Dissertations / Theses: 'Papillomavirus humain (HPV)'

1

Olivera-Botello, Gustavo. "Modélisation numérique des aspects immunologiques de la réaction à l’infection à HPV et de la vaccination anti-HPV par Gardasil®." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10038/document.

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L’infection au papillomavirus humain (HPV) est connue pour être le principal facteur causal d’une série de maladies aussi bien bénignes (condylomatose ano-génitale, papillomatose lyringée, et autres) que malignes (cancer du col de l’utérus, certains cancers ORL, et autres). Deux vaccins prophylactiques (Gardasil® et Cervarix®) sont sur la marché depuis à peu près quatre ans pour prévenir cette infection. Le présent travail de thèse comportait trois objectifs principaux : i) étudier in-silico l’immunogénicité du vaccin Gardasil® ; ii) étudier in-silico l’histoire naturelle d’une infection à HPV et iii) évaluer in-silico le potentiel de l’hypothèse thérapeutique suivante : l’administration intramusculaire du vaccin Gardasil® chez des patients atteints d’une papillomatose laryngée induirait un effet bénéfique car l’arrivée des immunoglobulines au tissu affecté empêcherait l’HPV de compléter son cycle de vie et, par conséquent, la maladie de se propager. Les principales conclusions sont : i) pour qu’une papillomatose laryngée ne s’étende pas il faudrait, d’après nos simulations, que le taux d’IgGs sériques soit maintenu au-dessus de 200 mMU/mL ; ii) pour rester, sur une période de 10 ans, le plus longtemps possible au-dessus de ce seuil (d´effet thérapeutique), en administrant la quantité minimale de vaccin, il faudrait, d’après nos simulations, suivre le protocole suivant : l’immunisation de base (à 0, 2 et 6 mois), suivie de trois rappels successifs tous les six mois jusqu’au 24ème mois, suivis d’un rappel 18 mois plus tard ; iii) par ailleurs, il semble inutile (voire contreproductif), d’après nos simulations, de modifier le schéma traditionnel de base (0-2-6 mois)
Two prophylactic vaccines have demonstrated to prevent infections with the human papillomavirus (HPV). Thus, they have been in the market for the last four years, or so. The three main objectives of the present project were: i) to study in-silico the immunogenicity of one of these vaccines (Gardasil®); ii) to study in-silico the natural history of an HPV infection, and iii) to assess in-silico the potential of the following therapeutic hypothesis : the intramuscular administration of Gardasil® to patients already suffering from a recurrent respiratory papillomatosis would result in a better prognosis thanks to the fact that the HPV-specific immunoglobulins that would bathe the affected tissue would impede the virus to complete its life cycle and, therefore, the disease to progress. The main conclusions are: i) according to our simulations, the minimum serum IgG titer required for hampering the progression of a recurrent respiratory papillomatosis would be 200 mMU/mL ; ii) in order to keep, within a time window of ten years, the anti-HPV IgG titer over the just-mentioned therapeutic-effect threshold, the biggest possible fraction of time and through the administration of the smallest possible number of booster doses, it would be necessary, according to our simulations, to adopt the following vaccination schedule: the basic three doses (at months 0, 2 and 6), followed by three successive booster doses, every six months, until reaching the 24th month, followed by a late final booster dose, 18 months later. iii) incidentally, it would seem to be inappropriate, according to our simulations, to modify the original initial vaccination schedule (at months 0, 2 and 6)

2

Bernard, Xavier. "Stabilisation de p53 et rôle du kinome humain dans l'oncogenèse HPV." Strasbourg, 2010. http://www.theses.fr/2010STRA6223.

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Troisième cause de mortalité par cancer chez la femme, les carcinomes du col utérin sont associés dans 99,7% des cas à une infection de virus du papillome humain (HPV de type 16 et 18 essentiellement). L’effet oncogène de ces HPV est principalement provoqué par l’intégration des gènes codant deux oncoprotéines virales, E6 et E7, dans le génome de la cellule infectée. L’inhibition spécifique de l’oncoprotéine E6 constitue un enjeu thérapeutique majeur. En effet, l’inhibition de E6 provoque la restauration de la protéine p53 et induit l’orientation des cellules cancéreuses vers la sénescence ou l’apoptose. Cependant, le développement de nouvelles stratégies thérapeutiques nécessite une bonne compréhension des mécanismes de carcinogenèse afin de découvrir de nouvelles cibles potentielles et de permettre l’élaboration de stratégies efficaces. C’est dans ce contexte scientifique que s’est inscrit mon projet de thèse portant sur la dissection des mécanismes moléculaires de dégradation de la protéine p53 par E6. Pour cela nous avons articulé nos travaux autour de deux axes de recherches: (i) déterminer les résidus de p53 impliqués dans le site de fixation avec les E6 à "haut risque", responsables de la dégradation de p53; (ii) identifier les kinases ayant un rôle sur la dégradation de p53 dans des cellules transformées par HPV. Ce travail a permis de démontrer l’importance de la conformation du domaine central de p53 dans la liaison avec E6, par des études portant sur les relations structure/fonction de mutants de p53. De plus, nous avons mis en évidence le rôle de la pseudo-kinase NRBP1 dans la régulation de p53 au sein des cellules transformées par HPV, via la voie NF-B
Third leading cause of cancer death in women, cervical carcinomas are associated in 99. 7% of cases with infection of human papillomavirus (HPV types 16 and 18 mostly). The oncogenic effect of these HPV is mainly caused by the integration of genes encoding two viral oncoproteins, E6 and E7 into the genome of infected cells. Specific inhibition of the E6 oncoprotein is a major therapeutic challenge. Indeed, inhibition of E6 leads to a restoration of p53 protein and induces the orientation of the cancer cells to senescence or apoptosis. However, the development of new therapeutic strategies requires an understanding of the carcinogenesis mechanisms in order to discover new targets and enable the development of effective strategies. It is within this scientific context that I entered my thesis project based on the molecular mechanisms dissection of the p53 protein degradation mediated by E6. For that, we articulated our work around two lines of research: (i) determination of the residues of p53 involved in the binding site with E6 of "high risk" HPV, responsible for the degradation of p53; (ii) identification of kinases involve in the p53 degradation in HPV transformed cells. This work demonstrated the importance of the conformation of the p53 core domain in the binding with the oncoprotein E6, by the structure / function studies of mutant p53. In addition, we have highlighted the role of the pseudo-kinase NRBP1 in the regulation of p53 in HPV transformed cells, via the NF-kB pathway

3

Mourareau, Céline. "Bio-CAD - Etude de biomarqueurs de progression tumorale dans les cancers des voies aéro-digestives supérieures en fonction de leur statut HPV." Thesis, Reims, 2016. http://www.theses.fr/2016REIMS029/document.

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Chaque année 610 000 cancers sont diagnostiqués dans le monde induits par une infection à papillomavirus humains à haut-risque (HPV-HR). Bien que les carcinomes des voies aéro-digestives supérieures (VADS) soient principalement associés à une forte consommation de tabac et d’alcool, 20 à 25% sont causés par une infection à HPV, particulièrement l’HPV de type 16. Les patients HPV positifs présentent un meilleur survi global, pourtant ils sont diagnostiqués avec plus de métastases à distance que les patients HPV négatifs. Au travers d’une étude sur des lignées cellulaires dérivées des VADS, nous avons montré que toutes les lignées cellulaires HPV+ présentaient une intégration du génome d’HPV au sein du génome cellulaire, avec des profils d’intégration différents. Les lignées pouvant être utilisées comme modèles caractéristiques des tumeurs HPV+ et HPV- sont respectivement les lignées UPCI:SCC090 et FaDu. La première par ses capacités migratoire et proliférative et la seconde par sa faible agressivité et une mutation du gène cellulaire p53. Dans une étude portant sur une série rétrospective de cancers de l’oropharynx éligible à une résection chirurgicale, 6 cancers sur 40 soit 15% présentaient une infection à HPV16 active (expression de l’ARNm E6*I). Nous avons étudié les marqueurs de TEM dans ces cancers oropharyngés en fonction du statut HPV. Nous avons retrouvé une perte plus importante du marqueur épithélial cadhérine-E au sein du groupe HPV+, associée à une moins bonne survie globale.Au total, nous montrons que le statut HPV et les marqueurs de TEM semblent être deux facteurs indépendants, qui peuvent se combiner pour définir des niveaux pronostiques différents
Each year, 610,000 cancers are diagnosed worldwide attributed to high risk human papillomavirus (HR-HPV) infection. Although head and neck squamous cell carcinoma (HNSCC) is mainly associated with tobacco and/or alcohol consumption, 20 to 25% are caused by HPV infection, particularly HPV type 16. Although patients with HPV+ tumors present a better overall survival, they are diagnosed with more lymph node metastasis than HPV-negative patients.Through a study of HNSCC derived cell lines, we showed that all HPV-positives cell lines harbored HPV genome integration through host genome, with different integration profiles. Cell lines identified as good HPV+ and HPV- tumors models are UPCI:SCC090 and FaDu respectively. The first one by its migratory and proliferative properties, the second through its poor aggressiveness and mutation of p53 cellular gene.In a study on a retrospective series of oropharyngeal carcinomas with surgical resection, 6 out of 40 cancers shown HPV16 active infection (expressing E6*I mRNA). We studied epithelial-to-mesenchymal transition (EMT) markers on this oropharyngeal cancers, according to HPV status. We found a larger loss of epithelial marker E-cadherin in HPV+ group and loss of this marker is associated with a worse overall survival.We showed that HPV and EMT status seem to be two independent factors that could combine differently to define different prognostic levels

4

Bonneault, Mélanie. "Modélisation dynamique des infections et co-infections génitales à papillomavirus humain (HPV) et de l’impact à long terme de la vaccination anti-HPV." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASR002.

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L’infection génitale au papillomavirus humain (HPV) concerne près d’un tiers des moins de 25 ans dès le début de leur activité sexuelle. Généralement asymptomatique, elle peut conduire au développement de lésions cancéreuses. Parmi la quarantaine de génotypes HPV transmis par les voies génitales, une quinzaine a été évaluée comme oncogène et agent causal du cancer du col de l’utérus. Deux vaccins proposés en France depuis 2007 aux jeunes filles ciblent deux génotypes HPV les plus à risque de cancer du col de l’utérus. Ces vaccins n’incluant qu’une fraction des HPV, l’évolution des prévalences d’infection et de co-infection reste incertaine. L’objectif de ce travail de thèse est de mieux comprendre l’impact des interactions entre génotypes HPV lors de co-infections intra-hôte sur l’évolution des prévalences des génotypes vaccinaux (V) et non vaccinaux (NV). Pour y répondre, ce travail s’appuie sur le développement d’un modèle individu-centré permettant de reproduire à la fois l’hétérogénéité des comportements sexuels et les dynamiques de transmission de génotypes V et NV en fonction de l’âge. Une première partie présente une description détaillée de ce modèle stochastique et de sa validation sur des données d’enquêtes. Ce modèle suppose que l’interaction entre génotypes se traduit par la réduction (compétition) ou la prolongation (synergie) de la durée d’infection par un génotype NV en cas d’infection préalable par un génotype V. La calibration des paramètres de transmission pour différentes forces d’interaction montre que plusieurs d’entre elles sont compatibles avec les données épidémiologiques pré-vaccinales d’infection et de co-infection. Dans les simulations, après introduction de la vaccination dans la population, nous observons que la prévalence des génotypes NV augmente en cas de compétition et diminue en cas de synergie et ce d’autant plus que l’interaction est forte. En cas de compétition, l’augmentation de la prévalence des NV pourrait entraîner une faible diminution voire une augmentation de la prévalence globale de tous les génotypes malgré la vaccination. La deuxième partie vise à explorer, par une étude de simulations, comment l’introduction de la vaccination modifie la diffusion de l’infection dans le réseau de contacts. Les simulations mettent en évidence des variations de prévalence des génotypes NV avant et après vaccination plus marquées chez les individus moins actifs. Dans la troisième partie, le modèle est utilisé pour émuler les schémas d’études épidémiologiques afin de déterminer les conditions (nombre de sujets, délai après l’introduction du vaccin) nécessaires à la détection d’une diminution ou augmentation des prévalences de HPV suite à l’introduction de la vaccination dans la population. Une revue systématique de la littérature fait ressortir deux schémas d’études observationnelles comparant les prévalences d’infection soit dans deux populations en périodes pré- et post-vaccinales, soit chez les vaccinés et les non vaccinés en période post-vaccinale. Les résultats obtenus suggèrent que les études publiées à ce jour quel qu’en soit le schéma manquent de puissance statistique pour détecter une variation de prévalence des génotypes NV. S’appuyant sur le développement d’un modèle validé pour reproduire des comportements sexuels et des prévalences d’infection à HPV réalistes, l’ensemble de ce travail de thèse participe donc à l’amélioration des connaissances épidémiologiques sur les infections et co-infections à HPV et permet d’anticiper l’impact des mesures de prévention vaccinale sur la prévalence de l’infection à HPV
Genital human papillomavirus (HPV) infection affects nearly one-third of people under the age of 25 years from the start of their sexual activity. Generally asymptomatic, it can lead to the development of cancerous lesions. Among the forty or so HPV genotypes transmitted via the genital tract, about fifteen have been evaluated as oncogenic and causal agents of cervical cancer. Two vaccines offered to young girls in France since 2007 target the two HPV genotypes most at risk of cervical cancer. As these vaccines only include a fraction of the HPV genotypes, the evolution of the prevalences of infection and co-infection remains uncertain. The aim of this thesis is to better understand the impact of interactions between HPV genotypes during intra-host co-infections on the evolution of the prevalences of vaccine (V) and non-vaccine (NV) genotypes. To meet this objective, this work is based on the development of an individual-based model that makes it possible to reproduce both the heterogeneity of sexual behaviour and the transmission dynamics of V and NV genotypes as functions of age. A first part of this thesis presents a detailed description of this stochastic model and its validation on survey data. This model assumes that the interaction between genotypes results in the reduction (competition) or extension (synergy) of the duration of infection by an NV genotype in the event of prior infection by a V genotype. Calibration of transmission parameters for various interaction strengths shows that several of them are compatible with pre-vaccine epidemiological data on infection and co-infection. In the simulations, after introduction of vaccination into the population, we observe that the prevalence of NV genotypes increases in the case of competition and decreases in the case of synergy, especially when the interaction is strong. In the event of competition, the increase in the prevalence of NV could lead to a slight decrease or even an increase in the overall prevalence of all genotypes despite vaccination. The second part aims to explore, through a simulation study, how the introduction of vaccination modifies the spread of infection in the contact network. The simulations highlight variations in NV prevalence before and after vaccination which are more marked in less active individuals. In the third part, the model is used to emulate epidemiological studies in order to determine the conditions (number of subjects, time after the introduction of the vaccine) necessary to detect a decrease or increase in HPV prevalences following vaccine introduction in the population. A systematic review of the literature reveals two observational study designs comparing the prevalences of infection either in two populations in the pre- and post-vaccination eras, or in vaccinated and unvaccinated people in the post-vaccination era. The results obtained suggest that the studies published to date, regardless of the design, lack statistical power to detect variation in NV prevalence. Based on the development of a model validated to reproduce realistic sexual behaviours and prevalences of HPV infection, this thesis work contributes to the improvement of epidemiological knowledge on HPV infections and co-infections and allows us to anticipate the impact of vaccine prevention measures on the prevalence of HPV infection

5

Fleury, Maxime Jean Jules. "Identification des épitopes inducteurs d'anticorps neutralisants de la protéine majeure de capside des papillomavirus humain de type 16 et 31." Tours, 2007. http://www.theses.fr/2007TOUR3309.

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Les papillomavirus humains (HPV) sont responsables du cancer du col de l'utérus. L'expression des protéines de capside en systèmes eucaryotes permet l'obtention de pseudo-particules virales (VLP) possédant des épitopes similaires aux virions et capable de transférer un gène rapporteur. Le but de ce travail était l'identification des épitopes des protéines L1 des HPV de type 16 et 31 à l'aide d'anticorps monoclonaux, de mutants de protéine L1, de banques de peptides, par BIACORE et par Bacterial display. L'épitope majeur de l'HPV 16 et la présence d'épitope chevauchants inducteurs d'anticorps neutralisants et cross-neutralisants a été confirmé sur la boucle FG. Les résultats indiquent que les épitopes inducteurs d'anticorps neutralisants seraient chevauchants et situés sur la boucle FG pour l'HPV 31. Des vecteurs faiblement immunogènes dérivés de l'HPV 16 ont été obtenus par changement de la boucle FG du type 16 en 31. Des pseudovirions 31 ont été produits en cellules de mammifère pour développer des tests de détections des anticorps neutralisants plus sensibles
Human papillomaviruses (HPV) are the ethiologic agent of cervix cancer. Virus like particles (VLP) can be obteined by expressing capsid protein into eucaryotic systems. Those VLP have virions similar epitopes and can transfert reporter genes. The aim of this study was to identify the L1 protein epitopes of HPV 16 and 31 using monoclonal antibodies, L1 protein mutants, peptides sets, BIACORE and Bacterial display. Presence of HPV 16 major epitope and overlapping epitopes inducing neutralizing antibodies and cross-neutralizing antibodies was confirmed into the FG loop. The results show that the epitopes which induce neutralizing antibodies could be overlapping and on the FG loop of the HPV 31. Immunogenicless vector derived from HPV 16 were obteined by replacement of the FG loop of type 16 by type 31. HPV 31 pseudovirions were produced in mammalian cells to developp more sensitive neutralizing antibodies assay

6

Olivera-Botello, Gustavo. "Modélisation numérique des aspects immunologiques de la réaction à l'infection à HPV et de la vaccination anti-HPV par Gardasil®." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00846182.

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L'infection au papillomavirus humain (HPV) est connue pour être le principal facteur causal d'une série de maladies aussi bien bénignes (condylomatose ano-génitale, papillomatose lyringée, et autres) que malignes (cancer du col de l'utérus, certains cancers ORL, et autres). Deux vaccins prophylactiques (Gardasil® et Cervarix®) sont sur la marché depuis à peu près quatre ans pour prévenir cette infection. Le présent travail de thèse comportait trois objectifs principaux : i) étudier in-silico l'immunogénicité du vaccin Gardasil® ; ii) étudier in-silico l'histoire naturelle d'une infection à HPV et iii) évaluer in-silico le potentiel de l'hypothèse thérapeutique suivante : l'administration intramusculaire du vaccin Gardasil® chez des patients atteints d'une papillomatose laryngée induirait un effet bénéfique car l'arrivée des immunoglobulines au tissu affecté empêcherait l'HPV de compléter son cycle de vie et, par conséquent, la maladie de se propager. Les principales conclusions sont : i) pour qu'une papillomatose laryngée ne s'étende pas il faudrait, d'après nos simulations, que le taux d'IgGs sériques soit maintenu au-dessus de 200 mMU/mL ; ii) pour rester, sur une période de 10 ans, le plus longtemps possible au-dessus de ce seuil (d'effet thérapeutique), en administrant la quantité minimale de vaccin, il faudrait, d'après nos simulations, suivre le protocole suivant : l'immunisation de base (à 0, 2 et 6 mois), suivie de trois rappels successifs tous les six mois jusqu'au 24ème mois, suivis d'un rappel 18 mois plus tard ; iii) par ailleurs, il semble inutile (voire contreproductif), d'après nos simulations, de modifier le schéma traditionnel de base (0-2-6 mois)

7

Tang, Alexandre. "Rôle des lymphocytes B dans l'immunité anti-tumorale dans un modèle murin de cancer lié au papillomavirus humain (HPV)." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC248.

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Le traitement des tumeurs de patients cancéreux aux stades avancés est difficile à cause du microenvironnement tumoral immunosuppresseur. Afin d'améliorer l'efficacité des vaccins thérapeutiques, il est nécessaire de renforcer l'immunité anti-tumorale et d'empêcher l'échappement des cellules tumorales aux réponses immunitaires. Les lymphocytes T régulateurs ainsi que les cellules suppressives myéloïdes ont été particulièrement étudiés et leur rôle dans l'inhibition de la réponse anti¬tumorale est aujourd'hui bien établi, contrairement aux lymphocytes B (LB). En effet, les LB peuvent sécréter des anticorps, présenter l'antigène et sécréter des cytokines pro-inflammatoires, mais aussi réguler l'inflammation par la production d'IL-10. Nos travaux montrent que les LB participent à la croissance tumorale. En effet, chez les souris MuMT, déficientes en LB, nous avons observé un rejet de latumeur, médié par les lymphocytes T CD4+ et CD8+. Nous montrons notamment que des LB exprimant les molécules PD-L1, CD39 et Ly6A/E s'accumulent dans le ganglion drainant des souris porteuses de tumeur et peuvent potentiellement inhiber la réponse immunitaire T. Cette inhibition ne dépend pas de l'IL-10 car la croissance tumorale n'est pas affectée chez des souris IL-104. De plus, les analyses des polymorphismes nucléotidiques ont montré une corrélation entre le rejet des tumeurs chez les souris § MuMT et la production de formes réactives de l'oxygène et l'activité des cellules NK. Nos résultats suggèrent que le ciblage spécifique des LB PD-L 1+ CD39+ Ly6A/Ehi pourrait améliorer la réponse anti¬tumorale et l'efficacité des vaccins thérapeutiques anti-cancer
Enhancing ante-tumor immunity and preventing tumor escape are efficient strategies to increase the efficacy of therapeutic cancer vaccines. However, the treatment of advanced tumors remains difficult, mainly due to the immunosuppressive tumor microenvironment. Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) have been extensively studied and their role in suppressing tumor immunity is now well established. In contrast, the role of B lymphocytes in tumor immunity remains unclear, since B cells can promote tumor immunity or display regulatory functions to control excessive inflammation, mainly through IL-10 secretion. Here, we demonstrate in a mouse model of HPV-related cancer that B cells play a detrimental role in anti-tumor immunity and participate in tumor promotion. Indeed, in B cell-deficient MuMT mice, the tumor growth was impaired and tumor rejection occurred due to a strong T cell dependent anti-tumor response. We show that B cells expressing PD-L1, CD39 and Ly6A/E markers accumulate in the tumor draining lymph node (dLN) which can directly impact T cell immunity. This inhibition is IL-10 independent since B cells from tumor-bearing mice did not show an increased ability to secrete IL-10 and deficiency in IL-10 production did not impair tumor growth. Furthermore, genetic analysis based on Single Nucleotide Polymorphisms (SNPs) also evidenced a relation between tumor rejection in MuMT mice and reactive oxygen species production and NK cell activity. Our results suggest that targeting B cell populations could enhance anti-tumor response and improve the efficacy of therapeutic cancer vaccines

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Mandy, Muller. "La cartographie comparative des interactions E2-hôte révèle de nouveaux rôles de E2 dans la pathogénie associée aux papillomavirus humain." Phd thesis, Université Paris-Diderot - Paris VII, 2013. http://tel.archives-ouvertes.fr/tel-00881786.

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Les HPV sont les agents d'infections latentes, d'hyperplasies bénignes ou encore de cancer. Afin de mieux comprendre leur pathogenèse, nous avons cartographié les réseaux d'interactions de protéines de régulation virale E2 pour 12 génotypes HPV. Par double hybride, nous avons procédé à l'identification des interacteurs des protéines E2 suivi par une validation en cellule de mammifère par une méthode basée sur la reconstitution d'une luciferase. Le regroupement des profiles d'interaction montre une corrélation avec la phylogénie, établissant ainsi la contribution de E2 dans la pathogénie associée aux HPV. L'étude des réseaux d'interaction a révélé le ciblage préférentiel de protéines cellulaires hautement connectées, impliquées dans 5 catégories fonctionnelles récapitulant les principales fonctions de E2 mais aussi ouvrant de nouvelles perspectives quant au rôle de cette protéine virale dans les mécanismes d'infection. Dans un deuxième temps, ce travail s'est focalisé sur l'étude d'une interaction impliquant spécifiquement la protéine E2 d'HPV16, le virus le plus représenté dans les cancers cervicaux, et une protéine cellulaire, CCHCR1. En identifiant la surface d'interaction de CCHCR1 sur E2, il s'est avéré qu'elle induisait une compétition avec BRD4, un interacteur majeur de E2, se traduisant par une diminution des capacités transcriptionelle de E2. De même, nous avons montré que CCHCR1 induisait la délocalisation de E2 du noyau vers le cytoplasme. Enfin, nos résultats indiquent qu'en présence de CCHCR1, HPV16 E2 est moins apte à induire la différentiation précoce des kératinocytes, ce qui pourrait potentiellement avoir un effet important sur le cycle viral.

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Sandoval, Federico. "Optimisation d’un vaccin thérapeutique contre les tumeurs des voies aérodigestives supérieures associées au virus de papilloma humain (HPV) : Mise en évidence du rôle de la compartimentalisation de la réponse immunitaire antitumorale." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T012.

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De récents essais cliniques ont montré les bénéfices thérapeutiques des nouvelles immunothérapies (Sipoleucel T pour le cancer de la prostate…). Mais jusqu’ici la majorité des essais cliniques de vaccins contre le cancer n’ont montré que de faibles effets sur les patients, ce qui contraste avec les résultats obtenus dans les modèles pré cliniques. Ceux-ci, comprennent la greffe sous cutanée de cellules tumorales ce qui ne mime pas la vrai localisation anatomique de la lésion tumorale. De plus, dans la plupart des cas les vaccins anti-cancéreux sont administrés par voie systémique et induisent une réponse antitumorale avec un effet thérapeutique au niveau du compartiment systémique. La réponse antitumorale induite par ces vaccins au niveau du microenvironnement tumoral et ses effets antitumoraux sur des modèles orthotopiques n’ont jamais été décrits sur des modèles pré cliniques. Comme la majorité des tumeurs humaines se développe dans des localisations muqueuses, nous avons étudié l’effet de la voie d’immunisation dans l’induction des réponses antitumorales au niveau du site anatomique de la tumeur en comparant l’induction de LT CD8+ spécifiques de l’antigène tumoral après une vaccination par voie systémique (intramusculaire) ou muqueuse (intranasale). Cette stratégie de vaccination repose sur l’utilisation d’un vecteur non réplicatif qui cible les antigènes in vivo aux cellules dendritiques et qui a été développé au sein de notre unité. Il s’agit de la sous unité B de la toxine de Shiga (STxB) associée à un antigène tumoral (protéine E7 de l’HPV16) nous avons également analysé l’effet antitumoral de cette vaccination sur deux modèles de tumeurs orthotopiques à localisations ORL et pulmonaires exprimant l’antigène E7. Nous avons montré que la vaccination i.n. induisait une plus forte réponse LT-CD8+ spécifique et des effets antitumoraux au niveau des localisations muqueuses que la vaccination par voie systémique, et que cette immunisation par voie i.n. induisait un phénotype particulier sur ces LT-CD8+ spécifiques et en particulier une augmentation de l’expression des intégrines CD103 et CD49a en opposition à la voie systémique. L’inhibition de CD49a réduit l’effet thérapeutique de la vaccination par voie i.n. et le nombre de LT-CD8+ infiltrant les tumeurs orthotopiques. Nos résultats montrent que la réponse LT-CD8+ systémique ne sert pas comme marqueur prédictif de la qualité de la réponse immunitaire antitumorale au niveau local. Nos observations mettent en évidence l’existence d’une compartimentalisation de la réponse muqueuse antitumorale, une découverte capitale pour le développement rationnel des vaccins anti cancer
Recent clinical trials have shown the therapeutic benefits of new promising immunotherapies (Sipoleucel T for prostate cancer, Ipilimumab in melanoma…). But by far, the majority of cancer vaccine clinical trials have shown modest clinical effects on cancer patients, contrasting with results found in preclinical models. Those preclinical models of cancer rely on subcutaneous grafts of tumor cells which do not mimic the true anatomic location of tumor lesions. In addition, in most cases cancer vaccines are administrated by systemic route, eliciting systemic antitumor responses and therapeutic effects. The antitumor response elicited by those vaccine strategies at the local environment of tumor location and their antitumor effect on orthotopic tumor models has not yet been addressed in preclinical cancer models. Since the majority of human tumors develop at mucosal surfaces, we addressed the question of the effect of the immunization route in the induction of local mucosal antitumor CD8+T cell responses by comparing a systemic intramuscular (i.m.) and intranasal (i.n.) route of administration of cancer vaccine. This vaccine consists of a non-replicative vaccine strategy that targets tumor antigen in vivo to dendritic cells developed at our laboratory and composed of the B subunit of the Shiga toxin (STxB) associated to a tumor antigen (E7 protein of HPV16). We also analyzed the antitumor effect of these vaccinations on two mucosal orthotopic tumor models of head and neck and lung cancer expressing the E7 antigen. We found that intranasal vaccination induced stronger specific CD8+T cell responses and antitumor effects at mucosal sites than systemic immunization, and, that mucosal vaccination induced a mucosal imprinting phenotype on mucosal derived antigen specific T cells as they expressed the mucosal integrins CD103 and CD49a, as opposed to systemic specific CD8+T cells or tumor infiltrating T cells in subcutaneous tumors. Inhibition of CD49a reduced the antitumor efficacy of the nasal vaccine and the number of tumor infiltrating CD8+T cells on orthotopic mucosal tumors. Our results showed that systemic antigen-specific T cell responses as typically assessed did not predict the quality of local mucosal immune response. Our observations provide direct evidence for the compartmentalization of mucosal tumor immunity, a critical finding for the rational design of better cancer vaccines

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Desaintes, Christian. "Etude de la régulation transcriptionnelle par la protéine E6 du papillomavirus humain de type 16(HPV 16), et par la protéine cellulaire "suppresseur de tumeur" p53." Doctoral thesis, Universite Libre de Bruxelles, 1994. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/212697.

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Mourtada, Jana. "Mécanismes d’activation de la réponse immunitaire par DNp63 dans les cancers des voies aérodigestives supérieures HPV-positifs." Electronic Thesis or Diss., Strasbourg, 2023. http://www.theses.fr/2023STRAJ127.

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Les tumeurs HPV+ de l’oropharynx sont hétérogènes d’un point de vue pronostic et moléculaire. Le pronostic des tumeurs se distinguent respectivement par la présence ou l’absence d’une signature moléculaire dépendante du facteur de transcription ΔNp63. Nous avions démontré que ΔNp63 inhibe les capacités migratoires et invasives des lignées cellulaires de cancer ORL HPV+, et augmente leur sensibilité aux chimiothérapies à base de sel de platine, suggérant son rôle dans la progression tumorale. Une analyse fonctionnelle de ΔNp63 nous a permis de montrer que son expression stimule la phagocytose de cellules cancéreuses par des macrophages in vitro. De manière cohérente, l’analyse du transcriptome de notre même modèle cellulaire met en évidence que ΔNp63 régule l’expression de facteurs diffusibles comme des chimiokines et des interleukines, parmi lesquels la protéine DKK3. Nos résultats montrent que la sécrétion de DKK3 par les cellules cancéreuses active la voie NF-kB dans les macrophages, et mimique les effets de ΔNp63 dans la régulation de la phagocytose. L’induction de la voie NF-kB par DKK3 dans les macrophages est réalisée par l’intermédiaire de son récepteur CKAP4. Enfin, nos analyses suggèrent que ∆Np63 régule l’expression de facteurs impliqués dans l’inflammasome, ainsi que celles d’autres cytokines comme TNFRSF11B, CCL26, CCL11, TIMP1 et TIMP2. L’ensemble de nos résultats montrent que ΔNp63 joue un rôle original dans le pronostic des patients HPV+ à travers la régulation de molécules sécrétées, impliquées dans le recrutement et l’activation de cellules immunitaires
HPV+ oropharyngeal tumors display both prognostic and molecular heterogeneity. Patients prognosis can be distinguished by the presence or absence of a molecular signature that depends on the ΔNp63 transcription factor. We demonstrated that ΔNp63 inhibits the migratory and invasive capabilities of HPV+ HNSCC cell lines and increases their sensitivity to platinum-based chemotherapy, implying its role in tumor progression. A functional analysis of ΔNp63 revealed its ability to stimulate the phagocytosis of cancer cells by macrophages in vitro. Consistently, a transcriptomic analysis of the same cellular model highlighted that ΔNp63 regulates the expression of secreted factors, including chemokines and interleukins, among which is the DKK3protein. Our findings indicate that DKK3 secretion by cancer cells activates the NF-κB pathway in macrophages, mimicking ΔNp63's effects on phagocytosis regulation. Induction of the NF-κB pathway by DKK3 in macrophages is mediated by its receptor CKAP4. Finally, our analyses suggest that ∆Np63 regulates the expression of factors involved in the inflammasome, as well as those of other cytokines such as TNFRSF11B, CCL26, CCL11, TIMP1 and TIMP2. Altogether, our results show that ΔNp63 plays a unique role in the prognosis of HPV+ patients by regulating secreted molecules involved in the recruitment and immune cell activation

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Ben, Hadj Yahia Mohamed-Béchir. "Données et outils pour l'optimisation de l’impact de la vaccination prophylactique contre les papillomavirus humains en France." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S041/document.

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Introduction : Depuis 2007, la vaccination contre les infections à papillomavirus humains (HPV) est recommandée en complément du dépistage du cancer du col utérin (CCU). Cependant, au vu de la faible couverture vaccinale en France, l’impact épidémiologique de la vaccination est discuté, ainsi que le choix de la population cible et les moyens déployés pour son adhésion à la recommandation. Cette thèse propose des données et des outils originaux pour l’évaluation et l’optimisation de l’impact de la vaccination HPV en France. Pour les aspects quantitatifs, une modélisation de la transmission de l’infection à HPV appuyée sur des données détaillées décrivant les partenariats sexuels dans la population générale est nécessaire. L’exploration du lien potentiel entre la participation au dépistage du CCU des femmes précaires et leur choix d’administrer le vaccin HPV à leurs filles, l’appréciation de l’acceptabilité de la vaccination à partir des réseaux sociaux, et l’évaluation médico-économique de la pertinence de l’extension de la vaccination aux hommes, sont déterminants pour parfaire le ciblage des populations à atteindre.Méthodes : Nous avons développé une plateforme de modélisation destinée à l'étude des contacts sexuels et de la dynamique de transmission des infections par les HPV à partir des données de l’enquête Contexte de la Sexualité en France. Grâce à des modèles de mélange de lois, nous avons identifié des classes latentes d’activité sexuelle, permettant de définir des profils à risque d’infections sexuellement transmissibles. Ensuite, nous avons interrogé les femmes consultant au sein du Centre de Prévention et d’Éducation pour la Santé de Lille, ayant au moins une fille éligible à la vaccination HPV, sur leurs attitudes vis-à-vis du dépistage du CCU et de la vaccination. Puis, nous avons analysé les opinions exprimées par les internautes sur le forum en ligne d’un site d’information en santé, concernant la sécurité, l’efficacité et la perception du vaccin HPV. Enfin, nous avons réalisé une revue systématique des études médico-économiques relatives à l’extension de la vaccination HPV aux hommes.Résultats : Les simulations sur la plateforme de modélisation ont permis de reproduire les données de prévalence des infections à HPV mais les résultats restent sensibles aux hypothèses sur les comportements sexuels qui présentent des incohérences entre les hommes et les femmes. Cinq classes latentes d’activité sexuelle ont été identifiées pour les hommes ainsi que pour les femmes. Le cluster correspondant au niveau d’activité sexuelle le plus élevé représente 3,3% chez les femmes et 4,8% chez les hommes. Par ailleurs, le statut vaccinal des filles ne diffère pas selon le profil de dépistage de leur mère. L’argument majoritairement rapporté par les mères pour justifier la non-vaccination de leurs filles concerne le manque d’information, surtout parmi celles qui ne se dépistent pas. De plus, les opinions négatives, exprimées sur le forum de discussion en ligne, sont passées de 28,6 % des avis exprimés en 2006 à 42,2 % en 2013. Les arguments avancés par les « anti-vaccinaux » concernent la sécurité du vaccin et la perception de la vaccination. Enfin, les modèles médico-économiques montrent que l’extension de la vaccination aux hommes est très rarement une stratégie coût-efficace. Néanmoins, la vaccination ciblée des homosexuels masculins semble être la stratégie optimale du point de vue éthique et médico-économique.Discussion : La plateforme de modélisation des contacts sexuels constitue le socle de l’évaluation de l’impact de la vaccination HPV. La surveillance des forums de discussion en ligne permet le monitoring de l’acceptabilité de la vaccination et le ciblage des actions d’information. L’optimisation de couverture vaccinale nécessite la mise en place d’un programme organisé de vaccination des jeunes filles. À défaut d’une implémentation en milieu scolaire, les centres de prévention offrent une alternative intéressante
Introduction: Since 2007, prophylactic vaccination against human papillomavirus (HPV) has been recommended in addition to cervical screening in French women. However, given the low vaccine coverage in France, the epidemiological impact of the vaccination is debated, as well as the choice of the target population and the means to ensure compliance with the recommendation. This doctoral thesis provides original data and tools for the evaluation and the improvement of the impact of HPV vaccination in France. For quantitative aspects, modelling HPV transmission based on the best data describing sexual partnerships in the general population is essential. The investigation of potential links between participation to cervical screening of deprived women and their choice of vaccinating their daughters, the appraisal of vaccine acceptability through social media and the cost-effectiveness evaluation of the relevance of extending the HPV vaccination program to include males are key elements to improve the focus on targeted populations.Methods: We developed a modelling platform to study the dynamics of HPV transmission, using data from Social Context of Sexuality, the latest national French sexual behavior study. Using finite mixture models, we identified latent classes of sexual activity to define profiles of partner acquisition with age, likely to have different risks of sexually transmitted infections. Then, we asked women attending the Centre for Preventive Medicine and Health Education of Lille, who had at least a daughter eligible for HPV vaccination, about their attitudes towards cervical screening and HPV vaccination. Next, we explored sentiments about HPV vaccine safety, efficacy and perceptions, spontaneously expressed by web users on the online discussion forum of a French-speaking health information website. Finally, we performed a systematic review of the cost-effectiveness studies about extending HPV vaccination to include males.Results: Simulations from the modelling platform reproduced HPV infection prevalence observed in France. Nevertheless, results were sensitive to assumptions about sexual behavior, with discrepancies between men and women. Five latent classes of sexual activity were identified in men and in women. The cluster describing the highest level of sexual behavior represents 3.3% in women and 4.8% in men. Besides, daughters’ vaccination profile did not differ with their mothers’ profile of participation to cervical screening. The main reason for not vaccinating their daughters reported by mothers was lack of information, especially for those non-compliant with cervical screening recommendations. Moreover, negative sentiments, reported by the health website forum, evolved from 28.6% of total opinions in 2006 to 42.2% in 2013. The arguments expressed by “anti-vaccine” postings involved most often vaccine safety and negative vaccine perceptions. Finally, cost-effectiveness analyses show that extending the HPV vaccination program to include males is rarely found to be a cost-effective strategy. Nevertheless, the targeted vaccination of men having sex with men seems to be the best strategy from ethical and cost-effectiveness points of view.Discussion: The modelling platform of sexual contacts represents the basis of the evaluation of HPV vaccination impact. The surveillance of online forums enables the monitoring of vaccine acceptability and hence the targeting of preventive messages. Improving the HPV vaccine coverage requires offering girls and young women an organized vaccination program. In the lack of a school-based vaccination program, Centres for Preventive Medicine and Health Education offer an interesting alternative

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Nizard, Mevyn. "Optimisation d'un vaccin thérapeutique dans les tumeurs des voies aérodigestives supérieures associées aux papillomavirus : rôle de l'induction d'une immunité muqueuse et de la combinaison à la radiothérapie." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015PA05T027/document.

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Le cancer est la seconde cause de mortalité dans le monde et les cancers de localisation muqueuse (poumon, estomac, colorectal, du col de l’utérus, …) représentent la première cause de mortalité due au cancer dans le monde. La majorité des vaccins contre les cancers muqueux n’ont à ce jour, pas montré de résultats cliniques significatifs. Au cours de ce travail, nous avons développé une immunothérapie efficace basée sur la sous-unité B non toxique de la toxine de Shiga et montré pour la première fois dans le domaine de la cancérologie que la localisation de l’immunisation était cruciale pour induire des réponses immunitaires anti-tumorales. En effet, dans un modèle préclinique, une immunisation systémique intramusculaire n’a pas permis d’induire de protection thérapeutique efficace contre le développement de tumeurs muqueuses de la langue, alors que la voie d’immunisation intranasale a induit une réponse clinique complète. Nous avons identifié les lymphocytes T CD8+ comme les cellules nécessaires à cette protection et plus précisément la population de lymphocytes T résidents mémoires (Trm). Ces Trm présentent le phénotype classique CD103+ mais expriment également l’intégrine CD49a qui joue un rôle dans la migration/rétention au sein des tumeurs mais également dans la survie à long terme des Trm. Par ailleurs nous avons montré que les cellules dendritiques muqueuses pulmonaires permettaient d’induire ce phénotype CD49a sur les lymphocytes T CD8+ alors que les cellules dendritiques de la rate non. Notre travail montre que l’aspect quantitatif de ces Trm joue un rôle dans la protection anti-tumorale, en effet nous avons pu pour la première fois moduler in vivo le nombre de Trm en traitant les souris par un anticorps anti-TGF-β. La diminution du nombre des Trm est corrélée à la diminution de la protection anti-tumorale. Les patients atteints de cancers des voies aérodigestives supérieures sont majoritairement traités par radiothérapie. Dans l’optique d’essais cliniques à court terme, nous avons montré que la radiothérapie localisée associée à notre immunothérapie permet une protection plus efficace que le traitement seul de l’un ou de l’autre notamment en provoquant un remodelage du microenvironnement tumoral associé à une normalisation vasculaire. Nos résultats ouvrent de nouvelles perspectives dans le développement d’immunothérapies thérapeutiques efficaces contre les cancers muqueux et pourront mener rapidement à des essais cliniques
Cancer is the second mortality cause worldwide while mucosal cancers (lung, stomac, …) is the first mortality cause from. The majority of cancer vaccines against mucosal tumors have not given rise yet to significant clinical results. In this work we developed a strong immunotherapy based on the nontoxic subunit B from shiga toxin and showed for the first time that the localization of the immunization is crucial to induce potent and effective anti-tumoral responses. In a preclinical model a systemic immunization failed to induce a therapeutical protection against mucosal tumor challenge while intranasal immunization completely succeed. We identified a CD8 T lymphocyte population as a required cells in this protection and more precisely the T resident memory (Trm) cells. This Trm showed the classical CD103 phenotype as well as the CD49a which can play a specific role in the retention or the migration of this cells in the tumor tissue and might play a role in the survival. We also demonstrate that dendritic cells from the mucosal parenchyma was required to induce the CD49a expression on CD8 T cells while dendritic cells from the spleen was not. Our work shows that the Trm number as an impact in the anti-tumoral protection. We were able to reduce the Trm number in vivo using an anti-TGF-β antibody. This number diminution was correlated with a less efficient anti-tumoral protection. Patients with head and neck cancers are treated with radiotherapy. In this situation we showed that the combination of radiotherapy and our immunotherapy was associated with a better protection than radiotherapy alone or immunotherapy alone thanks to a vascular normalization. These results might rapidly lead to clinical trials and might open new ways to work with immunotherapies

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Morel, Adrien. "Régulation épigénétique des gènes précoces d'HPV16." Thesis, Besançon, 2016. http://www.theses.fr/2016BESA3005.

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Les Papillomavirus Humains (HPV) à haut risque carcinogène, dont HPV16, sont les agents étiologiques du cancer du col de l'utérus. Le génom d'HPV est composé d'un ADN double brin comprenant deux régions codantes : précoce« E » et tardive« L » et une région régulatrice non codante, la LCR. La protéine E2 se fixe au niveau des E2BS, situés dans la LCR et réprime l'expression d'E6 et d'E7. La perte d'expression d'E2 suite à l'intégration du génome virale induit une surexpression d'E6 et d'E7 qui favorisent la dégradation de p53 et de pRb. Des dinucléotides CpG étant présents au niveau des E2BS d'HPV16, nous avons détenniné si l'expression d'E6 était soumise à une régulation épigénétique. Nous avons développé une PCR HRM pour étudier le niveau de méthylation des E2BS dans les lésions précancéreuses et cancéreuses et nous avons noté la présence de CpG méthylés uniquement dans les cancers. Par ailleurs, nous avons montré que la méthylation des E2BS limite la fixation d'E2 et pern1et probablement la surexpression d'E6 et d'E7. Enfin, nous avons montré que le traitement des cellules HPV16 dérivées de cancer du col utérin pi le 5azadC, induit une diminution de l'expression d'E6. Ce mécanisme est indépendant d'E2 et nous avons prouvé que la ré-expression du miR-375, qu cible les transcrits E6/E7, est responsable de la répression d'E6 après traitement par SazadC. L'ensemble de nos résultats ont montré que l'expression des oncoprotéines d'HPV16 est régulée épigénétiquement par des facteurs viraux et cellulaires
High risk Human Papillomaviruses (HPV) are responsible for cervical cancer. HPV genome consists in a double-strand circular DNA harboring early "E" and late "L" genes and a Long Control Region (LCR). The E2 protcin binds to E2 Binding Sites (E2BS) present on the LCR and represses E6 and E7 transcription. The loss of E2 expression after HPV DNA integration induces an overexpression of E6 and E7 that thus favor p53 and pRb degradation. Since CpG dinucleotides are present in HPVl6 E2BS, we investigated whether E6 HPV16 expression was also submitted to epigenetic regulation. We developed a HRM PCR to study the methylation status of E2BS in precanccrous and canccrous lesions. We observed methylated CpG only in cancer samples. Otherwise, we proved that E2BS methylation prevented E2 binding and probably permitted E6 and E7 overexpression. Finally, we showed that the treatment ofHPV16 cervical cancer cell lines with a demethylating agent (SazadC) decreased the E6 expression. This regulation was independent of E2 and we proved that the up-regulation of miR-375, which targets E6/E7 transcripts, was involved in E6 repression after SazadC treatment. Taken as a whole, our data demonstrate that HPV 16 oncoprotein expression is regulated in an epigenetic manncr via viral and cellular factors

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Brulet, Jean-Marc. "Cibler l’oncoprotéine E7 vers la voie de présentation du complexe majeur d’histocompatibilité de classe II: une piste vers un nouveau vaccin contre les lésions (pré)cancéreuses du col de l’utérus induites par le papillomavirus humain de type 16 (HPV-16)." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/221575.

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Les papillomavirus humains (HPV) oncogènes sont les agents étiologiques des cancers du col utérin. S’il est établi que 30 à 60% des femmes sont infectées par un HPV oncogène, seul 1% des cas d’infection évoluera vers un cancer invasif, les autres se résolvant spontanément, ce qui autorise à penser qu’une vaccination adéquate pourrait permettre de maîtriser, voire de guérir, les lésions (pré)cancéreuses induites par ces virus. A ce titre, les cibles préférentielles sont les protéines virales E6 et E7. En effet, non seulement ces protéines sont à la base du processus de transformation cellulaire et leur présence est requise pour le maintien du phénotype transformé mais, de plus, elles contiennent des épitopes reconnus par les lymphocytes T auxiliaires et cytotoxiques. Nous avons choisi d’orienter nos recherches sur le virus HPV de type 16 car son incidence est majeure. De même, le taux élevé d’expression de la protéine E7 dans les tumeurs nous a conduit à la choisir comme cible. Notre travail a consisté en la construction de vecteurs plasmidiques codant pour des protéines HPV-16 E7 native ou de fusion. Les fusions ont été réalisées afin de modifier la nature de la protéine E7 afin de la cibler vers les voies de présentation en association avec les molécules du complexe majeur d’histocompatibilité de classe I ou de classe II (MHC-I ou MHC-II). Nous avons étudié et comparé les réponses induites par nos vecteurs afin de déterminer le vecteur le plus efficace. Nous avons ensuite étudié le mécanisme d’action de ce vecteur afin de déterminer les points clés de l’élaboration d’une réponse immune anti-HPV-16 E7. Nous avons ainsi déterminé que cibler la protéine HPV-16 E7 vers la voie du MHC-I (protéines de fusion avec l’ubiquitine; Ub) n’augmentait pas son immunogénicité. A l’inverse, le ciblage de cet antigène vers la voie du MHC-II (protéine de fusion avec la chaîne invariante; Ii) permet à une majorité de souris C57BL/6 de résister à l’injection d’une dose léthale de cellules tumorales syngéniques E7-positives. Nous avons également montré que l’injection du vecteur ciblant E7 vers la voie du MHC-II permet l’élimination de cellules présentant un épitope classe I H-2Db. Cette réponse est médiée par des lymphocytes T CD8+. Nous avons également montré que, si la présence des cellules T CD4+ n’est pas nécessaire pour l’élimination proprement dite de cellules E7-positives, la génération des effecteurs de cette élimination requiert la présence de lymphocytes T CD4+. Nos investigations nous ont permis d’émettre l’hypothèse de l’apparition d’une réponse par transfection directe d’APC et présentation d’épitopes par les voies classiques sur MHC-I et –II, le phénomène de cross-présentation semblant ne pas être impliqué dans la genèse de la réponse. Nos résultats suggèrent donc que c’est l’instabilité de E7 qui fait de cet antigène abondamment synthétisé un piètre inducteur de réponses cytotoxiques. En effet, l’ubiquitination N-terminale de E7 provoque sa dégradation rapide et pourrait empêcher sa sécrétion. Lorsque l’on tient compte de la nécessité de l’activation de cellules T auxiliaires dans l’élaboration des réponses anti-E7 enregistrées, cette dégradation pourrait permettre à E7 de ne pas être présenté sur MHC-II et donc de ne pas générer les cellules CD4+ requises pour la génération des cellules CD8+. Finalement, nous avons montré que cibler une protéine E7 délétée de son motif oncogénique majeur vers la voie du MHC-II menait à l’apparition de réponses cytotoxiques anti-E7 efficaces.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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Meys, Rhonda. "Aspects of human papillomavirus (HPV) disease in human immunodeficiency virus (HIV) infection." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/10730.

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Cutaneous and genital human papillomavirus (HPV) infection in HIV patients, on suppressive anti-retroviral therapy (ART), poses under-investigated clinical challenges. HPV in HIV may represent a form of immune reconstitution associated disease (IRAD). HPV disease and IRADs have been separately correlated with human leucocyte antigen (HLA) genotype. HLA might also influence HPV in HIV. Comprehensive HPV typing of persistent warts obtained from HIV infected and healthy subjects was performed. Cutaneous HPV types were detected using nested PCR/sequencing and newly developed (Luminex based) HSLPCR/ MPG; genital and beta HPV types were identified using a reverse hybridisation line probe assay. Real time PCR was employed to determine HPV DNA viral loads. HLA alleles were defined in HIV infected and healthy patients by Luminex-based molecular typing using DNA derived from blood. The HPV profile of cutaneous and genital HIV warts differs significantly from warts from healthy individuals. In HIV, HPV 7 has been confirmed to be an important HPV type in cutaneous warts (p=0.001). In genital warts in HIV, HPV 11 is the predominant HPV type (p=0.15) and HPV 6 is less common (p=0.002), contrasting with the usual finding that HPV 6 is the principal type in the general population. Cross-over of HPV types between cutaneous and genital sites suggests that HPV tropism is less important than previously thought. An excess of beta HPV types, predominantly as mixed infections, is seen in cutaneous warts in HIV (p<0.0005). The HLA class I allele group HLA-B*44 (as the allele HLA-B*44:02 and the haplotype HLA-B*44, -C*05) has been identified more frequently in HIV than in controls (p=0.004, allele group; p=0.0006, allele; p=0.001, haplotype). The class II allele HLA-DQB1*06 may also be of interest (p=0.03). However, the differences are reduced after correction for multiple testing. Further work is required to ascertain if these HPV types and alleles are of importance.

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Raleigh, Sarah Elizabeth. "Hispanic Parents' Knowledge, Attitudes and Beliefs Toward Human Papillomavirus and Human Papillomavirus Vaccination in Arizona." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/612848.

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Human papillomavirus (HPV) is a sexually transmitted infection that represents a serious health issue that can lead to significant morbidity and mortality. Although FDA-approved vaccines for the prevention against the majority of strains responsible for cervical cancer and genital warts have been available for many years, immunization rates remain low. This study will consider cervical cancer as the main consequence of HPV and thus will investigate parents of daughters. This is of particular relevance to Arizona, given the large Hispanic population and the racial and ethnic disparities that exist in the incidence, mortality and survival of cervical cancer when compared to the national average. Administration of the three-dose series is recommended for girls and boys beginning at 12 years of age. The target population of this study was parents as the HPV vaccine necessitates parental consent and immunization rates remain low. This study specifically aimed to explore the knowledge, attitudes and beliefs of Hispanic parents in Maricopa County toward the HPV vaccine in efforts to identify barriers to immunization and create future implications for practice. Findings were consistent with previous literature: Hispanic parents exhibited suboptimal knowledge regarding HPV and HPV vaccination. Specific opportunities for education include the etiology, transmission and health consequences of HPV. Despite many areas for education, the majority of Hispanic parents indicated they would follow their health providers' recommendation on vaccination.

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Didelot, Céline. "Arrêts du cycle cellulaire et induction d'apoptose pour les lignées de carcinome humain de la tête et du cou HPV-18 positives, après exposition au 5-fluorouracile et aux radiations ionisantes : implication de NF-kB dans la radiosensibilité et l'apoptose spontanée." Nancy 1, 2002. http://docnum.univ-lorraine.fr/public/SCD_T_2002_0316_DIDELOT.pdf.

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Dans le cadre de l'étude de la réponse aux traitements anticancéreux, de nombreuses équipes se sont interessées aux comportements cellulaires après exposition aux stress génotoxiques. Les mécanismes cellulaires qu'ils induisent, tels que des blocages dans le cycle ou la mise en place de l'apoptose, ainsi que la sensibilité des cellules, varient selon la nature de ces stress. La protéine P53 occupe un rôle central dans le contrôle du cycle cellulaire ainsi que dans la régulation de l'apoptose. Cependant, dans de nombreux cancers, la fonctionnalité de la protéine P53 est abrogée par des mutations ou des délétions de son gène. D'autres facteurs peuvent entraîner la perte de fonctionnalité de P53. Ainsi, la protéine E6 codée par le virus du papillome humain (HPV), est responsable de la dégradation de P53. Les études portant sur le comportement de cellules HPV positives exposées à des stress génotoxiques comme le 5-fluorouracile (5FU) ou les radiations ionisantes restent rares. La répartition des cellules dans le cycle cellulaire ainsi que l'induction de l'apoptose ont été étudiées après exposition au 5FU ou aux radiations ionisantes, pour les lignées KB et KB3 de carcinome humain de la tête et du cou exprimant une protéine P53 sauvage et infectées par HVP-18. Les deux types de stress induisent une augmentation de l'expression de la protéine P53, en relation avec une diminution de l'expression de la protéine virale E6. Ainsi, malgré le statut HPV des cellules, la protéine P53 reste inductible est fonctionnelle. Le 5FU entraîne un arrêt des cellules en G Ils alors qu'après irradiation les cellules se bloquent en G2IM. L'arrêt en GIIS apparait avant l'induction de P53, mais celle-ci peut participer au maintien de ce blocage puisqu'elle induit l'expression de P21. Par contre, la mise en place de l'arrêt en G21M est indépendant de P53 mais celle-ci pourrait participer à la levée de ce blocage. Enfin, les deux types de stress peuvent induire de l'apoptose P53-dépendante après exposition au 5FU et P53-indépendante après irradiation. Selon le type de stress génotoxique, le comportement cellulaire peut être différent et l'implication de la protéine P53 sur les mécanismes cellulaires induits, peut se faire à différents niveaux même pour des lignées HVP-positives. Cependant, la protéine P53 n'est pas la seule à posséder un rôle important dans le contrôle du cycle cellulaire et de l'apoptose. En effet, le facteur de transcription NF-KB a été décrit comme étant impliqué dans ces mécanismes cellulaires ainsi que dans la sensibilité des cellules à un stress tel qu'une irradiation. Pour les lignées KB et KB3, une différence d'activité constitutive de NF-KB a été mise en évidence. La modulation de cette activité par exposition des cellules au TNFa. Et à la dexaméthasone, a permis de démontrer que l'activité constitutive de NF-KB était en relation avec le phénomène d'apoptose spontanée et le niveau de radiosensibilité. Ainsi, cette activité constitutive serait un paramètre prédictif de la radiosensibilité des cellules et son inhibition avant traitement pourrait être une nouvelle approche de radiopotentialisation.

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AZEVEDO, Karinne Silva. "Avaliação da prevalência do Papíloma Humano (HPV) em saliva de pacientes portadores do HIV." Universidade Federal de Pernambuco, 2015. https://repositorio.ufpe.br/handle/123456789/18071.

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CAPES
Identificar a presença dos sorotipos de alto risco do Papilomavírus Humano (HPV) na saliva de pacientes portadores do vírus HIV. A amostra de 90 pacientes foi oriunda de dois centros de referência em tratamento de ISTs da cidade do Recife, PE, Brasil. Uma entrevista foi realizada para identificar o perfil da amostra, sendo realizada uma coleta de saliva empregando tubos falcon e solução para bochecho com sacarose a 5%, com posterior armazenamento em freezer a -20°C para rastreamento do HPV e genotipagem para o sorotipo 16 e 18 por PCR convencional. Na amostra predominou a presença do sexo masculino 59 de 90 (65,6%), com idade média de 38,8 anos, variando entre 18 e 69 anos, renda familiar média de 1,95 Salários Mínimos (DP = 1,37). A prevalência de HPV nesta amostra foi de 23 de 90 (25,6%) e dos sorotipos 16 e 18 foi 8 de 90 (8,9%). A co-infecção por HPV é comumente observada em pacientes portadores de HIV.
To identify the presence of high-risk serotypes human papillomavirus (HPV) in patients with sexually transmitted infections (STIs). A sample of 90 patients were from two referral hospitals in treatment of STIs. An interview was conducted to identify the sample’s profile a saliva collections being perfomed using falcon tubs and mount rinse with 5% sucrose, subsequente storage in a freezer at -20ºC for HPV screening and genotyping for serotype 16 and 18 by conventional PCR. In the sample predominant male presence 59 of 90 (65.6%) with mean age of 38.8 years, ranging between 18 and 69 years, average family income of 1.95 minimum wages (SD = 1, 37). The prevalence of HPV in this sample was 23 of 90 (25.6%) and the serotype HPV 16 and 18 was 8 of 90 (8.9%). Co-infection with HPV is commonly observed in HIV patients.

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Jolly, Carol E. "The effects of leptomycin B on HPV-infected cells." Thesis, University of St Andrews, 2008. http://hdl.handle.net/10023/900.

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Cervical cancer is a major cause of death in women and is strongly associated with infection by human papillomavirus (HPV). Integration of HPV is thought to form a key step in the formation of cancer, and is thought to involve the upregulation of HPV E6 and E7 due to the loss of E2 transcriptional control. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in HPV-containing cancer cell lines and HPV 16 E7 or E6/E7 transduced primary keratinocytes, but not in normal cells. This thesis shows that LMB can induce apoptosis and a reduction in the colony survival of derivatives of the W12 cell line that contain HPV 16 in either episomal or integrated form. The HPV genome status, including variations in viral integration type, appears to influence the cumulative and temporal pattern of LMB-induced apoptosis. The effects of LMB were also apparent in cells grown in organotypic raft culture, with differences in behaviour again apparent between cells containing episomal and integrated HPV. As previously noted, treatment with LMB was associated with increased expression of the cell regulators p53 and p21; however, the induction of apoptosis was not dependent upon transcriptionally active p53. It is therefore likely that induction and mediation of LMB-induced apoptosis occurs via alternative, currently unidentified, pathways. These findings suggest that LMB can induce apoptosis in keratinocytes containing HPV 16 in either episomal or integrated form, with genome status and potentially lesion grade likely to influence the response of HPV-associated anogenital lesions to LMB treatment.

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Boulenouar, Selma. "Impacts of Human Papillomavirus type 16 (HPV-16) early proteins on trophoblastic cells." Doctoral thesis, Universite Libre de Bruxelles, 2010. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210188.

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Les infections génitales par les virus du papillome humains (HPV) sont les infections virales sexuellement transmises, les plus communes chez les femmes en âge de procréer. Il est désormais bien établi que l’infection persistante par les HPV classés «à haut risque» est l’un des facteurs indispensables au développement de lésions précancéreuses et cancéreuses du col de l’utérus. Ces HPV semblent aussi être impliqués dans le développement d’autres cancers de la région ano-génitale et pourraient être également impliqués dans les cancers de la tête et du cou. Durant cette dernière décennie, des études croissantes tendent à établir un rôle étiologique des HPV dans les dysfonctionnements gestationnels. La détection des ADN HPV dans les placentas issus d’avortements spontanés et leur capacité exceptionnelle à se répliquer in vitro dans les cellules trophoblastiques cultivées en monocouche, ont apporté de nouvelles perspectives quant à la possibilité que le placenta pourrait constituer aussi un tropisme naturel des infections par HPV.

Six jours après la fécondation et suite à l’accolement du blastocyste à l’épithélium utérin, le trophoblaste s’engage dans des processus actifs de prolifération, d’invasion et de différenciation complexe pour la construction de l’interface physiologique indispensable aux échanges essentiels entre la mère et l’enfant ;le placenta. De façon intéressante, ses propriétés sont similaires à celles de la cellule tumorale maligne. Néanmoins, ses mécanismes sont étroitement régulés dans le trophoblaste, à la fois dans l’espace et le temps, assurant un développement normal à chaque étape de la grossesse.

Devant toutes ces données, nous avions émis l’hypothèse que l’expression des protéines précoces E5, E6 et E7 d’HPV de type 16 (de haut risque), pourraient modifier le développement des trophoblastes infectés. Les résultats obtenus durant ce travail de doctorat démontrent que la protéine virale E5, hautement hydrophobe, est cytotoxique et affecte la viabilité du trophoblaste. Cette cytotoxicité est neutralisée, et la viabilité est améliorée, lorsque les oncoprotéines majeures E6 et E7 sont exprimées en présence de la protéine E5. Lorsque toutes les protéines précoces sont exprimées sous le contrôle de leur propre promoteur (LCR), la viabilité est favorisée. Ces observations ont été confirmées dans les cellules cervicales également. Il a été précédemment rapporté que les oncoprotéines E6 et E7 affectaient l’adhésion du trophoblaste aux cellules endométriales. Dans le présent travail, il a été retrouvé que la protéine E5 diminuait elle aussi l’adhésion, non seulement aux cellules endométriales, mais aussi au support de culture cellulaire. Les capacités de migration et d’invasion de la matrice extracellulaire sont augmentées par l’expression de E5 et dans une plus large proportion par l’expression de E6 et E7. Des résultats similaires ont été obtenus lorsque toutes les protéines de la région précoces sont exprimées sous le contrôle de leur propre promoteur (LCR). La diminution de l’expression de la E-cadhérine est considérée comme un marqueur de malignité et de mauvais pronostic pour les cancers. Nous avons démontré que l’expression de E5, E6 ou de E7, inhibait l’expression de la E-cadhérine, reflétant l’impact des oncoprotéines du virus HPV-16 sur la diminution de l’adhésion et l’augmentation du pouvoir invasif des cellules trophoblastiques. L’investigation d’autres marqueurs de malignité et de tolérance immunitaire, l’étude de l’impact du virus HPV-6 (de bas risque) sur la migration et l’invasion des cellules trophoblastiques, et l’étude de la capacité des protéines précoces d’HPV-16 à influencer l’entrée des particules virales, ont fait l’objet de résultats préliminaires, ouvrant de larges perspectives.

Genital Human Papillomavirus (HPV) infections are the most common sexually transmitted infections amongst women on the age of reproduction. It is well established that persistent infection with high-risk HPVs is the necessary factor in the causation of precancerous and cancerous cervical lesions. High-risk HPVs have also been reported to be involved in the causation of head and neck cancers and other anogenital cancers. On this last decade, growing data are attempting to study the potential etiological association of HPV with gestational dysfunctions. The detection of HPV DNA in placentas resulting from spontaneous abortions and the unique ability of multiple HPV types to replicate in vitro in trophoblastic cells cultured in a monolayer system, rise new questions over the HPV tropism.

Six days following fertilization and once the apposition of the blastocyst on the uterine wall takes place, the trophoblast, in a very active and complex process, starts to proliferate, invade and to differentiate in order to build a physiological interface; the placenta, from where multiple mother/foetus exchanges occur. Interestingly, the way that the trophoblast behaves is very similar to malignant tumoural cells. However, the trophoblast obeys to strict spatial-temporal regulatory confines, insuring a proper development all along the pregnancy.

In regard to these data, we hypothesised that the expression of the high-risk HPV type 16 oncoproteins E5, E6 and E7, might modify the development of the infected trophoblast. During my Ph.D study, I demonstrated that the highly hydrophobic protein E5 is localized in many interne membranes compartments of the transfected trophoblast. E5 affects the viability of transiently and stably transfected trophoblastic cells. E6 and E7, favouring cell growth, neutralised the E5 cytotoxic effect. All HPV-16 early proteins, when expressed under the control of their endogenous promoter (LCR), favoured trophoblastic growth. These observations were also observed in cervical cell lines. In addition, E5 decreased the adhesiveness of trophoblastic cells to the tissue culture plastic and to endometrial cells similarly as previously described for E6 and E7. Cells expressing E6, E7 and in less extend E5 favoured chemotaxic migration and matrigel invasion compared to the cells expressing the LacZ control. These effects were also observed when early proteins were expressed under the control of their own viral promoter (LCR). Interestingly, the E-cadherin was down regulated in trophoblastic cells expressing E5, E6 and E7. In conclusion, HPV-16 early proteins enhanced trophoblastic growth and intensify the malignant phenotype by impairing cell adhesion leading to increased cellular motile and invasive properties. HPV-16 E5 participated, with E6 and E7, in these changes by impairing E-cadherin expression, a hallmark of malignant progression. Additional preliminary results consisting on the investigation of other markers of malignancy and immune tolerance, on studying the impact of the low-risk HPV type 6 early proteins on the migratory and invasive properties of trophoblastic cells and on the study of the ability of HPV-16 to influence the entry of virus particules, allowed to open wide perspectives.

Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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Dareng, Eileen Onyeche. "Human papillomavirus infections and human papillomavirus associated diseases in Nigeria : distribution, determinants and control." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284551.

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Background: Persistent infection with high risk HPV is a necessary but insufficient cause of cervical cancer. Behavioural, viral and host factors modulate the risk of HPV persistence. In this thesis, I explore the role of the vaginal microbiota, a host factor and the presence of multiple HPV infections, a viral factor in HPV persistence. Considering the limited data on the epidemiology of HPV related diseases in low and middle-countries (LMIC), and the limited success of cervical cancer screening strategies in many LMIC, I provide data on the distribution of HPV related diseases in Nigeria and evaluate the acceptability of innovative strategies to increase cervical cancer screening uptake. Methods/Results: To achieve my aims, I implemented a longitudinal cohort study of 1,020 women in Nigeria. I begin my results chapters with two methodological papers. Attrition is an important consideration for every longitudinal cohort, particularly in LMIC, therefore, I present my findings on attrition, determinants of attrition and practical strategies to ensure low attrition in studies conducted in LMIC. Considering that sexual behaviour is an important potential confounder in all HPV studies, and the reliability of self-reported history is often questioned, I present findings on the test-retest reliability of self-reported sexual behaviour history collected in my study. Having found that attrition levels were low and that self-reported sexual behaviour history was generally reliable within my cohort, I present my findings on the association between the vaginal microbiota and persistent hrHPV; and the role of multiple HPV infections in viral persistence. I found that the vaginal microbiota was associated with persistent hrHPV in HIV negative women, but not in HIV positive women; and that multiple HPV infections did not increase the risk of viral persistence when compared to single HPV infections. Next, I present my findings on the prevalence and incidence of anogenital warts in Nigeria, with additional reports on the prevalence of cervical cancer and other HPV associated cancers using data from two population based cancer registries. Finally, I present my findings on the acceptability of innovative strategies to improve cervical cancer screening uptake in Nigeria. I found that Nigerian women had a favorable attitude to the use of HPV DNA based screening as part of routine antenatal care, however attitudes towards the use of self-sampling techniques for HPV based cervical cancer screening varied by religious affiliations. Conclusion: In my thesis, I was able to systematically investigate the epidemiology of HPV infections in a LMIC. I considered the distribution of HPV related diseases, host and viral determinants of HPV persistence and investigated control strategies to reduce the burden of cervical cancer in a LMIC. My results provide useful data for surveillance, monitoring and evaluation of control programs on HPV and cervical cancer in Nigeria and may be useful to cervical cancer control programs in other LMIC.

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Nielson, Carrie. "Human Papillomavirus Prevalence in Asymptomatic Men." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194193.

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Introduction: Human papillomavirus (HPV) is the sexually transmitted etiologic agent of cervical cancer. While HPV infects both men and women, little is known about HPV infection in men. Specifically, knowledge of the prevalence of type-specific HPV infection and the distribution of these infections by anogenital anatomic site in men is incomplete. Evaluation of factors associated with HPV infection based on complete anogenital sampling and with HPV-16 antibody detection may lead to a better understanding of HPV transmission and prevention.Methods: A total of 493 asymptomatic men ages 18 to 40 years old were recruited in Tucson, Arizona, and Tampa, Florida, from 2003 to 2006. Eligibility requirements included having had sex with a woman within the past year and having no history of genital warts. Testing for HPV from anogenital swabs from six anatomic sites and semen was conducted by PCR and reverse line blot genotyping for 37 HPV types. Serum antibodies for HPV-16 were detected by ELISA. Self-administered demographic, health, and sexual history/behavior questionnaires were collected. HPV prevalence and type distributions by anatomic site were calculated, as was seroprevalence of HPV-16 antibodies. Multivariate logistic regression was used to identify independent risk factors for HPV infection at any anatomic site and for having HPV-16 antibodies.Results: HPV was detected in at least one sample for 303 (65.4%) men, with 29.2% of men having an oncogenic infection and 36.3% having a non-oncogenic infection. Multiple HPV types were detected in 27.2% of men. Factors associated with infection were a greater lifetime number of female sexual partners, currently smoking 10 or more cigarettes per day, lack of condom use, and more sexual partners in the past three months. HPV-16 antibodies were detected in the serum of 63 (12.8%) men, and detection was associated with increasing age and concurrent detection of HPV DNA in perianal or anal canal samples.Discussion: The combination of more complete anogenital sampling and sensitive HPV detection for 37 HPV types resulted in a higher HPV prevalence in asymptomatic men than previously reported. Smoking and condom use were the most important modifiable risk factors for HPV in men. These results have implications for research of HPV transmission.

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Afrogheh, Amir. "The role of high-risk human papillomavirus in periocular cancers." University of the Western Cape, 2018. http://hdl.handle.net/11394/6554.

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Philosophiae Doctor - PhD
PURPOSE: High risk human papillomavirus (HR-HPV) is well established as a causative agent of squamous cell carcinoma (SCC) of the orophaynx. HR-HPV has also been reported in periocular cancers and precancers, but controversy exists about its overall incidence and clinicopathologic profile. The purpose of this study is to evaluate the role of HR-HPV infection in periocular cancers and precancers, using multiple methods of detection. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Sequential surgical samples of 87 carcinomas (invasive SCC, SCC in situ and sebaceous carcinoma) from three different periocular sites (conjunctiva, lacrimal sac and the eyelid) diagnosed over a 15-year period (2000-2015) were selected for evaluation. Unstained paraffin sections of 87 cases of periocular carcinomas were analyzed with immunohistochemistry (IHC) for p16 as a screening test. p16 positive conjunctival- and lacrimal sac SCC were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by DNA Polymerase Chain Reaction (DNA PCR). p16 positive periocular sebaceous carcinomas (SC) were analyzed with PCR, and a subset of 18cases was further studied with a novel method of mRNA ISH, an advanced technique with an enhanced sensitivity and specificity. Relevant patient clinical information was obtained from review of the electronic medical records.

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Leung, Tiem-yee, and 梁湉兒. "Literature review on parental acceptability of human papillomavirus (HPV) vaccine." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46939003.

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MATTOS, A. T. "Genotipagem Molecular de HPV Proveniente de Mulheres Soropositivas e Soronegativas para HIV Atendidas no Centro de Referência em DST/AIDS." Universidade Federal do Espírito Santo, 2010. http://repositorio.ufes.br/handle/10/4530.

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Made available in DSpace on 2016-08-29T15:34:47Z (GMT). No. of bitstreams: 1 tese_4464_.pdf: 3204606 bytes, checksum: a23da35b5188c96d619b059f83d1577a (MD5) Previous issue date: 2010-12-15
Os HPV são vírus epiteliotrópicos que infectam tecido cutâneo ou mucoso e estão relacionados com desenvolvimento de lesões que, no trato genital, variam de verrugas ao câncer cervical invasivo. As lesões são causadas por diferentes tipos de HPV, que são classificados em baixo e alto risco conforme sua associação com câncer cervical. Sabe-se que mulheres positivas para HIV são mais acometidas por infecções por HPV e estão mais propensas ao desenvolvimento de câncer cervical. O objetivo desse estudo foi avaliar a frequência de tipos de HPV em mulheres soropositivas e soronegativas para HIV. Para isso foram analisadas amostras de escovado cervical, mantidas congeladas, de mulheres conhecidamente positivas para HPV (n=87), atendidas no Centro de Referência DST/AIDS, em Vitória-ES, no período de março a dezembro de 2006. O DNA das amostras foi extraído utilizando kit comercial QIAamp® DNA Mini Kit ou através do método de isotiocinanato de guanidina e sílica. DNA do HPV foi amplificado por PCR utilizando os iniciadores degenerados MY09/MY11 e a genotipagem foi realizada por Restriction Fragment Length Polymorphism (RFLP) e por Reverse Line Blot (RLB). Do total de amostras, 97,7% foram genotipadas e 31 tipos distintos detectados: 6, 11, 13, 16, 18, 26, 31, 31b, 32, 33, 34, 35, 42, 44, 51, 52, 53, 55, 56, 58, 59, 61, 62, 64, 66, 68, 71, 81, 82, 83 e 84. O tipo mais prevalente foi o HPV16, tanto nas mulheres soropositivas quanto nas soronegativas para HIV, seguido pelos tipos 6, 53 e 11. O tipo 13, incomum em amostras cervicais, foi observado nesse estudo, porém a quantidade de amostras não foi suficiente para a realização de seqüenciamento para a confirmação deste tipo viral. Os tipos oncogênicos foram mais comuns nas amostras de mulheres soropositivas para HIV, porém com número semelhante e o número de infecções múltiplas foi maior entre as mulheres HIV positivas. Este estudo revelou uma grande diversidade de tipos de HPV na região. PALAVRAS CHAVES: Human papillomavirus (HPV), Human Immunodeficiency virus (HIV), Restriction Fragment Length Polymorphism (RFLP), Reverse Line Blot (RLB).

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Ebertz, Barika. "Factors influencing women's intentions to obtain the Human Papillomavirus (HPV) vaccine." Thesis, Högskolan Kristianstad, Sektionen för hälsa och samhälle, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-10745.

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Background: Cervical cancer is second most common cancer in women. The 15% incidence of cervical cancer in women worldwide can potentially be reduced by the vaccine against human papillomavirus (HPV). It is therefore important for all healthcare professionals including registered nurses to understand what affects women’s intentions and willingness to receive HPV vaccination so that they can overcome any inappropriate barriers and promote public health. Aim: The aim of this article was to describe factors influencing women’s intentions to obtain the HPV vaccine. Method: The following databases Cinahl, Medline, PsycINFO, Summon @ HKR and Pubmed were searched for articles that studied factors influencing women’s intention to obtain the HPV vaccine. Ten studies met the inclusion criteria, five qualitative and five quantitative. Results: Four main categories were identified that influenced women’s intention to obtain the HPV vaccine: knowledge, attitudes, the influence of other people and the safety of the vaccine. Discussion: Better access for women to accurate information is the key to increase women’s intention to obtain the HPV vaccine and improving public health. Conclusion: Correct information about HPV and HPV virus is needed to increase women’s intention to obtain the vaccine.
Bakgrund: Cervixcancer är den näst vanligaste cancern hos kvinnor med en global incidens på15 %. Cervixcancer leder till hög mortalitet. Genom Humant Papillomvirus (HPV)-vaccinering kan incidensen minskas kraftigt. Vaccintäckningen är suboptimal på många plaster i världen. Det är viktigt att vårdpersonal, inklusive sjuksköterskor, förstår vilka faktorer som påverkar viljan och beslutet att vaccinera sig. På så sätt kan sjukvårdspersonal påverka dessa beslut och faktorer och därigenom öka vaccinationstäckningen i befolkningen. Syfte: Syftet var att beskriva faktorer som påverkar kvinnors avsikt till att vaccinera sig mot HPV. Metod: I denna allmänna litteraturstudie användes databaserna Cinahl, Medline, PsycINFO, Summon @ HKR and Pubmed för att söka efter artiklar som studerade faktorer som påverkar kvinnor att vaccinera sig mot HPV. Totalt tio artiklar inkluderades, fem kvalitativa och fem kvantitativa studier. Resultat: Fyra huvudkategorier identifierades som påverkade kvinnor att vaccinera sig mot HPV: Kunskap, attityder, andras inflytande och vaccinets säkerhet. Diskussion: Bättre tillgång till korrekt information för kvinnor om HPV-vaccinet är nyckeln till att öka kvinnors avsikt att vaccinera sig och på så sätt förbättra folkhälsan. Slutsats: Det krävs korrekt information om HPV virus och vaccin för att öka kvinnors avsikt till att vaccinera sig.

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Jalil, Emilia Moreira. "Prevalência da infecção pelo papilomavírus humano (HPV) em gestantes infectadas ou não pelo vírus da imunodeficiência humana (HIV) tipo 1 em Ribeirão Preto, SP." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/17/17145/tde-06032008-102658/.

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A infecção genital pelo Papilomavírus Humano (HPV) é considerada a doença sexualmente transmissível mais freqüente em todo o mundo, representando importante problema de saúde pública devido à sua alta prevalência e transmissibilidade. Estima-se que cerca de 75% da população sexualmente ativa entre em contato com um ou mais tipos de HPV durante sua vida, com prevalência mais elevada entre mulheres jovens. Estudos epidemiológicos têm demonstrado que a infecção pelo vírus da imunodeficiência humana (HIV) está associada a elevadas prevalências da infecção pelo HPV. A literatura acerca da infecção pelo HPV em gestantes é escassa e controversa. O objetivo do trabalho foi identificar a prevalência da infecção pelo HPV em gestantes e identificar a possível influência da infecção pelo HIV-1 nesta prevalência. Foi realizada amostragem de pacientes do Ambulatório de Pré-natal do Setor de Moléstias Infecto-contagiosas e do Pré-natal de Baixo Risco do Departamento de Ginecologia e Obstetrícia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Todas as pacientes foram informadas sobre o estudo e assinaram o termo de consentimento livre e esclarecido. Foram coletados lavados cérvico-vaginais, que foram submetidos à extração do DNA utilizando a técnica de salting out. Realizou-se a detecção do HPV nas amostras de DNA através da técnica de reação em cadeia de polimerase (PCR), e as amostras positivas para o HPV foram testadas para os tipos 6, 11, 16 e 18. Foram arroladas ao todo 97 pacientes, sendo 44 portadoras do HIV e 53 sem esta infecção. Do total de pacientes avaliadas, 66 foram positivas para o HPV. A prevalência para a infecção pelo HPV foi de 79,5% e 58,5% nas pacientes portadoras ou não do HIV, respectivamente. A infecção pelo HIV aumentou o risco de ser portadora do HPV, principalmente do tipo oncogênico. Contagem de linfócitos T CD4+ abaixo de 200 células/mm3 e carga viral do HIV maior que 10000 cópias aumentaram o risco de infecção pelo HPV. Este estudo mostrou haver maior prevalência da infecção pelo HPV em grávidas portadoras do HIV, permitindo inferir que a infecção por esse retrovírus seja um fator de risco significativo para o aumento da infecção pelo HPV em gestantes.
Genital infection with human papillomavirus (HPV) is considered to be the most frequent sexually transmitted disease around the world, representing an important public health problem due to its high prevalence and transmissibility. It is estimated that 75% of the sexually active population gets in contact with one or more HPV types during their lives, with higher prevalence among younger women. Epidemiologic studies have demonstrated that human immunodeficiency virus (HIV) infection is associated with a high prevalence of HPV infection. The literature about HPV infection during pregnancy is scarce and controversial. The aim of this study was to estimate the prevalence of HPV infection in pregnant women and identify the possible influence of HIV-1 infection on this prevalence. Patients were selected from the Prenatal Outpatient Clinic of the Infectious Diseases Sector and from the Low-risk Prenatal Outpatient Clinic of the Obstetrics and Gynecology Department of the University Hospital, Medical School of Ribeirão Preto, São Paulo University. All patients were informed about the study and signed an informed consent term. Cervical-vaginal washes were collected and submitted to DNA extraction by the salting-out technique. HPV was detected in the DNA samples by the polymerase chain reaction (PCR) technique and the HPV-positive samples were tested for types 6, 11, 16 and 18. Ninety-seven patients were included in the study, 44 of them being HIV-positive and 53 HIV-negative. Of the patients evaluated, 66 were positive for HPV. The prevalence of HPV infection was 79.5% and 58.5% in HIV-positive and -negative women, respectively. HIV infection increased the risk of harboring HPV, mainly oncogenic types. A CD4+ T-cell count below 200 cells/mm3 and HIV viral load above 10000 copies/mL increased the risk of HPV infection. This study showed a higher prevalence of HPV infection in HIV-positive pregnant women, suggesting that this retrovirus infection is a significant risk factor for the increase of HPV infection in pregnant women.

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Rodrigues, Michelle Christine Carlos. "DETECÇÃO E GENOTIPAGEM DE MÚLTIPLOS TIPOS DO PAPILOMAVÍRUS HUMANO (HPV) EM MULHERES HIV-POSITIVAS E HIV-NEGATIVAS EM GOIÂNIA-GO." Pontifícia Universidade Católica de Goiás, 2011. http://localhost:8080/tede/handle/tede/2341.

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HIV-infected women are more likely to be infected with high-risk HPV genotypes that have the potential for progressing to cervical cancer. To Know the prevalence of type-specific human papillomavirus (HPV) infections in HIV-infected women is necessary in order to plan effective screening and preventive strategies in such population. Here, we compare the prevalence of infections with multiple HPV types and cytological abnormalities in two groups of women, HIV-positive and HIVnegative, in the city of Goiânia-GO, Brazil. Cervical smears obtained from 57 HIVpositive and 57 HIV-negative women were collected in a preservative medium and submitted to DNA extraction. HPV-DNA detection and genotyping were performed by using the Linear Array HPV Genotyping Test according to the manual provided by the manufacturer. Both groups were similar in regard to social aspects, demographics and behavioral characteristics. HPV DNA was significantly more prevalent in HIV-positive women, compared to HIV-negative women (56.7% vs. 28.3%, p = 0.003). Coinfections with HPV multiple genotypes was also more prevalent in the HIV-positive group (88.2% vs. 58.8%, p = 0.028). HPV16 was the most prevalent in both groups. Cytological abnormalities were observed in 5.3% of HIV-negative women and in 29.8% HIV-positive women. The presence of HPV was significantly associated with cytological abnormalities only in HIV-negative women. Our results demonstrated a greater prevalence of HPV infection in the HIV-positive group of women, with a greater prevalence of infection with multiple genotypes. We here emphasize the need of frequent monitoring of HIV-infected women, in order to allow early detection and efficient treatment for cervical intraepithelial neoplasia (CIN) in this high-risk group.
Mulheres infectadas pelo HIV são mais susceptíveis à infecção por HPVs de alto risco oncogênico, que apresentam um potencial para a progressão para o câncer cervical. Conhecer a prevalência dos tipos específicos do papilomavirus humano nas mulheres HIV infectadas é necessário para planejar um rastreamento eficaz e estabelecer estratégias preventivas em tal população. Aqui, pudemos comparar a prevalência de infecções por múltiplos genótipos de HPV e de alterações citológicas em dois grupos de mulheres, HIV-positivas e HIV-negativas, da cidade de Goiânia- GO, Brasil. Esfregaços cervicais obtidos de 57 mulheres HIV-positivas e 57 mulheres HIV-negativas foram colhidos em meio conservante e enviadas para extração de DNA. A detecção de DNA e genotipagem do HPV foram realizadas usando o Kit Linear Array HPV Genotyping Test, de acordo com o manual fornecido pelo fabricante. Ambos os grupos foram semelhantes no que diz respeito à demografia, aos aspectos sociais e comportamentais. A detecção do DNA de HPV foi significativamente mais prevalente em mulheres HIV positivas, em comparação com as mulheres HIV-negativas (56,7% vs. 28,3%, p = 0,003). Coinfecção por vários genótipos de HPV também foi mais prevalente no grupo de HIV-positivas (88,2% vs. 58,8%, p = 0,028). O HPV16 foi o genótipo mais prevalente em ambos. Anormalidades citológicas foram observadas em 5,3% das mulheres HIV-negativas e 29,8% das mulheres HIV-positivas. A presença de HPV foi significativamente associada com anormalidades citológicas somente nas mulheres HIV-negativas Nossos resultados demonstraram uma maior prevalência de infecção por HPV no grupo de mulheres HIV-positivas, com um elevado número de casos de infecção por vários genótipos. Enfatizamos aqui a necessidade de monitoramento frequente de mulheres infectadas pelo HIV, de modo a permitir o diagnóstico precoce e tratamento eficaz para neoplasia intra-epitelial cervical (NIC) neste grupo de alto risco.

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Defayette, D. Nicole, and L. Lee Glenn. "Marginal Effects of Patient Age on Human Papillomavirus Knowledge." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/7486.

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Ariyo, Oluwatosin. "Correlates of Human Papillomavirus (HPV) Vaccine Acceptance in Appalachian Tennessee." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etd/3238.

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Human papillomavirus (HPV) is the most prevalent sexually transmitted infection in the U.S., where one HPV-related cancer is diagnosed every 20 minutes. The most common HPV-related cancer is cervical cancer, with an estimated incidence of 12,000 cases annually, a third of which lead to death. Cervical cancer disparately affects women of ethnic minority groups and geographically isolated regions, such as Appalachia. Tennessee ranks third highest in cervical cancer incidence in the country. Many cases of cervical cancer could be prevented through vaccination against HPV, however, vaccination rates for females in Tennessee are among the lowest in the country. This mixed-methods study included an in-depth exploration of the factors that influence HPV vaccine acceptance in Appalachian Tennessee. Healthcare providers, mothers of adolescent girls, and college-aged women were recruited to participate in the study. From October 2016 to January 2017, interviews were conducted with healthcare providers (n=12), focus groups were conducted with mothers (n=13), and a survey was administered to college women (n=479). Interview and focus group sessions were recorded, transcribed and analyzed using a thematic framework. Survey responses were analyzed using descriptive tests, comparison of means, and regression analyses. The predominant barriers to vaccine acceptance identified in the study were: cost and novelty of the vaccine, vaccine safety, lack of school-entry requirement, and the implication of vaccine acceptance on adolescents’ sexual activity. Most negative perceptions towards the vaccine appeared to be propagated by the sociocultural influence on sex and reproductive health communication within the community. Perceived benefits for cancer prevention and receipt of strong and personal provider recommendations facilitated vaccine acceptance. Additionally, college students who reported vaccine acceptance reported discussing sexual health topics with their mothers more often than those who had not been vaccinated. The findings from this study provide foundational insights about the facilitators and barriers of HPV vaccine acceptance in Appalachian Tennessee. Identifying and understanding these factors is crucial to improving HPV vaccination rates and essential to maximizing the primary benefit of the vaccine in addressing the existing cervical cancer disparity in the region.

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Majeed, Gulnaz Syed. "Cytokine polymorphisms in low grade HPV associated cervical lesions." Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368642.

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Johnson, Chandrika. "College Students' HPV Knowledge and Intention to be HPV Vaccinated." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/dissertations/954.

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Combating HPV infection in males is a significant public health issue. In addition to the number of HPV-related cancers that develop each year, Palefsky (2007) reported that "HPV infection of men is of great importance given that sexual transmission is the primary mode of spread to women" (p. 261). In recent years, the development of the HPV vaccine has spurred controversy over whether or not males as well as females should obtain the vaccine against this disease. The purpose of this study was to examine male college students' intention to be HPV vaccinated and their HPV knowledge, attitudes, subjective norms, and perceived behavioral control towards the vaccination. A descriptive, correlational, cross-sectioned research design was employed. Two hundred and eight (208) male college students at a mid-sized public university participated in the study and completed an in-class questionnaire. The results of the descriptive statistics showed that, on average, the sample of 208 male college students had correct responses on only half of the 15 questions regarding knowledge about HPV based on the mean scores. Respondents had positive attitudes towards HPV vaccination, greater sense of control over being HPV vaccinated, and favorable intention to be HPV vaccinated. Subjective norms and perceived behavioral control were significant predictors of male college students' behavioral intention to be HPV vaccinated. Subjective norms and perceived behavioral control had a positive influence on male college students' behavioral intention to be HPV vaccinated. Lastly, male college students' level of HPV knowledge was not significantly correlated to their behavioral intention to be HPV vaccinated

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Weyn, Christine. "Human papillomavirus prevalence and expression in trophoblastic and cervical cells." Doctoral thesis, Universite Libre de Bruxelles, 2010. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210012.

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Human papillomavirus (HPV) is a double-stranded DNA virus, typically infecting mucosal or cutaneous epithelial keratinocytes. Today, more than 118 different HPV types have been formally described. Sexual transmission of mucosal HPVs is very common and generally asymptomatic, but HPV infection can be associated with benign lesions such as condylomata acuminata or, in rare cases, with malignant lesions such as cervical cancer. Two prophylactic vaccines are currently available in Europe, protecting against HPV-16 and HPV-18 (Cervarix&63720;) or against HPV-6, HPV-11, HPV-16 and HPV-18 (Gardasil&63720;). In order to assess the impact of the vaccination program, it is mandatory to obtain geographically widespread date on the baseline HPV prevalence and type distribution in cervical samples from women, presenting or not, normal or abnormal cytologic or histologic results. We undertook an epidemiological study in the Capital Region of Brussels to determine the HPV prevalence and type-distribution in 1526 cervical samples of women presenting a cytology within normal limits (WINL), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intra-epithelial lesions (LSIL), high-grade squamous intra-epithelial lesions (HSIL) or invasive cervical cancer (ICC). The HPV prevalence was 10.8% (95%CI: 8.8-12.8) for NILM, 34.5% (95%CI: 28.3-40.8) for ASC-US, 54.0% (95%CI: 47.4-60.6) for LSIL and 100% for HSIL and ICC. With an HPV-16 and HPV-18 prevalence of 63.3% (95%CI: 44.1-67.7) and 73.5% (95%CI: 63.0-84.0) in mono-infected HSIL and ICC, respectively, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the management and treatment of women suffering from HSIL and ICC in the Capital Region of Brussels. We also detected HPV-30, HPV-53, HPV-66 and HPV-68 in mono-infected HSIL and ICC samples, possibly providing arguments for the reconsideration of the carcinogenicity of these types.

Vertical transmission of HPV was also previously reported, but in most cases one could not exclude a placental contamination by HPV positive cells from an infected birth canal. In order to confirm that the placenta can be infected with HPV, we analysed residual cells from 35 transabdominally obtained placental samples from pregnant women undergoing chorionic villous sampling for screening of suspected foetal abnormalities and found that two samples were positive for HPV-16 and HPV-62, respectively. The clinical importance of these results remains to be elucidated, but the previously observed association between placental HPV infection and pregnancy loss might gain further in importance. HPV gene regulation in placental trophoblastic cells has not been studied so far. We studied the HPV-16 early gene expression regulation in transiently transfected monolayer cultured trophoblastic cells with an HPV-16 long control region (LCR) driven reporter plasmid. We observed important differences in constitutive HPV-16 LCR activities between trophoblastic cell lines and could identify progesterone as an important inducer of HPV-16 early gene expression. Steroid hormones are induced during pregnancy and could therefore lead to an enhanced expression of the E5, E6 and E7 proteins upon placental HPV infection. Since these proteins were previously shown to affect trophoblast adhesion, survival, migration and invasion, their enhanced expression might eventually contribute to pregnancy loss. We furthermore found that the transcription of episomally maintained HPV-16 is not regulated by E2 or E1, but by E5, E6 and/or E7.

Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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Weller, Giselle Schneider. "HPV-Related Stigma." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1178880918.

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Medeiros, Edinilza da Silva Machado. "CONHECIMENTO DE ENFERMEIRAS ACERCA DA VACINA ANTI-HPV, INFECÇÃO PELO HPV E CÂNCER DO COLO UTERINO." Pontifícia Universidade Católica de Goiás, 2016. http://tede2.pucgoias.edu.br:8080/handle/tede/3537.

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This is a cross-sectional cohort study, descriptive with quantitative approach, performed in Public Health Units of cities inside of Bahia, Brazil, with 33 professionals. Data were collected through a multiple-choice questionnaire that intended to investigate the knowledge of the anti-HPV vaccine, HPV infection and cervical cancer, as well as seek association between knowledge with time and institution of training, participation in continuing education and hours worked per week. Data were analyzed using the SPSS® statistical package, version 23. It was adopted a level of significance of 5% (p <0.05). For the verification of possible associations, it was adopted the Pearson's chi-square (χ2) using the verisimilitude ratio coefficients. The results showed nurses with an average age of 30.6 (± 7.3) years; more than 80% from private institution; 51.5% with training time between 2 and 5 years; 84.8% with participation at permanent education; 39.4% with a work load of over 40 hours. All of them knew of the HPV virus and the sexual transmission. However, few knew the other forms of transmission, the effectiveness of condoms, classification and purpose of the Pap test. 90.9% of Nurses understood the role of HPV in the genesis of cervical cancer and genital warts. 97.0% knew the anti-HPV vaccine, but 51.5% thought that only women could be immunized. There was no significant association between time and institution of training, participation in permanent education, as well as hours of weekly work with the knowledge of these professionals on the subject. The study revealed that the nurses have divergent knowledge about the anti-HPV vaccine, HPV infection and cervical cancer, which justifies the needing for improvement of these professionals.
Trata-se de um estudo de corte transversal, de caráter descritivo com abordagem quantitativa, realizado em Unidades Públicas de Saúde de um Município do interior da Bahia, Brasil, com 33 profissionais. Os dados foram coletados por meio de um questionário contendo questões de múltipla escolha que buscaram investigar o conhecimento sobre a vacina anti-HPV, a infecção pelo HPV e o câncer de colo uterino, além de buscar associação entre o conhecimento com o tempo e instituição de formação, participação em educação permanente e carga horária de trabalho semanal. Os dados foram analisados por meio do pacote estatístico SPSS®, versão 23. Adotou-se um nível de significância de 5% (p < 0,05). Em verificação das possíveis associações, adotou-se o teste do Qui-quadrado de Pearson (χ2), utilizando os coeficientes da razão de verossimilhança. Os resultados mostraram Enfermeiras com média de idade de 30,6 (± 7,3) anos; mais de 80% proveniente de instituição particular; 51,5% com tempo de formação entre 2 e 5 anos; 84,8% com participação em educação permanente; 39,4% com carga horária de trabalho de mais de 40 horas. Todas sabiam da existência do vírus HPV e a transmissão pela via sexual. Todavia, poucas conheciam as demais formas de transmissão, a eficácia do preservativo, a classificação e objetivo do exame de Papanicolau. Entendiam o papel do HPV na gênese do câncer cervical e das verrugas genitais 90,9% das Enfermeiras. 97,0% conheciam a vacina anti-HPV, mas 51,5% achavam que apenas as mulheres poderiam ser imunizadas. Não houve associação significativa entre tempo e instituição de formação, participação em educação permanente, bem como carga horária de trabalho semanal com o conhecimento destas profissionais sobre a temática. Ficou evidenciado que as Enfermeiras possuem conhecimentos divergentes sobre a vacina anti-HPV, infecção pelo HPV e câncer de colo uterino, o que justifica a necessidade de aprimoramento por partes destas profissionais.

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Southern, Shirley Anne. "Karyotypic analysis of cervical neoplasia : chromosomal aberrations and human papillomavirus infection." Thesis, University of Liverpool, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367063.

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Winer, Rachel L. "Genital HPV infection and E7 mRNA viral load : incidence, risk factors, and relations to genital neoplasias /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/10917.

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D'Ottaviano, Maria Gabriela Loffredo 1969. "Detecção dos tipos de HPV e integração do HPV DNA 16 em mulheres com NIC 2 seguidas por doze meses = HPV detection and HPV DNA 16 integration in women with CIN2 followed up for 12 month." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310566.

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Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A infecção pelo HPV é considerada fator etiológico da neoplasia do colo do útero e a integração do HPV DNA ao DNA da célula hospedeira são apontados como passo importante na carcinogênese do epitélio. O melhor conhecimento da infecção do vário tipo de HPV e o status físico do HPV 16 nas NIC 2 pode colaborar na identificação das lesões que teriam maior risco de progredir para NIC 3 e, portanto, deveriam ser consideradas como lesões precursoras do câncer do colo uterino. O objetivo desta série de casos foi descrever a presença dos diferentes tipos de HPV e a integração do HPV DNA 16 em mulheres com diagnóstico histológico de NIC 2 acompanhadas por 12 meses. Trinta e sete mulheres com citologia inicial, resultado de lesão de baixo grau e atípicas de células escamosas de significado indeterminado e NIC 2, confirmado por biópsia, foram seguidas por 12 meses com citologia, colposcopia, tipagem de HPV e determinação do status físico do HPV DNA 16 a cada três meses. A evolução clínica da NIC 2 foi classificada como regressão em 49% (18\37) dos casos, persistência em 22% (8\37) e progressão em 29% (11\37). A infecção por múltiplos tipos de HPV foi observada em 41% (15\37) dos casos na admissão e durante o seguimento 54% (20\37) dos casos apresentaram infecção por novos tipos de HPV. O HPV 16 foi considerado como possível causa em 67% (10\15) dos casos que persistiram ou progrediram e em 10% (1\10) dos que regrediram (p=0,01). Entre as 20 mulheres que apresentaram HPV 16 na admissão, a forma integrada foi detectada em 25% dos casos e a forma episomal em 75% dos casos. Não foram observados casos de progressão para NIC 3 sem integração do HPV DNA 16 em algum momento do seguimento. Entretanto, foram observados casos de integração do HPV DNA 16 e regressão da NIC 2. Concluindo, a infecção por múltiplos tipos de HPV é frequente nas mulheres com diagnóstico histológico de NIC 2, assim como a infecção por outros tipos de HPV durante o seguimento de 12 meses. As NIC 2 associadas à detecção do HPV 16 persistem ou progridem com maior frequência. As NIC 2 que progrediram para NIC 3 apresentaram o HPV DNA 16 na forma integrada na admissão ou em algum momento do seguimento
Abstract: Human papillomavirus (HPV) persistent infection is considered a necessary cause for the development of cervical cancer and HPV DNA integration considered an important step in the progression of persistent high risk HPV infection to invasive cancer.The knowledge of HPV infection and the HPV DNA 16 physical status in women with cervical intraepithelial neoplasia grade 2 (CIN 2) can better characterize the biological behavior of the lesion. This case series aimed to describe the HPV types and HPV DNA 16 physical status in women with CIN 2 biopsy proven followed for 12 months and clinical outcome. Thirty seven women with CIN 2 biopsy proven, cervical referral smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and with HPV type, were followed up 12 months with cervical smear, colposcopy, HPV type and HVP DNA 16 every three months. At the end of twelve months follow-up, the CIN 2 regression rate was 49% (18/37), persistence as CIN1 or CIN 2 was 22% (8/37), and progression to CIN 3 was 29% (11/37). Multiple HPV types were observed at admission in 41% (15/37) of cases. During follow-up, 54% (20/37) of the women showed one or more new HPV type detected. HPV 16 was considered possibly causal type in 67% (10/15) of the cases that persisted or progressed and in 10% (1/10) that regressed (p=0.01). Among the twenty women with HPV DNA 16, at admission, 25% showed integrated HPV DNA 16 and 75% episomal form. There were no cases of CIN 2 progression to CIN 3 without HPV DNA 16 integration, but there were cases of HPV DNA 16 integration and CIN 2 regression. Concluding, multiple HPV infections were frequently detected among women with CIN 2 at admission and during the follow up. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3. The HPV DNA 16 integration is associated with CIN 2 persistence and progression to CIN 3
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde

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Subramaniam, Natasha Marie. "Addressing Human Papillomavirus Vaccination in Primary Care Pediatrics." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7434.

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Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States. Despite most common transmission, HPV immunization in adolescents remains below target rates of 80% as outlined by Healthy People 2020 Objectives. Nearly all individuals will contract HPV during their lifetime. The purpose of this project was to educate providers on successfully promoting HPV immunization in adolescents utilizing evidence-based methods. The health belief model (HBM) was the theoretical underpinning utilized to teach providers on discussions about 9vHPV immunization with parents of adolescents. The practice focused question explored whether an education program using concepts from the HBM would increase provider perception of preparedness on recommending Gardasil 9 immunization in adolescents. Convenience sampling was utilized to recruit participants. There were 9 out of 25 providers that attended the educational in service with 8 completing the continuing education evaluation tool. Participants included providers who are affiliated and hold privileges with the health care system. Survey Monkey was used to analyze the participant evaluations. All the participants found the educational information relevant to increasing their perception of preparedness on recommending Gardasil 9 immunization in adolescents. The findings suggest that providers would benefit from training on recommending HPV immunization in adolescents. Continued training would help enhance timely immunization rates that could decrease cancer rates and reduce associated healthcare cost, in turn promoting population health and positive social change.

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Stewart, Deborah. "P53 regulatory mechanisms by human papillomavirus (HPV) E6 and alternative splicing." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85651.

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In normal cells, the p53 tumour suppressor induces cell cycle arrest or apoptosis in response to a variety of stresses, including DNA damage and ectopic oncogene expression. However, cellular pathways controlled by p53 are compromised in virtually all cancers. Defining the mechanisms regulating p53 activity in normal and tumour cells has therefore been a major priority in cell biology and cancer research.
In this study, we characterized two important regulatory mechanims of p53 activity: (i) Human papillomavirus (HPV) E6 interaction and (ii) alternative splicing. Recognized as the major etiological agents for cervical cancer, the oncogenic potential of HPVs correlates with their ability to target p53 for degradation. This study demonstrates that both p53 and HPV-18 E6 are exported from the nucleus when co-expressed, via a process that involves the C-terminal nuclear export signal (NES) of p53. However, neither nuclear export nor the p53 C-terminal NES is required for HPV-18 E6-mediated ubiquitination or degradation of p53.
This study also demonstrates that both low- and high-risk HPV E6 proteins are degraded by the ubiquitin-proteasome pathway, and thus provides an explanation for the low levels of E6 detected in cervical cancer cells.
Also reported in this study is a novel mechanism of p53 regulation arising through alternative splicing. This novel mRNA encodes a N-terminal deleted isoform of p53, termed p47. As demonstrated within, p47 does not supress cell viability but impairs both p53-mediated transcriptional activity and growth suppression. Interestingly, p47 increases both p53 monoubiquitination and nuclear export. We propose that p47 induces nuclear export of p53 by a mechanism involving monoubiquitination, as supported by recent findings from Li and colleagues (2003). The p47 protein also protects p53 from both Mdm2- and HPV-18 E6-mediated degradation. A number of cancers display abnormal localization of wildtype p53, and it will be important to examine the role of p47 in these tumours.
Taken together, the regulation of p53 activity by both HPV E6 and the alternative splice variant p47 involves alterations in p53 ubiquitination status, protein stability, and cell localization. Insight gained into these negative regulatory mechanisms may aid in the design of therapeutic strategies for reactivating wild-type p53 in HPV-associated and non-associated cancers.

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Batista-Ferrer, Harriet. "Factors influencing the uptake of the Human Papillomavirus (HPV) vaccination programme." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.682349.

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Primary prevention of Human Papillomavirus (HPV) infection through vaccination of young women before sexual debut is recommended by the World Health Organisation. HPV vaccination programmes are being implemented throughout the world, including the United Kingdom, and have the potential to reduce substantially cervical cancer mortality over the long term. To prevent existing inequalities in cervical cancer mortality from widening equitable provision of HPV immunisation is required. Using a mixed methods approach, the aim of this thesis was to examine inequalities of uptake of HPV vaccination by young women. Quantitative research methods were used to ascertain whether inequalities existed and identify factors associated with inequalities in uptake. A systematic review and metaanalysis indicated differences in HPV vaccine initiation by ethnicity and healthcare coverage, but no strong evidence for differences by socioeconomic variables. In the predominantly school-based HPV vaccination programme in the south west of England, uptake was not shown to vary markedly by social deprivation. However, associations with ethnicity and substantially lower uptake in non-mainstream educational settings were observed. Qualitative studies were undertaken to understand factors affecting lower HPV vaccine uptake. A qualitative systematic review and evidence synthesis indicated that decision making about HPV vaccination of young women in high-income countries is dominated by policy makers, healthcare professionals, and parents. Based on cultural perceptions about sexual activity, parents may decide not to allow their daughters to be vaccinated. A case study showed unresolved tension for responsibility of key aspects of the HPV vaccination programme in the south west of England prevents uptake. Overall, the findings from this thesis can be used to inform the development of interventions to increase uptake and address inequalities. A complex intervention, which addresses procedures for consent, increases access by setting of vaccine delivery, and overcomes cultural and literacy barriers faced by minority ethnic groups is recommended.

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Dugoni, Meredith L. "Role of the Pediatric Dental Provider in Human Papillomavirus (HPV) Education." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4733.

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Purpose: This study investigates knowledge about HPV and examines if pediatric dental providers should include HPV education for guardians of patients 10-18 years. Methods: Legal guardians of 10-18 year-old patients of the Virginia Commonwealth University Pediatric Dental Clinic were enrolled in this prospective cohort study. Participants completed a baseline survey, were provided HPV education, completed an initial follow-up survey, and then completed a 6-month follow-up survey. Results: A total of 54 participants completed the baseline and initial follow-up surveys and 17 completed the 6-month follow-up survey. The average number of correct responses was 3.4 of 6 knowledge questions, which significantly improved to 5.4 at follow-up (P<.0001). The greatest increase in the percent responding correctly was regarding HPV and oropharyngeal cancer from 22% baseline to 91% at initial follow-up (P<.0001). Regarding Stage of Change, 14 (23%) of those not initially in the Action group had improved at least 1 stage. At the 6-month follow-up, 3 (43%) guardians reported completing the HPV vaccine series. Conclusions: These results demonstrate limited knowledge about HPV and highlight the pediatric dental provider’s ability to educate. Since the greatest knowledge gap pertained to HPV and oropharyngeal cancer, it is important for pediatric dental providers to increase their role in HPV education. As oral cancers are the purview of dentists, practitioners should be involved with their patients’ consideration of the HPV vaccine.

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RONGA, LUIGI. "Human papillomavirus (HPV): space-time epidemiology and issues concerning laboratory diagnosis." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2010. http://hdl.handle.net/2108/208544.

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Human papilloma virus (HPV) is considered the most common sexually transmitted agent in the world. It is the main responsible of cervical cancer, the second more frequent cancer in women (Catsellsague et al., 2007, De Sanjosé et al., 2007). In particular, each year 529,409 women are diagnosed with cervical cancer, while women with older ages (65 years and over) have the greater mortality (WHO 2010, Catsellsague et al., 2007). For these reasons, HPV worldwide impact is consistent. Introduction of Papanicolau cytological test permitted a decrease of incidence and mortality rates of HPV-related cervical cancer. However, it can fails to reduce cervical cancer rates, especially in developing countries (Agorastos et al., 2010). For this reason, virological test is a promising tool to reveal HPV infection in early stages. Despite the importance of HPV testing and genotyping, actual tests are not uniform with regard to genotype-specific detection rates (Klug et al., 2008). Therefore, diagnostic methods for HPV genotyping must be implemented and improved. For the above mentioned reasons, the goal of the present thesis was to deepen the information on the diagnostic approaches and epidemiology of HPV infection. Two methods (Manos+GP PCRs, SPF/InnoLipa [SPF], ProDect ®HPV Typing [BCS]) for the diagnosis of HPV infection were compared. Differences in the identification of HPV infected samples and infectious genotypes identified by the two methods were evaluated. In the second part of the thesis, an analysis of the geographical distribution of HPV cases in Rome and surroundings was performed to evaluate a potential presence of HPV infection clusters and HPV genotypes clusters. Finally, a time-series analysis was conducted to evaluate the trend of HPV infection over time and potential of seasonal regularities of HPV cases. The evaluation of SPF and the BCS methods revealed that they are not perfectly concordant on HPV genotyping, as showed by the significant differences in the prevalence found for HPV73, 59, 56, 53, 52, 51, 35 and 31. On the other hand, the overall concordance between the two tests was 86.1%; in particular concordance for the detection of high-risk genotypes was 87.0%. Moreover, SPF and BCS were highly concordant in the detection of HPV18 and HPV16, the HPV genotypes most related with cervical cancer. Such result is particularly interesting in the era of HPV vaccination for the selection of the ideal candidates for prophylactic vaccination. Geostatistical analysis showed geographical differences of HPV infections and HPV genotypes. In particular, a different distribution of HPV16 and HPV18 in the different municipalities in the Latium region was observed. By time-series analysis, no seasonal component was found. Moreover, no growing trend was observed. Finally, a specific ARIMAX model was built for forecasting. The addition of birth rates as covariate in the model improved the quality. Such result could be useful to make short or medium term predictions about the prevalence of HPV infections. In conclusion, the findings obtained in the present thesis highlight the importance to have good diagnostic methods and the lead a careful epidemiological surveillance in infectious diseases, such as HPV infection, to correctly evaluate the impact of a specific health intervention.

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Muusha, Prudence. "Prevalence of Human papillomavirus among women following HPV vaccine introduction; a systematic review." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29833.

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Background: Worldwide efforts have been made by some countries to offer HPV vaccination since its introduction in 2006. Population effectiveness of HPV vaccines is presently an active area of research. We review available evidence on the effectiveness of HPV vaccine uptake among female adolescents to prevent HPV infection. Methods: A comprehensive search of published and grey literature was conducted in several electronic databases using a pre-defined search strategy related to HPV prevalence following vaccination. The database searches were complemented by hand-searches of reference lists of eligible studies. Data were extracted onto a purpose-designed data extraction form, pooled in a meta-analysis and stratified by continent considering vaccine type, cross protective and (high/low) risk HPV types as subgroups. Results: Our search yielded 1680 studies, of which thirteen met with our inclusion criteria (8332 vaccinated women aged 12 to 34 years from across the world). The pooled HPV (comprising types 6, 11, 16 and 18) prevalence among vaccinated female adolescents was 7% (95% Confidence Interval (CI): 5% to 9%, 13 studies, n=8,332). The 13 studies were conducted across 3 continents: HPV prevalence for North America was 5% (95% CI: 3% to 7%, 9 studies, n=5781, age range =13 to 34); Europe, 14% (95% CI: 9% to 18%, 3 studies, n=2213, age range =13 to 29) and Australia 5% (95% CI: 3% to 8%, 1 study, n=5781, age range=13 to 34). Of the studies which reported the effect of vaccination on other non-vaccine HPV type prevalence (known as cross protective types) HPV (31, 33, 45, 51 & 58), the overall pooled cross protective HPV prevalence was 9% (95% CI: 6% to 12%, 4 studies, n=3081 age range=13 to 29), by continent North America had 14% (95% CI: 12 to 17%, 1 study, n=753 age range=14 to 24), Europe 7% (95% CI: 6 to 8%, 2 studies, n=1990, age range=13 to 29) and Australia with 8% (95% CI: 5% to 11%, 1 study, n=338 age range=18 to 26). Conclusion: This study showed an HPV prevalence of 7% in women vaccinated against HPV types 6,11,16 and 18, which represents a substantial difference to the 22% HPV prevalence in non-vaccinated women. There was no statistically significant difference between HPV prevalence across the continents. There is however, still a dearth of information on vaccinated women and HPV prevalence, highlighting the need for further studies in this area. Strengths and limitation of this review • The review comprehensively searched multiple databases and bibliographies. We had no language restrictions. • We were stringent in the selection of studies as far as vaccination status was concerned. Studies considering HPV prevalence in unvaccinated women were excluded. • A variety of methods was utilised in collecting data across the studies. However, some of the study participants were not representative of the general population. Caution therefore, needs to be considered when using these results to make inferences or conclusions about prevalence of certain populations.

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Eisenberg, Dana J. "Information Amount and Patient Empowerment: Participation in the HPV Vaccination Decision-Making Process." Columbus, Ohio : Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1243830226.

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Stridh, Sandra, and Solvind Hammar. "Knowledge of Human papillomavirus (HPV) and attitudes towards HPV-vaccine among Thai female university students." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-214748.

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Introduction: Human papillomavirus (HPV) is the most common sexually transmitted infection and causes 529.000 cases of cervical cancer every year. Nowadays, there are vaccines available to prevent infection. Knowledge of HPV influence the attitude towards the vaccine and is therefore a factor of accepting the vaccine. Aim: The aim of this study was to examine the knowledge of HPV and attitudes towards HPV-vaccine among Thai female university students. Method: Descriptive and cross-sectional study with quantitative method using a questionnaire. Purposive sampling was used. The sample consisted of students from two different universities in Bangkok, Thailand and out of the 201 students whom filled in the questionnaire, 192 questionnaires were used. Result: There were 64.6% of the participants that had heard of HPV previously. Of these, the most common source of information was health professionals. The HPV-vaccine was known by 42.6% of the participants and 17.4% had taken the vaccination. Over 90% of the participants had a poor or moderate knowledge of HPV. In total, most of the participants in the sample were found to have a positive level of attitude towards the vaccine (72.4%). Almost all participants wanted to know more about HPV and the HPV-vaccine and 88.5% thought it was necessary for them to get the vaccination. Conclusion: As some gaps in knowledge among the participants were shown, the information to young women should be improved and aim to increase the motivation towards the use of preventive methods, such as taking the HPV-vaccine.

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Brotherton, Julia Mary Louise. "Human papillomavirus vaccination in Australia: assessing coverage and developing surveillance strategies." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/12112.

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The research in this thesis by publication explores some key aspects of the implementation of the world’s first government funded human papillomavirus (HPV) vaccination program. The work is focused around the HPV vaccination coverage achieved and the initiation of surveillance and evaluation activities for the Australian program. Australia’s National Human Papillomavirus Vaccination Program commenced in April 2007 and was notable as both the world’s first funded program and for its broad target group (providing catch up vaccination for all females aged 12-26 years between 2007-2009). It remains the world’s most broadly targeted funded catch-up program. As the first country to vaccinate a large proportion of the population with a prophylactic HPV vaccine, findings from coverage and surveillance data are of international interest and significance. The methods used to monitor and evaluate the program, some of which were developed during the research undertaken in this thesis, are key to providing robust coverage and surveillance data. The research indicates that the HPV vaccination catch-up program in Australia achieved a moderately high level of coverage and provides estimates of the extent of under-reporting to the register during the catch up program. The thesis research also addressed some aspects of Australian HPV surveillance, with two main research papers providing a baseline assessment of HPV prevalence pre-vaccination among Indigenous and non-Indigenous Australian women and the findings and implications of the investigation of a vaccine safety signal in the Australian program. The research in this thesis thus provides an important contribution to the evaluation of Australia’s program and to monitoring the ongoing impact of the program, which is of both national and international significance.

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Carrillo-Ng, Hugo, Lorena Becerra-Goicochea, Yordi Tarazona-Castro, Luis Pinillos-Vilca, Valle Luis J. Del, Miguel Angel Aguilar-Luis, Carmen Tinco-Valdez, et al. "Variations in cervico-vaginal microbiota among HPV-positive and HPV-negative asymptomatic women in Peru." BioMed Central Ltd, 2021. http://hdl.handle.net/10757/655810.

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Objective: To characterize the cervicovaginal microbiota of HPV-positive and HPV-negative asymptomatic Peruvian women, by identifying the presence of 13 representative bacteria genus. Results: A total of 100 HPV-positive and 100 HPV-negative women were matched by age for comparison of microbiota. The following bacteria were more frequently identified in HPV-positive patients compared to HPV-negative: Eubacterium (68 vs 32%), Actinobacteria (46 vs 33%), Fusobacterium (11 vs 6%) and Bacteroides (20 vs 13%). A comparison between high-risk and low-risk genotypes was performed and differences were found in the detection of Actinobacteria (50 vs 33.33%), Bifidobacterium (50 vs 20.83%) and Enterococcus (50 vs 29.17%).
Revisión por pares

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Ryan, Chelsea N., Kathryn L. Duvall, Emily C. Weyant, Kiana R. Johnson, and David L. Wood. "Human Papillomavirus Vaccine Uptake, Knowledge, and Acceptance for Youth: A Systematic Review of Appalachia." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/15.

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Though vaccine uptake and public support have risen since the release of the first HPV vaccines, the United States has far lower initiation and completion rates for the HPV vaccine series in comparison to other vaccines indicated for youth. Disparities are even greater in the Appalachian regions. Understanding factors contributing to these discrepancies is vital to improving raise vaccine rates in Appalachia. A comprehensive literature search identified all articles pertaining to HPV vaccination in children and adolescents living in Appalachia. The final 15 articles were included in a systematic review of the topic. Findings: HPV disease and HPV vaccine-related knowledge and communication were low in Appalachian communities, and vaccine uptake was lower in all areas of Appalachia as compared to non-Appalachian U.S. Moreover, large variations in uptake existed among Appalachian subregions. Many variables appear to contribute to this variation, including vaccine acceptance for younger adolescents, local and press-driven critical reports of the vaccine, physician communication, and views of the family matriarchs. Targeting the Appalachian subregions, specific campaigns or intervention may be more impactful than viewing the region as a homogenous whole.

Dissertations / Theses on the topic 'Papillomavirus humain (HPV)'

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