Submitted by (edna.saturno@ufrpe.br) on 2016-11-08T15:55:50Z No. of bitstreams: 1 Vanda Lucia da Cunha Monteiro.pdf: 2562841 bytes, checksum: a00a188e7c5dc2c8b041adfbeca80f48 (MD5) / Made available in DSpace on 2016-11-08T15:55:50Z (GMT). No. of bitstreams: 1 Vanda Lucia da Cunha Monteiro.pdf: 2562841 bytes, checksum: a00a188e7c5dc2c8b041adfbeca80f48 (MD5) Previous issue date: 2007-02-08 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The bovine viral papillomatosis is an infect-contagious disease with high prevalence in dairy bovines, causing considerable economical losses in this sector. Aiming to contribute with therapeutic research for this pathology, this work had as objective evaluating the efficacy of Thuya occidentalis in the treatment of cutaneous papillomatosis in dairy bovines by the clinical, histopathological and molecular aspects. This research was divided in 4 experiments. Were used in the experiments females of Holstein Friesian crossbred, nuliparous, primiparous and multiparous, exhibiting different types of cutaneous papilloma (typical, atypical, engastated atypical, filamentous and mixing) and of degrees defined for this study: light (25% of the body affected), moderate (with 50% of the body affected) and intensive (with more than 50% of affected body). The animals were kept in a semi intensive system of raising and were randomly distributed in groups with tem animals each. In the experiments I and II the animals were divided into 4 groups, were the groups 1 and 2 received solution of sodium chloride at 0.9% and cereal alcohol, respectively, being these considered controls, and the groups 3 and 4 received the phytotherapic medicines Thuya occidentalis (Simões®) mothre tincture (T.M.) at 30% and Thuya occidentalis mother tincture at 30% with propolis, respectively. The animals received, daily by oral via, 10mL of the products during 63 days. For histopathological evaluation, 50% of the animals were submitted to cutaneous biopsy of the lesions on the zero moment (M0) and the final moment (FM). In the present experiments, the partial and total regression were not observed in any group, once during the clinical and histopathological evaluations, in all moments and groups, the papillomas did not presented macroscopic alterations of remission, color and consistence. In the histopathological analysis it was observed epithelial and conjunctive hyperplasic alterations, with extensive vegetative growth of the epithelium with wide and deep epidermal crest, results that characterize development phase with viral replication and synthesis, being a characteristic finding of papillomatosis. It may be concluded that cutaneous papillomatosis in dairy bovines shows predilection for specific areas. The papillomas were most present on lateral abdomen, dewlap and snout, showing mixing lesions followed by basal and that the use of tinctures at 30% of Thuya occidentalis (Simões®) and Thuya occidentalis with propolis, on the experimental conditions used in this studies, do not cause remission of papillomas in dairy bovines. In experiment III there was used the homeopathic medicine Thuya occidentallis CH6. The animals were distributed at random in 3 groups. The groups 1 and 2 received NaCl 0.9% solution and alcohol cereal, respectively, being these considered controls, and the 3rd group received Thuya occidentalis CH6 in the treatment formula. For the three groups the administration was daily, being 10mL by oral via during 63 days. For histopathologycal evaluation, the animals were submitted to cutaneous biopsy of the papilloma lesions in the zero moment (0M) and final moment (FM). According to the achieved data, the partial or total remission occurred only in group 3 (Thuya occidentalis CH6), where were observed warts fall in 20% of the animals of this group, besides partial regression of the remaining animals, with macroscopic alterations of color and size, findings confirmed by the histopathological exam. In the histopathological analysis there was observed reduction of the thorny layer in all animals of the treated group (G3), showing reduction of epithelial layers with conjunctive tissue of dermal papilla showing active fibroblast and capillaries and rare lymphocytic inflammatory cells. Concluding that Thuya occidentallis CH6 contributes to the treatment of pedunculated papiloma in bovine, being indicated in the presence of this infection. Studies with Thuya occidentalis CH6 must have continuity with bovine carrying basal papillomas in a period of treatment superior to 63 days. The experiment IV had as objective to identify the Bthe Polimerase Chain Reaction (PCR). Using the general (FAP59/64 e MY 11/09) and the specific primers for BPV-2 there was obtained an assertiveness of 33 (82.5%) of the 40 analyzed samples. According to the obtained results it is concluded that the presence of BPV in Pernambuco State-Brazil is in agreement with the world findings, enhancing the importance of the diagnose and control of the infection and, consequently, adoption of an specific therapy. These results emphasize the therapeutic properties of the homeopathic medicine Thuya occidentallis CH6, concluding that its use contributes to the treatment of cutaneous papillomatosis in bovine, emphasizing the necessity of studies for period superior to 63 days with the phytotherapic Thuya occidentalis in bovine carrying cutaneous papilllomatosis, and the serum dosage of AST, GGT, urea and creatinine showed that the plant used in this study, during 63 days, was not able to cause hepatic and renal alterations in bovine with cutaneous papillomatosis. / A papilomatose viral bovina é uma enfermidade infecto-contagiosa que apresenta alta prevalência em bovinos leiteiros, causando consideráveis perdas econômicas para este setor. Com o objetivo de contribuir com a pesquisa terapêutica para esta virose, este trabalho teve como objetivo avaliar a eficácia de Thuya occidentalis, no tratamento da papilomatose cutânea em bovinos leiteiros, por meio dos aspectos clínicos, histopatológicos e moleculares. Esta pesquisa foi dividida em 4 experimentos. Foram incluídas nos experimentos fêmeas mestiças de holandês nulíparas, primíparas e multíparas, apresentando diferentes tipos de papilomas cutâneos (típicos, atípicos, atípicos engastados, filamentosos e mistos) e de graus assim definidos para este estudo: leve (25% do corpo acometido), moderado (50% do corpo acometido) e intenso (mais de 50% do corpo acometido). Os animais mantiveram-se em sistema semi-intensivo de criação e foram distribuídos aleatoriamente em grupos, com dez animais cada. Nos experimentos I e II, os animais foram divididos em 4 grupos, onde os grupos 1 e 2 receberam solução de cloreto de sódio a 0.9% e álcool de cereal, respectivamente, sendo estes considerados controles, e os grupos 3 e 4 receberam os medicamentos fitoterápicos Thuya occidentalis (Simões®) tintura mãe (T.M.) a 30% e Thuya occidentalis tintura mãe a 30% com própolis, respectivamente. Os animais receberam, diariamente por via oral, 10mL dos produtos durante 63 dias. Para avaliação histopatológica, 50% dos animais foram submetidos à biópsia cutânea das lesões no momento zero (M0) e no momento final (MF). Nos presentes experimentos, as regressões parcial e total não foram observadas em nenhum grupo, uma vez que durante as avaliações clínicas e histopatológicas, em todos os momentos e grupos, os papilomas não apresentaram alterações macroscópicas de remissão, coloração e consistência. Nas análises histopatológicas verificaram-se alterações hiperplásicas epiteliais e conjuntivas, com extenso crescimento vegetativo do epitélio com cristas epidérmicas extensas e profundas, estes resultados caracterizam fase de desenvolvimento com replicação e síntese viral, sendo um achado característico de papilomatose. Pode-se concluir que a papilomatose cutânea em bovinos leiteiros apresenta predileção por áreas específicas. Os papilomas estavam mais presentes no abdômen lateral, barbela e focinho,apresentando lesões mistas seguidas de basais e que o uso das tinturas a 30% de Thuya occidentalis (Simões®) e Thuya occidentalis com própolis, nas condições experimentais utilizadas nestes estudos, não provocam remissão de papilomas em bovinos leiteiros. No experimento III utilizou-se o medicamento homeopático Thuya occidentallis CH6. Os animais foram distribuídos aleatoriamente em 3 grupos. Os grupos 1 e 2 receberam solução de NaCl 0.9% e álcool de cereal, respectivamente, sendo estes considerados controles, e o grupo 3 recebeu a Thuya occidentalis CH6 na forma de tratamento. Para os três grupos a administração foi diária, sendo 10 mL por via oral, durante 63 dias. Para avaliação histopatológica, os animais foram submetidos à biópsia cutânea dos papilomas, no momento zero (M0) e no momento final (MF). De acordo com os dados obtidos, as regressões parcial e total ocorreram apenas no grupo 3 (Thuya occidentalis CH6), observando-se queda das verrugas em 20% dos animais deste grupo, além de regressão parcial em 80% nos animais restantes, com alterações macroscópicas de coloração e tamanho, achado este confirmado pelo exame histopatológico. Na análise histológica observou-se redução da camada espinhosa em todos os animais do grupo tratado (G3), evidenciando-se redução nas camadas epiteliais, com tecido conjuntivo da papila dérmica apresentado fibroblastos ativos e capilares e raras células inflamatórias linfocitárias. Concluindo-se que a Thuya occidentalis CH6 contribuiu no tratamento de papilomas pedunculados em bovinos, podendo ser indicada na presença desta infecção. Estudos com a Thuya occidentalis CH6 devem ter continuidade com bovinos portadores de papilomas basais, com período de tratamento superior a 63 dias. O experimento IV teve como objetivo identificar o BPV-2 em amostras de verrugas cutâneas de bovinos, utilizando a Reação em Cadeia pela Polimerase (PCR). Utilizando-se os primers gerais (FAP59/64 e MY 11/09) e específico para BPV-2 obteve-se uma positividade de 33 (82,5%) das 40 amostras analisadas. De acordo com os resultados obtidos, conclui-se que a presença da BPV no Estado de Pernambuco está em concordância com os achados mundiais, destacando-se a importância do diagnóstico no controle da infecção e, conseqüentemente, adoção de uma terapia específica. Estes resultados enfatizam as propriedades terapêuticas do medicamento homeopático Thuya occidentallis CH6, concluindo-se que o seu uso contribuiu no tratamento da papilomatose cutânea em bovinos, ressaltando a necessidade de estudos por períodos superiores a 63 dias com a Thuya occidentalis fitoterápica em bovinos portadores de papilomatose cutânea, e as dosagens séricas de AST, GGT, uréia e creatinina revelaram que a planta utilizada neste estudo, durante 63 dias, não foi capaz de causar alterações hepáticas e renais em bovinos com papilomatose cutânea.

Introduction: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is the commonest benign paediatric neoplasm. There is no curative treatment, but the condition is self-limiting. Current primary treatment is aimed at symptomatic relief, comprising of serial surgical debulking of obstructive papillomas along the respiratory tract, with voice preservation. Adjuvant therapy is indicated in severe cases. Objective: A review of children with JoRRP presenting to the ENT Department at Red Cross War Memorial Children’s Hospital (RCWMCH) over 2 years. Evaluation of the pattern of disease and factors that may contribute to disease severity were reviewed. Method: Retrospective folder review of children with histologically confirmed laryngeal papillomatosis over above the time period. Results: Twenty children were included. Nine were male, 11 were female. The median age at diagnosis was 2.4 years (11 - 109 months). Presentation at < 3 years was noted in 5/7 of the most severe cases. Nine of 20 were HPV serotyped; 5 were type 11, and 4 were type 6. Eighty percent (16/20) were HIV negative; 10% (2/20) HIV positive; and 10% (2/20) were unknown. A total of 90 surgical procedures were performed; the highest number of surgeries per child was 13. Inter-surgical time was 1 to 164 weeks (median 9 weeks). Four received Gardasil vaccination as adjuvant therapy, 3 of who showed a reduction in disease severity. Conclusion: JoRRP commonly presents around the first 3 years of life. Severe cases can be life-threatening, often with multiple hospital admissions for clearance of surgical papillomata. Severe cases presented before 3 years. Gardasil vaccination as adjuvant therapy has promise. No identifiable risk factors in our review were noted. HIV co-infection and HPV type were not risk factors for severity.

No description available.

This thesis focuses on the effects of the human papillomavirus (HPV) in tonsillar cancer, mobile tongue cancer, and recurrent respiratory papillomatosis (RRP). The purpose was to characterize patients with RRP in northern Sweden in order to identify more care-intensive RRP patients and to describe the voice and quality of life aspects that follow RRP. Further aims were to confirm the expected increase of HPV-positive tonsillar cancer cases in northern Sweden, and to study the correlation between HPV, its surrogate marker p16 and HPV receptor syndecan-1 in both tonsillar cancer and mobile tongue cancer. A total of 27 consecutive patients with RRP were evaluated at 3 months postoperatively using the voice handicap index (VHI) and SF-36 questionnaires to assess the impact on life and voice in a RRP population. The values were compared to normative data. This report was further extended by examining consecutive data from 21 new patients in order to characterize RRP patients in northern Sweden. In order to study HPV DNA in tonsillar (n= 65) and mobile tongue cancer (n=109), HPV DNA was extracted from paraffin-embedded biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of HPV surrogate marker p16 and the HPV receptor syndecan-1 was analysed by immunohistochemistry. Patients that underwent more than one RRP surgery per year were younger than those treated less frequently and they had significantly impaired voice quality as compared to normal subjects. Females, patients with frequent surgical treatment sessions, and patients with the high-risk HPV subtypes scored significantly lower in several domains of the quality of life assessment as compared with normal subjects. Forty-eight RRP patients had a median age of 44.5 years; 71% were men and 29% females, preferentially infected with HPV6. Patients with high surgical treatment frequency/year showed more widespread RRP in the larynx compared to the patients treated less frequently. A total of 214 tonsillar cancer cases were identified. The vast majority were men. They had a median age of 58 years at diagnosis and expressed HPV as well as p16. The incidence of tonsillar cancer revealed a 2,7-fold increase in men between the years 1990 and 2013. The study demonstrates a strong association between p16 and HPV infection in tonsillar malignancies. These findings are in contrast to the mobile tongue cancer cases, where no evidence of HPV DNA could be detected although one-third showed p16 staining. This demonstrated a poor correlation between HPV and p16 in mobile tongue cancer. There was no difference in the expression of the primary HPV receptor, syndecan-1, between tonsillar and mobile tongue cancer. In conclusion, the frequency of RRP operations, age at onset, gender and subtype of the HPV may be used as factors to predict voice disability. RRP patients with high surgical treatment frequency were significantly younger and had a more widespread laryngeal disease compared to the low-frequency treated group. This study confirms the existence of a clinical RRP group, not primarily related to HPV subtype, but to a more care-intensive RRP population. Our findings identify a 2,7-fold increase in the incidence of tonsillar cancer, HPV and p16 in men between 1990-2013. We can use p16 to detect HPV in tonsillar cancer but not in tongue cancer. The introduction of vaccination against HPV may have a role in the prevention of specific HPV-subtype positive head and neck malignancies and recurrent respiratory papillomatosis since the current vaccine protects against HPV6, 11, 16, 18, 31, 33, 45, 52 and 58. Males will definitely benefit indirectly from vaccination of females, though males will still remain at risk of cancers associated with HPV. This highlights the need for sex-neutral vaccination strategy. Our intention is that this thesis will provide scientific data to support a gender-neutral vaccination and to develop simple tools to detect HPV in tonsillar cancer. / Syftet med avhandlingen är att beskriva effekterna av humant papillomvirus (HPV) vid cancer i halsmandlarna, cancer i tungan och vid luftvägspapillom. Totalt 27 patienter med luftvägspapillom (RRP) under åren 2004-2012 utvärderades 3 månader efter operationen med röst handikapp index (VHI) och livskvalitetformuläret SF-36. Resultaten jämfördes med normal data. Studiematerialet utökades med 21 patienter till totalt 48 RRP patienter i syfte att karakterisera patientgruppen i norra Sverige. För att studera HPV-DNA i tonsillcancer (n = 65) och i cancer i mobil del av tungan (n = 109) extraherades HPV-DNA från paraffininbäddade provbitar som sedan analyserades med PCR teknik och GP5 + / 6 + och CPI/IIG primer. Uttryck av surrogatmarkör p16 och HPV-receptorn syndekan -1 analyserades med immunhistokemi. RRP patienter hade en medianålder på 44,5 år; 71% var män och 29% kvinnor, företrädesvis infekterade med HPV6. Patienter som opererades mer än en gång per år var yngre än de som behandlats mindre ofta och hade en statistiskt sämre röstkvalitet än friska kontroller. Kvinnor, patienter med täta kirurgiska behandlingsintervall och högrisk-HPV hade signifikant sämre livskvalitet jämfört med friska kontroller. Patienter med hög kirurgisk behandlingsfrekvens per år var signifikant yngre och hade mer utbredd RRP sjukdom i luftstrupen, jämfört med gruppen med låg behandlingsfrekvens. Sammanlagt, 214 fall av halsmandelscancer identifierades i norra Sverige under åren 1990-2013; majoriteten var män, med en medianålder på 58 år och positiva för både HPV och p16. Andelen halsmandelscancer fall ökade med 2,7 gånger bland männen på 23 år. Vi fann ett starkt samband mellan uttryck av p16 och HPV infektion i halsmandelscancer men inte i HPV-negativ, delvis p16-positiv (33%) mobil tungcancer. Det fanns ingen skillnad i uttrycket av den primära HPV-receptorn, syndekan -1, jämförande tung-, och halsmandelscancer. Antalet RRP operationer, ålder vid insjuknandet, kön och genetisk variant av HPV kan användas som indikatorer för att förutsäga grad av röststörning. RRP patienter med hög kirurgisk behandlingsfrekvens var signifikant yngre och hade en mer utbredd luftvägssjukdom jämfört med RRP patienter som behandlas mindre ofta. Vi har identifierat en undergrupp av RRP patienter som inte primärt karakteriseras efter HPV virusets genetik utan av ett mer vårdintensivt förlopp. Den aktuella avhandlingen har identifierat en 2,7-faldig ökning av antalet halsmandelscancer hos män och ett starkt samband mellan p16 och HPV infektion i halsmandlar men inte i HPV-negativ tungcancer som inte korrelerar till p16 uttryck. Vi kan använda p16 för att påvisa HPV i tonsillcancer men inte i cancer i mobil tunga. Idag ingår HPV vaccination i det allmänna vaccinationsprogrammet för flickor. Vi förväntar oss en tydlig profylaktisk effekt avseende insjuknande i HPV-relaterad huvud- och hals cancer samt luftvägspapillom eftersom vaccinet skyddar mot HPV bl.a. 6, 11, 16 och 18. Män kommer definitivt att gynnas indirekt genom vaccination av kvinnor men kommer att ha fortsatt högre risk än kvinnor att insjukna i HPV relaterad cancer vilket understryker behovet av könsneutral vaccination. Vår avsikt med avhandlingen är att ge vetenskapligt stöd för könsneutralt vaccination och enkla metoder att påvisa halsmandelscancer.

Introdução: A papilomatose recorrente respiratória (PRR) é uma doença benigna de enorme morbidade, com manifestações clínicas muito distintas, causada pelo papiloma vírus humano (HPV) dos tipos 6 e 11. Objetivo: Identificar os diferentes tipos de HPV e suas variantes relacionados com a PRR e estabelecer possível correlação clínica entre o tipo / variante viral e a agressividade da doença. Casuística e Métodos: Estudo prospectivo, realizado com 41 pacientes atendidos no Ambulatório de Laringologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, entre os anos de 2008 e 2015, que apresentaram quadro de PRR. Foi realizada genotipagem viral das biopsias laríngeas e os vírus presentes foram relacionados com a evolução clínica de cada paciente e a agressividade da doença, pelo escore de Derkay, número de cirurgias e traqueostomia. Resultados: Dos 41 pacientes avaliados, a maioria era do sexo masculino (68,29%), e maiores de 12 anos (63,41%). Os menores de 12 anos apresentaram número de cirurgias e escore de Derkay significativamente maiores do que os pacientes mais velhos. Foram identificados somente os HPV dos tipos 6 e 11, na frequência de 73,17% e 26,83%, respectivamente. A agressividade da doença não mostrou relação com o tipo ou a variante do vírus, mas sim com a idade de apresentação clínica da doença. Conclusão: Os tipos de HPV e as suas variantes não apresentaram comportamento clínico mais agressivo na PRR no grupo estudado. Em contrapartida, a idade foi determinante para a agressividade da doença. / Introduction: Recurrent respiratory papillomatosis (RRP) is a benign disease of enormous morbidity that presents very distincts clinical manifestations. It is usually caused by the human papillomavirus (HPV), mostly types 6 and 11. Purpose: To identify the different HPV types and variants related to RRP and to establish a possible correlation between HPV type/variant and viral disease aggressiveness. Casuistic and Methods: This prospective study included 41 patients followed at the Outpatient Clinic of Laryngology of the Medical School of Ribeirão Preto, University of São Paulo, between 2008 to 2015, due to RRP. Virus genotyping was performed on laryngeal biopsies by PCR, and this information was associated to each patient\'s data regarding aggressiveness of the disease and clinical evolution, by Derkay\'s score, number of surgeries and tracheostomy. Results: Most patients were male (68.29%) and older than 12 years-old (63.41%). Patients younger than 12 years had a significantly higher number of surgeries and Derkay score than older patients. In all samples, only HPV 6 and HPV 11 were detected, in a prevalence of 73.17% and 26.83%, respectively. The aggressiveness of the disease was not related to the type or variant of the virus, but to the age of patient when the clinical presentation of the disease occurred. Conclusions: HPV types and variant of HPV showed no more aggressive clinical behavior in recurrent respiratory papillomatosis in the studied group. In contrast, age was crucial to the aggressiveness of the disease.

Introdução: A papilomatose recorrente respiratória (PRR) é uma doença benigna de enorme morbidade, com manifestações clínicas muito distintas, causada pelo papiloma vírus humano (HPV) dos tipos 6 e 11. Objetivo: Identificar os diferentes tipos de HPV e suas variantes relacionados com a PRR e estabelecer possível correlação clínica entre o tipo / variante viral e a agressividade da doença. Casuística e Métodos: Estudo prospectivo, realizado com 41 pacientes atendidos no Ambulatório de Laringologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, entre os anos de 2008 e 2015, que apresentaram quadro de PRR. Foi realizada genotipagem viral das biopsias laríngeas e os vírus presentes foram relacionados com a evolução clínica de cada paciente e a agressividade da doença, pelo escore de Derkay, número de cirurgias e traqueostomia. Resultados: Dos 41 pacientes avaliados, a maioria era do sexo masculino (68,29%), e maiores de 12 anos (63,41%). Os menores de 12 anos apresentaram número de cirurgias e escore de Derkay significativamente maiores do que os pacientes mais velhos. Foram identificados somente os HPV dos tipos 6 e 11, na frequência de 73,17% e 26,83%, respectivamente. A agressividade da doença não mostrou relação com o tipo ou a variante do vírus, mas sim com a idade de apresentação clínica da doença. Conclusão: Os tipos de HPV e as suas variantes não apresentaram comportamento clínico mais agressivo na PRR no grupo estudado. Em contrapartida, a idade foi determinante para a agressividade da doença. / Introduction: Recurrent respiratory papillomatosis (RRP) is a benign disease of enormous morbidity that presents very distincts clinical manifestations. It is usually caused by the human papillomavirus (HPV), mostly types 6 and 11. Purpose: To identify the different HPV types and variants related to RRP and to establish a possible correlation between HPV type/variant and viral disease aggressiveness. Casuistic and Methods: This prospective study included 41 patients followed at the Outpatient Clinic of Laryngology of the Medical School of Ribeirão Preto, University of São Paulo, between 2008 to 2015, due to RRP. Virus genotyping was performed on laryngeal biopsies by PCR, and this information was associated to each patient\'s data regarding aggressiveness of the disease and clinical evolution, by Derkay\'s score, number of surgeries and tracheostomy. Results: Most patients were male (68.29%) and older than 12 years-old (63.41%). Patients younger than 12 years had a significantly higher number of surgeries and Derkay score than older patients. In all samples, only HPV 6 and HPV 11 were detected, in a prevalence of 73.17% and 26.83%, respectively. The aggressiveness of the disease was not related to the type or variant of the virus, but to the age of patient when the clinical presentation of the disease occurred. Conclusions: HPV types and variant of HPV showed no more aggressive clinical behavior in recurrent respiratory papillomatosis in the studied group. In contrast, age was crucial to the aggressiveness of the disease.

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)