, depending on the method used for diagnosis. The immune system clears most HPV naturally within 2 years (about 90%), but the ones that persist can cause serious diseases. HPV is an essential carcinogen being implicated increasingly in association with cancers occurring at numerous sites in the body. Though there does not occur any specific treatment for the HPV infection, the diseases it causes are treatable such as genital warts, cervical and other cancers. PMID:24339456

  16. Therapeutic Vaccine Strategies against Human Papillomavirus

    PubMed Central

    Khallouf, Hadeel; Grabowska, Agnieszka K.; Riemer, Angelika B.

    2014-01-01

    High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches. PMID:26344626

  17. Anti-human papillomavirus therapeutics: facts & future.

    PubMed

    Bharti, Alok C; Shukla, Shirish; Mahata, Sutapa; Hedau, Suresh; Das, Bhudev C

    2009-09-01

    Even after 25 years of establishing Human Papillomavirus (HPV) as the causative agent for cervical cancer, effective treatment of HPV infection still unavailable. Comprehensive efforts especially for targeting HPV infection have been made only in recent years. Conventional physical ablation of HPV-induced lesions such as cryo-therapy, photo-therapy, LEEP, laser cone-biopsy and localized radiotherapy are shown to be effective to some extent in treating localized lesions where the removal of diseased tissue is associated with removal of transforming keratinocytes harboring HPV. Apart from currently available prophylactic vaccines which prevent the viral entry and should be given prior to viral exposure, several attempts are being made to develop therapeutic vaccines that could treat prevailing HPV infection. In addition, immunomodulators like interferons and imiquimod that have been shown to elicit cytokine milieu to enhance host immune response against HPV infection. Also, antiviral approaches such as RNA interference (RNAi) nucleotide analogs, antioxidants and herbal derivatives have shown effective therapeutic potential against HPV infection. These leads are being tested in pre-clinical and clinical studies. Present article provides a brief overview of conventional therapies for HPV-associated diseases. Potential of non-ablative anti-HPV treatment modalities that could prove useful for either elimination of HPV in early stages of infection when the virus is not integrated into the host cell genome or suppression of the expression of viral oncogenes that dys-regulate the host cell cycle following transformation is discussed.

  18. Current status of human papillomavirus vaccines

    PubMed Central

    Yi, Seokjae

    2014-01-01

    Cervical cancer is a malignant neoplasm arising from cells that originate in the cervix uteri. It is the second most prevalent cancer among women. It can have several causes; an infection with some type of human papillomavirus (HPV) is the greatest risk factor for cervical cancer. Over 100 types of HPVs have been identified, and more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region. Among these, a number of HPVs types, containing types 16 and 18, are classified as "high-risk" HPVs that can cause cervical cancer. The HPVs vaccine prevents infection with certain species of HPVs associated with the development of cervical cancer, genital warts, and some less common cancers. Two HPVs vaccines are currently on the global market: quadrivalent HPVs vaccine and bivalent HPV vaccine that use virus-like particles as a vaccine antigen. This review discusses the current status of HPVs vaccines on the global market, clinical trials, and the future of HPVs vaccine development. PMID:25003090

  19. Human Papillomavirus Laboratory Testing: the Changing Paradigm

    PubMed Central

    2016-01-01

    SUMMARY High-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing. PMID:26912568

  20. Introducing human papillomavirus vaccines - questions remain.

    PubMed

    Paavonen, Jorma; Lehtinen, Matti

    2008-01-01

    Genital human papillomavirus (HPV) infection and HPV-associated cervical and other anogenital cancers are significant public health problems. HPV 16 and HPV 18 are responsible for approximately 70% of all invasive cervical cancers worldwide. The first prophylactic HPV virus-like particle (VLP) vaccine against HPV types 6/11/16/18 was licensed in 2006 for girls and women aged 9-26 years. The second prophylactic HPV vaccine against HPV types 16 and 18 has been licensed this year. These vaccines are almost 100% effective in preventing infection and high-grade precancer associated with the HPV types included in the vaccine. The vaccines are well tolerated, safe, and highly immunogenic when given in three doses within 6 months. Efficacy of the vaccine against external vulvar and HPV-related vaginal lesions is also high. Even though the vaccine is highly effective against high-grade cervical, vaginal, or vulvar precancers, this only applies to women unexposed to these HPV types and only to high-grade intraepithelial lesions caused by these HPV types. Therefore, it is important to understand that the population impact of the vaccines will be much lower than vaccinating naive populations. Implementing HPV vaccine is a great opportunity but also a great challenge. However, mandatory HPV vaccination may raise many questions, and more answers are needed.

  1. Human papillomaviruses. Applications, caveats and prevention.

    PubMed

    Crum, Christopher P; Berkowitz, Ross S

    2002-07-01

    Unlike cervical cytology, human papillomavirus (HPV) testing provides an objective assessment of neoplasia risk. The major advantages of this technology are the potential for "reflex testing" (when used with liquid-based cytology); efficient exclusion of HPV-negative women, who can be triaged to yearly follow-up; and identification of HPV-positive women, who require colposcopic triage. However, practitioners should be aware that highly sensitive HPV tests will also identify many women with little or no immediate risk of significant neoplasia, may impose a psychosocial burden on the patient and may be used or interpreted inappropriately by both practitioners and patients. However, these caveats are similar to those inherent in any screening program involving a sexually transmitted disease, and the disadvantages of HPV testing will be minimized by attention to patient concerns and a keen awareness of the limitations of this technology. Ultimately, control of cervical cancer and its precursors rests with active prevention via vaccination programs targeting HPV. If successful, such programs could radically alter the number of women requiring triage for preinvasive disease and initiate a progressive decline in cervical cancer incidence.

  2. Pathogenesis of infection by human papillomavirus.

    PubMed

    Brendle, Sarah A; Bywaters, Stephanie M; Christensen, Neil D

    2014-01-01

    Human papillomaviruses (HPVs) are associated with benign lesions known as warts and several cancer types including cancer of the cervix, penis, anus and oral cavity. HPVs are classified by their oncogenic potential and are divided into high-risk oncogenic HPVs and low-risk HPVs. Tissue tropism is used as another means of classifying the virus, and HPVs are divided into types that infect mucosal or cutaneous tissues. Several risk factors have been identified that elevate an individual's likelihood of becoming infected with HPV including cigarette smoking, a large number of lifetime sexual partners and immunosuppression. Most HPV infections are cleared naturally, although persistent infection with oncogenic HPV types can lead to the cancers mentioned above. HPV has employed several mechanisms to avoid detection by the host immune system. Virus is released along with shedding skin cells in a nonlytic manner, and the virus has an altered codon usage leading to reduced expression of viral proteins. Infections from high-risk oncogenic HPV types that progress cause neoplasias that are defined as CIN1-CIN3 depending on the amount of abnormal cell growth and the level of cellular differentiation.

  3. Human papillomavirus vaccination among adolescents in Georgia

    PubMed Central

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

    2015-01-01

    Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011–2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time. PMID:25912372

  4. Safety of human papillomavirus vaccines: a review

    PubMed Central

    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 rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872

  5. Papillomaviruses

    PubMed Central

    Félez-Sánchez, Marta

    2015-01-01

    Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. PMID:25634317

  6. The biology of beta human papillomaviruses.

    PubMed

    Tommasino, Massimo

    2017-03-02

    The beta genus comprises more than 50 beta human papillomavirus (HPV) types that are suspected to be involved, together with ultraviolet (UV) irradiation, in the development of non-melanoma skin cancer (NMSC), the most common form of human cancer. Two members of the genus beta, HPV5 and HPV8, were first identified in patients with a genetic disorder, epidermodysplasia verruciformis (EV), that confers high susceptibility to beta HPV infection and NMSC development. The fact that organ transplant recipients (OTRs) with an impaired immune system have an elevated risk of NMSC raised the hypothesis that beta HPV types may also be involved in skin carcinogenesis in non-EV patients. Epidemiological studies have shown that serological and viral DNA markers are weakly, but significantly, associated with history of NMSC in OTRs and the general population. Functional studies on mucosal high-risk (HR) HPV types have clearly demonstrated that the products of two early genes, E6 and E7, are the main viral oncoproteins, which are able to deregulate events closely linked to transformation, such as cell cycle progression and apoptosis. Studies on a small number of beta HPV types have shown that their E6 and E7 oncoproteins also have the ability to interfere with the regulation of key pathways/events associated with cellular transformation. However, the initial functional data indicate that the molecular mechanisms leading to cellular transformation are different from those of mucosal HR HPV types. Beta HPV types may act only at early stages of carcinogenesis, by potentiating the deleterious effects of other carcinogens, such as UV radiation.

  7. Human papillomaviruses genotyping in plantar warts.

    PubMed

    de Planell-Mas, Elena; Martínez-Garriga, Blanca; Zalacain, Antonio Jesús; Vinuesa, Teresa; Viñas, Miguel

    2017-05-01

    Plantar warts are caused by human papillomaviruses (HPVs) and have been associated with several HPV genotypes. However, there are few studies focused exclusively on plantar warts. In this work, we aim to identify the HPV genotypes of plantar warts and explore their relation to demographic and clinical characteristics of patients. A total of 72 patients diagnosed with plantar warts were recruited at the Laser unit at Podiatric Hospital, University of Barcelona, Spain. Inner hyperkeratosis laminar sections of warts were collected and DNA of samples were extracted. Amplification of a conserved region of the HPV L1 gene was performed with the SK-Polymerase chain reaction method. DNA amplicons were sequenced and HPV types identified. The most prevalent genotypes detected among the 105 analyzed plantar warts were HPV-57 (37.1%), HPV-27 (23.8%), HPV-1a (20.9%), HPV-2 (15.2%), and HPV-65 (2.8%). The majority of patients (78%) presented one single plantar wart, whereas multiple warts were detected in 22.2% of patients. One patient with multiple warts presented HPV types from two different genera, suggesting the spread of warts by self-inoculation as well as by de novo infection. No significant differences between the number of warts in toes, midfoot and heel were found. The most prevalent HPV types detected in all areas belonged to the alpha genus. This work provides new insight on plantar warts and their associated HPV genotypes, and evidences the usefulness and reliability of both the sample collection procedure and the PCR method used for HPV detection and typing. J. Med. Virol. 89:902-907, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    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.

  9. Committee opinion no. 588: human papillomavirus vaccination.

    PubMed

    2014-03-01

    The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that human papillomavirus (HPV) vaccination routinely be targeted to females and males aged 11 years or 12 years as part of the adolescent immunization platform to help reduce the incidence of anogenital cancers and genital warts associated with HPV infection. The quadrivalent HPV vaccine is approved for use in males and females, whereas the bivalent HPV vaccine is approved for use only in females. For those not vaccinated at the target age, catch-up vaccination is recommended up to age 26 years. The American College of Obstetricians and Gynecologists endorses these recommendations. Although obstetrician-gynecologists are not likely to care for many patients in the initial HPV vaccination target group, they have the opportunity to educate mothers about the importance of vaccinating their children at the recommended age and are critical to vaccinating adolescent girls and young women during the catch-up period. Obstetrician-gynecologists should advise patients and parents that HPV vaccines are most effective in preventing genital cancers when administered before the onset of sexual activity. However, sexually active individuals can receive some benefit from the vaccination because exposure to all HPV types prevented by the vaccines is unlikely in persons aged 13 years through 26 years. Although HPV vaccination in pregnancy is not recommended, neither is routine pregnancy testing before vaccination. Lactating women can receive either HPV vaccine. The need for ongoing cervical cytology screening should be emphasized in all women aged 21 years and older, even those who received HPV vaccination before the onset of sexual activity.

  10. Human papillomavirus infections: epidemiology, pathogenesis, and host immune response.

    PubMed

    Tyring, S K

    2000-07-01

    Human papillomaviruses (HPVs) are ubiquitous and often cause lesions on the skin that come to the attention of the dermatologist. Skin lesions, or warts, often occur on the hands or soles of the feet and can cause embarrassment or discomfort. Genital HPV infections are transmitted by sexual contact. Infections associated with some HPV types have a high risk of progressing to carcinoma. This review discusses the molecular biology and genetics of human papillomaviruses and provides an overview of the virology, pathology, clinical manifestations, and host immune response to infection.

  11. Evidence of recombination within human alpha-papillomavirus

    PubMed Central

    Angulo, Manuel; Carvajal-Rodríguez, Antonio

    2007-01-01

    Background Human papillomavirus (HPV) has a causal role in cervical cancer with almost half a million new cases occurring each year. Presence of the carcinogenic HPV is necessary for the development of the invasive carcinoma of the genital tract. Therefore, persistent infection with carcinogenic HPV causes virtually all cervical cancers. Some aspects of the molecular evolution of this virus, as the putative importance of recombination in its evolutionary history, are an opened current question. In addition, recombination could also be a significant issue nowadays since the frequency of co-infection with more than one HPV type is not a rare event and, thus, new recombinant types could be currently being generated. Results We have used human alpha-PV sequences from the public database at Los Alamos National Laboratory to report evidence that recombination may exist in this virus. A model-based population genetic approach was used to infer the recombination signal from the HPV DNA sequences grouped attending to phylogenetic and epidemiological information, as well as to clinical manifestations. Our results agree with recently published ones that use a different methodology to detect recombination associated to the gene L2. In addition, we have detected significant recombination signal in the genes E6, E7, L2 and L1 at different groups, and importantly within the high-risk type HPV16. The method used has recently been shown to be one of the most powerful and reliable procedures to detect the recombination signal. Conclusion We provide new support to the recent evidence of recombination in HPV. Additionally, we performed the recombination estimation assuming the best-fit model of nucleotide substitution and rate variation among sites, of the HPV DNA sequence sets. We found that the gene with recombination in most of the groups is L2 but the highest values were detected in L1 and E6. Gene E7 was recombinant only within the HPV16 type. The topic deserves further study

  12. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection.

    PubMed

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio

    2015-02-01

    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  13. Characterizing the spatio-temporal role of sorting nexin 17 in human papillomavirus trafficking.

    PubMed

    Bergant, Martina; Peternel, Špela; Pim, David; Broniarczyk, Justyna; Banks, Lawrence

    2017-04-01

    The human papillomavirus (HPV) L2 capsid protein plays an essential role during the early stages of viral infection. Previous studies have shown that the interaction between HPV L2 and endosomal sorting nexin 17 (SNX17) is conserved across multiple PV types where it plays an essential role in infectious entry, suggesting an evolutionarily conserved pathway of PV trafficking. Here we show that the peak time of interaction between HPV-16 L2 and SNX17 is rather early, at 2 h post-infection. Interestingly, the L2-SNX17 interaction appears to be important for facilitating capsid disassembly and L1 dissociation, suggesting that L2 recruitment of SNX17 occurs prior to capsid disassembly. Furthermore, we also found evidence of L2-SNX17 association at the later stages of infectious entry, suggesting that the SNX17-mediated sorting machinery is either involved at different stages of HPV trafficking or that L2-SNX17 interaction is a long-lasting event in HPV trafficking.

  14. The role of human papillomavirus in squamous carcinoma of the head and neck.

    PubMed

    Li, Guojun; Sturgis, Erich M

    2006-03-01

    Human papillomavirus type-16 infection is associated with a significant portion of squamous carcinoma of the head and neck, particularly for the oropharynx and for those lacking the other risk factors of tobacco and alcohol. The link between human papillomavirus type-16 and carcinoma of the oropharynx is based on the identification of human papillomavirus type-16 in oropharyngeal tumors and the association of human papillomavirus type-16 with the risk of oropharyngeal cancer estimated in case-control epidemiologic studies. This review highlights the molecular mechanism of human papillomavirus carcinogenesis and the association of human papillomavirus type-16 as a risk factor for squamous cell carcinoma of the oropharynx as well as recent research efforts utilizing human papillomavirus as a biomarker of clinical outcomes.

  15. Apparent Diffusion Coefficient Histograms of Human Papillomavirus-Positive and Human Papillomavirus-Negative Head and Neck Squamous Cell Carcinoma: Assessment of Tumor Heterogeneity and Comparison with Histopathology.

    PubMed

    de Perrot, T; Lenoir, V; Domingo Ayllón, M; Dulguerov, N; Pusztaszeri, M; Becker, M

    2017-09-14

    Head and neck squamous cell carcinoma associated with human papillomavirus infection represents a distinct tumor entity. We hypothesized that diffusion phenotypes based on the histogram analysis of ADC values reflect distinct degrees of tumor heterogeneity in human papillomavirus-positive and human papillomavirus-negative head and neck squamous cell carcinomas. One hundred five consecutive patients (mean age, 64 years; range, 45-87 years) with primary oropharyngeal (n = 52) and oral cavity (n = 53) head and neck squamous cell carcinoma underwent MR imaging with anatomic and diffusion-weighted sequences (b = 0, b = 1000 s/mm(2), monoexponential ADC calculation). The collected tumor voxels from the contoured ROIs provided histograms from which position, dispersion, and form parameters were computed. Histogram data were correlated with histopathology, p16-immunohistochemistry, and polymerase chain reaction for human papillomavirus DNA. There were 21 human papillomavirus-positive and 84 human papillomavirus-negative head and neck squamous cell carcinomas. At histopathology, human papillomavirus-positive cancers were more often nonkeratinizing (13/21, 62%) than human papillomavirus-negative cancers (19/84, 23%; P = .001), and their mitotic index was higher (71% versus 49%; P = .005). ROI-based mean and median ADCs were significantly lower in human papillomavirus-positive (1014 ± 178 × 10(-6) mm(2)/s and 970 ± 187 × 10(-6) mm(2)/s, respectively) than in human papillomavirus-negative tumors (1184 ± 168 × 10(-6) mm(2)/s and 1161 ± 175 × 10(-6) mm(2)/s, respectively; P < .001), whereas excess kurtosis and skewness were significantly higher in human papillomavirus-positive (1.934 ± 1.386 and 0.923 ± 0.510, respectively) than in human papillomavirus-negative tumors (0.643 ± 0.982 and 0.399 ± 0.516, respectively; P < .001). Human papillomavirus-negative head and neck squamous cell carcinoma had symmetric normally distributed ADC histograms, which corresponded

  16. Model systems of human papillomavirus-associated disease.

    PubMed

    Doorbar, John

    2016-01-01

    Human papillomaviruses (HPVs) cause a range of serious diseases, including the vast majority of cervical cancers, most anal cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult-to-manage diseases. As a result, there is a great need for model systems that accurately mimic papillomavirus infections in humans. This is complicated by the diverse variety of HPVs, which now number over 200 types, and the different strategies they have evolved to persist in the population. The most well-developed models involve the culture of HPV-containing keratinocytes in organotypic raft culture, an approach which appears to accurately mimic the life cycle of several of the high-risk cancer-associated HPV types. Included amongst these are HPV16 and 18, which cause the majority of cervical cancers. The low-risk HPV types persist less well in tissue-culture models, and our ability to study the productive life cycle of these viruses is more limited. Although ongoing research is likely to improve this situation, animal models of papillomavirus disease can provide considerable basic information as to how lesions form, regress and can be controlled by the immune system. The best studied are cottontail rabbit papillomavirus, rabbit oral papillomavirus and, more recently, mouse papillomavirus (MmuPV), the last of which is providing exciting new insights into viral tropisms and immune control. In addition, transgenic models of disease have helped us to understand the consequences of persistent viral gene expression and the importance of co-factors such as hormones and UV irradiation in the development of neoplasia and cancer. It is hoped that such disease models will eventually lead us to better understanding and better treatments for human disease.

  17. Immunogenicity of an HPV-16 L2 DNA vaccine

    PubMed Central

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

    2009-01-01

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

  18. [Pathogenesis of human papillomavirus infection in patients with epidermodysplasia verruciformis].

    PubMed

    Liang, Si; Zuo, Ya-Gang; Wang, Bao-Xi

    2009-02-01

    Epidermodysplasia verruciformis (EV), a rare inherited disease, is believed to be associated with human papillomavirus (HPV) infection. EVER1/2 genes, dendritic cells, T lymphocytes, and the biological characteristics of HPV itself may play roles in the pathogenesis of HPV infection.

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

    PubMed Central

    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. PMID:27127735

  20. Focal epithelial hyperplasia caused by human papillomavirus 13.

    PubMed

    Saunders, Natasha R; Scolnik, Dennis; Rebbapragada, Anuradha; Koelink, Eric; Craw, Lindsey; Roth, Sherryn; Aronson, Leya; Perusini, Stephen; Silverman, Michael S

    2010-06-01

    Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.

  1. Development of a Human Papillomavirus Vaccination Intervention for Australian Adolescents

    ERIC Educational Resources Information Center

    Cooper, Spring C.; Davies, Cristyn; McBride, Kate; Blades, Joanna; Stoney, Tanya; Marshall, Helen; Skinner, S. Rachel

    2016-01-01

    Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people's desire for involvement in decision-making…

  2. Intention of College Students to Receive the Human Papillomavirus Vaccine

    ERIC Educational Resources Information Center

    Richards, Keith

    2016-01-01

    Purpose: The purpose of this paper is to better understand what influences the intentions of college students to receive the human papillomavirus (HPV) vaccine. HPV is the most common sexually transmitted infection in the USA and cancers related to HPV are on the rise. Design/Methodology/Approach: A 2×2 experimental design was used to predict the…

  3. Human Papillomavirus Vaccine Intent and Uptake among Female College Students

    ERIC Educational Resources Information Center

    Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.

    2012-01-01

    Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…

  4. Human Papillomavirus Vaccine Intent and Uptake among Female College Students

    ERIC Educational Resources Information Center

    Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.

    2012-01-01

    Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…

  5. Intention of College Students to Receive the Human Papillomavirus Vaccine

    ERIC Educational Resources Information Center

    Richards, Keith

    2016-01-01

    Purpose: The purpose of this paper is to better understand what influences the intentions of college students to receive the human papillomavirus (HPV) vaccine. HPV is the most common sexually transmitted infection in the USA and cancers related to HPV are on the rise. Design/Methodology/Approach: A 2×2 experimental design was used to predict the…

  6. Development of a Human Papillomavirus Vaccination Intervention for Australian Adolescents

    ERIC Educational Resources Information Center

    Cooper, Spring C.; Davies, Cristyn; McBride, Kate; Blades, Joanna; Stoney, Tanya; Marshall, Helen; Skinner, S. Rachel

    2016-01-01

    Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people's desire for involvement in decision-making…

  7. Pathobiology of human papillomaviruses in human immunodeficiency virus - Infected persons.

    PubMed

    Krishnamurti, Uma; Unger, Elizabeth R

    2017-07-01

    There is a complex interrelationship between human papillomaviruses (HPV) and human immunodeficiency viruses (HIV) that has been recognized from the start of the HIV epidemic. Cervical cancer was used as a surveillance indicator for acquired immunodeficiency syndrome (AIDS) before definitive identification of the viral etiology of either condition were known. Careful epidemiologic studies combined with clinical and laboratory measures of HPV, HPV-associated disease, and HIV have helped us understand many aspects of the relationship between these two virus groups; however, questions remain. The histopathology associated with HPV is identical in HIV-positive and negative patients though the lesions are more frequent, with higher frequency of multiple HPV types, and persistent in HIV infected individuals. In this review we will briefly explain the pathobiology of HPV in HIV-infected persons and the potential impact of secondary (screening) and primary (vaccination) prevention to reduce HPV-associated disease in those infected with HIV. Published by Elsevier Inc.

  8. Identification of a role for the trans-Golgi network in human papillomavirus 16 pseudovirus infection.

    PubMed

    Day, Patricia M; Thompson, Cynthia D; Schowalter, Rachel M; Lowy, Douglas R; Schiller, John T

    2013-04-01

    Human papillomavirus 16 (HPV16) enters its host cells by a process that most closely resembles macropinocytosis. Uncoating occurs during passage through the endosomal compartment, and the low pH encountered in this environment is essential for infection. Furin cleavage of the minor capsid protein, L2, and cyclophilin B-mediated separation of L2 and the viral genome from the major capsid protein, L1, are necessary for escape from the late endosome (LE). Following this exodus, L2 and the genome are found colocalized at the ND10 nuclear subdomain, which is essential for efficient pseudogenome expression. However, the route by which L2 and the genome traverse the intervening cytoplasm between these two subcellular compartments has not been determined. This study extends our understanding of this phase in PV entry in demonstrating the involvement of the Golgi complex. With confocal microscopic analyses involving 5-ethynyl-2'-deoxyuridine (EdU)-labeled pseudogenomes and antibodies to virion and cellular proteins, we found that the viral pseudogenome and L2 travel to the trans-Golgi network (TGN) following exit from the LE, while L1 is retained. This transit is dependent upon furin cleavage of L2 and can be prevented pharmacologically with either brefeldin A or golgicide A, inhibitors of anterograde and retrograde Golgi trafficking. Additionally, Rab9a and Rab7b were determined to be mediators of this transit, as expression of dominant negative versions of these proteins, but not Rab7a, significantly inhibited HPV16 pseudovirus infection.

  9. Rabbits immunised with recombinant BCG expressing the cottontail rabbit papillomavirus (CRPV) L2E7E2 genes induces regression of established papillomas.

    PubMed

    Govan, V A; Williamson, A-L

    2007-07-01

    We previously demonstrated in a cottontail rabbit papillomavirus (CRPV) challenge model that recombinant Bacille Calmette-Guerin (rBCG) could potentially be used as a prophylactic vaccine vehicle to deliver papillomavirus proteins. In this study we investigated whether regression of CRPV-induced papillomas could be achieved following immunisation of out-bred New Zealand White rabbits with rBCG expressing CRPVL2, CRPVE2, CRPVE7 or CRPVL2E7E2 proteins. Rabbits immunised with rBCG/CRPVL2E7E2 had papillomas that were largely suppressed and were significantly smaller compared to the rBCG negative control group (Phuman papillomavirus proteins as a possible therapeutic vaccine.

  10. A study on the predictors of Korean male students' intention to receive human papillomavirus vaccination.

    PubMed

    Choi, Jeong Sil; Park, Seungmi

    2016-11-01

    The objective was to survey the current state of human papillomavirus (HPV) vaccination and the predictors of vaccination intention among Korean male students of high school (ages 15-19) and university (ages 17-27). Human papillomavirus is a sexually transmitted infectious agent causing uterine cervical, anal, and/or penile cancer and genital warts in males and females. Infection rate of human papillomavirus increases from the age when sexual intercourse first occurs. Therefore, motivation to receive human papillomavirus vaccination is needed to protect infection. Cross-sectional descriptive survey was performed only in male students. They are less aware of human papillomavirus than females, because human papillomavirus vaccination has been targeted on females for preventing cervical cancer in Korea. Data were collected using a self-reporting questionnaire for male high school and university students sampled from a city in Korea. Human papillomavirus vaccine-related knowledge, health beliefs, demographic, and sexual history information variables relating to intentions to vaccinate were assessed. The human papillomavirus vaccination rate was very low and the levels of knowledge and health beliefs were low. The significant predictors that raised the intention of human papillomavirus vaccination were a university student, experience of sexual intercourse and perceiving the benefits of human papillomavirus vaccination. To promote human papillomavirus vaccination, educational programming targeting males should include health beliefs and knowledge, emphasising that vaccination is important to prevent uterine cervical cancer and to role as a preventative measure against common male diseases. Male high school students should be included as a major target population for school human papillomavirus education programmes, as they are at the age of commencing sexual intercourse. In addition, public health policies including human papillomavirus vaccination in the national

  11. Maturation of the Human Papillomavirus 16 Capsid

    PubMed Central

    Cardone, Giovanni; Moyer, Adam L.; Cheng, Naiqian; Thompson, Cynthia D.; Dvoretzky, Israel; Lowy, Douglas R.; Schiller, John T.; Steven, Alasdair C.; Buck, Christopher B.

    2014-01-01

    ABSTRACT Papillomaviruses are a family of nonenveloped DNA viruses that infect the skin or mucosa of their vertebrate hosts. The viral life cycle is closely tied to the differentiation of infected keratinocytes. Papillomavirus virions are released into the environment through a process known as desquamation, in which keratinocytes lose structural integrity prior to being shed from the surface of the skin. During this process, virions are exposed to an increasingly oxidative environment, leading to their stabilization through the formation of disulfide cross-links between neighboring molecules of the major capsid protein, L1. We used time-lapse cryo-electron microscopy and image analysis to study the maturation of HPV16 capsids assembled in mammalian cells and exposed to an oxidizing environment after cell lysis. Initially, the virion is a loosely connected procapsid that, under in vitro conditions, condenses over several hours into the more familiar 60-nm-diameter papillomavirus capsid. In this process, the procapsid shrinks by ~5% in diameter, its pentameric capsomers change in structure (most markedly in the axial region), and the interaction surfaces between adjacent capsomers are consolidated. A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form. Pseudoatomic modeling based on a 9-Å resolution reconstruction of fully mature capsids revealed C-terminal disulfide-stabilized “suspended bridges” that form intercapsomeric cross-links. The data suggest a model in which procapsids exist in a range of dynamic intermediates that can be locked into increasingly mature configurations by disulfide cross-linking, possibly through a Brownian ratchet mechanism. PMID:25096873

  12. Molecular characterization of the L1 gene of papillomaviruses in epithelial lesions of cats and comparative analysis with corresponding gene sequences of human and feline papillomaviruses.

    PubMed

    Anis, Eman A; O'Neill, Sarah H; Newkirk, Kim M; Brahmbhatt, Rupal A; Abd-Eldaim, Mohamed; Frank, Linda A; Kania, Stephen A

    2010-12-01

    To characterize the L1 gene of papillomaviruses detected in epithelial lesions of cats and to determine the relationship between those L1 gene nucleotide sequences and known L1 gene sequences of human and feline papillomaviruses. 10 tissue samples of epithelial lesions from 8 cats. DNA was extracted from tissue samples. Primers were designed to amplify the L1 gene of papillomaviruses. Amplicons of DNA were sequenced; nucleotide sequences were compared with known L1 gene nucleotide sequences of papillomaviruses and used for phylogenetic analysis. Tissue samples were obtained from lesions (diagnosed as dysplasia [n=1], squamous cell carcinoma in situ [3], or squamous cell carcinoma [6]) of the skin (9) and oral mucosa [1]. Two amplicons had 99% homology with the L1 gene nucleotide sequence of human papillomavirus type 38b subtype FA125. Another amplicon had 84% homology with the L1 gene nucleotide sequence of human papillomavirus type 80 and was considered to be a new type of papillomavirus. Phylogenetic tree analysis revealed that these 3 papillomaviruses were grouped into 2 clades that were not similar to the clades of Felis domesticus papillomavirus type 1 or F domesticus papillomavirus type 2 (FdPV2). The remaining 7 amplicons had 98% to 100% homology with the L1 gene nucleotide sequence of FdPV2. Phylogenetic tree analysis revealed that those 7 papillomaviruses were grouped nto a single clade with FdPV2. Results support the likelihood of transmission of papillomaviruses between humans and cats.

  13. Papilloma formation in human foreskin xenografts after inoculation of human papillomavirus type 16 DNA.

    PubMed Central

    Brandsma, J L; Brownstein, D G; Xiao, W; Longley, B J

    1995-01-01

    A mouse model of high-risk human papillomavirus infection was developed in which human papillomavirus (HPV) type 16 DNA was inoculated into human foreskin grafted to the skin of severe combined immunodeficient (scid) mice. Grafted skin contained human epidermis and dermis and, like normal human skin, expressed involucrin in differentiating keratinocytes. HPV type 16 DNA, attached to gold particles, was delivered directly into human epidermal cells and induced exophytic papilloma with histologic features of papillomavirus infection, including koilocytosis and expression of papillomavirus capsid antigen. This model should be useful for determining in vivo the functions of viral genes and for developing strategies to prevent and treat HPV-associated disease. It may also be of value in developing animal models of other human skin diseases. PMID:7884930

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

    SciTech Connect

    Pittayakhajonwut, Daraporn; Angeletti, Peter C.

    2008-05-10

    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. Characterization of human papillomavirus type 16 pseudovirus containing histones.

    PubMed

    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

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

    PubMed

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

    2015-10-01

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

  17. Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

    PubMed

    Park, E; Jung, K-Y; Kwon, S-Y; Woo, J-S; Cho, J-G; Park, M W; Kim, I S; Kim, S J; Baek, S-K

    2015-01-01

    To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

  18. Human papillomavirus in virgins and behaviour at risk.

    PubMed

    Frega, Antonio; Cenci, Maria; Stentella, Patrizia; Cipriano, Luca; De Ioris, Andrea; Alderisio, Mauro; Vecchione, Aldo

    2003-05-08

    Human papillomavirus (HPV) infection is one of the most common sexual transmitted diseases (STDs). We compared two groups of virgins with genital HPV lesions to evaluate the behaviour at risk in the transmission of HPV infection. Partners were also examined. HPV lesions were detected in 88 virgins, who have never had sexual intercourse. This can be due to vertical transmission, fomities and skin-to-skin contact. Many other hypothesis can be proposed to explain HPV genital infection, however, further studies are required.

  19. Human Papillomavirus-Related Oropharyngeal Cancer in Women.

    PubMed

    Scaffidi, Rose M; Gerhardt, Jill; Eisele, Cheryle

    2016-05-01

    The number of women diagnosed with oropharyngeal cancer related to the human papillomavirus (HPV) is increasing in the United States. Educating health care providers and women about the link between HPV and oropharyngeal cancers can aid in earlier diagnosis and treatment. This article discusses the etiology and clinical presentation of HPV-positive and HPV-negative oropharyngeal cancer, noting distinctions between the 2 types. Recommendations for screening and prevention are provided. © 2016 by the American College of Nurse-Midwives.

  20. Vesicular trafficking of incoming human papillomavirus 16 to the Golgi apparatus and endoplasmic reticulum requires γ-secretase activity.

    PubMed

    Zhang, Wei; Kazakov, Teymur; Popa, Andreea; DiMaio, Daniel

    2014-09-16

    The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry. The human papillomaviruses are small nonenveloped DNA viruses responsible for approximately 5% of all human cancer deaths, but little is known about the process by which these viruses transit from the cell surface to the nucleus. Here we show that incoming HPV16, the most common high-risk HPV, traffics though a series of vesicular compartments during infectious entry, including the endosome, Golgi apparatus, and endoplasmic reticulum. Furthermore, we show that γ-secretase, a cellular membrane-associated protease, is required for entry of the L2 minor capsid protein and viral DNA into the Golgi apparatus and endoplasmic reticulum. These studies reveal a new pathway of cell entry by DNA viruses and suggest that components of this pathway are candidate

  1. Implication of human papillomavirus-66 in vulvar carcinoma: a case report.

    PubMed

    Kotsopoulos, Ioannis C; Tampakoudis, Georgios P; Evaggelinos, Dimitrios G; Nikolaidou, Anastasia I; Fytili, Panagiota A; Kartsiounis, Vasilios C; Gerasimidou, Domniki K

    2011-06-25

    Vulvar cancer in older women is seldom associated with human papillomavirus infection. We present the case of an 80-year-old Greek Caucasian woman with an undetermined obstetric and gynecologic history. The patient underwent radical vulvectomy and bilateral inguinal lymphadenectomy for a vulvar carcinoma. A human papillomavirus infection was suggested on the basis of histological and cytological examinations followed by human papillomavirus DNA typing, which revealed the presence of human papillomavirus-66. Even though human papillomavirus-16 and human papillomavirus-18 are most frequently implicated in the pathogenesis of vulvar carcinoma, human papillomavirus-66 can also be regarded as a causative factor. Suspicious lesions should be biopsied, and in the presence of carcinoma, vulvectomy with bilateral lymphadenectomy, if necessary, must be performed. Furthermore, polymerase chain reaction assay analysis with clinical arrays in cytological samples is an accurate test for the detection of a wide range of human papillomavirus genotypes and can be used to verify the infection and specify the human papillomavirus type implicated.

  2. Rates of human papillomavirus vaccination, attitudes about vaccination, and human papillomavirus prevalence in young women.

    PubMed

    Kahn, Jessica A; Rosenthal, Susan L; Jin, Yan; Huang, Bin; Namakydoust, Azadeh; Zimet, Gregory D

    2008-05-01

    To estimate rates of human papillomavirus (HPV) vaccination, factors associated with intention and belief in one's ability (self-efficacy) to receive the vaccine, and prevalence of vaccine-type HPV during the first year after an HPV-6, HPV-11, HPV-16, HPV-18 vaccine was licensed. Sexually experienced females 13-26 years of age (N=409) were recruited from three primary care clinics, completed a questionnaire, and underwent cervicovaginal HPV DNA testing. Outcome measures were HPV vaccination, intention and belief in one's ability to receive the HPV vaccine in the next year, and prevalence of vaccine-type HPV. Factors independently associated with intention and belief in one's ability to receive the HPV vaccine were determined by logistic regression. Five percent of participants had received at least one HPV vaccine dose, 66% intended to receive the vaccine, 65% were confident they could find the time to get vaccinated, 54% believed that they could receive all three shots, and 42% believed that they could afford vaccination. Sixty-eight percent of women were HPV-positive: 9% for HPV-6, 3% for HPV-11, 17% for HPV-16, and 12% for HPV-18. Factors independently associated with intention included believing that influential people would approve of vaccination, higher perceived severity of cervical cancer or genital warts, fewer safety barriers, and pregnancy history. Factors associated with a high belief in one's ability to receive the vaccine included perceived severity of HPV, sexually transmitted disease history, insurance coverage, and fewer practical barriers to vaccination. Interventions that aim to increase intention and belief in one's ability to receive HPV vaccines, which may lead to higher vaccination rates, should address personal beliefs about vaccination as well as systemic barriers to vaccination. III.

  3. Papillomaviruses: Molecular and clinical aspects

    SciTech Connect

    Howley, P.M.; Broker, T.R.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section headings are : Papillomaviruses and Human Genital Tract Diseases;Papillomaviruses and Human Cutaneous Diseases, Papillomaviruses and Human Oral and Laryngeal Diseases;Therapeutic Approaches to Papillomavirus Infections;Animal Papillomaviruses;Molecular Biology;Transcription, Replication, and Genome Organization;Epithelial Cell Culture;Papillomavirus Transformation;and Viral Vectors.

  4. Identification of a Novel Human Papillomavirus by Metagenomic Analysis of Samples from Patients with Febrile Respiratory Illness

    PubMed Central

    Mokili, John L.; Dutilh, Bas E.; Lim, Yan Wei; Schneider, Bradley S.; Taylor, Travis; Haynes, Matthew R.; Metzgar, David; Myers, Christopher A.; Blair, Patrick J.; Nosrat, Bahador; Wolfe, Nathan D.; Rohwer, Forest

    2013-01-01

    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. PMID:23554892

  5. Healthy Skin of Many Animal Species Harbors Papillomaviruses Which Are Closely Related to Their Human Counterparts

    PubMed Central

    Antonsson, Annika; Hansson, Bengt Göran

    2002-01-01

    Papillomaviruses associated with clinical symptoms have been found in many vertebrate species. In this study, we have used an L1 gene consensus PCR test designed to detect a broad spectrum of human skin papillomaviruses to analyze swab samples from healthy skin of 111 animals belonging to 19 vertebrate species. In eight of the species, papillomavirus DNA was found with the following prevalences: chimpanzees, 9 of 11 samples positive; gorillas, 3 of 4; long-tailed macaques, 14 of 16; spider monkeys, 2 of 2; ruffed lemurs, 1 of 2; cows, 6 of 10; European elks, 4 of 4; aurochs, 1 of 1. In total, 53 new putative animal papillomavirus types were found. The results show that skin papillomaviruses can be detected in healthy skin from many different animal species and are sufficiently related genetically to their human counterparts to be identified by a human skin papillomavirus primer set (FAP59 and FAP64). PMID:12438579

  6. Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer.

    PubMed

    Shimada, Takako; Yamaguchi, Naohiro; Nishida, Noriyuki; Yamasaki, Kentaro; Miura, Kiyonori; Katamine, Shigeru; Masuzaki, Hideaki

    2010-05-01

    The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment.

  7. Prevalence and genotyping of human papillomavirus infection in women with vulvodynia.

    PubMed

    Orlandi, Augusto; Francesconi, Arianna; Angeloni, Caterina; Palmieri, Giampiero; Fulvia, Gloria; Ciotti, Marco; Criscuolo, Anna; Sesti, Francesco; Spagnoli, Luigi Giusto

    2007-01-01

    Evidence of vulvar human papillomavirus infection varies and the frequency of the different genotypes has not been adequately assessed. Fifty consecutive sexually active healthy patients with vulvodynia and suspected of human papillomavirus infection underwent a vulvoscopy and biopsy. Ten normal vulvar samples were also enrolled as control. Histological and vulvoscopic findings were compared in relation to human papillomavirus-DNA presence and genotyping by a broad-spectrum polymerase chain reaction and reverse hybridization line probe assay. Although the clinical and histological diagnoses did not always coincide, a good association was found (p<0.0001). Human papillomavirus-DNA was detected in 42% of all biopsies and in none of the controls, and less frequently in acetowhite-positive patients (33.3%, p<0.03). Squamous papillomatosis (74%) was the most frequent histological diagnosis, followed by condyloma (20%). Condyloma (90%) but not squamous papillomatosis (29.7%) was significantly associated with human papillomavirus-DNA presence. Out of the vulvoscopically normal patients, one (33%) was human papillomavirus-DNA positive. Out of the recorded microscopic features, only koilocytosis was associated with human papillomavirus-DNA presence. Eight different human papillomavirus genotypes were detected: high-risk 16 (43%), 31 (19%), 52 (14.3%), 68, and 59 (4.8% each), and low-risk types 6 (71.4%), 11, and 40 (4.8% each); 33.3% of infections were multiple, ranging from 2 to 4 genotypes. Out of the human papillomavirus-DNA positive squamous papillomatosis, 72.7% showed a high-risk type but the infection remained episomal. Our data confirm human papillomavirus as a frequent cause of vulvodynia and its frequent association with squamous papillomatosis or condyloma. The high-risk human papillomavirus in squamous papillomatosis suggests screening for possible undiagnosed cervical infection.

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

    PubMed

    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

    2017-01-01

    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 = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic 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.

  9. Human Papillomaviruses As Therapeutic Targets in Human Cancer

    PubMed Central

    Hellner, Karin; Münger, Karl

    2011-01-01

    Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. HPV oncoproteins contribute to cancer initiation and progression and their expression is necessary for the maintenance of the transformed state. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression, is common to almost all cervical cancers offers unique opportunities for prevention, early detection, and therapy. The potential for prevention has been realized by introduction of prophylactic vaccines that are to prevent transmission of specific high-risk HPVs. Given, however, that these vaccines have no therapeutic efficacy and HPV-associated cervical cancers arise years if not decades after the initial infection, it has been estimated that there will be no measurable decline of HPV-associated tumors before 2040. Cervical cancer alone will be diagnosed in more than 375,000 US women between now and 2040. Other HPV-associated anogenital and head and neck cancers are predicted to afflict another 700,000 men and women over this time period. Hence, therapeutic efforts to combat high-risk HPV-associated disease remain of critical importance. PMID:21220591

  10. Partner Human Papillomavirus Viral Load and Incident Human Papillomavirus Detection in Heterosexual Couples.

    PubMed

    Grabowski, Mary K; Kong, Xiangrong; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Redd, Andrew D; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R

    2016-03-15

    The association between partner human papillomavirus (HPV) viral load and incident HPV detection in heterosexual couples is unknown. HPV genotypes were detected in 632 human immunodeficiency virus (HIV)-negative couples followed for 2 years in a male circumcision trial in Rakai, Uganda, using the Roche HPV Linear Array. This assay detects 37 genotypes and provides a semiquantitative measure of viral load based on the intensity (graded 1-4) of the genotype-specific band; a band intensity of 1 indicates a low genotype-specific HPV load, whereas an intensity of 4 indicates a high load. Using Poisson regression with generalized estimating equations, we measured the association between partner's genotype-specific viral load and detection of that genotype in the HPV-discordant partner 1 year later. Incident detection of HPV genotypes was 10.6% among men (54 of 508 genotype-specific visit intervals) and 9.0% among women (55 of 611 genotype-specific visit intervals). Use of male partners with a baseline genotype-specific band intensity of 1 as a reference yielded adjusted relative risks (aRRs) of 1.14 (95% confidence interval [CI], .58-2.27]) for incident detection of that genotype among women whose male partner had a baseline band intensity of 2, 1.75 (95% CI, .97-3.17) among those whose partner had an intensity of 3, and 2.52 (95% CI, 1.40-4.54) among those whose partner had an intensity of 4. Use of female partners with a baseline genotype-specific band intensity of 1 as a reference yielded an aRR of 2.83 (95% CI, 1.50-5.33) for incident detection of that genotype among men whose female partner had a baseline band intensity of 4. These associations were similar for high-risk and low-risk genotypes. Male circumcision also was associated with significant reductions in incident HPV detection in men (aRR, 0.53 [95% CI, .30-.95]) and women (aRR, 0.42 [95% CI, .23-.76]). In heterosexual couples, the genotype-specific HPV load in one partner is associated with the risk of new

  11. Tetraspanins in infections by human cytomegalo- and papillomaviruses.

    PubMed

    Fast, Laura A; Lieber, Diana; Lang, Thorsten; Florin, Luise

    2017-04-15

    Members of the tetraspanin family have been identified as essential cellular membrane proteins in infectious diseases by nearly all types of pathogens. The present review highlights recently published data on the role of tetraspanin CD151, CD81, and CD63 and their interaction partners in host cell entry by human cytomegalo- and human papillomaviruses. Moreover, we discuss a model for tetraspanin assembly into trafficking platforms at the plasma membrane. These platforms might persist during intracellular viral trafficking. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  12. By how much could screening by primary human papillomavirus testing reduce cervical cancer incidence in England?

    PubMed

    Castanon, Alejandra; Landy, Rebecca; Sasieni, Peter

    2017-06-01

    Objective The replacement of cytology with human papillomavirus testing as the primary cervical screening test in England is imminent. In light of newly available evidence, we revised our previous estimates of the likely impact of primary human papillomavirus testing on incidence of cervical cancer. Method and results Using screening data on women aged 25-64 diagnosed with cervical cancer in England between 1988 and 2012, we previously reported that 38.8% had a negative test six months to six years prior to diagnosis. However, not all of these cancers would be prevented by human papillomavirus testing: for 1.0% the human papillomavirus positive test would come too late (within 18 months of diagnosis) to make a difference; 7.6% will have a negative human papillomavirus test (based on 79.9% sensitivity of human papillomavirus testing in cytology negative women); and 2.0% will develop cancer despite a positive human papillomavirus test. Additionally, we estimate that some women (equivalent to 4.3% of current incidence) whose cancers are currently prevented by cytology-based screening will have a false-negative human papillomavirus test. Conclusion Overall, we estimate that 23.9% (95% CI: 19.3-27.6%) of current cases in women invited for screening could be prevented. Based on 2013 cancer incidence statistics, absolute numbers could be reduced by 487 (95% CI 394 to 563) or 3.4 (95% CI 2.8 to 4.0) per 100,000 women per year.

  13. Kallikrein-8 Proteolytically Processes Human Papillomaviruses in the Extracellular Space To Facilitate Entry into Host Cells

    PubMed Central

    Cerqueira, Carla; Samperio Ventayol, Pilar; Vogeley, Christian

    2015-01-01

    ABSTRACT The entry of human papillomaviruses into host cells is a complex process. It involves conformational changes at the cell surface, receptor switching, internalization by a novel endocytic mechanism, uncoating in endosomes, trafficking of a subviral complex to the Golgi complex, and nuclear entry during mitosis. Here, we addressed how the stabilizing contacts in the capsid of human papillomavirus 16 (HPV16) may be reversed to allow uncoating of the viral genome. Using biochemical and cell-biological analyses, we determined that the major capsid protein L1 underwent proteolytic cleavage during entry. In addition to a dispensable cathepsin-mediated proteolysis that occurred likely after removal of capsomers from the subviral complex in endosomes, at least two further proteolytic cleavages of L1 were observed, one of which was independent of the low-pH environment of endosomes. This cleavage occurred extracellularly. Further analysis showed that the responsible protease was the secreted trypsin-like serine protease kallikrein-8 (KLK8) involved in epidermal homeostasis and wound healing. Required for infection, the cleavage was facilitated by prior interaction of viral particles with heparan sulfate proteoglycans. KLK8-mediated cleavage was crucial for further conformational changes exposing an important epitope of the minor capsid protein L2. Occurring independently of cyclophilins and of furin that mediate L2 exposure, KLK8-mediated cleavage of L1 likely facilitated access to L2, located in the capsid lumen, and potentially uncoating. Since HPV6 and HPV18 also required KLK8 for entry, we propose that the KLK8-dependent entry step is conserved. IMPORTANCE Our analysis of the proteolytic processing of incoming HPV16, an etiological agent of cervical cancer, demonstrated that the capsid is cleaved extracellularly by a serine protease active during wound healing and that this cleavage was crucial for infection. The cleavage of L1 is one of at least four structural

  14. Kallikrein-8 Proteolytically Processes Human Papillomaviruses in the Extracellular Space To Facilitate Entry into Host Cells.

    PubMed

    Cerqueira, Carla; Samperio Ventayol, Pilar; Vogeley, Christian; Schelhaas, Mario

    2015-07-01

    The entry of human papillomaviruses into host cells is a complex process. It involves conformational changes at the cell surface, receptor switching, internalization by a novel endocytic mechanism, uncoating in endosomes, trafficking of a subviral complex to the Golgi complex, and nuclear entry during mitosis. Here, we addressed how the stabilizing contacts in the capsid of human papillomavirus 16 (HPV16) may be reversed to allow uncoating of the viral genome. Using biochemical and cell-biological analyses, we determined that the major capsid protein L1 underwent proteolytic cleavage during entry. In addition to a dispensable cathepsin-mediated proteolysis that occurred likely after removal of capsomers from the subviral complex in endosomes, at least two further proteolytic cleavages of L1 were observed, one of which was independent of the low-pH environment of endosomes. This cleavage occurred extracellularly. Further analysis showed that the responsible protease was the secreted trypsin-like serine protease kallikrein-8 (KLK8) involved in epidermal homeostasis and wound healing. Required for infection, the cleavage was facilitated by prior interaction of viral particles with heparan sulfate proteoglycans. KLK8-mediated cleavage was crucial for further conformational changes exposing an important epitope of the minor capsid protein L2. Occurring independently of cyclophilins and of furin that mediate L2 exposure, KLK8-mediated cleavage of L1 likely facilitated access to L2, located in the capsid lumen, and potentially uncoating. Since HPV6 and HPV18 also required KLK8 for entry, we propose that the KLK8-dependent entry step is conserved. Our analysis of the proteolytic processing of incoming HPV16, an etiological agent of cervical cancer, demonstrated that the capsid is cleaved extracellularly by a serine protease active during wound healing and that this cleavage was crucial for infection. The cleavage of L1 is one of at least four structural alterations that

  15. Human Papillomavirus Vaccine and Postural Orthostatic Tachycardia Syndrome: A Review of Current Literature.

    PubMed

    Butts, Breann N; Fischer, Philip R; Mack, Kenneth J

    2017-10-01

    The human papillomavirus (HPV) vaccine is efficacious in preventing complications of human papillomavirus infection including cervical cancer. However, there have been case reports of adverse events occurring after vaccination, one being postural orthostatic tachycardia syndrome (POTS). This article reviews published data and other available information regarding the relationship between the human papillomavirus vaccine and POTS. Background information is provided regarding the human papillomavirus vaccine and the proposed post-vaccination adverse event POTS. Peer-reviewed literature, statements by government and medical advisory committees, and publicly available information published on this topic are examined. At this time, there is no conclusive evidence supporting a causal relationship between the human papillomavirus vaccine and POTS. Though a causal relationship has been postulated, it is of utmost importance to recognize that while temporal associations may be observed, conclusions of causality cannot be drawn from case reports and case series due to the small sample size and lack of control population.

  16. Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity

    PubMed Central

    Zhang, Wei; Kazakov, Teymur; Popa, Andreea

    2014-01-01

    ABSTRACT The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry. PMID:25227470

  17. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    PubMed

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study.

  18. Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses.

    PubMed

    Boxman, I L; Russell, A; Mulder, L H; Bavinck, J N; ter Schegget, J; Green, A

    2001-11-01

    Epidermodysplasia-verruciformis-associated human papillomavirus DNA has been demonstrated in squamous cell carcinomas and plucked hair from immunocompetent patients and renal transplant recipients. This study investigated the association between infection with epidermodysplasia-verruciformis-associated human papillomavirus, identified by the detection of viral DNA in plucked eyebrow hairs, and solar keratoses. These lesions are strongly predictive of squamous cell carcinoma. In a cross-sectional study 518 individuals were enrolled from a randomly selected sample of a subtropical Australian community. Epidermodysplasia-verruciformis-associated human papillomavirus DNA in eyebrow hair was detected using a nested polymerase chain reaction specific for epidermodysplasia-verruciformis-associated human papillomavirus types. Epidermo dysplasia-verruciformis-associated human papillomavirus DNA was present in 121 (49%) of 245 men and 116 (44%) of 262 women. There was a strongly significant increase in epidermodysplasia-verruciformis-associated human papillomavirus infection with age (p < 0.00001), with prevalences of 29% in the 25-39 y age group, 42% at 40-59 y and 65% in the 60-79 y age group. Among men there was a strong association between epidermodysplasia-verruciformis-associated human papillomavirus and solar keratoses with an odds ratio, adjusted for age, skin color, and occupational sun exposure, of 3.40 (95% confidence interval, 1.77-6.53). No such association was found among women [odds ratio 1.03 (95% confidence interval 0.59-1.77, after adjustment for the same factors)]. Differences in occupational sun exposure and smoking histories could not explain these apparently different associations between epidermodysplasia-verruciformis-associated human papillomavirus infection and solar keratoses in men and women. In conclusion, epidermodysplasia-verruciformis-associated human papillomavirus infection is associated with solar keratoses in men suggesting that

  19. Vaccines for human papillomavirus infection: a critical analysis.

    PubMed

    Nath, Amiya Kumar; Thappa, Devinder Mohan

    2009-01-01

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

  20. The Moral Justification for a Compulsory Human Papillomavirus Vaccination Program

    PubMed Central

    2009-01-01

    Compulsory human papillomavirus (HPV) vaccination of young girls has been proposed as a public health intervention to reduce the threat of the disease. Such a program would entail a symbiotic relationship between scientific interests in reducing mortality and morbidity and philosophical interests in promoting morality. This proposal raises the issue of whether government should use its police powers to restrict liberty and parental autonomy for the purpose of preventing harm to young people. I reviewed the scientific literature that questions the value of a HPV vaccination. Applying a principle-based approach to moral reasoning, I concluded that compulsory HPV vaccinations can be justified on moral, scientific, and public health grounds. PMID:19197085

  1. [Human papillomavirus vaccines: a new challenge for pediatricians].

    PubMed

    Martinón-Torres, F; Bernaola Iturbe, E; Giménez Sánchez, F; Baca Cots, M; De Juan Martín, F; Díez Domingo, J; Garcés Sánchez, M; Gómez Campderá, J A; Picazo, J J; Pineda Solas, V

    2006-11-01

    Human papillomavirus (HPV) infections are the most common sexually transmitted infections in the world. This infection is a necessary cause of cervical cancer, has been related to other forms of anogenital, airway and digestive cancers, and also causes anogenital warts. The recent advances in HPV prophylactic vaccines and their imminent commercial availability will post a new challenge to pediatricians: the indication and administration of these vaccines for the prevention of HPV infection, and consequently, of cervical cancer and other HPV-related diseases. The present article reviews the essentials of HPV infection, its relationship with cervical cancer, the advances in prophylactic HPV vaccines, and the role of the pediatrician in this context.

  2. Human Papillomavirus and Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Hennessey, P.T.; Westra, W.H.; Califano, J.A.

    2009-01-01

    Over the past 20 years, high-risk human papillomavirus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancer and a small minority of oral cavity cancers. In this review, we summarize what is currently known about the biology of HPV, the mechanisms by which it effects malignant transformation, and the potential impact of HPV status on the clinical management of persons with head and neck cancer. PMID:19407148

  3. Focal epithelial hyperplasia: a multifocal oral human papillomavirus infection.

    PubMed

    Flaitz, C M

    2000-01-01

    Widespread, slightly elevated and confluent nodules are observed throughout the oral mucosa in a young Hispanic girl. Repeated irritation of the soft tissues from a compromised occlusion is an aggravating factor for the spread of these lesions. A diagnosis of focal epithelial hyperplasia, a human papillomavirus infection, is made following histopathologic diagnosis and viral typing. Recognition of this specific type of warts is important in order to avoid the mistaken identification of condyloma acuminata, which may have significant repercussions in the life of a young child.

  4. Development and psychometric evaluation of the Thai Human Papillomavirus Beliefs Scale.

    PubMed

    Juntasopeepun, Phanida; Davidson, Patricia M; Chang, Sungwon; Suwan, Natthawan; Phianmongkhol, Yupin; Srisomboon, Jatupol

    2011-12-01

    In this study, we developed and evaluated the psychometric properties of the Thai Human Papillomavirus Beliefs Scale. The Scale was tested on 386 young women aged 18-24 years in Chiang Mai, Thailand. Content validity of the Scale was evaluated by a panel of experts, construct validity was determined using exploratory factor analysis, and reliability was assessed for stability and internal consistency. Factor analysis provided empirical support for the existence of four factors, which accounted for 67.7% of the total variance: perceived susceptibility, perceived seriousness, perceived benefits, and perceived barriers. Cronbach's α reliability coefficients for the four subscales ranged from 0.59 to 0.86. Factors predicting intention to receive the papillomavirus vaccine were perceived susceptibility, perceived benefits, and perceived barriers. The Thai Human Papillomavirus Beliefs Scale demonstrated promising psychometric properties, indicating that it might be a useful instrument for assessing young women's human papillomavirus and cervical cancer-associated beliefs, and for predicting human papillomavirus vaccination intention.

  5. Mucosal and Cutaneous Human Papillomaviruses Detected in Raw Sewages

    PubMed Central

    La Rosa, Giuseppina; Fratini, Marta; Accardi, Luisa; D'Oro, Graziana; Della Libera, Simonetta; Muscillo, Michele; Di Bonito, Paola

    2013-01-01

    Epitheliotropic viruses can find their way into sewage. The aim of the present study was to investigate the occurrence, distribution, and genetic diversity of Human Papillomaviruses (HPVs) in urban wastewaters. Sewage samples were collected from treatment plants distributed throughout Italy. The DNA extracted from these samples was analyzed by PCR using five PV-specific sets of primers targeting the L1 (GP5/GP6, MY09/MY11, FAP59/64, SKF/SKR) and E1 regions (PM-A/PM-B), according to the protocols previously validated for the detection of mucosal and cutaneous HPV genotypes. PCR products underwent sequencing analysis and the sequences were aligned to reference genomes from the Papillomavirus Episteme database. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. A broad spectrum of sequences related to mucosal and cutaneous HPV types was detected in 81% of the sewage samples analyzed. Surprisingly, sequences related to the anogenital HPV6 and 11 were detected in 19% of the samples, and sequences related to the “high risk” oncogenic HPV16 were identified in two samples. Sequences related to HPV9, HPV20, HPV25, HPV76, HPV80, HPV104, HPV110, HPV111, HPV120 and HPV145 beta Papillomaviruses were detected in 76% of the samples. In addition, similarity searches and phylogenetic analysis of some sequences suggest that they could belong to putative new genotypes of the beta genus. In this study, for the first time, the presence of HPV viruses strongly related to human cancer is reported in sewage samples. Our data increases the knowledge of HPV genomic diversity and suggests that virological analysis of urban sewage can provide key information useful in supporting epidemiological studies. PMID:23341898

  6. Mucosal and cutaneous human papillomaviruses detected in raw sewages.

    PubMed

    La Rosa, Giuseppina; Fratini, Marta; Accardi, Luisa; D'Oro, Graziana; Della Libera, Simonetta; Muscillo, Michele; Di Bonito, Paola

    2013-01-01

    Epitheliotropic viruses can find their way into sewage. The aim of the present study was to investigate the occurrence, distribution, and genetic diversity of Human Papillomaviruses (HPVs) in urban wastewaters. Sewage samples were collected from treatment plants distributed throughout Italy. The DNA extracted from these samples was analyzed by PCR using five PV-specific sets of primers targeting the L1 (GP5/GP6, MY09/MY11, FAP59/64, SKF/SKR) and E1 regions (PM-A/PM-B), according to the protocols previously validated for the detection of mucosal and cutaneous HPV genotypes. PCR products underwent sequencing analysis and the sequences were aligned to reference genomes from the Papillomavirus Episteme database. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. A broad spectrum of sequences related to mucosal and cutaneous HPV types was detected in 81% of the sewage samples analyzed. Surprisingly, sequences related to the anogenital HPV6 and 11 were detected in 19% of the samples, and sequences related to the "high risk" oncogenic HPV16 were identified in two samples. Sequences related to HPV9, HPV20, HPV25, HPV76, HPV80, HPV104, HPV110, HPV111, HPV120 and HPV145 beta Papillomaviruses were detected in 76% of the samples. In addition, similarity searches and phylogenetic analysis of some sequences suggest that they could belong to putative new genotypes of the beta genus. In this study, for the first time, the presence of HPV viruses strongly related to human cancer is reported in sewage samples. Our data increases the knowledge of HPV genomic diversity and suggests that virological analysis of urban sewage can provide key information useful in supporting epidemiological studies.

  7. Structural basis for acyl-group discrimination by human Gcn5L2

    PubMed Central

    Ringel, Alison E.; Wolberger, Cynthia

    2016-01-01

    Gcn5 is a conserved acetyltransferase that regulates transcription by acetylating the N-terminal tails of histones. Motivated by recent studies identifying a chemically diverse array of lysine acyl modifications in vivo, the acyl-chain specificity of the acetyltransferase human Gcn5 (Gcn5L2) was examined. Whereas Gcn5L2 robustly catalyzes lysine acetylation, the acyltransferase activity of Gcn5L2 becomes progressively weaker with increasing acyl-chain length. To understand how Gcn5 discriminates between different acyl-CoA molecules, structures of the catalytic domain of human Gcn5L2 bound to propionyl-CoA and butyryl-CoA were determined. Although the active site of Gcn5L2 can accommodate propionyl-CoA and butyryl-CoA without major structural rearrangements, butyryl-CoA adopts a conformation incompatible with catalysis that obstructs the path of the incoming lysine residue and acts as a competitive inhibitor of Gcn5L2 versus acetyl-CoA. These structures demonstrate how Gcn5L2 discriminates between acyl-chain donors and explain why Gcn5L2 has weak activity for acyl moieties that are larger than an acetyl group. PMID:27377381

  8. Human papillomavirus DNA and mRNA prevalence and association with cervical cytological abnormalities in the Irish HIV population.

    PubMed

    Loy, Aisling; McInerney, Jamie; Pilkington, Loretto; Keegan, Helen; Delamere, Sandra; Martin, Cara M; Sheils, Orla; O'Leary, John J; Mulcahy, Fiona

    2015-10-01

    The complex interplay between HIV and human papillomavirus and its link to cervical dysplasia is poorly understood. This is the first study to assess the prevalence of oncogenic human papillomavirus mRNA in HIV-positive women, its relationship to HIV and its potential use in the triage of cervical cancer screening in HIV-positive women. In this cross-sectional study, we included 321 HIV-positive women. In all, 28.7% had abnormal cervical cytology, 51.1% were human papillomavirus DNA-positive and 21.8% tested positive for human papillomavirus mRNA. Women with a CD4 count of <200 × 10(6)/L were more likely to test positive for human papillomavirus DNA and mRNA. Virally suppressed women were less likely to be human papillomavirus DNA-positive; however, the same did not hold true for human papillomavirus mRNA. We found the human papillomavirus mRNA screening to be more specific when screening for low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion than human papillomavirus DNA at 84.53% compared to 57.36%. However, the sensitivity was less at 51.59% versus 91.07% for human papillomavirus DNA. It may be possible in the future to use human papillomavirus mRNA/DNA testing within a triage algorithm for the screening and management of cervical cancer in the HIV-positive patient. © The Author(s) 2015.

  9. Study of the partners of women with human papillomavirus infection.

    PubMed

    Kokelj, F; Baraggino, E; Stinco, G; Wiesenfeld, U

    1993-09-01

    Genital human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases, and it has been identified as a significant risk factor for the development of dysplasia and cancer of the uterine cervix. The possible influence of male HPV lesions on female cervix oncogenesis has not been elucidated so far. In the present study we evaluate the male partners of women with clinical or subclinical HPV infection with particular interest in the clinical features of this infection in both partners. We examined 81 male partners of women affected with human papillomavirus infections. Condylomata acuminata were searched for by visual inspection. Subclinical lesions were searched by 5 power optical magnification lens after application of 5% acetic acid. In men we observed the following percentage of infection: 67% of the partners of women affected with condylomata acuminata, 46% of the partners of women affected with subclinical lesions (acetic acid positive), and 40% of the partners of women with association of HPV and cervical intraepithelial neoplasia. Our data stress that very often the partners of women with HPV subclinical infection, especially when associated with CIN, do not present lesions, and consequently primary prevention may be very difficult.

  10. hpvPDB: An Online Proteome Reserve for Human Papillomavirus

    PubMed Central

    Jena, Lingaraja; Daf, Sangeeta; Mohod, Kanchan; Goyal, Peyush; Varma, Ashok K.

    2013-01-01

    Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB) domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design. PMID:24465243

  11. [Human papillomavirus infection in male genitalia].

    PubMed

    Cano Garfias, R; Villarreal Peral, C; Juárez Azpilcueta, A

    1995-10-01

    A prospective and transversal study in 100 patients since January to December of 1994, was done, to know the human papiloma virus infection prevalence in male genitals. The patients were studied by a clinical history, genital area colposcopic revision after acetic acid 5% application, biopsy of the lesion and histopathology study. The patients age was among 16 to 71 years old, with a media of 38.8 years old. The sexual activity beginning was from 12 to 27 years old, with an average of 18 years old. Forty one percent of the patients have had sexual relations with prostitutes, 26% have had sexually transmitted diseases, 9% of the patients referred only 1 sexual mate and 82% had human papiloma virus infection.

  12. Sp100 provides intrinsic immunity against human papillomavirus infection.

    PubMed

    Stepp, Wesley H; Meyers, Jordan M; McBride, Alison A

    2013-11-05

    Most DNA viruses associate with, and reorganize, nuclear domain 10 (ND10) bodies upon entry into the host nucleus. In this study, we examine the roles of the ND10 components PML, Sp100, and Daxx in the establishment of human papillomavirus type 18 (HPV18) infection of primary human keratinocytes. HPV18 DNA or HPV18 quasivirus was introduced into primary human keratinocytes depleted of each ND10 protein by small interfering RNA technology, and genome establishment was determined by using a quantitative immortalization assay and measurements of viral transcription and DNA replication. Keratinocyte depletion of Sp100 resulted in a substantial increase in the number of HPV18-immortalized colonies and a corresponding increase in viral transcription and DNA replication. However, Sp100 repressed viral transcription and replication only during the initial stages of viral establishment, suggesting that Sp100 acts as a repressor of incoming HPV DNA. The intrinsic immune system provides a first-line defense against invading pathogens. Host cells contain nuclear bodies (ND10) that are important for antiviral defense, yet many DNA viruses localize here upon cell entry. However, viruses also disrupt, reorganize, and modify individual components of the bodies. In this study, we show that one of the ND10 components, Sp100, limits the infection of human skin cells by human papillomavirus (HPV). HPVs are important pathogens that cause many types of infection of the cutaneous and mucosal epithelium and are the causative agents of several human cancers. Understanding how host cells counteract HPV infection could provide insight into antimicrobial therapies that could limit initial infection.

  13. Presence of highly oncogenic human papillomavirus in the oral mucosa of asymptomatic men.

    PubMed

    Machado, Ana Paula; Gatto de Almeida, Flávia; Bonin, Camila Mareti; Martins Prata, Thiago Theodoro; Sobrinho Ávilla, Leandro; Junqueira Padovani, Cacilda Tezelli; Teixeira Ferreira, Alda Maria; dos Santos Fernandes, Carlos Eurico; Tozetti, Inês Aparecida

    2014-01-01

    The aim of this study was to identify highly oncogenic forms of human papillomavirus in the oral mucosa of asymptomatic men. In this study, we analyzed samples of exfoliated cells from the oral cavity of 559 asymptomatic men. DNA-human papillomavirus was detected using the consensus primers PGMY09/11; viral genotyping was performed using type-specific PCR and restriction fragment length polymorphism. DNA-human papillomavirus was detected in 1.3% of the study participants and of those 42.8% were infected by more than one type of virus. Viral types included HPV6, 11, 89 (low oncogenic risk), and HPV52, 53 (high oncogenic risk). Increased vulnerability to human papillomavirus infection was observed in individuals aged over 26 years, among those who reported oral sex practices, and in those who have had more than 16 sexual partners since first engaging in sexual intercourse. There was a low prevalence of human papillomavirus detection in the oral mucosa of asymptomatic men. Highly oncogenic human papillomavirus types and infection by more than one viral type was observed. Oral sex practices and a large number of sexual partners may increase the risk of acquiring human papillomavirus infection. Copyright © 2014. Published by Elsevier Editora Ltda.

  14. Role of antibodies to human papillomavirus 16 in prostate cancer: A seroscreening by peptide microarray.

    PubMed

    Zhao, Xiaojun; Zhou, Zheng; Chen, Ye; Chen, Wen; Ma, Hongwei; Pu, Jinxian

    2017-06-01

    Evidence is accumulating in estimating the potential role of human papillomavirus infection in prostate carcinogenesis. However, the results remain inconclusive. We measured the serostatus of antibodies to one of the high-risk human papillomaviruses, human papillomavirus 16, with a newly developed peptide microarray. Serum samples were collected from 75 untreated prostate cancer patients, along with 80 control subjects. We identified 12 peptides with significant differences in prostate cancer samples from all 241 peptides derived from human papillomavirus 16. Our results showed human papillomavirus 16 infection in 64.0% of prostate cancer serum samples, which is significantly different compared with the controls ( p < 0.01) because only 17.5% of the control serum was considered seropositive. The area under the receiver operator characteristic curve was 0.793 (95% confidence interval 0.721-0.864), indicating that the new microarray technique may have diagnostic value. The results showed an association between serological evidence for human papillomavirus 16 infection and risk of prostate cancer. The different serostatus of antibodies in the two subgroups indicated that human papillomavirus 16 infection might occur and play a potential role of progression in a minority of prostate cancer.

  15. Human papillomavirus type 18 infection in a female renal allograft recipient: a case report.

    PubMed

    Cistjakovs, Maksims; Sultanova, Alina; Jermakova, Olga; Chapenko, Svetlana; Lesina-Korne, Baiba; Rozental, Rafail; Razeberga, Dace; Murovska, Modra; Ziedina, Ieva

    2016-11-09

    Human papillomavirus type 18 is the second most common cause of cervical cancer and is found in 7 to 20 % of cases of cervical cancer. The oncogenic potential of high-risk human papillomavirus is associated with expression of early proteins E6 and E7. Due to long-term immunosuppressive therapy, renal transplant recipients have a higher risk of developing persistent human papillomavirus infection. A 29-year-old white woman from Latvia with chronic focal segmental glomerulosclerosis received renal allograft transplantation and was prescribed immunosuppressive therapy with cyclosporine, prednisolone, and mycophenolate mofetil. Two weeks after renal transplantation, her cervical swab was positive for human papillomavirus consensus sequences. After 6 months, quantitative polymerase chain reaction showed a high viral load of 3,630,789 copies/10(5) cells of high-risk human papillomavirus type 18 and expression of E6 and E7 oncogenes in her cervical swab and urine sample. One year after renal transplantation, the viral load in her cervical swab increased significantly to 7,413,102 copies/10(5) cells. Messenger ribonucleic acid of human papillomavirus type 18 E6 and E7 oncogenes were also detected. Shortly after this, she had an unsuccessful pregnancy which resulted in a spontaneous abortion at 6/7 weeks. Two months after the abortion her viral load sharply decreased to 39 copies/10(5) cells. Oncogenes E6 and E7 messenger ribonucleic acid expression was not observed in this period. This case report represents data which show that immunosuppressive therapy may increase the risk of developing persistent high-risk human papillomavirus infection with expression of E6 and E7 oncogenes in renal transplant recipients. However, even during this therapy the immune status of a recipient can improve and contribute to human papillomavirus viral load reduction. Spontaneous abortion can be considered a possible contributory factor in human papillomavirus clearance.

  16. The effect of intrauterine devices on acquisition and clearance of human papillomavirus.

    PubMed

    Averbach, Sarah H; Ma, Yifei; Smith-McCune, Karen; Shiboski, Stephen; Moscicki, Anna B

    2017-04-01

    Previous studies have shown a decrease in cervical cancer associated with intrauterine device use. It has been hypothesized that intrauterine device use may alter the natural history of human papillomavirus infections, preempting development of precancerous lesions of the cervix and cervical cancer, but the effect of intrauterine devices on the natural history of human papillomavirus infection and subsequent development of cervical cancer is poorly understood. The purpose of this study was to evaluate the association between intrauterine device use and cervical high-risk human papillomavirus acquisition and clearance. This is a prospective cohort study conducted from October 2000 through June 2014 among 676 sexually active young women and girls enrolled from family planning clinics in San Francisco, CA. Data were analyzed using a Cox proportional hazards model, including time-varying indicators of intrauterine device use, and adjusting for fixed and time-dependent predictor variables. A total of 85 women used an intrauterine device at some time during follow-up. Among 14,513 study visits, women reported intrauterine device use at 505 visits. After adjusting for potential behavioral confounders, there was no association between intrauterine device use and human papillomavirus acquisition (hazard ratio, 0.50; 95% confidence interval, 0.20-1.23; P = .13) or clearance of human papillomavirus infection (hazard ratio, 1.44; 95% confidence interval, 0.76-2.72; P = .26). Current intrauterine device use is not associated with acquisition or persistence of human papillomavirus infection. Intrauterine device use is safe among women and girls with human papillomavirus infections and at risk for human papillomavirus acquisition. Intrauterine device use may play a role further downstream in the natural history of cervical cancer by inhibiting the development of precancerous lesions of the cervix in human papillomavirus-infected women, or enhancing clearance of established

  17. The roles of the exoribonucleases DIS3L2 and XRN1 in human disease.

    PubMed

    Pashler, Amy L; Towler, Benjamin P; Jones, Christopher I; Newbury, Sarah F

    2016-10-15

    RNA degradation is a vital post-transcriptional process which ensures that transcripts are maintained at the correct level within the cell. DIS3L2 and XRN1 are conserved exoribonucleases that are critical for the degradation of cytoplasmic RNAs. Although the molecular mechanisms of RNA degradation by DIS3L2 and XRN1 have been well studied, less is known about their specific roles in the development of multicellular organisms or human disease. This review focusses on the roles of DIS3L2 and XRN1 in the pathogenesis of human disease, particularly in relation to phenotypes seen in model organisms. The known diseases associated with loss of activity of DIS3L2 and XRN1 are discussed, together with possible mechanisms and cellular pathways leading to these disease conditions. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  18. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer.

    PubMed

    Whitaker, Noel J; Glenn, Wendy K; Sahrudin, Arisha; Orde, Matthew M; Delprado, Warick; Lawson, James S

    2013-02-15

    The purpose of this study is to determine if high risk human papillomaviruses (HPV) and Epstein Barr virus (EBV) are both present in the same prostate cancer specimens. We used a range of analytical techniques including in situ polymerase chain reaction (IS-PCR) and standard liquid PCR followed by sequencing of the product to seek to identify HPV and EBV in normal, benign, and malignant prostate tissues. Both HPV type 18 and EBV gene sequences were identified in a high and approximately equal proportion of normal, benign, and prostate cancer specimens. These sequences were located in the nuclei of prostate epithelial cells. HPV associated koilocytes were identified in 24% of prostate cancer specimens. The presence of both HPV and EBV gene sequences in most of the same normal, benign, and malignant prostate specimens is particularly noteworthy because of recent experimental evidence demonstrating that EBV and HPV can collaborate to increase proliferation of cultured cervical cells. Because the presence of EBV and HPV in normal, benign, and malignant prostate tissues appears to be ubiquitous, it is possible that they are harmless. On the other hand HPV type 18 in particular, has high oncogenic potential and may be associated with some prostate cancers. The identification of HPV associated koilocytes in prostate cancer specimens is an indication of HPV infection and potential oncogenic influences of human papillomavirus in prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

  19. Evasion of host immune defenses by human papillomavirus.

    PubMed

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

    2017-03-02

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

  20. [Transfer factor effectiveness patients with persistent genital human papillomavirus infection].

    PubMed

    Morfin-Maciel, Blanca María; Sotelo-Ortiz, Julieta Margarita

    2012-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.

  1. Human papillomavirus vaccine: A boon or curse

    PubMed Central

    Chawla, Sumit; Singh, Inderjeet; Jain, Rambilas; Mehta, Bharti; Kumari, Sneh; Sahoo, Soumya Swaroop

    2015-01-01

    Cervical cancer is the second most common cancer among women worldwide, with about 493,000 new cases diagnosed annually. Of 274,000 deaths due to cervical cancer each year, more than 80% occur in developing countries, and this proportion is expected to increase to 90% by 2020. Up to 70% of sexually active women will become infected with human papilloma virus (HPV) during their lifetime. Even though screening reduces the risk of cervical cancer, it does not prevent HPV infection or development of precancerous lesions which need careful follow-up and often need excision. It was observed in a study, pre-adolescent vaccination alone reduced cancer incidence by 44% and was more effective than screening alone. A combined approach of pre-adolescent vaccination and screening of adult women was more effective than either alone. The high probability of acquiring HPV infection once, one has become sexually active raises the question of whether the vaccine will be effective if given to girls who have already been infected with HPV type 16 or 18. In April 2010, The Indian parliament's Standing Committee on Health, began probing the use of HPV vaccines in 2 states after the reported deaths of 7 girls, and concluded that “safety and rights of children were highly compromised and violated.” Though the question of immunization of older girls and women deserves attention, from a public health perspective, the first priority in resource-poor settings would be to vaccinate young adolescent girls. PMID:25668662

  2. Human papillomavirus vaccine: a boon or curse.

    PubMed

    Chawla, Sumit; Singh, Inderjeet; Jain, Rambilas; Mehta, Bharti; Kumari, Sneh; Sahoo, Soumya Swaroop

    2014-01-01

    Cervical cancer is the second most common cancer among women worldwide, with about 493,000 new cases diagnosed annually. Of 274,000 deaths due to cervical cancer each year, more than 80% occur in developing countries, and this proportion is expected to increase to 90% by 2020. Up to 70% of sexually active women will become infected with human papilloma virus (HPV) during their lifetime. Even though screening reduces the risk of cervical cancer, it does not prevent HPV infection or development of precancerous lesions which need careful follow-up and often need excision. It was observed in a study, pre-adolescent vaccination alone reduced cancer incidence by 44% and was more effective than screening alone. A combined approach of pre-adolescent vaccination and screening of adult women was more effective than either alone. The high probability of acquiring HPV infection once, one has become sexually active raises the question of whether the vaccine will be effective if given to girls who have already been infected with HPV type 16 or 18. In April 2010, The Indian parliament's Standing Committee on Health, began probing the use of HPV vaccines in 2 states after the reported deaths of 7 girls, and concluded that "safety and rights of children were highly compromised and violated." Though the question of immunization of older girls and women deserves attention, from a public health perspective, the first priority in resource-poor settings would be to vaccinate young adolescent girls.

  3. Preclinical Model To Test Human Papillomavirus Virus (HPV) Capsid Vaccines In Vivo Using Infectious HPV/Cottontail Rabbit Papillomavirus Chimeric Papillomavirus Particles▿

    PubMed Central

    Mejia, Andres F.; Culp, Timothy D.; Cladel, Nancy M.; Balogh, Karla K.; Budgeon, Lynn R.; Buck, Christopher B.; Christensen, Neil D.

    2006-01-01

    A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach. PMID:17005666

  4. Lessons learned from domestic and international human papillomavirus vaccination programs: a review.

    PubMed

    Miller, Kathryn; Dilley, Sarah E; Huh, Warner K

    2017-09-06

    Since the development of the human papillomavirus vaccine, many countries have created implementation programs to bolster vaccination rates and protect their populations. Despite demonstrated efficacy with decreased human papillomavirus-related disease abroad, the vaccine's potential to prevent morbidity and mortality in the United States is not being met. The purpose of this review is to discuss strategies of both international and domestic vaccination programs, their impact on human papillomavirus-related diseases, the unique obstacles faced by the United States, and future directions for success. Copyright © 2017. Published by Elsevier Inc.

  5. Roles of Human Papillomaviruses and p16 in Oral Cancer.

    PubMed

    Sritippho, Thanun; Chotjumlong, Pareena; Iamaroon, Anak

    2015-01-01

    Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

  6. Human Papillomavirus (HPV)-associated Oral Cancers and Treatment Strategies.

    PubMed

    Sathish, N; Wang, X; Yuan, Y

    2014-07-01

    Human papillomavirus (HPV) is known to be associated with several types of human cancer, including cervical, vulvar, vaginal, penile, anal, and head-and-neck cancers. Among these cancers, HPV-associated head-and-neck cancers, inclusive of oropharyngeal squamous cell carcinoma (OSCC) and oral cavity squamous cell carcinomas (OCSCC), have recently risen dramatically in men under 50 years old. Within 20 years, the percentage of HPV-positive OSCC in total OSCC went from less than 20% to more than 70% in the United States and some European countries. This article reviews the incidence trend and pathogenesis of HPV-associated head-and-neck cancers as well as current treatment modalities for the disease.

  7. Manipulation of the innate immune response by human papillomaviruses.

    PubMed

    Hong, Shiyuan; Laimins, Laimonis A

    2017-03-02

    The innate immune response constitutes the first line of defense against infections by pathogens. Successful pathogens such as human papillomaviruses (HPVs) have evolved mechanisms that target several points in these pathways including sensing of viral genomes, blocking the synthesis of interferons and inhibiting the action of JAK/STAT transcription factors. Disruption of these inhibitory mechanisms contributes to the ability of HPVs to establish persistent infections, which is the major etiological factor in the development of anogenital cancers. Interestingly, HPVs also positively activate several members of these pathways such as STAT-5 that are important for their differentiation-dependent life cycle. STAT-5 activation induces the ATM and ATR DNA damage response pathways that play critical roles in HPV genome amplification. Targeting of these pathways by pharmaceuticals can provide novel opportunities to inhibit infections by these important human pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Human papillomaviruses and carcinogenesis: well-established and novel models.

    PubMed

    Viarisio, Daniele; Gissmann, Lutz; Tommasino, Massimo

    2017-08-01

    Human papillomaviruses (HPVs) infect the cutaneous or mucosal epithelia and are classified phylogenetically as genera and species. Persistent infections by the mucosal high-risk (HR) HPV types from genus alpha are associated with cancer development of the genital and upper respiratory tracts. The products of two early genes, E6 and E7, are the major HR HPV oncoproteins, being essential in all steps of the carcinogenic process. Cutaneous beta HPV types are proposed, together with ultraviolet (UV) radiation, to promote non-melanoma skin cancer development. However, in contrast to the HR HPV types, beta HPV types appear to be required only at an early stage of carcinogenesis, facilitating the accumulation of UV-induced DNA mutations. Although findings in experimental models also suggest that beta HPV types and other carcinogens may synergize in the induction of malignancies, these possibilities need to be confirmed in human studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A DNA methylation classifier of cervical precancer based on human papillomavirus and human genes.

    PubMed

    Brentnall, Adam R; Vasiljević, Nataša; Scibior-Bentkowska, Dorota; Cadman, Louise; Austin, Janet; Szarewski, Anne; Cuzick, Jack; Lorincz, Attila T

    2014-09-15

    Testing for high-risk (hr) types of human papillomavirus (HPV) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (CIN2/3) disease, the precursor of cervical cancer. However, it has a relatively low specificity. Our objective was to develop a prediction rule with a higher specificity, using combinations of human and HPV DNA methylation. Exfoliated cervical specimens from colposcopy-referral cohorts in London were analyzed for DNA methylation levels by pyrosequencing in the L1 and L2 regions of HPV16, HPV18, HPV31 and human genes EPB41L3, DPYS and MAL. Samples from 1,493 hrHPV-positive women were assessed and of these 556 were found to have CIN2/3 at biopsy; 556 tested positive for HPV16 (323 CIN2/3), 201 for HPV18 (73 CIN2/3) and 202 for HPV31 (98 CIN2/3). The prediction rule included EPB41L3 and HPV and had area under curve 0.80 (95% CI 0.78-0.82). For 90% sensitivity, specificity was 36% (33-40) and positive predictive value (PPV) was 46% (43-48). By HPV type, 90% sensitivity corresponded to the following specificities and PPV, respectively: HPV16, 38% (32-45) and 67% (63-71); HPV18, 53% (45-62) and 52% (45-59); HPV31, 39% (31-49) and 58% (51-65); HPV16, 18 or 31, 44% (40-49) and 62% (59-65) and other hrHPV 17% (14-21) and 21% (18-24). We conclude that a methylation assay in hrHPV-positive women might improve PPV with minimal sensitivity loss. © 2014 The Authors. UICC.

  10. Ancient Evolution and Dispersion of Human Papillomavirus Type 58 Variants.

    PubMed

    Chen, Zigui; Ho, Wendy C S; Boon, Siaw Shi; Law, Priscilla T Y; Chan, Martin C W; DeSalle, Rob; Burk, Robert D; Chan, Paul K S

    2017-08-09

    Human papillomavirus type 58 is found in 10-18% of cervical cancers in East Asia but rather uncommon elsewhere. The distribution and oncogenic potential of HPV58 variants appear to be heterogeneous since the E7 T20I/G63S variant is more prevalent in East Asia and confers 7-9 fold higher risk for cervical precancer and cancer. However, the underlying genomic mechanisms that explain the geographic and carcinogenic diversity of HPV58 variants are still poorly understood. In this study, we used a combination of phylogenetic analyses and bioinformatics to investigate the deep evolutionary history of HPV58 complete genome variants. The initial splitting of HPV58 variants was estimated to occur 478,600 (95% HPD 391,000 - 569,600) years ago. This divergence time is well among the era of the speciation between Homo sapiens and Neanderthal/Denisova, and around three times longer than the modern Homo sapiens divergence times. The expansion of present-day variants in Eurasia could be the consequence of viral transmission from Neanderthal/Denisova to non-African modern human populations through gene flow. A whole genome sequence signature analysis identified 3 amino acid changes, 16 synonymous nucleotide changes and a 12-bp insertion strongly associated with the E7 T20I/G63S variant that represents A3 sublineage and carries higher carcinogenetic potential. Compared with the capsid proteins, the oncogenes E7 and E6 had increased substitution rates indicative of higher selection pressure. These data provide a comprehensive evolutionary history and genomic basis of HPV58 variants to assist further investigation on carcinogenic association and development of diagnostic and therapeutic strategies.Importance Papillomaviruses (PVs) are an ancient and heterogeneous group of double stranded DNA viruses preferentially infecting the cutaneous and mucocutaneous epithelium of vertebrates. Persistent infection by specific oncogenic human papillomavirus (HPV) types including HPV58 has been

  11. Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women.

    PubMed

    Azuma, Yukari; Kusumoto-Matsuo, Rika; Takeuchi, Fumihiko; Uenoyama, Asami; Kondo, Kazunari; Tsunoda, Hajime; Nagasaka, Kazunori; Kawana, Kei; Morisada, Tohru; Iwata, Takashi; Aoki, Daisuke; Kukimoto, Iwao

    2014-10-01

    Human papillomavirus vaccines are being introduced worldwide and are expected to reduce the incidence of cervical cancer. Here we report a cross-sectional study using a validated human papillomavirus genotyping method to reveal the human papillomavirus prevalence and genotype distribution in Japanese women with cervical intraepithelial neoplasia Grade 2/3 and invasive cervical cancer. Cervical exfoliated cells were collected from 647 patients with abnormal cervical histology (cervical intraepithelial neoplasia Grade 2, n = 164; cervical intraepithelial neoplasia Grade 3, n = 334; and invasive cervical cancer, n = 149), and subjected to the PGMY-PCR-based genotyping assay. The association between human papillomavirus infection and lesion severity was calculated using a prevalence ratio. Overall, the prevalence of human papillomavirus deoxyribonucleic acid was 96.3% in cervical intraepithelial neoplasia Grade 2, 98.8% in cervical intraepithelial neoplasia Grade 3 and 88.0% in invasive cervical cancer (97.8% in squamous cell carcinoma and 71.4% in adenocarcinoma). The three most prevalent types were as follows: human papillomavirus 16 (29.3%), human papillomavirus 52 (27.4%) and human papillomavirus 58 (22.0%) in cervical intraepithelial neoplasia Grade 2; human papillomavirus 16 (44.9%), human papillomavirus 52 (26.0%) and human papillomavirus 58 (17.4%) in cervical intraepithelial neoplasia Grade 3; and human papillomavirus 16 (47.7%), human papillomavirus 18 (23.5%) and human papillomavirus 52 (8.7%) in invasive cervical cancer. The prevalence ratio of human papillomavirus 16 was significantly higher in cervical intraepithelial neoplasia Grade 3 compared with cervical intraepithelial neoplasia Grade 2 (prevalence ratio, 1.62; 95% confidence interval, 1.26-2.13) and in squamous cell carcinoma compared with cervical intraepithelial neoplasia Grade 3 (prevalence ratio, 1.55; 95% confidence interval, 1.25-1.87). Multiple infections decreased from cervical

  12. Human Papillomavirus Infection Requires Cell Surface Heparan Sulfate

    PubMed Central

    Giroglou, Tzenan; Florin, Luise; Schäfer, Frank; Streeck, Rolf E.; Sapp, Martin

    2001-01-01

    Using pseudoinfection of cell lines, we demonstrate that cell surface heparan sulfate is required for infection by human papillomavirus type 16 (HPV-16) and HPV-33 pseudovirions. Pseudoinfection was inhibited by heparin but not dermatan or chondroitin sulfate, reduced by reducing the level of surface sulfation, and abolished by heparinase treatment. Carboxy-terminally deleted HPV-33 virus-like particles still bound efficiently to heparin. The kinetics of postattachment neutralization by antiserum or heparin indicated that pseudovirions were shifted on the cell surface from a heparin-sensitive into a heparin-resistant mode of binding, possibly involving a secondary receptor. Alpha-6 integrin is not a receptor for HPV-33 pseudoinfection. PMID:11152531

  13. Malakoplakia of the esophagus caused by human papillomavirus infection.

    PubMed

    Yang, Ya-Li; Xie, Yu-Cheng; Li, Xiao-Ling; Guo, Jing; Sun, Tao; Tang, Jing

    2012-12-07

    Malakoplakia is a rare granulomatous disease probably caused by infection and characterized histologically by Michaelis-Gutmann bodies. We report a more rarely seen case esophageal malakoplakia in a 54-year-old woman. She presented with coughing while eating and drinking. Gastroscopy showed yellow nodules in the esophagus, and endoscopic ultrasonography showed a space-occupying lesion in the substratum of the esophageal mucosa. All findings highly resembled esophageal cancer. Histopathological examination finally indentified this space-occupying lesion as malakoplakia and not cancer. Immunohistochemistry showed that she had human papillomavirus (HPV) infection in the esophagus, which indicates that infection was responsible for the malakoplakia. This is believed to be the first case of malakoplakia in the esophagus, and more importantly, we established that HPV infection was the initiator of esophageal malakoplakia.

  14. Another Look at the Human Papillomavirus Vaccine Experience in Canada

    PubMed Central

    Deber, Raisa B.; Guttmann, Astrid; McGeer, Allison; Krahn, Murray

    2011-01-01

    Policy debates about immunization frequently focus on classic trade-offs between individual versus collective well-being. Publicly funded immunization programs are usually justified on the basis of widespread public benefit with minimal individual risk. We discuss the example of the policy process surrounding the adoption of the human papillomavirus (HPV) vaccine in Canada to consider whether public good arguments continue to dominate immunization policymaking. Specifically, we show how a range of stakeholders framed HPV vaccination as a personal—rather than a public—matter, despite the absence of a controversy over mandatory immunization as was the case in the United States. Our findings suggest an erosion of the persuasiveness of public good arguments around collective immunization programs in the policy discourse. PMID:21852642

  15. Human Papillomavirus and the HPV Vaccine: Where Are We Today?

    PubMed

    Khan, Leah

    2017-01-01

    Vaccine discussions are an important part of the general pediatrician's day. The human papillomavirus (HPV) vaccine, in particular, has been slow to gain acceptance by the general public. It has recently gained momentum (both positive and negative) on social media, which has led to an increase in questions and concerns from families. It is important that providers are equipped to address these concerns, answer questions, and provide quality information for families to help guide them in their vaccination decisions. Not only is it crucial to be knowledgeable about the vaccines themselves, but providers should also be informed about HPV and its potential disease burden. The HPV vaccine recommendations are also evolving, so it is important to stay abreast with current data to provide the best care for all patients. [Pediatr Ann. 2017;46(1):e2-e5.]. Copyright 2017, SLACK Incorporated.

  16. Progress in prophylactic and therapeutic vaccines for human papillomavirus infection.

    PubMed

    Stanley, Margaret A

    2003-06-01

    Virus-like particle (VLP) subunit vaccines composed of the major capsid protein L1 of the genital human papillomaviruses (HPVs) are now in Phase III clinical trials. The vaccines are immunogenic and safe and early results indicate efficacy. VLPs induce strong cell-mediated as well as humoral immune responses and chimeric VLPs including an HPV early protein may have therapeutic potential. Polynucleotide and recombinant viral vaccines encoding nonstructural viral proteins show therapeutic and prophylactic efficacy in animal models and are candidate immunotherapies for established low-grade benign genital infections. Vaccines designed to elicit cytotoxic T-lymphocytes specific for the HPV oncoproteins E6 and E7 show immunogenicity and efficacy in transplantable tumor models in rodents. In Phase I and II trials these vaccines are immunogenic and safe but show limited efficacy.

  17. Human Papillomavirus Vaccination Guideline Update: American Cancer Society Guideline Endorsement

    PubMed Central

    Saslow, Debbie; Andrews, Kimberly S.; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E.; Fisher-Borne, Marcie; Smith, Robert A.; Fontham, Elizabeth T. H.

    2017-01-01

    The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. PMID:27434803

  18. Young Hispanic Men and Human Papillomavirus Vaccination Choices.

    PubMed

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

    2016-03-01

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

  19. Human papillomavirus infection: a concise review of natural history.

    PubMed

    Huh, Warner K

    2009-07-01

    Persistent infection with oncogenic human papillomavirus (HPV), leading to precancerous lesions and potentially cervical cancer, is a serious health burden. The natural history of infection is one that enables the virus to remain immunoevasive within the cervical epithelium and persist for decades. Many studies have provided important information on why some women clear infection and why others do not. The infectious process of HPV may be affected by many cofactors, adding to the complexity of disease development. Vaccination against oncogenic HPV along with cervical screening are two methods that have been developed to provide protection and eliminate the overall burden of disease in women. This article highlights the natural history of oncogenic HPV infection of the cervix and the limitations that currently exist on the literature.

  20. International standardization and classification of human papillomavirus types.

    PubMed

    Bzhalava, Davit; Eklund, Carina; Dillner, Joakim

    2015-02-01

    Established Human Papillomavirus (HPV) types, up to HPV202, belong to 49 species in five genera. International standardization in classification and quality standards for HPV type designation and detection is ensured by the International HPV Reference Center. The center i) receives clones of potentially novel HPV types, re-clones and re-sequences them. If confirmed, an HPV type number is assigned and posted on www.hpvcenter.se. ii) distributes reference clone samples, for academic research, under Material Transfer Agreements agreed with the originator. iii) provides preliminary checking of whether new sequences represent novel types iv) issues international proficiency panels for HPV genotyping. The rate of HPV type discovery is increasing, probably because of metagenomic sequencing. γ-genus today contains 79HPV types and 27 species, surpassing ∝ and β genera with 65 and 51HPV types, respectively. Regular issuing of proficiency panels based on HPV reference clones has resulted in global improvement of HPV genotyping services.

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

    PubMed

    Cortés-Bordoy, Javier; Martinón-Torres, Federico

    2010-08-01

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

  2. Human papillomavirus vaccination in males: the state of the science.

    PubMed

    Barroso, Luis F; Wilkin, Timothy

    2011-04-01

    Human papillomavirus (HPV) is an extremely prevalent sexually transmitted infection that is typically acquired soon after onset of sexual activity. The burden of HPV-related malignant and nonmalignant disease is high in men and women. High-risk or oncogenic types of HPV cause cervical, vaginal, and vulvar cancer in women. These types have also been shown to cause penile cancer in men and a substantial proportion of oropharyngeal and anal malignancy in men and women. Low-risk types of HPV cause anogenital warts. Prevention of penile, anal, and oropharyngeal cancers and anogenital warts represents potential benefits of the HPV vaccine in men. This review focuses on HPV disease in men, existing data on HPV vaccination in men, and various factors associated with the decision to vaccinate boys and young men, as well as the timing of vaccination.

  3. Low prevalence of Human Papillomavirus in oral cavity carcinomas

    PubMed Central

    2010-01-01

    Background Increasing evidence shows that Human Papillomavirus (HPV) is preferentially associated with some head and neck squamous cell carcinomas (HNSCCs), with variable infection rates reported. Methods We assessed HPV involvement in HNSCC using the Roche Linear Array HPV Genotyping Test, which can detect 37 different HPV types. We examined the prevalence of HPV infection in 92 HNSCCs (oropharynx, oral cavity, and other HNSCC sites). Results HPV was frequently detected in oropharyngeal cancers (OPCs) (16/22, 73%), but was uncommon in oral cavity cancers (2/53, 4%), and in other HNSCC subsites (1/17, 6%). HPV positive tumors were associated with patients that were 40-60 years old (p = 0.02), and node positive (p = < 0.0001). HPV 16 was the most prevalent type, but other types detected included 6, 18, 33, 35, 45, and 52/58. Conclusion Our results show that in contrast to oropharyngeal cancers, oral cancers and other HNSCCs infrequently harbor HPV. PMID:20226055

  4. Nursing care and treatment of the patient with human papillomavirus.

    PubMed

    Peate, Ian

    Human papillomavirus is a common and highly contagious virus that causes genital warts, which are not only unsightly, but the treatment may also be complex and the results of such treatment variable. For the patient this may result in physical and psychological trauma. Over 100 genotypes of the virus have been identified and a number of these can result in benign tumours of the skin and mucosa. Others however, are associated with intraepithelial neoplaisa of the vulva, cervix, penis and anus and squamous cell carcinoma. The nurse can provide the patient with the physical and psychological support the patient needs only if he/she has insight and understanding regarding the infection, its natural history, the diagnosis and subsequent management. Care should be provided in a non-judgmental manner, with respect and empathy.

  5. Patient-provider communication and human papillomavirus vaccine acceptance.

    PubMed

    Rand, Cynthia M; Schaffer, Stanley J; Humiston, Sharon G; Albertin, Christina S; Shone, Laura P; Heintz, Eric V; Blumkin, Aaron K; Stokley, Shannon; Szilagyi, Peter G

    2011-02-01

    The authors performed telephone interviews of parents of adolescents (n = 430) and their older adolescents (n = 208) in Monroe County, New York to measure parent and adolescent acceptance of human papillomavirus (HPV) vaccine, its association with ratings of provider communication, and vaccine-related topics discussed with the adolescent's provider. More than half of adolescent girls had already received an HPV vaccination, with fewer than one quarter refusing. Parent and teen ratings of provider communication was high, and not related to HPV vaccine refusal. Parents were more likely to refuse if they were Hispanic (odds ratio [OR] = 5.88, P = .05) or did not consider vaccines "very safe" (OR = 2.76, P = .04). Most parents of boys (85%) believed males should be given HPV vaccine if recommended. Few parents and teens recalled discussing that vaccination does not preclude future Pap smear testing. Providers should address cultural and vaccine safety concerns in discussions about HPV vaccine.

  6. The case for vaccinating boys against human papillomavirus.

    PubMed

    Hull, Sarah C; Caplan, Arthur L

    2009-01-01

    Vaccination policy in the case of human papillomavirus (HPV) has remained a constant source of controversy ever since Gardasil, Merck's vaccine against HPV, received US Food and Drug Administration approval in the summer of 2006. This controversy has centered on the risks and benefits of vaccinating girls and women in rich and poor nations alike. However, despite all of the attention created by this important policy question, relatively little has been focused on another key public health question: should boys be vaccinated against HPV as well? If herd immunity against the most carcinogenic strains of HPV could be more rapidly and efficiently achieved by vaccinating everyone at risk for being a carrier, it logically follows that vaccine policy should expand to include boys and men.

  7. Human papillomavirus infection in female sex workers in Lima, Peru.

    PubMed

    Montano, Silvia M; Hsieh, Evelyn J; Calderón, Martha; Ton, Thanh G N; Quijano, Eberth; Solari, Vicky; Zunt, Joseph R

    2011-02-01

    To determine the prevalence and risk factors for human papillomavirus (HPV) infection in female sex workers (FSW) in Lima, Peru. Cross-sectional study of 87 FSW. Information regarding demographics, sex work practices, and genital and blood specimens was collected. Forty-four (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected by at least one high-risk HPV type, representing 70.5% of women with HPV infection. HPV infection was associated with younger age but not with any demographic or sexual characteristics. Our study confirms the high prevalence of HPV infection in FSW reported by other groups and suggests that brothel-based FSW may be at lower risk for acquiring high-risk HPV infection.

  8. Human papillomavirus infection in female sex workers in Lima, Peru

    PubMed Central

    Montano, Silvia M; Hsieh, Evelyn J; Calderón, Martha; Ton, Thanh G N; Quijano, Eberth; Solari, Vicky; Zunt, Joseph R

    2012-01-01

    Objectives To determine the prevalence and risk factors for human papillomavirus (HPV) infection in female sex workers (FSW) in Lima, Peru. Methods Cross-sectional study of 87 FSW. Information regarding demographics, sex work practices, and genital and blood specimens was collected. Results Forty-four (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected by at least one high-risk HPV type, representing 70.5% of women with HPV infection. HPV infection was associated with younger age but not with any demographic or sexual characteristics. Conclusions Our study confirms the high prevalence of HPV infection in FSW reported by other groups and suggests that brothel-based FSW may be at lower risk for acquiring high-risk HPV infection. PMID:20813720

  9. The transmembrane channel-like protein family and human papillomaviruses

    PubMed Central

    Horton, Jaime S; Stokes, Alexander J

    2014-01-01

    Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by increased sensitivity to infection by the β-subtype of human papillomaviruses (β-HPVs), causing persistent, tinea versicolor-like dermal lesions. In a majority of affected individuals, these macular lesions progress to invasive cutaneous squamous cell carcinoma (CSCC) in sun-exposed areas. While mutations in transmembrane channel-like 6 (TMC6 / EVER1) and 8 (TMC8 / EVER2) have been causally linked to EV, their molecular functions are unclear. It is likely that their protective effects involve regulation of the β-HPV life cycle, host keratinocyte apoptosis vs. survival balance and/or T-cell interaction with infected host cells. PMID:24800179

  10. Human papillomaviruses: research priorities for the next decade.

    PubMed

    Langsfeld, Erika; Laimins, Laimonis A

    2016-05-01

    Human papillomaviruses are the causative agents of cervical, anal as well as many oropharyngeal cancers. While prophylactic vaccines have been developed, uptake is low in the US and other Western countries, and access is limited in less developed countries. A number of areas are emerging as critical for future study. These include investigation of the mechanisms regulating infection and progression to cancer at both cervical and oropharyngeal sites as these appear to be distinct. HPV-induced cancers also may be susceptible to immune therapy, revealing opportunities for treating advanced cervical disease and reducing the morbidity of treatments for oropharyngeal cancers. We believe these areas are critical focal points for HPV cancer research in the next decade.

  11. Human papillomaviruses: shared and distinct pathways for pathogenesis

    PubMed Central

    Galloway, Denise A.; Laimins, Laimonis A.

    2015-01-01

    Over 200 types of human papillomaviruses (HPV) have been identified that infect epithelial cells at different anatomic locations. HPVs are grouped into five genra with the alpha and beta viruses being the most commonly studied. Members of the alpha HPV genus infect genital epithelia and are the causative agents of many anogenital cancers. Beta HPVs infect cutaneous epithelia and have been suggested as co-factors in the development of non-melanoma skin cancers. Recent studies have shown that activation of DNA damage pathways is important for the productive life cycle of the alpha HPVs while the beta viruses suppress their activation. These differences likely contribute to the varying types of lesions and malignancies that are associated with these viruses. PMID:26398222

  12. Human papillomaviruses: shared and distinct pathways for pathogenesis.

    PubMed

    Galloway, Denise A; Laimins, Laimonis A

    2015-10-01

    Over 200 types of human papillomaviruses (HPV) have been identified that infect epithelial cells at different anatomic locations. HPVs are grouped into five genera with the alpha and beta viruses being the most commonly studied. Members of the alpha HPV genus infect genital epithelia and are the causative agents of many anogenital cancers. Beta HPVs infect cutaneous epithelia and have been suggested as co-factors in the development of non-melanoma skin cancers. Recent studies have shown that activation of DNA damage pathways is important for the productive life cycle of the alpha HPVs while the beta viruses suppress their activation. These differences likely contribute to the varying types of lesions and malignancies that are associated with these viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Home-Based or Clinic-Based Human Papillomavirus (HPV) Screening

    ClinicalTrials.gov

    2017-01-23

    Atypical Squamous Cell of Undetermined Significance; Cervical Carcinoma; Cervical Intraepithelial Neoplasia Grade 2/3; Health Status Unknown; Human Papillomavirus Infection; Low Grade Cervical Squamous Intraepithelial Neoplasia; Stage 0 Cervical Cancer

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

    MedlinePlus

    ... 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® ...

  15. Distribution and attribution of high-risk human papillomavirus genotypes in cervical precancerous lesions in China.

    PubMed

    Wang, Wenpeng; An, Jusheng; Song, Yan; Wang, Minjie; Huang, Manni; Wu, Lingying

    2017-07-01

    While human papillomavirus vaccine was recently approved by China Food and Drug Administration, mapping of high-risk human papillomavirus distribution and attribution in cervical precancerous lesions in China becomes critical in development of a high-risk human papillomavirus-based cervical cancer screening and prevention strategy. In total, 1016 patients with cervical precancerous lesions diagnosed in the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively, including 111 patients with low-grade squamous intraepithelial lesions and 905 patients with high-grade squamous intraepithelial lesions. HPV16, 58, 52, 33, and 31 were the most common high-risk human papillomavirus genotypes in order of decreasing frequency among high-risk human papillomavirus-positive high-grade squamous intraepithelial lesions; this differed from the high-risk human papillomavirus distribution in low-grade squamous intraepithelial lesions (HPV16, 52, 39, 56, and 58). The distribution of high-risk human papillomavirus genotypes in single-type infections for high-grade squamous intraepithelial lesions (HPV16, 58, 33, and 52) was similar to that in multiple-type infections (HPV16, 58, 52, and 33). By contrast, a more diverse distribution spectrum of high-risk human papillomavirus genotypes for low-grade squamous intraepithelial lesions was observed between single-type (HPV16, 52, 39, and 56) and multiple-type infection (HPV52, 68, 58, 59, 39 and 56). A previously published method was adopted to calculate the fractional proportion of individual high-risk human papillomavirus genotypes in multiple infections. For this proportional attribution, HPV16 (48.9%), 58 (10.0%), 33 (5.5%), and 52 (5.5%) were the most frequent among all high-grade squamous intraepithelial lesions, whereas HPV16 (13.2%), 52 (11.6%), 39 (9.5%), and 56 (7.6%) were the most frequent among all low-grade squamous intraepithelial lesions. Differences in high-risk human

  16. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection.

    PubMed

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi

    2017-04-01

    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls ( p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5

  17. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer

    PubMed Central

    Schlecht, Nicolas F.; Brandwein-Gensler, Margaret; Nuovo, Gerard J.; Li, Maomi; Dunne, Anne; Kawachi, Nicole; Smith, Richard V.; Burk, Robert D.; Prystowsky, Michael B.

    2011-01-01

    Detection of human papillomavirus in head and neck cancer has therapeutic implications. In-situ hybridization and immuno-histochemistry for p16 are used by surgical pathologists. We compared the sensitivity and specificity of three popular commercial tests for human papillomavirus detection in head and neck squamous cell carcinomas to a “gold standard” human papillomavirus PCR assay. One hundred-and-ten prospectively collected, formalin fixed tumor specimens were compiled onto tissue microarrays and tested for human papillomavirus DNA by in-situ hybridization with two probe sets: a biotinylated probe for high-risk human papillomavirus types 16/18 (Dako, CA), and a probe cocktail for 16/18 plus 10 additional high-risk types (Ventana, AZ). P16INK4 expression was also assessed using a Pharmingen immuno-histochemistry antibody (BD Biosciences, CA). Tissue microarrays were stained and scored at expert laboratories. Human papillomavirus DNA was detected by MY09/11-PCR using Gold AmpliTaq and dot-blot hybridization on matched fresh frozen specimens in a research laboratory. Human papillomavirus 16 E6 and E7-RNA expression was also measured using RT-PCR. Test performance was assessed by receiver operating characteristic analysis. High-risk human papillomavirus DNA types 16, 18 and 35 were detected by MY-PCR in 28% of tumors, with the majority (97%) testing positive for type 16. Compared to MY-PCR, the sensitivity and specificity for high-risk human papillomavirus DNA detection with Dako in-situ hybridization was 21% (95%CI:7–42) and 100% (95%CI:93–100), respectively. Corresponding test results by Ventana in-situ hybridization were 59% (95%CI:39–78) and 58% (95%CI:45–71), respectively. P16 immuno-histochemistry performed better overall than Dako (p=0.042) and Ventana (p=0.055), with a sensitivity of 52% (95%CI:32–71) and specificity of 93% (95%CI:84–98). Compared to a gold standard human papillomavirus PCR assays, HPV detection by in-situ hybridization was

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

    PubMed

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

    2016-05-31

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

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

    PubMed Central

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

    2016-01-01

    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. PMID:27190090

  20. Biphenotypic human papillomavirus-associated head and neck squamous cell carcinoma: a report of two cases.

    PubMed

    Pitiyage, Gayani; Lei, Mary; Guererro Urbano, Teresa; Odell, Edward; Thavaraj, Selvam

    2015-07-11

    Human papillomavirus-associated oropharyngeal squamous cell carcinoma is now recognised as a subtype of head and neck cancer with distinct clinical, molecular and histological characteristics. The majority of these carcinomas are of non-keratinising squamous type but there is a growing number of histomorphologic variants of this disease. Here we describe the clinical, histomorphologic and immunophenotypic features of two cases of human papillomavirus-associated oropharyngeal squamous cell carcinoma demonstrating a clearly delineated biphasic differentiated and undifferentiated phenotype.

  1. Cigarette smoking and human papillomavirus in patients with reported cervical cytological abnormality.

    PubMed Central

    Burger, M P; Hollema, H; Gouw, A S; Pieters, W J; Quint, W G

    1993-01-01

    OBJECTIVE--To assess the relation between two risk factors for cervical neoplasia: smoking and infection with oncogenic human papillomavirus. It has been suggested that smoking causes a local immunological defect, which could facilitate the infection and persistence of human papillomavirus. DESIGN--Cross sectional epidemiological study. Completion of a structured questionnaire by the patients, analysis of cervical scrapes for human papillomavirus, and morphological examination of biopsy specimens. SETTING--Outpatient gynaecological clinic. SUBJECTS--181 women with a report of cervical cytological abnormality. MAIN OUTCOME MEASURES--Prevalence of infection with oncogenic human papillomavirus and smoking habits. RESULTS--Oncogenic human papillomavirus was found in the cervix of 26 (41%) of the 63 women who did not smoke, 22 (58%) of the 38 who smoked 1-10 cigarettes a day, 28 (61%) of the 46 who smoked 11-20 cigarettes a day, and 26 (76%) of the 34 who smoked > or = 21 cigarettes a day. The prevalence of the virus thus increased in accordance with the number of cigarettes smoked (p = 0.001). This relation remained after adjustment for age at first intercourse and lifetime number of sexual partners. Of the 63 non-smokers, 23 had previously smoked at least 10 cigarettes a day at some time. Of these 23 women, 14 (61%) had oncogenic human papillomavirus in their cervix. Of the 40 women who had never smoked at least 10 cigarettes a day, 12 (30%) had the virus. The prevalence of oncogenic human papillomavirus in non-smokers therefore depended on previous smoking habits (p = 0.03). CONCLUSION--The dose dependent effect of cigarette smoking on the occurrence of oncogenic human papillomavirus favours a causal relation between these risk factors for cervical neoplasia. PMID:8387842

  2. A multimodal approach to improving human papillomavirus vaccination in a community pharmacy setting

    PubMed Central

    Hohmeier, Kenneth C; Randolph, Donna D; Smith, Cindy Taliaferro; Hagemann, Tracy M

    2016-01-01

    Background: Community pharmacy has become a major access point for several types of vaccinations. Despite the success of vaccination programs like influenza, pneumococcal, and herpes zoster, the rates of human papillomavirus vaccination continue to lag. Objectives: The primary objective is to describe and report on the impact of a multimodal series of pharmacist-led educational interventions on human papillomavirus vaccination rates in a community pharmacy setting. The primary outcome of this study was change in pharmacist-delivered human papillomavirus vaccination throughout a corresponding 8-week period in 2014 and 2015. Methods: A single-center, quasi-experimental interrupted time series mixed-methods pilot study was used to investigate a pharmacist-led, multimodal educational intervention approach to improve human papillomavirus vaccination rates in the community. Results: During the 2014 control period, there were no human papillomavirus vaccines dispensed or administered according to the internal prescription dispensing software. In 2015, a total of 10 patients indicated that they were vaccinated, with 9 patients receiving their first dose and 1 patient receiving his or her second dose at the pharmacy. Pharmacist recommendation was the most reported education method for increasing patient awareness of the human papillomavirus vaccine (n = 10). Conclusion: This study demonstrates pharmacist designed, educational interventions may impact human papillomavirus vaccination rates in the community. Further community-based research with larger sample sizes is warranted to verify these results. Due to the unique barriers to human papillomavirus vaccination, a multimodal and inter-professional approach such as the one presented here is warranted. PMID:28348735

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

    SciTech Connect

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

    1987-02-01

    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.

  4. Cloning of monomeric human papillomavirus type 16 DNA integrated within cell DNA from a cervical carcinoma

    SciTech Connect

    Matsukura, T.; Kanda, T.; Furuno, A.; Yoshikawa, H.; Kawana, T.; Yoshiike, K.

    1986-06-01

    The authors have molecularly cloned and characterized monomeric human papillomavirus type 16 DNA with flanking cell DNA sequences from a cervical carcinoma. Determination of nucleotide sequence around the junctions of human papillomavirus and cell DNAs revealed that at the site of integration within cell DNA the cloned viral DNA had a deletion between nucleotides 1284 and 4471 (numbering system from K. Seedorf, G. Kraemmer, M. Duerst, S. Suhai, and W.G. Roewkamp), which includes the greater part of E1 gene and the entire E2 gene. In the remaining part of the E1 gene, three guanines were found at the location where two guanines at nucleotides 1137 and 1138 have been recorded. This additional guanine shifted the reading frame and erased an interruption in the E1 gene. The data strongly suggest that, like other papillomaviruses, human papillomavirus type 16 has an uninterrupted E1 gene.

  5. Human papillomavirus genotyping and integration in ovarian cancer Saudi patients

    PubMed Central

    2013-01-01

    Background Human papillomavirus (HPV) is associated with different malignancies but its role in the pathogenesis of ovarian cancer is controversial. This study investigated the prevalence, genotyping and physical state of HPV in ovarian cancer Saudi patients. Methods Hundred formalin fixed paraffin embedded (FFPE) ovarian carcinoma tissues and their normal adjacent tissues (NAT) were included in the study. HPV was detected by nested polymerase chain reaction (PCR) using degenerated HPVL1 consensus primer pairs MY09/MY11 and GP5+/GP6 + to amplify a broad spectrum of HPV genotypes in a single reaction. The HPV positive samples were further genotyped using DNA sequencing. The physical state of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in the samples positive for HPV16 and/or HPV18. Results High percentage of HPV (42%) was observed in ovarian carcinoma compared to 8% in the NAT. The high-risk HPV types 16, 18 and 45 were highly associated with the advanced stages of tumor, while low-risk types 6 and 11 were present in NAT. In malignant tissues, HPV-16 was the most predominant genotype followed by HPV-18 and -45. The percentage of viral integration into the host genome was significantly high (61.1%) compared to 38.9% episomal in HPV positive tumors tissues. In HPV18 genotype the percentage of viral integration was 54.5% compared to 45.5% episomal. Conclusion The high risk HPV genotypes in ovarian cancer may indicate its role in ovarian carcinogenesis. The HPV vaccination is highly recommended to reduce this type of cancer. PMID:24252426

  6. Tumorigenic transformation of murine keratinocytes by the E5 genes of bovine papillomavirus type 1 and human papillomavirus type 16.

    PubMed Central

    Leptak, C; Ramon y Cajal, S; Kulke, R; Horwitz, B H; Riese, D J; Dotto, G P; DiMaio, D

    1991-01-01

    To examine the biological properties of the bovine papillomavirus type 1 (BPV) and human papillomavirus type 16 (HPV16) E5 genes, each was cloned separately into a retroviral expression vector and helper-free recombinant viruses were generated in packaging cell lines. The BPV E5 retroviruses efficiently caused morphologic and tumorigenic transformation of cultured lines of murine fibroblasts, whereas the HPV16 E5 viruses were inactive in these assays. In contrast, infection of the p117 established line of murine epidermal keratinocytes with either the BPV or the HPV16 E5 retrovirus resulted in the generation of tumorigenic cells. Pam212 murine keratinocytes were also transformed to tumorigenicity by the HPV16 E5 gene but not by the gene carrying a frameshift mutation. These results establish that the HPV16 E5 gene is a transforming gene in cells related to its normal host epithelial cells. Images PMID:1658398

  7. Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia.

    PubMed

    Piyathilake, Chandrika J; Badiga, Suguna; Chambers, Michelle M; Brill, Ilene K; Matthews, Roland; Partridge, Edward E

    2016-09-15

    Although urine-based testing for human papillomavirus (HPV) is being explored as a practical approach for cervical cancer screening, whether the results differ by age, race, or indicators of excess body weight or in populations exposed to HPV vaccines has not been documented by previous studies. The purpose of this study was to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and high-grade cervical intraepithelial lesions (grade 2 and 3 cervical intraepithelial neoplasia [CIN]) by the aforementioned population characteristics. The study population consisted of 502 women diagnosed with different grades of CIN. HPV testing was performed with paired urine and cervical cell DNA with the Roche Diagnostics Linear Array test. Agreement coefficient 1 and probabilities were calculated to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and CIN lesions. Substantial to almost perfect agreement (0.66-0.83) was observed in the detection of any HPV genotype in urine specimens versus cervical specimens, regardless of the population characteristics. Although the positive predictive value for the detection of CIN lesions was relatively low, the negative predictive value for CIN-3 was high (≥90%) among women positive for any of the urinary or cervical high-risk human papillomavirus (HR-HPV) genotypes or HPV genotypes not included in currently available HPV vaccines. The results demonstrate that urinary HPV testing provides highly satisfactory results for excluding the possibility of any cervical HPV infections, including HPV types not included in vaccines and CIN lesions associated with any HR-HPV, regardless of a woman's age, race, or excess body weight. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2836-2844. © 2016 American Cancer Society. © 2016 American Cancer Society.

  8. Involvement of human papillomavirus infections in prostate cancer progression.

    PubMed

    Al Moustafa, Ala-Eddin

    2008-08-01

    High-risk human papillomaviruses (HPVs) are sexually transmitted and have been associated with several human carcinomas especially cervical and colorectal. On the other hand, a small number of studies have examined the presence of high-risk HPV in human prostate cancer tissues. Currently, the presence and role of high-risk HPV infections in prostate carcinogenesis remain unclear because of the limited number of investigations. This raises the question whether high-risk HPV infections play any role in human prostate cancer development. However, other investigators and our group were able to immortalize normal and cancer prostate epithelial cells in vitro by E6/E7 of HPV type 16. In this paper, we propose the hypothesis that normal and cancer prostate epithelial cells are susceptible to persistent HPV infections; therefore, high-risk HPV infections play an important role in the progression of prostate cancer. We believe that an international collaboration of epidemiological studies and more molecular biology investigations are necessary to answer these important questions.

  9. Human papillomavirus capsids preferentially bind and infect tumor cells

    PubMed Central

    Kines, Rhonda C.; Cerio, Rebecca J.; Roberts, Jeffrey N.; Thompson, Cynthia D.; de Los Pinos, Elisabet; Lowy, Douglas R.; Schiller, John T.

    2015-01-01

    We previously determined that human papillomavirus (HPV) virus-like particles (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact epithelium of the cervicovaginal tract. However, they strongly bound heparin sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and infected the keratinocytes that subsequently entered the disrupted site. We here report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide variety of disrupted epithelial and mesothelial tissues, whereas intact tissues remain resistant to binding. However, the HPV capsids directly bind and infect most tumor-derived cell lines in vitro and have analogous tumor-specific properties in vivo, after local or intravenous injection, using orthotopic models for human ovarian and lung cancer, respectively. The pseudovirions also specifically infected implanted primary human ovarian tumors. Heparin and ι-carrageenan blocked binding and infection of all tumor lines tested, implying that tumor cell binding is HSPG-dependent. A survey using a panel of modified heparins indicate that N-sulfation and, to a lesser degree O-6 sulfation of the surface HSPG on the tumors are important for HPV binding. Therefore, it appears that tumor cells consistently evolve HSPG modification patterns that mimic the pattern normally found on the basement membrane but not on the apical surfaces of normal epithelial or mesothelial cells. Consequently, appropriately modified HPV VLPs and/or PsV could be useful reagents to detect and potentially treat a remarkably broad spectrum of cancers. PMID:26317490

  10. Human papillomavirus capsids preferentially bind and infect tumor cells.

    PubMed

    Kines, Rhonda C; Cerio, Rebecca J; Roberts, Jeffrey N; Thompson, Cynthia D; de Los Pinos, Elisabet; Lowy, Douglas R; Schiller, John T

    2016-02-15

    We previously determined that human papillomavirus (HPV) virus-like particles (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact epithelium of the cervicovaginal tract. However, they strongly bound heparan sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and infected the keratinocytes that subsequently entered the disrupted site. We here report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide variety of disrupted epithelial and mesothelial tissues, whereas intact tissues remain resistant to binding. However, the HPV capsids directly bind and infect most tumor-derived cell lines in vitro and have analogous tumor-specific properties in vivo, after local or intravenous injection, using orthotopic models for human ovarian and lung cancer, respectively. The pseudovirions also specifically infected implanted primary human ovarian tumors. Heparin and ι-carrageenan blocked binding and infection of all tumor lines tested, implying that tumor cell binding is HSPG-dependent. A survey using a panel of modified heparins indicates that N-sulfation and, to a lesser degree, O-6 sulfation of the surface HSPG on the tumors are important for HPV binding. Therefore, it appears that tumor cells consistently evolve HSPG modification patterns that mimic the pattern normally found on the basement membrane but not on the apical surfaces of normal epithelial or mesothelial cells. Consequently, appropriately modified HPV VLPs and/or PsV could be useful reagents to detect and potentially treat a remarkably broad spectrum of cancers. © 2015 UICC.

  11. The interaction between human papillomavirus and other viruses.

    PubMed

    Guidry, J T; Scott, R S

    2017-03-02

    The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas.

  12. Cutaneous Human Papillomaviruses Found in Sun-Exposed Skin: Beta-papillomavirus Species 2 Predominates in Squamous Cell Carcinoma

    PubMed Central

    Forslund, Ola; Iftner, Thomas; Andersson, Kristin; Lindelöf, Bernt; Hradil, Eva; Nordin, Peter; Stenquist, Bo; Kirnbauer, Reinhard; Dillner, Joakim; de Villiers, Ethel-Michele

    2013-01-01

    Background A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear. Methods We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples—from the lesion and from healthy skin from the same patient—were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models. Results Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44–8.11]) and for the healthy skin samples (OR, 3.65 [95% CI 1.79–7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92–10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72–6.99]). Conclusions Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma. PMID:17703418

  13. Cancerl cells 5. Papillomaviruses

    SciTech Connect

    Steinberg, B.M.; Brandsma, J.L. ); Taichman, L.B. )

    1987-01-01

    This book contains over 30 selections. Some of the titles are: Elements that Control the Transcription of Genital Human Papillomavirus Type 18; Human Paillomavirus Gene Expression; RNA Probes to Analyze Human Papillomavirus Gene Expression in Squamous Papilloma of the Respiratory Tract; Expression of Human Papillomavirus Type-1 E4 Gene Products in Warts; and Underreplication of Human Papillomavirus Type-1 DNA in Cultures of Foreskin Keratinocytes.

  14. The role of human papillomavirus infection in prostate carcinoma.

    PubMed

    Aghakhani, Arezoo; Hamkar, Rasool; Parvin, Mahmoud; Ghavami, Nastaran; Nadri, Mahsa; Pakfetrat, Attesa; Banifazl, Mohammad; Eslamifar, Ali; Izadi, Nabiollah; Jam, Sara; Ramezani, Amitis

    2011-01-01

    Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

  15. [Human papillomavirus: a vaccine against cervical carcinoma uterine].

    PubMed

    Franceschi, Silvia

    2002-01-01

    Human papillomavirus (HPV) has been identified in fewer than 20 years as the central cause of cervical carcinoma and one of the most powerful known human carcinogens. At least 20 different types of HPV have been associated with relative risks of approximately 100 for both squamous-cell carcinoma and the rarer adenocarcinoma of the cervix uteri. Cytologic screening programs have contributed to the decline of cervical cancer mortality in Europe and the United States. Long-term screening programs remain, however, outside the reach of the poorest countries, where 80% of deaths for cervical carcinoma occurs. More than 20 different types of prophylactic and/or therapeutic vaccines against HPV are being evaluated in clinical or preclinical studies. One such type, a prophylactic vaccine based on the marked immunogenicity and safety of the empty viral capsid, will start being evaluated in 2002 in 3 phase-III randomized studies, mostly in the United States and Latin America. The International Agency for Research on Cancer and World Health Organization are planning, in parallel with the studies above, a double blind randomized phase IV study of approximately 40,000 adolescent and young women in Asia. Such study, which should include a cluster randomization (by village of birth); a comparison with another vaccine (rather than with placebo); and, possibly, the inclusion of adolescents and young adults of male sex. Such trial may accelerate by many years the availability of an anti-HPV vaccine among populations at highest risk for cervical carcinoma.

  16. Epigenetic Alterations in Human Papillomavirus-Associated Cancers.

    PubMed

    Soto, David; Song, Christine; McLaughlin-Drubin, Margaret E

    2017-09-01

    Approximately 15-20% of human cancers are caused by viruses, including human papillomaviruses (HPVs). Viruses are obligatory intracellular parasites and encode proteins that reprogram the regulatory networks governing host cellular signaling pathways that control recognition by the immune system, proliferation, differentiation, genomic integrity, and cell death. Given that key proteins in these regulatory networks are also subject to mutation in non-virally associated diseases and cancers, the study of oncogenic viruses has also been instrumental to the discovery and analysis of many fundamental cellular processes, including messenger RNA (mRNA) splicing, transcriptional enhancers, oncogenes and tumor suppressors, signal transduction, immune regulation, and cell cycle control. More recently, tumor viruses, in particular HPV, have proven themselves invaluable in the study of the cancer epigenome. Epigenetic silencing or de-silencing of genes can have cellular consequences that are akin to genetic mutations, i.e., the loss and gain of expression of genes that are not usually expressed in a certain cell type and/or genes that have tumor suppressive or oncogenic activities, respectively. Unlike genetic mutations, the reversible nature of epigenetic modifications affords an opportunity of epigenetic therapy for cancer. This review summarizes the current knowledge on epigenetic regulation in HPV-infected cells with a focus on those elements with relevance to carcinogenesis.

  17. The fanconi anemia pathway limits human papillomavirus replication.

    PubMed

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

    2012-08-01

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

  18. Human papillomavirus infections: new perspectives for prevention and treatment.

    PubMed

    Menzo, Stefano; Marinelli, Katia; Bagnarelli, Patrizia; Rolla, Serena; Clementi, Massimo

    2007-07-01

    Human papillomaviruses (HPVs) have been recognized as the main etiologic agent of cervical cancer and other anogenital neoplasms, and a leading cause of death from cancer worldwide. In the last twenty years, extensive research has contributed to document the molecular mechanisms of virus persistence and malignant transformation, confirming a direct role of viral proteins in these processes. A clear understanding of the molecular epidemiology of HPVs and the availability of powerful molecular diagnostic techniques have provided the background for prevention strategies of HPV-related carcinomas. Since these viruses are highly prevalent in the general population, strict screening programs are still necessary. Recently, major breakthroughs have emerged from immunological studies. Indeed, these studies have paved the way for medical treatment of HPV infections and provided the first highly effective preventive vaccines. For these principal reasons, the time has come for a great effort towards the eradication of these important human pathogens. The present review summarizes the main aspects of the virology, molecular epidemiology and molecular biology of HPV infection and highlights the recent perspectives of prevention and treatment of the HPV-related disease.

  19. [Enhanced molecular techniques for the diagnosis of human papillomavirus infections].

    PubMed

    Ursu, Ramona Gabriela; Onofriescu, M; Nemescu, D; Iancu, Luminiţa Smaranda

    2009-01-01

    optimisation of Real Time PCR technique for quantifying oncogenic types 16 and 18 of Human Papilloma Viruses, genotyped through classic PCR, followed by hybridisation. DNA/ HPV was purified with High Pure PCR Template Preparation kit (ROCHE DIAGNOSTICS), genotyping was performed with Linear Array HPV Genotyping (ROCHE DIAGNOSTICS) and PCR reaction was realized with ABI 9700 Gold Plate System. Absolute quantification of HPV 16 and 18 was performed with Path-HPV16/18 Real-time PCR detection kit for Human Papillomavirus, 2 x Precision Mastermix kits (PrimerDesign), and the instrument used was MX3000P STRATAGENE. I. HPV genotyping was optimised through testing of 12 cervical samples, collected from patients who have signed the informed consent approved by the local Bioethical Committee. Among the tested samples, 5 were negative for any HPV type, 3 patients had unique infections with oncogenic HPV type, and 2 patients had multiple infections, with oncogenic and non-oncogenic HPV types. Negative and positive controls were validated, identical as the internal control - beta globin gene. II. Absolute quantification for HPV 16 and 18 were performed on two samples tested by the previous method. The number of viral copies was determined using the standard curves procedure, whose parameters values were between the accepted limits. We fulfilled the quality criteria for both techniques: genotyping assay and viral load quantification by Real Time PCR. This allows us to start the study for monitoring persistent infections with HPV 16 and HPV 18.

  20. Prevalence of human papillomavirus in university young women

    PubMed Central

    MONTALVO, MARIA T.; LOBATO, ISMELDA; VILLANUEVA, HILDA; BORQUEZ, CELIA; NAVARRETE, DANIELA; ABARCA, JUAN; CALAF, GLORIA M.

    2011-01-01

    Cervical cancer is the second most prevalent female cancer worldwide. The majority of cases appear between the age of 30 and 50. Human papillomavirus (HPV) plays a central role in cervical cancer with 99.7% of HPV DNA identified in invasive cervical carcinomas. The prevalence of the HPV infection varies substantially among countries and according to age and lifestyle. HPV is a common sexually transmitted infection among males and females with a 70% higher incidence in sexually active females. This study aimed to determine the prevalence of human papillomavirus in young university women by analyzing the correlation between Papanicolaou (PAP)-stained cervical tests and HPV detection by genotyping, as well as other risk factors. A total of 200 women aged between 18 and 25 years were enrolled in this study, which took place between September 2008 and May 2009 at the Universidad de Tarapacá, Arica, Chile. Results of the PAP smears showed that 97.5% of cells had normal characteristics, although an inflammatory pattern was noted. The prevalence of generic HPV infection was 3.5% when testing for HPV DNA using the polymerase chain reaction (PCR) method. An analysis of the genotype of infected female individuals indicated that high-risk HPV types, such as HPV 16 and 31 were present in 42.84 and 14.29% of females, respectively, and low-risk types such as HPV 6, in 14.29%. Only one sample with differentiated non-HPV (14.29%) was found. A 95% correlation between PAP-stained cervical tests and the method of testing for HPV was observed. Using the PCR method, it was found that of the 195 negative PAP smears, 5 were positive for HPV and two of the samples that were positive for ASC-US were also positive. A significantly increased (P<0.05) HPV infection risk was observed in the 18–21 age group with a higher prevalence (71.40%) when compared to the 22–25 age group (28.6%). A significant (P<0.042) difference was found between smoking and HPV infection. In conclusion, a

  1. An exploration of human papillomavirus-related cervical cancer prevention experiences among college women: a descriptive qualitative approach.

    PubMed

    Tu, Yu-Ching; Wang, Hsiu-Hung

    2013-12-01

    To enhance understanding of young women's experiences of human papillomavirus-related cervical cancer prevention in Taiwan. High-risk types of human papillomavirus are a key aetiologic factor behind cervical cancer. Recently, human papillomavirus vaccination is considered an effective approach to prevent vaccine-specific typed human papillomavirus-related cervical cancer in women. However, several controversial issues still arise about routine administration of human papillomavirus vaccines, and the literature on young women's protection against human papillomavirus-related cervical cancer is limited. A descriptive qualitative design categorised responses into themes. Sixteen sexually active college women (aged 20-22 years) were recruited via purposive and snow-ball sampling in Southern Taiwan. Every participant underwent an in-depth interview which was audio-recorded and fully transcribed. Analysis of the interview material was inductive and followed a thematic analysis approach. Procedures to confirm confidentiality, credibility and consistency were considered. This article provides an insight into the college women's experiences in the obstacles to and striving towards breakthroughs of human papillomavirus-related cervical cancer prevention. The obstacles include inadequate health literacy, financial difficulty, negative medical experiences and gender myths. The striving towards breakthroughs consists in self-protection and knowledge support. College women experience difficulties with human papillomavirus-related cervical cancer prevention. They desire to have a publicly funded human papillomavirus immunisation programme, friendly medical environments, sufficient knowledge and open-minded society to maintain their health. Such reflection information is helpful to design effective human papillomavirus-related cervical cancer prevention campaigns. Young women do not know how to protect against human papillomavirus infection, although human papillomavirus

  2. Human papillomavirus vaccine acceptability among female undergraduate students in China: the role of knowledge and psychosocial factors.

    PubMed

    Gu, Can; Niccolai, Linda M; Yang, Shengbo; Wang, Xiuhua; Tao, Lijian

    2015-10-01

    To examine young women's perceptions and acceptability of human papillomavirus vaccination and factors influencing acceptability in mainland China. In the light of current concepts, human papillomavirus vaccines serve as new paradigms in cervical cancer prevention programme for young women. However, knowledge and acceptability of human papillomavirus vaccination and factors influencing acceptability among young Chinese women are not known. We implemented a cross-sectional descriptive study in the Hunan province of China. One hundred and seventeen female undergraduate students completed confidential surveys in 2012. The questionnaire included five parts: background information, awareness and knowledge of human papillomavirus vaccine and cervical cancer, attitudes towards the vaccine and intentions to be vaccinated, psychosocial burden of human papillomavirus infection, and human papillomavirus-related sexual stigma. Only 44% of the participants were willing to be vaccinated in the future. Young women demonstrated low awareness and knowledge about human papillomavirus vaccine and cervical cancer. Their intention to receive future vaccination was associated with the high levels of knowledge about risk factors for cervical cancer and perceptions that infected women are responsible for their own infection of human papillomavirus. The results of this study suggest low awareness and knowledge among young Chinese women about the preventive nature and value of human papillomavirus vaccination. Social and cultural factors including moral obligation and STD-related stigma may influence young women's intention to future vaccination. Educational interventions are necessary to promote public awareness and deliver information about human papillomavirus vaccination and cervical cancer prevention. Results of this study can help health care practitioners develop appropriate programmes for the promotion of human papillomavirus vaccination among this population. © 2015 John Wiley

  3. Human papillomavirus infections in nonsexually active perinatally HIV infected children.

    PubMed

    Moscicki, Anna-Barbara; Puga, Ana; Farhat, Sepideh; Ma, Yifei

    2014-02-01

    Although human papillomavirus (HPV) infections are common in HIV-infected adults, little is known about children. Our objective was to examine the prevalence of and risks for HPV of the oral mucosal and external genital areas in nonsexually active (NSA) perinatally (P) HIV+ children and compare with HIV-exposed but uninfected (HEU) children. A convenience sample attending a pediatric clinic were enrolled. Samples for HPV were obtained from the oral and anogenital areas and tested for one of 37 HPV types. The mean age of the 48 PHIV+ children was 14.3±3.9 years vs. 6.2±4.8 for the 52 HEU (p<0.001). Of the 23 PHIV+ girls, 30.4% had anogenital and 17% had oral HPV, and of the 27 HEU girls, 2 (7.4%) anogenital and 0 had oral HPV. Of the boys, 4/23 (17.4%) and 1/25 (4%) PHIV+ had anogenital and oral HPV, respectively, and 3/24 (12.5%) and 1/25 (4%) HEU had anogenital and oral HPV, respectively. Rates of HPV did not differ by age among the PHIV+, whereas older HEU were more likely to have HPV than younger HEU (p=0.07). This large age gap precluded statistical comparison by HIV status. The presence of HPV in NSA PHIV+ children may have implications regarding HPV vaccination efficacy.

  4. Association between human papillomavirus DNA and temporal arteritis.

    PubMed

    Mohammadi, Amir; Pfeifer, John D; Lewis, James S

    2012-07-25

    To examine the relationship between human papillomavirus (HPV) and giant cell arteritis (GCA) of the temporal artery. The study group consisted of 22 cases of histologically positive/biopsy confirmed GCA. The control groups consisted of 21 histologically negative temporal artery biopsies and fifteen cases of vascular margins of nephrectomies. For detection of the presence of HPV, two methods were used: 1) polymerase chain reaction (PCR) with INNO-LiPA HPV Genotyping Extra, 2) Cervista™ HPV HR. All cases were from the files of the Barnes-Jewish Hospital and Washington University in St. Louis. HPV DNA was detected by PCR and genotyping in 16 of 22 (73%) histologically positive cases of GCA and in only five of 21 (24%) histologically negative temporal artery biopsies. Among the vascular margin controls, only three of 15 (20%) were positive for HPV DNA. The second, independent method (CervistaTM) confirmed the aforesaid results with 100% concordance with the exception of three cases which had low genomic DNA for which it was not possible to perform the test. The differences in HPV positivity between the histologically positive and negative temporal artery biopsies and between the histologically positive temporal artery biopsies and controls were both statistically significant (p = 0.001 and 0.002, respectively). The results of our study revealed a statistically significant association between HPV positivity and biopsy confirmed temporal giant cell arteritis GCA (p = 0.001). Further studies are necessary to elucidate the pathophysiology underlying this association.

  5. Human Papillomavirus Vaccination at a Time of Changing Sexual Behavior

    PubMed Central

    Lazzarato, Fulvio; Brisson, Marc; Franceschi, Silvia

    2016-01-01

    Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women <35 years of age can result in increased (2.6-fold in our study) HPV16 prevalence. Our model shows that reductions in HPV16 prevalence are larger if vaccination occurs in populations before transitions in sexual behavior and that increased risk for HPV infection attributable to transition is preventable by early vaccination. Our study highlights the importance of using time-limited opportunities to introduce HPV vaccination in traditional populations before changes in age-specific sexual patterns occur. PMID:26691673

  6. Human papillomavirus (HPV) genotyping of cutaneous warts in Greek children.

    PubMed

    Giannaki, Maria; Kakourou, Talia; Theodoridou, Maria; Syriopoulou, Vassiliki; Kabouris, Marios; Louizou, Eirini; Chrousos, George

    2013-01-01

    The human papillomavirus (HPV) infects the squamous epithelium of the skin and produces common warts, plantar warts, and flat warts, which occur commonly on the hands, face, and feet. The objective of this study was to determine the presence of HPV in warts in children in order to associate the virus with the disease. Sixty-eight children with clinically diagnosed cutaneous warts were recruited. Skin biopsy samples were examined and DNA was extracted using a commercially available kit. To distinguish between the HPV types, we used a specific pair of primers to amplify the HPV DNA. Polymerase chain reaction amplification of the L1 region was followed by restriction fragment length polymorphism analysis and Luminex xMAP technology. HPV 57 was the predominant type in our study, although the detection of the high-risk HPV type 16 in 33% of our positive samples indicates the presence of mucosal high-risk HPV types in the skin of children. It seems that the newly introduced Luminex assay maximized the discrimination of genotypes even in the case of multiple HPV infections. Or findings also suggest the presence of high-risk HPV types in cutaneous warts. © 2013 Wiley Periodicals, Inc.

  7. Committee Opinion No. 704 Summary: Human Papillomavirus Vaccination.

    PubMed

    2017-06-01

    Human papillomavirus (HPV) is associated with anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. The HPV vaccination significantly reduces the incidence of anogenital cancer and genital warts. Despite the benefits of HPV vaccines, only 41.9% of girls in the recommended age group, and only 28.1% of males in the recommended age group have received all recom-mended doses. Compared with many other countries, HPV vaccination rates in the United States are unacceptably low. The U.S. Food and Drug Administration has approved three vaccines that are effective at preventing HPV infection. These vaccines cover 2, 4, or 9 HPV serotypes, respectively. Safety data for all three HPV vaccines are reassuring. The HPV vaccines are recommended for girls and boys aged 11-12 years and can be given to females and males up to age 26 years. The Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists recommend routine HPV vaccination for girls and boys at the target age of 11-12 years (but it may be given from the age of 9 years) as part of the adolescent immunization platform in order to help reduce the incidence of anogenital cancer and genital warts associated with HPV infection. Obstetrician-gynecologists and other health care providers should stress to parents and patients the benefits and safety of HPV vaccination and offer HPV vaccines in their offices.

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

    PubMed

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

    2015-01-01

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

  9. Human Papillomavirus in Brazilian women with and without cervical lesions

    PubMed Central

    2011-01-01

    Background Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women. Results We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age. Conclusions Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age. PMID:21208414

  10. Human Papillomavirus Vaccination at a Time of Changing Sexual Behavior.

    PubMed

    Baussano, Iacopo; Lazzarato, Fulvio; Brisson, Marc; Franceschi, Silvia

    2016-01-01

    Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women <35 years of age can result in increased (2.6-fold in our study) HPV16 prevalence. Our model shows that reductions in HPV16 prevalence are larger if vaccination occurs in populations before transitions in sexual behavior and that increased risk for HPV infection attributable to transition is preventable by early vaccination. Our study highlights the importance of using time-limited opportunities to introduce HPV vaccination in traditional populations before changes in age-specific sexual patterns occur.

  11. Identification of human papillomavirus in esophageal squamous papillomas

    PubMed Central

    Bohn, Olga L; Navarro, Leticia; Saldivar, Jesus; Sanchez-Sosa, Sergio

    2008-01-01

    AIM: To investigate the presence of human papillomavirus (HPV) in esophageal squamous papilloma (ESP) and determine p16, p53 and Ki67 expression in a Mexican cohort. METHODS: Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by amplified chromogenic in situ hybridization (ACISH) using a wide spectrum-cocktail probe and PCR. RESULTS: The average age at presentation was 46.3 years (range 28-72 years). Patients included four (22.22%) males and 14 (77.77%) females. The most frequent location was upper third (11 cases), followed by middle third (3 cases) and unknown site (5 cases). Immunohistochemistry (IHC) revealed basal and focal p53 expression in 17 cases (89%); p16 was expressed in eight cases (42.10%) and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases (87.5%) by ACISH: Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases (85.7%). Low-risk HPV types were detected in the most of the cases. CONCLUSION: This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESP. PMID:19084918

  12. Pathogenesis of human papillomavirus-associated mucosal disease.

    PubMed

    Groves, Ian J; Coleman, Nicholas

    2015-03-01

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

  13. Resequencing Microarray Technology for Genotyping Human Papillomavirus in Cervical Smears

    PubMed Central

    Berthet, Nicolas; Falguières, Michael; Filippone, Claudia; Bertolus, Chloé; Bole-Feysot, Christine; Brisse, Sylvain; Gessain, Antoine; Heard, Isabelle; Favre, Michel

    2014-01-01

    There are more than 40 human papillomaviruses (HPVs) belonging to the alpha genus that cause sexually transmitted infections; these infections are among the most frequent and can lead to condylomas and anogenital intra-epithelial neoplasia. At least 18 of these viruses are causative agents of anogenital carcinomas. We evaluated the performance of a resequencing microarray for the detection and genotyping of alpha HPV of clinical significance using cloned HPV DNA. To reduce the number of HPV genotypes tiled on microarray, we used reconstructed ancestral sequences (RASs) as they are more closely related to the various genotypes than the current genotypes are among themselves. The performance of this approach was tested by genotyping with a set of 40 cervical smears already genotyped using the commercial PapilloCheck kit. The results of the two tests were concordant for 70% (28/40) of the samples and compatible for 30% (12/40). Our findings indicate that RASs were able to detect and identify one or several HPV in clinical samples. Associating RASs with homonym sequences improved the genotyping of HPV present in cases of multiple infection. In conclusion, we demonstrate the diagnostic potential of resequencing technology for genotyping of HPV, and illustrate its value both for epidemiological studies and for monitoring the distribution of HPV in the post-vaccination era. PMID:25383888

  14. Association of oncogenic and nononcogenic human papillomavirus with HIV incidence

    PubMed Central

    Auvert, Bertran; Lissouba, Pascale; Cutler, Ewalde; Zarca, Kevin; Puren, Adrian; Taljaard, Dirk

    2010-01-01

    Objective Little is known about the interaction between HPV and HIV. This study aimed to explore the association of oncogenic (HR) and non oncogenic (LR) human papillomavirus (HPV) with HIV incidence. Methods We used urethral swabs collected at the last follow-up visit of a male circumcision trial conducted in Orange Farm (South Africa). Swabs analyses and HPV genotyping were performed by polymerase chain reaction. We estimated HIV adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) using survival analysis. Background characteristics, male circumcision status, sexual behavior, HPV status and other sexually transmitted infections were used as covariates. Results The prevalence of HR and LR HPV was 14.0% (95%CI: 12.4 to 15.7) and 17.3% (95%CI: 15.6 to 19.2), respectively. When controlling for HR-HPV status, LR-HPV status was not associated with HIV incidence (aIRR = 1.13, 95%CI: 0.40 to 3.16; P = 0.82). When controlling for all covariates, HIV incidence increased significantly with HR-HPV positivity (aIRR=3.76, 95%CI: 1.83 to 7.73, P < 0.001) and with the number of HR-HPV genotypes (adjusted-P linear trend = 0.0074). Conclusions Several explanations could account for our findings. One is that HR-HPV facilitates HIV acquisition. The association of HPV with HIV acquisition requires further investigations. PMID:19779357

  15. [Relationship between nasal inverted papilloma and human papillomavirus subtypes].

    PubMed

    Sun, Pu; Chen, Xiao-ping; Pei, Fei; Ma, Rui-xia; Zhang, Yi; Chen, Qun; Dong, Wei-gang; Chen, Wei-xiang; Huang, Hui-li

    2010-04-01

    To study the distribution of human papillomavirus (HPV) subtypes in nasal inverted papilloma (NIP), and to evaluate the relationship between HPV and NIP. Twenty-one HPV subtypes were detected in paraffin-embedded tissues of 101 cases of NIP by flow through hybridization and gene chip (HybriMax), 24 cases of normal nasal mucosa were used as controls. HPV positive rates of NIP were 64.36% (65/101). Benign NIP group, NIP with atypical hyperplasia group, NIP with cancerous group of HPV positive rates were 59.7% (46/77), 81.8% (18/22) and 50% (1/2) respectively. The control group was negative (0/24). The comparison between NIP group and control group was statistically significant (chi(2) = 32.178, P < 0.05). Benign NIP group and NIP with atypical hyperplasia group were compared, but no statistically significance (chi(2) = 3.649, P = 0.056) was found. The constituent ratio of benign NIP group and NIP with atypical hyperplasia group in high, low-risk HPV subtypes infections was compared, a statistically significance (chi(2) = 10.412, P < 0.05) was found. The occurrence of NIP was related with HPV infection. High-risk HPV subtype infections or multiple infections will prompt benign NIP to NIP with atypical hyperplasia. Understanding the distribution of HPV subtypes in the NIP is helpful to predict the clinical behavior.

  16. Gnathic and peripheral ameloblastomas lack human papillomavirus DNA.

    PubMed

    Verduin, Lindsey; Bishop, Justin; Mills, Stacey E

    2015-10-01

    Human papillomavirus (HPV) has been associated with a variety of head and neck neoplasms, including squamous cell carcinomas and Schneiderian papillomas. Ameloblastomas can arise from either the gnathic bones or peripheral soft tissues. Peripheral sinonasal ameloblastomas share clinical features with Schneiderian papillomas. A small number of reports have described detection of HPV DNA within ameloblastomas. However, Most of these cases was reported in the 1990s, used the polymerase chain reaction technique, and only examined gnathic tumors. The current study was designed to determine whether low- or high-risk HPV DNA could be detected in gnathic or peripheral ameloblastomas using in situ hybridization. Twenty-nine examples of gnathic osseous and peripheral head and neck ameloblastomas were obtained from the authors' archives (University of Virginia and the Johns Hopkins Hospital). High-risk HPV DNA was not detected in any of the 29 tumors analyzed. Low-risk HPV DNA was identified in only 1 tumor, which was peripheral in origin, and from an immunocompromised patient. We believe that the HPV in this case represents a background "passenger" infection. This study demonstrates that HPV of either high- or low-risk subtypes is unlikely to play a role in the pathogenesis of sinonasal ameloblastomas. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Prevalence and genotypes of human papillomavirus among Thai women.

    PubMed

    Chansaenroj, Jira; Lurchachaiwong, Woradee; Termrungruanglert, Wichai; Tresukosol, Damrong; Niruthisard, Somchai; Trivijitsilp, Prasert; Sampatanukul, Pichet; Poovorawan, Yong

    2010-01-01

    One of the most common cancers in women worldwide is cervical cancer, with death rates highest in less developed countries, including Thailand. This study was conducted to explore the prevalence of human papillomavirus (HPV) and its related cytological abnormalities among women attending cervical screening clinics in Thailand using the polymerase chain reaction (PCR). LBC specimens (ThinPrep, Hologic, West Sussex, UK) were subjected to PCR of the E1 region to identify the most prevalent HPV types. Information on age and cytology grade was also collected. Among a total of 1,662 women, 29 different HPV types were found and the overall HPV prevalence was 8.7%. HPV prevalence among the general population amounted to 7.8%. The following HPV types were identified: HPV16 (17.9%), HPV90 (16.6%) and HPV71 (10.3%). The rates of other types were as follows; HPV66 (6.9%), HPV52 (6.2%), HPV34 (5.5%), HPV31 (5.3%), HPV42 (4.8%) and HPV39 (3.4%). HPV infection peaked in women aged around 20-39 years and thereafter gradually declined. As expected, HPV DNA can be found in normal cytology specimens. These results which elucidate HPV distribution in Thailand could be useful for vaccine development and the national cervical cancer prevention program.

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

    PubMed

    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.

  19. [Human papillomavirus and public health: cervical cancer prevention].

    PubMed

    Reis, Angela Adamski da Silva; Monteiro, Caroline Dias; Paula, Leonardo Barcelos de; Santos, Rodrigo da Silva; Saddi, Vera Aparecida; Cruz, Aparecido Divino da

    2010-06-01

    The present study aimed to evaluate the applicability of an educational booklet that contained information for the general population about promotion and prevention of infections and neoplasic process caused by the human papillomavirus (HPV). The study was arranged in two phases. First, the booklet was given to 200 volunteers in the city of Goiânia, Goiás State. The applicability of the booklet was evaluated without the necessity of proving former knowledge. In the second phase, a detailed analysis of the data was made and the booklet revealed applicable. Then, the educational material was published and 2000 copies were distributed in a social event held by the Pontifícia Universidade Católica de Góias in the city of Goiânia. In the event, the booklet raised the interest of the general public and gave the volunteers a chance to participate in a study that investigated the presence of the HPV in the genital microbiote. The booklet proved to be applicable and reached its objective to inform and prevent. However, it's necessary to promote and improve campaigns to the population about the HPV and its relations with the neoplasic process.

  20. Human papillomavirus and invasive cervical cancer in Brazil.

    PubMed Central

    Eluf-Neto, J.; Booth, M.; Muñoz, N.; Bosch, F. X.; Meijer, C. J.; Walboomers, J. M.

    1994-01-01

    A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer. PMID:8286192

  1. A review of methods for detect human Papillomavirus infection

    PubMed Central

    2012-01-01

    Human Papillomavirus (HPV) is the most common sexually transmitted virus. Worldwide, the most common high-risk (HR)-HPV are -16/18, and approximately 70% of cervical cancers (CC) are due to infection by these genotypes. Persistent infection by HR-HPV is a necessary but not sufficient cause of this cancer, which develops over a long period through precursor lesions, which can be detected by cytological screening. Although this screening has decreased the incidence of CC, HPV-related cervical disease, including premalignant and malignant lesions, continues to be a major burden on health-care systems. Although not completely elucidated, the HPV-driven molecular mechanisms underlying the development of cervical lesions have provided a number of potential biomarkers for both diagnostic and prognostic use in the clinical management of women with HPV-related cervical disease, and these biomarkers can also be used to increase the positive predictive value of current screening methods. In addition, they can provide insights into the biology of HPV-induced cancer and thus lead to the development of nonsurgical therapies. Considering the importance of detecting HPV and related biomarkers, a variety of methods are being developed for these purposes. This review summarizes current knowledge of detection methods for HPV, and related biomarkers that can be used to discriminate lesions with a high risk of progression to CC. PMID:23131123

  2. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

    PubMed Central

    Ward, Harvey Rodrick Grenville

    2014-01-01

    Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV) vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence. PMID:26425627

  3. Human papillomavirus DNA in plasma of patients with cervical cancer

    PubMed Central

    Pornthanakasem, Wichai; Shotelersuk, Kanjana; Termrungruanglert, Wichai; Voravud, Narin; Niruthisard, Somchai; Mutirangura, Apiwat

    2001-01-01

    Background Human papillomavirus (HPV) is a crucial etiological factor for cervical cancer (CC) development. From a diagnostic view-point, the consistent presence of HPV in CC allows the viral DNA to be used as a genetic marker. The aims of this study were to evaluate the presence, physical status and clinical significant of HPV DNA in circulation of CC patients. Results Whereas 6 out of 50 (12%) HPV positive CC patients revealed plasma HPV DNA, it was detected in none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited an HPV type identical to the HPV in the primary tumors and the DNA from both sources was integrated into host genome. Interestingly, several findings suggested an association between plasma HPV DNA and metastasis. First, three of the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence with distance metastases (P = 0.001, RR = 15.67). Second, the amount of plasma HPV DNA from metastatic patients to be three times more than three other patients without metastases. Finally, the later cases had tendency to develop recurrence distant metastases within one year after complete treatment when compared with other HPV associated CC patients with the same stage but without the present of plasma HPV DNA. Conclusions The plasma HPV DNA originated from the CC, was associated with metastasis and could be used as a marker representing the circulating free CC DNA. PMID:11244579

  4. Human papillomavirus in men: comparison of different genital sites

    PubMed Central

    Aguilar, L V; Lazcano‐Ponce, E; Vaccarella, S; Cruz, A; Hernández, P; Smith, J S; Muñoz, N; Kornegay, J R; Hernández‐Avila, M; Franceschi, S

    2006-01-01

    Objective To elucidate which anatomical sites need to be sampled to detect human papillomavirus (HPV) infection in the lower male genital tract. Method In an HPV survey of Mexican soldiers (median age 24 years; range 16–50 years), a cell sample from 2 cm deep into the distal urethra (group 1; n = 168 men), or 0.5 cm deep into the meatus urethralis (group 2; n = 414 men) was collected, along with a sample from the external genitalia. The different samples were tested for 27 HPV types using a polymerase chain reaction based strip assay. Results HPV DNA was detected more frequently in external genitalia samples (46.4%) than in the urethra (20.8%) or meatus samples (12.1%). Lack of samples from the urethra or meatus would have led to 5.1% and 1.5% false HPV negative results, respectively. The most frequently detected high risk HPV types (HPV 59, 52, 51, and 16) were similar in different sites, whereas low risk types were found rarely in urethra samples. Conclusions The addition of cell samples from the meatus to those from external genitalia contributed negligibly to the evaluation of the prevalence of HPV in men. HPV detection was slightly improved by the addition of urethra samples, but the gain may not justify the discomfort of the procedure in large epidemiological studies. PMID:16461598

  5. Maternal Support for Human Papillomavirus Vaccination in Honduras

    PubMed Central

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

    2011-01-01

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

  6. Evaluating knowledge about human papillomavirus infection among Brazilian health professionals.

    PubMed

    Villar, Livia Melo; Rabello, Aline Dutra; de Paula, Vanessa Salete

    2011-01-01

    Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases worldwide. Although two safe and clinically effective vaccines against HPV have been developed, they are not available to the public health network in Brazil. This study was performed to assess knowledge about HPV among seventy-nine professionals who completed a questionnaire about diagnosis, transmission, symptoms, prevention and general information. General knowledge about HPV was high, as most of them recognized that HPV is transmitted sexually (98.7%), the disease can be asymptomatic (82.3%) or warts can be present on the genitals (84.8 ) and the Pap smear is the screening method to identify cellular changes on the cervix (88.6%). However, many professionals did not know that there are now vaccines available for many HPV variants (38.0%) and that not all of them are oncogenic (44.3%). These data show that further educational programs, especially about HPV prevention, are needed in Brazil.

  7. Correlates of human papillomavirus vaccination among female university students

    PubMed Central

    Kelly, Kate M.; Vasilenko, Sara A.; Maggs, Jennifer L.

    2014-01-01

    Human papillomavirus (HPV) is the most frequently occurring sexually transmitted infection in the United States, but only one third of adolescent girls have received the HPV vaccine. Understanding correlates of vaccination behavior among young women has important implications for health care delivery and public service messages targeting HPV vaccination. Female college students (N = 313) completed web-based surveys during their sophomore (second) year of college, Fall, 2008. Surveys included questions about HPV vaccination, demographic factors (ethnicity/race, socioeconomic status [SES]), individual characteristics (romantic relationship status, grade point average, religiosity), and sexual behavior. Lifetime HPV vaccination was reported by 46.5% of participants. Being African-American/Black was associated with a lower likelihood of vaccination. Having a mother with more education, adhering to one’s religion’s teachings about sex-related principles, and having engaged in recent penetrative sex were associated with a higher likelihood of vaccination. Health care providers should consider young women to be an important group for HPV vaccine education and catch-up, particularly for African American/Black young women and young women from lower SES backgrounds. Providing vaccine education and access to young women before they become sexually active is critical. PMID:24964295

  8. Prevalence of human papillomavirus infection in Italian and immigrant women.

    PubMed

    Paba, P; Morosetti, G; Criscuolo, A A; Chiusuri, V; Marcuccilli, F; Sesti, F; Piccione, E; Perno, C F; Ciotti, M

    2012-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Prevalence varies according to the geographic regions, and is highest in developing countries. Geographic differences exist also in the detection rate of oncogenic types in malignant cervical lesions. In this study, the prevalence of HPV infection as well as the spectrum of HPV types was evaluated in Italian and immigrant women of the urban area of Rome. Several risk factors (age at first intercourse, number of partners, smoking, pregnancy, age at first pregnancy, contraception, education, and menarche) were taken into consideration. Overall, there was a high prevalence of HPV infection in the two groups studied. No significant differences were observed in the spectrum of HPV types detected. HPV 16 and 18 were the types detected more frequently in both groups. Interestingly, HPV 54 and 70 were found only in the immigrants. Whether this finding reflects a recent introduction of these HPV types in the population studied remains to be established. Monitoring of HPV types in the population is advisable, especially in countries like Italy which is a destination and a gateway for immigrants directed towards north and central Europe. The introduction of high risk HPV variants may have a clinical impact and affect the diagnostic procedures.

  9. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement.

    PubMed

    Saslow, Debbie; Andrews, Kimberly S; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E; Fisher-Borne, Marcie; Smith, Robert A; Fontham, Elizabeth T H

    2016-09-01

    Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society.

  10. Human papillomavirus (HPV): making the case for 'Immunisation for All'.

    PubMed

    Prue, G; Lawler, M; Baker, P; Warnakulasuriya, S

    2016-08-05

    Human papillomavirus (HPV) contributes to the most common sexually transmitted infections, with repeated and persistent infection with particular types causing disease in both men and women. Infection with low-risk HPV types can lead to genital warts and benign lesions of the oral cavity, while high-risk types can cause various HPV-related malignancies. The incidence of head and neck cancers has been rising in the past number of decades mostly due to oropharyngeal cancer linked to HPV infection. HPV vaccination has been shown to be effective for cervical and other anogenital HPV-related cancers, and there is significant potential for HPV vaccination to prevent oropharyngeal cancers, given that the HPV types implicated in this disease can be protected against by the HPV vaccine. Few countries have implemented a universal HPV vaccination programme for males and females, with many countries arguing that female-only vaccination programmes protect males via herd immunity and that men who have sex with men will be protected via targeted vaccination programmes. We argue these may be limited in their effectiveness. We propose that the most effective, practical, ethical and potentially cost-effective solution is universal HPV vaccination that might lead to control of HPV-related diseases in men and women alike.

  11. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

    SciTech Connect

    Moy, R.L.; Eliezri, Y.D.; Bennett, R.G. ); Nuovo, G.J.; Siverstein, S. Columbia Univ., New York, NY ); Zitelli, J.A. )

    1989-05-12

    Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. The high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.

  12. Management of human papillomavirus-related head and neck cancer.

    PubMed

    Coughlin, A M; Qiu, S; Underbrink, M P

    2014-01-01

    Human papillomavirus (HPV)-related head and neck malignancies (HNMs) have become a serious health risk over the past 20 years. Despite decreases in non-HPV-related HNMs, the incidence of HPV-related HNMs has skyrocketed, and a new form of tumorigenesis is developing. HPV type 16 is the primary offender, and the majority of these tumors present in the oropharynx, with a smaller proportion in the larynx and oral cavity. While traditionally treated with surgery, the paradigm has shifted to more of a nonoperative chemoradiation therapy approach, with the hope of improving vital functions after therapy. Unfortunately, we continue to see significant dysphagia in these patients after treatment, and work is being done to improve outcomes. With the advent of transoral robotic surgery, we have again been able to reconsider treatment options for these patients, although it has been met with some skepticism and resistance. Here we discuss the scope of HPV-related HNMs, the treatment options and prognosis for the disease, and finally touch upon psychosocial issues related to HPV-related HNMs. © 2014 S. Karger AG, Basel.

  13. Human Papillomavirus and the Development of Different Cancers.

    PubMed

    Gao, Ge; Smith, David I

    2017-03-01

    Human papillomaviruses (HPV) are responsible for the development of almost all cervical cancers. HPV is also found in 85% of anal cancer and in 50% of penile, vulvar, and vaginal cancers, and they are increasingly found in a subset of head and neck cancers, i.e., oropharyngeal squamous cell carcinomas (OPSCC). The model for how HPV causes cancer is derived from several decades of study on cervical cancer, and it is just presumed that this model is not only completely valid for cervical cancer but for all other HPV-driven cancers as well. Next-generation sequencing (NGS) has now provided the necessary tools to characterize genomic alterations in cancer cells and can precisely determine the physical status of HPV in those cells as well. We discuss recent discoveries from different applications of NGS in both cervical cancer and OPSCCs, including whole-genome sequencing and mate-pair NGS. We also discuss what NGS studies have revealed about the different ways that HPV can be involved in cancer formation, specifically comparing cervical cancer and OPSCC.

  14. Could the human papillomavirus vaccines drive virulence evolution?

    PubMed

    Murall, Carmen Lía; Bauch, Chris T; Day, Troy

    2015-01-07

    The human papillomavirus (HPV) vaccines hold great promise for preventing several cancers caused by HPV infections. Yet little attention has been given to whether HPV could respond evolutionarily to the new selection pressures imposed on it by the novel immunity response created by the vaccine. Here, we present and theoretically validate a mechanism by which the vaccine alters the transmission-recovery trade-off that constrains HPV's virulence such that higher oncogene expression is favoured. With a high oncogene expression strategy, the virus is able to increase its viral load and infected cell population before clearance by the vaccine, thus improving its chances of transmission. This new rapid cell-proliferation strategy is able to circulate between hosts with medium to high turnover rates of sexual partners. We also discuss the importance of better quantifying the duration of challenge infections and the degree to which a vaccinated host can shed virus. The generality of the models presented here suggests a wider applicability of this mechanism, and thus highlights the need to investigate viral oncogenicity from an evolutionary perspective.

  15. Is Human Papillomavirus Associated with Prostate Cancer Survival?

    PubMed Central

    Barbazza, Renzo; Marongiu, Barbara; Bonin, Serena; Stanta, Giorgio

    2013-01-01

    The role of human papillomavirus (HPV) in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa), whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67%) patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS) (median 4.59 years) compared to HPV-negative (median 8.24 years, P = 0.0381). In multivariate analysis age (P < 0.001), Gleason score (P < 0.001), nuclear grading (P = 0.002), and HPV status (P = 0.034) were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis. PMID:24288430

  16. Laboratory and clinical aspects of human papillomavirus testing

    PubMed Central

    Chan, Paul K.S.; Picconi, María Alejandra; Cheung, Tak Hong; Giovannelli, Lucia; Park, Jong Sup

    2012-01-01

    Human papillomavirus (HPV) infection is associated with a wide spectrum of disease that ranges from self-limited skin warts to life-threatening cancers. Since HPV plays a necessary etiological role in cervical cancer, it is logical to use HPV as a marker for early detection of cervical cancer and precancer. Recent advances in technology enable the development of high-throughput HPV assays of different formats, including DNA-based, mRNA-based, high-risk group-specific and type-specific methods. The ultimate goal of these assays is to improve the accuracy and cost-effiectiveness of cervical screening programs. HPV testing has several potential advantages compared to cytology-based screening. However, since the cancer to transient infection ratio is always low in the general population, HPV test results are bound to have a low positive predictive value that may subject women to unnecessary follow-up investigations. The wide-spread administration of prophylactic HPV vaccine will substantially decrease the incidence of cancer and precancer. This poses a number of challenges to cytology-based screening, and the role of HPV testing is expected to increase. Finally, apart from technical and cost-effiectiveness considerations, one should also keep in mind the psycho-social impact of using sexually-transmitted agents as a marker for cancer screening. PMID:22913405

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

    PubMed Central

    Pereira, Nigel; Kucharczyk, Katherine M.; Estes, Jaclyn L.; Gerber, Rachel S.; Lekovich, Jovana P.; Elias, Rony T.; Spandorfer, Steven D.

    2015-01-01

    The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage. PMID:26609434

  18. Human Papillomavirus Testing in the Prevention of Cervical Cancer

    PubMed Central

    Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.

    2011-01-01

    Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563

  19. Prospects and prejudices of human papillomavirus vaccines in India.

    PubMed

    Das, Bhudev C; Hussain, Showket; Nasare, Vilas; Bharadwaj, Mausumi

    2008-05-23

    Cervical cancer is the most common cancer and a leading cause of cancer deaths among women in developing countries. The disease is caused due to persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly by HPV types 16/18. In India, over 98% of cervical cancer cases harbor HPV infection and HPV 16 is the type exclusively (80-90%) prevalent. Unlike the West, HPV infection is most common in women in their third decade (26-35 years) of sexual activity and invasive cancer also arises much later with a peak at about 45-55 years of age. Recently, two successful prophylactic HPV vaccines, a quadrivalent (HPV16/18/6/11) 'Gardasil' by Merck and a bivalent (HPV16/18) 'Cervarix' by GSK have been developed. Several other approaches including plant-based edible, pentameric capsomere-based intranasal and DNA-based vaccines have also been employed to develop prophylactic vaccines. Also, several therapeutic vaccines either protein/peptide based or DNA based are in clinical trials but are yet to establish their efficacy. Though there are several issues regarding implementation of the already developed vaccines in resource limited countries, efforts are being made to develop cost-effective second-generation vaccines. If cost minimized, HPV related new technologies involved in screening tests and vaccines are expected to reduce incidence of cervical cancer and deaths it causes in women from developing countries.

  20. Human Beta-papillomavirus infection and keratinocyte carcinomas.

    PubMed

    Quint, Koen D; Genders, Roel E; de Koning, Maurits N C; Borgogna, Cinzia; Gariglio, Marisa; Bouwes Bavinck, Jan Nico; Doorbar, John; Feltkamp, Mariet C

    2015-01-01

    Although the role of oncogenic human Alpha-papillomaviruses (HPVs) in the development of mucosal carcinomas at different body sites (eg cervix, anus, oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KCs; basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the most common cancers in Caucasians, with the major risk factor being ultraviolet (UV) light exposure. A possible role for Beta-HPV types (BetaPV) in the development of KC was suggested several decades ago, supported by a number of epidemiological studies. Our current review summarizes the recent molecular and histopathological evidence in support of a causal association between BetaPV and the development of KC, and outlines the suspected synergistic effect of viral gene expression with UV radiation and immune suppression. Further insights into the molecular pathways and protein interactions used by BetaPV and the host cell is likely to extend our understanding of the role of BetaPV in KC.

  1. Human papillomavirus vaccination in the United Kingdom: what about boys?

    PubMed

    Kubba, Tamara

    2008-11-01

    In September 2008 the UK Department of Health initiated a human papillomavirus (HPV) immunisation programme for girls aged 12-13 for prevention of cervical cancer, which is most often caused by two HPV types. An important question, yet to be addressed, is whether boys should also be vaccinated. Men also get HPV and transmit it sexually, not just women. Certain HPV types are associated with genital warts, which have significant morbidity, and with difficult to treat non-cervical malignancies, including vulval, penile, anal and oro-pharyngeal cancer, which are best prevented through vaccination. Moreover, increased persistence of HPV infection is associated with HIV infection. A review of the literature and evidence from modelling suggest that vaccinating boys would increase vaccination impact and may be necessary to achieve herd immunity targets. Excluding boys sends the wrong message that girls and women alone are responsible for sexual health. Although protective efficacy of the vaccine in men has not yet been fully established, the rationale for vaccinating boys as well as girls at an early age is strong, assuming efficacy is established. Meanwhile, provision of the quadrivalent vaccine should become UK policy, in order to include protection against genital warts, the argument for which is strengthened if boys are also vaccinated.

  2. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids.

    PubMed

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-02-16

    Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx.

  3. Host defenses against human papillomaviruses: lessons from epidermodysplasia verruciformis.

    PubMed

    Orth, G

    2008-01-01

    Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive genodermatosis associated with a high risk of skin carcinoma (MIM 226400). EV is characterized by the abnormal susceptibility of otherwise healthy patients to infection by specific, weakly virulent human papillomaviruses (HPVs), including the potentially oncogenic HPV-5. Inactivating mutations in either of the related EVER1/TMC6 and EVER2/TMC8 genes cause most EV cases. New insights in EV pathogenesis have been gained from the following recent observations: (1) EV-specific HPVs (betapapillomaviruses) are defective for an important growth-promoting function encoded by an E5/E8 gene present in other HPVs, and inactivation of EVER proteins may compensate for the missing viral function; (2) the transmembrane viral E5/E8 and cellular EVER proteins interact both with the zinc transporter ZnT1, and are likely to modulate zinc homeostasis. EV may thus represent a primary deficiency in intrinsic, constitutive immunity to betapapillomaviruses, or constitute a primary deficiency in innate immunity (or both). Keratinocytes, the home cells of HPVs, are likely to play a central role in both cases. An important issue is to establish which cellular genes involved in intrinsic and innate antiviral responses play a part in the outcome of infections with other HPV types, such as genital oncogenic HPVs.

  4. Race, ethnicity, and income factors impacting human papillomavirus vaccination rates.

    PubMed

    Jeudin, Patricia; Liveright, Elizabeth; Del Carmen, Marcela G; Perkins, Rebecca B

    2014-01-01

    Human papillomavirus (HPV) infection and cervical cancer disproportionately affect low-income and minority women. HPV vaccines have the potential to either reduce or exacerbate racial disparities in HPV-related diseases and cervical cancers, depending on the equitability of vaccine uptake. This review aims to identify barriers and facilitators of equitable uptake of HPV vaccination among low-income and minority girls. This review discusses factors related to race, ethnicity, and income that are associated with initiation and completion rates of the 3-dose HPV vaccine series and presents targets for intervention. We reviewed relevant English-language literature to identify current vaccination rates and factors associated with vaccine uptake. Study findings related to race (black, Latino, Asian), and incomes were summarized. Current trends in the United States indicate low uptake among all adolescents, and that rates stagnated between 2011 and 2012. Low-income and minority adolescents are equally or more likely to start the HPV vaccination series than are white and higher-income adolescents, but are less likely to complete all 3 shots. Provider recommendation is a key factor in HPV vaccination, and minorities are less likely to report receiving recommendations for HPV vaccination. As black, Hispanic, and Asian populations continue to grow in the United States over the next several decades, it is imperative that we not only improve HPV vaccination rates overall, but also focus on high-risk populations to prevent an increase in cervical cancer disparities. © 2014 Published by Elsevier HS Journals, Inc.

  5. Differences in transcriptional activity of cutaneous human papillomaviruses.

    PubMed

    Vasiljević, Natasa; Nielsen, Lone; Doherty, Geoff; Dillner, Joakim; Forslund, Ola; Norrild, Bodil

    2008-11-01

    The interaction between UV-B irradiation and cutaneous human papillomaviruses (HPV) has been suggested to be of relevance for the development of non-melanoma skin cancers. We investigated the activity within the upstream regulatory region (URR) of the HPV types 8, 38, 92, 93 and 96, as well as their responsiveness to UV-B irradiation and cellular differentiation. Promoter activities were higher in HaCaT than in SiHa cells, corresponding to the HPV tissue tropism. Transcriptional start sites were mapped at P(92) (HPV-38), P(45) (HPV-92), P(7439) (HPV-93) and P(256) (HPV-96). Transcription from HPV-8, 93 and 96 URR was up-regulated by cellular differentiation, linking the activity of these HPVs to the cellular state. UV-B irradiation activated HPV-8 but inhibited HPV-38 and HPV-93 whereas HPV-92 and 96 were not affected. As there are variable UV-B responses among the HPV types, further studies of interactions between UV-B and HPV need to consider the HPV type.

  6. Human papillomavirus (HPV) information needs: a theoretical framework.

    PubMed

    Marlow, Laura A V; Wardle, Jane; Grant, Nina; Waller, Jo

    2009-01-01

    With the introduction of human papillomavirus (HPV) testing and vaccination in the UK, health professionals will start to receive questions about the virus from their patients. This study aimed to identify the key questions about HPV that British women will ask when considering having an HPV test or vaccination. Face-to-face interviews were carried out with 21 women to discover what they wanted to know about HPV. A thematic framework approach was used to analyse the data and identify key themes in women's HPV knowledge requirements. Women's questions about HPV fell into six areas: identity (e.g. What are the symptoms?), cause (e.g. How do you get HPV?), timeline (e.g. How long does it last?), consequences (e.g. Does it always cause cervical cancer?) and control-cure (e.g. Can you prevent infection?). In addition, they asked procedural questions about testing and vaccination (e.g. Where do I get an HPV test?). These mapped well onto the dimensions identified in Leventhal's description of lay models of illness, called the 'Common Sense Model' (CSM). These results indicated that the majority of the questions women asked about HPV fitted well into the CSM, which therefore provides a structure for women's information needs. The findings could help health professionals understand what questions they may be expected to answer. Framing educational materials using the CSM themes may also help health educators achieve a good fit with what the public want to know.

  7. Indications and efficacy of the human papillomavirus vaccine.

    PubMed

    Hakim, Amy A; Lin, Paul S; Wilczynski, Sharon; Nguyen, Kimhuynh; Lynes, Billie; Wakabayashi, Mark T

    2007-12-01

    In the United States, there are 11,150 cases and 3670 deaths projected due to invasive cervical cancer for 2007. Approximately 500,000 new cases and 274,000 deaths will occur in women throughout the world. Human papillomavirus (HPV) has been designated by the World Health Organization (WHO) as a "necessary cause" of cervical cancer. There are 6.2 million new cases of HPV diagnosed each year. In addition to cervical cancer, the virus has also been implicated in vaginal, vulvar, penile, anal, and head and neck cancers. Current methods for prevention of cervical cancer include Pap smears, HPV testing, ablative procedures, cervical conization, and hysterectomy. These are costly as well as invasive. The HPV vaccine is the most recent breakthrough for the prevention of cervical cancer. The quadrivalent HPV vaccine (Gardasil) covers types 6, 11, 16, & 18. The bivalent vaccine (Cervarix) covers types 16 & 18, and is expected to come out in the early part of 2007. Approximately 70% of cervical cancer is caused by HPV types 16 & 18. HPV types 6 &11 are responsible for 90% of anogenital warts. Females of ages 11-12 and those prior to their sexual debut should be vaccinated, with all females in the age range of 9-26 also eligible. This vaccination strategy can prevent the above HPV infections, cervical dysplasia, and possibly cervical cancer.

  8. Human papillomavirus DNA in squamous cell carcinoma of the lung.

    PubMed Central

    Hirayasu, T; Iwamasa, T; Kamada, Y; Koyanagi, Y; Usuda, H; Genka, K

    1996-01-01

    AIM: To compare the incidence of squamous cell carcinoma (SCC) of the lung in Okinawa with that in Niigata on the mainland. METHODS: All patients presenting with SCC of the lung in Okinawa and Niigata in 1993 were included in the study. Diagnoses were confirmed by conventional histological examination of paraffin wax sections. Human papillomavirus (HPV) was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for the E6 and E7 regions of the HPV genome. PCR products were analysed by Southern and dot blotting. RESULTS: The incidence of well differentiated SCC of the lung was high in patients from Okinawa compared with moderately and poorly differentiated types, and compared with the incidence of SCC in patients from Niigata. This is despite similar patterns of age, sex (predominatly male), and smoking habit. More patients from Okinawa, however, were positive for HPV DNA by PCR (79%) and NISH (53%). Many patients haboured HPV types 6, 16, and 18. Only 30% of patients from Niigata were positive for HPV DNA by PCR and 20% by NISH. These patients all harboured one HPV type only. CONCLUSION: Surprisingly large numbers of patients from Okinawa were positive for HPV DNA. The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation. Images PMID:8943746

  9. Bacterial Vaginosis and the Natural History of Human Papillomavirus

    PubMed Central

    King, Caroline C.; Jamieson, Denise J.; Wiener, Jeffrey; Cu-Uvin, Susan; Klein, Robert S.; Rompalo, Anne M.; Shah, Keerti V.; Sobel, Jack D.

    2011-01-01

    Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV). Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis. PMID:21869857

  10. [Cervical infection epidemiology of human papillomavirus in Ushuaia, Argentina].

    PubMed

    Sijvarger, C C; González, J V; Prieto, A; Messmer, A G; Mallimaci, M C; Alonio, V L; Teyssié, A R; Picconi, M A

    2006-01-01

    Genital infection with human papillomavirus (HPV) is decisive in the causation of cervical cancer. In order to evaluate the epidemiology of HPV infection in Ushuaia, Province of Tierra del Fuego, Argentina, 132 endocervical cytobrushes from preneoplastic and neoplastic cases and controls were studied. Detection and typing of the viral genome was performed by polymerase chain reaction, combined with a restriction fragment length polymorphism assay or hybridization. The overall prevalence of HPV infection was 41% in the population examined, with a frequency of 26% in the controls and 71% in the cases under study. The 14-24 age group showed the highest HPV prevalence. The most common viral types in the infected population were HPV 16 (23%), HPV 18 (11%), HPV 33 (8%) and HPV 35 (8%), while high risk viral types were detected in 30% of the samples, 16% of the controls and 60% of the cases. This study provides the first data on the predominant viral types in Ushuaia. Our results show lower levels of infection than in regions with a high incidence of cervical cancer, HPV 16 being the most prevalent viral type. This research may be useful for selecting a specific vaccine targeting the population examined.

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

    PubMed Central

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

    2015-01-01

    Background 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. Objective Our goal was to describe the HPV intratypic variants and associated baseline characteristics. Design 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. Results 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. Conclusions 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. PMID:26653084

  12. Human Papillomavirus Infectious Entry and Trafficking Is a Rapid Process

    PubMed Central

    Broniarczyk, Justyna; Massimi, Paola; Bergant, Martina

    2015-01-01

    ABSTRACT Previous studies have indicated that human papillomavirus (HPV) infectious entry is slow, requiring many hours after initial infection for the virus to gain entry into the nucleus. However, intracellular transport pathways typically are very rapid, and in the context of a natural HPV infection in a wounded epithelium, such slow intracellular transport would seem to be at odds with a normal viral infection. Using synchronized cell populations, we show that HPV trafficking can be a rapid process. In cells that are infected in the late S-early G2/M phase of the cell cycle, HPV16 pseudovirion (PsV) reporter DNA gene expression is detectable by 8 h postinfection. Likewise, reporter DNA can be visualized within the nucleus in conjunction with PML nuclear bodies 1 h to 2 h postinfection in cells that are infected with PsVs just prior to mitotic entry. This demonstrates that endosomal trafficking of HPV is rapid, with mitosis being the main restriction on nuclear entry. IMPORTANCE HPV infectious entry appears to be slow and requires mitosis to occur before the incoming viral DNA can access the nucleus. In this study, we show that HPV trafficking in the cell actually is very rapid. This demonstrates that in the context of a normal virus infection, the cell cycle state will have a major influence on the time it takes for an incoming virus to enter the nucleus and initiate viral gene expression. PMID:26063434

  13. Human papillomavirus genotypes and cervical cancer in northeast Thailand.

    PubMed

    Natphopsuk, Sitakan; Settheetham-Ishida, Wannapa; Pientong, Chamsai; Sinawat, Supat; Yuenyao, Pissamai; Ishida, Takafumi; Settheetham, Dariwan

    2013-01-01

    Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region.

  14. Human Papillomavirus Vaccination: A Case Study in Translational Science

    PubMed Central

    Palmer, Allyson K.; Harris, Antoneicka L.; Jacobson, Robert M.

    2014-01-01

    Each year 610,000 cases of anogenital and oropharyngeal cancers caused by human papillomavirus (HPV) occur worldwide. HPV vaccination represents a promising opportunity to prevent cancer on a global scale. The vaccine’s story dates back to discoveries in chickens at the beginning of the 20th century with evidence that a cell-free filtrate could transmit the propensity to grow cancers. Later, studies with similarly derived filtrates from mammalian tumors showed that hosts could develop immunity to subsequent exposures. Epidemiologic studies linked cervical cancer to members of a family of viruses that cause papillomatosis and common warts. This led to work with DNA hybridization demonstrating a causal relationship. The formation of virus-like particles (VLPs) from viral capsid proteins led to the development of models for safe and effective vaccines. While much work remains with the acceptance of universal vaccination, the HPV vaccines Gardasil® and Cervarix® thus represent a century of successful translational research. PMID:24841923

  15. Different Modes of Human Papillomavirus DNA Replication during Maintenance

    PubMed Central

    Hoffmann, Ralf; Hirt, Bernhard; Bechtold, Viviane; Beard, Peter; Raj, Kenneth

    2006-01-01

    Human papillomavirus (HPV) begins its life cycle by infecting the basal cells of the epithelium. Within these proliferating cells, the viral genomes are replicated, maintained, and passed on to the daughter cells. Using HPV episome-containing cell lines that were derived from naturally infected cervical tissues, we investigated the mode by which the viral DNAs replicate in these cells. We observed that, whereas HPV16 DNA replicated in an ordered once-per-S-phase manner in W12 cells, HPV31 DNA replicated via a random-choice mechanism in CIN612 cells. However, when HPV16 and HPV31 DNAs were separately introduced into an alternate keratinocyte cell line NIKS, they both replicated randomly. This indicates that HPV DNA is inherently capable of replicating by either random-choice or once-per-S-phase mechanisms and that the mode of HPV DNA replication is dependent on the cells that harbor the viral episome. High expression of the viral replication protein E1 in W12 cells converted HPV16 DNA replication to random-choice replication and, as such, it appears that the mode of HPV DNA replication in proliferating cells is dependent on the presence or the increased level of this protein in the host cell. The implications of these observations on maintenance, latency, and persistence are discussed. PMID:16611903

  16. Parental acceptance of a mandatory human papillomavirus (HPV) vaccination program.

    PubMed

    Ferris, Daron; Horn, Leslie; Waller, Jennifer L

    2010-01-01

    The objective of this study was to determine factors that influence parent's acceptance of a mandatory school-based human papillomavirus (HPV) vaccination program. A convenience sample of 325 parents, with children aged 9 to 17 years old, completed a 53-item survey. Survey questions targeted their opinions about HPV, the HPV vaccine, and a mandatory HPV vaccination program. chi(2) tests were used to examine relationships between survey items. Characteristics of parents who believed the HPV vaccine should be mandated included limited financial resources (P = .03), history of HPV-related disease (P = .04), understanding their child's susceptibility (P = .03), interest in HPV vaccination for their child (P = .0001), and knowledge that the vaccine reduces the risk of cervical cancer (P = .001). Parents of children aged 12 to 14 years old (P = .02) or who knew the vaccine reduced their child's risk of developing genital warts (P = .02) and cervical cancer (P = .001) would be more likely to comply with a mandatory HPV vaccine program. Certain characteristics define parents who support a mandatory HPV vaccination program. Greater education of parents and health care providers should improve vaccination uptake, which ultimately reduces morbidity and mortality from HPV related diseases.

  17. The Interaction Between Human Papillomaviruses and the Stromal Microenvironment.

    PubMed

    Woodby, B; Scott, M; Bodily, J

    2016-01-01

    Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs, or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology, focusing on stromal fibroblasts, immune cells, and endothelial cells. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection. © 2016 Elsevier Inc. All rights reserved.

  18. Human papillomaviruses and non-melanoma skin cancer.

    PubMed

    McLaughlin-Drubin, Margaret E

    2015-04-01

    Human papillomaviruses (HPVs) infect the squamous epithelium and can induce benign and malignant lesions. To date, more than 200 different HPV types have been identified and classified into five genera, α, β, γ, μ, and ν. While high-risk α mucosal HPVs have a well-established role in cervical carcinoma and a significant percentage of other anogenital tract and oral carcinomas, the biology of the cutaneous β HPVs and their contribution to non-melanoma skin cancer (NMSC) has been less studied. Although the association of β HPV infection with NMSC in patients with a rare, genetically determined condition, epidermodysplasia verruciformis has been well established, the role of β HPV infection with NMSC in the normal population remains controversial. In stark contrast to α HPV-associated cancers, the presence of the β HPV genome does not appear to be mandatory for the maintenance of the malignant phenotype. Moreover, the mechanism of action of the β HPV E6 and E7 oncoproteins differs from the β HPV oncoproteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    PubMed Central

    Tummers, Bart; Van Der Burg, Sjoerd H.

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697

  20. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids

    PubMed Central

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-01-01

    Background: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. Methods: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. Results: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. Conclusions: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx. PMID:26867163

  1. Cervical cancer in the human papillomavirus vaccination era.

    PubMed

    Tay, Sun-Kuie

    2012-02-01

    To evaluate the potential changes in the epidemiology of cervical cancer based on recently emerged information from mass vaccination programs beyond clinical trials. Limited sensitivity and unequal access to screening have resulted in an imbalance in distribution of the burden of cervical cancer between developed and developing countries, between metropolitan and rural areas in developed countries, and among women from different ethnic groups. In screened populations, there is a relative increase in incidence of cervical cancer in young and elderly women, and an increased proportion of adenocarcinoma. A high coverage of the target population has been achieved in human papillomavirus (HPV) vaccination programs in many countries. After 3 years of mass vaccination of adolescent girls, surveillance data in Australia confirmed a significant reduction in high-grade abnormalities for girls aged 18 years and below. HPV vaccination is more feasible than cytology screening for universal implementation across geographic sectors and demographic groups within individual countries and over the world. The high vaccine efficacy should significantly reduce the total burden and unequal distribution of invasive cervical cancer, including adenocarcinoma hitherto observed. These epidemiological changes provoke consideration for appropriate modifications of the current screening program.

  2. Transmission between Archaic and Modern Human Ancestors during the Evolution of the Oncogenic Human Papillomavirus 16.

    PubMed

    Pimenoff, Ville N; de Oliveira, Cristina Mendes; Bravo, Ignacio G

    2017-01-01

    Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections by Human papillomavirus 16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history was still wanting. We have analyzed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively. We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesize that differential coevolution of HPV16 lineages with different but closely related ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants.

  3. Establishment of Human Papillomavirus Infection Requires Cell Cycle Progression

    PubMed Central

    Pyeon, Dohun; Pearce, Shane M.; Lank, Simon M.; Ahlquist, Paul; Lambert, Paul F.

    2009-01-01

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

  4. Multiplexed Serologic Assay for Nine Anogenital Human Papillomavirus Types▿

    PubMed Central

    Opalka, David; Matys, Katie; Bojczuk, Paul; Green, Tina; Gesser, Richard; Saah, Alfred; Haupt, Richard; Dutko, Frank; Esser, Mark T.

    2010-01-01

    A multiplexed human papillomavirus (HPV) immunoassay has been developed for the detection of human IgG antibodies to HPV type 6, 11, 16, 18, 31, 33, 45, 52, and 58 virus-like particle (VLP) types in serum following natural infection or immunization with VLP-based vaccines. The VLP antigens were covalently conjugated to carboxyl Luminex microspheres (MS) using a carbodiimide chemistry. Antibody (Ab) titers were determined in a direct binding format, in which an IgG1- to -4-specific, phycoerythrin (PE)-labeled monoclonal antibody (MAb) (HP6043) binds to human serum IgG antibodies. Pooled serum samples from rhesus macaques immunized with a 9-valent VLP-based vaccine served as the reference standard. The overall specificity of the assay was >99%, and the linearity (parallelism) of the assay was <7% per 10-fold dilution. Total assay precision was <19% across 3 different VLP-microsphere lots, 2 secondary antibody lots, and 2 different operators over a period of 3 weeks. Three different methods were used to evaluate serostatus cutoffs (SCO): (i) a clinical sensitivity/specificity analysis based on “likely negative” and “likely positive” samples from nonvaccinees, (ii) stringent upper tolerance limits on samples from “likely negatives,” and (iii) stringent upper tolerance limits from the same “likely negative” sample set after VLP adsorption. Depending on the method to set the serostatus cutoff, the percentage of seropositive samples at the month 48 time point following vaccination with the HPV 6/11/16/18 quadrivalent vaccine ranged from 70% to 100%. This assay has proven useful for measuring the levels of serum antibody to the nine HPV VLPs following natural infection or administration of VLP-based vaccines. PMID:20237197

  5. Multiplexed serologic assay for nine anogenital human papillomavirus types.

    PubMed

    Opalka, David; Matys, Katie; Bojczuk, Paul; Green, Tina; Gesser, Richard; Saah, Alfred; Haupt, Richard; Dutko, Frank; Esser, Mark T

    2010-05-01

    A multiplexed human papillomavirus (HPV) immunoassay has been developed for the detection of human IgG antibodies to HPV type 6, 11, 16, 18, 31, 33, 45, 52, and 58 virus-like particle (VLP) types in serum following natural infection or immunization with VLP-based vaccines. The VLP antigens were covalently conjugated to carboxyl Luminex microspheres (MS) using a carbodiimide chemistry. Antibody (Ab) titers were determined in a direct binding format, in which an IgG1- to -4-specific, phycoerythrin (PE)-labeled monoclonal antibody (MAb) (HP6043) binds to human serum IgG antibodies. Pooled serum samples from rhesus macaques immunized with a 9-valent VLP-based vaccine served as the reference standard. The overall specificity of the assay was >99%, and the linearity (parallelism) of the assay was <7% per 10-fold dilution. Total assay precision was <19% across 3 different VLP-microsphere lots, 2 secondary antibody lots, and 2 different operators over a period of 3 weeks. Three different methods were used to evaluate serostatus cutoffs (SCO): (i) a clinical sensitivity/specificity analysis based on "likely negative" and "likely positive" samples from nonvaccinees, (ii) stringent upper tolerance limits on samples from "likely negatives," and (iii) stringent upper tolerance limits from the same "likely negative" sample set after VLP adsorption. Depending on the method to set the serostatus cutoff, the percentage of seropositive samples at the month 48 time point following vaccination with the HPV 6/11/16/18 quadrivalent vaccine ranged from 70% to 100%. This assay has proven useful for measuring the levels of serum antibody to the nine HPV VLPs following natural infection or administration of VLP-based vaccines.

  6. Clinical and serological manifestations of genital human papillomavirus infection.

    PubMed

    Wikström, A

    1995-01-01

    Efficacy of chemical and/or surgical treatment for penile and anal condylomata acuminata was investigated in two retrospective studies of hetero- and homosexual men. Variation in clinical features and symptomatology as well as the reliability of diagnostic criteria by different methods for acetowhite penile lesions was also studied. Furthermore, the antibody response in the course of penile wart disease as well as in asymptomatic genitoanal papillomavirus infection (GPVI) was analysed. In the first retrospective study, as much as 23% of patients still had condylomas after one year of chemical and/or surgical treatment. On the other hand, 38% were cured after a single treatment session. In the group mainly with anal warts, concurrent penile warts were significantly more common among heterosexual men compared to homosexual men (p < 0.001), while intra-anal wart growth was more common among the homosexual males (p < 0.001). When comparing diagnostic methods for subclinical penile HPV infection, conventional histopathology appeared to be the most valuable diagnostic aid to penoscopy, while the additional use of Southern blot, in situ hybridisation and PCR assays for HPV DNA detection did not increase the predictive value of GPVI. We also describe a new distinct clinical entity, HPV-associated balanoposthitis, comprising a wide range of often long-lasting symptoms, such as itching, burning and dyspareunia. A significant increase in the IgG antibody response against defined epitopes in the L1 and L2 capsid proteins of HPV 6, was found among men with previous condylomata. By following a cohort of STD clinic patients with multiple brush samples from the genitoanal region as well as serum samples taken at several consecutive clinical visits, we identified 16 patients who had seroconverted to HPV seropositivity during follow-up. Antibody responses to several HPV-derived peptide and protein antigens were induced at the same time. Seroconversions were usually seen

  7. A highly conserved nucleotide string shared by all genomes of human papillomaviruses.

    PubMed

    Campione-Piccardo, J; Montpetit, M L; Grégoire, L; Arella, M

    1991-10-01

    The nucleotide string TAAAACGAAAGT is the longest perfect homology shared by all sequenced human papillomavirus genomes. This nucleotide string, which was also found to be highly specific for human papillomavirus genomes, shares the same genomic position in all viral types (5' end of the E1 open reading frame) and putatively codes in every case for the same amino acids. One possible evolutionary model was used to estimate the probability of random occurrence of the nucleotide string in 10 human papillomavirus genomes. It assumed that the universal string had been subjected to the same mutation rate as the entire E1 open reading frame. The estimated probability was found to be very low, suggesting that the conservation of the string could not have resulted from random divergence and that its conservation among human papillomaviruses is likely to reflect the occurrence of biological constraints. It is speculated that this nucleotide string may be required to code for amino acids indispensable for the nuclear localization of E1-coded peptides or to bind cellular factors affecting viral replicative functions. Definitive evidence is expected to come from oligonucleotide-protein binding experiments and from site-directed mutagenesis of cloned HPV genomes. This motif, universal among human papillomaviruses, is being successfully used in the design of consensus primers from the early region.

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

    PubMed

    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.

  9. Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses

    PubMed Central

    Snijder, Berend; Samperio Ventayol, Pilar; Kühbacher, Andreas; Becker, Miriam; Day, Patricia M.; Schiller, John T.; Kann, Michael; Pelkmans, Lucas; Helenius, Ari; Schelhaas, Mario

    2014-01-01

    A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies. PMID:24874089

  10. Large scale RNAi reveals the requirement of nuclear envelope breakdown for nuclear import of human papillomaviruses.

    PubMed

    Aydin, Inci; Weber, Susanne; Snijder, Berend; Samperio Ventayol, Pilar; Kühbacher, Andreas; Becker, Miriam; Day, Patricia M; Schiller, John T; Kann, Michael; Pelkmans, Lucas; Helenius, Ari; Schelhaas, Mario

    2014-05-01

    A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies.

  11. Fluorescently Labeled Human Papillomavirus Pseudovirions for Use in Virus Entry Experiments.

    PubMed

    Samperio Ventayol, Pilar; Schelhaas, Mario

    2015-05-01

    Human papillomaviruses (HPV) infect skin or mucosal epidermis. The simplistic capsid consists of a major capsid protein L1, a minor capsid protein L2, and a double-stranded circular DNA of about 8 kB in size. The development of HPV-based vectors [i.e., pseudovirions (PsV)] as tools to study the initial infection has facilitated our understanding of HPV entry. The covalent coupling of fluorescent molecules to these PsV allows following the viruses en route to the nucleus, i.e., the site of replication. In the first section, we describe a facile method to covalently label HPV PsV that retain their infectivity. In this method, fluorophores coupled to a reactive succinimidyl ester are covalently attached to amine residues in the virion in a one-step chemical reaction. In the second section of this unit, several assays are outlined that use the fluorescently labeled virions for entry studies in live and fixed cells.

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

    PubMed

    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.

  13. Human papillomavirus and squamous cell cancer of the skin--epidermodysplasia verruciformis-associated human papillomavirus revisited.

    PubMed

    Arnold, Andreas W; Hofbauer, Günther F L

    2012-01-01

    As squamous cell cancer (SCC) is the most common malignancy in organ transplant recipients, a viral etiology has been proposed. Human papillomavirus (HPV) is found more often in organ transplant recipients than in the general population, but its role in cancer development has been debated for years. As a model of susceptibility of HPV the inherited disease epidermodysplasia verruciformis (EV) has been investigated intensively. EV is an autosomal-recessive skin disease leading to multiple flat warts and pityriasis versicolor-like macules in early youth. EV patients are at great risk of developing skin cancer due to a lack of defense against beta HPV. Beta HPV are causally involved in the formation of skin cancer in patients afflicted with EV. Beta HPV has frequently been detected in SCC and its early lesions such as actinic keratoses. Depending on the methods used, a prevalence of 30-90% has been reported for beta HPV for SCC in organ transplant recipients, while this prevalence in the general population is lower, but still considerable at 50%. Epidemiologic studies in the general population seem to suggest that beta HPV plays a role in the formation of SCC, both for invasive and in situ lesions.

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

    PubMed Central

    Thurman, Natalie; Halliday, Darron; Butler, Raleigh; Francis, Dorita; Joseph, Madeline; Thompson, Jahzreel; Andraos-Selim, Cecile; Taioli, Emanuela; Hagan, Kourtney L.; Jones, Erin A.; Jones, Jade; Moss, Cierra M.; Smith, Ar'Lena C.; Ashing, Kimlin Tam; Ragin, Camille C.

    2013-01-01

    Objective. To compare knowledge and attitudes of human papillomavirus (HPV) and the vaccine between different cultures of African descent. Methods. A cross-sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US and the Bahamas (BHM) was conducted. Results. General knowledge about HPV and the HPV vaccine differed between the two countries significantly. Bahamian respondents were less likely to have higher numbers of correct knowledge answers when compared to Americans (Adjusted Odds Ratio [Adj. OR] 0.47, 95% Confidence Interval [CI] 0.30–0.75). Older age, regardless of location, was also associated with answering fewer questions correctly (Adj. OR 0.61, 95% CI 0.40–0.92). Attitudes related to HPV vaccination were similar between the US and BHM, but nearly 80% of BHM respondents felt that children should not be able to receive the vaccine without parental consent compared to 57% of American respondents. Conclusions. Grave lack of knowledge, safety and cost concerns, and influence of parental restrictions may negatively impact vaccine uptake among African-American and Afro-Caribbean persons. Interventions to increase the vaccine uptake in the Caribbean must include medical provider and parental involvement. Effective strategies for education and increasing vaccine uptake in BHM are crucial for decreasing cervical cancer burden in the Caribbean. PMID:23956612

  15. Human Papillomavirus Typing in HIV-Positive Women

    PubMed Central

    Hameed, Meera; Fernandes, Helen; Skurnick, Joan; Moore, Dorothy; Kloser, Patricia

    2001-01-01

    Objective: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), whichwere predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low- and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear. Study design: HPV DNA typing (low- and high-risk) by Digene™ (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis. Results: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears whichwere read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes. Conclusion: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears. PMID:11495559

  16. The biology and life-cycle of human papillomaviruses.

    PubMed

    Doorbar, John; Quint, Wim; Banks, Lawrence; Bravo, Ignacio G; Stoler, Mark; Broker, Tom R; Stanley, Margaret A

    2012-11-20

    Human papillomaviruses (HPVs) comprise a diverse group, and have different epithelial tropisms and life-cycle strategies. Many HPVs are classified as low-risk, as they are only very rarely associated with neoplasia or cancer in the general population. These HPVs typically cause inapparent/inconspicuous infections, or benign papillomas, which can persist for months or years, but which are eventually resolved by the host's immune system. Low-risk HPVs are difficult to manage in immunosuppressed people and in individuals with genetic predispositions, and can give rise to papillomatosis, and in rare instances, to cancer. The high-risk HPV types are, by contrast, a cause of several important human cancers, including almost all cases of cervical cancer, a large proportion of other anogenital cancers and a growing number of head and neck tumours. The high-risk HPV types constitute a subset of the genus Alphapapillomavirus that are prevalent in the general population, and in most individuals cause only inconspicuous oral and genital lesions. Cancer progression is associated with persistent high-risk HPV infection and with deregulated viral gene expression, which leads to excessive cell proliferation, deficient DNA repair, and the accumulation of genetic damage in the infected cell. Although their life-cycle organisation is broadly similar to that of the low-risk HPV types, the two groups differ significantly in their capacity to drive cell cycle entry and cell proliferation in the basal/parabasal cell layers. This is thought to be linked, at least in part, to different abilities of the high- and low-risk E6 proteins to modulate the activity of p53 and PDZ-domain proteins, and the differential ability of the E7 proteins to target the several different members of the retinoblastoma protein family. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Crown Copyright

  17. Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial.

    PubMed

    Elfgren, Kristina; Elfström, K Miriam; Naucler, Pontus; Arnheim-Dahlström, Lisen; Dillner, Joakim

    2017-03-01

    Introduction of human papillomavirus-based screening is ongoing in many countries, given its higher sensitivity and longer-lasting protection compared with cytology-based screening. However, optimal clinical management of human papillomavirus-positive but cytology-negative women is unclear, and additional studies with clinical follow-up are warranted. The aim of the current study was to investigate the long-term outcomes of the clinical management used in a double-blind, randomized clinical trial of human papillomavirus screening conducted in the context of the routine, organized screening program in Sweden. Among 12,527 women aged 32-38 years enrolled in the trial, we followed up the 195 women who attended the colposcopy screening who were cytologically normal but persistently human papillomavirus positive (at least 12 months later; median, 19 months) in the human papillomavirus testing arm (n = 100) or were randomly selected from the control arm (n = 95). Women in the human papillomavirus testing arm were followed up with repeated human papillomavirus testing, cytologies, and colposcopies if persistently human papillomavirus-positive without cervical intraepithelial neoplasia grade 2 or worse. A similar number of random colposcopies and tests were carried out in the control arm. Women were followed up over 13 years for the main outcome measures: cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse and cervical intraepithelial neoplasia grade 3 or worse. Among women who continued to attend and had continuous human papillomavirus persistence, all (40 of 40, 100% [95% confidence interval, 91-100%]) developed cervical intraepithelial neoplasia grade 2 or worse. There were no cases among women who cleared their human papillomavirus persistence (0 of 35, 0% (95% confidence interval, 0-10%) (P < .001). Among women who had had human papillomavirus persistence but did not continue with repeated human papillomavirus tests (unknown persistence

  18. Association of Schistosoma haematobium and human papillomavirus in cervical cancer: a case report.

    PubMed

    Savardekar, Lalita S; Balaiah, Donta; Mali, Bapurao N

    2010-01-01

    The association between Schistosoma haematobium and cervical cancer has been reported for a long time. However, recently human papillomavirus, a cofactor in the genesis of cervical cancer, has been confirmed. A case of squamous intraepithelial lesion after S haematobium infection is presented, and the relation between schistosomiasis, human papillomavirus and squamous intraepithelial lesion, with long-term follow-up by Papanicolaou smear, is discussed. A 33-year-old, normal, healthy woman with a history of Copper intrauterine device (IUD) use for 3.9 years presented for her annual contraceptive follow-up. Her Pap smear revealed inflammation with a S haematobium egg. She was followed up with Pap smears for 4 years. Retrospective contraceptive history revealed use ofa copper IUD on 5 occasions with a total duration of 13 years and 1 month. Similarly, annual follow-up of Pap smears for the past 13 years showed mild inflammation with bacterial vaginitis and monilial infection. Subsequent smears showed an Actinomyces-like organism and then human papillomavirus infection with atypical squamous cells of undetermined significance followed by human papillomavirus-associated low/high grade squamous intraepithelial lesion. Caution is required while screening routine Pap smears. Apart from nuclear abnormalities, one can observe unusual findings. Long-term followup by Pap smear following detection of S haematobium revealed that in the absence of human papillomavirus, S haematobium alone is not the causative agent for the abnormal proliferation of squamous epithelium of the cervix. Genital Schistosomia acts as a cofactor by traumatizing the genital epithelium or immune suppression to favor human papillomavirus infection.

  19. Human papillomavirus-induced oropharyngeal cancer in Hispanics in the United States.

    PubMed

    Thomas, Giovana R; Lo, Kaming; Nwojo, Raphael

    2017-05-01

    Determine disparities in survival outcome and clinical presentation between Hispanic and non-Hispanic white patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma. Retrospective clinical research. Clinical data on Hispanics and non-Hispanic white patients with diagnosis of human papillomavirus/p16-positive oropharyngeal squamous cell carcinoma were drawn from a tumor registry from the University of Miami Hospitals and Clinics from 2008 to 2014. Of 436 patients with oropharyngeal squamous cell carcinoma, 237 patents met inclusion criteria. Patient's age, gender, smoking history, alcohol history, race/ethnicity, tumor T stage, nodal N stage, and composite TNM stage were included in the analysis. Associations between race and other categorical variables were explored with χ(2) test or Fisher exact test where appropriate. Survival curves were generated using the Kaplan-Meier method. Significant differences in clinical presentation was detected between Hispanic (N = 70) and non-Hispanic white (N = 167) patients. Hispanic human papillomavirus-positive oropharyngeal squamous cell carcinoma patients showed a higher proportion of women with disease, a higher proportion of patients presenting with tonsil rather than tongue base primary subsite cancer, and a higher proportion of patients who do not consume alcohol compared to non-Hispanic white human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. A statistically significant survival difference between these two ethnic groups was not detected in the current dataset. Unique differences in clinical presentations between Hispanic patients and non-Hispanic whites with human papillomavirus-positive oropharyngeal squamous cell carcinoma were detected. This may be the first study to report novel clinical presentation in Hispanic human papillomavirus-positive patients with oropharyngeal squamous cell carcinoma living in the United States. 4. Laryngoscope, 127:1097-1101, 2017.

  20. Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study.

    PubMed

    Moscicki, Anna-Barbara; Farhat, Sepideh; Yao, Tzy-Jyun; Ryder, Mark I; Russell, Jonathan S; Van Dyke, Russell B; Hazra, Rohan; Shiboski, Caroline H

    2016-08-01

    In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

  1. Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide

    PubMed Central

    Chen, Alyce A.; Gheit, Tarik; Franceschi, Silvia

    2015-01-01

    ABSTRACT Human papillomavirus 18 (HPV18) is the second most carcinogenic HPV type, after HPV16, and it accounts for approximately 12% of squamous cell carcinoma (SCC) as well as 37% of adenocarcinoma (ADC) of the cervix worldwide. We aimed to evaluate the worldwide diversity and carcinogenicity of HPV18 genetic variants by sequencing the entire long control region (LCR) and the E6 open reading frame of 711 HPV18-positive cervical samples from 39 countries, taking advantage of the International Agency for Research on Cancer biobank. A total of 209 unique HPV18 sequence variants were identified that formed three phylogenetic lineages (A, B, and C). A and B lineages each divided into four sublineages, including a newly identified candidate B4 sublineage. The distribution of lineages varied by geographical region, with B and C lineages found principally in Africa. HPV18 (sub)lineages were compared between 453 cancer cases and 236 controls, as well as between 81 ADC and 160 matched SCC cases. In region-stratified analyses, there were no significant differences in the distribution of HPV18 variant lineages between cervical cancer cases and controls or between ADC and SCC. In conclusion, our findings do not support the role of HPV18 (sub)lineages for discriminating cancer risk or explaining why HPV18 is more strongly linked with ADC than SCC. IMPORTANCE This is the largest and most geographically/ethnically diverse study of the genetic variation of HPV18 to date, providing a comprehensive reference for phylogenetic classification of HPV18 sublineages for epidemiological and biological studies. PMID:26269181

  2. Association between human papillomavirus DNA and temporal arteritis

    PubMed Central

    2012-01-01

    Background To examine the relationship between human papillomavirus (HPV) and giant cell arteritis (GCA) of the temporal artery. Methods The study group consisted of 22 cases of histologically positive/biopsy confirmed GCA. The control groups consisted of 21 histologically negative temporal artery biopsies and fifteen cases of vascular margins of nephrectomies. For detection of the presence of HPV, two methods were used: 1) polymerase chain reaction (PCR) with INNO-LiPA HPV Genotyping Extra, 2) Cervista™ HPV HR. All cases were from the files of the Barnes-Jewish Hospital and Washington University in St. Louis. Results HPV DNA was detected by PCR and genotyping in 16 of 22 (73%) histologically positive cases of GCA and in only five of 21 (24%) histologically negative temporal artery biopsies. Among the vascular margin controls, only three of 15 (20%) were positive for HPV DNA. The second, independent method (CervistaTM) confirmed the aforesaid results with 100% concordance with the exception of three cases which had low genomic DNA for which it was not possible to perform the test. The differences in HPV positivity between the histologically positive and negative temporal artery biopsies and between the histologically positive temporal artery biopsies and controls were both statistically significant (p = 0.001 and 0.002, respectively). Conclusions The results of our study revealed a statistically significant association between HPV positivity and biopsy confirmed temporal giant cell arteritis GCA (p = 0.001). Further studies are necessary to elucidate the pathophysiology underlying this association. PMID:22831396

  3. Meta-analysis of human papillomavirus infection concordance

    PubMed Central

    Reiter, Paul L.; Pendergraft, William F.; Brewer, Noel T.

    2010-01-01

    Background Estimates of human papillomavirus (HPV) concordance among sexual partners are important for various public health activities, from counseling individual patients to predicting the impact of HPV vaccination. Methods We systematically searched PubMed and EMBASE for studies of HPV concordance among heterosexual couples published through 2008 in English. Two coders independently abstracted data using standardized forms. We integrated concordance data using random-effects meta-analysis. Results Thirty studies (33 study populations) that met inclusion criteria reported concordance data for 2,972 couples. Most studies were cross-sectional, cohort studies conducted in Europe or Asia that used DNA hybridization to test for HPV, sometimes in conjunction with polymerase chain reaction (PCR). Overall, 25.5% (95% CI: 17.2%-36.1%) of couples were infected with 1 or more of the same HPV types. Among couples with both members HPV-positive, 63.2% (95% CI: 49.1%-75.3%) were infected with 1 or more of the same viral types. Positive concordance was higher for female partners of men with HPV infections than for male partners of women with HPV infections. Positive concordance was also higher for studies using PCR and for the few studies that recruited men with HPV-related disease. Conclusions Sexual partners of HPV-infected individuals had high rates of HPV infection, suggesting a need for increased attention to this group. Impact Our refined estimates of HPV concordance can inform clinical encounters and public health planning. Future HPV concordance studies should use more rigorous research designs, characterize their participants in greater detail, and study more meaningful populations. PMID:20833971

  4. Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review

    PubMed Central

    Stein, Andrew P.; Saha, Sandeep; Kraninger, Jennifer L.; Swick, Adam D.; Yu, Menggang; Lambertg, Paul F.; Kimple, Randall

    2015-01-01

    Purpose The global incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing, and it has been proposed that a rising rate of human papillomavirus (HPV) associated cancers is driving the observed changes in OPSCC incidence. We carried out this systematic review to further examine the prevalence of HPV in OPSCC over time worldwide. Methods A systematic literature search was performed to identify all articles through January 31, 2014 that reported on the prevalence of HPV in OPSCC. Articles that met inclusion criteria were divided into four time frames (pre-1995, 1995—1999, 2000—2004, and 2005—present) based on the median year of the study's sample collection period. Employing a weighted analysis of variance (ANOVA) model, we examined the trends of HPV-positivity over time worldwide, in North America, and in Europe. Results Our literature search identified 699 unique articles. 175 underwent review of the entire study and 105 met inclusion criteria. These 105 articles reported on the HPV prevalence in 9541 OPSCC specimens across 23 nations. We demonstrated significant increases in the percentage change of HPV-positive OPSCCs from pre-1995 to present: 20.6% worldwide (p-value for trend: p<0.001), 21.6% in North America (p=0.013) and 21.5% in Europe (p=0.033). Discussion Interestingly, while in Europe there was a steady increase in HPV prevalence across all time frames, reaching nearly 50% most recently, in North America HPV prevalence appears to have plateaued over the past decade at about 65%. These findings may have important implications regarding predictions for the future incidence of OPSCC. PMID:26049691

  5. A rapid DNA extraction method suitable for human papillomavirus detection.

    PubMed

    Brestovac, Brian; Wong, Michelle E; Costantino, Paul S; Groth, David

    2014-04-01

    Infection with oncogenic human papillomavirus (HPV) genotypes is necessary for the development of cervical cancer. Testing for HPV DNA from liquid based cervical samples can be used as an adjunct to traditional cytological screening. In addition there are ongoing viral load, genotyping, and prevalence studies. Therefore, a sensitive DNA extraction method is needed to maximize the efficiency of HPV DNA detection. The XytXtract Tissue kit is a DNA extraction kit that is rapid and so could be useful for HPV testing, particularly in screening protocols. This study was undertaken to determine the suitability of this method for HPV detection. DNA extraction from HeLa and Caski cell lines containing HPV 18 and 16 respectively together with DNA from five liquid based cervical samples were used in a HPV PCR assay. DNA was also extracted using the QIAamp DNA mini kit (Qiagen, Hilden, Germany) as a comparison. DNA extracts were serially diluted and assayed. HPV DNA was successfully detected in cell lines and cervical samples using the XytXtract Tissue kit. In addition, the XytXtract method was found to be more sensitive than the QIAmp method as determined by a dilution series of the extracted DNA. While the XytXtract method is a closed, the QIAamp method uses a spin column with possible loss of DNA through DNA binding competition of the matrix, which could impact on the final extraction efficiency. The XytXtract is a cheap, rapid and efficient method for extracting HPV DNA from both cell lines and liquid based cervical samples.

  6. Human papillomavirus in upper digestive tract tumors from three countries

    PubMed Central

    Castillo, Andres; Koriyama, Chihaya; Higashi, Michiyo; Anwar, Muhammad; Bukhari, Mulazim Hussain; Carrascal, Edwin; Mancilla, Lida; Okumura, Hiroshi; Matsumoto, Masataka; Sugihara, Kazumasa; Natsugoe, Shoji; Eizuru, Yoshito; Akiba, Suminori

    2011-01-01

    AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus. PMID:22219599

  7. Association of human papillomavirus 7 with warts in toe webs.

    PubMed

    Sun, C; Chen, K; Gu, H; Chang, B; Jiang, M

    2010-03-01

    There have been no studies on the prevalence of types of human papillomavirus (HPV) in cutaneous warts that focus on warts in toe webs (WTW). There is no documented association between HPV 7 and WTW. To explore the clinical and histopathological features of WTW, and the distribution of HPV genotypes in patients with WTW. The study group consisted of 20 patients with WTW; 31 patients with typical verruca vulgaris (VV) were enrolled as the disease control group, and 53 patients with tinea pedis and 48 healthy volunteers were enrolled as the disease-negative control group. Tissue specimens were analysed for clinical and histological features and distribution of HPV genotypes. Polymerase chain reaction (PCR)-based direct sequencing, TA cloning and type-specific PCR (TS-PCR) were performed in the WTW and VV groups. Interdigital scale specimens from patients with tinea pedis and from healthy volunteers were analysed for HPV DNA by nested PCR and TS-PCR (HPV 7). All the patients with WTW were male and nearly all were immunocompetent; their mean age was 41 +/- 10 years. The lesions presented mainly as soft, friable and vegetating clusters. HPV 7 was the predominant genotype in WTW with a frequency of 80% (16/20). Fourteen specimens were taken for histopathological examination. The most frequent histological results (seven out of 14) revealed characteristics of HPV 7 infections such as heavily stained cells containing medium-sized keratohyaline granules and a pronounced hyperkeratosis with parakeratosis. TA cloning showed that the sequence shared 90% or more homology with the HPV genotype in direct sequencing. No HPV 7 DNA was found in the scales taken from toe webs without warts. This is the first study evaluating the prevalence of HPV types in WTW and the first report of the association between HPV 7 and specific subgroups of patients with warts.

  8. Human papillomavirus genotypes in cervical intraepithelial neoplasia grade 3.

    PubMed

    Castle, Philip E; Schiffman, Mark; Wheeler, Cosette M; Wentzensen, Nicolas; Gravitt, Patti E

    2010-07-01

    There are few large case series describing the human papillomavirus (HPV) genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer. The Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS) was a clinical trial to evaluate the best management strategies for women with equivocal (ASCUS) or mildly abnormal (LSIL) Pap tests. During enrollment and the 2-year follow-up, 608 women had a histopathologic diagnosis of CIN3 and PCR-based HPV genotyping results on cervical specimens. The genotyping results were ranked hierarchically according to cancer risk: HPV16 > other carcinogenic HPV > noncarcinogenic HPV > PCR negative. Among the 608 women diagnosed with CIN3, 601 (98.8%) cases were positive for any HPV genotype and 95.4% for any carcinogenic HPV. HPV16 (59.9%), HPV31 (18.1%), HPV52 (14.8%), HPV51 (14.0%), and HPV18 (13.2%) were the five most common HPV genotypes detected. Younger age, consensus histologic confirmation, smoking, and multiparity increased the likelihood of testing HPV 16 positive. Specifically, HPV16-positive CIN3 occurred at a younger age than CIN3 positive for other carcinogenic HPV genotypes (median of 23.5 years versus 25 years, respectively; P = 0.0003, Kruskal-Wallis). HPV16-positive CIN3 was more commonly diagnosed in younger women (versus older women), with consensus diagnosis (versus some disagreement between reviewers), and in smokers (versus nonsmokers), and was less commonly diagnosed in multiparous women compared CIN3 positive for other carcinogenic HPV genotypes. In populations vaccinated against HPV16 (and HPV18), the median age of CIN3 in women with ASCUS and LSIL cytology should shift to older ages, possibly permitting later age at first screening.

  9. Epithelial cell responses to infection with human papillomavirus.

    PubMed

    Stanley, Margaret A

    2012-04-01

    Human papillomavirus (HPV) infection of the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. Most of those who do develop benign lesions eventually mount an effective cell-mediated immune (CMI) response, and the lesions regress. Regression of anogenital warts is accompanied histologically by a CD4(+) T cell-dominated Th1 response; animal models support this and provide evidence that the response is modulated by antigen-specific CD4(+) T cell-dependent mechanisms. Failure to develop an effective CMI response to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to high-grade intraepithelial neoplasia and invasive carcinoma. Effective evasion of innate immune recognition seems to be the hallmark of HPV infections. The viral infectious cycle is exclusively intraepithelial: there is no viremia and no virus-induced cytolysis or cell death, and viral replication and release are not associated with inflammation. HPV globally downregulates the innate immune signaling pathways in the infected keratinocyte. Proinflammatory cytokines, particularly the type I interferons, are not released, and the signals for Langerhans cell (LC) activation and migration, together with recruitment of stromal dendritic cells and macrophages, are either not present or inadequate. This immune ignorance results in chronic infections that persist over weeks and months. Progression to high-grade intraepithelial neoplasia with concomitant upregulation of the E6 and E7 oncoproteins is associated with further deregulation of immunologically relevant molecules, particularly chemotactic chemokines and their receptors, on keratinocytes and endothelial cells of the underlying microvasculature, limiting or preventing the ingress of cytotoxic effectors into the lesions. Recent evidence suggests that HPV infection of basal keratinocytes

  10. Increasing human papillomavirus vaccine initiation among publicly insured Florida adolescents.

    PubMed

    Staras, Stephanie A S; Vadaparampil, Susan T; Livingston, Melvin D; Thompson, Lindsay A; Sanders, Ashley H; Shenkman, Elizabeth A

    2015-05-01

    We evaluated the feasibility of a multilevel intervention to increase the human papillomavirus (HPV) vaccine initiation among adolescents. We used a four-arm factorial, quasi-experimental trial to assess feasibility and short-term, preliminary effectiveness of a health system-level, gender-specific postcard campaign and an in-clinic health information technology (HIT) system. Between August and November 2013, we tested the intervention among 11- to 17-year-olds without prior HPV vaccine claims in the Florida Medicaid or Children's Health Insurance Program encounters (2,773 girls and 3,350 boys) who attended or were assigned to primary care clinics in North Central Florida. At least one postcard was deliverable to 95% of the parents. Most parents (91% boys' and 80% girls') who participated in the process evaluation survey (n = 162) reported seeking additional information about the vaccine after receiving the postcard. Only 8% (57 of 1,062) of the adolescents assigned to a HIT provider with an office visit during the study used the HIT system. When compared with arms not containing that component, HPV vaccine initiation increased with the postcard campaign (girls, odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.3 and boys, not significant), the HIT system (girls, OR = 1.5; 95% CI = 1.0-2.3 and boys, OR = 1.4; 95% CI = 1.0-2.0), and the combined HIT and postcard intervention (girls, OR = 2.4; 95% CI = 1.4-4.3 and boys, OR = 1.6; 95% CI = 1.0-2.5). A system-level postcard campaign was feasible. Despite low recruitment to the in-clinic HIT system, the intervention demonstrated short-term, preliminary effectiveness similar to prior HPV vaccine interventions. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  11. The Cell Cycle Timing of Human Papillomavirus DNA Replication.

    PubMed

    Reinson, Tormi; Henno, Liisi; Toots, Mart; Ustav, Mart; Ustav, Mart

    2015-01-01

    Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research.

  12. Genital human papillomaviruses among women of reproductive age in Jamaica.

    PubMed

    Lewis-Bell, Karen; Luciani, Silvana; Unger, Elizabeth R; Hariri, Susan; McFarlane, Shelly; Steinau, Martin; Prieto-Lara, Elisa; Vicari, Andrea S; Irons, Beryl; Lewis, Merle J; Andrus, Jon Kim

    2013-03-01

    To characterize the prevalence and distribution of genital human papillomavirus (HPV) types among women in Jamaica, and to explore risk factors associated with HPV infection. This was a cross-sectional study that took place in April-July 2010 with 852 sexually-active women, 16-49 years of age, who had attended a selected public or private primary health clinic in one of Jamaica's four health authority regions. Sociodemographic data was collected from each participant by trained study staff. Each participant had a gynecological examination that included a clinical Pap test and a cervical sample for HPV detection and typing-performed using the Research Use Only Linear Array (LA) genotyping assay (Roche Diagnostics Corp., Indianapolis, Indiana, United States). Overall and type-specific prevalence of HPV infection was calculated for 37 HPV types included in the LA genotyping assay. HPV DNA was detected in 460 of the 852 women (54.0%). Oncogenic HPV was detected in 297 women (34.9%) and HPV types 16/18 were found in 86 women (10.1%). The most frequently occurring HPV types were: 16 (6.2%); 35 (6.0%); 62 and 83 (5.5%); 61 and 58 (5.4%); 84 (4.7%); 18 (4.3%); and, 66 and 81 (4.2%). HPV prevalence was highest among women who were single, young (16-19 years), and had had more than three sexual partners in their lifetime. These results, coupled with high rates of cervical cancer, support introducing HPV vaccines while maintaining and strengthening cervical cancer screening services. Policy decision-making that reflects these results is instrumental to establishing a comprehensive cervical cancer program in Jamaica.

  13. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan.

    PubMed

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F Xavier; Alemany, Laia

    2016-07-30

    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases.

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

    PubMed

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

    2012-11-20

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

  15. Predictors of Human Papillomavirus Awareness and Knowledge in 2013

    PubMed Central

    Blake, Kelly D.; Ottenbacher, Allison J.; Rutten, Lila J. Finney; Grady, Meredith A.; Kobrin, Sarah C.; Jacobson, Robert M.; Hesse, Bradford W.

    2014-01-01

    Background Nearly 80 million people in the U.S. are currently infected with at least one of two strains of human papillomavirus (HPV), which is associated with 70% of cervical cancers. Greater cervical cancer mortality has been observed among women of lower SES and those living in rural, versus urban, areas. African American and Hispanic women are significantly more likely to die from cervical cancer than non-Hispanic white women. Purpose To assess current population awareness of and knowledge about HPV and the HPV vaccine, as well as the contribution of sociodemographic characteristics to disparities in HPV awareness and knowledge. Methods Cross-sectional data were obtained from the National Cancer Institute’s 2013 Health Information National Trends Survey (HINTS; N=3,185). Multivariable logistic regression was employed to identify gaps in awareness and knowledge by sex, education, income, race/ethnicity, geographic area, and other important sociodemographic characteristics. Analyses were conducted in 2014. Results Sixty-eight percent of Americans had heard of HPV and the HPV vaccine. Consistent with the Knowledge Gap Hypothesis, awareness and knowledge were patterned by sex, age, education, and other important sociodemographic factors. Those in rural areas were less likely than those in urban areas to know that HPV causes cervical cancer. Less than 5% of Americans were aware that HPV often clears on its own without treatment. Conclusions Although awareness and knowledge of HPV is increasing, there are opportunities to target communication with populations for whom knowledge gaps currently exist, in order to promote dialogue about the vaccine among patients and their providers. PMID:25700651

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

    PubMed

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

    2014-12-01

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

  17. Prevalence of High-Risk Human Papillomavirus Among Older Women

    PubMed Central

    Lindau, Stacy Tessler; Drum, Melinda L.; Gaumer, Elyzabeth; Surawska, Hanna; Jordan, Jeanne A.

    2009-01-01

    Objective To estimate the prevalence, genotypes, and individual-level correlates of high-risk human papillomavirus (HPV) among women aged 57–85. Methods Community-residing women (n=1550), aged 57–85, were drawn from a nationally-representative probability sample. In-home interviews and biomeasures, including a self-collected vaginal specimen, were obtained between 2005 and 2006. Specimens were analyzed for high-risk HPV DNA using probe hybridization and signal amplification (hc2); of 1,028 specimens provided, 1,010 were adequate for analysis. All samples testing positive were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Results The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). Current marital and smoking status, frequency of sexual activity, history of cancer, and hysterectomy were associated with high-risk HPV positivity. Among high-risk HPV+ women, 63% had multiple type infections. HPV 16 or 18 was present in 17.4% of all high-risk HPV+ women. The most common high-risk genotypes among high-risk HPV+ women were HPV 61 (19.1%), 31 (13.1%), 52 (12.9%), 58 (12.5%), 83 (12.3%), 66(12.0%), 51 (11.7%), 45 (11.2%), 56 (10.3%), 53 (10.2%), 16 (9.7%), and 62 (9.2%). Being married and having an intact uterus were independently associated with lower prevalence of high-risk HPV. Among unmarried women, current sexual activity and smoking were independently and positively associated with high-risk HPV infection. Conclusions In this nationally representative population, nearly 1 in 16 women aged 57–85 were found to have high-risk HPV and prevalence was stable across older age groups. PMID:18978096

  18. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan

    PubMed Central

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F. Xavier; Alemany, Laia

    2016-01-01

    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0–91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7–83.3), compared to Asia (71.6%; 69.9–73.4) and worldwide (70.8%; 69.9–71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9–15.7 vs. 19.8%; 18.3–21.3 and 18.5%; 17.7–19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases. PMID:27483322

  19. Immune therapy for human papillomaviruses-related cancers.

    PubMed

    Rosales, Ricardo; Rosales, Carlos

    2014-12-10

    Human papillomaviruses (HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered low-risk such as HPV 6 and 11, produce warts; while high-risk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of pre-cancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cells by the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virus-host interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.

  20. Immune therapy for human papillomaviruses-related cancers

    PubMed Central

    Rosales, Ricardo; Rosales, Carlos

    2014-01-01

    Human papillomaviruses (HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered low-risk such as HPV 6 and 11, produce warts; while high-risk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of pre-cancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cells by the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virus-host interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested. PMID:25493236

  1. Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study

    PubMed Central

    2013-01-01

    Background Incidence of condyloma, or genital warts (GW), is the earliest possible disease outcome to measure when assessing the effectiveness of human papillomavirus (HPV) vaccination strategies. Efficacy trials that follow prespecified inclusion and exclusion criteria may not be fully generalizable to real-life HPV vaccination programs, which target a broader segment of the population. We assessed GW incidence after on-demand vaccination with quadrivalent HPV vaccine using individual-level data from the entire Swedish population. Methods An open cohort of girls and women aged 10 to 44 years living in Sweden between 2006 and 2010 (N > 2.2 million) was linked to multiple population registers to identify incident GW in relation to HPV vaccination. For vaccine effectiveness, incidence rate ratios of GW were estimated using time-to-event analyses with adjustment for attained age and parental education level, stratifying on age at first vaccination. Results A total of 124 000 girls and women were vaccinated between 2006 and 2010. Girls and women with at least one university-educated parent were 15 times more likely to be vaccinated before age 20 years than girls and women whose parents did not complete high school (relative risk ratio = 15.45, 95% confidence interval [CI] = 14.65 to 16.30). Among those aged older than 20 years, GW rates declined among the unvaccinated, suggesting that HPV vaccines were preferentially used by women at high risk of GW. Vaccination effectiveness was 76% (95% CI = 73% to 79%) among those who received three doses of the vaccine with their first dose before age 20 years. Vaccine effectiveness was highest in girls vaccinated before age 14 years (effectiveness = 93%, 95% CI = 73% to 98%). Conclusions Young age at first vaccination is imperative for maximizing quadrivalent HPV vaccine effectiveness. PMID:23486550

  2. Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma.

    PubMed

    Dalianis, Tina

    2014-12-01

    Numerous reports in recent decades have shown that, in addition to smoking and alcohol, human papillomavirus (HPV) is also associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), predominantly in the tonsils and base of the tongue. In 2007, the International Agency on Research against Cancer (IARC) therefore declared HPV to be a risk factor for OPSCC and noted that 80% of those affected are men. In addition, patients with HPV-positive OPSCC, in particular never-smokers, have a much better clinical response to therapy than patients with HPV-negative OPSCC and other head and neck cancers. Most patients with HPV-positive OPSCC may thus not need the increasingly intensive chemo-radiotherapy currently administered today to most patients with head neck cancers and associated with many adverse effects. Furthermore, an increase in the incidence of OPSCC has been observed in many western countries, accompanied by a rise in the proportion of HPV-positive tumors. Patients with HPV-positive OPSCC, like those with cervical cancer, more often have an earlier sexual debut and have more sexual partners. It has therefore been proposed that the increased incidence of OPSCC observed might be due to an epidemic of sexually transmitted HPV. The important issues today regarding this growing cohort of patients with HPV-positive OPSCC are therefore individualized treatment and prevention. More specifically, selected HPV-positive OPSCC patients with biomarkers of good prognosis might be included in randomized trials with less intensive treatment. HPV vaccination should also be considered for boys, in addition to the current recommendations for immunization of girls.

  3. Potential benefits of second-generation human papillomavirus vaccines.

    PubMed

    Kiatpongsan, Sorapop; Campos, Nicole Gastineau; Kim, Jane J

    2012-01-01

    Current prophylactic vaccines against human papillomavirus (HPV) target two oncogenic types (16 and 18) that contribute to 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to expand protection to five additional oncogenic types (31, 33, 45, 52 and 58). A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda) was used to estimate reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the independent and joint impact of uncertain factors (i.e., distribution of HPV types, co-infection with multiple HPV types, and unidentifiable HPV types in cancer) and vaccine properties (i.e., cross-protection against non-targeted HPV types), compared against currently-available vaccines. Assuming complete uptake of the second-generation vaccine, reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda, representing an absolute increase in cervical cancer reduction of 26.1% in Kenya and 17.9% in Uganda, compared with complete uptake of current vaccines. The range of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda, depending on assumptions of cancers attributable to multiple HPV infections and unidentifiable HPV types. These effects were blunted in both countries when assuming vaccine cross-protection with both the current and second-generation vaccines. Second-generation HPV vaccines that protect against additional oncogenic HPV types have the potential to improve cervical cancer prevention. Co-infection with multiple HPV infections and unidentifiable HPV types can influence vaccine effectiveness, but the magnitude of effect may be moderated by vaccine cross-protective effects. These benefits must be weighed against the cost of the vaccines in future analyses.

  4. Barriers to Human Papillomavirus Vaccination Among US Adolescents

    PubMed Central

    Holman, Dawn M.; Benard, Vicki; Roland, Katherine B.; Watson, Meg; Liddon, Nicole; Stokley, Shannon

    2015-01-01

    IMPORTANCE Since licensure of the human papillomavirus (HPV) vaccine in 2006, HPV vaccine coverage among US adolescents has increased but remains low compared with other recommended vaccines. OBJECTIVE To systematically review the literature on barriers to HPV vaccination among US adolescents to inform future efforts to increase HPV vaccine coverage. EVIDENCE REVIEW We searched PubMed and previous review articles to identify original research articles describing barriers to HPV vaccine initiation and completion among US adolescents. Only articles reporting data collected in 2009 or later were included. Findings from 55 relevant articles were summarized by target populations: health care professionals, parents, underserved and disadvantaged populations, and males. FINDINGS Health care professionals cited financial concerns and parental attitudes and concerns as barriers to providing the HPV vaccine to patients. Parents often reported needing more information before vaccinating their children. Concerns about the vaccine’s effect on sexual behavior, low perceived risk of HPV infection, social influences, irregular preventive care, and vaccine cost were also identified as potential barriers among parents. Some parents of sons reported not vaccinating their sons because of the perceived lack of direct benefit. Parents consistently cited health care professional recommendations as one of the most important factors in their decision to vaccinate their children. CONCLUSIONS AND RELEVANCE Continued efforts are needed to ensure that health care professionals and parents understand the importance of vaccinating adolescents before they become sexually active. Health care professionals may benefit from guidance on communicating HPV recommendations to patients and parents. Further efforts are also needed to reduce missed opportunities for HPV vaccination when adolescents interface with the health care system. Efforts to increase uptake should take into account the specific

  5. Human papillomavirus testing for primary cervical cancer screening.

    PubMed

    Grce, Magdalena; Davies, Philip

    2008-09-01

    Cervical cancer is the second most common cancer in women worldwide and the seventh most common cause of cancer deaths in women in Europe. Today, we know how to prevent almost every case of this disease; organized cervical cancer screening based on the Papanicolaou or Pap smear has been proven to prevent 80% of cervical cancer deaths, while new technologies for the detection of the human papillomavirus (HPV) or the prevention of HPV infection offer the potential to make even more progress in the battle against this disease. Testing for carcinogenic or high-risk HPV types is gaining acceptance for the triage of women with borderline cytology and for follow-up after treatment of high-grade cervical lesions. Now, a number of large-scale randomized controlled trials have shown that HPV testing as a primary screening test can detect approximately 50% more high-grade lesions than the Pap test, albeit with a lower specificity if all HPV-positive women are followed up. However, alternative screening algorithms in which HPV-positive women are triaged with cytology have been shown to have equivalent specificity to the Pap test without compromising the increased sensitivity. Further advantages of HPV testing come from the fact that it is an objective and automatable test with a dichotomous result. These attributes can yield cost savings through reductions in staff numbers and simplification of quality control procedures while reducing turnaround times. In countries seeking to improve cervical cancer prevention, the implementation of HPV testing as the primary screening test with cytology for the triage of HPV-positive women is an option that should be fully evaluated. This review summarizes the recent advances in HPV testing in cervical cancer prevention.

  6. Human papillomavirus typing of warts and response to cryotherapy.

    PubMed

    Tomson, N; Sterling, J; Ahmed, I; Hague, J; Berth-Jones, J

    2011-09-01

    Cutaneous warts are common and caused by a number of different types of human papillomaviruses (HPVs). The aim of this study was to investigate the HPV types causing common warts and to determine any association between the HPV type and the duration of warts and response to cryotherapy. Eighty wart samples from 76 immunocompetent patients were taken from warts by paring prior to cryotherapy and analysed by in situ hybridization (ISH) with HPV probes specific to HPV 1, 2, 3, 4, 7, 10 and 57 and PCR analysis using degenerate cutaneous HPV primers with subsequent DNA sequencing. Each patient's details, including site, duration and response of the wart to cryotherapy were recorded. Cryotherapy was performed at 2 week intervals for a maximum of 12 weeks. An HPV type was identified in 65 samples. The majority of warts (58 samples) were typed as HPV 2/27/57 by ISH and/or PCR. Three of the 18 samples that were HPV negative with ISH were HPV positive by PCR. Response to treatment did not correlate with HPV type, duration or location. In the 21 wart parings taken from patients aged 16 and under, response to treatment did not correlate with HPV type but warts of shorter duration were more likely to resolve with cryotherapy treatment than longer standing lesions. This study demonstrates that HPV type can be determined from wart parings. HPV-2 related viruses are the prevalent HPV types causing common warts on the hands and feet in this population. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  7. Human papillomavirus (HPV) vaccine initiation in minority Americans.

    PubMed

    De, P; Budhwani, H

    2017-03-01

    Transmission of the human papillomavirus (HPV) is a significant public health concern. HPV is preventable through a series of vaccinations; however, knowledge gaps exist as to which groups are least likely to initiate vaccination. Considering this gap, the aim of this study is to examine HPV vaccine initiation rates in racial minorities, comparing foreign-born individuals to their American-born peers. Population-based data from the 2013 National Health Interview Survey (NHIS), a repeated large-scale household interview survey of a statistically representative sample of the United States civilian non-institutionalized population, were applied. Data were derived from two survey modules: the family and summary adult modules. Sampling weights were employed to logistic regression modelling the outcome of HPV vaccine initiation. Foreign-born persons, African Americans, males, those lacking health insurance coverage and those without a medical home (usual place to receive care) held statistically lower rates of HPV vaccine initiation. Being college educated was associated with higher odds of HPV vaccine initiation. Our findings support the persistence of health disparities in racial minorities and foreign-born persons residing in the United States. Addressing these gaps will likely require both individual-level (e.g. targeted health education) and system-level (e.g. HPV vaccine promoting policies) interventions. Since health insurance coverage and having a medical home were significant associates of HPV vaccine initiation, attempts to coverage may improve HPV vaccine initiation rates. Additionally, policies which require HPV vaccination for school entry could boost coverage across all population groups, including boys, foreign-born persons and racial minorities. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  8. Prevalence of cervical human papillomavirus (HPV) infection in Vanuatu.

    PubMed

    Aruhuri, Bernadette; Tarivonda, Len; Tenet, Vanessa; Sinha, Rohit; Snijders, Peter J F; Clifford, Gary; Pang, James; McAdam, Margaret; Meijer, Chris J L M; Frazer, Ian H; Franceschi, Silvia

    2012-05-01

    To provide information on human papillomavirus (HPV) prevalence and the distribution of individual HPV types in Pacific Islands, we conducted a population-based survey in Vanuatu, South Pacific. Nine hundred and eighty-seven women between 18 and 64 years of age were included. GP5(+)/6(+)-mediated PCR assay was used for HPV testing. The prevalence of 44 HPV types was 28.4% corresponding to an age (world)-standardized prevalence of 25.0% [95% confidence interval (CI), 21.9%-28.0%]. The prevalence of high-risk (HR) HPV types was 21.7% (age-standardized prevalence of 19.2%; 95% CI, 16.4%-22.0%). Among 840 women with adequate cytologic results, 13.6% showed cervical abnormalities, including 3.6% with high-grade squamous intraepithelial lesions (HSIL) and 0.8% with invasive cervical carcinoma. HPV prevalence declined from 46.1% in women aged ≤21 to 15.3% in those ≥45 years. Being single was significantly associated with HPV positivity. HR HPV findings by PCR assay and hybrid capture 2 (HC2; conducted in Vanuatu) were moderately correlated (κ test = 0.59). The positive predictive values of HR HPV positivity for HSIL or worse were 27.6% for PCR and 35.2% for HC2 among women aged ≥30. Nearly half of screening-positive women could not be reevaluated mainly on account of the difficulty to trace back women. The availability of a rapid HPV testing method that allows see-and-treat approaches at the same visit would be, therefore, essential. On account of their high cumulative burden of cervical lesions, also women older than 40 years should be included in at least the first screening round in unscreened populations.

  9. Human papillomavirus infection in women from tlaxcala, Mexico.

    PubMed

    Velázquez-Márquez, Noé; Jaime Jiménez-Aranda, Lucio; Sánchez-Alonso, Patricia; Santos-López, Gerardo; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2010-07-01

    Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31.

  10. Human Papillomavirus Infection in Women from Tlaxcala, Mexico

    PubMed Central

    Velázquez-Márquez, Noé; Jaime Jiménez-Aranda, Lucio; Sánchez-Alonso, Patricia; Santos-López, Gerardo; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2010-01-01

    Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31. PMID:24031552

  11. Attitudes about human papillomavirus vaccine among family physicians.

    PubMed

    Riedesel, J M; Rosenthal, S L; Zimet, G D; Bernstein, D I; Huang, B; Lan, D; Kahn, J A

    2005-12-01

    Human papillomavirus (HPV) vaccines will soon be available for clinical use, and the effectiveness of vaccine delivery programs will depend largely upon whether providers recommend the vaccine. The objectives of this study were to examine family physicians' attitudes about HPV immunization and to identify predictors of intention to recommend immunization. Cross-sectional survey instrument assessing provider and practice characteristics, knowledge about HPV, attitudes about HPV vaccination, and intention to administer two hypothetical HPV vaccines. Surveys were mailed to a national random sample of 1,000 American Academy of Family Physicians (AAFP) members. Intention to administer two hypothetical HPV vaccines (a cervical cancer/genital wart vaccine and a cervical cancer vaccine) to boys and girls of different ages. One hundred fifty-five surveys (15.5%) were returned and 145 were used in the final sample. Participants reported higher intention to recommend both hypothetical HPV vaccines to girls vs. boys (P < 0.0001) and to older vs. younger adolescents (P < 0.0001). They were more likely to recommend a cervical cancer/genital wart vaccine than a cervical cancer vaccine to boys and girls (P < 0.001). Variables independently associated with intention (P < 0.05) included: female gender of provider, knowledge about HPV, belief that organizations such as the AAFP would endorse vaccination, and fewer perceived barriers to vaccination. Female gender, knowledge about HPV, and attitudes about vaccination were independently associated with family physicians' intention to recommend HPV vaccines. Vaccination initiatives directed toward family physicians should focus on modifiable predictors of intention to vaccinate, such as HPV knowledge and attitudes about vaccination.

  12. Understanding suboptimal human papillomavirus vaccine uptake among ethnic minority girls.

    PubMed

    Bastani, Roshan; Glenn, Beth A; Tsui, Jennifer; Chang, L Cindy; Marchand, Erica J; Taylor, Victoria M; Singhal, Rita

    2011-07-01

    The introduction of human papillomavirus (HPV) vaccines represents a breakthrough in the primary prevention of cervical cancer. However, little is known about vaccination uptake and correlates among low-income, ethnic minority, and immigrant populations in the U.S. who may benefit most from the vaccine. Telephone interviews (N = 490) were conducted in six languages between January and November 2009 among mothers of vaccine-eligible girls (ages 9-18) using the Los Angeles County Department of Public Health, Office of Women's Health service referral hotline. HPV and vaccine awareness, knowledge, beliefs, barriers, and daughter's vaccine receipt were assessed. The sample consisted of low-income, uninsured, ethnic minority, and immigrant women. Only 29% of daughters initiated the vaccine and 11% received all three doses. No ethnic differences were observed in initiation or completion rates. Ethnic differences were observed in HPV awareness, perceived risk, and other vaccine-related beliefs. The strongest predictor of initiation was vaccine awareness (OR = 12.00). Daughter's age and reporting a younger acceptable age for vaccination were positively associated with initiation. Mothers of unvaccinated girls reported lacking information about the vaccine to make a decision (66%) and not knowing where they could obtain the vaccine (74%). Vaccination rates in this sample were lower than state and national estimates, and were associated with low levels of vaccine awareness. Interventions, including culturally targeted messaging, may be helpful for enhancing HPV-vaccine knowledge, modifying vaccine-related beliefs and increasing uptake. Our findings provide valuable guidance for developing interventions to address suboptimal HPV vaccination in high-risk groups. ©2011 AACR

  13. Parents' opinions of mandatory human papillomavirus vaccination: does ethnicity matter?

    PubMed

    Perkins, Rebecca B; Pierre-Joseph, Natalie; Marquez, Cecilia; Iloka, Sandra; Clark, Jack A

    2010-01-01

    To explore parents' opinions of school-entry requirements for human papillomavirus (HPV) vaccination. We interviewed parents of vaccine-eligible girls attending medical appointments in an urban academic medical center and an affiliated community health center. We used qualitative methods to explore parents' opinions about mandating routine childhood vaccines and HPV vaccine, as well as their feelings about vaccinating their own daughters against HPV. We included 19 Caucasian, 18 African-American, 12 Afro-Caribbean, 3 African, and 21 Latino parents. Nearly all parents had allowed their children to receive routine vaccinations and expressed support for mandating these vaccines. Most parents also vaccinated their daughters against HPV: 100% of Caucasian parents, 90% of African-American parents, 73% of Afro-Caribbean/African parents, and 90% of Latino parents. Only 11% of Caucasian parents supported HPV vaccine mandates, however, compared with 78% of African-American, 60% of Afro-Caribbean/African, and 90% of Latino parents. Immigrants supported mandates more frequently than U.S.-born parents. Most Caucasian parents opposed mandatory HPV vaccination because they believed the HPV vaccine should be an individual decision because the virus can only be spread by sexual contact. African-American, Afro-Caribbean, African, and Latino parents generally viewed mandates as the most effective way to protect their daughters from cervical cancer. Latino parents gave special importance to protecting their daughters from sexually transmitted infections. Parents from different racial and ethnic backgrounds expressed unique perspectives about mandatory HPV vaccination. Caucasians were less likely than parents of other races/ethnicities to support vaccine mandates. Copyright © 2010 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  14. Barriers to human papillomavirus vaccine acceptability in Israel.

    PubMed

    Fisher, William A; Laniado, Hila; Shoval, Hila; Hakim, Marwan; Bornstein, Jacob

    2013-11-22

    Barriers to human papillomavirus (HPV) vaccine acceptability in Israel include Israel's relatively low incidence of cervical cancer; the religiously-based 80% circumcision rate in Israel, which is regarded as contributing to the lower incidence of HPV infection in the country; the fact that HPV vaccine provides immunity against only few virus types; the vaccine's high cost; and the perception that HPV transmission is associated with unacceptable sexual relations. A recent survey has demonstrated that, following media two campaigns, Israeli's level of awareness of the vaccine increased but the actual vaccination rate remained low, at approximately 10%. Survey findings also indicated that an enduring barrier to HPV vaccination is the vaccine's high cost. Recent research on a convenience sample of Israeli undergraduate women 21 to 24 years of age showed that intentions to receive HPV vaccination in the coming year were a function of women's attitudes towards getting vaccinated and their perceptions of social support for doing so. Undergraduate women who intended to be vaccinated perceived the prevention of cervical cancer, avoidance of personal health threat, and avoidance of HPV infection per se to be the advantages of undergoing HPV vaccination. Disadvantages of getting vaccinated included fear of vaccine side effects, cost of the vaccine, and newness of the vaccine, doubts about vaccines, time required to undergo multiple vaccinations, and dislike of injections. Friends', mothers' and physicians' recommendations influenced women's intentions to be vaccinated in the coming year as well. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-11-01

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

  17. Present status of human papillomavirus vaccine development and implementation.

    PubMed

    Herrero, Rolando; González, Paula; Markowitz, Lauri E

    2015-05-01

    Oncogenic human papillomavirus (HPV) infection is the cause of nearly all cervical cancers and a proportion of other anogenital and oropharyngeal cancers. A bivalent vaccine containing HPV 16 and 18 and a quadrivalent vaccine containing HPV 6, 11, 16, and 18 antigens are in use in vaccination programmes around the world. In clinical trials, three vaccine doses provided 90-100% protection against cervical infection and pre-cancer related to HPV 16 and 18 in women aged 15-26 years who were not infected at vaccination. Partial cross-protection against other HPV types has been reported but its duration is unknown. The vaccines were also efficacious at the prevention of HPV 16 and 18 infections at other anatomical sites in both sexes. Immunobridging studies allowed licensing of the vaccines for use starting at age 9 years for both sexes. Two-dose schedules elicit high antibody concentrations, leading to the recommendation of two-dose schedules for girls aged 9-14 years. Pre-licensure and post-licensure studies have provided data supporting vaccine safety. In 2014, a nonavalent vaccine containing HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens was licensed by the US Food and Drug Administration. HPV vaccination was first introduced in high-income countries owing to vaccine cost, logistic challenges, and competing health priorities. Since 2011, vaccine prices have lowered, allowing the introduction of the vaccine in some middle-income countries. Funding of the vaccine by the GAVI Alliance in 2012 led to demonstration projects in some low-income countries. By 2014, more than 57 countries had included the HPV vaccine in their national health programmes. Data from several countries have shown the effect of vaccination on HPV infection and associated disease, and provided evidence of herd immunity. Expansion of programmes to countries with the highest burden of disease is beginning, but further efforts are needed to realise the potential of HPV vaccines.

  18. Human papillomavirus-associated cancers - United States, 2004-2008.

    PubMed

    2012-04-20

    Oncogenic human papillomavirus (HPV) has a causal role in nearly all cervical cancers and in many vulvar, vaginal, penile, anal, and oropharyngeal cancers. Most HPV infections clear within 1-2 years, but those that persist can progress to precancer or cancer. In the United States, public health prevention of cervical cancer includes both secondary prevention through cervical cancer screening and primary prevention through HPV vaccination. Transmission of HPV also can be reduced through condom use and limiting the number of sexual partners. Two vaccines (bivalent and quadrivalent) are available to protect against HPV types 16 and 18, which are responsible for 70% of cervical cancers. HPV 16 also is the most common HPV type found in the other five cancers often associated with HPV. To assess the incidence of HPV-associated cancers (i.e., cancers at specific anatomic sites and with specific cell types in which HPV DNA frequently is found), CDC analyzed 2004-2008 data from the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology, and End Results (SEER) program. During 2004-2008, an average of 33,369 HPV-associated cancers were diagnosed annually (rate: 10.8 per 100,000 population), including 12,080 among males (8.1 per 100,000) and 21,290 among females (13.2). Multiplying the counts for HPV-associated cancers by percentages attributable to HPV, CDC estimated that approximately 26,000 new cancers attributable to HPV occurred each year, including 18,000 among females and 8,000 among males. Population-based cancer registries are important surveillance tools to measure the impact on cancer rates of public health interventions such as vaccination and screening.

  19. Factors associated with human papillomavirus vaccine-series initiation and healthcare provider recommendation in US adolescent females: 2007 National Survey of Children's Health.

    PubMed

    Lau, May; Lin, Hua; Flores, Glenn

    2012-04-26

    To identify factors associated with initiation of the human papillomavirus vaccine series and parental report of a healthcare provider recommendation of the human papillomavirus vaccine in adolescent females. Cross-sectional analysis of 2007 National Survey of Children's Health. Parents of 12-17 year-old US adolescent females. Associations of sociodemographic and healthcare factors with initiation of the human papillomavirus vaccine series and parental report of a healthcare provider recommendation of the human papillomavirus vaccine. Data were analyzed for 16,139 adolescent females. Almost 20% of adolescent females initiated the HPV vaccine series. Significantly higher proportions of adolescent females who initiated the human papillomavirus vaccine series vs. those who did not initiate the human papillomavirus vaccine series had a parental report of their healthcare provider recommending the human papillomavirus vaccine (84% vs. 20%). In multivariable analyses, adolescent females who were American Indian/Alaska Native, were multiracial, received the meningococcal vaccine, received the tetanus/tetanus-diphtheria/tetanus-diphtheria-acellular pertussis vaccine, or were poor had higher adjusted odds of initiating the human papillomavirus vaccine series; parental report of a healthcare provider recommendation of the human papillomavirus vaccine was associated with about 18 times the adjusted odds of initiating the human papillomavirus vaccine series. In separate multivariable analyses, adolescent females who were African-American and uninsured had lower adjusted odds of a parental report of a healthcare provider recommendation of the human papillomavirus vaccine. Parental report of a healthcare provider recommendation is significantly associated with human papillomavirus vaccine-series initiation. African-American race/ethnicity and uninsurance were associated with lower odds of a parental report of a healthcare provider recommendation of the human papillomavirus

  20. High risk human papillomavirus and Epstein Barr virus in human breast milk

    PubMed Central

    2012-01-01

    Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV) and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV) sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid) and in situ polymerase chain reaction (PCR) techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15%) from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%). Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers. PMID:22937830

  1. Gay and bisexual men's human papillomavirus vaccine intentions: a theory-based structural equation analysis.

    PubMed

    Wheldon, Christopher W; Buhi, Eric R; Daley, Ellen M

    2013-09-01

    In this study, we examined the structural relationships among constructs from the Health Belief Model as they relate to human papillomavirus vaccine intentions in young gay and bisexual men in the United States (N = 183). A model was identified that fit the data well and accounted for 56% of the variance in vaccine intentions. Perceived benefits and barriers were the most proximate predictors of intentions, whereas knowledge and perceived threat exerted only indirect influence. Clarifying the propositional structures within the Health Belief Model can help to advance our understanding of human papillomavirus-related cognitions and behaviors and inform vaccine promotion programs.

  2. Interaction of human papillomaviruses with the host immune system: a well evolved relationship.

    PubMed

    Frazer, Ian H

    2009-02-20

    Human papillomavirus (HPV) infections are generally long lasting, and a host immune response to infection is hard to detect. Nevertheless immunocompromised subjects control HPV infection less well than those with intact immunity. Immune responses are best documented for the papillomavirus groups that cause evident human disease, particularly those responsible for anogenital cancers and genital warts. Humoral immunity to the viral capsid has been shown sufficient for protection against infection, while innate and adaptive cell mediated immunity appears important for eventual elimination of HPV infection. However, molecular and cellular mechanisms responsible for protection from and clearance of HPV infection are not completely established.

  3. Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment.

    PubMed

    Hildesheim, Allan; Gonzalez, Paula; Kreimer, Aimee R; Wacholder, Sholom; Schussler, John; Rodriguez, Ana C; Porras, Carolina; Schiffman, Mark; Sidawy, Mary; Schiller, John T; Lowy, Douglas R; Herrero, Rolando

    2016-08-01

    Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. We included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human

  4. Widespread flat warts associated with human papillomavirus type 5: a cutaneous manifestation of human immunodeficiency virus infection.

    PubMed

    Prose, N S; von Knebel-Doeberitz, C; Miller, S; Milburn, P B; Heilman, E

    1990-11-01

    Numerous flat and tinea versicolor-like warts developed on the face, trunk, and upper extremities of a 10-year-old boy with human immunodeficiency virus infection. Nucleic acid analysis of involved skin revealed human papillomavirus type 5, which has sometimes been associated with epidermodysplasia verruciformis. This human papillomavirus type has also been described in patients with common variable immunodeficiency and dyskeratosis congenita and in renal allograft recipients. Human immunodeficiency virus infection should be added to the list of immune-related disorders that predispose to widespread flat warts.

  5. Multiple heparan sulfate binding site engagements are required for the infectious entry of human papillomavirus type 16.

    PubMed

    Richards, Kathleen F; Bienkowska-Haba, Malgorzata; Dasgupta, Jhimli; Chen, Xiaojiang S; Sapp, Martin

    2013-11-01

    Human papillomavirus (HPV) entry is accompanied by multiple receptor-induced conformational changes (CCs) affecting both the major and minor capsid proteins, L1 and L2. Interaction of heparan sulfate (HS) with L1 is essential for successful HPV16 entry. Recently, cocrystallization of HPV16 with heparin revealed four distinct binding sites. Here we characterize mutant HPV16 to delineate the role of engagement with HS binding sites during infectious internalization. Site 1 (Lys278, Lys361), which mediates primary binding, is sufficient to trigger an L2 CC, exposing the amino terminus. Site 2 (Lys54, Lys356) and site 3 (Asn57, Lys59, Lys442, Lys443) are engaged following primary attachment and are required for infectious entry. Site 2 mutant particles are efficiently internalized but fail to undergo an L1 CC on the cell surface and subsequent uncoating in the endocytic compartment. After initial attachment to the cell, site 3 mutants undergo L1 and L2 CCs and then accumulate on the extracellular matrix (ECM). We conclude that the induction of CCs following site 1 and site 2 interactions results in reduced affinity for the primary HS binding site(s) on the cell surface, which allows engagement with site 3. Taken together, our findings suggest that HS binding site engagement induces CCs that prepare the virus for downstream events, such as the exposure of secondary binding sites, CCs, transfer to the uptake receptor, and uncoating.

  6. Multiple Heparan Sulfate Binding Site Engagements Are Required for the Infectious Entry of Human Papillomavirus Type 16

    PubMed Central

    Richards, Kathleen F.; Bienkowska-Haba, Malgorzata; Dasgupta, Jhimli; Chen, Xiaojiang S.

    2013-01-01

    Human papillomavirus (HPV) entry is accompanied by multiple receptor-induced conformational changes (CCs) affecting both the major and minor capsid proteins, L1 and L2. Interaction of heparan sulfate (HS) with L1 is essential for successful HPV16 entry. Recently, cocrystallization of HPV16 with heparin revealed four distinct binding sites. Here we characterize mutant HPV16 to delineate the role of engagement with HS binding sites during infectious internalization. Site 1 (Lys278, Lys361), which mediates primary binding, is sufficient to trigger an L2 CC, exposing the amino terminus. Site 2 (Lys54, Lys356) and site 3 (Asn57, Lys59, Lys442, Lys443) are engaged following primary attachment and are required for infectious entry. Site 2 mutant particles are efficiently internalized but fail to undergo an L1 CC on the cell surface and subsequent uncoating in the endocytic compartment. After initial attachment to the cell, site 3 mutants undergo L1 and L2 CCs and then accumulate on the extracellular matrix (ECM). We conclude that the induction of CCs following site 1 and site 2 interactions results in reduced affinity for the primary HS binding site(s) on the cell surface, which allows engagement with site 3. Taken together, our findings suggest that HS binding site engagement induces CCs that prepare the virus for downstream events, such as the exposure of secondary binding sites, CCs, transfer to the uptake receptor, and uncoating. PMID:23966387

  7. The Student Human Papillomavirus Survey: Nurse-Led Instrument Development and Psychometric Testing to Increase Human Papillomavirus Vaccine Series Completion in Young Adults.

    PubMed

    Thomas, Tami; Dalmida, Safyia; Higgins, Melinda

    2016-01-01

    The Student Human Papillomavirus Survey (SHPVS) was developed to examine students' perceived benefits or barriers to human papillomavirus (HPV) vaccination. Survey development included (a) 2-phase integrative literature reviews; (b) draft of survey items based on the literature; (c) critique of survey items by young adults, nursing and psychology faculty, and health care providers; and (d) pilot testing. The psychometric properties of the SHPVS were evaluated using classical item analysis and exploratory factor analysis (EFA) among a sample of 527 university students' ages 18-24 years. The estimated Cronbach's alpha for the SHPVS is .74. The SHPVS is a measure of young adults HPV perceived vulnerability, perceived severity, perceived barriers, and perceived benefits of HPV vaccination.

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

    PubMed

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

    2017-04-01

    Sexual behavior and oral human papillomavirus (HPV) infection are risk factors for oral squamous cell carcinoma (OSCC). The effects of OSCC diagnosis and treatment on subsequent relationship stress and sexual behavior are unknown. Incident cases of HPV-positive or HPV-negative OSCC in patients who had a partnered relationship and partners of patients with oropharyngeal cancer were eligible for a study in which surveys were administered at diagnosis and at the 6-month follow-up time point to assess relationship distress, HPV transmission and concerns about health consequences, and sexual behavior. The frequency distributions of responses, stratified by tumor HPV status, were compared at baseline and follow-up. In total, 262 patients with OSCC and 81 partners were enrolled. Among the patients, 142 (54.2%) had HPV-positive OSCC, and 120 (45.8%) had HPV-negative OSCC. Relationship distress was infrequently reported, and 69% of patients felt that their relationship had strengthened since the cancer diagnosis. Both HPV-positive patients (25%) and their partners (14%) reported feelings of guilt or responsibility for the diagnosis of an HPV-caused cancer. Concern over sexual, but not nonsexual, HPV transmission to partners was reported by 50%. Significant declines in the frequency of vaginal and oral sexual behaviors were reported at follow-up, regardless of tumor HPV status. From baseline to 6 months, significant increases in abstinence from vaginal sex (from 10% to 34%; P < .01) and oral sex (from 25% to 80%; P < .01) were reported. Diagnosis and treatment of OSCC are associated with significant declines in the frequency of vaginal and oral sex, regardless of tumor HPV status. Sexual behavior is an important quality-of-life outcome to assess within clinical trials. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:1156-1165. © 2016 American Cancer Society. © 2017 American Cancer Society.

  9. Racial and Ethnic Group Knowledge, Perceptions and Behaviors about Human Papillomavirus, Human Papillomavirus Vaccination, and Cervical Cancer among Adolescent Females.

    PubMed

    Bond, Sharon M; Cartmell, Kathleen B; Lopez, Cristina M; Ford, Marvella E; Brandt, Heather M; Gore, Elena I; Zapka, Jane G; Alberg, Anthony J

    2016-10-01

    Human papillomavirus (HPV) vaccines provide an opportunity to greatly reduce the burden of cervical cancer. Although there has been improvement in uptake, there are notable ethnic/racial disparities. This qualitative study was conducted to better understand factors related to vaccine uptake among female adolescents from 3 racial/ethnic groups: African American (AA), Hispanic, and Caucasian. Findings can inform the development of optimal messages and strategies for clinical and population-based interventions. This mixed-methods descriptive study included completion of a brief structured survey and focus group discussion. Six focus groups were conducted with female adolescents, 2 each in the AA, Hispanic, and Caucasian groups. Brief structured survey questions and the focus group protocol addressed knowledge, perceptions, and behaviors related to HPV, HPV vaccination, and cervical cancer. Participants were 60 female adolescents (ages 13-19, mean age = 16.6 years) recruited from high schools, public health clinics, and churches. Themes across questions were remarkably similar among AA, Hispanic, and Caucasian participants. Each group had high awareness of the terms HPV, HPV vaccination, and cervical cancer, but with little in-depth knowledge about these topics. There was a high acceptance of HPV vaccination. Misperceptions about optimal cervical cancer prevention strategies such as simply knowing one's partner and good hygiene were most common among Hispanic adolescents. Awareness about Pap testing was most common among Caucasian adolescents. Predominantly uniform perceptions of HPV vaccines across racial/ethnic groups suggest a "one size fits all" approach will likely have greater reach with cervical cancer prevention messaging than culturally tailored interventions. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  10. Prevalence, Acquisition, and Clearance of Cervical Human Papillomavirus Infection among Women with Normal Cytology: Hawaii Human Papillomavirus Cohort Study

    PubMed Central

    Goodman, Marc T.; Shvetsov, Yurii B.; McDuffie, Katharine; Wilkens, Lynne R.; Zhu, Xuemei; Thompson, Pamela J.; Ning, Lily; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y.

    2009-01-01

    Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2–56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs. PMID:18974124

  11. Human papillomavirus detection in head and neck squamous cell carcinoma.

    PubMed

    Vietía, Dayahindara; Liuzzi, Juan; Avila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression.

  12. Human papillomavirus detection in head and neck squamous cell carcinoma

    PubMed Central

    Vietía, Dayahindara; Liuzzi, Juan; Ávila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Introduction Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). Methods We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. Results The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. Conclusions This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression. PMID:25374623

  13. Viral entry mechanisms: human papillomavirus and a long journey from extracellular matrix to the nucleus

    PubMed Central

    Sapp, Martin; Bienkowska-Haba, Malgorzata

    2009-01-01

    Papillomaviruses are epitheliotropic non-enveloped double stranded DNA viruses, whose replication is strictly dependent on the terminally differentiating tissue of the epidermis. They induce self-limiting benign tumors of skin and mucosa, which may progress to malignancy like cervical carcinoma. Prior to entry into basal cells, virions attach to heparan sulfate moieties of the basement membrane. This triggers conformational changes, which affect both capsid proteins, L1 and L2, and which are a prerequisite for interaction with the elusive uptake receptor. These processes are very slow resulting in an uptake halftime of up to 14 h. This review summarizes recent advances in our understanding of cell surface events, internalization and subsequent intracellular trafficking of Papillomaviruses. PMID:19878308

  14. Viral entry mechanisms: human papillomavirus and a long journey from extracellular matrix to the nucleus.

    PubMed

    Sapp, Martin; Bienkowska-Haba, Malgorzata

    2009-12-01

    Papillomaviruses are epitheliotropic non-enveloped double-stranded DNA viruses, whose replication is strictly dependent on the terminally differentiating tissue of the epidermis. They induce self-limiting benign tumors of skin and mucosa, which may progress to malignancy (e.g. cervical carcinoma). Prior to entry into basal cells, virions attach to heparan sulfate moieties of the basement membrane. This triggers conformational changes, which affect both capsid proteins, L1 and L2, and such changes are a prerequisite for interaction with the elusive uptake receptor. These processes are very slow, resulting in an uptake half-time of up to 14 h. This minireview summarizes recent advances in our understanding of cell surface events, internalization and the subsequent intracellular trafficking of papillomaviruses.

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

    SciTech Connect

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

    1986-08-01

    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.

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

    PubMed

    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.

  17. Human papillomavirus infection, vaccination, and cervical cancer communication: the protection dilemma faced by women in southern Appalachia.

    PubMed

    Hutson, Sadie P; Dorgan, Kelly A; Duvall, Kathryn L; Garrett, Linda H

    2011-11-30

    Human papillomavirus is the most frequently occurring sexually transmitted infection and has been recognized as the necessary cause of cervical cancer. Understanding the shift in public awareness caused by recent changes to cervical prevention is critical to addressing cervical cancer disparities in Appalachia. Since the human papillomavirus vaccine was approved for prevention, little data have been collected regarding human papillomavirus risk assessment and vaccine perceptions among Appalachian women. The purpose of the authors in this study was to investigate communication and cultural issues via a social scripting framework that could influence human papillomavirus vaccine uptake among southern Appalachian women; and explore participants' perceptions of human papillomavirus, cervical cancer, and the vaccine. A qualitative, descriptive design was employed to examine these issues in eight counties in northeast Tennessee and southwest Virginia. Thirty-nine women aged 18-49 years participated in a single individual interview or focus group session from October 2007 through August 2008. Interview and focus group data were audio-taped and transcribed verbatim. Two major themes emerged from the data: the human papillomavirus vaccine protection dilemma and spheres of silence surrounding the human papillomavirus vaccine protection dilemma. Study findings suggested areas for future research and may assist healthcare professionals in approaching southern Appalachian women as they make decisions regarding cervical cancer prevention.

  18. Genital human papillomavirus infection in women from the Zagreb region.

    PubMed

    Marijan, Tatjana; Vranes, Jasmina; Mlinarić-Dzepina, Ana; Leskovar, Vladimira; Knezević, Jasna; Kvaternik, Matea

    2007-04-01

    Human papillomavirus (HPV) infection is the most common sexually transmitted infection, especially among young, sexually active individuals. As persistent infection with oncogenic types may lead to cervical cancer, HPV testing is a useful tool to screen for women at risk for subsequent development of cervical cancer. The aim of the study was to determine the prevalence of high-risk HPV (hrHPV) infection in different age groups of cytologically selected women from the Zagreb region, and to evaluate the frequency and results of repeat hrHPV testing. During a one-year study period (November 2005 to November 2006), a total of 3,440 cervical samples from women attending gynecological services of public and private health care systems were received. They were tested for 13 hrHPV genotypes by the polymerase chain reaction based AMPLICOR HPV test (Roche Molecular Systems). The overall prevalence of hrHPV was 34.6%. Most samples were obtained from women aged 21-30 years (44.2%), followed by the 31-40 (27.6%), 41-50 (15.7%), 51-60 (5.3%) and 261 (2.4%) age groups. Out of 3,227 cervical samples obtained from women of known age, 4.9% were obtained from the group of girls younger than 21, in which the highest prevalence of hrHPV (49.4%) was found. A similar prevalence was observed in women aged 21-30 (45.1%). The prevalence gradually decreased with age. During the study period, repeat hrHPV testing was performed in samples from 66 women at different intervals. Out of 28 women that were hrHPV negative on initial testing, only five women turned positive on repeat testing. Out of 38 women that were positive on initial testing, in one-third hrHPV could not be detected on repeat testing. As expected, hrHPV infection was highly prevalent in female adolescents and young women. Further investigation on repeat hrHPV testing is needed to assess virus clearance and rate of newly acquired infection.

  19. Implementation of human papillomavirus immunization in the developing world.

    PubMed

    Kane, Mark A; Serrano, Beatriz; de Sanjosé, Silvia; Wittet, Scott

    2012-11-20

    Cervical cancer is the second leading cause of cancer death in women in less developed regions of the world and the leading cause of cancer deaths in GAVI-eligible countries, where 54% of worldwide cervical cancer deaths occur. If prevention is not implemented in these countries, population growth alone will lead to a 63% increase in deaths by 2025. Human papillomavirus (HPV) vaccines are routinely used in the National Immunization Programs in most industrial countries, and the decision by the GAVI Alliance to accept applications from eligible developing countries for HPV vaccine support is the single most important opportunity for children in these countries to be protected against HPV-related diseases. As it has done for other vaccines, such as Haemophilus influenzae type b, rotavirus and pneumococcal conjugate vaccines, GAVI should strongly consider developing and funding a group dedicated to working on all aspects of HPV vaccine introduction in the developing world. Immunization in middle-income developing countries not eligible for GAVI support will depend on "tiered" pricing policies or regional procurement schemes to make vaccine available at prices significantly lower than those in industrial countries. Immunization coverage of infants has reached high levels in many of the poorest developing countries where complementary strategies for HPV control, such as adult screening and treatment, are poorly developed. Immunizing young adolescents will require expansion of immunization infrastructure to reach cohorts that currently are largely unreached, but the success of school-based strategies in industrial countries and developing country demonstration projects provides hope that relatively high coverage may be achieved in many countries. Communication and advocacy strategies for HPV control need to carefully consider local cultural attitudes toward HPV-related issues. Current strategies supported by health economic analyses call for female only immunization, but

  20. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

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

    2013-12-29

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

  1. Human papillomavirus: burden of illness and treatment cost considerations.

    PubMed

    Fox, Paul A; Tung, Mun-Yee

    2005-01-01

    The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination

  2. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    PubMed Central

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

    2014-01-01

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

  3. Parental intention to have daughters receive the human papillomavirus vaccine

    PubMed Central

    Ogilvie, Gina S.; Remple, Valencia P.; Marra, Fawziah; McNeil, Shelly A.; Naus, Monika; Pielak, Karen L.; Ehlen, Thomas G.; Dobson, Simon R.; Money, Deborah M.; Patrick, David M.

    2007-01-01

    Background Concerns have been raised that parents may be reluctant to have their daughters receive the human papillomavirus (HPV) vaccine, because of a belief that doing so might be interpreted as condoning earlier and more frequent sexual activity. We determined intentions regarding vaccination among Canadian parents and factors that predicted parental intention to have their daughters vaccinated against HPV. Methods Parents of children 8–18 years of age, recruited from across Canada, were asked to respond to questions in the context of a grade 6, publicly funded, school-based HPV vaccine program. We performed backward logistic regression analysis to identify factors predictive of parents' intention to have their daughters vaccinated against HPV. Results Of the 1350 respondents with female children, more than 70% (73.8%; 95% confidence interval [CI] 71.5%– 76.1%) intended to have their daughters undergo vaccination against HPV. In multivariable modelling, parents who had positive attitudes toward vaccines (odds ratio [OR] 9.9, 95% CI 4.7–21.1), those who were influenced by subjective norms (OR 9.2, 95% CI 6.6–12.9), those who felt that the vaccine had limited influence on sexual behaviour (OR 3.2, 95% CI 2.2–4.6) and those who thought someone they knew was likely to get cervical cancer (OR 1.5, 95% CI 1.1–2.1) were more likely to intend that their daughters receive the HPV vaccine. Parents who were older (v. younger) (OR 0.6, 95% CI 0.4–0.8) and those who resided in British Columbia or Yukon Territory (v. Atlantic Canada) (OR 0.5, 95% CI 0.3–0.9) were less likely to intend that their daughters receive the HPV vaccine. Interpretation Most of the parents surveyed intended that their daughters would receive vaccination against HPV. Overall attitudes toward vaccines in general and toward the HPV vaccine in particular constituted the most significant predictor of parental intention with regard to vaccination. PMID:18056599

  4. Cost-effectiveness of human papillomavirus vaccination in Germany.

    PubMed

    Damm, Oliver; Horn, Johannes; Mikolajczyk, Rafael T; Kretzschmar, Mirjam E E; Kaufmann, Andreas M; Deleré, Yvonne; Ultsch, Bernhard; Wichmann, Ole; Krämer, Alexander; Greiner, Wolfgang

    2017-01-01

    The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model. Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys. From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were €34,249 per quality-adjusted life year (QALY) for the bivalent and €14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to €19,450 per QALY for the bivalent and to €3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of €13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding €50,000 per QALY, except for scenarios with low coverage (20%) in girls. Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost

  5. Distribution of human papillomavirus genotypes in cervical lesions

    PubMed Central

    Ma, Li; Cong, Xiao; Shi, Mai; Wang, Xiu-Hong; Liu, Hai-Yan; Bian, Mei-Lu

    2017-01-01

    The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P<0.001). Single HPV subtype infection was primarily associated with HPV16, HPV52 and HPV58. In conclusion, HPV type detection had a may be important in screening of cervical lesions as a difference in pathogenic ability was noted among different HPV genotypes. As cervical cancer is an infectious disease, HPV testing may help detect more precancerous lesions, thus reducing the morbidity and mortality of cervical cancer. HPV16, HPV52 and HPV58 were associated with severe cervical squamous epithelial lesions; HPV18 was associated with cervical severe glandular cell pathological changes, although it was not the most common HPV genotype in China. When positive, a clinical cervical

  6. Long-term efficacy and safety of human papillomavirus vaccination

    PubMed Central

    De Vincenzo, Rosa; Conte, Carmine; Ricci, Caterina; Scambia, Giovanni; Capelli, Giovanni

    2014-01-01

    In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV) and quadrivalent (qHPV) – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish

  7. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

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

    2013-12-31

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

  8. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

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

    2013-12-30

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

  9. Comprehensive control of human papillomavirus infections and related diseases.

    PubMed

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

    2013-11-22

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

  10. Human Papillomavirus Vaccination Rates in Young Cancer Survivors.

    PubMed

    Klosky, James L; Hudson, Melissa M; Chen, Yanjun; Connelly, James A; Wasilewski-Masker, Karen; Sun, Can-Lan; Francisco, Liton; Gustafson, Laura; Russell, Kathryn M; Sabbatini, Gina; Flynn, Jessica S; York, Jocelyn M; Giuliano, Anna R; Robison, Leslie L; Wong, F Lennie; Bhatia, Smita; Landier, Wendy

    2017-08-24

    Purpose Cancer survivors are at high risk for human papillomavirus (HPV)-related morbidities; we estimated the prevalence of HPV vaccine initiation in cancer survivors versus the US population and examined predictors of noninitiation. Methods Participants included 982 cancer survivors (9 to 26 years of age; 1 to 5 years postcompletion of therapy); we assessed HPV vaccine initiation, sociodemographic and clinical characteristics, and vaccine-specific health beliefs; age-, sex-, and year-matched US population comparisons were from the National Immunization Survey-Teen and the National Health Interview Survey (2012-2015). Results The mean age at the time of the study was 16.3 ± 4.7 years; the mean time off therapy was 2.7 ± 1.2 years; participants were 55% male and 66% non-Hispanic white; 59% had leukemia/lymphoma. Vaccine initiation rates were significantly lower in cancer survivors versus the general population (23.8%; 95% CI, 20.6% to 27.0% v 40.5%; 95% CI, 40.2% to 40.7%; P < .001); survivors were more likely to be HPV vaccine-naïve than general population peers (odds ratio [OR], 1.72; 95% CI, 1.41 to 2.09; P < .001). Initiation in adolescent survivors (ages 13 to 17 years) was 22.0% (95% CI, 17.3% to 26.7%), significantly lower than population peers (42.5%; 95% CI, 42.2% to 42.8%; P < .001). Initiation in young adult survivors and peers (ages 18 to 26 years) was comparably low (25.3%; 95% CI, 20.9% to 29.7% v 24.2%; 95% CI, 23.6% to 24.9%). Predictors of noninitiation included lack of provider recommendation (OR, 10.8; 95% CI, 6.5 to 18.0; P < .001), survivors' perceived lack of insurance coverage for HPV vaccine (OR, 6.6; 95% CI, 3.9 to 11.0; P < .001), male sex (OR, 2.9; 95% CI, 1.7 to 4.8; P < .001), endorsement of vaccine-related barriers (OR, 2.7; 95% CI, 1.6 to 4.6; P < .001), and younger age (9 to 12 years; OR, 3.7; 95% CI, 1.8-7.6; P < .001; comparison, 13 to 17 years). Conclusion HPV vaccine initiation rates in cancer survivors are low. Lack of

  11. Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus.

    PubMed

    Kim, Jane J; Burger, Emily A; Sy, Stephen; Campos, Nicole G

    2017-02-01

    Current US cervical cancer screening guidelines do not differentiate recommendations based on a woman's human papillomavirus (HPV) vaccination status. Changes to cervical cancer screening policies in HPV-vaccinated women should be evaluated. We utilized an individual-based mathematical model of HPV and cervical cancer in US women to project the health benefits, costs, and harms associated with screening strategies in women vaccinated with the bivalent, quadrivalent, or nonavalent vaccine. Strategies varied by the primary screening test, including cytology, HPV, and combined cytology and HPV "cotesting"; age of screening initiation and/or switching to a new test; and interval between routine screens. Cost-effectiveness analysis was conducted from the societal perspective to identify screening strategies that would be considered good value for money according to thresholds of $50 000 to $200 000 per quality-adjusted life-year (QALY) gained. Among women fully vaccinated with the bivalent or quadrivalent vaccine, optimal screening strategies involved either cytology or HPV testing alone every five years starting at age 25 or 30 years, with cost-effectiveness ratios ranging from $34 680 to $138 560 per QALY gained. Screening earlier or more frequently was either not cost-effective or associated with exceedingly high cost-effectiveness ratios. In women vaccinated with the nonavalent vaccine, only primary HPV testing was efficient, involving decreased frequency (ie, every 10 years) starting at either age 35 years ($40 210 per QALY) or age 30 years ($127 010 per QALY); with lower nonavalent vaccine efficacy, 10-year HPV testing starting at earlier ages of 25 or 30 years was optimal. Importantly, current US guidelines for screening were inefficient in HPV-vaccinated women. This model-based analysis suggests screening can be modified to start at later ages, occur at decreased frequency, and involve primary HPV testing in HPV-vaccinated women, providing more health benefit at

  12. High prevalence of human papillomaviruses in Ghanaian pregnant women.

    PubMed

    Schulze, Marco H; Völker, Fabian M; Lugert, Raimond; Cooper, Paul; Hasenclever, Kai; Groß, Uwe; Pfister, Herbert; Silling, Steffi

    2016-12-01

    Data about the prevalence of human papillomaviruses (HPV) in African women with normal and abnormal cervical cytology are still scarce. Current HPV vaccines contain HPV types, which mainly represent the HPV epidemiology of industrial countries. As further developments of HPV vaccines are going on, it is necessary to regard regional differences in HPV type prevalence to ensure optimal protection by the vaccine. Vaginal swabs of Ghanaian pregnant women, routinely collected before delivery to rule out bacterial infections causing early onset sepsis, were screened for 12 high-risk (HR), 13 probably/possibly (pHR), and 18 low-risk (LR) HPV types. Most pregnant women come for delivery to the hospital. This was considered as appropriate possibility to have an unselected group of women. HPV DNA were detected in 55/165 women (33.3, 95 % CI 26.3-41.1 %). Thirty-four out of fifty-five (61.8, 95 % CI 47.7-74.3 %) of HPV-positive women were infected with HR and/or pHR HPV types. The five most prevalent HR or pHR HPV types were HPV-52 and HPV-67 (7 women each, 4.2, 95 % CI 1.9-8.9 %), HPV-53 (six women, 3.6, 95 % CI 1.5-8.1 %), HPV-45 (five women, 3.0, 95 % CI 1.1-7.3 %), and HPV-18 (four women, 2.4, 95 % CI 0.8-6.5 %), respectively. HPV-16 was found in two women only (1.2, 95 % CI 0.2-4.8 %). Future HPV vaccine research may devote special interest to HPV-67 and HPV-53 provided further studies confirm their high prevalence in the general population of Sub-Saharan African countries. The true carcinogenic potential of HPV-67, which is a member of species alpha9 including HPV-16, and so far categorized as pHR, should be clarified.

  13. Biological relevance of human papillomaviruses in vulvar cancer.

    PubMed

    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-LiPA25 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.

  14. A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

    PubMed Central

    Schiller, John T.; Castellsagué, Xavier; Garland, Suzanne M.

    2015-01-01

    End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as

  15. Print News Coverage of School-Based Human Papillomavirus Vaccine Mandates

    ERIC Educational Resources Information Center

    Casciotti, Dana M.; Smith, Katherine C.; Andon, Lindsay; Vernick, Jon; Tsui, Amy; Klassen, Ann C.

    2014-01-01

    Background: In 2007, legislation was proposed in 24 states and the District of Columbia for school-based human papillomavirus (HPV) vaccine mandates, and mandates were enacted in Texas, Virginia, and the District of Columbia. Media coverage of these events was extensive, and media messages both reflected and contributed to controversy surrounding…

  16. Evolution and classification of oncogenic human papillomavirus types and variants associated with cervical cancer

    PubMed Central

    Chen, Zigui; de Freitas, Luciana Bueno; Burk, Robert D.

    2015-01-01

    The nomenclature of human papillomavirus (HPV) is established by the International Committee on Taxonomy of Virus (ICTV). However, the ICTV does not set standards for HPV below species levels. This chapter describes detailed genotyping methods for determining and classifying HPV variants. PMID:25348294

  17. Receipt of the Human Papillomavirus Vaccine among Female College Students in the United States, 2009

    ERIC Educational Resources Information Center

    Lindley, Lisa L.; Elkind, Julia S.; Landi, Suzanne N.; Brandt, Heather M.

    2013-01-01

    Objective: To determine receipt of the human papillomavirus (HPV) vaccine among female college students by demographic/descriptive characteristics and sexual behaviors. Methods: A secondary analysis of the Spring 2009 National College Health Assessment-II was conducted with 40,610 female college students (aged 18 to 24 years) attending 4-year…

  18. Human Papillomavirus Vaccine Intention among College Men: What's Oral Sex Got to Do with It?

    ERIC Educational Resources Information Center

    Crosby, Richard A.; DiClemente, Ralph J.; Salazar, Laura F.; Nash, Rachel; Younge, Sinead; Head, Sara

    2012-01-01

    Objective: To identify associations between engaging in oral sex and perceived risk of oral cancer among college men. Also, to identify associations, and their moderating factors, between oral sex and human papillomavirus (HPV) vaccine acceptance. Methods: Young men were recruited from 2 university campuses in the South (N = 150). Men completed an…

  19. Disclosure of Genital Human Papillomavirus Infection to Female Sex Partners by Young Men

    PubMed Central

    Arima, Yuzo; Winer, Rachel L; Kurth, Ann E; Martin, Diane P; Hughes, James P; Stern, Michael E; Feng, Qinghua; Kiviat, Nancy B; Koutsky, Laura A

    2012-01-01

    A survey was administered to male university students testing positive for high-risk human papillomavirus. Disclosure was more likely in men with fewer partners, in main partnerships, and in longer partnerships. Disclosure was associated with discussing the Pap test/HPV vaccine with female partners and not associated with a worsening relationship. PMID:22797688

  20. [Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysis].

    PubMed

    Coelho, Pedro Luiz Spinelli; da Silva Calestini, Gustavo Lacerda; Alvo, Fernando Salgueiro; de Moura Freitas, Jefferson Michel; Castro, Paula Marcela Vilela; Konstantyner, Tulio

    2015-12-01

    To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Fourteen studies were included. The most commons adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: Pain-Risk Difference (RD)=11% (p<0.001); edema-RD=8% (p<0.001); erythema-RD=5% (p<0.001); fever-RD=2% (p<0.003). The recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

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

    ERIC Educational Resources Information Center

    Sandfort, Jessica R.; Pleasant, Andrew

    2009-01-01

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

  2. Men's Perceptions and Knowledge of Human Papillomavirus (HPV) Infection and Cervical Cancer

    ERIC Educational Resources Information Center

    McPartland, Tara S.; Weaver, Bethany A.; Lee, Shu-Kuang; Koutsky, Laura A.

    2005-01-01

    The authors assessed young men's knowledge and perceptions of genital human papillomavirus (HPV) infection to identify factors that predict intention to make positive behavioral changes. Male university students aged 18 to 25 years completed a self-report instrument to assess knowledge and perceptions of genital HPV infection. If diagnosed with…

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

    ERIC Educational Resources Information Center

    Sandfort, Jessica R.; Pleasant, Andrew

    2009-01-01

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

  4. Knowledge, Beliefs, and Behaviors: Examining Human Papillomavirus-Related Gender Differences among African American College Students

    ERIC Educational Resources Information Center

    Bynum, Shalanda A.; Brandt, Heather M.; Friedman, Daniela B.; Annang, Lucy; Tanner, Andrea

    2011-01-01

    Objective: Given recent approval for administration of a human papillomavirus (HPV) vaccine to men, it is important to assess the HPV-related perspectives of men and women. The purpose of this study was to examine gender differences in HPV knowledge, beliefs, and vaccine acceptance among college students attending 3 historically black…

  5. Print News Coverage of School-Based Human Papillomavirus Vaccine Mandates

    ERIC Educational Resources Information Center

    Casciotti, Dana M.; Smith, Katherine C.; Andon, Lindsay; Vernick, Jon; Tsui, Amy; Klassen, Ann C.

    2014-01-01

    Background: In 2007, legislation was proposed in 24 states and the District of Columbia for school-based human papillomavirus (HPV) vaccine mandates, and mandates were enacted in Texas, Virginia, and the District of Columbia. Media coverage of these events was extensive, and media messages both reflected and contributed to controversy surrounding…

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  7. Resolution of novel human papillomavirus-induced warts after HPV vaccination.

    PubMed

    Silling, Steffi; Wieland, Ulrike; Werner, Marko; Pfister, Herbert; Potthoff, Anja; Kreuter, Alexander

    2014-01-01

    Human papillomavirus (HPV) XS2 was isolated from warts on an immunosuppressed patient. After HPV vaccination, the warts resolved. HPVXS2 was also found in warts and normal skin of HIV-positive patients and rarely in HIV-negative controls. Further studies should elucidate the mechanisms that lead to wart clearance.

  8. Detection of human papillomavirus in sanitary napkins: a new paradigm in cervical cancer screening.

    PubMed

    Tong, Tommy R; Chan, Olivia W H; Chow, Tat-Chong; Yu, Vivian; Leung, Kai-Man; To, Shui-Him

    2003-03-01

    Human papillomavirus was successfully detected by polymerase chain reaction (PCR) in menstrual blood or vaginal discharge collected in sanitary napkins in 100% of 17 women having koilocytosis, cervical intraepithelial neoplasia, or squamous carcinoma. We advocate this form of cervical cancer screening because of its high sensitivity and acceptance by patients. Copyright 2003 Wiley-Liss, Inc.

  9. Beliefs and Knowledge about the Human Papillomavirus Vaccine among Undergraduate Men

    ERIC Educational Resources Information Center

    Hunter, Theresa; Weinstein, Melissa

    2016-01-01

    Objective: The objective of this study was to assess male undergraduate students' human papillomavirus (HPV) knowledge and intentions to receive the HPV vaccination. Design: Cross-sectional survey. Method: A sample of 116 male undergraduate students from a university in the Midwestern USA completed a survey questionnaire assessing various aspects…

  10. The Acceptability of Human Papillomavirus (HPV) Vaccination among Women with Physical Disabilities

    ERIC Educational Resources Information Center

    Yen, Chia-Feng; Chen, Si-Fan; Lin, Lan-Ping; Hsu, Shang-Wei; Chang, Mao-Jung; Wu, Chia-Ling; Lin, Jin-Ding

    2011-01-01

    The present paper aims to explore awareness and acceptability of human papillomavirus (HPV) vaccination and to identify factors influencing HPV acceptability among women with physical disabilities in Taiwan. The study participants were 438 adult women with physical disabilities, aged 18-69 years. The participants were all officially registered as…

  11. Human Papillomavirus Vaccine Stages of Change among Male and Female University Students: Ready or Not?

    ERIC Educational Resources Information Center

    Patel, Divya A.; Grunzweig, Katherine A.; Zochowski, Melissa K.; Dempsey, Amanda F.; Carlos, Ruth C.; Dalton, Vanessa K.

    2013-01-01

    Objective: To examine gender differences in human papillomavirus (HPV) vaccine stages of change following the recommendations for permissive use of HPV vaccine in males. Participants: Students aged 18-26 attending a large, public, Midwest university in April 2010. Methods: Participants completed a self-administered, online questionnaire. HPV…

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  13. Knowledge, Beliefs, and Behaviors: Examining Human Papillomavirus-Related Gender Differences among African American College Students

    ERIC Educational Resources Information Center

    Bynum, Shalanda A.; Brandt, Heather M.; Friedman, Daniela B.; Annang, Lucy; Tanner, Andrea

    2011-01-01

    Objective: Given recent approval for administration of a human papillomavirus (HPV) vaccine to men, it is important to assess the HPV-related perspectives of men and women. The purpose of this study was to examine gender differences in HPV knowledge, beliefs, and vaccine acceptance among college students attending 3 historically black…

  14. Men's Perceptions and Knowledge of Human Papillomavirus (HPV) Infection and Cervical Cancer

    ERIC Educational Resources Information Center

    McPartland, Tara S.; Weaver, Bethany A.; Lee, Shu-Kuang; Koutsky, Laura A.

    2005-01-01

    The authors assessed young men's knowledge and perceptions of genital human papillomavirus (HPV) infection to identify factors that predict intention to make positive behavioral changes. Male university students aged 18 to 25 years completed a self-report instrument to assess knowledge and perceptions of genital HPV infection. If diagnosed with…

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  16. Improving Human Papillomavirus Vaccination Uptake in College Students: A Socioecological Perspective

    ERIC Educational Resources Information Center

    Lanning, Beth; Golman, Mandy; Crosslin, Katie

    2017-01-01

    Background: Human papillomavirus (HPV) vaccination rates remain relatively low, despite new recommendations found in "Healthy People 2020." Purpose: The purpose of this study was to determine vaccination rates, identify factors that influenced initiation/continuance of HPV vaccine series, and identify levels of influence for HPV health…

  17. The Acceptability of Human Papillomavirus (HPV) Vaccination among Women with Physical Disabilities

    ERIC Educational Resources Information Center

    Yen, Chia-Feng; Chen, Si-Fan; Lin, Lan-Ping; Hsu, Shang-Wei; Chang, Mao-Jung; Wu, Chia-Ling; Lin, Jin-Ding

    2011-01-01

    The present paper aims to explore awareness and acceptability of human papillomavirus (HPV) vaccination and to identify factors influencing HPV acceptability among women with physical disabilities in Taiwan. The study participants were 438 adult women with physical disabilities, aged 18-69 years. The participants were all officially registered as…

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  19. Beliefs and Knowledge about the Human Papillomavirus Vaccine among Undergraduate Men

    ERIC Educational Resources Information Center

    Hunter, Theresa; Weinstein, Melissa

    2016-01-01

    Objective: The objective of this study was to assess male undergraduate students' human papillomavirus (HPV) knowledge and intentions to receive the HPV vaccination. Design: Cross-sectional survey. Method: A sample of 116 male undergraduate students from a university in the Midwestern USA completed a survey questionnaire assessing various aspects…

  20. Human Papillomavirus Vaccine Stages of Change among Male and Female University Students: Ready or Not?

    ERIC Educational Resources Information Center

    Patel, Divya A.; Grunzweig, Katherine A.; Zochowski, Melissa K.; Dempsey, Amanda F.; Carlos, Ruth C.; Dalton, Vanessa K.

    2013-01-01

    Objective: To examine gender differences in human papillomavirus (HPV) vaccine stages of change following the recommendations for permissive use of HPV vaccine in males. Participants: Students aged 18-26 attending a large, public, Midwest university in April 2010. Methods: Participants completed a self-administered, online questionnaire. HPV…

  1. Human Papillomavirus Vaccine Intention among College Men: What's Oral Sex Got to Do with It?

    ERIC Educational Resources Information Center

    Crosby, Richard A.; DiClemente, Ralph J.; Salazar, Laura F.; Nash, Rachel; Younge, Sinead; Head, Sara

    2012-01-01

    Objective: To identify associations between engaging in oral sex and perceived risk of oral cancer among college men. Also, to identify associations, and their moderating factors, between oral sex and human papillomavirus (HPV) vaccine acceptance. Methods: Young men were recruited from 2 university campuses in the South (N = 150). Men completed an…

  2. Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysis

    PubMed Central

    Coelho, Pedro Luiz Spinelli; Calestini, Gustavo Lacerda da Silva; Alvo, Fernando Salgueiro; Freitas, Jefferson Michel de Moura; Castro, Paula Marcela Vilela; Konstantyner, Tulio

    2015-01-01

    Objective: To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Data source: Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Data synthesis: Fourteen studies were included. The most common adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: pain-risk difference (RD)=11% (p<0.001); edema-RD=8% (p<0.001); erythema-RD=5% (p<0.001); fever-RD=2% (p<0.003). Conclusions: The recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. PMID:26376359

  3. Receipt of the Human Papillomavirus Vaccine among Female College Students in the United States, 2009

    ERIC Educational Resources Information Center

    Lindley, Lisa L.; Elkind, Julia S.; Landi, Suzanne N.; Brandt, Heather M.

    2013-01-01

    Objective: To determine receipt of the human papillomavirus (HPV) vaccine among female college students by demographic/descriptive characteristics and sexual behaviors. Methods: A secondary analysis of the Spring 2009 National College Health Assessment-II was conducted with 40,610 female college students (aged 18 to 24 years) attending 4-year…

  4. The EVER Proteins as a Natural Barrier against Papillomaviruses: a New Insight into the Pathogenesis of Human Papillomavirus Infections

    PubMed Central

    Lazarczyk, Maciej; Cassonnet, Patricia; Pons, Christian; Jacob, Yves; Favre, Michel

    2009-01-01

    Summary: Infections by human papillomaviruses (HPVs) are the most frequently occurring sexually transmitted diseases. The crucial role of genital oncogenic HPV in cervical carcinoma development is now well established. In contrast, the role of cutaneous HPV in skin cancer development remains a matter of debate. Cutaneous beta-HPV strains show an amazing ubiquity. The fact that a few oncogenic genotypes cause cancers in patients suffering from epidermodysplasia verruciformis is in sharp contrast to the unapparent course of infection in the general population. Our recent investigations revealed that a natural barrier exists in humans, which protects them against infection with these papillomaviruses. A central role in the function of this HPV-specific barrier is played by a complex of the zinc-transporting proteins EVER1, EVER2, and ZnT-1, which maintain cellular zinc homeostasis. Apparently, the deregulation of the cellular zinc balance emerges as an important step in the life cycles not only of cutaneous but also of genital HPVs, although the latter viruses have developed a mechanism by which they can break the barrier and impose a zinc imbalance. Herein, we present a previously unpublished list of the cellular partners of EVER proteins, which points to future directions concerning investigations of the mechanisms of action of the EVER/ZnT-1 complex. We also present a general overview of the pathogenesis of HPV infections, taking into account the latest discoveries regarding the role of cellular zinc homeostasis in the HPV life cycle. We propose a potential model for the mechanism of function of the anti-HPV barrier. PMID:19487731

  5. Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells

    SciTech Connect

    Klingelhutz, A.J.; Barber, S.A.; Smith, P.P.

    1994-02-01

    Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate. 55 refs., 7 figs., 1 tab.

  6. Detection of human serum antibodies that neutralize infectious human papillomavirus type 11 virions.

    PubMed

    Christensen, N D; Kreider, J W; Shah, K V; Rando, R F

    1992-05-01

    A selection of human sera were tested for the presence of antibodies that neutralized infectious human papillomavirus (HPV) type 11. Neutralizing antibodies were detected by prevention of HPV-11-induced condylomatous transformation of human foreskin chips transplanted subrenally into athymic mice. Test sera were obtained from 21 female patients with genital condylomas and eight patients with laryngeal papillomas. Control patients consisted of 57 adult random blood donors and five asymptomatic children. ELISAs demonstrated that all sera from patients with genital papillomas were strongly reactive to disrupted papillomavirus (PV) antigens of HPV-11, bovine PV type 1 and cottontail rabbit PV, but only two were weakly reactive to intact HPV-11. None of the eight sera from the laryngeal papilloma bearers reacted significantly to disrupted PV antigens, but four of the eight showed strong specific responses to intact HPV-11 only. The majority of the sera that were reactive to intact HPV-11 by ELISA neutralized HPV-11 infectivity in the athymic mouse xenograft system. The data indicated that ELISA reactivity to intact HPV-11 virions was a good predictor for the presence of HPV-11 neutralizing antibodies.

  7. Rates of human papillomavirus vaccine uptake amongst girls five years after introduction of statewide mandate in Virginia.

    PubMed

    Cuff, Ryan D; Buchanan, Tommy; Pelkofski, Elizabeth; Korte, Jeffrey; Modesitt, Susan P; Pierce, Jennifer Young

    2016-06-01

    The Commonwealth of Virginia enacted statewide school-entry human papillomavirus vaccine mandate in 2008 requiring all girls to receive the vaccine before starting the 6th grade. The mandate, one of very few in the country, has been in effect for 5 years. This study assesses the impact that it has had on the rates of human papillomavirus uptake. The purpose of this study was to evaluate the uptake of the human papillomavirus vaccine among girls seeking well-child care 5 years after the introduction of a statewide mandate in Virginia in October 2008. This prospective cohort study used the Clinical Data Repository at the University of Virginia to identify girls 11-12 years old who was seen for well-child care from January to December 2014. Billing and diagnosis codes were used to establish human papillomavirus vaccine administration. Those girls who were identified through the Clinical Data Repository were then contacted by advance letter followed by a representative from the University of Virginia Center for Survey Research who invited the responsible parent or guardian to complete a 50-item telephone questionnaire. Questionnaire results were used to inform objective findings and to assess parental attitudes that were related to human papillomavirus vaccination. Findings were compared against those of Pierce et al (2013), who evaluated human papillomavirus vaccination levels in a similar cohort of patients in 2008, before mandate enactment, to assess relative change attributable to vaccine mandate. Nine hundred eight girls were identified through the Clinical Data Repository; 50.9% of the girls received at least 1 dose of human papillomavirus vaccine. White race and private insurance coverage were found to be associated negatively with human papillomavirus vaccine uptake (relative risk, 0.74 and 0.71; 95% confidence interval, 0.64-0.85 and 0.62-0.81, respectively). Black race and public insurance coverage were found to be associated positively with vaccine

  8. Deep sequencing extends the diversity of human papillomaviruses in human skin

    PubMed Central

    Bzhalava, Davit; Mühr, Laila Sara Arroyo; Lagheden, Camilla; Ekström, Johanna; Forslund, Ola; Dillner, Joakim; Hultin, Emilie

    2014-01-01

    Most viruses in human skin are known to be human papillomaviruses (HPVs). Previous sequencing of skin samples has identified 273 different cutaneous HPV types, including 47 previously unknown types. In the present study, we wished to extend prior studies using deeper sequencing. This deeper sequencing without prior PCR of a pool of 142 whole genome amplified skin lesions identified 23 known HPV types, 3 novel putative HPV types and 4 non-HPV viruses. The complete sequence was obtained for one of the known putative types and almost the complete sequence was obtained for one of the novel putative types. In addition, sequencing of amplimers from HPV consensus PCR of 326 skin lesions detected 385 different HPV types, including 226 previously unknown putative types. In conclusion, metagenomic deep sequencing of human skin samples identified no less than 396 different HPV types in human skin, out of which 229 putative HPV types were previously unknown. PMID:25055967

  9. Correlates of human papillomavirus vaccine coverage: a state-level analysis.

    PubMed

    Moss, Jennifer L; Reiter, Paul L; Brewer, Noel T

    2015-02-01

    We tested the hypothesis that states with higher rates of cancers associated with human papillomavirus (HPV) would have lower HPV vaccine coverage. We gathered state-level data on HPV-related cancer rates and HPV vaccine initiation coverage for girls and boys, separately, and HPV vaccine follow-through (i.e., receipt of 3 doses among those initiating the series) for girls only. In addition, we gathered state-level data on demographic composition and contact with the health care system. We calculated Pearson correlations for these ecological relationships. Human papillomavirus vaccine initiation among girls was lower in states with higher levels of cervical cancer incidence and mortality (r = -0.29 and -0.46, respectively). In addition, vaccine follow-through among girls was lower in states with higher levels of cervical cancer mortality (r = -0.30). Other cancer rates were associated with HPV vaccine initiation and follow-through among girls, but not among boys. Human papillomavirus vaccine initiation among girls was lower in states with higher proportions of non-Hispanic black residents and lower proportions of higher-income residents. Human papillomavirus vaccine follow-through was higher in states with greater levels of adolescents' contact with the health care system. Human papillomavirus vaccine coverage for girls was lower in states with higher HPV-related cancer rates. Public health efforts should concentrate on geographic areas with higher cancer rates. Strengthening adolescent preventive health care use may be particularly important to increase vaccine follow-through. Cost-effectiveness analyses may overestimate the benefits of current vaccination coverage and underestimate the benefits of increasing coverage.

  10. Next-generation sequencing analysis for detecting human papillomavirus in oral verrucous carcinoma.

    PubMed

    Samman, Manar; Wood, Henry; Conway, Caroline; Berri, Stefano; Pentenero, Monica; Gandolfo, Sergio; Cassenti, Adele; Cassoni, Paola; Al Ajlan, Abdulaziz; Barrett, A William; Chengot, Preetha; MacLennan, Kenneth; High, Alec S; Rabbitts, Pamela

    2014-07-01

    The etiology of oral verrucous carcinoma is unknown, and human papillomavirus 'involvement' remains contentious. The uncertainty can be attributed to varied detection procedures and difficulties in defining 'gold-standard' histologic criteria for diagnosing 'verrucous' lesions. Their paucity also hampers investigation. We aimed to analyze oral verrucous lesions for human papillomavirus (HPV) subtype genomes. We used next-generation sequencing for the detection of papillomavirus sequences, identifying subtypes and computing viral loads. We identified a total of 78 oral verrucous cases (62 carcinomas and 16 hyperplasias). DNA was extracted from all and sequenced at a coverage between 2.5% and 13%. An HPV-16 sequence was detected in 1 carcinoma and 1 hyperplasia, and an HPV-2 sequence was detected in 1 carcinoma out of the 78 cases, with viral loads of 2.24, 8.16, and 0.33 viral genomes per cell, respectively. Our results indicate no conclusive human papillomavirus involvement in oral verrucous carcinoma or hyperplasia. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Isolation and Propagation of Human Papillomavirus Type 16 in Human Xenografts Implanted in the Severe Combined Immunodeficiency Mouse

    PubMed Central

    Bonnez, William; DaRin, Carrie; Borkhuis, Christine; de Mesy Jensen, Karen; Reichman, Richard C.; Rose, Robert C.

    1998-01-01

    We report the isolation and propagation of human papillomavirus type 16, the main agent of cervical cancer, using human foreskin fragments implanted in severe combined immunodeficiency mice. The infection produced viral particles, and with each passage of the virus it caused lesions identical to intraepithelial neoplasia, the precursor to carcinoma. PMID:9573300

  12. Enhanced transcriptional activation by E2 proteins from the oncogenic human papillomaviruses.

    PubMed Central

    Kovelman, R; Bilter, G K; Glezer, E; Tsou, A Y; Barbosa, M S

    1996-01-01

    A systematic comparison of transcriptional activation by papillomavirus E2 proteins revealed that the E2 proteins from high-risk human papillomaviruses (human papillomavirus type 16 [HPV-16] and HPV-18) are much more active than are the E2 proteins from low-risk HPVs (HPV-6b and HPV-11). Despite the tropism of HPVs for particular epithelial cell types, this difference in transcriptional activation was observed in a number of different epithelial and nonepithelial cells. The enhanced activities of the E2 proteins from high-risk HPVs did not result from higher steady-state levels of protein in vivo, and in vitro DNA-binding assays revealed similar binding properties for these two classes of E2 proteins. These results demonstrate that the E2 proteins from high-risk HPVs have an intrinsically enhanced potential to activate transcription from promoters with E2-responsive elements. We found that there are also substantial differences between the activation properties of the bovine papillomavirus type 1 E2 protein and those of either of the two classes of HPV E2 proteins, especially with regard to requirements for particular configurations of E2 binding sites in the target promoter. Our results indicate that there are at least three distinct functional classes of E2 proteins and that these classes of E2 proteins may perform different roles during the respective viral life cycles. PMID:8892874

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

    PubMed

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

    2015-07-16

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

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

    PubMed Central

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

    2015-01-01

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

  15. Comparison of two PCR-based human p