The Transcription Factors TBX2 and TBX3 Interact with Human Papillomavirus 16 (HPV16) L2 and Repress the Long Control Region of HPVs

PubMed Central

Schneider, Marc A.; Scheffer, Konstanze D.; Bund, Timo; Boukhallouk, Fatima; Lambert, Carsten; Cotarelo, Cristina; Pflugfelder, Gert O.

2013-01-01

The minor capsid protein L2 of human papillomaviruses (HPVs) has multiple functions during the viral life cycle. Although L2 is required for effective invasion and morphogenesis, only a few cellular interaction partners are known so far. Using yeast two-hybrid screening, we identified the transcription factor TBX2 as a novel interaction partner of HPV type 16 (HPV16) L2. Coimmunoprecipitations and immunofluorescence analyses confirmed the L2-TBX2 interaction and revealed that L2 also interacts with TBX3, another member of the T-box family. Transcription of the early genes during HPV infection is under the control of an upstream enhancer and early promoter region, the long control region (LCR). In promoter-reporter gene assays, we observed that TBX2 and TBX3 repress transcription from the LCR and that this effect is enhanced by L2. Repression of the HPV LCR by TBX2/3 seems to be a conserved mechanism, as it was also observed with the LCRs of different HPV types. Finally, interaction of TBX2 with the LCR was detected by chromatin immunoprecipitation, and we found a strong colocalization of L2 and TBX2 in HPV16-positive cervical intraepithelial neoplasia (CIN) I-II tissue sections. These results suggest that TBX2/3 might play a role in the regulation of HPV gene expression during the viral life cycle. PMID:23388722

Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus-associated invasive carcinoma.

PubMed

Jeannot, Emmanuelle; Becette, Véronique; Campitelli, Maura; Calméjane, Marie-Ange; Lappartient, Emmanuelle; Ruff, Evelyne; Saada, Stéphanie; Holmes, Allyson; Bellet, Dominique; Sastre-Garau, Xavier

2016-10-01

Specific human papillomavirus genotypes are associated with most ano-genital carcinomas and a large subset of oro-pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus-associated carcinomas. A series of 70 serum specimens, taken at the time of diagnosis, between 2002 and 2013, were retrospectively analyzed in patients with human papillomavirus-16 or human papillomavirus-18-associated carcinomas, composed of 47 cases from the uterine cervix, 15 from the anal canal and 8 from the oro-pharynx. As negative controls, 18 serum samples from women with human papillomavirus-16-associated high-grade cervical intraepithelial neoplasia were also analyzed. Serum samples were stored at -80°C (27 cases) or at -20°C (43 cases). DNA was isolated from 200 µl of serum or plasma and droplet digital PCR was performed using human papillomavirus-16 E7 and human papillomavirus-18 E7 specific primers. Circulating human papillomavirus DNA was detected in 61/70 (87%) serum samples from patients with carcinoma and in no serum from patients with cervical intraepithelial neoplasia. The positivity rate increased to 93% when using only serum stored at -80°C. Importantly, the two patients with microinvasive carcinomas in this series were positive. Quantitative evaluation showed that circulating viral DNA levels in cervical cancer patients were related to the clinical stage and tumour size, ranging from 55 ± 85 copies/ml (stage I) to 1774 ± 3676 copies/ml (stage IV). Circulating human papillomavirus DNA is present in patients with

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

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

Structure of the E2 DNA-binding domain from human papillomavirus serotype 31 at 2.4 A.

PubMed

Bussiere, D E; Kong, X; Egan, D A; Walter, K; Holzman, T F; Lindh, F; Robins, T; Giranda, V L

1998-11-01

The papillomaviruses are a family of small double-stranded DNA viruses which exclusively infect epithelial cells and stimulate the proliferation of those cells. A key protein within the papillomavirus life-cycle is known as the E2 (Early 2) protein and is responsible for regulating viral transcription from all viral promoters as well as for replication of the papillomavirus genome in tandem with another protein known as E1. The E2 protein itself consists of three functional domains: an N-terminal trans-activation domain, a proline-rich linker, and a C-terminal DNA-binding domain. The first crystal structure of the human papillomavirus, serotype 31 (HPV-31), E2 DNA-binding domain has been determined at 2.4 A resolution. The HPV DNA-binding domain monomer consists of two beta-alpha-beta repeats of approximately equal length and is arranged as to have an anti-parallel beta-sheet flanked by the two alpha-helices. The monomers form the functional in vivo dimer by association of the beta-sheets of each monomer so as to form an eight-stranded anti-parallel beta-barrel at the center of the dimer, with the alpha-helices lining the outside of the barrel. The overall structure of HVP-31 E2 DNA-binding domain is similar to both the bovine papillomavirus E2-binding domain and the Epstein-Barr nuclear antigen-1 DNA-binding domain.

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.

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

Human papillomavirus and cutaneous warts in meat handlers.

PubMed Central

Melchers, W; de Mare, S; Kuitert, E; Galama, J; Walboomers, J; van den Brule, A J

1993-01-01

The association of papillomavirus and hand warts in meat handlers was examined. Human papillomavirus (HPV) DNA was found in 23 (88%) of 26 cutaneous warts, with HPV 7 (27%) and a yet unidentified HPV (HPV X) (42%) being the predominant types. HPV 2 was found in two (7.5%) patients, and HPV 4 was found in three (11.5%) patients. No bovine papillomavirus sequences were detected. In most patients, the warts developed in less than 2 years after they started working with meat. A possible HPV transmission route by protection gloves and professional equipment is suggested. Images PMID:8408588

A Membrane-Destabilizing Peptide in Capsid Protein L2 Is Required for Egress of Papillomavirus Genomes from Endosomes

PubMed Central

Kämper, Nadine; Day, Patricia M.; Nowak, Thorsten; Selinka, Hans-Christoph; Florin, Luise; Bolscher, Jan; Hilbig, Lydia; Schiller, John T.; Sapp, Martin

2006-01-01

Papillomaviruses are internalized via clathrin-dependent endocytosis. However, the mechanism by which viral genomes pass endosomal membranes has not been elucidated. In this report we show that the minor capsid protein L2 is required for egress of viral genomes from endosomes but not for initial uptake and uncoating and that a 23-amino-acid peptide at the C terminus of L2 is necessary for this function. Pseudogenomes encapsidated by L1 and L2 lacking this peptide accumulated in vesicular compartments similar to that observed with L1-only viral particles, and these mutant pseudoviruses were noninfectious. This L2 peptide displayed strong membrane-disrupting activity, induced cytolysis of bacteria and eukaryotic cells in a pH-dependent manner, and permeabilized cells after exogenous addition. Fusions between green fluorescent protein and the L2 peptide integrated into cellular membranes like the wild type but not like C-terminal mutants of L2. Our data indicate that the L2 C terminus facilitates escape of viral genomes from the endocytic compartment and that this feature is conserved among papillomaviruses. Furthermore, the characteristic of this peptide differs from the classical virus-encoded membrane-penetrating peptides. PMID:16378978

HPV (Human Papillomavirus)

MedlinePlus

... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... to be used for women over 30 years old. It may find HPV even before there are ...

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

Bovine papillomavirus type 4 L1 gene transfection in a Drosophila S2 cell expression system: absence of L1 protein expression

PubMed Central

Góes, Luiz Gustavo Bentim; de Freitas, Antonio Carlos; Ferraz, Oilita Pereira; Rieger, Tania Tassinari; dos Santos, José Ferreira; Pereira, Alexandre; Beçak, Willy; Lindsey, Charles J.; de Cassia Stocco, Rita

2008-01-01

The development of a bovine papillomavirus (BPV) vaccine is an outstanding challenge. BPV protein L1 gene transfection in the Drosophila melanogaster S2 cell expression system failed to produce L1 protein notwithstanding correct L1 gene insertion. Severe genetic inbalance in the host cell line, including cytogenetic alterations, may account for the lack of protein expression. PMID:24031166

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

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.

Analysis of the L1 gene product of human papillomavirus type 16 by expression in a vaccinia virus recombinant.

PubMed

Browne, H M; Churcher, M J; Stanley, M A; Smith, G L; Minson, A C

1988-06-01

The L1 open reading frame of human papillomavirus type 16 (HPV16) has been expressed in vaccinia virus under the control of both the 7.5K early and late promoter, and the 4b major late promoter. Antibodies to a beta-galactosidase fusion protein containing a C-terminal portion of the HPV16 L1 gene product were used to compare the levels of L1 expression in the two recombinants, and showed that greater levels of expression were obtained when the gene was placed under the control of the 4b late promoter. Immunofluorescence studies revealed a nuclear location of the L1 gene product when expressed in vaccinia virus. Antibodies to the beta-galactosidase fusion protein detected a major polypeptide species of 57K and a minor species of 64K in Western blots of recombinant-infected cell lysates. The 64K species was not detected when cells were infected in the presence of tunicamycin, indicating that the primary translation product of the HPV16 L1 open reading frame is modified by N-linked glycosylation when expressed in vaccinia virus. Whereas antibodies to HPV16 L1 fusion proteins and to a peptide containing amino acids from the C terminus of HPV16 L1 reacted well in Western blots with the HPV16 L1 target expressed in vaccinia virus, no reactivity was observed with antibodies to bovine papillomavirus type 1 particles or to a HPV6b fusion protein.

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

PubMed

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

2012-03-01

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

Human papillomavirus type 18 chimeras containing the L2/L1 capsid genes from evolutionarily diverse papillomavirus types generate infectious virus

PubMed Central

Bowser, Brian S.; Chen, Horng-Shen; Conway, Michael J.; Christensen, Neil D.; Meyers, Craig

2011-01-01

Papillomaviruses (PVs) comprise a large family of viruses infecting nearly all vertebrate species, with more than 100 human PVs identified. Our previous studies showed that a mutant chimera HPV18/16 genome, consisting of the upper regulatory region and early ORFs of HPV18 and the late ORFs of HPV16, was capable of producing infectious virus in organotypic raft cultures. We were interested in determining whether the ability of this chimeric genome to produce infectious virus was the result of HPV18 and HPV16 being similarly oncogenic, anogenital types and whether more disparate PV types could also interact functionally. To test this we created a series of HPV18 chimeric genomes where the ORFs for the HPV18 capsid genes were replaced with the capsid genes of HPV45, HPV39, HPV33, HPV31, HPV11, HPV6b, HPV1a, CRPV, and BPV1. All chimeras were able to produce infectious chimeric viral particles, although with lower infectivity than wild-type HPV18. Steps in the viral life cycle and characteristics of the viral particles were examined to identify potential causes for the decrease in infectivity. PMID:21762735

Frequency of human papillomavirus infection in patients with gastrointestinal cancer.

PubMed

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

2018-02-15

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

Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

PubMed Central

López-Contreras, Mario; Rosales, Carlos; Magallanes-Molina, Jose-Roberto; Gonzalez-Vergara, Roberto; Arroyo-Cazarez, Jose Martin; Ricardez-Arenas, Antonio; del Follo-Valencia, Armando; Padilla-Arriaga, Santiago; Guerrero, Miriam Veronica; Pirez, Miguel Angel; Arellano-Fiore, Claudia; Villarreal, Freddy

2014-01-01

Abstract Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 107 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2–treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally. PMID:25275724

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

Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

NASA Astrophysics Data System (ADS)

Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

1995-12-01

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

Mapping the B cell epitopes within the major capsid protein L1 of human papillomavirus type 16.

PubMed

Wang, Aiping; Li, Ning; Zhou, Jingming; Chen, Yumei; Jiang, Min; Qi, Yanhua; Liu, Hongliang; Liu, Yankai; Liu, Dongmin; Zhao, Jianguo; Wang, Yanwei; Zhang, Gaiping

2018-06-26

Persistent infection with human papillomavirus type16 (HPV16) has much association with the development of cervical cancer. L1 is the major capsid protein of HPV, it has been well investigated as a potential vaccine candidate. However, B cell epitopes present on L1 have not been well characterized. To identify the potential B-cell antigenic epitopes within HPV16 L1 protein, sixteen serial overlapping truncations (H1-H16) covering the whole region were expressed in E. coli and used in mice immunization. The mice antisera were tested in ELISA binding, IFA and HI assays. Finally, four fragments (H2, H4, H11, H12) were found to contain B cell epitopes of HPV16 L1 protein in ELISA and IFA assays, three fragments (H2, H3, H9) might contain neutralizing epitopes of HPV16 L1 protein in HI assay. Among them, H11 and H12 fragments contain B cell epitopes have never been reported before, and H3 was found as hemagglutination inhibition epitope for the first time. This work provides new insights to B cell epitopes on HPV16 L1 protein. Several new epitopes were identified and may provide some guidance for HPV16 subunit vaccine design. The results of this study might open new perspectives on the antibody-antigen reaction and have important implications for the development of epitopes-based protective HPV16 vaccines. Copyright © 2018. Published by Elsevier B.V.

Plant-Produced Cottontail Rabbit Papillomavirus L1 Protein Protects against Tumor Challenge: a Proof-of-Concept Study

PubMed Central

Kohl, T.; Hitzeroth, I. I.; Stewart, D.; Varsani, A.; Govan, V. A.; Christensen, N. D.; Williamson, A.-L.; Rybicki, E. P.

2006-01-01

The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically via Agrobacterium tumefaciens transformation and transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants. PMID:16893983

[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.

Identification of Human Papillomavirus Type 16 L1 Surface Loops Required for Neutralization by Human Sera†

PubMed Central

Carter, Joseph J.; Wipf, Greg C.; Madeleine, Margaret M.; Schwartz, Stephen M.; Koutsky, Laura A.; Galloway, Denise A.

2006-01-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface. PMID:16641259

Identification of human papillomavirus type 16 L1 surface loops required for neutralization by human sera.

PubMed

Carter, Joseph J; Wipf, Greg C; Madeleine, Margaret M; Schwartz, Stephen M; Koutsky, Laura A; Galloway, Denise A

2006-05-01

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface.

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

ClinicalTrials.gov

2018-04-16

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

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.

Longitudinal Psychosocial Adjustment of Women to Human Papillomavirus Infection.

PubMed

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

2018-05-29

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

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

MedlinePlus

... taken in its entirety from the CDC HPV (Human Papillomavirus) Cervarix® Vaccine Information Statement: www.cdc.gov/ ... WHAT IS HPV? Genital human papillomavirus (HPV) is the most common ... in the United States. More than half of sexually active men ...

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.

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.

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.

Novel snake papillomavirus does not cluster with other non-mammalian papillomaviruses.

PubMed

Lange, Christian E; Favrot, Claude; Ackermann, Mathias; Gull, Jessica; Vetsch, Elisabeth; Tobler, Kurt

2011-09-12

Papillomaviruses (PVs) are associated with the development of neoplasias and have been found in several different species, most of them in humans and other mammals. We identified, cloned and sequenced PV DNA from pigmented papilloma-like lesions of a diamond python (Morelia spilota spilota). This represents the first complete PV genome discovered in a Squamata host (MsPV1). It consists of 7048 nt and contains the characteristic open reading (ORF) frames E6, E7, E1, E2, L1 and L2. The L1 ORF sequence showed the highest percentage of sequence identities to human PV5 (57.9%) and Caribbean manatee (Trichechus manatus) PV1 (55.4%), thus, establishing a new clade. According to phylogenetic analysis, the MsPV1 genome clusters with PVs of mammalian rather than sauropsid hosts.

Prevention of carcinoma of cervix with human papillomavirus vaccine.

PubMed

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

2000-01-01

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

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

Cytologic regression in women with atypical squamous cells of unknown significance and negative human papillomavirus test.

PubMed

Wang, Shu; Lang, Jing He; Cheng, Xue Mei

2009-12-01

The aim of this study was to investigate the cytologic regression in women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus test. The 45 women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus at baseline were analyzed about the cytologic regression during 2 years of follow-up. The cumulative rate of cytologic regression was calculated by Kaplan-Meier curves. Of 45 women, the cumulative rates were as follows: 55.6% obtained cytologic regression before 6 months, 84.4% by 1 year, and 95.6% at 2 years. Cytologic regression was not influenced by age, menopausal status, and baseline human papillomavirus load. However, the 1-year cumulative regression rate in women with previous cervical lesions was significantly lower than those without (P=.02), even much lower in women with high-grade intraepithelial neoplasia or worse (P=.008). Most women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus could obtain cytologic regression within 2 years. Women with antecedent cervical lesions need longer time to reach this regression.

Detection of Human Papillomavirus Type 2 Related Sequence in Oral Papilloma

PubMed Central

Yamaguchi, Taihei; Shindoh, Masanobu; Amemiya, Akira; Inoue, Nobuo; Kawamura, Masaaki; Sakaoka, Hiroshi; Inoue, Masakazu; Fujinaga, Kei

1998-01-01

Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma. PMID:9699941

Novel snake papillomavirus does not cluster with other non-mammalian papillomaviruses

PubMed Central

2011-01-01

Papillomaviruses (PVs) are associated with the development of neoplasias and have been found in several different species, most of them in humans and other mammals. We identified, cloned and sequenced PV DNA from pigmented papilloma-like lesions of a diamond python (Morelia spilota spilota). This represents the first complete PV genome discovered in a Squamata host (MsPV1). It consists of 7048 nt and contains the characteristic open reading (ORF) frames E6, E7, E1, E2, L1 and L2. The L1 ORF sequence showed the highest percentage of sequence identities to human PV5 (57.9%) and Caribbean manatee (Trichechus manatus) PV1 (55.4%), thus, establishing a new clade. According to phylogenetic analysis, the MsPV1 genome clusters with PVs of mammalian rather than sauropsid hosts. PMID:21910860

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

PubMed Central

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

2016-01-01

BACKGROUND Human papillomavirus (HPV) vaccines prevent HPV infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an HPV-associated lesion is not fully understood. OBJECTIVES To determine whether HPV-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN 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 HPV-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+. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS 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 papillomavirus types present at

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.

Regulation of human genome expression and RNA splicing by human papillomavirus 16 E2 protein.

PubMed

Gauson, Elaine J; Windle, Brad; Donaldson, Mary M; Caffarel, Maria M; Dornan, Edward S; Coleman, Nicholas; Herzyk, Pawel; Henderson, Scott C; Wang, Xu; Morgan, Iain M

2014-11-01

Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein regulates transcription from and replication of the viral genome; the role of E2 in regulating the host genome has been less well studied. We have expressed HPV16 E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene expression analysis identified 74 genes showing differential expression specific to E2. Analysis of published gene expression data sets during cervical cancer progression identified 20 of the genes as being altered in a similar direction as the E2 specific genes. In addition, E2 altered the splicing of many genes implicated in cancer and cell motility. The E2 expressing cells showed no alteration in cell growth but were altered in cell motility, consistent with the E2 induced altered splicing predicted to affect this cellular function. The results present a model system for investigating E2 regulation of the host genome. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Cancerl cells 5. Papillomaviruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

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.

Prevalence of human papillomavirus among STD clinic attenders in Jamaica: association of younger age and increased sexual activity.

PubMed

Figueroa, J P; Ward, E; Luthi, T E; Vermund, S H; Brathwaite, A R; Burk, R D

1995-01-01

Human papillomavirus is the major etiologic agent of cervical cancer. Although the incidence of cancer of the cervix is high in Jamaica, the prevalence of human papillomavirus among Jamaican women has not been defined. To estimate the prevalence of human papillomavirus infection and associated risk factors in women attending an STD clinic in Kingston, Jamaica. A cross-sectional survey was done of 202 women attending an STD clinic in Kingston in 1990. Cervical and vaginal cells were collected by lavage, and human papillomavirus genomes were detected in extracted DNA using low-stringency Southern blot hybridization. Fifty-eight (28.7%) women were identified as HPV positive. Prevalence of HPV by age group was 39% in women 15-19 years old, 33% of women 20-24 years old, 31% in women 25-29 years old, and 17% in those 30 years or older. Increasing age was significantly associated with a lower prevalence of human papillomavirus infection (test for trend, P = 0.025). The effect of age was independent of years of sexual activity. Women reporting more than one sexual partner per month on average were found to have a significantly higher HPV prevalence (odds ratio 2.87, 95% confidence Interval 1.29-6.38), as were women who reported more frequent sex (test for trend, P = 0.006). Sexual behavior is associated with risk of human papillomavirus infection. The decrease of human papillomavirus prevalence in older women agrees with other studies that argue in favor of a biological effect, such as increased immunity to human papillomavirus with age. A better understanding of why immunity to human papillomavirus may develop in older women may provide the basis for developing an effective vaccine to prevent cancer of the cervix.

Prevalence of HIV, human papillomavirus type 16 and herpes simplex virus type 2 among female sex workers in Guinea and associated factors.

PubMed

Aho, Joséphine; Koushik, Anita; Coutlée, François; Diakité, Soumaïla Laye; Rashed, Sélim

2014-03-01

Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings.

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…

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

The Papillomavirus E2 proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

McBride, Alison A., E-mail: amcbride@nih.gov

2013-10-15

The papillomavirus E2 proteins are pivotal to the viral life cycle and have well characterized functions in transcriptional regulation, initiation of DNA replication and partitioning the viral genome. The E2 proteins also function in vegetative DNA replication, post-transcriptional processes and possibly packaging. This review describes structural and functional aspects of the E2 proteins and their binding sites on the viral genome. It is intended to be a reference guide to this viral protein. - Highlights: • Overview of E2 protein functions. • Structural domains of the papillomavirus E2 proteins. • Analysis of E2 binding sites in different genera of papillomaviruses.more » • Compilation of E2 associated proteins. • Comparison of key mutations in distinct E2 functions.« less

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

Active sites prediction and binding analysis E1-E2 protein human papillomavirus with biphenylsulfonacetic acid

NASA Astrophysics Data System (ADS)

Iryani, I.; Amelia, F.; Iswendi, I.

2018-04-01

Cervix cancer triggered by Human papillomavirus infection is the second cause to woman death in worldwide. The binding site of E1-E2 protein of HPV 16 is not known from a 3-D structure yet, so in this study we address this issue to study the structure of E1-E2 protein from Human papillomavirus type 16 and to find its potential binding sites using biphenylsulfonacetic acid as inhibitor. Swiss model was used for 3D structure prediction and PDB: 2V9P (E1 protein) and 2NNU (E2 protein) having 52.32% and 100% identity respectively was selected as a template. The 3D model structure developed of E1 and E2 in the core and allowed regions were 99.2% and 99.5%. The ligand binding sites were predicted using online server meta pocket 2.0 and MOE 2009.10 was used for docking. E1-and E2 protein of HPV-16 has three potential binding site that can interact with the inhibitors. The Docking biphenylsulfonacetic acid using these binding sites shows that ligand interact with the protein through hydrogen bonds on Lys 403, Arg 410, His 551 in the first pocket, on Tyr 32, Leu 99 in the second pocket, and Lys 558m Lys 517 in the third pocket.

Characterization of Human Papillomavirus Type 154 and Tissue Tropism of Gammapapillomaviruses

PubMed Central

Ure, Agustín Enrique; Forslund, Ola

2014-01-01

The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus. PMID:24551244

Association of cystic neck metastases and human papillomavirus-positive oropharyngeal squamous cell carcinoma.

PubMed

McHugh, Jonathan B

2009-11-01

Human papillomavirus is an established cause of oropharyngeal squamous cell carcinoma. Similar to cervical cancer, these cancers are usually caused by high-risk human papillomavirus types 16 and 18 and are associated with high-risk sexual behaviors. Human papillomavirus-associated oropharyngeal squamous cell carcinoma typically affects the palatine and lingual tonsils and frequently results in cystic neck metastases. The histopathology of this subset of head and neck squamous cell carcinoma is unique and typically characterized by poorly differentiated, nonkeratinizing morphology with a basaloid appearance. These tumors occur in younger patients and are more often seen in nonsmokers compared with conventional oral cavity and oropharyngeal squamous cell carcinomas. The incidence of human papillomavirus-associated squamous cell carcinoma is increasing. Recognition of this unique clinicopathologic subset of head and neck carcinoma is important because these patients typically respond more favorably to organ-sparing treatment modalities and have an improved prognosis.

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

The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: Reviewed according to the Bradford Hill criteria for causality.

PubMed

Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe; Lajer, Christel Bræmer

2016-12-01

There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils. The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident. Copyright © 2016 Elsevier Ltd. All rights reserved.

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…

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…

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.

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

PubMed

Gargano, Julia W; Wilkinson, Edward J; Unger, Elizabeth R; Steinau, Martin; Watson, Meg; Huang, Youjie; Copeland, Glenn; Cozen, Wendy; Goodman, Marc T; Hopenhayn, Claudia; Lynch, Charles F; Hernandez, Brenda Y; Peters, Edward S; Saber, Maria Sibug; Lyu, Christopher W; Sands, Lauren A; Saraiya, Mona

2012-10-01

The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin-stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

Feline papillomas and papillomaviruses.

PubMed

Sundberg, J P; Van Ranst, M; Montali, R; Homer, B L; Miller, W H; Rowland, P H; Scott, D W; England, J J; Dunstan, R W; Mikaelian, I; Jenson, A B

2000-01-01

Papillomaviruses (PVs) are highly species- and site-specific pathogens of stratified squamous epithelium. Although PV infections in the various Felidae are rarely reported, we identified productive infections in six cat species. PV-induced proliferative skin or mucous membrane lesions were confirmed by immunohistochemical screening for papillomavirus-specific capsid antigens. Seven monoclonal antibodies, each of which reacts with an immunodominant antigenic determinant of the bovine papillomavirus L1 gene product, revealed that feline PV capsid epitopes were conserved to various degrees. This battery of monoclonal antibodies established differential expression patterns among cutaneous and oral PVs of snow leopards and domestic cats, suggesting that they represent distinct viruses. Clinically, the lesions in all species and anatomic sites were locally extensive and frequently multiple. Histologically, the areas of epidermal hyperplasia were flat with a similarity to benign tumors induced by cutaneotropic, carcinogenic PVs in immunosuppressed human patients. Limited restriction endonuclease analyses of viral genomic DNA confirmed the variability among three viral genomes recovered from available frozen tissue. Because most previous PV isolates have been species specific, these studies suggest that at least eight different cat papillomaviruses infect the oral cavity (tentative designations: Asian lion, Panthera leo, P1PV; snow leopard, Panthera uncia, PuPV-1; bobcat, Felis rufus, FrPV; Florida panther, Felis concolor, FcPV; clouded leopard, Neofelis nebulosa, NnPV; and domestic cat, Felis domesticus, FdPV-2) or skin (domestic cat, F. domesticus, FdPV-1; and snow leopard, P. uncia, PuPV-2).

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

PubMed

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

2018-05-30

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

Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes

PubMed Central

Jagu, Subhashini; Karanam, Balusubramanyam; Wang, Joshua W.; Zayed, Hatem; Weghofer, Margit; Brendle, Sarah A.; Balogh, Karla K.; Tossi, Kerstin Pino; Roden, Richard B.S.; Christensen, Neil D.

2016-01-01

Vaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum ± MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant. PMID:26382603

[Preparation and activity detection of chicken egg yolk IgY antibody against human papillomavirus 16 type L1 main capsid protein].

PubMed

Yang, Jun; Zhang, Ming-juan; Qiang, Lei; Su, Bao-shan; Wang, Yi-li; Si, Lü-sheng

2008-03-01

To prepare highly specific chicken egg yolk IgY antibody against human papillomavirus 16 type L1 main capsid protein (HPV16L1) for detection of HPV16L1. Purified HPV16L1 protein was used to immunize the hens, from which the eggs were collected since one week after the first immunization. The egg yolk was separated and the IgY antibody purified by PEG-6000 method. The bioactivity of the antibody was tested using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was performed to detect the HPV16L1 in the CHO cells transfected with the recombinant pcDNA-EGFP-HPV16L1 plasmid (containing EGFP-HPV16L1 fusion gene) for assessing the specific affinity of IgY to HPV16L1. After 3 immunizations of the hens, the titer of the purified IgY antibody against HPV16L1 from the egg yolk reached 1:10240. The IgY bound specifically to the EGFP-HPV16L1 protein expressed in the transfected CHO cells. High titer IgY can be prepared by immunization of the hens with HPV16L1 protein, and the prepared IgY can be used for HPV16L1 detection at the cellular level.

Human papillomavirus type 2 associated with pyogenic granuloma in patients without clinical evidence of warts.

PubMed

Vázquez-Martínez, Osvaldo T; González-Betancourt, Anajulia; Barboza-Cerda, María Carmen; González-González, Sergio E; Lugo-Trampe, Ángel; Welsh, Oliverio; Rojas-Martínez, Augusto; Martínez-Rodríguez, Herminia G; Ocampo-Candiani, Jorge; Ortiz-López, Rocío

2016-07-01

Pyogenic granuloma is a non-neoplastic lesion that frequently occurs in the skin and mucous membranes of children and pregnant women. The anatomical sites of pyogenic granulomas overlap with those of wart infections caused by the human papillomavirus (HPV). This study assessed the presence of HPV DNA in pyogenic granuloma samples by polymerase chain reaction. Eighteen pyogenic granuloma biopsies from patients without a clinical history or evidence of verruca in the studied area were tested for the presence of the HPV genome. The presence of HPV DNA was screened by three independent polymerase chain reaction reactions using standard consensus primer sets targeted to the L1 or E1 consensus regions of HPV genome. The HPV DNA-positive samples were genotyped using methodologies enabling the identification of up to 30 HPVs, including oncogenic, nononcogenic, and cutaneous viral types. The HPV DNA was detected in 44.4% (eight of 18) of the samples, with HPV-2 being the only type in the eight HPV DNA-positive samples. Contamination with HPV-2 sequences throughout the entire process was reliably eliminated. This report is the first to suggest an association between HPV-2 and pyogenic granuloma. This relationship is similar to that observed between HPV-2 and nongenital warts. © 2015 The International Society of Dermatology.

Insights into the mechanism of human papillomavirus E2-induced procaspase-8 activation and cell death

NASA Astrophysics Data System (ADS)

Singh, Nitu; Senapati, Sanjib; Bose, Kakoli

2016-02-01

High-risk human papillomavirus (HR-HPV) E2 protein, the master regulator of viral life cycle, induces apoptosis of host cell that is independent of its virus-associated regulatory functions. E2 protein of HR-HPV18 has been found to be involved in novel FADD-independent activation of caspase-8, however, the molecular basis of this unique non-death-fold E2-mediated apoptosis is poorly understood. Here, with an interdisciplinary approach that involves in silico, mutational, biochemical and biophysical probes, we dissected and characterized the E2-procasapse-8 binding interface. Our data demonstrate direct non-homotypic interaction of HPV18 E2 transactivation domain (TAD) with α2/α5 helices of procaspase-8 death effector domain-B (DED-B). The observed interaction mimics the homotypic DED-DED complexes, wherein the conserved hydrophobic motif of procaspase-8 DED-B (F122/L123) occupies a groove between α2/α3 helices of E2 TAD. This interaction possibly drives DED oligomerization leading to caspase-8 activation and subsequent cell death. Furthermore, our data establish a model for E2-induced apoptosis in HR-HPV types and provide important clues for designing E2 analogs that might modulate procaspase-8 activation and hence apoptosis.

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…

Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

PubMed Central

Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

2011-01-01

Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells. PMID:22056390

Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses.

PubMed

Carney, Daniel W; Nelson, Christian D S; Ferris, Bennett D; Stevens, Julia P; Lipovsky, Alex; Kazakov, Teymur; DiMaio, Daniel; Atwood, Walter J; Sello, Jason K

2014-09-01

Human polyoma- and papillomaviruses are non-enveloped DNA viruses that cause severe pathologies and mortalities. Under circumstances of immunosuppression, JC polyomavirus causes a fatal demyelinating disease called progressive multifocal leukoencephalopathy (PML) and the BK polyomavirus is the etiological agent of polyomavirus-induced nephropathy and hemorrhagic cystitis. Human papillomavirus type 16, another non-enveloped DNA virus, is associated with the development of cancers in tissues like the uterine cervix and oropharynx. Currently, there are no approved drugs or vaccines to treat or prevent polyomavirus infections. We recently discovered that the small molecule Retro-2(cycl), an inhibitor of host retrograde trafficking, blocked infection by several human and monkey polyomaviruses. Here, we report diversity-oriented syntheses of Retro-2(cycl) and evaluation of the resulting analogs using an assay of human cell infections by JC polyomavirus. We defined structure-activity relationships and also discovered analogs with significantly improved potency as suppressors of human polyoma- and papillomavirus infection in vitro. Our findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human Papillomavirus Genital Infections among Men, China, 2007–2009

PubMed Central

He, Zhonghu; Liu, Ying; Sun, Yuan; Xi, Long Fu; Chen, Ke; Zhao, Yiqiang; Gao, Lei; Liu, Fangfang; Pan, Yaqi; Ning, Tao; Zhang, Lixin; Cai, Hong

2013-01-01

To determine prevalence of genital human papillomavirus (HPV) infection among men in rural China, we analyzed genital swab specimens. Among 2,236 male residents of rural Henan Province, HPV infection prevalence was 17.5%. The most common oncogenic and nononcogenic types were HPV-16 and HPV-3, respectively. Infection was associated with younger age and multiple sex partners. PMID:23735236

Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

PubMed

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

2018-03-15

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

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

PubMed

Onon, Toli S

2011-10-01

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

Distribution of Human papillomavirus load in clinical specimens.

PubMed

Lowe, Brian; O'Neil, Dominic; Loeffert, Dirk; Nazarenko, Irina

2011-04-01

The information about the range and distribution of Human papillomavirus load in clinical specimens is important for the design of accurate clinical tests. The amount of Human papillomavirus in cervical specimens was estimated using the digene HC2 HPV DNA Test(®) (QIAGEN). This semi-quantitative assay is based on linear signal amplification with an analytical limit-of-detection of approximately 2500 virus copies per assay and 3-4 log dynamic range. The dynamic range of the assay was extended by a serial dilution strategy. Two large sets of positive specimens (n=501 and 569) were analyzed and 9-11% of specimens was estimated to contain more than 7 × 10(7) copies of virus. The viral load was also assessed for an assortment of specimens with known cytology diagnoses (n=9435) and histological diagnoses (n=2056). The percentage of specimens with more than 7 × 10(7) copies of virus was estimated to be 0.89 for normal cells, 4.2 for atypical cells (unknown significance), 14.31 for cells of low-grade lesions and 22.24 for cells of high-grade lesions. The viral load increased with disease severity, but its broad distribution may not support its use as a disease biomarker. This information is important for assay design and automation, where cross-reactivity and sample-to-sample contamination must be addressed rigorously. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

García-Carrancá, A; Gariglio, P V

1993-01-01

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

Genetic variability in E6, E7, and L1 genes of human papillomavirus genotype 52 from Southwest China.

PubMed

Zhang, Yiwen; Cao, Man; Wang, Mengting; Ding, Xianping; Jing, Yaling; Chen, Zuyi; Ma, Tengjiao; Chen, Honghan

2016-07-01

Human papillomavirus (HPV) is the major causative agent of cervical cancer, which accounts for the second highest cancer burden in women worldwide. HPV-52, the prevalent subtype in Asia, especially in southwest China, was analyzed in this study. To analyze polymorphisms, intratypic variants, and genetic variability in the E6-E7 (n=26) and L1 (n=53) genes of HPV-52, these genes were sequenced and the sequences were submitted to GenBank. Phylogenetic trees were constructed using the neighbor-joining and Kimura 2-parameters methods, followed by analysis of the diversity of secondary structure. Finally, we estimated the selection pressures acting on the E6-E7 and L1 genes. Fifty-one novel variants of HPV-52 L1, and two novel variants of HPV-52 E6-E7 were identified in this study. Thirty single nucleotide changes were observed in HPV-52 E6-E7 sequences with 19/30 non-synonymous mutations and 11/30 synonymous mutations (five in the alpha helix and five in the beta sheet). Fifty-five single nucleotide changes were observed in HPV-52 L1 sequences with 17/55 non-synonymous mutations (seven in the alpha helix and fourteen in the beta sheet) and 38/55 synonymous mutations. Selective pressure analysis predicted that most of these mutations reflect positive selection. Identifying new variants in HPV-52 may inform the rational design of new vaccines specifically for women in southwest China. Knowledge of genetic variation in HPV may be useful as an epidemiologic correlate of cervical cancer risk, or may even provide critical information for developing diagnostic probes. Copyright © 2016 Elsevier B.V. All rights reserved.

A teat papillomatosis case in a Damascus goat (Shami goat) in Hatay province, Turkey: a new putative papillomavirus?

PubMed

Dogan, Fırat; Dorttas, Selvi Deniz; Bilge Dagalp, Seval; Ataseven, Veysel Soydal; Alkan, Feray

2018-06-01

Papillomaviruses (PVs) are epitheliotropic viruses that cause benign proliferative lesions in the skin (warts or papillomas) and mucous membranes of their natural hosts. Recently, new PVs have been found in many animal species. The most common current approach for identifying novel PV types is based on PCR, using various consensus or degenerated primer (broad-range primers), designed on the basis of the multiple alignment of nucleotide or amino acid sequences of a large number of different human papillomaviruses (HPV). PVs have been classified according to the sequence similarity of one of their capsid proteins, L1, without taking into account other regions of the genome and without considering the phenotypic characteristics of the viral infection. In this study, we performed molecular detection and typing of a PV in a goat with teat papillomatosis. Firstly, PCR was performed using the FAP59/FAP64 and MY09/MY11 primer pairs for the L1 gene region. The PV DNA was found to be positive only with the FAP59/FAP64 primer pair. PV DNA was then tested with three primer sets in four different combinations (L2Bf/FAP64, L2Bf/L1Br, FAP59/FAP64, L1Bf/LCRBr) for the gene region encoding the L1, L2 and LCR proteins. The goat teat papilloma sample was amplified using FAP59/FAP64 primers and two primer pairs (L2Bf/FAP64 and L2Bf/L1Br). We obtained products matching approximately 604 bp of the L1 region of the virus. PV DNA was used for typing using sequence analysis/PCR with some type-specific primers for bovids, caprids and cervids. The results of the sequence analysis suggested one new putative PV type with sequence identity ranging from 46.45 to 80.09% to other known papillomaviruses, including Capra hircus papillomavirus (ChPV-2), bovine papillomavirus (BPV) 6, 7, 10, 11 and 12, Rangifer tarandus papillomavirus 3 (RtPV-3) and BPV-7Z (Alpine wild ruminant papillomavirus; Cervus elaphus papillomavirus). We therefore propose that this is the first identification of a new putative

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

PubMed

Gottschalk, Elinor Y; Meneses, Patricio I

2015-09-01

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

Human papillomaviruses in anogenital warts in children: typing by in situ hybridisation.

PubMed Central

Padel, A F; Venning, V A; Evans, M F; Quantrill, A M; Fleming, K A

1990-01-01

OBJECTIVE--To identify the types of human papillomaviruses found in anogenital warts in children and to relate these to clinical and social information. DESIGN--In situ hybridisation using biotin labelled DNA probes to 11 types of human papillomavirus was performed on biopsy specimens from 17 children with anogenital warts. SETTING--Nuffield department of pathology and the department of dermatology, Oxford. PATIENTS--Children in one group were referred by general practitioners or paediatricians to the dermatology department, where biopsies were performed. The other children were seen in four different hospitals, and biopsy specimens were submitted to the laboratory at the physician's or pathologist's request. RESULTS--Of the 17 biopsy specimens, 10 contained cells positive with a probe to a genital human papillomavirus type (types 6 or 11), while six were positive with a skin virus type (types 2 or 3). One was negative. The virus type present bore no relation to the site or appearance of the warts. The virus type did, however, appear to correlate with groups of children. Skin types were commoner in older children (over 4 years), in those with a relative who had skin warts, and in children with warts elsewhere; there was no relation with the child's sex and no suspicion of sexual abuse in these children. These circumstances suggested non-sexual transmission, such as autoinoculation. In contrast, genital types were commoner in girls, in children under 3 years, in children with relatives with genital warts, and in those with no warts elsewhere. Nevertheless, there was suspicion or evidence of sexual abuse in only half these children, suggesting that other routes of transmission--for example, perinatal--might have been implicated. CONCLUSION--Anogenital warts in children may contain either skin or genital wart virus type. Although the type of human papillomavirus present may give some indication of the likely mode of transmission, this can be interpreted only in

Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus‐associated invasive carcinoma

PubMed Central

Jeannot, Emmanuelle; Becette, Véronique; Campitelli, Maura; Calméjane, Marie‐Ange; Lappartient, Emmanuelle; Ruff, Evelyne; Saada, Stéphanie; Holmes, Allyson; Bellet, Dominique

2016-01-01

Abstract Specific human papillomavirus genotypes are associated with most ano‐genital carcinomas and a large subset of oro‐pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus‐associated carcinomas. A series of 70 serum specimens, taken at the time of diagnosis, between 2002 and 2013, were retrospectively analyzed in patients with human papillomavirus‐16 or human papillomavirus‐18‐associated carcinomas, composed of 47 cases from the uterine cervix, 15 from the anal canal and 8 from the oro‐pharynx. As negative controls, 18 serum samples from women with human papillomavirus‐16‐associated high‐grade cervical intraepithelial neoplasia were also analyzed. Serum samples were stored at −80°C (27 cases) or at −20°C (43 cases). DNA was isolated from 200 µl of serum or plasma and droplet digital PCR was performed using human papillomavirus‐16 E7 and human papillomavirus‐18 E7 specific primers. Circulating human papillomavirus DNA was detected in 61/70 (87%) serum samples from patients with carcinoma and in no serum from patients with cervical intraepithelial neoplasia. The positivity rate increased to 93% when using only serum stored at −80°C. Importantly, the two patients with microinvasive carcinomas in this series were positive. Quantitative evaluation showed that circulating viral DNA levels in cervical cancer patients were related to the clinical stage and tumour size, ranging from 55 ± 85 copies/ml (stage I) to 1774 ± 3676 copies/ml (stage IV). Circulating human

DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes.

PubMed

La-Touche, Susannah; Lemetre, Christophe; Lambros, Maryou; Stankiewicz, Elzbieta; Ng, Charlotte K Y; Weigelt, Britta; Rajab, Ramzi; Tinwell, Brendan; Corbishley, Cathy; Watkin, Nick; Berney, Dan; Reis-Filho, Jorge S

2016-01-01

Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.

DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes

PubMed Central

Lambros, Maryou; Stankiewicz, Elzbieta; Ng, Charlotte K. Y.; Weigelt, Britta; Rajab, Ramzi; Tinwell, Brendan; Corbishley, Cathy; Watkin, Nick; Berney, Dan; Reis-Filho, Jorge S.

2016-01-01

Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents. PMID:26901676

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

PubMed

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

2017-03-21

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

Comparison of human papillomavirus DNA tests, liquid-based cytology and conventional cytology for the early detection of cervix uteri cancer.

PubMed

Girianelli, Vania R; Thuler, Luiz Claudio S; Szklo, Moyses; Donato, Alexandre; Zardo, Lucilia M G; Lozana, José A; Almeida Neto, Olimpio F; Carvalho, Aurenice C L; Matos, Jorge H; Figueiredo, Valeska

2006-12-01

To compare the performance of human papillomavirus DNA tests (samples collected by a healthcare professional and self-collected) and liquid-based cytology with conventional cytology in the detection of cervix uteri cancer and its precursor lesions. A cross-sectional study was carried out in 1777 women living in poor communities in Rio de Janeiro State, Brazil. Eligibility criteria included ages 25-59 years and not having had a Papanicolau test within at least 3 years prior to the study. Cytology (conventional or liquid-based) and human papillomavirus DNA (collected by a healthcare professional or self-collected) tests were performed using samples collected in a single visit. Women with abnormalities in at least one test and a systematic sample of 70 women with negative test results were referred to a colposcopic examination. Test readings were double-masked, and the outcome of interest was high-grade squamous intraepithelial lesion or worse. The pathology report was used as the gold standard. The prevalence of high-grade squamous intraepithelial lesion or worse was 2.0%. Human papillomavirus DNA test collected by a health professional alone or combined with conventional cytology had the highest sensitivity (91.4 and 97.1%, respectively). The highest specificity was found for conventional cytology (91.6%) and for a human papillomavirus DNA test collected by a healthcare professional (90.2%). On the basis of only test performance, the use of human papillomavirus DNA tests, alone or combined with cytology, would seem to be recommended. Its population-wide implementation, however, is conditional on a cost-effectiveness analysis.

Impact of Gender-Specific Human Papillomavirus Vaccine Recommendations on Uptake of Other Adolescent Vaccines: Analysis of the NIS-Teen (2008-2012).

PubMed

Bednarczyk, Robert A; Orenstein, Walter A; Omer, Saad B

In the United States, human papillomavirus vaccination was routinely recommended for adolescent females in 2006 and provisionally recommended for adolescent males in 2009. We evaluated the hypothesis that gender-specific human papillomavirus vaccination recommendations would impact gender-specific uptake of other vaccines using National Immunization Survey-Teen public use data sets (2008-2012). Female adolescents had higher coverage than males of at least 1 other adolescent vaccine in 2008 (3.0% higher) and 2009 (4.3% higher). Gender differences abated in 2010, 2011, and 2012 (0.2%, 0.9%, and 0.4%, respectively). To evaluate unintended consequences of gender-based recommendations, countries with female-only human papillomavirus vaccination recommendations should evaluate gender-specific uptake of other adolescent vaccines.

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.

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

PubMed

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

2014-05-15

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

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.

Giving It Our Best Shot? Human Papillomavirus and Hepatitis B Virus Immunization Among Refugees, Massachusetts, 2011-2013.

PubMed

Berman, Rachel Stein; Smock, Laura; Bair-Merritt, Megan H; Cochran, Jennifer; Geltman, Paul L

2017-06-22

The receipt rate of hepatitis B virus vaccine among adolescents in the United States is high, while the receipt rate of human papillomavirus vaccine is low. Rates have not been closely studied among refugees, whose home countries have high rates of disease caused by these viruses. We examined human papillomavirus and hepatitis B virus immunization rates among 2,269 refugees aged 9 to 26 years who resettled in Massachusetts from 2011 through 2013. This was a secondary analysis of data from their medical screenings. We used binary logistic regression to assess characteristics associated with immunization and bivariate analyses to compare refugee immunization rates with those of the general US population. Forty-five percent of US adolescents aged 13 to 17 years received 1 dose of human papillomavirus vaccine, compared with 68% of similarly aged refugees. Males (adjusted odds ratio [aOR], 0.62; 95% confidence interval [CI], 0.52-0.74), refugees older than 13 years (aOR, 0.74; 95% CI, 0.60-0.93), and refugees not from Sub-Saharan Africa (aOR, 0.74; 95% CI, 0.59-0.92) were less likely to receive human papillomavirus vaccine, while arrivals in 2012 through 2013 were more likely (aOR, 1.6; 95% CI, 1.3-1.9) than those arriving in 2011. Refugees older than 13 years were less likely to receive 2 doses of hepatitis B virus vaccine (aOR, 0.49; 95% CI, 0.37-0.63) than older refugees. Specialized post-arrival health assessment may improve refugees' immunization rates.

Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58

PubMed Central

Xu, Wan-Xiang; Wang, Jian; Tang, Hai-Ping; He, Ya-Ping; Zhu, Qian-Xi; Gupta, Satish K.; Gu, Shao-Hua; Huang, Qiang; Ji, Chao-Neng; Liu, Ling-Feng; Li, Gui-Ling; Xu, Cong-Jian; Xie, Yi

2016-01-01

To enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate complete IgG-epitome of the protein. Here, we describe results of IgG-epitome decoding of three proteins from high-risk (HR-) oncogenic human papillomavirus type 58 (HPV58). To reveal their entire epitomes, employing peptide biosynthetic approach, 30 precise linear B-cell epitopes (BCEs) were mapped on E6, E7 and L1 proteins using rabbits antisera to the respective recombinant proteins. Using sequence alignment based on BCE minimal motif, the specificity and conservativeness of each mapped BCE were delineated mainly among known HR-HPVs, including finding 3 broadly antibody cross-reactive BCEs of L1 that each covers almost all HR-HPVs. Western blots revealed that 13 of the 18 BCEs within L1-epitome were recognized by murine antisera to HPV58 virus-like particles, suggesting that these are antibody accessible BCEs. Also, a highly conserved epitope (YGD/XTL) of E6 was found to exist only in known common HR-HPVs, which could be used as the first peptide reference marker for judging HR-HPVs. Altogether, this study provides systemic and exhaustive information on linear BCEs of HR-HPV58 that will facilitate development of novel multi-epitope diagnostic reagents/chips for testing viral antibodies and ‘universal’ preventive HPV peptide vaccine based on L1 conserved BCEs. PMID:27708433

The psychosocial burden of human papillomavirus related disease and screening interventions.

PubMed

Pirotta, M; Ung, L; Stein, A; Conway, E L; Mast, T C; Fairley, C K; Garland, S

2009-12-01

(i) To assess the psychosocial burden of testing for human papillomavirus (HPV) related genital disease or of a HPV-related diagnosis; (ii) to compare an instrument specifically designed to measure HPV-related psychosocial burden with other generic quality of life (QoL) instruments. A cross-sectional design. Researchers recruited women from outpatient clinics at a major tertiary women's hospital and a sexual health centre who completed surveys within 3 months of receiving 331 women, 18-45 years, who had experienced a normal cervical Papanicolaou (Pap) result, an abnormal Pap result, biopsy confirmed cervical intraepithelial neoplasia (CIN) or external genital warts (EGW). The HPV impact profile (HIP) designed to assess the psychosocial impact of HPV; two general health-related QoL surveys-the EuroQoL VAS and the Sheehan disability scale; and a HPV knowledge survey. Response rate was 78%. Significant psychosocial impacts were found for women screened for, or having a diagnosis of, HPV-related genital disease. The largest impact was in women with CIN 2/3 and EGW. This HPV-related psychosocial impact was most sensitively detected with the HIP. Relative to generic measures of QoL, the HIP provided insight into the full range of psychosocial impacts of HPV testing and diagnoses. Clinicians need to be aware of the potential psychosocial impact of testing for or diagnosing HPV-related genital disease, in particular CIN 2/3 and EGW. The HIP survey is a more sensitive measure of the psychosocial impact of HPV-related genital disease than generic QoL surveys.

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

PubMed

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

2017-06-25

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

Human papillomavirus DNA detected in breast milk.

PubMed

Sarkola, Marja; Rintala, Marjut; Grénman, Seija; Syrjänen, Stina

2008-06-01

Human papillomavirus (HPV) testing of 223 breast milk samples 3 days postpartum was performed with polymerase chain reaction, hybridization, and sequencing. HPV-16-DNA was detected in 4.0% of the samples. HPV carriage in the breast milk was not correlated with mother's oral or cervical HPV-status or the demographic data. Oral HPV-infection of the spouse at month 6 and 12 postpartum was statistically significantly associated with HPV carriage in the breast milk.

Integrative approach to diagnosis of genital human papillomaviruses (HPV) infection of female.

PubMed

Dunjic, Momir; Stanisic, Slavisa; Krstic, Dejan; Stanisic, Miodrag; Ignjatic, Z Jovanovic; Dunjic, Marija

2014-01-01

Human papillomavirus (HPV) is a virus from the papillomavirus family that is capable of infecting humans. Some types of HPVs cause warts, while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus. High-risk human papillomavirus (hr HPV) has been detected in almost all cervical squamous cell carcinomas and adenocarcinomas. All patients examined by colposcopy. Cervical swab is routinely done and patients are screened with both HPV DNA by Real Time Polimerase Chain Reaction (RT PCR) testing and Pap testing. Pictures obtained by colposcopy were examined by indirect Bi-Digital O-Ring Test (BDORT) by using reference control substance (RCS): HPV 16, HPV 18, and Integrin α5 β1. BDORT was developed by Prof. Omura Y. of New York and received U.S. patent in 1993. For detection of HPV DNA we used RT PCR and standard Qiagen method which detect 18 types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 6, 11, 42, 43, 44) of HPV from smear. From 63 patients where is BDORT indicated presence of HPV, in 49 patients (77.8%) RT PCR confirmed presence of HPV. From 63 patients in 54 patients (85.7%), we detected, by colposcopic exam, some kind of lesions associated with HPV infection. Results obtained by RT PCR: one type (1/18) of DNA HPV in 25 patients (51.02%), 2 types (2/18) in 15 patients (30.61%) and 3 types (3/18) in 9 patients (18.37%). Although BDORT results usually have higher sensitivity and detection rate is much higher, it can be used together with RT PCR in detection of HPV and cervical lesions associated with HPV infection.

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

PubMed Central

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

2014-01-01

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

Targeting the Human Papillomavirus E6 and E7 Oncogenes through Expression of the Bovine Papillomavirus Type 1 E2 Protein Stimulates Cellular Motility▿†

PubMed Central

Morrison, Monique A.; Morreale, Richard J.; Akunuru, Shailaja; Kofron, Matthew; Zheng, Yi; Wells, Susanne I.

2011-01-01

Expression of the high-risk human papillomavirus (HPV) E6 and E7 oncogenes is essential for the initiation and maintenance of cervical cancer. The repression of both was previously shown to result in activation of their respective tumor suppressor targets, p53 and pRb, and subsequent senescence induction in cervical cancer cells. Consequently, viral oncogene suppression is a promising approach for the treatment of HPV-positive tumors. One well-established method of E6/E7 repression involves the reexpression of the viral E2 protein which is usually deleted in HPV-positive cancer cells. Here, we show that, surprisingly, bovine papillomavirus type 1 (BPV1) E2 but not RNA interference-mediated E6/E7 repression in HPV-positive cervical cancer cells stimulates cellular motility and invasion. Migration correlated with the dynamic formation of cellular protrusions and was dependent upon cell-to-cell contact. While E2-expressing migratory cells were senescent, migration was not a general feature of cellular senescence or cell cycle arrest and was specifically observed in HPV-positive cervical cancer cells. Interestingly, E2-expressing cells not only were themselves motile but also conferred increased motility to admixed HeLa cervical cancer cells. Together, our data suggest that repression of the viral oncogenes by E2 stimulates the motility of E6/E7-targeted cells as well as adjacent nontargeted cancer cells, thus raising the possibility that E2 expression may unfavorably increase the local invasiveness of HPV-positive tumors. PMID:21835799

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

PubMed

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

2016-07-01

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

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

PubMed

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

2017-01-01

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

Diverse papillomaviruses identified in Weddell seals.

PubMed

Smeele, Zoe E; Burns, Jennifer M; Van Doorsaler, Koenraad; Fontenele, Rafaela S; Waits, Kara; Stainton, Daisy; Shero, Michelle R; Beltran, Roxanne S; Kirkham, Amy L; Berngartt, Rachel; Kraberger, Simona; Varsani, Arvind

2018-04-01

Papillomaviridae is a diverse family of circular, double-stranded DNA (dsDNA) viruses that infect a broad range of mammalian, avian and fish hosts. While papillomaviruses have been characterized most extensively in humans, the study of non-human papillomaviruses has contributed greatly to our understanding of their pathogenicity and evolution. Using high-throughput sequencing approaches, we identified 7 novel papillomaviruses from vaginal swabs collected from 81 adult female Weddell seals (Leptonychotes weddellii) in the Ross Sea of Antarctica between 2014-2017. These seven papillomavirus genomes were amplified from seven individual seals, and six of the seven genomes represented novel species with distinct evolutionary lineages. This highlights the diversity of papillomaviruses among the relatively small number of Weddell seal samples tested. Viruses associated with large vertebrates are poorly studied in Antarctica, and this study adds information about papillomaviruses associated with Weddell seals and contributes to our understanding of the evolutionary history of papillomaviruses.

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

PubMed

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

2011-01-01

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

Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data.

PubMed

Ali, Hammad; Donovan, Basil; Wand, Handan; Read, Tim R H; Regan, David G; Grulich, Andrew E; Fairley, Christopher K; Guy, Rebecca J

2013-04-18

To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. Trend analysis of national surveillance data. Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. Between 2004 and 2011, 85,770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period-from 11.5% in 2007 to 0.85% in 2011 (P<0.001) and from 11.3% in 2007 to 3.1% in 2011 (P<0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period-from 12.1% in 2007 to 2.2% in 2011 (P<0.001) and from 18.2% in 2007 to 8.9% in 2011 (P<0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.

Detection of Human Papillomavirus Type 16 DNA and Papillomavirus Genus‐specific Antigens in Vulva and Cervix from Patients with Bowenoid Papulosis

PubMed Central

Sugase, Motoyasu; Moriyama, Shin‐ichi; Hata, Satoru; Matsukura, Toshihiko

1989-01-01

The warty disordered lesions of the vulva in three female patients were diagnosed as Bowenoid papulosis on the basis of clinical and histopathological findings. In all three vulvar lesions, human Papillomavirus type 16 (HPV 16) DNA was identified hy Southern blot hybridization and Papillomavirus genus‐specific (PGS) antigen was detected in one case immunohistochemically. Furthermore, colposcopic examination revealed the presence of abnormal uterine cervical lesions in two cases. They were found to be intraepithelial neoplasia which harbored HPV 16 DNA and were positive for PGS antigen. PMID:2540130

Productive Infection of Bovine Papillomavirus Type 2 in the Placenta of Pregnant Cows Affected with Urinary Bladder Tumors

PubMed Central

Roperto, Sante; Borzacchiello, Giuseppe; Esposito, Iolanda; Riccardi, Marita; Urraro, Chiara; Lucà, Roberta; Corteggio, Annunziata; Tatè, Rosarita; Cermola, Michele; Paciello, Orlando; Roperto, Franco

2012-01-01

Papillomaviruses (PVs) are believed to be highly epitheliotropic as they usually establish productive infections within stratified epithelia. In vitro, various PVs appear to complete their entire life-cycle in different trophoblastic cell lines. In this study, infection by and protein expression of bovine papillomavirus type 2 (BPV-2) in the uterine and chorionic epithelium of the placenta has been described in four cows suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected both by Western blot analysis and immunohistochemically. It appears to be complexed and perfectly co-localized with the activated platelet-derived growth factor ß receptor (PDGFßR) by laser scanning confocal microscopy. The activated PDGFßR might be involved in organogenesis and neo-angiogenesis rather than in cell transformation during pregnancy. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection has been detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the uterine and chorionic epithelium. Trophoblastic cells appear to be the major target for L1 protein expression. Finally, the early protein E2, required for viral DNA replication and known to be expressed during a productive infection, has been detected by Western blot and immunohistochemically. Electron microscopic investigations detected viral particles in nuclei of uterine and chorionic epithelium. This study shows that both active and productive infections by BPV-2 in the placenta of pregnant cows can occur in vivo. PMID:22479413

Productive infection of bovine papillomavirus type 2 in the placenta of pregnant cows affected with urinary bladder tumors.

PubMed

Roperto, Sante; Borzacchiello, Giuseppe; Esposito, Iolanda; Riccardi, Marita; Urraro, Chiara; Lucà, Roberta; Corteggio, Annunziata; Tatè, Rosarita; Cermola, Michele; Paciello, Orlando; Roperto, Franco

2012-01-01

Papillomaviruses (PVs) are believed to be highly epitheliotropic as they usually establish productive infections within stratified epithelia. In vitro, various PVs appear to complete their entire life-cycle in different trophoblastic cell lines. In this study, infection by and protein expression of bovine papillomavirus type 2 (BPV-2) in the uterine and chorionic epithelium of the placenta has been described in four cows suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected both by Western blot analysis and immunohistochemically. It appears to be complexed and perfectly co-localized with the activated platelet-derived growth factor ß receptor (PDGFßR) by laser scanning confocal microscopy. The activated PDGFßR might be involved in organogenesis and neo-angiogenesis rather than in cell transformation during pregnancy. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection has been detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the uterine and chorionic epithelium. Trophoblastic cells appear to be the major target for L1 protein expression. Finally, the early protein E2, required for viral DNA replication and known to be expressed during a productive infection, has been detected by Western blot and immunohistochemically. Electron microscopic investigations detected viral particles in nuclei of uterine and chorionic epithelium. This study shows that both active and productive infections by BPV-2 in the placenta of pregnant cows can occur in vivo.

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

PubMed

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

2008-03-15

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

Giving It Our Best Shot? Human Papillomavirus and Hepatitis B Virus Immunization Among Refugees, Massachusetts, 2011–2013

PubMed Central

Smock, Laura; Bair-Merritt, Megan H.; Cochran, Jennifer; Geltman, Paul L.

2017-01-01

Introduction The receipt rate of hepatitis B virus vaccine among adolescents in the United States is high, while the receipt rate of human papillomavirus vaccine is low. Rates have not been closely studied among refugees, whose home countries have high rates of disease caused by these viruses. Methods We examined human papillomavirus and hepatitis B virus immunization rates among 2,269 refugees aged 9 to 26 years who resettled in Massachusetts from 2011 through 2013. This was a secondary analysis of data from their medical screenings. We used binary logistic regression to assess characteristics associated with immunization and bivariate analyses to compare refugee immunization rates with those of the general US population. Results Forty-five percent of US adolescents aged 13 to 17 years received 1 dose of human papillomavirus vaccine, compared with 68% of similarly aged refugees. Males (adjusted odds ratio [aOR], 0.62; 95% confidence interval [CI], 0.52–0.74), refugees older than 13 years (aOR, 0.74; 95% CI, 0.60–0.93), and refugees not from Sub-Saharan Africa (aOR, 0.74; 95% CI, 0.59–0.92) were less likely to receive human papillomavirus vaccine, while arrivals in 2012 through 2013 were more likely (aOR, 1.6; 95% CI, 1.3–1.9) than those arriving in 2011. Refugees older than 13 years were less likely to receive 2 doses of hepatitis B virus vaccine (aOR, 0.49; 95% CI, 0.37–0.63) than older refugees. Conclusion Specialized post-arrival health assessment may improve refugees’ immunization rates. PMID:28641071

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

PubMed Central

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

2016-01-01

Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8+ T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers. PMID:26653678

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

PubMed

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

2016-05-01

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

Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid capture 2

PubMed Central

González-Losa, Maria del Refugio; Manzano-Cabrera, Luis; Rueda-Gordillo, Florencio; Hernández-Solís, Sandra E.; Puerto-Solís, Luis

2008-01-01

High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to development cervical cancer. During the last decade many studies have found HR-HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the association between HR-HPV and OSCC is still uncertain. The aim of the study was to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross-sectional study was performed; samples from 77 patients with normal oral cavity were collected at the Dentistry school, Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV was detected by hybrid capture 2. One sample out of 77(1.2%) was positive for HR-PVH. It was from a man of 50 years old. HRHPV is present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good methodology for large epidemiology studies. PMID:24031173

Genomic characterization of the first oral avian papillomavirus in a colony of breeding canaries (Serinus canaria).

PubMed

Truchado, Daniel A; Moens, Michaël A J; Callejas, Sergio; Pérez-Tris, Javier; Benítez, Laura

2018-06-01

Papillomaviruses are non-enveloped, DNA viruses that infect skin and mucosa of a wide variety of vertebrates, causing neoplasias or simply persisting asymptomatically. Avian papillomaviruses, with six fully sequenced genomes, are the second most studied group after mammalian papillomaviruses. In this study, we describe the first oral avian papillomavirus, detected in the tongue of a dead Yorkshire canary (Serinus canaria) and in oral swabs of the same bird and other two live canaries from an aviary in Madrid, Spain. Its genome is 8,071 bp and presents the canonical papillomavirus architecture with six early (E6, E7, E1, E9, E2, E4) and two late open reading frames (L1 and L2) and a long control region between L1 and E6. This new avian papillomavirus L1 gene shares a 64% pairwise identity with FcPV1 L1, so it has been classified as a new species (ScPV1) within the Ethapapillomavirus genus. Although the canary died after showing breathing problems, there is no evidence that the papillomavirus caused those symptoms so it could be part of the oral microbiota of the birds. Hence, future investigations are needed to evaluate the clinical relevance of the virus.

Host control of human papillomavirus infection and disease.

PubMed

Doorbar, John

2018-02-01

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

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…

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.

High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

PubMed

Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

2015-09-01

High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

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…

The Evolving Field of Human Papillomavirus Receptor Research: a Review of Binding and Entry

PubMed Central

Raff, Adam B.; Woodham, Andrew W.; Raff, Laura M.; Skeate, Joseph G.; Yan, Lisa; Da Silva, Diane M.; Schelhaas, Mario

2013-01-01

Human papillomaviruses (HPVs) infect epithelia and can lead to the development of lesions, some of which have malignant potential. HPV type 16 (HPV16) is the most oncogenic genotype and causes various types of cancer, including cervical, anal, and head and neck cancers. However, despite significant research, our understanding of the mechanism by which HPV16 binds to and enters host cells remains fragmented. Over several decades, many HPV receptors and entry pathways have been described. This review puts those studies into context and offers a model of HPV16 binding and entry as a framework for future research. Our model suggests that HPV16 binds to heparin sulfate proteoglycans (HSPGs) on either the epithelial cell surface or basement membrane through interactions with the L1 major capsid protein. Growth factor receptors may also become activated through HSPG/growth factor/HPV16 complexes that initiate signaling cascades during early virion-host cell interactions. After binding to HSPGs, the virion undergoes conformational changes, leading to isomerization by cyclophilin B and proprotein convertase-mediated L2 minor capsid protein cleavage that increases L2 N terminus exposure. Along with binding to HSPGs, HPV16 binds to α6 integrins, which initiate further intracellular signaling events. Following these primary binding events, HPV16 binds to a newly identified L2-specific receptor, the annexin A2 heterotetramer. Subsequently, clathrin-, caveolin-, lipid raft-, flotillin-, cholesterol-, and dynamin-independent endocytosis of HPV16 occurs. PMID:23536685

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

PubMed

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

2018-05-09

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

Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas.

PubMed

Bezerra, Stephania M; Chaux, Alcides; Ball, Mark W; Faraj, Sheila F; Munari, Enrico; Gonzalez-Roibon, Nilda; Sharma, Rajni; Bivalacqua, Trinity J; Burnett, Arthur L; Netto, George J

2015-04-01

Approximately 50% of penile squamous cell carcinomas (SCC) are associated with high-risk human papillomavirus (HR-HPV) infection. We evaluated the correlation of p16(INK4a) expression and HR-HPV with clinicopathological features and outcome in a cohort of patients with penile SCC. Two tissue microarrays were constructed from 53 invasive penile SCC at our hospital. p16(INK4a) expression was assessed by immunohistochemistry (CINtec Kit). High-risk human papillomavirus status was assessed by in situ hybridization (INFORM HPV III family 16 probe B cocktail). High-risk human papillomavirus was detected in 8 cases (15%), and p16(INK4a) overexpression was found in 23 cases (44%). Both markers showed a significant association with histologic subtype (P = .017 and P = .01, respectively) and lymphovascular invasion (P = .015 and P = .015, respectively). Regarding outcome analyses, neither HPV infection nor p16(INK4a) overexpression significantly predicted overall survival or cancer-specific survival using Cox proportional hazards regression model. High-risk human papillomavirus positivity and p16(INK4a) overexpression were significantly associated with histologic subtype and presence of lymphovascular invasion. Human papillomavirus status was not predictive of outcome in our cohort. Copyright © 2015 Elsevier Inc. All rights reserved.

The Interaction Between Human Papillomavirus and Other Viruses

PubMed Central

Guidry, J. T.; Scott, R. S.

2016-01-01

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. PMID:27826043

High Baseline Anal Human Papillomavirus and Abnormal Anal Cytology in a Phase 3 Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Individuals Older Than 26 Years: ACTG 5298.

PubMed

Cranston, Ross D; Cespedes, Michelle S; Paczuski, Pawel; Yang, Ming; Coombs, Robert W; Dragavon, Joan; Saah, Alfred; Godfrey, Catherine; Webster-Cyriaque, Jennifer Y; Chiao, Elizabeth Y; Bastow, Barbara; Wilkin, Timothy

2018-04-01

The quadrivalent human papillomavirus (HPV) vaccine (qHPV; types 6, 11, 16, 18) is indicated for men and women aged 9 to 26 years to prevent HPV associated anogenital high-grade squamous intraepithelial lesions (HSIL) and cancer. ACTG 5298 was a randomized placebo controlled Phase 3 study in human immunodeficiency virus (HIV)-infected men who have sex with men, and women of qHPV to prevent persistent anal HPV infection. Baseline data are presented here. Human immunodeficiency virus-infected men who have sex with men, and women 27 years or older without previous anogenital or oral cancer were enrolled. Baseline anal cytology, high-resolution anoscopy and collection of anal, oral, and vaginal specimens for HPV genotyping were performed and acceptability assessed. Five hundred seventy-five (575) participants were enrolled (82% men and 18% women). Median age was 47 years. Race/ethnicity was 46% white, 31% black, and 20% Hispanic. Plasma HIV-1 RNA was less than 50 copies/mL in 83% and median CD4 T count was 602 cells/μL. Abnormal anal cytology was detected in 62%, with corresponding HSIL on biopsy (bHSIL) in 33%. Anal HPV 6, 11, 16, and 18 were detected in 25%, 13%, 32%, and 18% of the participants, respectively. Prevalence of 0, 1, 2, 3, and 4 qHPV types was 40%, 38%, 17%, 4%, and 1%, respectively. Oral infection with 1 or more qHPV type was detected in 10% of the participants. Study procedures were generally acceptable. At study baseline, there was a high prevalence of abnormal anal cytology, bHSIL, and HPV infection. Sixty percent of the participants had anal infection with preventable qHPV types.

Role of the Akt/mTOR signaling pathway in human papillomavirus-associated nasal and sinonasal inverted papilloma.

PubMed

Liu, Yongliang; Duan, Lihua; Tian, Jie; Song, Daoliang; Zhang, Min; Zhao, Shenlin; Yin, Zhaofu; Xiang, Xinxin; Li, Xuezhong

2017-12-01

Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The immunohistochemistry showed statistically significant differences in phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69-SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling pathway in NSIP. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnosis of 25 genotypes of human papillomaviruses for their physical statuses in cervical precancerous/cancerous lesions: a comparison of E2/E6E7 ratio-based vs. multiple E1-L1/E6E7 ratio-based detection techniques.

PubMed

Zhang, Rong; He, Yi-feng; Chen, Mo; Chen, Chun-mei; Zhu, Qiu-jing; Lu, Huan; Wei, Zhen-hong; Li, Fang; Zhang, Xiao-xin; Xu, Cong-jian; Yu, Long

2014-10-02

Cervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance. The target population comprised 1162 women with an HPV infection history of > six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique "detection of integrated papillomavirus sequences" (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established. The integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75

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…

Evasion of Host Immune Defenses by Human Papillomavirus

PubMed Central

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

2016-01-01

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. PMID:27890631

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…

[Human papillomavirus vaccines].

PubMed

Brun, J-L

2008-02-01

To assess the efficacy, the tolerance, the duration of protection and the limitations of papillomavirus vaccines and to determine the potential indications for prophylactic vaccination. Medline, Biosis and Pascal contents were searched to July 2007. Of 546 abstracts, 30 studies were selected. Prophylactic vaccines are composed of L1 virus-like particles. They are well-tolerated and effective in preventing HPV 16/18 infections and related cervical diseases in young women who are naive to HPV 16/18 after five years of follow-up. In addition, the quadrivalent vaccine prevents HPV 6/11 infections and their consequences. The bivalent vaccine may also prevent HPV 31/45 infections by cross-protection. Young girls before sexual debut are the main target for prophylactic vaccines. Indeed, they demonstrate an excellent immune response after injection and the prevalence of HPV infection increases dramatically after the first sexual intercourse. However, vaccines are ineffective in healthy HPV 16/18 carriers or on existing lesions. Prophylactic vaccines are not effective in women infected by other oncogenic HPV. Therapeutic vaccine effects against cervical dysplasia are currently being assessed. Prophylactic vaccination against HPV is effective, well-tolerated, and should be associated with screening to optimize the prevention of cervical cancer.

Efficacy of human papillomavirus-based screen-and-treat for cervical cancer prevention among HIV-infected women.

PubMed

Kuhn, Louise; Wang, Chunhui; Tsai, Wei-Yann; Wright, Thomas C; Denny, Lynette

2010-10-23

Cervical cancer prevention should be provided as part of primary healthcare services for HIV-infected women but conventional screening programs are difficult to implement in low-resource settings. Here, we evaluate the efficacy among HIV-infected women of a simpler, screen-and-treat strategy in which all women with a positive screening test are treated with cryotherapy. We conducted a randomized clinical trial of two screen-and-treat strategies among 6555 women in Cape Town, South Africa, among whom 956 were HIV-positive. Women were randomized to screen-and-treat utilizing either human papillomavirus DNA testing or visual inspection with acetic acid as the screening method or to a control group. Women were followed for up to 36 months after randomization with colposcopy and biopsy to determine the study endpoint of cervical intraepithelial neoplasia grade 2 or higher. In the control group, HIV-positive women had higher rates of cervical intraepithelial neoplasia grade 2 or higher detected by 36 months (14.9%) than HIV-negative women (4.6%) (P = 0.0006). Screen-and-treat utilizing human papillomavirus DNA testing significantly reduced cervical intraepithelial neoplasia grade 2 or higher through 36 months in both HIV-positive (relative risk = 0.20, 95% confidence interval 0.06-0.69) and HIV-negative women (relative risk = 0.31, 95% confidence interval 0.20-0.50). Reductions in the visual inspection with acetic acid-and-treat group were less marked. Complications of cryotherapy were mostly minor and did not differ in frequency between HIV-positive and HIV-negative women. Screen-and-treat using human papillomavirus testing is a simple and effective method to reduce high-grade cervical cancer precursors in HIV-infected women.

High-throughput detection of human papillomavirus-18 L1 gene methylation, a candidate biomarker for the progression of cervical neoplasia.

PubMed

Turan, Tolga; Kalantari, Mina; Cuschieri, Kate; Cubie, Heather A; Skomedal, Hanne; Bernard, Hans-Ulrich

2007-04-25

The L1 gene of human papillomavirus-18 (HPV-18) is consistently hypermethylated in cervical carcinomas, but frequently hypo- or unmethylated in exfoliated cells from asymptomatic patients. In precancerous lesions, L1 is sporadically hypermethylated, correlating with the severity of the neoplasia. In order to explore the potential of using L1 methylation as a workable biomarker for carcinogenic progression of HPV-18 infections in routinely taken samples, our aim was to develop methylation-detection techniques that were sensitive and rapid without being overly complex technically. Therein, we developed a methylation-specific PCR (MSP) through the design of primer sets that specifically amplify either methylated or unmethylated HPV-18 L1 DNA within bisulfite-modified sample DNA. Amplification of unmethylated and in vitro methylated HPV-18 DNA by MSP resulted in 2500 copies of either of the two L1 DNA species being detected, a satisfactory sensitivity considering that bisulfite treatment leads to the fragmentation of about 99% of sample DNA. The primers proved specific and did not generate false positive results at concentrations exceeding the lowest limit of detection by a factor of 400. DNA from carcinomas yielded PCR signals only with the methylation-specific primers, and not with primers specific for unmethylated L1 genes. The inverse result was obtained with DNA from precursor lesions that contained only hypomethylated DNA. High-grade precursor lesions and carcinomas that contained hyper- as well as hypomethylated L1 DNA yielded PCR signals with both primers. By developing a fluorescence based real-time PCR, we quantitatively analyzed samples with in vitro methylated and unmethylated L1 DNA, and could distinguish clinical samples with hyper- and hypomethylated DNA or mixtures of both DNAs. The methylation-specific and real-time PCR techniques permitted efficient HPV-18 L1 methylation analyses and open the door for larger-scale clinical studies where the utility of

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…

Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells.

PubMed

Batman, Gavin; Oliver, Anthony W; Zehbe, Ingeborg; Richard, Christina; Hampson, Lynne; Hampson, Ian N

2011-01-01

We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism. SiHa cervical carcinoma cells were stably transfected with the proteasome sensor vector pZsProSensor-1 to confirm lopinavir inhibits the proteasome in these cells. The Panorama Xpress profiler 725 antibody array was then used to analyse specific changes in protein expression in lopinavir-treated versus control untreated SiHa cells followed by PCR and western blotting. Colorimetric growth assays of lopinavir-treated E6/E7 immortalised versus control human keratinocytes were performed. Targeted small interfering RNA gene silencing followed by growth assay comparison of lopinavir-treated/untreated SiHa cells was also used. Lopinavir induced an increase in the fluorescence of pZsProSensor-1 transfected SiHa cells, indicative of proteasomal inhibition. Ribonuclease L (RNASEL) protein was shown to be up-regulated in lopinavir-treated SiHa cells, which was confirmed by PCR and western blot. Targeted silencing of RNASEL reduced the sensitivity of SiHa cells to lopinavir. Selective toxicity against E6/E7 immortalised keratinocytes versus control cells was also seen with lopinavir and was associated with up-regulated RNASEL expression. These data are consistent with the toxicity of lopinavir against HPV-positive cervical carcinoma cells being related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein RNASEL. This is supported by the drug's selective toxicity and up-regulation of RNASEL in E6/E7 immortalised keratinocytes combined with the increased resistance to lopinavir observed in SiHa cells following silencing of RNASEL gene expression.

[Rate of human papillomavirus infection in rural areas diagnosed by direct visualization with acetic acid and lugol].

PubMed

José Daniel, Flores-Alatriste; Karla Georgina, Saldivar-Gutiérrez; Josué Sarmiento-Ángeles; Jaime Claudio, Granados-Marin; Marco Antonio, Olaya-Rivera; Stark, Carlotta; Hugo, Flores-Navarro; Jaroslav, Stern-Colin

2015-07-01

Infection by HPV is a major global health problem and the main risk factor for cervical cancer with high morbidity and mortality. Simple diagnostic methods, such as visual inspection with the naked eye of the cervix with acetic acid application 5% (VAT) or solution of iodine (tincture of iodine) are simple to detect early lesions, sensitivity varies from 87 to 99% and specificity varies from 23 to 87%. To find the proportion of infection by human papillomavirus in a population of extreme poverty. Linear, observational and descriptive pilot study was done in patients of marginalized communities in extreme poverty in Chiapas (Mexico), from 1 to 30 November 2013. The existence of acetowhite lesions suggestive of virus was verified human papillomavirus, and medical history of all patients was formed for the incidence of risk factors. 214 women with age limits of 19 and 78 years, median age of 37 years were studied. Of the total, 66 (31%) had acetowhite lesions consistent with human papillomavirus at the time of the study. Marginalized populations have a higher risk of infection with human papillomavirus, consequently high rate of progression to cervical cancer due to sociodemographic characteristics, risk factors and lack of resources in health. Diagnostic tests like the simple display with acetic acid are ideal for people such as this.

Human papillomavirus hpv-16 DNA as an epitheliotropic virus that induces hyperproliferation in squamous penile tissue.

PubMed

Salazar, Edith L; Mercado, E; Calzada, L

2005-01-01

The prevalence of human papillomavirus HPV-16DNA sequences in 57 penile carcinoma biopsies was examined using the polymerase chain reaction (PCR) with type specific internal probes, employing HPV consensus primers from the L1 region. The cases comprised 39 typical squamous cell carcinoma and 18 specimens with different subtype. PCR products were analyzed and HPV-16DNA was detected in a high percentage of specimens. Thirty-eight biopsies were HPV-16DNA positive. This determination was correlated with cellular differentiation and growth pattern. Our data corroborates that squamous cell carcinoma was invariably associated with HPV-16DNA.

First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

PubMed

Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

2017-09-01

Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

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

ERIC Educational Resources Information Center

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

2016-01-01

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

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

PubMed

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

2010-01-01

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

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…

[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.

Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2

PubMed Central

Ma, Tianzhong; Su, Zhongjing; Chen, Ling; Liu, Shuyan; Zhu, Ningxia; Wen, Lifeng; Yuan, Yan; Lv, Leili; Chen, Xiancai; Huang, Jianmin; Chen, Haibin

2012-01-01

Background and Objectives Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study. PMID:22655088

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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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

PubMed Central

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

2015-01-01

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

Characterization of human papillomavirus antibodies in individuals with head and neck cancer

PubMed Central

Lang Kuhs, Krystle A.; Pawlita, Michael; Gibson, Sandra P.; Schmitt, Nicole C.; Trivedi, Sumita; Argiris, Athanassios; Kreimer, Aimée R.; Ferris, Robert L.; Waterboer, Tim

2016-01-01

BACKGROUND Human papillomavirus type 16 (HPV16) E6 antibodies are a promising biomarker of oropharyngeal cancer (OPC); however, seropositivity among non-OPC cases is not well characterized. METHODS Pre-treatment sera from 260 (38 OPC, 222 non-OPC) incident head and neck cancers diagnosed at the University of Pittsburgh between 2003 and 2006 were tested for HPV16 (L1,E1,E2,E4,E6,E7) and non-HPV16 E6 (HPV6,11,18,33) antibodies. Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven tumors was evaluated among tumors with known HPV status (n=25). RESULTS 63.2% of OPC versus 27.5% of non-OPC cases were HPV16 seropositive; HPV16 E6 seroprevalence was 60.5% and 6.3% respectively, odds ratio 22.8 (95% confidence interval [CI] 9.8–53.1). Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven OPC was 100% [95%CI:50%–100%; n=6] and 100% [95%CI:60%–100%, n=4] compared to 0% (n=2) and 0% (n=13) for non-OPC cases. CONCLUSIONS HPV16 antibodies were significantly more common in OPC versus non-OPC cases, particularly HPV16 E6 antibodies. PMID:27010729

Characterization of human papillomavirus antibodies in individuals with head and neck cancer.

PubMed

Lang Kuhs, Krystle A; Pawlita, Michael; Gibson, Sandra P; Schmitt, Nicole C; Trivedi, Sumita; Argiris, Athanassios; Kreimer, Aimée R; Ferris, Robert L; Waterboer, Tim

2016-06-01

Human papillomavirus type 16 (HPV16) E6 antibodies are a promising biomarker of oropharyngeal cancer (OPC); however, seropositivity among non-OPC cases is not well characterized. Pre-treatment sera from 260 (38 OPC, 222 non-OPC) incident head and neck cancers diagnosed at the University of Pittsburgh between 2003 and 2006 were tested for HPV16 (L1,E1,E2,E4,E6,E7) and non-HPV16 E6 (HPV6,11,18,33) antibodies. Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven tumors was evaluated among tumors with known HPV status (n=25). 63.2% of OPC versus 27.5% of non-OPC cases were HPV16 seropositive; HPV16 E6 seroprevalence was 60.5% and 6.3% respectively, odds ratio 22.8 (95% confidence interval [CI] 9.8-53.1). Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven OPC was 100% [95% CI: 50-100%; n=6] and 100% [95% CI: 60-100%, n=4] compared to 0% (n=2) and 0% (n=13) for non-OPC cases. HPV16 antibodies were significantly more common in OPC versus non-OPC cases, particularly HPV16 E6 antibodies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human Papillomavirus Vaccination Among Young Men Who Have Sex With Men and Transgender Women in 2 US Cities, 2012-2014.

PubMed

Gorbach, Pamina M; Cook, Ryan; Gratzer, Beau; Collins, Thomas; Parrish, Adam; Moore, Janell; Kerndt, Peter R; Crosby, Richard A; Markowitz, Lauri E; Meites, Elissa

2017-07-01

Since 2011, in the United States, quadrivalent human papillomavirus (HPV) vaccine has been recommended for boys aged 11 to 12 years, men through age 21, and men who have sex with men (MSM) through age 26. We assessed HPV vaccination coverage and factors associated with vaccination among young MSM (YMSM) and transgender women (TGW) in 2 cities. During 2012-2014, 808 YMSM and TGW aged 18 to 26 years reported vaccination status in a self-administered computerized questionnaire at 3 sexually transmitted disease (STD) clinics in Los Angeles and Chicago. Associations with HPV vaccination were assessed using bivariate and multivariable models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Few of the diverse participants (Hispanic/Latino, 38.0%; white, 27.0%; and black/African American, 17.9%) reported receiving 1 or more HPV vaccine doses (n = 111 [13.7%]) and even fewer reported 3 doses (n = 37 [4.6%]). A multivariable model found associations between vaccination and having a 4-year college degree or higher (aOR, 2.83; CI, 1.55-5.17) and self-reported STDs (aOR, 1.21; CI, 1.03-1.42). In a model including recommendation variables, the strongest predictor of vaccination was a health care provider recommendation (aOR, 11.85; CI, 6.70-20.98). Human papillomavirus vaccination coverage was low among YMSM and TGW in this 2-US city study. Our findings suggest further efforts are needed to reach YMSM seeking care in STD clinics, increase strong recommendations from health care providers, and integrate HPV vaccination with other clinical services such as STD testing.

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…

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…

Human papillomavirus in larynx.

PubMed

Aaltonen, Leena-Maija; Rihkanen, Heikki; Vaheri, Antti

2002-04-01

The core of the present clinical and basic research knowledge of laryngeal human papillomavirus (HPV) infection is described. Review. A computer-aided search of MEDLINE database supplemented by hand searches of key journals was conducted. One of the tumor-promoting factors in the larynx is the HPV found both in normal laryngeal epithelium and in laryngeal tumors. The most important manifestation of laryngeal HPV infection is laryngeal papillomatosis, a rare disease caused by HPV types 6 and 11. In laryngeal carcinogenesis, the role of HPV remains uncertain. The means of transmission of HPV are partly unknown, and the course of laryngeal HPV infection is unpredictable and variable. Treatment of laryngeal papillomatosis is based on surgery, especially on CO2 laser and shaver. Alpha-interferon is the drug of choice in patients whose response to surgery is poor. However, neither interferon nor other antiviral drugs are able to eradicate the virus from laryngeal mucosa. Little is known about immunological mechanisms involved in laryngeal HPV infection, but in defense against HPV cellular immunity is considered a more important mechanism than humoral immunity. A good experimental model of HPV infection is lacking in which the entire viral life cycle can take place. Organotypic cell cultures (collagen rafts) are useful, but the rate-limiting step in this method is the difficulties in culturing HPV-positive epithelial cells. Although laryngeal papillomatosis is clinically well defined, the mechanisms and treatment modalities of laryngeal HPV infection need further investigations.

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanginakudru, Sriramana, E-mail: skangina@iu.edu; DeSmet, Marsha, E-mail: mdesmet@iupui.edu; Thomas, Yanique, E-mail: ysthomas@umail.iu.edu

2015-04-15

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reducedmore » viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.« less

Design, Synthesis, and Use of Peptides Derived from Human Papillomavirus L1 Protein for the Modification of Gold Electrode Surfaces by Self-Assembled Monolayers.

PubMed

Lara Carrillo, John Alejandro; Fierro Medina, Ricardo; Manríquez Rocha, Juan; Bustos Bustos, Erika; Insuasty Cepeda, Diego Sebastián; García Castañeda, Javier Eduardo; Rivera Monroy, Zuly Jenny

2017-11-14

In order to obtain gold electrode surfaces modified with Human Papillomavirus L1 protein (HPV L1)-derived peptides, two sequences, SPINNTKPHEAR and YIK, were chosen. Both have been recognized by means of sera from patients infected with HPV. The molecules, Fc-Ahx-SPINNTKPHEAR, Ac-C- Ahx -(Fc)KSPINNTKPHEAR, Ac-C- Ahx -SPINNTKPHEAR(Fc)K, C- Ahx -SPINNTKPHEAR, and (YIK)₂- Ahx -C, were designed, synthesized, and characterized. Our results suggest that peptides derived from the SPINNTKPHEAR sequence, containing ferrocene and cysteine residues, are not stable and not adequate for electrode surface modification. The surface of polycrystalline gold electrodes was modified with the peptides C-Ahx-SPINNTKPHEAR or (YIK)₂-Ahx-C through self-assembly. The modified polycrystalline gold electrodes were characterized via infrared spectroscopy and electrochemical measurements. The thermodynamic parameters, surface coverage factor, and medium pH effect were determined for these surfaces. The results indicate that surface modification depends on the peptide sequence (length, amino acid composition, polyvalence, etc.). The influence of antipeptide antibodies on the voltammetric response of the modified electrode was evaluated by comparing results obtained with pre-immune and post-immune serum samples.

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

PubMed Central

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

2013-01-01

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

Association between high risk papillomavirus DNA and nitric oxide release in the human uterine cervix.

PubMed

Rahkola, Paivi; Mikkola, Tomi S; Ylikorkala, Olavi; Vaisanen-Tommiska, Mervi

2009-08-01

Local cervical factors may determine the outcome of human papillomavirus (HPV) infection. Nitric oxide (NO) may be one such factor, since it is produced by uterine cervical cells and it takes part in both immunological and carcinogenic reactions. We studied the association between the presence of cervical high risk (hr) HPV DNA and NO in the cervical canal in women. High risk HPV DNA status was assessed from 328 women by using a specific DNA test and the release of cervical NO was assessed as nitrate/nitrite in cervical fluid. Cervical NO was then compared between women showing different status of hr HPV DNA and different cytological and histological findings. High risk HPV DNA was present in 175/328 (53%) women. The cervical NO release in women with hr HPV DNA was 90% higher compared to hr HPV DNA negative women (p<0.001) (median 45.2 micromol/L; 95% CI 35.2-53.1 vs. 23.8 micromol/L; 95% CI 21.0-26.1). This elevation was not affected by parity, use of oral contraception, intrauterine devices, or signs of bacterial vaginosis or candida infection. Cytologically healthy epithelium and epithelium with mild cytological or histological changes showed elevated NO release if hr HPV DNA was present. The presence of hr HPV DNA is associated with an increased release of NO in the human uterine cervix. The clinical significance of this phenomenon remains open.

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

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…

Public awareness of human papillomavirus.

PubMed

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

2006-01-01

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

Role of Ultraviolet Radiation in Papillomavirus-Induced Disease

PubMed Central

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

2016-01-01

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

Role of Ultraviolet Radiation in Papillomavirus-Induced Disease.

PubMed

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

2016-05-01

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

Observations on the expression of human papillomavirus major capsid protein in HeLa cells.

PubMed

Xiao, Chang-Yi; Fu, Bing-Bing; Li, Zhi-Ying; Mushtaq, Gohar; Kamal, Mohammad Amjad; Li, Jia-Hua; Tang, Gui-Cheng; Xiao, Shuo-Shuang

2015-01-01

The goal of this study was to identify the nature of the inclusion bodies that have been found in HeLa cells (cervical cancer immortal cell line) by electron microscope and to determine whether the major capsid protein (L1) of human papillomavirus (HPV) can be expressed in HPV-positive uterine cervix cancer cells. HPV L1 protein expression in HeLa cells was detected with anti-HPV L1 multivalent mice monoclonal antibody and rabbit polyclonal anti-HPV L1 antibody by ELISA, light microscope immunohistochemistry, electron microscope immunocytochemistry and Western blotting assays. Reverse transcriptional PCR (RT-PCR) was performed to detect the transcription of L1 mRNA in HeLa cells. The immortalized human keratinocyte HeCat was used as the negative control. HPV L1 proteins reacted positively in the lysate of HeLa cells by ELISA assays. HRP labeled light microscope immunohistochemistry assay showed that there was a strong HPV L1 positive reaction in HeLa cells. Under the electron microscope, irregular shaped inclusion bodies, assembled by many small and uniform granules, had been observed in the cytoplasm of some HeLa cells. These granules could be labeled by the colloidal gold carried by HPV L1 antibody. The Western blotting assay showed that there was a L1 reaction strap at 80-85 kDa in the HeLa cell lysates, hence demonstrating the existence of HPV18 L1 in HeLa cells. RT-PCR assay showed that the L1 mRNA was transcribed in HeLa cells. The inclusion bodies found in the cytoplasm of HeLa cells are composed of HPV18 L1 protein. Since HeLa cell line is a type of cervical cancer cells, this implies that HeLa cells have the ability to express HPV L1 proteins.

Simultaneous detection, typing and quantitation of oncogenic human papillomavirus by multiplex consensus real-time PCR.

PubMed

Jenkins, Andrew; Allum, Anne-Gry; Strand, Linda; Aakre, Randi Kersten

2013-02-01

A consensus multiplex real-time PCR test (PT13-RT) for the oncogenic human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66 is described. The test targets the L1 gene. Analytical sensitivity is between 4 and 400 GU (genomic units) in the presence of 500 ng of human DNA, corresponding to 75,000 human cells. HPV types are grouped into multiplex groups of 3 or 4 resulting in the use of 4 wells per sample and permitting up to 24 samples per run (including controls) in a standard 96-well real-time PCR instrument. False negative results are avoided by (a) measuring sample DNA concentration to control that sufficient cellular material is present and (b) including HPV type 6 as a homologous internal control in order to detect PCR inhibition or competition from other (non-oncogenic) HPV types. Analysis time from refrigerator to report is 8 h, including 2.5 h hands-on time. Relative to the HC2 test, the sensitivity and specificity were respectively 98% and 83%, the lower specificity being attributable to the higher analytical sensitivity of PT13-RT. To assess type determination comparison was made with a reversed line-blot test. Type concordance was high (κ=0.79) with discrepancies occurring mostly in multiple-positive samples. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

Ozbun, Michelle A; Patterson, Nicole A

2014-08-01

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

Comparison of the AdvanSure human papillomavirus screening real-time PCR, the Abbott RealTime High Risk human papillomavirus test, and the Hybrid Capture human papillomavirus DNA test for the detection of human papillomavirus.

PubMed

Hwang, Yusun; Lee, Miae

2012-05-01

We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or sequencing. On the basis of these results, we obtained a consensus HPV result, and the performance of each test was evaluated. We also evaluated high-risk HPV 16/18 detection by using the 2 real-time PCR assays. Among the 177 samples, 65 were negative and 75 were positive in all 3 assays; however, the results of the 3 assays with 37 samples were discrepant. Compared with the consensus HPV result, the sensitivities and specificities of HC2, AdvanSure PCR, and Abbott PCR were 97.6%, 91.7%, and 86.9% and 83.9%, 98.8%, and 100.0%, respectively. For HPV type 16/18 detection, the concordance rate between the AdvanSure PCR and Abbott PCR assays was 98.3%; however, 3 samples were discrepant (positive in AdvanSure PCR and negative in Abbott PCR) and were confirmed as HPV type 16 by INNO-LiPA genotyping and/or sequencing. For HPV detection, the AdvanSure HPV Screening real-time PCR assay and the Abbott PCR assay are less sensitive but more specific than the HC2 assay, but can simultaneously differentiate type 16/18 HPV from other types.

Anogenital warts contain several distinct species of human papillomavirus.

PubMed Central

Krzyzek, R A; Watts, S L; Anderson, D L; Faras, A J; Pass, F

1980-01-01

Anogenital warts from 26 patients were examined for the presence of human papillomavirus (HPV). Although no whole, intact virus could be identified, varying amounts of nonintegrated HPV DNA were detected in 18 tissue specimens (70%) by employing both an agarose gel-ethidium bromide staining method and the Southern blot hybridization procedure. When hybridization analysis was performed under stringent conditions, six anogenital warts were observed to contain HPV genomic sequences related to either of the cutaneous viruses HPV type 1 (HPV-1) or HPV-2. In 12 tissue samples lacking sequence homology to either HPV-1 or HPV-2 under stringent conditions, HPV-related sequences were detected when the hybridization was performed under less stringent conditions, indicating that an HPV distinct from both HPV-1 and HPV-2 is also associated with these lesions. This anogenital HPV also appeared to be distinct from the other characterized types of HPV. These data indicate that at least three HPVs are associated with anogenital wart disease. Images PMID:6255208

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

PubMed

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

2015-01-01

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

Human papillomavirus vaccination among adolescents in Georgia.

PubMed

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.

Relationship Between Pelvic Organ Prolapse and Non-Human Papillomavirus Pap Smear Abnormalities.

PubMed

Menhaji, Kimia; Harvie, Heidi S; Cheston, Emily; Levin, Pamela J; Arya, Lily A; Andy, Uduak U

2017-07-13

The aim of this study was to determine the association between pelvic organ prolapse (POP) and non-human papillomavirus (HPV) Papanicolaou (Pap) smear abnormalities. This was a retrospective cohort study of women aged 40 to 70 years who presented for consultation at our institution between 2010 and 2015 and had results of a Pap smear and HPV test available within 5 years of their visit. We extracted demographic information, medical and social history, Pap smear, and HPV results from the electronic medical record. Associations between the presence of POP and non-HPV Pap smear abnormalities were estimated using univariable and multivariable analyses. We reviewed 1590 charts and excluded 980 women, leaving 610 women in the study: 183 with POP and 427 without POP. Women with POP were significantly older (58.2 ± 7.2 vs 55.6 ± 6.6, P < 0.01) and more likely to have a remote (>10 year) history of abnormal Pap smear (24.0% vs 14.8%, P < 0.01). The rate of non-HPV-associated abnormal Pap smears was higher in the POP group than in the non-POP group (12/183 [6.6%] vs 12/427 [2.8%], P = 0.029). In the POP group, the rate of non-HPV Pap smear abnormality was significantly associated with increasing prolapse stage (stage 1: 0/16 [0%], stage 2: 5/77 [6.5%], stage 3: 3/73 [4.1%], stage 4: 4/17 [23.5%]; P = 0.02). After controlling for age and remote history of abnormal Pap smear, the odds ratio for non-HPV Pap smear abnormalities in the POP group remained significant (2.49; 95% confidence interval, 1.08-5.79). Human papillomavirus-negative Pap smear abnormalities may be related to POP. Our findings have important implications for surgeons seeking to leave the cervix in situ in women with POP.

Scale-Up of an Human Papillomavirus Testing Implementation Program in El Salvador.

PubMed

Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Morales Velado, Mario; Felix, Juan; Castle, Philip E; Kim, Jane; Gage, Julia C

2017-01-01

The Cervical Cancer Prevention in El Salvador is a demonstration project to introduce a lower-cost human papillomavirus (HPV)-DNA test into a public sector project. Started in October 2012, The Cervical Cancer Prevention in El Salvador consists of 3 phases and will ultimately screen 30,000 women. Results of phase 2 of the project are presented. The objective of this project was to compare colposcopy and noncolposcopy-based management for HPV-positive women. In phase 2, a total of 8,050 women, aged 30 to 49 years, were screened; 6,761 provided both self- and provider-collected specimens and 1,289 provided only provider-testing specimens. HPV results from self-collected specimens were not used in clinical management decisions. Women with provider-collected HPV-positive results were treated based on the strategy assigned to their community; the strategy was colposcopy management (CM) or screen-and-treat (ST) management if they were cryotherapy eligible or colposcopy if not eligible. Outcomes were assessed 6 months after screening. Overall, 489 (12.3%) of 3,963 women receiving CM and 465 (11.4%) of 4,087 women receiving ST tested HPV positive. In the CM cohort, 216 (44.2%) of 489 completed their intervention (203 treated, 11 diagnosed negative, 2 pregnant). In the ST cohort, 411 (88.4%) of 465 completed their intervention (407 treated, 2 diagnosed negative, 1 pregnant). Overall agreement between HPV test results from self-collected and provider-collected specimens was 93.7%, with a κ value of 0.70 (95% CI = 0.68-0.73). Human papillomavirus testing with ST management resulted in an approximately twice completion rate compared with CM management. Agreement between self- and provider-based sampling was good and might be used to extend screening to women in areas that are more difficult to reach.

Scale-Up of an Human Papillomavirus Testing Implementation Program in El Salvador

PubMed Central

Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Morales Velado, Mario; Felix, Juan; Castle, Philip E.; Kim, Jane; Gage, Julia C.

2017-01-01

Objective The Cervical Cancer Prevention in El Salvador is a demonstration project to introduce a lower-cost human papillomavirus (HPV)-DNA test into a public sector project. Started in October 2012, The Cervical Cancer Prevention in El Salvador consists of 3 phases and will ultimately screen 30,000 women. Results of phase 2 of the project are presented. The objective of this project was to compare colposcopy and noncolposcopy-based management for HPV-positive women. Material and Methods In phase 2, a total of 8,050 women, aged 30 to 49 years, were screened; 6,761 provided both self- and provider-collected specimens and 1,289 provided only provider-testing specimens. HPV results from self-collected specimens were not used in clinical management decisions. Women with provider-collected HPV-positive results were treated based on the strategy assigned to their community; the strategy was colposcopy management (CM) or screen-and-treat (ST) management if they were cryotherapy eligible or colposcopy if not eligible. Outcomes were assessed 6 months after screening. Results Overall, 489 (12.3%) of 3,963 women receiving CM and 465 (11.4%) of 4,087 women receiving ST tested HPV positive. In the CM cohort, 216 (44.2%) of 489 completed their intervention (203 treated, 11 diagnosed negative, 2 pregnant). In the ST cohort, 411 (88.4%) of 465 completed their intervention (407 treated, 2 diagnosed negative, 1 pregnant). Overall agreement between HPV test results from self-collected and provider-collected specimens was 93.7%, with a κ value of 0.70 (95% CI = 0.68–0.73). Conclusions Human papillomavirus testing with ST management resulted in an approximately twice completion rate compared with CM management. Agreement between self- and provider-based sampling was good and might be used to extend screening to women in areas that are more difficult to reach. PMID:27922905

Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.

PubMed

Da Silva, Diane M; Movius, Carly A; Raff, Adam B; Brand, Heike E; Skeate, Joseph G; Wong, Michael K; Kast, W Martin

2014-03-01

Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events. Copyright © 2014 Elsevier Inc. All rights reserved.

Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

PubMed Central

Didelot-Rousseau, M-N; Nagot, N; Costes-Martineau, V; Vallès, X; Ouedraogo, A; Konate, I; Weiss, H A; Van de Perre, P; Mayaud, P; Segondy, M

2006-01-01

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2–7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR)=1.61, 95% confidence interval (CI): 1.4–1.8). High-risk HPV types (71 vs 40%, PR=1.79, 95% CI: 1.5–2.2), in particular HPV-16+18 (22 vs 9%, PR=2.35, 95% CI: 1.4–4.0), and multiple HPV infections (56 vs 23%, PR=2.45, 95% CI: 1.8–3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio=17.0; 95% CI 2.2–134.1, P=0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine. PMID:16832413

How to Inform: Comparing Written and Video Education Interventions to Increase Human Papillomavirus Knowledge and Vaccination Intentions in Young Adults

ERIC Educational Resources Information Center

Krawczyk, Andrea; Lau, Elsa; Perez, Samara; Delisle, Vanessa; Amsel, Rhonda; Rosberger, Zeev

2012-01-01

Objective: To compare the efficacy of 2 human papillomavirus (HPV) educational interventions on increasing HPV knowledge and vaccination intentions in college students. Participants: Male (n = 60) and female (n = 140) undergraduates (M[subscript age] = 20.4, SD = 2.3) recruited from a university in Montreal, Quebec, Canada, from October 2009 to…

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.

Human papillomavirus in the oral cavity of children.

PubMed

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

2011-02-01

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

Will vaccination against human papillomavirus prevent eye disease? A review of the evidence.

PubMed

Hughes, D S; Powell, N; Fiander, A N

2008-04-01

The role of human papillomavirus (HPV) infection in eye disease is controversial. However, a recent case illustrates the possible role of HPV in conjunctival squamous carcinoma and the potentially devastating effects of this disease. The development of two vaccines to prevent infection with HPV types most commonly associated with anogenital cancers has led to debate about the pros and cons of a national immunisation programme to prevent cervical cancer. The introduction of such a vaccination programme may have an additional beneficial effect on the occurrence of some head and neck, including ocular, cancers. This review discusses the nature of papillomaviruses, mechanisms of infection and carcinogenesis, the possible role of HPV in eye disease, and finally the likely impact of the new prophylactic vaccines.

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

PubMed

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

2018-03-01

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

In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: potential treatment for genital warts.

PubMed Central

Cowsert, L M; Fox, M C; Zon, G; Mirabelli, C K

1993-01-01

Papillomaviruses induce benign proliferative lesions, such as genital warts, in humans. The E2 gene product is thought to play a major role in the regulation of viral transcription and DNA replication and may represent a rational target for an antisense oligonucleotide drug action. Phosphorothioate oligonucleotides complementary to E2 mRNAs were synthesized and tested in a series of in vitro bovine papillomavirus (BPV) and human papillomavirus (HPV) models for the ability to inhibit E2 transactivation and virus-induced focus formation. The most active BPV-specific compounds were complementary to the mRNA cap region (ISIS 1751), the translation initiation region for the full-length E2 transactivator (ISIS 1753), and the translation initiation region for the E2 transrepressor mRNA (ISIS 1755). ISIS 1751 and ISIS 1753 were found to reduce E2-dependent transactivation and viral focus formation in a sequence-specific and concentration-dependent manner. ISIS 1755 increased E2 transactivation in a dose-dependent manner but had no effect on focus formation. Oligonucleotides with a chain length of 20 residues had optimal activity in the E2 transactivation assay. On the basis of the above observations, ISIS 2105, a 20-residue phosphorothioate oligonucleotide targeted to the translation initiation of both HPV type 6 (HPV-6) and HPV-11 E2 mRNA, was designed and shown to inhibit E2-dependent transactivation by HPV-11 E2 expressed from a surrogate promoter. These observations support the rationale of E2 as a target for antiviral therapy against papillomavirus infections and specifically identify ISIS 2105 as a candidate antisense oligonucleotide for the treatment of genital warts induced by HPV-6 and HPV-11. Images PMID:8383937

The full transcription map of mouse papillomavirus type 1 (MmuPV1) in mouse wart tissues

PubMed Central

Kim, Bong-Hyun; Gotte, Deanna; Chen, Xiongfong; Cam, Maggie; Lambert, Paul F.

2017-01-01

Mouse papillomavirus type 1 (MmuPV1) provides, for the first time, the opportunity to study infection and pathogenesis of papillomaviruses in the context of laboratory mice. In this report, we define the transcriptome of MmuPV1 genome present in papillomas arising in experimentally infected mice using a combination of RNA-seq, PacBio Iso-seq, 5’ RACE, 3’ RACE, primer-walking RT-PCR, RNase protection, Northern blot and in situ hybridization analyses. We demonstrate that the MmuPV1 genome is transcribed unidirectionally from five major promoters (P) or transcription start sites (TSS) and polyadenylates its transcripts at two major polyadenylation (pA) sites. We designate the P7503, P360 and P859 as “early” promoters because they give rise to transcripts mostly utilizing the polyadenylation signal at nt 3844 and therefore can only encode early genes, and P7107 and P533 as “late” promoters because they give rise to transcripts utilizing polyadenylation signals at either nt 3844 or nt 7047, the latter being able to encode late, capsid proteins. MmuPV1 genome contains five splice donor sites and three acceptor sites that produce thirty-six RNA isoforms deduced to express seven predicted early gene products (E6, E7, E1, E1^M1, E1^M2, E2 and E8^E2) and three predicted late gene products (E1^E4, L2 and L1). The majority of the viral early transcripts are spliced once from nt 757 to 3139, while viral late transcripts, which are predicted to encode L1, are spliced twice, first from nt 7243 to either nt 3139 (P7107) or nt 757 to 3139 (P533) and second from nt 3431 to nt 5372. Thirteen of these viral transcripts were detectable by Northern blot analysis, with the P533-derived late E1^E4 transcripts being the most abundant. The late transcripts could be detected in highly differentiated keratinocytes of MmuPV1-infected tissues as early as ten days after MmuPV1 inoculation and correlated with detection of L1 protein and viral DNA amplification. In mature warts

Type-Specific Detection of 30 Oncogenic Human Papillomaviruses by Genotyping both E6 and L1 Genes

PubMed Central

Peng, Junping; Gao, Lei; Guo, Junhua; Wang, Ting; Wang, Ling; Yao, Qing; Zhu, Haijun

2013-01-01

Human papillomavirus (HPV) is the principal cause of invasive cervical cancer and benign genital lesions. There are currently 30 HPV types linked to cervical cancer. HPV infection also leads to other types of cancer. We developed a 61-plex analysis of these 30 HPV types by examining two genes, E6 and L1, using MassARRAY matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS). Two hundred samples from homosexual males (HM) were screened by PCR-MS and MY09/MY11 primer set-mediated PCR (MY-PCR) followed by sequencing. One hundred thirty-five formalin-fixed, paraffin-embedded (FFPE) cervical cancer samples were also analyzed by PCR-MS, and results were compared to those of the commercially available GenoArray (GA) assay. One or more HPV types were identified in 64.5% (129/200) of the samples from HM. Comprising all 30 HPV types, PCR-MS detected 51.9% (67/129) of samples with multiple HPV types, whereas MY-PCR detected only one single HPV type in these samples. All PCR-MS results were confirmed by MY-PCR. In the cervical cancer samples, PCR-MS and GA detected 97% (131/135) and 90.4% (122/135) of HPV-positive samples, respectively. PCR-MS and GA results were fully concordant for 122 positive and 4 negative samples. The sequencing results for the 9 samples that tested negative by GA were completely concordant with the positive PCR-MS results. Multiple HPV types were identified in 25.2% (34/135) and 55.6% (75/135) of the cervical cancer samples by GA and PCR-MS, respectively, and results were confirmed by sequencing. The new assay allows the genotyping of >1,000 samples per day. It provides a good alternative to current methods, especially for large-scale investigations of multiple HPV infections and degraded FFPE samples. PMID:23152557

Prevalence of human papillomavirus and herpes simplex virus type 2 infection in Korean commercial sex workers.

PubMed

Yun, Haesun; Park, Jeongjoo; Choi, Inkyung; Kee, Meekyung; Choi, Byeongsun; Kim, Sungsoon

2008-02-01

In order to investigate the prevalence of sexually transmitted viruses such as human papillomavirus (HPV) and herpes simplex virus (HSV) in Korean commercial sex workers (CSWs), we selected 188 CSWs (age range 20-44 years, median age 24 years) who regularly visited one public health center in Seoul, Korea. HPV genotypes were analyzed by using a HPV DNA chip, and an enzyme-linked immunosorbent assay (ELISA) was used to detect type-specific IgG against HSV2 antibody identifying seropositivity for HSV2 infection. Polymerase chain reaction (PCR) was performed with specific primers to detect HPV and HSV1/2 in cervical swabs from the CSWs. The prevalence of HPV infection was 83.5% in 188 cervical swab specimens and the main high-risk HPV genotypes were HPV16, 18, 56, and 58. The principal low-risk HPV genotypes were HPV6 and 11. The prevalence of HSV1/2 DNA was 13.8% and HSV2 seroprevalence was 86.2%. These results suggest that high frequencies of HPV and HSV2 infection might contribute to the rapid spread of STD viruses in CSWs in Korea. Additionally, an understanding of why high-risk HPV genotypes are so prevalent could provide guidelines for prophylactic vaccine development in Korea.

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

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

PubMed

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

2011-01-01

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

Human papillomavirus types and recurrent cervical warts

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 CINsmore » 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.« less

Transcriptome analysis of Mastomys natalensis papillomavirus in productive lesions after natural infection.

PubMed

Salvermoser, Melanie; Chotewutmontri, Sasithorn; Braspenning-Wesch, Ilona; Hasche, Daniel; Rösl, Frank; Vinzón, Sabrina E

2016-07-01

Mastomys coucha, an African rodent, is a useful animal model of papillomavirus infection, as it develops both premalignant and malignant skin tumors as a consequence of a persistent infection with Mastomys natalensis papillomavirus (MnPV). In this study, we mapped the MnPV transcriptome in productive lesions by both classical molecular techniques and high-throughput RNA sequencing. Combination of these methods revealed a complex and comprehensive transcription map, with novel splicing events not described in other papillomaviruses. Furthermore, these splicing occurrences could potentially lead to the expression of novel E2, E1∧E4, E7 and L2 isoforms. Expression level estimation of each transcript showed that late-region mRNAs considerably outnumber early transcripts, with species coding for L1 and E1∧E4 being the most abundant. In summary, the full transcription map assembled in this study will allow us to further understand MnPV gene expression and the mechanisms that lead to natural tumour development.

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,…

Identification of a novel species of papillomavirus in giraffe lesions using nanopore sequencing.

PubMed

Vanmechelen, Bert; Bertelsen, Mads Frost; Rector, Annabel; Van den Oord, Joost J; Laenen, Lies; Vergote, Valentijn; Maes, Piet

2017-03-01

Papillomaviridae form a large family of viruses that are known to infect a variety of vertebrates, including mammals, reptiles, birds and fish. Infections usually give rise to minor skin lesions but can in some cases lead to the development of malignant neoplasia. In this study, we identified a novel species of papillomavirus (PV), isolated from warts of four giraffes (Giraffa camelopardalis). The sequence of the L1 gene was determined and found to be identical for all isolates. Using nanopore sequencing, the full sequence of the PV genome could be determined. The coding region of the genome was found to contain seven open reading frames (ORF), encoding the early proteins E1, E2 and E5-E7 as well as the late proteins L1 and L2. In addition to these ORFs, a region located within the E2 gene is thought, based on sequence similarities to other papillomaviruses, to encode an E4 protein, although no start codon could be identified. Based on the sequence of the L1 gene, this novel PV was found to be most similar to Capreolus capreolus papillomavirus 1 (CcaPV1), with 67.96% nucleotide identity. We therefore suggest that the virus identified here is given the name Giraffa camelopardalis papillomavirus 1 (GcPV1) and is classified as a novel species within the genus Deltapapillomavirus, in line with the current guidelines for the nomenclature and classification of PVs. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Early experience with human papillomavirus vaccine introduction in the United States, Canada and Australia.

PubMed

Shefer, Abigail; Markowitz, Lauri; Deeks, Shelley; Tam, Theresa; Irwin, Kathleen; Garland, Suzanne M; Schuchat, Anne

2008-08-19

Successful incorporation of a new vaccine into a nation's vaccination program requires addressing a number of issues, including: 1) establishing national recommendations; 2) assuring education of and acceptance by the public and medical community; 3) establishing and maintaining an appropriate infrastructure for vaccine delivery; 4) financing the vaccine and the program, in addition to political will. This article reviews the early experience with implementation of human papillomavirus (HPV) vaccination programs. It focuses on the United States of America and Canada and provides a brief report on Australia, where introduction is underway.

Reported changes in sexual behaviour and human papillomavirus knowledge in Peruvian female sex workers following participation in a human papillomavirus vaccine trial.

PubMed

Brown, B; Blas, M M; Heidari, O; Carcamo, C; Halsey, N A

2013-07-01

Limited data exist on the effect of clinical trial participation on sexual behavioural change. Two hundred female sex workers working in Lima, Peru received human papillomavirus (HPV) vaccine in either the standard (0, 2, 6 months) or modified (0, 3, 6 months) schedule. Participants received comprehensive screening and treatment for sexually transmitted infections (STIs), counselling on safe sex practices, education about HPV and the HPV vaccine, contraceptives (oral and condoms) and family planning at each visit. We assessed vaccine completion rates, change in sexual practices, and changes in HPV knowledge before and after participation in the vaccine trial. There were high rates of vaccine completion, 91% overall. The estimated number of reported new and total clients over a 30-day period decreased significantly (P < 0.001). Knowledge about HPV and HPV-related disease increased among all participants. In addition, all participants listed at least one preventive strategy during the month 7 follow-up survey.

[Human papillomavirus and cervical cancer in México: a constant struggle].

PubMed

Torres-Poveda, Kirvis; Madrid-Marina, Vicente

2015-01-01

Given that human papillomavirus and cervical cancer are a health problem in México, since they affect women of reproductive age and have a negative impact on our society, it is crucial to prevent those diseases and to raise awareness among physicians who deal with their clinical and therapeutic management. That is the reason why we show three Original contributions and 13 Current themes in this supplement of the Revista Médica del Instituto Mexicano del Seguro Social.

The Enigmatic Origin of Papillomavirus Protein Domains

PubMed Central

Kirsip, Heleri; Gaston, Kevin

2017-01-01

Almost a century has passed since the discovery of papillomaviruses. A few decades of research have given a wealth of information on the molecular biology of papillomaviruses. Several excellent studies have been performed looking at the long- and short-term evolution of these viruses. However, when and how papillomaviruses originate is still a mystery. In this study, we systematically searched the (sequenced) biosphere to find distant homologs of papillomaviral protein domains. Our data show that, even including structural information, which allows us to find deeper evolutionary relationships compared to sequence-only based methods, only half of the protein domains in papillomaviruses have relatives in the rest of the biosphere. We show that the major capsid protein L1 and the replication protein E1 have relatives in several viral families, sharing three protein domains with Polyomaviridae and Parvoviridae. However, only the E1 replication protein has connections with cellular organisms. Most likely, the papillomavirus ancestor is of marine origin, a biotope that is not very well sequenced at the present time. Nevertheless, there is no evidence as to how papillomaviruses originated and how they became vertebrate and epithelium specific. PMID:28832519

The Enigmatic Origin of Papillomavirus Protein Domains.

PubMed

Puustusmaa, Mikk; Kirsip, Heleri; Gaston, Kevin; Abroi, Aare

2017-08-23

Almost a century has passed since the discovery of papillomaviruses. A few decades of research have given a wealth of information on the molecular biology of papillomaviruses. Several excellent studies have been performed looking at the long- and short-term evolution of these viruses. However, when and how papillomaviruses originate is still a mystery. In this study, we systematically searched the (sequenced) biosphere to find distant homologs of papillomaviral protein domains. Our data show that, even including structural information, which allows us to find deeper evolutionary relationships compared to sequence-only based methods, only half of the protein domains in papillomaviruses have relatives in the rest of the biosphere. We show that the major capsid protein L1 and the replication protein E1 have relatives in several viral families, sharing three protein domains with Polyomaviridae and Parvoviridae . However, only the E1 replication protein has connections with cellular organisms. Most likely, the papillomavirus ancestor is of marine origin, a biotope that is not very well sequenced at the present time. Nevertheless, there is no evidence as to how papillomaviruses originated and how they became vertebrate and epithelium specific.

MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin.

PubMed

Geng, Dianzhong; Song, Xiaohua; Ning, Fangling; Song, Qianhua; Yin, Honghua

2015-05-01

Previous studies confirmed that high-risk human papillomavirus (HR-HPV) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced miR-34a expression during carcinogenesis. However, the downstream targets of miR-34a and their roles are still not well understood. This study explored the regulative role of miR-34a on E2F3 and survivin expression and the viability and invasion of HPV-positive cervical cancer cells. MiR-34a and survivin expression in 56 cases of HR-HPV-positive patients, 28 cases of HR-HPV-negative patients, and 28 normal cases without HR-HPV infections were measured. Human papillomavirus-18-positive HeLa cervical cancer cells and HPV-16-positive SiHa cells were used to explore the effect of miR-34a on cell viability and invasion. The molecular target of miR-34a was also explored in cervical cancer cells. The results showed that miR-34a overexpression could inhibit HPV-positive cancer cell viability, whereas its downregulation promoted cell viability. E2F3 is a direct target of miR-34a in HPV-positive cervical cancer cells. By targeting E2F3, miR-34a could regulate the expression of survivin. Thus, through regulating E2F3 and survivin, miR-34a could reduce the viability and invasion of HPV-positive cervical cancer cells. This study confirmed a novel miR-34a-E2F3-survivin axis in the tumor suppressor role of miR-34a in cervical cancer.

Felis catus papillomavirus type-2 but not type-1 is detectable and transcriptionally active in the blood of healthy cats.

PubMed

Altamura, G; Jebara, G; Cardeti, G; Borzacchiello, G

2018-04-01

Papillomaviruses (PVs) are small DNA viruses that induce benign and/or malignant epithelial tumours in different species, including the domestic cat (Felis catus). To date, five F. catus papillomavirus genotypes have been identified (FcaPV-1 to FcaPV-5). FcaPV-1 is associated with skin and oral benign lesions, while FcaPV-2 infection is widely associated with feline squamous cell carcinomas. Several human and animal PVs have been found in body fluids such as peripheral blood; however, the presence of FcaPVs in non-epithelial tissues has not previously been investigated. The aim of this study was to assess the presence and gene expression of FcaPV-1 and FcaPV-2 in the blood of healthy cats. We detected FcaPV-2 DNA in 26 of 103 (25%) blood samples. Importantly, FcaPV-2 L1, E2, E6 and E7 genes were found to be expressed in 3 (25%), 11 (92%), 6 (50%) and 5 (42%) of the samples available for mRNA analysis, respectively. FcaPV-1 was not detected in any of the blood samples analysed here. The data obtained in this work suggest active and eventually productive infection of FcaPV-2 in the blood of healthy cats, implying a possible role in intra-individual spreading as well as in vertical and horizontal transmission. © 2017 Blackwell Verlag GmbH.

Cellular immunogenicity of human papillomavirus vaccines Cervarix and Gardasil in adults with HIV infection

PubMed Central

Zurek Munk-Madsen, Maria; Toft, Lars; Kube, Tina; Richter, Rolf; Ostergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Kaufmann, Andreas M.

2018-01-01

ABSTRACT Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation. PMID:29172992

Cellular immunogenicity of human papillomavirus vaccines Cervarix and Gardasil in adults with HIV infection.

PubMed

Zurek Munk-Madsen, Maria; Toft, Lars; Kube, Tina; Richter, Rolf; Ostergaard, Lars; Søgaard, Ole S; Tolstrup, Martin; Kaufmann, Andreas M

2018-04-03

Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154 + /IL-2 + or CD154 + / IFNγ + ) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.

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

PubMed

Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

2015-02-01

Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

Fas Ligand-Mediated Lysis of Self Bystander Targets by Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes

PubMed Central

Smyth, Mark J.; Krasovskis, Erika; Johnstone, Ricky W.

1998-01-01

Mouse cytotoxic T lymphocytes (CTL) reactive with a H-2Db-presented 9-mer peptide of the human papillomavirus type 16 protein E749-57 (RAHYNIVTF) were generated from the spleen cells of wild-type C57BL/6 (B6) or B6 perforin-deficient (B6.P0) mice. CD8+ B6 CTL displayed peptide-specific perforin- and Fas-mediated lysis of E7-transfected mouse RMA lymphoma cells (RMA-E7), while CD8+ CTL from B6.P0 mice lysed RMA-E7 cells via Fas ligand (FasL) exclusively. Rapid and efficient lysis of syngeneic bystander B6 blasts or RMA cells by either B6 or B6.P0 Ag-activated CTL was mediated by a FasL-Fas mechanism. Fas-resistant bystanders were not lysed, nor were allogeneic Fas-sensitive C3H/HeJ (H-2k) or BALB/c (H-2d) bystander blasts. Interestingly, however, phorbol myristate acetate-ionomycin preactivation of B6.P0 effectors enabled lysis of allogeneic H-2k and H-2d bystanders even in the absence of antigenic stimulation. Lysis of syngeneic bystander cells was always FasL-Fas dependent and required effector-bystander contact and, in particular, an interaction between CTL LFA-1 and bystander ICAM-1. Thus, in the context of major histocompatibility complex class I molecule-peptide ligation of the T-cell receptors of CD8+ CTL, neighboring bystander cells that are syngeneic and Fas sensitive and express the adhesion molecule ICAM-1 are potential targets of CTL attack. PMID:9621057

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.

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

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.

Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17-36.

PubMed

Bywaters, Stephanie M; Brendle, Sarah A; Tossi, Kerstin P; Biryukov, Jennifer; Meyers, Craig; Christensen, Neil D

2017-11-10

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17-36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers.

Immune evasion mechanisms of human papillomavirus: An update.

PubMed

Steinbach, Alina; Riemer, Angelika B

2018-01-15

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

Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status.

PubMed

Vlashi, Erina; Chen, Allen M; Boyrie, Sabrina; Yu, Garrett; Nguyen, Andrea; Brower, Philip A; Hess, Clayton B; Pajonk, Frank

2016-04-01

To test the hypothesis that the radiation response of cancer stem cells (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation response of the bulk tumor populations, that radiation therapy (RT) can dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced dedifferentiation depends on the HPV status. Records of a cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell lines expressing a reporter for CSCs, we characterized HPV-positive and HPV-negative lines via flow cytometry, sphere-forming capacity assays in vitro, and limiting dilution assays in vivo. Non-CSCs were treated with different doses of radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via flow cytometry and quantitative reverse transcription-polymerase chain reaction for re-expression of reprogramming factors. Patients with HPV-positive tumors have superior overall survival and local-regional control. Human papillomavirus-positive HNSCC cell lines have lower numbers of CSCs, which inversely correlates with radiosensitivity. Human papillomavirus-negative HNSCC cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non-CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation compared with HPV-positive lines, and RT induced re-expression of Yamanaka reprogramming factors. Supporting the favorable prognosis of HPV-positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced dedifferentiation depends on the HPV status of the tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of 2-Dose and 3-Dose 9-Valent Human Papillomavirus Vaccine Schedules in the United States: A Cost-effectiveness Analysis.

PubMed

Laprise, Jean-François; Markowitz, Lauri E; Chesson, Harrell W; Drolet, Mélanie; Brisson, Marc

2016-09-01

A recent clinical trial using the 9-valent human papillomavirus virus (HPV) vaccine has shown that antibody responses after 2 doses are noninferior to those after 3 doses, suggesting that 2 and 3 doses may have comparable vaccine efficacy. We used an individual-based transmission-dynamic model to compare the population-level effectiveness and cost-effectiveness of 2- and 3-dose schedules of 9-valent HPV vaccine in the United States. Our model predicts that if 2 doses of 9-valent vaccine protect for ≥20 years, the additional benefits of a 3-dose schedule are small as compared to those of 2-dose schedules, and 2-dose schedules are likely much more cost-efficient than 3-dose schedules. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

PubMed

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

2017-08-01

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

Acceptability of School-Based Health Centers for Human Papillomavirus Vaccination Visits: A Mixed-Methods Study

ERIC Educational Resources Information Center

Hansen, Caitlin E.; Okoloko, Edirin; Ogunbajo, Adedotun; North, Anna; Niccolai, Linda M.

2017-01-01

Background: Countries with high human papillomavirus (HPV) vaccination rates have achieved this success largely through school-based vaccination. Using school-based health centers (SBHCs) in the United States, where HPV vaccine remains underutilized, could improve uptake. In this mixed-methods study, we examined acceptability, facilitators, and…

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…

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

PubMed

Fesenfeld, Michaela; Hutubessy, Raymond; Jit, Mark

2013-08-20

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

Human papillomavirus vaccines versus cervical cancer screening.

PubMed

Stanley, M

2008-08-01

Prophylactic vaccination with human papillomavirus (HPV) virus-like particle (VLP) vaccines against HPV 16 and HPV 18, which are the cause of 70% or more of cervical cancers in women, has transformed our prospects for reducing the incidence of this disease on a global scale. HPV VLP vaccines are immunogenic, well tolerated and show remarkable efficacy, achieving >98% protection in randomised clinical trials against the obligate precursor lesions cervical intraepithelial neoplasia grade 2/3 (CIN2/3) and adenocarcinoma in situ. The implementation of these vaccines as a public health intervention is, however, complex. Cervical cancer screening can be a highly effective secondary intervention, but in the developing world these programmes are either not available or are ineffective. HPV vaccination represents the most effective intervention in that scenario. In countries with successful well-organised cervical cancer screening programmes, such as the UK, the cost-effectiveness of vaccination as opposed to screening is a major factor. Screening will have to continue, as only two of the 15 oncogenic HPV types are in the vaccines and for two to three decades at least unvaccinated sexually active women will remain at risk for the disease. However, if both vaccination and screening are combined then the virtual elimination of cervical cancer and the other HPV 16 and 18-associated cancers is possible.

Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

PubMed

Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

2013-02-01

To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

Characterization of Mus musculus Papillomavirus 1 Infection In Situ Reveals an Unusual Pattern of Late Gene Expression and Capsid Protein Localization

PubMed Central

Handisurya, Alessandra; Day, Patricia M.; Thompson, Cynthia D.; Buck, Christopher B.; Pang, Yuk-Ying S.; Lowy, Douglas R.

2013-01-01

Full-length genomic DNA of the recently identified laboratory mouse papillomavirus 1 (MusPV1) was synthesized in vitro and was used to establish and characterize a mouse model of papillomavirus pathobiology. MusPV1 DNA, whether naked or encapsidated by MusPV1 or human papillomavirus 16 (HPV 16) capsids, efficiently induced the outgrowth of papillomas as early as 3 weeks after application to abraded skin on the muzzles and tails of athymic NCr nude mice. High concentrations of virions were extracted from homogenized papillomatous tissues and were serially passaged for >10 generations. Neutralization by L1 antisera confirmed that infectious transmission was capsid mediated. Unexpectedly, the skin of the murine back was much less susceptible to virion-induced papillomas than the muzzle or tail. Although reporter pseudovirions readily transduced the skin of the back, infection with native MusPV1 resulted in less viral genome amplification and gene expression on the back, including reduced expression of the L1 protein and very low expression of the L2 protein, results that imply skin region-specific control of postentry aspects of the viral life cycle. Unexpectedly, L1 protein on the back was predominantly cytoplasmic, while on the tail the abundant L1 was cytoplasmic in the lower epithelial layers and nuclear in the upper layers. Nuclear localization of L1 occurred only in cells that coexpressed the minor capsid protein, L2. The pattern of L1 protein staining in the infected epithelium suggests that L1 expression occurs earlier in the MusPV1 life cycle than in the life cycle of high-risk HPV and that virion assembly is regulated by a previously undescribed mechanism. PMID:24067981

Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus

PubMed Central

Dey, Sumanta; De, Antara; Nandy, Ashesh

2016-01-01

Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time. PMID:27279731

Human Immunodeficiency Virus Status Differentially Associated With Genital and Anal Human Papillomavirus Infection Among Chinese Men Who Have Sex With Men: A Cross-Sectional Survey.

PubMed

Qian, Han-Zhu; Hu, Yifei; Carlucci, James G; Yin, Lu; Li, Xiangwei; Giuliano, Anna R; Li, Dongliang; Gao, Lei; Shao, Yiming; Vermund, Sten H

2017-11-01

Little is known about human papillomavirus (HPV) infection and genotypes when considering both anatomic site and human immunodeficiency virus (HIV) status among men who have sex with men (MSM) in low- and middle-income countries. A cross-sectional study was conducted among MSM in Beijing, China. HIV serostatus was determined, and genital and anal HPV genotyping were performed from respective swabs. Of 1155 MSM, 817 (70.7%) had testing for genital (611; 52.9%) and/or anal (671; 58.1%) HPV. Preference for insertive anal sex (adjusted odds ratio [aOR], 2.60; 95% confidence interval [CI], 1.42-4.75) and syphilis (aOR, 1.50; 95% CI, 1.01-2.23) were associated with genital HPV. Inconsistent condom use during receptive anal sex (aOR, 1.82; 95% CI, 1.17-2.84), and HIV seropositivity (aOR, 2.90; 95% CI, 1.91-4.42) were associated with anal HPV. Among 465 (40.3%) MSM with specimens from both anatomic sites, anal HPV (68%) was more common than genital HPV (37.8%). Prevalence of anal HPV was higher among HIV-infected than uninfected MSM (P < 0.01). Some oncogenic HPV types were more commonly found at the anal site of HIV-infected MSM (P < 0.01). Human papillomavirus is highly prevalent among Chinese MSM. Anal HPV was more common than genital HPV, and HIV seropositivity was associated with oncogenic HPV types at the anal site.

Immune responses in macaques to a prototype recombinant adenovirus live oral human papillomavirus 16 vaccine.

PubMed

Berg, Michael G; Adams, Robert J; Gambhira, Ratish; Siracusa, Mark C; Scott, Alan L; Roden, Richard B S; Ketner, Gary

2014-09-01

Immunization with human papillomavirus (HPV) L1 virus-like particles (VLPs) prevents infection with HPV. However, the expense and logistical demands of current VLP vaccines will limit their widespread use in resource-limited settings, where most HPV-induced cervical cancer occurs. Live oral adenovirus vaccines have properties that are well-suited for use in such settings. We have described a live recombinant adenovirus vaccine prototype that produces abundant HPV16 L1 protein from the adenovirus major late transcriptional unit and directs the assembly of HPV16 VLPs in tissue culture. Recombinant-derived VLPs potently elicit neutralizing antibodies in mice. Here, we characterize the immune response to the recombinant after dual oral and intranasal immunization of pigtail macaques, in which the virus replicates as it would in immunized humans. The immunization of macaques induced vigorous humoral responses to adenovirus capsid and nonstructural proteins, although, surprisingly, not against HPV L1. In contrast, immunization elicited strong T-cell responses to HPV VLPs as well as adenovirus virions. T-cell responses arose immediately after the primary immunization and were boosted by a second immunization with recombinant virus. T-cell immunity contributes to protection against a wide variety of pathogens, including many viruses. The induction of a strong cellular response by the recombinant indicates that live adenovirus recombinants have potential as vaccines for those agents. These studies encourage and will inform the continued development of viable recombinant adenovirus vaccines. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Informing adolescents about human papillomavirus vaccination: what will parents allow?

PubMed

Vallely, Lorraine A; Roberts, Stephen A; Kitchener, Henry C; Brabin, Loretta

2008-04-24

With the introduction of human papillomavirus (HPV) vaccination an evidence base on effective adolescent educational interventions is urgently required. We undertook formative research to develop and evaluate a film on HPV and cervical cancer prevention for school children who will be offered HPV vaccination in the UK. The main outcome measures were the number of children allowed by parents to view the film and children's knowledge. Our results indicated that the film's four key messages were acceptable to parents and largely understood by adolescents but these messages will need reinforcing if the full potential of a prophylactic vaccine is to be realised.

Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17–36

PubMed Central

Bywaters, Stephanie M.; Brendle, Sarah A.; Tossi, Kerstin P.; Biryukov, Jennifer; Meyers, Craig; Christensen, Neil D.

2017-01-01

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17–36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers. PMID:29125554

[Knowledge about herpes simplex virus type 2 and human papillomavirus, and risk perception to acquire infections among college students].

PubMed

Herrera-Ortiz, Antonia; Arriaga-Demeza, Carlos Rodolfo; Conde-González, Carlos Jesús; Sánchez-Alemán, Miguel Ángel

2013-01-01

herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) are the most frequent sexually transmitted infections (STI) among college students 18-24 years old. Educational interventions for STI prevention can help to decrease viral STI prevalence among students. to know the change in knowledge, perception of risk and sexual behavior among 182 students of the Autonomous University of the State of Morelos. a community intervention trial (before-after) was carried out, using brochures for prevention of HSV-2 and HPV, including information about these STI, with emphasis on the risk factors identified in students of the same university. we found a change in the perception of STI risk during the intervention (56.5 before vs. 67.7% after intervention), possibly the brochures assisted students to learn more about their own risk behaviors. Likewise, there was an increase in knowledge in both HPV and HSV-2. it is necessary to increase the sample size in future interventions to assess further the change in knowledge, sexual behaviors and the prevalence of infections.

Human papillomavirus detection using PCR and ATR-FTIR for cervical cancer screening

NASA Astrophysics Data System (ADS)

Rymsza, Taciana; Ribeiro, Eliane Aline; de Carvalho, Luis Felipe das Chagas e. Silva; Bhattacharjee, Tanmoy; de Azevedo Canevari, Renata

2018-05-01

The human papillomavirus (HPV) genital infection is considered one of the most common sexually transmitted diseases worldwide, and has been associated with cervical cancer. The objective of this study was to investigate the efficacy of the diagnostic methods: polymerase chain reaction (PCR) and Fourier transform infrared (FTIR) equipped with an ATR (Attenuated Total Reflectance) unit (Pike Tech) spectroscopy, to diagnose HPV infection in women undergoing gynecological examination. Seventeen patients (41.46%) of the 41 patients analyzed were diagnosed with exophytic/condyloma acuminate lesions by clinical analysis, 29 patients (70.7%) (G1 group) of the 41 patients, showed positive result for HPV cell injury by oncotic colpocitology and 12 patients (29.3%) (G2 group), presented negative result for cellular lesion and absence of clinical HPV lesion. Four samples were obtained per patient, which were submitted oncotic colpocitology analysis (Papanicolau staining, two samples), PCR (one sample) and ATR-FTIR analysis (one sample). L1 gene was amplified by PCR technique with specific GP5+/GP6+ and MY09/MY11 primers. PCR results were uniformly positive for presence of HPV in all analyzed samples. Multivariate analysis of ATR-FTIR spectra suggests no significant biochemical changes between groups and no clustering formed, concurring with results of PCR. This study suggests that PCR and ATR-FTIR are highly sensitive technique for HPV detection.

Human papillomavirus detection using PCR and ATR-FTIR for cervical cancer screening.

PubMed

Rymsza, Taciana; Ribeiro, Eliane Aline; de Carvalho, Luis Felipe das Chagas E Silva; Bhattacharjee, Tanmoy; de Azevedo Canevari, Renata

2018-05-05

The human papillomavirus (HPV) genital infection is considered one of the most common sexually transmitted diseases worldwide, and has been associated with cervical cancer. The objective of this study was to investigate the efficacy of the diagnostic methods: polymerase chain reaction (PCR) and Fourier transform infrared (FTIR) equipped with an ATR (Attenuated Total Reflectance) unit (Pike Tech) spectroscopy, to diagnose HPV infection in women undergoing gynecological examination. Seventeen patients (41.46%) of the 41 patients analyzed were diagnosed with exophytic/condyloma acuminate lesions by clinical analysis, 29 patients (70.7%) (G1 group) of the 41 patients, showed positive result for HPV cell injury by oncotic colpocitology and 12 patients (29.3%) (G2 group), presented negative result for cellular lesion and absence of clinical HPV lesion. Four samples were obtained per patient, which were submitted oncotic colpocitology analysis (Papanicolau staining, two samples), PCR (one sample) and ATR-FTIR analysis (one sample). L1 gene was amplified by PCR technique with specific GP5+/GP6+ and MY09/MY11 primers. PCR results were uniformly positive for presence of HPV in all analyzed samples. Multivariate analysis of ATR-FTIR spectra suggests no significant biochemical changes between groups and no clustering formed, concurring with results of PCR. This study suggests that PCR and ATR-FTIR are highly sensitive technique for HPV detection. Copyright © 2018 Elsevier B.V. All rights reserved.

Human papillomavirus types in invasive cervical cancer specimens from Turkey.

PubMed

Usubütün, Alp; Alemany, Laia; Küçükali, Türkan; Ayhan, Ali; Yüce, Kunter; de Sanjosé, Silvia; Font, Rebeca; Lloveras, Belen; Klaustermeier, Joellen; Quint, Wim; Muñoz, Nubia; Bosch, Francesc Xavier

2009-11-01

The main aim of the study is to describe the human papillomavirus (HPV) type-specific distribution in invasive cervical cancer (ICC) specimens from Turkey. Paraffin-embedded ICC specimens were identified from the histopathologic archives of the Hacettepe University Medical School in Turkey. HPV detection was carried out through amplification of HPV DNA by a SPF-10 broad-spectrum primer polymerase chain reaction and subsequently followed by DNA enzyme immunoassay and genotyping by LiPA25 (version 1). Two hundred seventy-seven ICC cases diagnosed between 1993 and 2004 were retrieved. After histologic evaluation and human beta-globin gene analysis for sample quality, 248 cases were considered suitable for HPV/DNA testing. HPV prevalence was 93.5% (232/248; 95% confidence interval: 90.5%-96.6%). The five most common HPV types identified as single types among HPV-positive cases were HPV16 (64.7%), HPV18 (9.9%), HPV45 (9.9%), HPV31 (3.0%), and HPV33 (2.2%). The study shows that in Turkey, HPV16/HPV18 accounted for 75.4% (95% confidence interval: 69.9%-81.0%) of HPV-positive ICC cases. This information is essential to evaluate the potential impact of the HPV vaccines in the country.

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

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. Copyright 2009 S. Karger AG, Basel.

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. © The Author(s) 2014.

Identification of a Novel Human Papillomavirus, Type HPV199, Isolated from a Nasopharynx and Anal Canal, and Complete Genomic Characterization of Papillomavirus Species Gamma-12

PubMed Central

Oštrbenk, Anja; Kocjan, Boštjan J.; Hošnjak, Lea; Li, Jingjing; Deng, Qiuju; Šterbenc, Anja; Poljak, Mario

2015-01-01

The novel human papillomavirus type 199 (HPV199) was initially identified in a nasopharyngeal swab sample obtained from a 25 year-old immunocompetent male. The complete genome of HPV199 is 7,184 bp in length with a GC content of 36.5%. Comparative genomic characterization of HPV199 and its closest relatives showed the classical genomic organization of Gammapapillomaviruses (Gamma-PVs). HPV199 has seven major open reading frames (ORFs), encoding five early (E1, E2, E4, E6, and E7) and two late (L1 and L2) proteins, while lacking the E5 ORF. The long control region (LCR) of 513 bp is located between the L1 and E6 ORFs. Phylogenetic analysis additionally confirmed that HPV-199 clusters into the Gamma-PV genus, species Gamma-12, additionally containing HPV127, HV132, HPV148, HPV165, and three putative HPV types: KC5, CG2 and CG3. HPV199 is most closely related to HPV127 (nucleotide identity 77%). The complete viral genome sequence of additional HPV199 isolate was determined from anal canal swab sample. Two HPV199 complete viral sequences exhibit 99.4% nucleotide identity. To the best of our knowledge, this is the first member of Gamma-PV with complete nucleotide sequences determined from two independent clinical samples. To evaluate the tissue tropism of the novel HPV type, 916 clinical samples were tested using HPV199 type-specific real-time PCR: HPV199 was detected in 2/76 tissue samples of histologically confirmed common warts, 2/108 samples of eyebrow hair follicles, 2/137 anal canal swabs obtained from individuals with clinically evident anal pathology, 4/184 nasopharyngeal swabs and 3/411 cervical swabs obtained from women with normal cervical cytology. Although HPV199 was found in 1.4% of cutaneous and mucosal samples only, it exhibits dual tissue tropism. According to the results of our study and literature data, dual tropism of all Gamma-12 members is highly possible. PMID:26375679

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…

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…

Genetic variability in E6, E7 and L1 genes of Human Papillomavirus 62 and its prevalence in Mexico.

PubMed

Artaza-Irigaray, Cristina; Flores-Miramontes, María Guadalupe; Olszewski, Dominik; Magaña-Torres, María Teresa; López-Cardona, María Guadalupe; Leal-Herrera, Yelda Aurora; Piña-Sánchez, Patricia; Jave-Suárez, Luis Felipe; Aguilar-Lemarroy, Adriana

2017-01-01

Human papillomavirus (HPV) is the main etiological agent of cervical cancer, the third most common cancer among women globally and the second most frequent in Mexico. Persistent infection with high-risk HPV genotypes is associated with premalignant lesions and cervical cancer development. HPVs considered as low risk or not yet classified, are often found in coinfection with different HPV genotypes. Indeed, HPV62 is one of the most prevalent HPV detected in some countries, but there is limited information about its prevalence in other regions and there are no HPV62 variants currently described. The aim of this study was to determine the prevalence of HPV62 in cervical samples from Mexican women and to identify mutations in the L1, E6 and E7 genes, which have never been reported in our population. HPV screening was performed by Cobas HPV Test in women who attended prevention health programs and dysplasia clinics. All HPV positive samples ( n  = 491) and 87 additional cervical cancer samples were then genotyped with Linear Array HPV Genotyping test. Some samples were selected to corroborate genotyping by Next-Generation sequencing. On the other hand, nucleotide changes in L1, E6 and E7 genes were determined using PCR, Sanger sequencing and analysis with the CLC-MainWorkbench 7.6.1 software. L1 protein structure was predicted with the I-TASSER server. Using Linear Array, HPV62 prevalence was 7.6% in general population, 8% in Cervical Intraepithelial Neoplasia grade 1 (CIN1) samples and 4.6% in cervical samples. The presence of HPV62 was confirmed with Next-Generation sequencing. Regarding L1 gene, novel sequence variations were detected, but they did not alter the tertiary structure of the protein. Moreover, several nucleotide substitutions were found in E6 and E7 genes compared to reference HPV62 genomic sequence. Specifically, three non-synonymous sequence variations were detected, two in E6 and one in E7. HPV62 is a frequent HPV genotype found mainly in general

Human papillomavirus-related oropharyngeal cancer.

PubMed

Taberna, M; Mena, M; Pavón, M A; Alemany, L; Gillison, M L; Mesía, R

2017-10-01

High-risk human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world. The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into an OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability. Patients affected by HPV-related OPSCC tend to be younger and have better outcomes. This observation has lead current research to evaluate treatment de-escalation options to reduce long-term associated morbidity. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new options for targeted therapy and immunotherapy approaches. This paper comprehensively reviews our accumulated knowledge regarding the role of HPV in OPSCC spanning from infection to cancer development, including its clinical diagnosis, management and preventive strategies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High prevalence of human papillomavirus type 58 in Mexican colposcopy patients.

PubMed

González-Losa, Maria del Refugio; Rosado-Lopez, Iván; Valdez-González, Nina; Puerto-Solís, Marylín

2004-03-01

Cervical cancer is the second most common cancer of the women worldwide. Infection with some genotypes of human papillomavirus is the most important risk factor associated to cervical cancer. To determine the prevalence and genotypes of papillomavirus in biopsies of women with squamous intraepithelial lesion and cervical cancer. Two hundred sequential patients of colposcopy clinic were studied. HPV diagnosis was done by polymerase chain reaction using MY09/MY11 primers, for genotyping line blot hybridization was used. A total of 186 women were beta globin positive; 104 (55.9%) had histology diagnosis of low-grade squamous intraepitelial lesions (LSIL), 67 (36.0%) high-grade squamous intraepitelial lesions (HSIL) and 15 (8.1%) invasive cervical cancer (IC). The prevalence of HPV was 56.4% (104/185); HPV 58 was founded in 28.5% of all positive women, HPV 16 in 25.7%, HPV 18 in 13.3%, HPV 33 in 11.4% and 31 in 8.5%. In all grades of the lesions HPV 58 was the most frequently. The high prevalence of HPV 58 among Mexican women with HSIL and IC, has important implications in prophylaxis.

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

PubMed

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

2014-01-01

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

The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network

PubMed Central

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

2014-01-01

The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. PMID:24928042

Papillomavirus E7 Oncoproteins Share Functions with Polyomavirus Small T Antigens

PubMed Central

White, Elizabeth A.; Kramer, Rebecca E.; Hwang, Justin H.; Pores Fernando, Arun T.; Naetar, Nana; Hahn, William C.; Roberts, Thomas M.; Schaffhausen, Brian S.; Livingston, David M.

2014-01-01

ABSTRACT Many of the small DNA tumor viruses encode transforming proteins that function by targeting critical cellular pathways involved in cell proliferation and survival. In this study, we have examined whether some of the functions of the polyomavirus small T antigens (ST) are shared by the E6 and E7 oncoproteins of two oncogenic papillomaviruses. Using three different assays, we have found that E7 can provide some simian virus 40 (SV40) or murine polyomavirus (PyV) ST functions. Both human papillomavirus 16 (HPV16) and bovine papillomavirus (BPV1) E7 proteins are capable of partially substituting for SV40 ST in a transformation assay that also includes SV40 large T antigen, the catalytic subunit of cellular telomerase, and oncogenic Ras. Like SV40 ST, HPV16 E7 has the ability to override a quiescence block induced by mitogen deprivation. Like PyV ST, it also has the ability to inhibit myoblast differentiation. At least two of these activities are dependent upon the interaction of HPV16 E7 with retinoblastoma protein family members. For small T antigens, interaction with PP2A is needed for each of these functions. Even though there is no strong evidence that E6 or E7 share the ability of small T to interact with PP2A, E7 provides these functions related to cellular transformation. IMPORTANCE DNA tumor viruses have provided major insights into how cancers develop. Some viruses, like the human papillomaviruses, can cause cancer directly. Both the papillomaviruses and the polyomaviruses have served as tools for understanding pathways that are often perturbed in cancer. Here, we have compared the functions of transforming proteins from several DNA tumor viruses, including two papillomaviruses and two polyomaviruses. We tested the papillomavirus E6 and E7 oncoproteins in three functional assays and found that E7 can provide some or all of the functions of the SV40 small T antigen, another well-characterized oncoprotein, in two of these assays. In a third assay

Strong Inverse Correlation Between MicroRNA-125b and Human Papillomavirus DNA in Productive Infection

PubMed Central

Nuovo, Gerard J.; Wu, Xin; Volinia, Stefano; Yan, Fengting; di Leva, Gianpiero; Chin, Nena; Nicol, Alcina F.; Jiang, Jinmai; Otterson, Gregory; Schmittgen, Thomas D.; Croce, Carlo

2014-01-01

Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, — 99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis. PMID:20736742

Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection.

PubMed

Nuovo, Gerard J; Wu, Xin; Volinia, Stefano; Yan, Fengting; di Leva, Gianpiero; Chin, Nena; Nicol, Alcina F; Jiang, Jinmai; Otterson, Gregory; Schmittgen, Thomas D; Croce, Carlo

2010-09-01

Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis.

Natural immune responses against eight oncogenic human papillomaviruses in the ASCUS-LSIL triage study

PubMed Central

Wilson, Lauren E.; Pawlita, Michael; Castle, Phillip E.; Waterboer, Tim; Sahasrabuddhe, Vikrant; Gravitt, Patti E.; Schiffman, Mark; Wentzensen, Nicolas

2014-01-01

Only a subset of women with human papillomavirus (HPV) infections will become seropositive, and the factors influencing seroconversion are not well-understood. We used a multiplex serology assay in women with mildly abnormal cytology results to examine seroreactivity to oncogenic HPV genotypes. An unbiased subset of women in the atypical squamous cell of undetermined significance /low-grade squamous intraepithelial lesion Triage Study (ALTS) provided blood samples at trial enrollment for serological testing. A Luminex assay based on GST-L1 fusion proteins as antigens was used to test seroreactivity against eight carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52, 58). We analyzed the relationship between seroprevalence in women free of precancer (N=2464) and HPV DNA status, age, sexual behavior, and other HPV-related risk factors. The overall seroprevalence was 24.5% for HPV16 L1 and ~ 20% for 18L1 and 31L1. Among women free of precancer, seroprevalence peaked in women less than 29 years and decreased with age. Type-specific seroprevalence was associated with baseline DNA detection for HPV16 (OR= 1.36, 95%CI: 1.04–1.79) and HPV18 (OR= 2.31, 95%CI: 1.61–3.32), as well as for HPV52 and HPV58. Correlates of sexual exposure were associated with increased seroprevalence across most genotypes. Women who were current or former smokers were less likely to be seropositive for all eight of the tested oncogenic genotypes. The multiplex assay showed associations between seroprevalence and known risk factors for HPV infection across nearly all tested HPV genotypes but associations between DNA- and serostatus were weak, suggesting possible misclassification of the participants’ HPV serostatus. PMID:23588935

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

PubMed

De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Risk of Delayed Human Papillomavirus Vaccination in Inner-City Adolescent Women

PubMed Central

Schlecht, Nicolas F.; Diaz, Angela; Shankar, Viswanathan; Szporn, Arnold H.; Wu, Maoxin; Nucci-Sack, Anne; Peake, Ken; Strickler, Howard D.; Burk, Robert D.

2016-01-01

Background. Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations. Methods. We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses. Results. Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1–.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2–1.0] and 0.3 [95% CI, .1–.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2–.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0–8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7–26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen. Conclusions. Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities. PMID:27738056

Variants of human papillomavirus type 16 predispose toward persistent infection

PubMed Central

Zhang, Lei; Liao, Hong; Yang, Binlie; Geffre, Christopher P; Zhang, Ai; Zhou, Aizhi; Cao, Huimin; Wang, Jieru; Zhang, Zhenbo; Zheng, Wenxin

2015-01-01

A cohort study of 292 Chinese women was conducted to determine the relationship between human papillomavirus (HPV) type 16 variants and persistent viral infection. Enrolled patients were HPV16 positive and had both normal cytology and histology. Flow-through hybridization and gene chip technology was used to identify the HPV type. A PCR sequencing assay was performed to find HPV16 E2, E6 and E7 gene variants. The associations between these variants and HPV16 persistent infection was analyzed by Fisher’s exact test. It was found that the variants T178G, T350G and A442C in the E6 gene, as well as C3158A and G3248A variants in the E2 gene were associated with persistent HPV16 infection. No link was observed between E7 variants and persistent viral infection. Our findings suggest that detection of specific HPV variants would help identify patients who are at high risk for viral persistence and development of cervical neoplasia. PMID:26339417

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.

Autoimmune hepatitis type 2 following anti-papillomavirus vaccination in a 11-year-old girl.

PubMed

Della Corte, Claudia; Carlucci, Antonio; Francalanci, Paola; Alisi, Anna; Nobili, Valerio

2011-06-24

In the last years numerous reports describing a possible association between administration of vaccines and development of autoimmune phenomena and overt autoimmune disease were published. Possible mechanisms of induction of autoimmune phenomena by vaccines and their excipients are probably similar to those implicated in induction by infectious agents. Here we report the case of an 11-year-old girl who developed autoimmune hepatitis type II after four weeks from vaccination against human papillomavirus. The possible relationships between the use of adjuvated vaccine against papillomavirus and autoimmune hepatitis are discussed. Although we do not provide evidence for a causal link, we suggest that the occurrence of the autoimmune hepatitis may be related to the stimulation of immune system by adjuvated-vaccine, that could have triggered the disease in a genetically predisposed individual. Therefore a monitoring of liver function test following administration of vaccine against papillomavirus may be useful in adolescent girl with signs of hepatopathy, as jaundice, dark urine or hepatomegaly, to early identify and to promptly treat autoimmune liver disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Epigenetic Alterations in Human Papillomavirus-Associated Cancers

PubMed Central

Song, Christine; McLaughlin-Drubin, Margaret E.

2017-01-01

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. PMID:28862667

Predicting Human Papillomavirus Vaccine Intentions of College-Aged Males: An Examination of Parents' and Son's Perceptions

ERIC Educational Resources Information Center

Katz, Mira L.; Kam, Jennifer A.; Krieger, Janice L.; Roberto, Anthony J.

2012-01-01

Objective: To examine male students' and their parents' human papillomavirus (HPV) vaccine communication in relation to males' willingness to discuss the vaccine with their health care provider and the likelihood of being vaccinated. Participants: Dyads (n = 111) of students and parents. Methods: Participants completed a HPV vaccine survey based…

Biochemical and Functional Interactions of Human Papillomavirus Proteins with Polycomb Group Proteins

PubMed Central

McLaughlin-Drubin, Margaret E.; Munger, Karl

2013-01-01

The role of enzymes involved in polycomb repression of gene transcription has been studied extensively in human cancer. Polycomb repressive complexes mediate oncogene-induced senescence, a principal innate cell-intrinsic tumor suppressor pathway that thwarts expansion of cells that have suffered oncogenic hits. Infections with human cancer viruses including human papillomaviruses (HPVs) and Epstein-Barr virus can trigger oncogene-induced senescence, and the viruses have evolved strategies to abrogate this response in order to establish an infection and reprogram their host cells to establish a long-term persistent infection. As a consequence of inhibiting polycomb repression and evading oncogene induced-senescence, HPV infected cells have an altered epigenetic program as evidenced by aberrant homeobox gene expression. Similar alterations are frequently observed in non-virus associated human cancers and may be harnessed for diagnosis and therapy. PMID:23673719

Characterization of a novel papillomavirus species (ZcPV1) from two California sea lions (Zalophus californianus).

PubMed

Rivera, Rebecca; Robles-Sikisaka, Refugio; Hoffman, Elizabeth M; Stacy, Brian A; Jensen, Eric D; Nollens, Hendrik H; Wellehan, James F X

2012-03-23

A seven-year old California sea lion (Zalophus californianus) presented with focally extensive, bilaterally symmetric, proliferative axillary skin lesions and preputial lesions. A second California sea lion in the same population presented with similar proliferative lesions on the underside of the tail. Histopathology revealed epidermal hyperplasia with severe hyperkeratosis, with proliferating keratinocytes forming broad, branching pegs that extended into the dermis. Pan-papillomaviral consensus PCR was used to obtain initial E1 sequence template and the complete genome was determined using a combination of rolling circle amplification and specific-primer PCR. Analysis revealed a novel papillomavirus, Zalophus californianus papillomavirus 1 (ZcPV1), with seven open reading frames encoding five early proteins (E6, E7, E1, E2 and E4) and two late proteins (L1 and L2). Phylogenetic analysis revealed that (ZcPV1) is most closely related to Equine papillomavirus 1 (EcPV1) in the genus Zetapapillomavirus, and Canine papillomaviruses 3 and 4 (CPV3, CPV4) in the genus Chipapillomavirus. The lesions regressed without intervention over a period of several months. Copyright © 2011 Elsevier B.V. All rights reserved.

Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: Detection and protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sawchuk, W.S.; Weber, P.J.; Lowy, D.R.

1989-07-01

Papillomavirus DNA has been reported recently in the vapor (smoke plume) derived from warts treated with carbon dioxide laser; this raises concerns for operator safety. We therefore have studied a group of human and bovine warts to define further the potential risk of wart therapy and to test whether a surgical mask could reduce exposure. Half of each wart was treated with carbon dioxide laser and the other half with electrocoagulation. The vapor produced by each form of therapy was collected with a dry filter vacuum apparatus and analyzed for the presence of papillomavirus. Vapor from human plantar warts wasmore » analyzed for the presence of human papillomavirus DNA, because there is no infectivity assay for human papillomavirus. Of plantar warts treated, five of eight laser-derived vapors and four of seven electrocoagulation-derived vapors were positive for human papillomavirus DNA. Greater amounts of papillomavirus DNA were usually recovered in the laser vapor than in the electrocoagulation vapor from the same wart. Bioassay readily detected infectious bovine papillomavirus in the vapor from bovine warts treated with either modality; more virus was present in laser-derived material. A surgical mask was found capable of removing virtually all laser- or electrocoagulation-derived virus, strongly suggesting that such masks can protect operators from potential inhalation exposure to papillomavirus.« less

AHNS series: Do you know your guidelines? Management of head and neck cancer in the era of human papillomavirus: Educating our patients on human papillomavirus.

PubMed

Guo, Theresa; Goldenberg, David; Fakhry, Carole

2017-05-01

Human papillomavirus (HPV) has changed the face of head and neck cancer over the past 2 decades. No longer is this solely a disease of older patients with a history of heavy tobacco and alcohol use. Patients with HPV-related head and neck cancers tend to be younger, healthier, and have an improved prognosis, compared with those with HPV-negative tumors. As more patients are diagnosed with HPV-related head and neck cancer, physicians have important topics to consider. These include prevalence, transmission, and natural history of HPV, the role of screening, vaccines, and HPV testing in head and neck cancer. This article continues a series developed by the American Head and Neck Society's Education Committee entitled "Do you know your guidelines?" and is intended to provide guidance for navigating common questions and concerns patients may have about HPV infection and HPV-related head and neck cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 833-839, 2017. © 2017 Wiley Periodicals, Inc.

Strain-Specific Properties and T Cells Regulate the Susceptibility to Papilloma Induction by Mus musculus Papillomavirus 1

PubMed Central

Handisurya, Alessandra; Day, Patricia M.; Thompson, Cynthia D.; Bonelli, Michael; Lowy, Douglas R.; Schiller, John T.

2014-01-01

The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6×1010 MusPV1 virions, the recently identified domestic mouse papillomavirus (also designated “MmuPV1”), but were uniformly resistant to MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A resulted in variable induction of papillomas after experimental infection with a similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional outgrowth correlating with early viral gene expression and partly with reported strain-specific susceptibility to chemical carcinogens, but not with H-2 haplotype. Challenge with 1×1012 virions in the absence of immunosuppression induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice. Antibody-induced depletion of CD3+ T cells permitted efficient virus replication and papilloma formation in both strains, providing experimental proof for the crucial role of T cells in controlling papillomavirus infection and associated disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells was sufficient for efficient infection and papillomatosis, although deletion of one subset did not inhibit the recruitment of the other subset to the infected epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+ and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or CD8+ T cell-independent mechanisms exist that can protect this particular strain from MusPV1-associated disease. These findings may help to explain the diversity of pathological outcomes in immunocompetent humans after infection with a specific

Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers.

PubMed Central

Crum, C P; Nuovo, G; Friedman, D; Silverstein, S J

1988-01-01

The accumulation of human papillomavirus type 16 (HPV-16)-specific RNAs in tissue sections from biopsies of patients with genital precancers was studied by in situ hybridization with single-stranded 35S-labeled RNA. These analyses revealed that the most abundant early-region RNAs were derived from the E4 and E5 open reading frames (ORFs). RNAs homologous to the E6/E7 ORFs were also detected, whereas RNAs homologous to the intervening E1 ORF were not. This suggests that the E4 and E5 mRNAs are derived by splicing to the upstream E6/E7 ORFs, consistent with studies of HPV-11 in condylomata (L. T. Chow et al., Cancer Cells (Cold Spring Harbor) 5:55-72, 1987). Abundant RNAs homologous to the 5' portion of L1 were also detected. These RNAs were localized to the apical strata of the epithelium. HPV-16 RNAs accumulated in discrete regions of these lesions, and when present were most abundant in the upper cell layers of the precancerous epithelium. RNAs homologous to early ORFs were also detected in some germinal cells within the basal layer of the epithelium. Images PMID:2824859

Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers.

PubMed

Crum, C P; Nuovo, G; Friedman, D; Silverstein, S J

1988-01-01

The accumulation of human papillomavirus type 16 (HPV-16)-specific RNAs in tissue sections from biopsies of patients with genital precancers was studied by in situ hybridization with single-stranded 35S-labeled RNA. These analyses revealed that the most abundant early-region RNAs were derived from the E4 and E5 open reading frames (ORFs). RNAs homologous to the E6/E7 ORFs were also detected, whereas RNAs homologous to the intervening E1 ORF were not. This suggests that the E4 and E5 mRNAs are derived by splicing to the upstream E6/E7 ORFs, consistent with studies of HPV-11 in condylomata (L. T. Chow et al., Cancer Cells (Cold Spring Harbor) 5:55-72, 1987). Abundant RNAs homologous to the 5' portion of L1 were also detected. These RNAs were localized to the apical strata of the epithelium. HPV-16 RNAs accumulated in discrete regions of these lesions, and when present were most abundant in the upper cell layers of the precancerous epithelium. RNAs homologous to early ORFs were also detected in some germinal cells within the basal layer of the epithelium.

Laboratory production in vivo of infectious human papillomavirus type 11.

PubMed Central

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

1987-01-01

Human papillomaviruses (HPV) induce among patients natural lesions which produce small amounts of virus. Infection of human cell cultures does not lead to the multiplication of virus, which also does not replicate in experimental animals. We 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. Images PMID:3027386

Impact of 6-month frozen storage of cervical specimens in alkaline buffer conditions on human papillomavirus genotyping.

PubMed

LaMere, Brandon J; Howell, Renee; Fetterman, Barbara; Shieh, Jen; Castle, Philip E

2008-08-01

The impact of 6-month storage of cervical specimens under alkaline conditions that occurs as the result of Hybrid Capture 2 testing on human papillomavirus (HPV) genotyping is not well documented. To examine this issue, 143 frozen hc2-positive specimens in specimen transport medium were selected at random from each of the following groups: specimens stored for 6 months, 4 months, and 2.5 months under alkaline pH (pH 12-13) and specimens stored 1 month at neutral pH (pH 6-7) as controls. Specimens were tested in a masked fashion for 20 HPV genotypes (HPV6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82) using a prototype, research-use-only GP5+/6+ L1 consensus PCR method and multiplex hybridization using Luminex xMAP for detection of specific HPV genotypes One control specimen had missing test results. There were no statistical differences in the number of HPV genotypes detected, number of carcinogenic HPV genotypes detected, or in the signal strength among HPV-positive results across groups. Six-month frozen storage of cervical specimens at alkaline pH had little impact on testing for HPV genotypes among hc2-positive women using this HPV genotyping method.

[Ten years of human papillomavirus vaccination. From dermatology to oncology via infectology].

PubMed

Moraga-Llop, Fernando A

2018-05-01

Human papillomavirus (HPV) was first identified in dermatology, and it was subsequently demonstrated that is was required for the development of uterine cervical cancer and other tumours, after a persistent infection by any of its oncogenic genotypes. Ten years ago, the most common infections and cancers associated with HPV could be prevented by immunisation with 2vaccines, one bivalent, and another tetravalent, and having just marketed a nonavalent one. During the period 2007-2008, the HPV vaccine was included in the Autonomous Communities vaccination calendar, and it is the second vaccine, after that of Hepatitis B, that prevents cancer. In these 10 years that these vaccines have been available the knowledge has progressed and there have been significant advances in vaccination strategies, as well as in the indications and recommendations. These include, lowering the age in the vaccination schedule, prescribing of 2doses at 9 years and at 13-14 years, systematic vaccination of the male in some countries, immunisation of the woman after adolescence, implementation of vaccination programmes in developed countries, prevention of other cancers, recommendations for vaccinations for populations at high risk of HPV infection, scientific evidence on the impact and effectiveness of vaccination, and confirmation of the safety of these vaccines, with more than 270 million doses administered, as has already been observed in clinical trials. The role of health professionals is essential to achieve and maintain high vaccine coverage. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Why Human Papillomavirus Acute Infections Matter

PubMed Central

2017-01-01

Most infections by human papillomaviruses (HPVs) are ‘acute’, that is non-persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms. From a dynamical perspective, adopting concepts from spatial ecology, such as meta-populations or meta-communities, can help explain why HPV acute infections sometimes last for years. Furthermore, cervical cancer screening and vaccines impose novel iatrogenic pressures on HPVs, implying that anticipating any viral evolutionary response remains essential. Finally, hints at the associations between HPV acute infections and fertility deserve further investigation given their high, worldwide prevalence. Overall, understanding asymptomatic and benign infections may be instrumental in reducing HPV virulence. PMID:28994707

Does Mother Know Best? An Actor-Partner Model of College-Age Women's Human Papillomavirus Vaccination Behavior

ERIC Educational Resources Information Center

Krieger, Janice L.; Kam, Jennifer A.; Katz, Mira L.; Roberto, Anthony J.

2011-01-01

This study examined the associations of perceived threat, perceived efficacy, and parent-child communication with the extent to which college-age women received the human papillomavirus (HPV) vaccine. Daughters and their mothers completed a survey about the HPV vaccine (N = 182 dyads). The results showed that mothers' perceived self-efficacy to…

The potential impact of a prophylactic vaccine for human papillomavirus on the current cervical screening programme in Hong Kong.

PubMed

Koljonen, Paul A

2007-08-01

To review and summarise current controversies in cervical screening in Hong Kong and discuss the potential impact of prophylactic human papillomavirus vaccination. Literature search of Medline to December 2006, the Hong Kong Cancer Registry, and Centre of Disease Control. Key words search terms were: 'human papillomavirus', 'vaccine', 'cervical cancer', 'screening programme', and 'Hong Kong'. Original articles, review papers, books, and the worldwide web. Cervical cancer is one of the most common cancers in Hong Kong, and can be prevented if detected at its pre-cancerous stage. Despite the huge disease burden this imposes on our society and robust advocacy by the academic sector, an appropriate screening programme is still not in place. Existence of a vaccine that could potentially reduce the costs of universal screening should prompt our government to re-consider subsidising such a programme. While a combined screening-vaccination programme may be more cost-effective than screening alone, the vaccine is still costly, and the government must consider all the pros and cons. The new human papillomavirus vaccine, combined with an organised screening programme, is probably a more cost-effective way of preventing morbidity and mortality due to cervical cancer than the current programme in Hong Kong. More research and cost-effectiveness analyses are needed to decide on the ideal ages for primary vaccination and the requirement for booster shots.

[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.

Role of Human Papillomavirus in Penile Carcinomas Worldwide.

PubMed

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

2016-05-01

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

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule.

PubMed

Germar, Maria Julieta; Purugganan, Carrie; Bernardino, Ma Socorro; Cuenca, Benjamin; Chen, Y-Chen; Li, Xiao; Van Kriekinge, Georges; Lee, I-Heng

2017-05-04

Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs.

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule

PubMed Central

Germar, Maria Julieta; Purugganan, Carrie; Bernardino, Ma. Socorro; Cuenca, Benjamin; Chen, Y-Chen; Li, Xiao; Van Kriekinge, Georges; Lee, I-Heng

2017-01-01

ABSTRACT Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs. PMID:28075249

Prevalence of anal infection due to high-risk human papillomavirus and analysis of E2 gene integrity among women with cervical abnormalities.

PubMed

Gonzalez-Losa, María Del Refugio; Puerto-Solís, Marylin; Ayora-Talavera, Guadalupe; Gómez-Carvallo, Jesús; Euán-López, Alejandra; Cisneros-Cutz, José I; Rosado-López, Ariel; Echeverría Salazar, Jesúa; Conde-Ferráez, Laura

2018-04-01

High-risk human papillomaviruses (HR-HPV) infection has been associated with 90% of anal cancer cases. Women with abnormal cytology are a high-risk group to develop anal neoplasia. The aim of this study is to describe the prevalence and epidemiology of HR-HPV 16, 18, 45, and 58 anal infections in women with cervical abnormalities, as well as to assess E2 gene integrity. A cross-sectional study was performed on 311 cervical and 311 anal samples from patients with abnormal cytology in two colposcopy clinics in Yucatan, Mexico. A specific PCR for oncogenes was performed in order to identify HVP 16, 18, 45 and 58. Real time PCR was used to amplify the whole HPV 16, 18, and 58 E2 gene to verify its integrity in anal samples. High risk HPV 16, 18, 58, and/or 45 were found in 41.47% (129/311) of cervical samples, and in 30.8% (96/331) of anal samples, with 18% (57/311) of the patients being positive in both samples. The same genotypes in both anatomical sites were observed in 11.25% (35/311). The E2 gene was disrupted in 82% of all tested samples. The frequency of genome disruption viral integration in anal samples by genotype was: HPV 58 (97.2%); HPV 16 (72.4%), and HPV 18 (0%). Women with cervical disease have HR-HPV anal infections, and most of them have the E2 gene disrupted, which represents a risk to develop anal cancer. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

[The relationship between human papillomavirus (HPV) infection and penile cancer].

PubMed

Yumura, Yasushi; Hattori, Yusuke; Noda, Hideyuki; Kondo, Kei-Ichi; Noguchi, Kazumi; Sasaki, Takeshi; Kasuga, Jun; Kubota, Yoshinobu

2009-11-01

Human papillomavirus (HPV) may be carcinogenic effectors in a variety of human lower genital tract malignancies. We evaluated HPV status with respect to clinical and pathological features and prognosis of penile carcinoma. We searched for HPV infected cells (Koilocytosis) within the primary lesion of cancer tissue from 78 patients with penile squamous cell carcinoma. The following variables were recorded : age, tumor size, clinical stage, lymphatic and venous invasion, histologic and nuclear grade, Broders grade, infiltration status, and lymph node and distant metastasis. Koilocytosis were detected 55.1% (43 of 78) of patients. Tumors with Koilocytosis had better differentiation (p=0.0443) and lower grade (better keratinized) in Broders grading system (p=0.0116) than HPV negative tumors. No difference was found in the 5-year survival rate (p=0.5693). Our data suggest that the presence of Koilocytosis does not influence prognosis in penile cancer.

Human papillomavirus detection in Corrientes, Argentina: High prevalence of type 58 and its phylodynamics.

PubMed

Marín, Héctor M; Torres, Carolina; Deluca, Gerardo D; Mbayed, Viviana A

2015-01-01

Human papillomavirus (HPV) has the highest mortality rate due to cervical cancer in Northeastern Argentina. The aim of this work was to detect and characterize HPV in samples from the Province of Corrientes, Argentina. HPV detection and typing was performed using PCR-RFLP on samples with different cervical lesions (n=255). Seventeen viruses typified as HPV-58 were sequenced (E6 and E7 genes) and mutations were analyzed. HPV DNA was detected in 56.1% of the cervical lesions (143/255). Twenty-two different HPV types were detected. The type most frequently found among the total number of samples and HPV-positive samples was HPV-16 (14.5% and 25.9%, respectively), followed by HPV-58 (8.2%/14.7%, respectively), which is also considered a high-risk viral type. Increased severity of the cytological status was associated with greater rates of HPV detection and, especially, with the detection of greater rates of high-risk types. In addition, the evolutionary dynamics of the alpha-9 species group and HPV-58 was studied. All HPV-58 viruses reported in this work belonged to lineage A, sublineage A2. The phylodynamic analysis indicated that diversification of main groups within lineage A might have accompanied or preceded human migrations across the globe. Given that the most prevalent viruses found belonged to high-risk HPV types, some concerns might arise about the extent of cross protection of the vaccines against the types not included in their design. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

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. © The Author(s) 2015.

Anaphylaxis following quadrivalent human papillomavirus vaccination

PubMed Central

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

2008-01-01

Background 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. Methods 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. Results 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. Interpretation 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. PMID:18762618

College Students' Perceptions of and Experiences with Human Papillomavirus and Herpes: Implications for College Sexual Health Education

ERIC Educational Resources Information Center

Hirschler, Christopher; Hope, Andrea; Myers, Jaime L.

2015-01-01

Sexually transmitted infections spread through skin-to-skin contact represent unique prevention challenges. This study examines how college students perceive safer sex practices with respect to human papillomavirus (HPV) and herpes. Qualitative and quantitative data (n = 275) were collected using an online questionnaire. College students'…

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

NASA Astrophysics Data System (ADS)

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

1994-07-01

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

Gender and age-specific seroprevalence of human papillomavirus 16 and 18 in general population in Tehran, Iran.

PubMed

Aghakhani, Arezoo; Mamishi, Setareh; Sabeti, Shahram; Bidari-Zerehpoosh, Farahnaz; Banifazl, Mohammad; Bavand, Anahita; Ramezani, Amitis

2017-04-01

The assessment of the gender and age-specific seroprevalence of human papillomavirus (HPV) is essential for planning of HPV vaccine implementation into the preventive programs. In this study, we aimed to determine the age-specific seroprevalence of HPV-16 and 18 in both males and females in Tehran, Iran. Three hundred and seventy-eight women (10-35 years) and 162 men (10-25 years) from Tehran, Iran, were enrolled. Anti-HPV IgG antibodies against HPV-16 and HPV-18 were detected by ELISA using papillomavirus type 16 and 18 L1-capsids as antigen. HPV-16 antibody was detected in 15.6 and 13.6% of women and men, respectively. Antibody against HPV-18 was found positive in 12.7 and 8% of women and men, respectively. The highest seroprevalence of HPV-16 and 18 were seen in women aged 26-30 years (22.2 and 19.4%, respectively), and the lowest HPV-16 and 18 seropositivity rates were seen in males and females aged 10-15 years (9.3 and 1.9%, respectively). In our cohort of study, in males, both anti-HPV-16 and 18 increased after age 15 years, peaking in men aged 21-25 years. In women, both HPV-16 and 18 seropositivity increased after 15 years, declined at 21-25 years, peaked in women aged 26-30 years and again decreased after 30 years. Our data showed increasing exposure rate to high-risk HPV vaccine types in our studied population over 15 years of age. In order to prevent the HPV-related cancers, implementation of HPV vaccine into the national immunization program in Iran and vaccination of females and males less than 15 years of age are suggested.

Detection of human papillomaviruses by polymerase chain reaction and ligation reaction on universal microarray.

PubMed

Ritari, Jarmo; Hultman, Jenni; Fingerroos, Rita; Tarkkanen, Jussi; Pullat, Janne; Paulin, Lars; Kivi, Niina; Auvinen, Petri; Auvinen, Eeva

2012-01-01

Sensitive and specific detection of human papillomaviruses (HPV) in cervical samples is a useful tool for the early diagnosis of epithelial neoplasia and anogenital lesions. Recent studies support the feasibility of HPV DNA testing instead of cytology (Pap smear) as a primary test in population screening for cervical cancer. This is likely to be an option in the near future in many countries, and it would increase the efficiency of screening for cervical abnormalities. We present here a microarray test for the detection and typing of 15 most important high-risk HPV types and two low risk types. The method is based on type specific multiplex PCR amplification of the L1 viral genomic region followed by ligation detection reaction where two specific ssDNA probes, one containing a fluorescent label and the other a flanking ZipCode sequence, are joined by enzymatic ligation in the presence of the correct HPV PCR product. Human beta-globin is amplified in the same reaction to control for sample quality and adequacy. The genotyping capacity of our approach was evaluated against Linear Array test using cervical samples collected in transport medium. Altogether 14 out of 15 valid samples (93%) gave concordant results between our test and Linear Array. One sample was HPV56 positive in our test and high-risk positive in Hybrid Capture 2 but remained negative in Linear Array. The preliminary results suggest that our test has accurate multiple HPV genotyping capability with the additional advantages of generic detection format, and potential for high-throughput screening.

Evolutionary and biophysical relationships among the papillomavirus E2 proteins.

PubMed

Blakaj, Dukagjin M; Fernandez-Fuentes, Narcis; Chen, Zigui; Hegde, Rashmi; Fiser, Andras; Burk, Robert D; Brenowitz, Michael

2009-01-01

Infection by human papillomavirus (HPV) may result in clinical conditions ranging from benign warts to invasive cancer. The HPV E2 protein represses oncoprotein transcription and is required for viral replication. HPV E2 binds to palindromic DNA sequences of highly conserved four base pair sequences flanking an identical length variable 'spacer'. E2 proteins directly contact the conserved but not the spacer DNA. Variation in naturally occurring spacer sequences results in differential protein affinity that is dependent on their sensitivity to the spacer DNA's unique conformational and/or dynamic properties. This article explores the biophysical character of this core viral protein with the goal of identifying characteristics that associated with risk of virally caused malignancy. The amino acid sequence, 3d structure and electrostatic features of the E2 protein DNA binding domain are highly conserved; specific interactions with DNA binding sites have also been conserved. In contrast, the E2 protein's transactivation domain does not have extensive surfaces of highly conserved residues. Rather, regions of high conservation are localized to small surface patches. Implications to cancer biology are discussed.

Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

PubMed Central

2010-01-01

Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection

PubMed Central

Gameiro, Steven F.; Zhang, Ali; Ghasemi, Farhad; Barrett, John W.; Mymryk, Joe S.

2017-01-01

Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain. Unexpectedly, these genes were all expressed at high levels in HPV positive (HPV+) cancers compared with normal control tissues. Indeed, many of these genes were expressed at significantly enhanced levels in HPV+ tumors. Similarly, the transcript levels of several other components of the MHC-I peptide-loading complex were also high in HPV+ cancers. The coordinated expression of high mRNA levels of the MHC-I antigen presentation apparatus could be a consequence of the higher intratumoral levels of interferon γ in HPV+ carcinomas, which correlate with signatures of increased infiltration by T- and NK-cells. These data, which were obtained from both cervical and oral tumors in large human cohorts, indicates that HPV oncoproteins do not efficiently suppress the transcription of the antigen presentation apparatus in human tumors. PMID:28891951

Human Papillomavirus (HPV) Risk Factors, Vaccination Patterns, and Vaccine Perceptions among a Sample of Male College Students

ERIC Educational Resources Information Center

Fontenot, Holly B.; Collins Fantasia, Heidi; Charyk, Anna; Sutherland, Melissa A.

2014-01-01

Objective: To examine human papillomavirus (HPV) vaccination rates, including initiation and completion of the vaccine series, and barriers to vaccination in a sample of male college students. Participants: Male students between the ages of 18 and 25 who reported being currently or previously sexually active (N = 735). Methods: A cross-sectional…

Human Papillomavirus Vaccine Sources of Information and Adolescents’ Knowledge and Perceptions

PubMed Central

Rosen, Brittany L.; Shew, Marcia L.; Zimet, Gregory D.; Ding, Lili; Mullins, Tanya L. K.; Kahn, Jessica A.

2017-01-01

Understanding where adolescents obtain information about human papillomavirus (HPV) vaccines may be helpful in designing public health interventions promoting HPV vaccination. This study assessed the following: (1) exposure to specific sources of information about HPV vaccines, (2) self-reported helpfulness of these sources of information, and (3) whether the specific source of information was associated with knowledge and perceptions about HPV vaccines among adolescent girls. There were 339 adolescent girls (mean age = 16.8 years) recruited into the study. Television advertisements, the Internet, doctors/nurses, and mothers were the most frequently reported sources of vaccine information; more than 90% of participants who received information from these sources reported they were helpful. Adolescents who received information about HPV vaccines from television advertisements, the Internet, clinicians, and mothers had higher knowledge about HPV vaccines and more positive perceptions. Assuring the accuracy of messages from these sources will be essential, given their importance in influencing adolescents’ knowledge and perceptions about HPV vaccines. PMID:29204462

[Sexual risk behaviours and PAP testing in university women vaccinated against human papillomavirus].

PubMed

Fernández-Feito, Ana; Antón-Fernández, Raquel; Paz-Zulueta, María

2018-05-01

To estimate the association between the human papillomavirus (HPV) vaccine and sexual risk behaviour, as well as the participation in the Cervical Cancer Screening Program (CCSP). Cross-sectional study. School of Medicine and Health Sciences, School of Law, and School of Economics and Business (University of Oviedo). Female university students. Information was collected about contraceptive methods, sexual behaviours, HPV knowledge, and participation in the CCSP. Furthermore, proportions and odds ratio (OR) were estimated with their corresponding 95% confidence intervals (95%CI). Approximately two-thirds (67.7%) of the sample was vaccinated against HPV, and 216 women (65.3%) were sexually active. Barrier contraceptive methods were used by 67.6% during their current intimate relationships, being less frequent in non-vaccinated women (54.9% vs. 75.4% in vaccinated female students) (P=.002). The risk of having at least one sexual risk behaviour was higher in non-vaccinated women: OR2.29 (95%CI: 1.29-4.07). In addition, the probability of having a PAP test within the CCSP was higher in non-vaccinated women: OR2.18 (95%CI: 1.07-4.47). The prevalence of sexual risk behaviours in non-vaccinated women is elevated, and it is related to the lack of use of barrier contraceptive methods. The vaccination against HPV could affect sexual behaviours and the participation in the CCSP. Therefore, the information received by young people about contraceptive methods, sexually transmitted diseases, and cancer prevention should be reinforced. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[Human papillomavirus and penile cancer : Thinking about measures for prevention].

PubMed

Schneede, P; Schlenker, B

2018-04-01

Two major pathways of penile carcinogenesis are known: human papillomavirus (HPV)-induced penile cancer and HPV-negative cancers associated with chronic dermatoses. Therefore, modern measures for prevention of penile cancer may for example include prophylactic HPV vaccination. The resulting B‑cell-mediated immunity to HPV capsid proteins is effective protection against future HPV infections. Contrarily when treating existing HPV infections or HPV-associated cancers an antigen-specific T‑cell immunity is necessary. To date, screening and treatment of precancerous lesions to prevent penile cancer are not established in the German health care program and the highly expected therapeutic HPV vaccines are still on the horizon. In this article, we focus on possible strategies to prevent HPV-related penile cancer on different levels of carcinogenesis.

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

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

PubMed Central

Soldan, Kate; Lehtinen, Matti; Beddows, Simon; Brisson, Marc; Brotherton, Julia M.L.; Chow, Eric P.F.; Cummings, Teresa; Drolet, Mélanie; Fairley, Christopher K.; Garland, Suzanne M.; Kahn, Jessica A.; Kavanagh, Kimberley; Markowitz, Lauri; Pollock, Kevin G.; Söderlund-Strand, Anna; Sonnenberg, Pam; Tabrizi, Sepehr N.; Tanton, Clare; Unger, Elizabeth; Thomas, Sara L.

2016-01-01

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important. PMID:27648688

Knowledge of Human Papillomavirus and Perceived Barriers to Vaccination in a Sample of US Female College Students

ERIC Educational Resources Information Center

Dillard, James Price; Spear, Margaret E.

2010-01-01

Objective: To assess knowledge of human papillomavirus (HPV) and perceived barriers to being vaccinated against the virus. Participants: Three hundred ninety-six undergraduate women enrolled at Penn State University in Fall 2008. Methods: A random sample of students were invited to participate in a Web-based survey. Results: Awareness of HPV and…

Correlates to Human Papillomavirus Vaccination Status and Willingness to Vaccinate in Low-Income Philadelphia High School Students

ERIC Educational Resources Information Center

Bass, Sarah B.; Leader, Amy; Shwarz, Michelle; Greener, Judith; Patterson, Freda

2015-01-01

Background: Little is known about the correlates of human papillomavirus (HPV) vaccination or willingness to be vaccinated in urban, minority adolescents. Methods: Using responses to the 2013 Youth Risk Behavior Survey in Philadelphia, a random sample of high schools provided weighted data representing 20,941 9th to 12th graders. Stratified by…

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

ERIC Educational Resources Information Center

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

2013-01-01

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

Relative Persuasiveness of Gain- versus Loss-Framed Human Papillomavirus Vaccination Messages for the Present- and Future-Minded

ERIC Educational Resources Information Center

Nan, Xiaoli

2012-01-01

This research examines how young adults' attitudes toward human papillomavirus (HPV) vaccination and their intentions to get the vaccine are influenced by the framing of health messages (gain vs. loss) and time orientation (i.e., the extent to which people value immediate vs. distant consequences of their decisions). Results of an experiment…

Prevalence of and Risk Factors for Anal Oncogenic Human Papillomavirus Infection Among HIV-Infected Women in France in the Combination Antiretroviral Therapy Era.

PubMed

Heard, Isabelle; Poizot-Martin, Isabelle; Potard, Valérie; Etienney, Isabelle; Crenn-Hebert, Catherine; Moore, Catherine; Touraine, Philippe; Cubie, Heather; Costagliola, Dominique

2016-05-01

Little is known about the type-specific prevalence of anal human papillomavirus (HPV) infection and risk factors for anal high-risk (HR) HPV infection in human immunodeficiency virus (HIV)-infected women. A cross-sectional study of anal and cervical HPV infection was nested within a gynecological cohort of HIV-infected women. Specimens were tested for type-specific DNA using a polymerase chain reaction-based assay. The study population consisted of 311 women with a median age of 45.3 years, of whom 42.8% originated from sub-Saharan Africa and 96.8% were receiving combination antiretroviral therapy. The median CD4(+)cell count was 612/μL, and the HIV load was <50 copies/mL in 84.1%. HR-HPV types were detected in the anal canal in 148 women (47.6%) and in the cervix in 82 (26.4%). HPV-16 was the most prevalent type in both the anal canal (13.2% of women) and the cervix (5.1%). In multivariable analysis, factors associated with prevalent anal HR-HPV infection were CD4(+)count <350/μL (odds ratio, 2.9; 95% confidence interval, 1.3-6.5), concurrent cervical lesions (2.6; 1.0-4.3), and cervical HR-HPV infection (1.8; 1.0-3.2). The high prevalence of HR-HPV types, including HPV-16, in the anal canal of HIV-positive women is concerning. Anal cancer screening should be considered for HIV-positive women as part of their routine care. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India

PubMed Central

Chakravarty, Jaya; Chourasia, Ankita; Thakur, Minaxi; Singh, Abhishek Kumar; Sundar, Shyam; Agrawal, Nisha Rani

2016-01-01

Background & objectives: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. Methods: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Results: Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤350/μl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤350/μl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Interpretation &conclusions: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women. PMID:26997018

A molecular dynamics study of loop fluctuation in human papillomavirus type 16 virus-like particles: a possible indicator of immunogenicity.

PubMed

Joshi, Harshad; Cheluvaraja, Srinath; Somogyi, Endre; Brown, Darron R; Ortoleva, Peter

2011-11-28

Immunogenicity varies between the human papillomavirus (HPV) L1 monomer assemblies of various sizes (e.g., monomers, pentamers or whole capsids). The hypothesis that this can be attributed to the intensity of fluctuations of important loops containing neutralizing epitopes for the various assemblies is proposed for HPV L1 assemblies. Molecular dynamics simulations were utilized to begin testing this hypothesis. Fluctuations of loops that contain critical neutralizing epitopes (especially FG loop) were quantified via root-mean-square fluctuation and features in the frequency spectrum of dynamic changes in loop conformation. If this fluctuation-immunogenicity hypothesis is a universal aspect of immunogenicity (i.e., immune system recognition of an epitope within a loop is more reliable when it is presented via a more stable delivery structure), then fluctuation measures can serve as one predictor of immunogenicity as part of a computer-aided vaccine design strategy. Copyright © 2011 Elsevier Ltd. All rights reserved.

The role of human papillomavirus vaccines in cervical cancer: Prevention and treatment.

PubMed

Bogani, Giorgio; Leone Roberti Maggiore, Umberto; Signorelli, Mauro; Martinelli, Fabio; Ditto, Antonino; Sabatucci, Ilaria; Mosca, Lavinia; Lorusso, Domenica; Raspagliesi, Francesco

2018-02-01

Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed. Copyright © 2017 Elsevier B.V. All rights reserved.

Human papillomavirus vaccination coverage using two-dose or three-dose schedule criteria.

PubMed

Lin, Xia; Rodgers, Loren; Zhu, Liping; Stokley, Shannon; Meites, Elissa; Markowitz, Lauri E

2017-10-13

In October 2016, the Advisory Committee on Immunization Practices (ACIP) updated the human papillomavirus (HPV) vaccination recommendation to include a 2-dose schedule for U.S. adolescents initiating the vaccine series before their 15th birthday. We analyzed records for >4million persons aged 9-17years receiving any HPV vaccine by the end of each quarter during January 1, 2014-September 30, 2016 from six Immunization Information Systems Sentinel Sites, and reclassified HPV vaccination up-to-date coverage according to the updated recommendations. Compared with HPV vaccination up-to-date coverage by the 3-dose schedule only, including criteria for either a 2-dose or 3-dose schedule increased up-to-date coverage in 11-12, 13-14, and 15-17 year-olds by 4.5-8.5 percentage points. The difference between 3-dose up-to-date coverage and 2- or 3-dose up-to-date coverage was greatest in late 2016. These data provide baseline HPV vaccination coverage using current ACIP recommendations. Published by Elsevier Ltd.

Human papillomavirus burden in different cancers in Iran: a systematic assessment.

PubMed

Jalilvand, Somayeh; Shoja, Zabihollah; Hamkar, Rasool

2014-01-01

Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investigation covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.

Human papillomavirus type 16 is an important infectious factor in the high incidence of esophageal cancer in Anyang area of China.

PubMed

Li, T; Lu, Z M; Chen, K N; Guo, M; Xing, H P; Mei, Q; Yang, H H; Lechner, J F; Ke, Y

2001-06-01

To investigate the potential role of human papillomavirus (HPV) infection in the pathogenesis of esophageal carcinomas in the Anyang area of China, we have evaluated specimens collected by balloon cytology examination from volunteers in two regions with significantly different incidences of esophageal carcinoma. 138 donors were from a village in a county with an esophageal carcinoma (EC) age-adjusted mortality rate of 132x10(5), the remaining 68 were resident in a second village from another county with an EC mortality rate of 52x10(5). Specimens were evaluated using both polymerase chain reaction (PCR) amplification and in situ hybridization (ISH) protocols. PCR results showed that the prevalence of the human papillomavirus type 16 (HPV-16) E6 gene in the high incidence area was 1.9-fold higher than that of the low incidence area (72 and 37%, respectively, P < 0.01). Moreover, the positive rate corresponded with pathology grade. Similar results were obtained with the HPV-16 E7 gene. As the cells undergoing cytopathological progress, the HPV-16 E6 positive rate was increased, in both villages. In contrast to HPV-16 E6 and E7, detection of the HPV L1 gene was consistently lower, and its prevalence decreased with increasing dysplasia grades (P < 0.05). By ISH analyses, the expression rate of HPV-16 E6 in the specimens collected from the high incidence area was 2.2-fold higher than those from the low incidence area (49 versus 22%, respectively; P < 0.05), and transcription of the E6 gene paralleled cytopathology. HPV-18 was also detected in 17 and 15% of the specimens from the high and low incidence areas, respectively, but most of these samples were also simultaneously HVP-16 positive. These results suggest that HVP-16 plays a causative role in the high incidence of esophageal cancer in the Anyang region of CHINA:

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

PubMed

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

2011-02-01

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

Mucoepidermoid carcinoma does not harbor transcriptionally active high risk human papillomavirus even in the absence of the MAML2 translocation.

PubMed

Bishop, Justin A; Yonescu, Raluca; Batista, Denise; Yemelyanova, Anna; Ha, Patrick K; Westra, William H

2014-01-01

High risk human papillomavirus (HPV) is firmly established as an important cause of oropharyngeal carcinoma. Recent studies have also implicated HPV as a cause of mucoepidermoid carcinoma (MEC)-a tumor of salivary gland origin that frequently harbors MAML2 translocations. The purpose of this study was to determine the prevalence of transcriptionally active HPV in a large group of MECs and to determine whether HPV infection and the MAML2 translocation are mutually exclusive events. Break-apart fluorescence in situ hybridization for MAML2 was performed on a tissue microarray containing 92 MECs. HPV testing was performed using RNA in situ hybridization targeting high risk HPV mRNA E6/E7 transcripts. Of the 71 MECs that could be evaluated by FISH, 57 (80 %) harbored the MAML2 rearrangement. HPV was not detected in any of the 57 MECs that contained a MAML2 rearrangement, in any of the 14 MECs that did not contain the rearrangement, or in any of the 21 MECs where MAML2 status was unknown. High risk HPV does not appear to play any significant role in the development of MEC. It neither complements nor replaces MAML2 translocation in the tumorigenesis of MEC.

Power and Culture in Emerging Medical Technology Policymaking: The Case of the Human Papillomavirus (HPV) Vaccine in Canada

ERIC Educational Resources Information Center

Wyndham-West, Michelle; Wiktorowicz, Mary; Tsasis, Peter

2018-01-01

This article captures how scientific uncertainty is negotiated and its implications on public health policy. Through the case study of the Human Papillomavirus vaccine in Canada, we investigated how policymakers engage in 'sensemaking', the process whereby policymakers mediate shifting informational terrain to come to an understanding of what…

Interplay Between the Temporal Dynamics of the Vaginal Microbiota and Human Papillomavirus Detection

PubMed Central

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

2014-01-01

Background. We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection. Methods. Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models. Results. Participants had an average of 29 samples, with HPV point prevalence between 58%–77%. CST was associated with changes in HPV status (P < .001). Lactobacillus gasseri–dominated CSTs had the fastest HPV remission rate, and a low Lactobacillus community with high proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to L. crispatus–dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95% confidence interval [CI], 1.11–17.7; aTRR, 0.33, 95% CI, .12–1.19, respectively). The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI, .52–6.74). Conclusions. Vaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota. PMID:24943724

Induction of dormancy in hypoxic human papillomavirus-positive cancer cells

PubMed Central

Hoppe-Seyler, Karin; Bossler, Felicitas; Lohrey, Claudia; Bulkescher, Julia; Rösl, Frank; Jansen, Lars; Mayer, Arnulf; Vaupel, Peter; Dürst, Matthias; Hoppe-Seyler, Felix

2017-01-01

Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation. PMID:28115701

Induction of dormancy in hypoxic human papillomavirus-positive cancer cells.

PubMed

Hoppe-Seyler, Karin; Bossler, Felicitas; Lohrey, Claudia; Bulkescher, Julia; Rösl, Frank; Jansen, Lars; Mayer, Arnulf; Vaupel, Peter; Dürst, Matthias; Hoppe-Seyler, Felix

2017-02-07

Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation.

Effects of Information Framing on Human Papillomavirus Vaccination

PubMed Central

Weiner, Judith L.; Kelly, Bridget J.; Hornik, Robert C.; Cappella, Joseph N.

2009-01-01

Abstract Background In June 2006, the first vaccine to prevent human papillomavirus (HPV) transmission was approved for use in females in the United States. Because the vaccine was approved for females as young as 9, its success depends on parents' and individuals' willingness to accept vaccination. Little is known about how attitudes toward this vaccine will be influenced by the way the vaccine is portrayed in the media or in public debate. Methods To assess the effects of information framing on intentions to vaccinate self or female children, if appropriate, 635 adults read one of three short descriptive paragraphs about the vaccine, each of which emphasized a different aspect of the vaccine. Participants were then asked about their intentions to vaccinate under cost or no-cost conditions. Results Women who read that the vaccine protects only against cervical cancer had significantly higher intentions to vaccinate themselves when the vaccine was available at little or no cost compared with women who read alternate versions of the descriptive paragraph, F(2,325) = 5.74, p = 0.004. Conclusions How the HPV vaccine is framed may affect vaccination intentions under certain conditions. Women may be more receptive to the vaccine if it is framed as a cervical cancer prevention tool rather than a sexually transmitted infection (STI) prevention tool. PMID:19183094

Parental Refusal of the Human Papillomavirus Vaccine.

PubMed

DiAnna Kinder, Frances

The purpose of this study was to explore reasons why parents may defer administration of the human papillomavirus (HPV) vaccine to their children. The literature suggests that parents choose to defer administration of this vaccine for several reasons. Data from this pilot study will contribute to our understanding of why parents defer administration of the vaccine. This mixed-methods study took place in a pediatric practice. After a health care visit in which the vaccine was deferred, a survey was provided to the parent in a private room. The survey was confidential and anonymous. A total of 23 surveys were completed. Demographic data were reported. Data were analyzed for descriptive statistics and themes from open-ended questions. The majority of parents (75%) deferred administration of the HPV vaccine because they believed it was too new or required further research. Nurse practitioners are in an excellent position to dispel myths and clarify information about HPV vaccination. The data are useful in communicating with parents and promoting best practices to facilitate good health in children. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

PubMed Central

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

Human papillomavirus 16/18 infections in lung cancer patients in Mexico.

PubMed

Badillo-Almaraz, I; Zapata-Benavides, P; Saavedra-Alonso, S; Zamora-Avila, D; Reséndez-Pérez, D; Tamez-Guerra, R; Herrera-Esparza, R; Rodríguez-Padilla, C

2013-01-01

Human papillomavirus (HPV) is an epitheliotropic, double-stranded DNA virus, and its high-risk genotypes are associated with human cancer. HPV genome has been detected in lung carcinomas in certain places around the world, including Mexico; however, the prevalence of this is unclear. In this study, we examine the frequency of high-risk HPV 16/18 in lung cancer tissues from a Mexican population. 39 lung cancer specimens were analyzed by polymerase chain reaction (PCR) using HPV GP5+/GP6+ primers and then were genotyped using specific primers to HPV 16/18. Additionally, in situ hybridization (ISH) was performed using BIO-labeled oligonucleotide probes. Our results identified 15 positive cases (38.46%) for HPV 16 and 1 positive case (2.56%) for HPV 18 by PCR. ISH showed the presence of HPV DNA in 13 of 16 (81%) samples, in agreement with the PCR results. In this study, we detected HPV 16/18 gene sequences in lung cancer samples obtained from Mexican patients by PCR and ISH. We found the highest prevalence of HPV 16 infection in lung adenocarcinomas, suggesting that HPV infection may be associated with lung cancer. However, further studies are needed to elucidate the role of HPV in lung carcinogenesis. Copyright © 2013 S. Karger AG, Basel.

[Characteristics of the Videos in Spanish Posted on Youtube about Human Papillomavirus Vaccines].

PubMed

Tuells, José; Martínez-Martínez, Pedro Javier; Duro-Torrijos, José Luis; Caballero, Pablo; Fraga-Freijeiro, Paula; Navarro-López, Vicente

2015-01-01

Internet is a resource to search for health-related information. The aim of this work was to know the content of the videos in Spanish language of YouTube related to the vaccine against the human papilloma virus (HPV). An observational study was conducted from a search on YouTube on 26th July 2013 by using keywords such as: "human papilloma virus vaccine", "HPV vaccine", "Gardasil vaccine", "Cervarix vaccine". Different categories were established according to: the type of vaccine, the published source and the favorable or unfavorable predisposition towards the human papillomavirus vaccination. The number of visits and the duration of the videos were gathered, with analysis of variables in the 20 most visited videos. A total of 170 videos were classified like: local news (n=39; 37 favorable, 2 unfavorable; 2:06:29; 42972 visits), national news (n=32; 30/2; 1:49:27; 50138 visits), created by YouTube subscribers (n=21; 21/1; 1:44:39; 10991 visits), advertisements (n=21; 19/2; 0:27:05; 28435 visits), conferences (n=17; 15/2; 3:25:39; 27206 visits), documentaries (n=16; 12/4; 2:11:31; 30629 visits). From all of the 20 most viewed YouTube videos predominated those which were favorable to the vaccination (n=12; 0:43:43; 161789 visits) against the unfavorable (n=8; 2:44:14; 86583 visits). Most of the videos have a favorable opinion towards HPV vaccine, although videos with a negative content were the longest and most viewed.

The Interaction between Human Papillomaviruses and the Stromal Microenvironment

PubMed Central

Woodby, Brittany; Scott, Matthew; Bodily, Jason

2017-01-01

Human papillomaviruses (HPV) 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. 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. PMID:27865458

Social representations of human papillomavirus in Bogotá, Colombia.

PubMed

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

2012-01-01

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

Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study.

PubMed

Gao, Weijiao; Weng, Jinlong; Gao, Yunong; Chen, Xiaochi

2013-06-10

The female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota. A total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects. We found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles. Our study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.

CpG methylation in human papillomavirus (HPV) type 31 long control region (LCR) in cervical infections associated with cytological abnormalities.

PubMed

László, Brigitta; Ferenczi, Annamária; Madar, László; Gyöngyösi, Eszter; Szalmás, Anita; Szakács, Levente; Veress, György; Kónya, József

2016-08-01

The mechanisms that regulate papillomavirus gene expression include DNA methylation. The transcription of papillomavirus oncogenes E6 and E7 is controlled by certain regulatory elements in the LCR, which include binding sites for the E2 protein, a viral regulator of oncogene expression. In HPV-31-infected exfoliated cervical cells, the CpG methylation of the entire LCR was determined by next-generation sequencing after bisulfite modification. Six of the 22 cases had methylated CpG sites in the HPV-31 LCR, including position 7479 and/or 7485, at the promoter distal E2 binding site, thus suggesting a potential regulatory mechanism for papillomavirus transcription.

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.

Expression and characterization of HPV-16 L1 capsid protein in Pichia pastoris

PubMed Central

Bazan, Silvia Boschi; de Alencar Muniz Chaves, Agtha; Aires, Karina Araújo; Cianciarullo, Aurora Marques; Garcea, Robert L.; Ho, Paulo Lee

2013-01-01

Human papillomaviruses (HPVs) are responsible for the most common human sexually transmitted viral infections. Infection with high-risk HPVs, particularly HPV16, is associated with the development of cervical cancer. The papillomavirus L1 major capsid protein, the basis of the currently marketed vaccines, self-assembles into virus-like particles (VLPs). Here, we describe the expression, purification and characterization of recombinant HPV16 L1 produced by a methylotrophic yeast. A codon-optimized HPV16 L1 gene was cloned into a non-integrative expression vector under the regulation of a methanol-inducible promoter and used to transform competent Pichia pastoris cells. Purification of L1 protein from yeast extracts was performed using heparin–sepharose chromatography, followed by a disassembly/reassembly step. VLPs could be assembled from the purified L1 protein, as demonstrated by electron microscopy. The display of conformational epitopes on the VLPs surface was confirmed by hemagglutination and hemagglutination inhibition assays and by immuno-electron microscopy. This study has implications for the development of an alternative platform for the production of a papillomavirus vaccine that could be provided by public health programs, especially in resource-poor areas, where there is a great demand for low-cost vaccines. PMID:19756360

Oral sex practices, oral human papillomavirus and correlations between oral and cervical human papillomavirus prevalence among female sex workers in Lima, Peru.

PubMed

Brown, B; Blas, M M; Cabral, A; Carcamo, C; Gravitt, P E; Halsey, N

2011-11-01

Few data exist on oral human papillomavirus (HPV) prevalence in female sex workers (FSWs). Information regarding oral sex practices of 185 Peruvian FSWs, 18-26 years of age, was obtained via survey and compared with HPV testing results of oral rinse samples. Oral HPV prevalence was 14/185 (7.6%); four (28.9%) HPV genotypes were carcinogenic. One hundred and eighty-two participants reported having had oral sex; 95% reported condom use during oral sex with clients and 9.5% with partners. Women who had oral sex more than three times with their partners in the past month were more likely to have oral HPV than women who had oral sex three times or less (P = 0.06). Ten (71.4%) women with oral HPV were HPV-positive at the cervix; conversely 8.3% of women with cervical HPV were HPV-positive in the oral cavity. The prevalence of oral HPV was relatively low, considering the high rates of oral sex practiced by these women.

Human Papillomavirus Genotyping Using an Automated Film-Based Chip Array

PubMed Central

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

2009-01-01

The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (−) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (−) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping. PMID:19644025

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

PubMed

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

2009-09-01

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

Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guan, Jian; Bywaters, Stephanie M.; Brendle, Sarah A.

2015-09-15

Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope.more » Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays. - Highlights: • We present HPV16-Fab complexes from neutralizing mAbs: H16.1A, H16.14J, and H263.A2. • The structure-function analysis revealed predominantly monovalent binding of each mAb. • Capsid–Fab interactions involved multiple loops from symmetry related L1 proteins. • Besides the known FG and HI loops, epitope mapping also identified DE, EF, and BC loops. • Neutralizing assays complement the structures to show multiple neutralization mechanisms.« less

Detection of human papillomavirus and Epstein-Barr virus DNA sequences in oral mucosa of HIV-infected patients by the polymerase chain reaction.

PubMed Central

Snijders, P. J.; Schulten, E. A.; Mullink, H.; ten Kate, R. W.; Jiwa, M.; van der Waal, I.; Meijer, C. J.; Walboomers, J. M.

1990-01-01

The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) was analyzed in 21 oral biopsy specimens of HIV-infected patients using the polymerase chain reaction (PCR) method. Biopsies were categorized as hairy leukoplakia (HL) (n = 12), candidiasis (n = 3), oral warts (n = 2), and clinically normal epithelium (n = 4). For HPV detection a modified general primer-mediated PCR method (GP-PCR), which detects a broad spectrum of HPV genotypes at sub-picogram levels, was used. Human papillomavirus DNA was only found in two oral warts and was identified as HPV type 32. Epstein-Barr virus DNA was detected in 16 biopsy specimens, including the 12 HLs, 2 cases of candidiasis, and 2 samples of normal epithelium. Epstein-Barr virus positivity in HL could be confirmed by Southern blot analysis and DNA in situ hybridization using biotinylated DNA probes (bio-DISH). Epstein-Barr virus bio-DISH was also positive in one sample of normal epithelium from a patient with HL. The results indicate that HL is strongly associated with EBV and not with any of the common HPV types that react with general HPV primers in the PCR. However the detection of EBV in normal oral epithelium by PCR and bio-DISH suggests that the presence of this virus is not exclusively related to HL. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2169191

High Prevalence of Anal Human Papillomavirus-Associated Cancer Precursors in a Contemporary Cohort of Asymptomatic HIV-Infected Women.

PubMed

Heard, Isabelle; Etienney, Isabelle; Potard, Valérie; Poizot-Martin, Isabelle; Moore, Catherine; Lesage, Anne-Carole; Ressiot, Emmanuelle; Crenn-Hebert, Catherine; Fléjou, Jean-François; Cubie, Heather; Costagliola, Dominique; Darragh, Teresa M

2015-05-15

Although human immunodeficiency virus (HIV)-infected women are at high risk for anal cancer, few data have been published on prevalence of and risk factors for anal precancer and potential screening strategies in this risk group. A cross-sectional anal screening study was nested in a gynecological cohort of HIV-infected women. Anal swab specimens were collected for cytology and human papillomavirus (HPV) testing. High-resolution anoscopy, with biopsy when indicated, was systematically performed. Among the 171 enrolled women, median age was 47.3 years and 98% were receiving combination antiretroviral therapy. Median CD4(+) count was 655 cells/µL and HIV load was <50 copies/mL in 89% of subjects. High-grade anal intraepithelial neoplasia or worse (HG-AIN+) was diagnosed in 12.9% (n = 21). In multivariable analysis, a history of cervical squamous intraepithelial lesion (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.1-16.4) and anal HPV-16 infection (OR, 16.1; 95% CI, 5.4-48.3) was associated with increased risk of HG-AIN+. Abnormal anal cytology and HPV-16 infection performed best as a screening strategy for HG-AIN+ histology, with positive likelihood ratios of 3.4 (95% CI, 2.3-5.1) and 4.7 (95% CI, 2.5-8.7) and negative likelihood ratios of 0.2 (95% CI, .07-.8) and 0.4 (95% CI, .2-.9), respectively. HIV-infected women with a history of HPV-associated cervical disease are at increased risk for HG-AIN+ and should be offered anal cancer screening. Anal cytology and HPV-16 genotyping had the best screening performance. Anal cytology is easy to perform routinely; it may be the best candidate for screening for HG-AIN among HIV-infected women. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma.

PubMed

Ram, Babul Moni; Dolpady, Jayashree; Kulkarni, Rakesh; Usha, R; Bhoria, Usha; Poli, Usha Rani; Islam, Mojahidul; Trehanpati, Nirupma; Ramakrishna, Gayatri

2018-01-01

The calcineurin-NFAT signaling pathway regulates cell proliferation, differentiation, and development in diverse cell types and organ systems. Deregulation of calcineurin-NFAT signaling has been reported in leukaemias and few solid tumors such as breast and colon. In the present study, we found elevated calcineurin protein levels and phosphatase activity in cervical cancer cell lines and depletion of the same attenuated cell proliferation. Additionally, nuclear levels of NFAT2, a downstream target of calcineurin, viz, was found elevated in human papillomavirus (HPV) infected cells, HeLa and SiHa, compared to the HPV negative cells, HaCaT and C33A, indicative of its higher DNA binding activity. The nuclear levels of both NFAT1 and NFAT3 remain unaltered implicating they have little role in cervical carcinogenesis. Similar to the in vitro studies, the HPV infected human squamous cell carcinoma specimens showed higher NFAT2 levels compared to the normal cervical epithelium. Depletion of NFAT2 by RNAi attenuated growth of SiHa cells. Overexpression of HPV16 oncoproteins viz, E6 and E7 increased NFAT2 expression levels and DNA binding activity, while knockdown of E6 by RNAi decreased the same. Briefly, we now report an activation of calcineurin-NFAT2 axis in cervical cancer and a novel role of HPV oncoprotein in facilitating NFAT2 dependent cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein-Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines.

PubMed

Chang, Ann Margaret V; Chiosea, Simion I; Altman, Alexey; Pagdanganan, Hester A; Ma, Changqing

2017-06-01

Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry. One case with MMR deficiency was also assessed for microsatellite instability (MSI) by polymerase chain reaction. EBV and human papillomavirus (HPV) status were tested by in situ hybridization. All NPCs were p16 negative. Three of the 56 NPCs (5%) were EBV negative (EBV-) and HPV negative, while one NPC (1/56, 2%) was EBV positive and showed MSI (EBV+/MSI). Positive PD-L1 expression (PD-L1+), defined as membranous staining in ≥1% tumor cells, was seen in 64% (36/56) of NPCs. All three EBV- NPCs were PD-L1+ as was the EBV+/MSI NPC. PD-L1+ was seen significantly more often in NPCs from non-smokers than those from smokers (23/28, 82% vs 9/18, 50%; P = 0.047). PD-L1+ was not associated with pT, pN, distant metastasis, or clinical stage (P > 0.05). PD-L1+ was not associated with overall survival (P = 0.473). In summary, our results show frequent PD-L1 expression in NPCs regardless of EBV status and a preferential PD-L1 expression in non-smokers. MSI and HPV positivity are exceedingly rare in NPCs.

Multicenter study of human papillomavirus and the human papillomavirus vaccine: knowledge and attitudes among people of African descent.

PubMed

Blackman, Elizabeth; Thurman, Natalie; Halliday, Darron; Butler, Raleigh; Francis, Dorita; Joseph, Madeline; Thompson, Jahzreel; Akers, Aletha; Andraos-Selim, Cecile; Bondzi, Cornelius; 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

To compare knowledge and attitudes of human papillomavirus (HPV) and the vaccine between different cultures of African descent. A cross-sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US and the Bahamas (BHM) was conducted. 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. 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.

The anti-papillomavirus activity of human and bovine lactoferricin.

PubMed

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

2007-09-01

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

College sorority members' knowledge and behaviors regarding human papillomavirus and cervical cancer.

PubMed

Aleshire, Mollie E; Lock, Sharon E; Jensen, Lynne A

2013-06-01

The incidence of human papillomavirus (HPV) is higher in college students than in many other populations. HPV puts young women at risk for developing cervical cancer. The relationship between HPV and risky sexual behaviors has been well established. This study describes female college students' knowledge regarding HPV and cervical cancer, identifies sexual risk behaviors in this group, and assesses whether there is any relationship between knowledge of HPV and cervical cancer and the sexual risk behaviors in this population. Health care providers need to be aware of this health issue and actively promote appropriate prevention strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

[Demyelinating disease and vaccination of the human papillomavirus].

PubMed

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

2011-04-16

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

Human Papillomavirus (HPV) Genotyping: Automation and Application in Routine Laboratory Testing

PubMed Central

Torres, M; Fraile, L; Echevarria, JM; Hernandez Novoa, B; Ortiz, M

2012-01-01

A large number of assays designed for genotyping human papillomaviruses (HPV) have been developed in the last years. They perform within a wide range of analytical sensitivity and specificity values for the different viral types, and are used either for diagnosis, epidemiological studies, evaluation of vaccines and implementing and monitoring of vaccination programs. Methods for specific genotyping of HPV-16 and HPV-18 are also useful for the prevention of cervical cancer in screening programs. Some commercial tests are, in addition, fully or partially automated. Automation of HPV genotyping presents advantages such as the simplicity of the testing procedure for the operator, the ability to process a large number of samples in a short time, and the reduction of human errors from manual operations, allowing a better quality assurance and a reduction of cost. The present review collects information about the current HPV genotyping tests, with special attention to practical aspects influencing their use in clinical laboratories. PMID:23248734

THE ECONOMIC BURDEN OF NONCERVICAL HUMAN PAPILLOMAVIRUS DISEASE IN THE UNITED STATES

PubMed Central

Hu, Delphine; Goldie, Sue J.

2008-01-01

Objective The purpose of this study was: (1) to estimate the direct medical costs of 7 major noncervical human papillomavirus (HPV)-related conditions, including genital cancers, mouth and oropharyngeal cancers, anogenital warts, and juvenile-onset recurrent respiratory papillomatosis; and (2) to approximate the economic burden of noncervical HPV disease. Study Design For each condition, we synthesized the best available secondary data to produce lifetime cost per case estimates, expressed in present value. Using an incidence-based approach, we then applied these costs to develop an aggregrate measure of economic burden. Results The economic burden associated with noncervical HPV 6,11,16, and 18-related conditions occurring in Americans in the year 2003 approximates $418 million (range, $160 million-$1.6 billion). Conclusion The economic burden of noncervical HPV disease is substantial. Analyses that assess the value of investments in HPV prevention and control programs, should take into account the costs, morbidity, and mortality associated with these conditions. PMID:18455524

Concordance of Penile and Oral Human Papillomavirus Infections Among Men in the United States

PubMed Central

Patel, Eshan U.; Rositch, Anne F.; Gravitt, Patti E.

2017-01-01

Abstract This study examined the concordance of penile and oral human papillomavirus (HPV) infections in the United States. A total of 1683 men aged 18–59 years who participated in the 2013–2014 National Health and Nutrition Examination Survey and had results of oral and penile HPV DNA testing were examined. The prevalence of any HPV genotype was 45.3% on the penis, 11.2% in the oral cavity, and 8.8% at both sites. The prevalence of HPV in the oral cavity was higher among those with than among those without penile HPV infection (19.3% vs 4.4%; prevalence ratio, 4.37 [95% confidence interval, 2.66–7.16]). The prevalence of ≥1 genotype-concordant HPV infection was 3.2% and was associated with sexual behavior, independent of demographic characteristics and smoking status. Sexual behavior may partly explain the observed association between penile and oral HPV infections. PMID:28329127

Understanding Human Papillomavirus: An Internet Survey of Knowledge, Risk, and Experience among Female and Male College Students in Hawaii

ERIC Educational Resources Information Center

Bertram, Cathy C.; Niederhauser, Victoria P.

2008-01-01

Background: Persistent Human Papillomavirus (HPV) is an etiologic agent in the development of cervical cancer. Despite the increasingly high prevalence of HPV, people at risk of exposure lack knowledge about the virus, its relationship to cervical cancer, and a realistic perspective regarding HPV consequences. Purpose: To describe knowledge about…

The Uptake of Human Papillomavirus (HPV) Vaccine among Adolescent Females in the United States: A Review of the Literature

ERIC Educational Resources Information Center

Bartlett, Jacqueline A.; Peterson, Jane Anthony

2011-01-01

A comprehensive review of literature was conducted to identify the barriers and facilitators, from the parents'/guardians' and primary care providers' (PCPs) perspective, that are associated with the uptake of Human Papillomavirus (HPV) vaccine among adolescent females. Findings from 14 peer-reviewed articles indicate that 37% of adolescent…

Low human papillomavirus (HPV) vaccine knowledge among Latino parents in Utah.

PubMed

Kepka, Deanna; Warner, Echo L; Kinney, Anita Y; Spigarelli, Michael G; Mooney, Kathi

2015-02-01

Latinas have the highest incidence of cervical cancer, yet Latino parents/guardians' knowledge about and willingness to have their children receive the human papillomavirus (HPV) vaccine is unknown. Latino parents/guardians (N = 67) of children aged 11-17 were recruited from two community organizations to complete a survey, including HPV vaccine knowledge, child's uptake, demographic characteristics, and acculturation. Descriptive statistics and correlates of parents' HPV knowledge and uptake were calculated using Chi square tests and multivariable logistic regression. Receipt of at least one dose of the HPV vaccine was moderate for daughters (49.1%) and low for sons (23.4%). Parents/guardians reported limited knowledge as the main barrier to vaccine receipt. Among parents/guardians with vaccinated daughters, 92.6% did not know the vaccine requires three doses. Adjusting for income, low-acculturated parents were more likely than high-acculturated parents to report inadequate information (OR 8.59, 95% CI 2.11-34.92). Interventions addressing low knowledge and children's uptake of the HPV vaccine are needed among Latino parents/guardians.

SNIPER: a novel assay for human papillomavirus testing among women in Guizhou, China.

PubMed

Belinson, Suzanne E; Wulan, Na; Li, Ruizhen; Zhang, Wei; Rong, Xuan; Zhu, Yasha; Wu, Ruifang; Belinson, Jerome L

2010-08-01

Clinically validate the SNIPER human papillomavirus (HPV) DNA assay for the detection of cervical intraepithelial neoplasia (CIN)2 or higher and CIN2 or higher in a prospective cross-sectional screening study in Guizhou Province, China. Between March and April, 2008, 1000 nonpregnant women aged 30 or older were recruited in Guizhou Province, China. Women positive by SNIPER or cytological examination were requested to return for follow-up. A biopsy of all colposcopically detected abnormalities was performed by quadrant. In normal quadrants, biopsies were obtained at the squamocolumnar junction (2-, 4-, 8-, and 10-o'clock positions depending on the quadrant). Samples were placed in 2 mL of saline solution and maintained between 2 degrees C and 30 degrees C for up to 1 week. One milliliter of this suspension was then prepared and tested. For polymerase chain reaction amplification, a pool of HPV primers was designed to amplify HPV DNA from 13 high-risk-HPV genotypes (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Test characteristics were calculated according to standard definitions. One thousand women were screened; 175 tested HPV positive, 36 women tested negative but had positive Papanicolaou test results. All but 21 (90%) returned for follow-up. Median age and proportions having CIN2 or higher and CIN3 or higher differed by HPV status. Twenty-five women had CIN2 or higher and 16 had CIN3 or higher. The SNIPER assay was 93.3% and 94% sensitive and 86% and 85% specific for the detection of CIN2 or higher and CIN3 or higher, respectively. The positive predictive value was 17.4 % and 9.9% for CIN2 or higher and CIN3 or higher, respectively. Negative predictive value approached 100% for CIN2 or higher and CIN3 or higher. The SNIPER assay is functionally competitive and in terms of cost holds an advantage over Hybrid Capture 2 in a Chinese healthcare market, and potentially others, around the world.

Performing piety in sexual health research: gender, health and evangelical Christianities in a Mexican human papillomavirus (HPV) study.

PubMed

Wentzell, Emily

2017-12-01

Recent research suggests that health surveillance experiences like clinical trial participation might have unanticipated social consequences. I investigate how evangelical Christians participating in longitudinal, observational sexual health research incorporate that long-term medical surveillance into their religious practice. This exploratory research focuses on Mexican Cristianos' participation in the Cuernavaca arm of the multinational 'Human Papillomavirus in Men' ('HIM') study, which tested men for the common and usually asymptomatic sexually transmitted infection human papillomavirus (HPV) over time. I draw on interviews with heterosexual male research participants and their female partners throughout their medical research involvement, and data from church-based participant observation, to understand how couples framed the HIM study as an arena for performing piety. I argue that evangelical understandings of piety as moral practice encouraged participants to view long-term sexual health surveillance as assistance for living out the health, gender, and marital behaviors promoted by their congregations. This finding suggests that health research designers and ethics committees should consider the health and social outcomes of research participants' agentive incorporation of religious observance into study protocols.

Hybrid Capture II detection of oncogenic human papillomavirus: a useful tool when evaluating men who have sex with men with atypical squamous cells of undetermined significance on anal cytology.

PubMed

Goldstone, Stephen E; Kawalek, Adam Z; Goldstone, Robert N; Goldstone, Andrew B

2008-07-01

In the cervix and anus, patients with atypical squamous cells of undetermined significance often do not have high-grade squamous intraepithelial lesions. In women with atypical squamous cells of undetermined significance, Hybrid-Capture II testing for oncogenic high-risk human papillomavirus is performed and those without high-risk human papillomavirus often are observed. We endeavored to determine whether Hybrid-Capture II testing would be beneficial in men who have sex with men with atypical squamous cells of undetermined significance. We performed a retrospective chart review of men who have sex with men with atypical squamous cells of undetermined significance who had high-resolution anoscopy and Hybrid-Capture II. A total of 290 men were identified (mean age, 42 years), and 212 (73 percent) were HIV-negative. High-grade squamous intraepithelial lesions were found in 50 (17 percent): 23 (10 percent) who were HIV-negative and 27 (35 percent) who were HIV-positive men. High-risk human papillomavirus was found in 138 (48 percent); 91 (43 percent) of HIV-negative and 47 (60 percent) of HIV-positive men. The sensitivity, specificity, positive predictive value, and negative predictive value of atypical cells of undetermined significance cytology combined with Hybrid-Capture II were 84, 60, 30, and 95 percent, respectively. There was no significant difference between all men vs. those who were HIV-positive or HIV-negative except for the positive predictive value. Hybrid-Capture II testing for high-risk human papillomavirus in men who have sex with men with atypical cells of undetermined significance and referring only those with high-risk human papillomavirus reduces the number who require high-resolution anoscopy by more than half. Five percent with high-grade squamous intraepithelial lesions would be missed.

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

PubMed

Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

2014-09-01

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

Specificity of L1 Peptides versus Virus-Like Particles for Detection of Human Papillomavirus-Positive Cervical Lesions in Females Attending Engativa Hospital, Bogota, Colombia▿

PubMed Central

Urquiza, Mauricio; Sánchez, Ricardo; Amaya, Jairo; León, Sandra; Acosta, Jenny; Patarroyo, Manuel A.; Camargo, Milena; Patarroyo, Manuel E.

2008-01-01

A serological test for the detection of human papillomavirus (HPV) infection in females at risk of developing cervical cancer could be based on conserved L1 peptides with low levels of antigenicity specifically recognized by antibodies from patients with cervical lesions infected with high-risk HPV (HR-HPV) types. The aim was to assess the ability of L1 peptides 18283, 18294, and 18301 compared with the ability of virus-like particles (VLPs) to identify these infections in females. A total of 391 HPV-infected female volunteers were interviewed, and peripheral blood and cervical cells were obtained for detection of anti-HPV antibodies and HPV DNA; all of the patients had a Pap smear test; 287 patients were referred for colposcopy or biopsy, according to gynecological criteria. The level of agreement, as determined by the use of the Lin coefficient (rho value), showed that 75 to 83% of females with HR-HPV DNA-positive cervical lesions had antibodies that recognized VLPs and peptide 18283, 18294, or 18301, while 15 to 23% of the HPV DNA-negative females with a normal cytology had antibodies that recognized these three peptides and 45% had antibodies that recognized VLPs. The rate of agreement between peptides and VLPs for antibody detection was higher for patients with HPV DNA-positive cervical lesions. Peptides 18283, 18294, and 18301 showed similar sensitivities for the detection of HR-HPV DNA-positive cervical lesions and were more specific than VLPs. Peptide 18301 might be detecting protective antibodies in HPV DNA-negative females with atypical squamous cells of undetermined significance. These peptides could be useful for the design of a serology test for the detection of HR-HPV infection in females with cervical lesions and at risk of cervical cancer. PMID:18799706

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.

Intraepithelial and invasive neoplasia of the vulva in association with human papillomavirus infection.

PubMed

Planner, R S; Hobbs, J B

1988-06-01

Colposcopic examination of 335 women with cytologically detected human papillomavirus (HPV) revealed involvement of the cervix in 316 patients (94%), vagina in 276 (82%) and vulva in 148 (44%). A symptom complex of pruritus and superficial dyspareunia was found in 98 of the 148 patients with vulvar infection (66%). Histologic examination revealed HPV-associated vulvar intraepithelial neoplasia (VIN) in 11 of 148 biopsies (7.4%). Follow-up of the patients with HPV infection with or without VIN showed a spontaneous regression rate of 56% but also demonstrated progression to VIN 3 in two patients and to invasive carcinoma of the vulva in one.

Inhibition of Human Papillomavirus Type 16 Infection Using an RNA Aptamer.

PubMed

Valencia-Reséndiz, Diana Gabriela; Palomino-Vizcaino, Giovanni; Tapia-Vieyra, Juana Virginia; Benítez-Hess, María Luisa; Leija-Montoya, Ana Gabriela; Alvarez-Salas, Luis Marat

2018-04-01

Human papillomavirus type 16 (HPV16) DNA has been found in ∼50% of cervical tumors worldwide. HPV infection starts with the binding of the virus capsid to heparan sulfate (HS) receptors exposed on the surface of epithelial basal layer keratinocytes. Previously, our group isolated a high-affinity RNA aptamer (Sc5c3) specific for HPV16 L1 virus-like particles (VLPs). In this study, we report the inhibition of HPV16 infection by Sc5c3 in a pseudovirus (PsVs) model. 293TT cells were infected by HPV16 PsVs containing the yellow fluorescent protein (YFP) as reporter gene. Incubation of HPV16 PsVs with Sc5c3 before infection resulted in a dose-dependent decrease in YFP fluorescence, suggesting infection inhibition. Aptamer degradation by RNase A restored PsVs infectivity, supporting the previous observation that Sc5c3 aptamer can inhibit infection. VLP mutants with removed HS binding sites were used in binding assays to elucidate the Sc5c3 blocking mechanism; however, no binding difference was observed between wild-type and mutant VLPs, suggesting that pseudoinfection inhibition relies on mechanisms additional to electrostatic HS binding site interaction. A DNA/RNA Sc5c3 version also inhibited HPV PsVs infection, suggesting that a modified, nuclease-resistant Sc5c3 may be used to inhibit HPV16 infection in vivo.

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

Prevalence of human papillomavirus in middle ear carcinoma associated with chronic otitis media.

PubMed Central

Jin, Y. T.; Tsai, S. T.; Li, C.; Chang, K. C.; Yan, J. J.; Chao, W. Y.; Eng, H. L.; Chou, T. Y.; Wu, T. C.; Su, I. J.

1997-01-01

Squamous cell carcinoma of the middle ear (MESCC) is an uncommon tumor and is associated with a history of long-term chronic otitis media (COM) in most cases. Although the human papillomaviruses (HPVs) have been implicated in many human neoplasms, its role in the pathogenesis of MESCC has not been studied. Polymerase chain reaction (PCR) using consensus primers for the detection of HPV types 6, 11, 16, 18, 31, 33, 52b, and 58 was applied in screening fourteen cases of MESCC from archival material. Further subtyping was performed by restriction enzyme digestion of PCR products and by in situ hybridization method on tissue sections. Of the fourteen cases of MESCC, eleven were found to have HPV DNA. HPV-16 was detected in all positive cases. Five cases revealed both HPV-16 and -18. A history of long-term COM (> 3 years) was found in thirteen of the cases. This is the first report to localize HPV-16/18 in MESCC on both the tissue level and the molecular level. The high prevalence of HPV in COM-associated MESCC therefore provides a good model to explain the pathogenesis of chronic-inflammation-related human malignancies. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 4 PMID:9094989

School Nurses' Knowledge, Attitudes, Perceptions of Role as Opinion Leader, and Professional Practice Regarding Human Papillomavirus Vaccine for Youth

ERIC Educational Resources Information Center

Rosen, Brittany L.; Goodson, Patricia; Thompson, Bruce; Wilson, Kelly L.

2015-01-01

Background: Because human papillomavirus (HPV) vaccine rates remain low, we evaluated US school nurses' knowledge, attitudes, perceptions of their role as opinion leaders, and professional practice regarding HPV vaccine, and assessed whether knowledge, attitudes, and perceptions of being an opinion leader influenced their professional…

Oral and cervical human papillomavirus infection among female sex workers in Japan.

PubMed

Matsushita, Kaori; Sasagawa, Toshiyuki; Miyashita, Michiko; Ishizaki, Azumi; Morishita, Atsushi; Hosaka, Norimitsu; Saikawa, Kunikazu; Hoshina, Shinji; Bi, Xiuqiong; Ichimura, Hiroshi

2011-01-01

It has been reported recently that oral human papillomavirus (HPV) infection is associated with oropharyngeal squamous cell carcinomas. The aim of this study was to determine the prevalence of HPV infection and HPV types in the oral cavity and cervix of female sex workers in Japan. Oral and cervical swabs were taken from 196 female sex workers who visited a clinic for regular medical checkups in 2007, and genomic DNA was extracted from those specimens. The HPV L1 gene was amplified by polymerase chain reaction (PCR) using original and modified GP5(+)/6(+) primers, and genotyping was performed using the Kurabo GeneSquare Microarray or by sequencing cloned PCR products. HPV DNA was detected in the oral cavity of 12 (6.1%) women, with HPV-56 being the most common type (7/12). Likewise, HPV DNA was detected in the cervix of 103 (52.6%) women, with HPV-52 (30/103, 29.1%), followed by HPV-16 (24.3%) and HPV-56 (18.4%), being the most common. Of the 12 women with oral HPV infection, only two were infected with the concordant HPV genotype in the cervix. These findings suggest that oral HPV infection occurs independently of cervical HPV infection in this population, and that oral HPV infection may play a role in HPV transmission in Japan.

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

PubMed

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

2015-03-24

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2011-05-01

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

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

PubMed

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

2014-12-01

We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection. Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models. Participants had an average of 29 samples, with HPV point prevalence between 58%-77%. CST was associated with changes in HPV status (P<.001). Lactobacillus gasseri-dominated CSTs had the fastest HPV remission rate, and a low Lactobacillus community with high proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to L. crispatus-dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95% confidence interval [CI], 1.11-17.7; aTRR, 0.33, 95% CI, .12-1.19, respectively). The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI, .52-6.74). Vaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Patterns of human papillomavirus types in multiple infections: an analysis in women and men of the high throughput human papillomavirus monitoring study.

PubMed

Vaccarella, Salvatore; Söderlund-Strand, Anna; Franceschi, Silvia; Plummer, Martyn; Dillner, Joakim

2013-01-01

To evaluate the pattern of co-infection of human papillomavirus (HPV) types in both sexes in Sweden. Cell samples from genital swabs, first-void urine, and genital swabs immersed in first-void urine were collected in the present cross-sectional High Throughput HPV Monitoring study. Overall, 31,717 samples from women and 9,949 from men (mean age 25) were tested for 16 HPV types using mass spectrometry. Multilevel logistic regression was used to estimate the expected number of multiple infections with specific HPV types, adjusted for age, type of sample, and accounting for correlations between HPV types due to unobserved risk factors using sample-level random effects. Bonferroni correction was used to allow for multiple comparisons (120). Observed-to-expected ratio for any multiple infections was slightly above unity in both sexes, but, for most 2-type combinations, there was no evidence of significant departure from expected numbers. HPV6/18 was found more often and HPV51/68 and 6/68 less often than expected. However, HPV68 tended to be generally underrepresented in co-infections, suggesting a sub-optimal performance of our testing method for this HPV type. We found no evidence for positive or negative clustering between HPV types included in the current prophylactic vaccines and other untargeted oncogenic types, in either sex.

Molecular analysis of human papillomavirus virus-like particle activated Langerhans cells in vitro.

PubMed

Woodham, Andrew W; Raff, Adam B; Da Silva, Diane M; Kast, W Martin

2015-01-01

Langerhans cells (LC) are the resident antigen-presenting cells in human epithelium, and are therefore responsible for initiating immune responses against human papillomaviruses (HPV) entering the epithelial and mucosal layers in vivo. Upon proper pathogenic stimulation, LC become activated causing an internal signaling cascade that results in the up-regulation of co-stimulatory molecules and the release of inflammatory cytokines. Activated LC then migrate to lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response. However, HPV manipulates LC in a suppressive manner that alters these normal maturation responses. Here, in vitro LC activation assays for the detection of phosphorylated signaling intermediates, the up-regulation of activation-associated surface markers, and the release of inflammatory cytokines in response to HPV particles are described.

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

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

Safety of human papillomavirus vaccines: a review.

PubMed

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

2015-05-01

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

The Human Papillomavirus Type 8 E6 Protein Interferes with NOTCH Activation during Keratinocyte Differentiation

PubMed Central

Meyers, Jordan M.; Spangle, Jennifer M.

2013-01-01

Cutaneous β-human papillomavirus (β-HPV) E6 proteins inhibit NOTCH signaling by associating with the transcriptional coactivator MAML1. NOTCH has tumor suppressor activities in epithelial cells and is activated during keratinocyte differentiation. Here we report that HPV type 8 (HPV8) E6 subverts NOTCH activation during keratinocyte differentiation by inhibiting RBPJ/MAML1 transcriptional activator complexes at NOTCH target DNA. NOTCH inhibition impairs epithelial differentiation and may thus contribute to β-HPV replication and viral oncogenesis. PMID:23365452

Evaluation of the Acceptability and Feasibility of a Computer-Tailored Intervention to Increase Human Papillomavirus Vaccination among Young Adult Women

ERIC Educational Resources Information Center

Paiva, Andrea L.; Lipschitz, Jessica M.; Fernandez, Anne C.; Redding, Colleen A.; Prochaska, James O.

2014-01-01

Objective: To examine acceptability and feasibility of a Transtheoretical Model (TTM)-based computer-tailored intervention (CTI) for increasing human papillomavirus (HPV) vaccination in college-aged women. Participants: Two hundred forty-three women aged 18-26 were recruited between February and May of 2011. Methods: Participants completed the…

Human papillomavirus-driven immune deviation: challenge and novel opportunity for immunotherapy.

PubMed

Smola, Sigrun; Trimble, Connie; Stern, Peter L

2017-06-01

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with

DNA plasmid vaccine carrying Chlamydia trachomatis (Ct) major outer membrane and human papillomavirus 16L2 proteins for anti-Ct infection.

PubMed

Wang, Ledan; Cai, Yiqi; Xiong, Yirong; Du, Wangqi; Cen, Danwei; Zhang, Chanqiong; Song, Yiling; Zhu, Shanli; Xue, Xiangyang; Zhang, Lifang

2017-05-16

Chlamydia trachomatis (Ct) is one of the most frequently encountered sexual infection all over the world, yielding tremendous reproductive problems (e.g. infertility and ectopic pregnancy) in the women. This work described the design of a plasmid vaccine that protect mice from Ct infection, and reduce productive tract damage by generating effective antibody and cytotoxic T cell immunity. The vaccine, s was composed of MOMP multi-epitope and HPV16L2 genes carried in pcDNA plasmid (i.e. pcDNA3.1/MOMP/HPV16L). In transfection, the vaccine expressed the chimeric genes (i.e. MOMP and HPV16L2), as demonstrated via western blot, RT-PCR and fluorescence imaging. In vitro, the vaccine transfected COS-7 cells and expressed the proteins corresponding to the genes carried in the vaccine. Through intramuscular immunization in BALB/c mice, the vaccine induced higher levels of anti-Ct IgG titer, anti-HPV16L2 IgG titer in serum and IgA titer in local mucosal secretions, compared to plasmid vaccines that carry only Ct MOMP multi-epitope or HPV16L2 chimeric component only. In mice intravaginally challenged with Ct, the vaccines pcDNA3.1/MOMP/HPV16L2 generated a higher level of genital protection compared to other vaccine formulations. Additionally, histochemical staining indicated that pcDNA3.1/MOMP/HPV16L2 eliminated mouse genital tract tissue pathologies induced by Ct infection. This work demonstrated that pcDNA/MOMP/HPV16L2 vaccine can protect against Ct infection by regulating antibody production, cytotoxic T cell killing functions and reducing pathological damage in mice genital tract. This work can potentially offer us a new vaccine platform against Ct infection.

Deregulation of SYCP2 predicts early stage human papillomavirus-positive oropharyngeal carcinoma: A prospective whole transcriptome analysis.

PubMed

Masterson, Liam; Sorgeloos, Frederic; Winder, David; Lechner, Matt; Marker, Alison; Malhotra, Shalini; Sudhoff, Holger; Jani, Piyush; Goon, Peter; Sterling, Jane

2015-11-01

This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT-quantitative real-time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin-fixed, paraffin-embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high-risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV-associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV-associated cancer development. If further corroborated, this data may contribute to the development of a non-invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945). © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pecoraro, G.; Morgan, D.; Defendi, V.

1989-01-01

The human papillomaviruses (HPVs) are associated with specific benign and malignant lesions of the skin and mucosal epithelia. Cloned viral DNAs from HPV types 6b, 16, and 18 associated with different pathological manifestations of genital neoplasia in vivo were introduced into primary human cervical epithelial cells by electroporation. Cells transfected with HPV16 or HPV18 DNA acquired indefinite lifespans, distinct morphological alterations, and anchorage-independent growth (HPV18), and contain integrated transcriptionally active viral genomes. HPV6b or plasmid electroporated cells senesced at low passage. The alterations in growth and differentiation of the cells appear to reflect the progressive oncogenic processes that result inmore » cervical carcinoma in vivo.« less

Urine human papillomavirus prevalence in women with high-grade cervical lesions.

PubMed

Nicolau, P; Mancebo, G; Agramunt, S; Solé-Sedeño, J M; Bellosillo, B; Muset, M M; Lloveras, B; Alameda, F; Carreras, R

2014-12-01

To determine the prevalence of human papillomavirus (HPV) in urine samples from women with high-grade cervical lesions. Secondary objectives are to identify the influence of socio-demographic factors and the different genotypes with urinary HPV positivity. 75 women with a positive biopsy for CIN2+ were included in the study from October 2010 to July 2011. A sample of urine was collected immediately before conization at the outpatient clinic. We analyzed the presence of HPV using a PCR technique. The mean age of the patients was 34.8 years (range 24 to 61). All patients had histological CIN2+, of whom 54.67% had CIN3. The prevalence of HPV in urine test was 58.82% in CIN2 population versus 78.05% in CIN3 patients (p 0.072). 31 different genotypes were found. The most frequent HPV genotype was 16-HPV, which was identified in 58% of women with positive HPV-DNA in urine samples. No demographic characteristics were significantly associated to urinary HPV prevalence. Most of the patients with CIN2+ showed positive results for urine HPV test. The prevalence of positive urinary HPV test was higher for patients with CIN3. HPV urine detection could be considered as an acceptable option for high-risk population who skip regular screening programs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2008-01-01

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

Comprehensive Morpho-Electrotonic Analysis Shows 2 Distinct Classes of L2 and L3 Pyramidal Neurons in Human Temporal Cortex

PubMed Central

Deitcher, Yair; Eyal, Guy; Kanari, Lida; Verhoog, Matthijs B; Atenekeng Kahou, Guy Antoine; Mansvelder, Huibert D; de Kock, Christiaan P J; Segev, Idan

2017-01-01

Abstract There have been few quantitative characterizations of the morphological, biophysical, and cable properties of neurons in the human neocortex. We employed feature-based statistical methods on a rare data set of 60 3D reconstructed pyramidal neurons from L2 and L3 in the human temporal cortex (HL2/L3 PCs) removed after brain surgery. Of these cells, 25 neurons were also characterized physiologically. Thirty-two morphological features were analyzed (e.g., dendritic surface area, 36 333 ± 18 157 μm2; number of basal trees, 5.55 ± 1.47; dendritic diameter, 0.76 ± 0.28 μm). Eighteen features showed a significant gradual increase with depth from the pia (e.g., dendritic length and soma radius). The other features showed weak or no correlation with depth (e.g., dendritic diameter). The basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites. Unlike the morphological features, the active biophysical features (e.g., spike shapes and rates) and passive/cable features (e.g., somatic input resistance, 47.68 ± 15.26 MΩ, membrane time constant, 12.03 ± 1.79 ms, average dendritic cable length, 0.99 ± 0.24) were depth-independent. A novel descriptor for apical dendritic topology yielded 2 distinct classes, termed hereby as “slim-tufted” and “profuse-tufted” HL2/L3 PCs; the latter class tends to fire at higher rates. Thus, our morpho-electrotonic analysis shows 2 distinct classes of HL2/L3 PCs. PMID:28968789

Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

PubMed Central

Tonon, S A; Picconi, M A; Zinovich, J B; Liotta, D J; Bos, P D; Galuppo, J A; Alonio, L V; Ferreras, J A; Teyssié, A R

1999-01-01

OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence. PMID:10524669

Vaccination against Human Papillomavirus in relation to Financial Crisis: The "Evaluation and Education of Greek Female Adolescents on Human Papillomaviruses' Prevention Strategies" ELEFTHERIA Study.

PubMed

Mammas, Ioannis N; Theodoridou, Maria; Koutsaftiki, Chryssie; Bertsias, George; Sourvinos, George; Spandidos, Demetrios A

2016-08-01

In this study we aimed to explore financial and other sociodemographic factors that affect nonvaccination against the human papillomavirus (HPV) in Greece, one of the first European Union countries to introduce the vaccination against HPV into its National Immunization Programme in 2008. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Six hundred thirty-two female adolescents (aged 11-16 years) from Greece completed a pilot cross-sectional questionnaire-based survey (ELEFTHERIA study) from 2008 to 2014. Overall, only 8.9% (56 of 632) of the female adolescents reported that they had received all 3 doses of the HPV vaccination. The HPV vaccination uptake rates increased gradually from 3.2% (3 of 95) in 2008 to 17.1% (14 of 82) in 2011. However, it abruptly decreased to 2.1% (2 of 95) in 2012 and it reached 9.2% (8 of 87) in 2013 and 11.5% (11 of 96) in 2014. The most common factors for nonvaccination included fear of side effects, which decreased (Spearman ρ = -0.860; P = .024) and financial issues, which increased statistically significantly (Spearman ρ = 0.890; P = .012) during the years 2008 to 2014. In our study we addressed the novel topic of the association of financial issues with HPV vaccination compliance and highlighted the urgent need to provide and maintain health insurance coverage to children in Greece, a country in financial crisis. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1.

PubMed

Anacker, Daniel C; Gautam, Dipendra; Gillespie, Kenric A; Chappell, William H; Moody, Cary A

2014-08-01

Activation of the ATM (ataxia telangiectasia-mutated kinase)-dependent DNA damage response (DDR) is necessary for productive replication of human papillomavirus 31 (HPV31). We previously found that DNA repair and homologous recombination (HR) factors localize to sites of HPV replication, suggesting that ATM activity is required to recruit factors to viral genomes that can productively replicate viral DNA in a recombination-dependent manner. The Mre11-Rad50-Nbs1 (MRN) complex is an essential component of the DDR that is necessary for ATM-mediated HR repair and localizes to HPV DNA foci. In this study, we demonstrate that the HPV E7 protein is sufficient to increase levels of the MRN complex and also interacts with MRN components. We have found that Nbs1 depletion blocks productive viral replication and results in decreased localization of Mre11, Rad50, and the principal HR factor Rad51 to HPV DNA foci upon differentiation. Nbs1 contributes to the DDR by acting as an upstream activator of ATM in response to double-strand DNA breaks (DSBs) and as a downstream effector of ATM activity in the intra-S-phase checkpoint. We have found that phosphorylation of ATM and its downstream target Chk2, as well as SMC1 (structural maintenance of chromosome 1), is maintained upon Nbs1 knockdown in differentiating cells. Given that ATM and Chk2 are required for productive replication, our results suggest that Nbs1 contributes to viral replication outside its role as an ATM activator, potentially through ensuring localization of DNA repair factors to viral genomes that are necessary for efficient productive replication. The mechanisms that regulate human papillomavirus (HPV) replication during the viral life cycle are not well understood. Our finding that Nbs1 is necessary for productive replication even in the presence of ATM (ataxia telangiectasia-mutated kinase) and Chk2 phosphorylation offers evidence that Nbs1 contributes to viral replication downstream of facilitating ATM

Productive Replication of Human Papillomavirus 31 Requires DNA Repair Factor Nbs1

PubMed Central

Anacker, Daniel C.; Gautam, Dipendra; Gillespie, Kenric A.; Chappell, William H.

2014-01-01

ABSTRACT Activation of the ATM (ataxia telangiectasia-mutated kinase)-dependent DNA damage response (DDR) is necessary for productive replication of human papillomavirus 31 (HPV31). We previously found that DNA repair and homologous recombination (HR) factors localize to sites of HPV replication, suggesting that ATM activity is required to recruit factors to viral genomes that can productively replicate viral DNA in a recombination-dependent manner. The Mre11-Rad50-Nbs1 (MRN) complex is an essential component of the DDR that is necessary for ATM-mediated HR repair and localizes to HPV DNA foci. In this study, we demonstrate that the HPV E7 protein is sufficient to increase levels of the MRN complex and also interacts with MRN components. We have found that Nbs1 depletion blocks productive viral replication and results in decreased localization of Mre11, Rad50, and the principal HR factor Rad51 to HPV DNA foci upon differentiation. Nbs1 contributes to the DDR by acting as an upstream activator of ATM in response to double-strand DNA breaks (DSBs) and as a downstream effector of ATM activity in the intra-S-phase checkpoint. We have found that phosphorylation of ATM and its downstream target Chk2, as well as SMC1 (structural maintenance of chromosome 1), is maintained upon Nbs1 knockdown in differentiating cells. Given that ATM and Chk2 are required for productive replication, our results suggest that Nbs1 contributes to viral replication outside its role as an ATM activator, potentially through ensuring localization of DNA repair factors to viral genomes that are necessary for efficient productive replication. IMPORTANCE The mechanisms that regulate human papillomavirus (HPV) replication during the viral life cycle are not well understood. Our finding that Nbs1 is necessary for productive replication even in the presence of ATM (ataxia telangiectasia-mutated kinase) and Chk2 phosphorylation offers evidence that Nbs1 contributes to viral replication downstream of

Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crum, C.P.; Nuovo, G.; Friedman, D.

1988-01-01

The accumulation of human papillomavirus type 16 (HPV-16)-specific RNAs in tissue sections from biopsies of patients with genital precancers was studied by in situ hybridization with single-stranded /sup 35/S-labeled RNA. These analyses revealed that the most abundant early-region RNAs were derived from the E4 and E5 open reading frames (ORFs). RNAs homologous to the E6/E7 ORFs were also detected, whereas RNAs homologous to the intervening E1 ORF were not. This suggest that the E4 and E5 mRNAs are derived by splicing to the upstream E6/E7 ORFs, consistent with studies of HPV-11 in condylomata. Abundant RNAs homologous to the 5' portionmore » of L1 were also detected. These RNAs were localized to the apical strata of the epithelium. HPV-16 RNAs accumulated in discrete regions of these lesions, and when present were most abundant in the upper cell layers of the precancerous epithelium. RNAs homologous to early ORFs were also detected in some germinal cells within the basal layer of the epithelium.« less

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

Cost-effectiveness of human papillomavirus vaccination in the United States.

PubMed

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

2008-02-01

We describe a simplified model, based on the current economic and health effects of human papillomavirus (HPV), to estimate the cost-effectiveness of HPV vaccination of 12-year-old girls in the United States. Under base-case parameter values, the estimated cost per quality-adjusted life year gained by vaccination in the context of current cervical cancer screening practices in the United States ranged from $3,906 to $14,723 (2005 US dollars), depending on factors such as whether herd immunity effects were assumed; the types of HPV targeted by the vaccine; and whether the benefits of preventing anal, vaginal, vulvar, and oropharyngeal cancers were included. The results of our simplified model were consistent with published studies based on more complex models when key assumptions were similar. This consistency is reassuring because models of varying complexity will be essential tools for policy makers in the development of optimal HPV vaccination strategies.

Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial.

PubMed

Ronco, Guglielmo; Segnan, Nereo; Giorgi-Rossi, Paolo; Zappa, Marco; Casadei, Gian Piero; Carozzi, Francesca; Dalla Palma, Paolo; Del Mistro, Annarosa; Folicaldi, Stefania; Gillio-Tos, Anna; Nardo, Gaetano; Naldoni, Carlo; Schincaglia, Patrizia; Zorzi, Manuel; Confortini, Massimo; Cuzick, Jack

2006-06-07

Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology

Human papillomavirus type-18 prevalence in oesophageal cancer in the Chinese population: a meta-analysis.

PubMed

Guo, L W; Zhang, S K; Liu, S Z; Chen, Q; Zhang, M; Quan, P L; Lu, J B; Sun, X B

2016-02-01

Globally, the prevalence of oesophageal cancer cases is particularly high in China. Since 1982, oncogenic human papillomavirus (HPV) has been hypothesized as a risk factor for oesophageal cancer, but no firm evidence of HPV infection in oesophageal cancer has been established to date. We aimed to conduct a meta-analysis to estimate the high-risk HPV-18 prevalence of oesophageal cancer in the Chinese population. Eligible studies published from 1 January 2005 to 12 July 2014 were retrieved via computer searches of English and Chinese literature databases (including Medline, EMBASE, Chinese National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform). A random-effects model was used to calculate pooled prevalence and corresponding 95% confidence intervals (CIs). A total of 2556 oesophageal cancer cases from 19 studies were included in this meta-analysis. Overall, the pooled HPV-18 prevalence in oesophageal cancer cases was 4·1% (95% CI 2·7-5·5) in China, 6·1% (95% CI 2·9-9·3) in fresh or frozen biopsies and 4·0% (95% CI 2·3-5·8) in paraffin-embedded fixed biopsies, 8·2% (95% CI 4·6-11·7) by the E6/E7 region and 2·2% (95% CI 0·9-3·6) by the L1 region of the HPV gene. This meta-analysis indicated that China has a moderate HPV-18 prevalence of oesophageal cancer compared to cervical cancer, although there is variation between different variables. Further studies are needed to elucidate the role of HPV in oesophagus carcinogenesis with careful consideration of study design and laboratory detection method, providing more accurate assessment of HPV status in oesophageal cancer.

Prevalence of and risk factors for anal human papillomavirus infection in heterosexual men.

PubMed

Nyitray, Alan; Nielson, Carrie M; Harris, Robin B; Flores, Roberto; Abrahamsen, Martha; Dunne, Eileen F; Giuliano, Anna R

2008-06-15

In US men, the incidence of anal cancer, the primary cause of which is human papillomavirus (HPV) infection, has increased almost 3-fold in 3 decades; however, little is known about the epidemiology of anal HPV infection, especially in heterosexual men. In 2 US cities, behavioral data and anal biological specimens were collected from 253 men who acknowledged having engaged in sexual intercourse with a woman during the preceding year. On the basis of DNA analysis, overall prevalence of anal HPV infection was found to be 24.8% in 222 men who acknowledged having had no prior sexual intercourse with men. Of the men with anal HPV infection, 33.3% had an oncogenic HPV type. Risk factors independently associated with anal HPV were lifetime number of female sex partners and frequency of sex with females during the preceding month. These results suggest that anal HPV infection may be common in heterosexual men.

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