Human papillomavirus (HPV) is the most common cause of sexually transmitted diseases. It is the causative agent of cervical cancer, anal, and penile cancers. The purpose of the study was to determine the knowledge, attitude and behaviour of parents towards HPV and HPV vaccine in preventing cervical cancer in girls aged 9 to 13 years and HPV vaccine uptake. The study was conducted in Sefhare village, in the Central District of Botswana. The researcher selected a quantitative, descriptive cross-sectional research design and data was collected using a questionnaire in face-to-face interviews. The study population consisted of parents of adolescent girls of ages 9-13 years living in four wards of Sefhare village. Data was analysed using SPSS version 19. The study found a high level (71.8%) of knowledge about HPV infection, cervical cancer and HPV vaccine and a positive attitude (81.5%) and behaviour (62%) towards the HPV vaccine. / Health Studies / M.P.H.

Made available in DSpace on 2014-12-17T15:32:22Z (GMT). No. of bitstreams: 1 KaruzaMAP.pdf: 544780 bytes, checksum: e0fadeed7d2d1ec7568970935306d05c (MD5) Previous issue date: 2006-02-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The Human Papillomavirus (HPV) has been strongly implicated on development of some cases of oral squamous cell carcinoma (OSCC). However, the immunological system somehow reacts against the presence of this virus. Among the cells involved on such mechanism of defense detaches the Langerhans cells (LC), which are responsible for processing and presenting antigens. The purpose of this study was to evaluate the immunohistochemical reactivity for Langerhans cells between HPV positive and HPV negative OSCC, as well as, the relation of the immunoreactivity for this cells and the histological grading of malignancy proposed by Bryne (1998) and modified by Miranda (2002). Additionally, HPV infection was evaluated in relation to sex, age, lesion localization and histological grading of malignancy. In the total, 27 cases of OSSC were evaluated, 09 of them HPV positive and 18 HPV negative. Anti S-100 antibody was utilized for the immunohistochemical labelling, followed by the counting of LCs in 5 highpower fields (400x). No statistically significant difference was verified between the variables sex, age, lesion localization, histological grading of malignancy and HPV presence in OSSC. There was neither association between the immunohistochemical labeling for LCs (S-100+) and HPV infection nor correlation between the quantity of LCs labeled and the histological grading of malignancy of OSSC. The results suggest that despite the absence of statistically significant difference, the presence of HPV in such cases of OSCC can alter the immunological system, particularly the Langerhans cells / O Papilomav?rus Humano (HPV) tem sido implicado fortemente no desenvolvimento de alguns carcinomas epiderm?ides orais (CEOs). Contudo, o sistema imunol?gico reage de alguma forma ? presen?a desse v?rus. Dentre as c?lulas envolvidas nesse mecanismo de defesa, destaca-se a c?lula de Langerhans (CL), por serem c?lulas processadoras e apresentadoras de ant?genos. O objetivo desse estudo foi avaliar a marca??o imuno-histoqu?mica das c?lulas de Langerhans entre os casos de CEOs HPV positivos e negativos, bem como a rela??o da imunomarca??o dessas c?lulas e a grada??o histol?gica de malignidade proposta por Bryne (1998) e modificada por Miranda (2002). Adicionalmente, a infec??o pelo HPV foi estudada com rela??o ao sexo, idade, localiza??o da les?o e a grada??o histol?gica de malignidade. Foram analisados 27 casos de CEOs, sendo 09 destes HPV positivos e 18 casos negativos. Para a marca??o imuno-histoqu?mica utilizou-se o anticorpo anti S-100, sendo as CLs quantificadas em 5 campos de maior aumento (400x). A an?lise estat?stica revelou n?o existir rela??o das vari?veis, sexo, idade, localiza??o da les?o e grada??o histol?gica, com a presen?a do HPV nos CEOs estudados. N?o existiu associa??o entre a marca??o imuno-histoqu?mica das CLs(S-100+) e a infec??o pelo HPV, e tamb?m n?o houve correla??o entre as CLs imunomarcadas e a grada??o histol?gica nos casos de CEOs analisados. Diante desses resultados, pode-se sugerir que mesmo n?o havendo diferen?a significativa, a presen?a do HPV nos casos de carcinoma epiderm?ide oral pode alterar o sistema imune, particularmente as c?lulas de Langerhans

Nos últimos anos, inúmeros estudos epidemiológicos evidenciaram a forte associação entre o carcinoma do colo uterino e a infecção por papilomavírus humano (HPV). Esta associação deriva do reconhecimento de que estes vírus codificam oncoproteínas, dentre as quais E6 e E7, que apresentam propriedades transformantes. O produto do gene E7 se liga ao produto do gene retinoblastoma que perde a sua função de regular negativamente o ciclo celular. O produto do gene E6 se liga ao produto do gene supressor de tumor p53 levando a sua degradação pela via de proteólise dependente de ubiquitina. O gene p53 é um supressor tumoral com função de regulação do ciclo celular que apresenta vários polimorfismos distintos em diversos grupos étnicos e tem sido amplamente estudado tanto em tecidos normais quanto em tecidos tumorais. O polimorfismo do códon 72 do gene i>p53 é o mais estudado e pode apresentar três alelos diferentes na população. Um alelo codifica arginina (Arg), um codifica prolina (Pro) e outro, raramente encontrado, codifica cisteína (Cys). Em 1993 foi iniciado um estudo epidemiológico da história natural da infecção por HPV e neoplasia da cérvice uterina em uma população feminina de baixa renda em São Paulo (Brasil), uma das áreas de maior risco em todo o mundo. O estudo focaliza a infecção persistente por tipos oncogênicos de HPV como evento precursor que leva à carcinogênese do colo do útero e visa entender os atributos da história natural da infecção viral e das doenças associadas ao colo uterino. Um dos objetivos deste estudo é avaliar se o polimorfismo do códon 72 do gene p53 pode, ou não, ser utilizado como marcador de predisposição ao câncer do colo do útero uma vez que um estudo inicial relatou que pacientes portando o genótipo p53Arg homozigoto seriam 7 vezes mais susceptíveis ao desenvolvimento de neoplasia da cérvice uterina que pacientes contendo o genótipo p53Pro e heterozigoto p53Pro/ Arg. Contudo, vários estudos posteriores contradizem e corroboram esses achados. O presente projeto teve como objetivos, portanto, verificar se o polimorfismo do códon 72 do gene p53 poderia estar associado a infecções persistentes por HPV e ao risco de neoplasia do colo do útero, além de comparar metodologias de detecção utilizadas por outros estudos, visando esclarecer se os motivos que levam à discordância dos resultados podem ser atribuídos a ocorrência de erros classificatórios metodológicos. Ao todo, sete metodologias de detecção foram comparadas. Apenas uma delas, PCR alelo-específica, apresentou resultado discordante das demais utilizadas. Coincidentemente, essa metodologia foi amplamente utilizada por muitos estudos que encontraram associações tanto positivas quanto negativas. Isso poderia nos dar indícios de que os erros classificatórios dependentes de metodologia poderiam influenciar os resultados de correlação entre o polimorfismo do códon 72 e o risco de neoplasia do colo do útero. As correlações observadas por este trabalho entre este polimorfismo do códon 72 e o risco de neoplasia do colo uterino não mostraram associação deste polimorfismo com o risco de infecções persistentes por HPV e as lesões precursoras do carcinoma do colo uterino. / In recent years, a number of epidemiological studies have pointed toward a strong association between cervical cancer and infection by Human Papillomavirus (HPV). This association derives from the discovery that these viruses code for oncoproteins, among them E6 and E7 that have transforming properties. The E7 gene product associates with the retinoblastoma gene product, causing the latter to lose its function as a negative regulator of the cell cycle. The E6 gene product interacts with the tumor suppressor p53 gene product, resulting in its degradation via ubiquitin dependent proteolysis. The p53 gene is a tumor suppressor that funcions in the regulation of the cell cycle. It presents a number of distinct polymorfisms in diverse ethnic groups, and has been widely studied, both in normal and tumor tissues. The polymorfism of codon 72 is the most studied, and may present three different alleles in the population. One allele codes for arginine (Arg), another codes for proline (Pro), and a third, rarely found, codes for cystein (Cys). In 1993 an epidemilogical study of the natural history of infection by HPV and its possible association with cervical neoplasia was initiated in a population of low income females in São Paulo, Brazil, one of the areas of greatest risk in the world. The study focuses on persistent infection by oncogenic types of HPV as a precursor to carcinogenesis of the cervix, and seeks to understand the attributes of the natural history of viral infection and of illnesses associated with the cervix. One of the objectives of the study is to evaluate if the polymorfisms of codon 72 of p53 can or not be used as a marker of predisposition to cervical cancer, given the finding in the initial study that patients who were homozygous for the p53Arg genotype were 7 times more susceptible to developing cervical neoplasias than those patients who were homozygous for p53Pro, or heterozygous p53 Pro/ Arg. Previous studies have been realized both supporting and disputing these findings. The current study had two main objectives: to verify if the polymorfism of p53 codon 72 could be associated with persistent infections of HPV and the risk of cervical neoplasia, as well as to compare methods of detection used by other studies, in an attempt to clarify if the discording results of past studies could be due to methodological classification errors. Seven detection methods were compared. Only one of these, allele specific PCR, presented discording results from the rest. Coincidentally, this method was widely used in a number of studies which found both positive and negative associations. This might indicate that the method-dependent classification errors could influence the results of correlation between codon 72 polymorphism and the risk of cervical neoplasia. The correlations observed by this study did not demonstrate an association between codon 72 polymorphism and the risk of persistent HPV infection and precursor lesions of cervical cancer.

Made available in DSpace on 2014-07-29T15:21:56Z (GMT). No. of bitstreams: 1 DIS J V S FILHO 2006.pdf: 804840 bytes, checksum: 74be1a5db70d292dc48c7621acb661f3 (MD5) Previous issue date: 2006-11-27 / Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the bucal cavity, and one of its variants is verrucous carcinoma (VC), of low degree malignancy. The diagnosis of VC is difficult from the clinical as well as from the histopathological point of view, and an effective diagnosis is vital when deciding on the treatment and prognosis of this tumor. The aim of this research was to evaluate cell proliferation and investigate the presence of HPV in spindle cell carcinoma of the mouth so as to check for possible differences in the aetiopathogenesis and biological behavior of these lesions. Forty-seven samples were selected and divided as follows: 39 SCCs, 8 VCs and 9 control (CT). Cell proliferation was qualitatively evaluated according to the location of the expression of the immunomarker in the cell and epithelium layers and by quantitatively considering the percentage of positive cells expressed. The analysis of HPV+ carcinomas was undertaken by means of the polymerase chain reaction (PCR), having GP5+/6+ as primers for identification of the virus. The qualitative analysis showed that the immunomarking in the VC as well as in the control group was concentrated mainly in the basal and parabasal layers and the counting of the positive cells at the base of the epithelium showed a significant statistical difference in the expressions of all three markers (p<0,05). The quantitative analysis of the cell proliferation markers was calculated by means of the Mann-Whitney and Kruskal Wallis tests and through the Pearson and Spermans correlation. They pointed to differences between the SCC and VC groups for the PCNA and cyclin B1 markers (p<0,05). On considering the three groups, it was proved that there was a positive correlation between Ki67 and the cyclin B1 (r=0,56) but not between the PCNA and the Ki67. The PCNA immunomarking was greater in the control group (average=100%), and the Ki67 showed itself to be effective as a proliferation cell marker although it showed no significant difference between the carcinoma variants. Whereas the cyclin B1 showed a significant difference in the comparison between the SCC and the VC groups (p<0,05), and a positive correlation to the extent that the histological grading of the malignancy (WHO model) of the carcinomas increased (r=0,44). All tumor samples were negative for HPV. Although the lesions showed different biological behaviors, the cell proliferation index in both types of mouth carcinoma was higher than in the control group, as shown by the analysis of the Ki67 and cyclin B1 markers. On considering the total sample of carcinomas, independently of the tumor variety, cyclin B1 showed a positive correlation with the histological degree of malignancy according to WHO. There is a need for further study to be carried out in the field of cell proliferation and detection of HPV especially with regard to VC, because it is a rare variant of SCC. / O carcinoma espinocelular (CEC) é a neoplasia maligna mais comum na cavidade bucal, e uma de suas variantes é o carcinoma verrucoso (CV), considerado de baixo grau de malignidade. O diagnóstico do CV é difícil, tanto do ponto de vista clínico quanto histopatológico e um efetivo diagnóstico é fundamental para estabelecer o tratamento e o prognóstico desse tumor. Neste estudo foi avaliada a proliferação celular e investigada a presença de HPV em carcinomas espinocelulares de boca com intuito de verificar possíveis diferenças na etiopatogênese e comportamento biológico destas lesões. Foram selecionadas 47 amostras de CEC assim distribuídas: 39 CECs, 8 CVs e 9 controles (CT). A proliferação celular foi avaliada qualitativamente de acordo com a localização da expressão do imunomarcador na célula e nas camadas do epitélio e quantitativamente considerando o percentual de células positivas expressas. A análise de carcinomas HPV+ foi realizada por meio da reação em cadeia da polimerase (PCR), tendo como primers GP5+/6+ na identificação do vírus. A análise qualitativa revelou que a imunomarcação tanto no CV como no controle concentrava se principalmente nas camadas basal e parabasal e a contagem das células positivas na base do epitélio mostraram diferença estatisticamente significativa na expressão dos três marcadores (p<0,05). A análise quantitativa dos marcadores de proliferação celular foi calculada pelos testes estatísticos Mann-Whitney, Kruskal Wallis, correlação de Pearson e Spermans, que revelaram diferenças entre o grupo CEC e CV para os marcadores PCNA e ciclina B1 (p<0,05). Considerando os três grupos, verificou-se correlação positiva entre Ki67 e a ciclina B1 (r=0,56) e inexistência de correlação entre o PCNA e Ki67. A imunomarcação do PCNA foi maior no grupo controle (média=100%), e o Ki67, mostrou-se efetivo como marcador de proliferação celular, entretanto, não mostrou diferença significativa entre as variantes de carcinomas. Já a ciclina B1 apresentou diferença significativa na comparação entre o grupo CEC e o grupo CV (p<0,05) e correlação positiva na medida em que a gradação histológica de malignidade (padrão OMS) dos carcinomas aumentava (r=0,44). Todas as amostras de tumores foram negativas para o HPV. Embora as lesões apresentem comportamento biológico diferente, o índice de proliferação celular nos dois tipos de carcinomas de boca mostrou ser superior ao do grupo controle, por meio da análise dos marcadores Ki67 e ciclina B1. Quando considerada a amostra total de carcinomas, independente da variante tumoral, a ciclina B1 mostrou correlação positiva com o grau histológico de malignidade segundo a OMS. Há necessidade que mais estudos possam ser empreendidos na área de proliferação celular e detecção de HPV em especial com relação ao CV, por se tratar de uma variante rara do CEC.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Estudo de prevalÃncia (estudo transversal) sobre infecÃÃo por HPV em colo uterino de gestantes, avaliando o(s) subgrupo(s) de HPV mais prevalentes e a associaÃÃo quanto ao desenvolvimento de lesÃes intraepiteliais escamosas. A metodologia constituiu-se de questionÃrio aplicado diretamente a 272 gestantes, independente da idade gestacional e de estarem sintomÃticas ou nÃo na primeira consulta de prÃ-natal, alÃm da coleta de material cÃrvico-vaginal (paredes vaginais, ectocÃrvice e endocÃrvice) para realizaÃÃo de Citologia oncÃtica convencional pelo mÃtodo de coloraÃÃo proposto por Papanicolaou e do teste de Captura HÃbrida IIÂ. Procedeu-se a seguir a identificaÃÃo das lesÃes intraepiteliais escamosas e da presenÃa do vÃrus HPV de alto, baixo e mÃdio risco oncogÃnico. Os achados da Captura HÃbrida IIÂ foram correlacionados com os achados citolÃgicos, comparando-se a freqÃÃncia dos resultados anormais nos dois mÃtodos. Procedeu-se tambÃm a associaÃÃo com aspectos biossociais que pudessem interferir na infecÃÃo produzida pelo HPV e no possÃvel desenvolvimento de lesÃes intraepiteliais escamosas. Realizaram-se anÃlises de correlaÃÃo univariada e bivariada, com cÃlculo do Qui-quadrado de Pearson e valor p< 0,05. Utilizou-se tambÃm de regressÃo logÃstica para estimar a magnitude das associaÃÃes. A prevalÃncia de infecÃÃo por HPV e citologias oncÃticas anormais foi de 32,3% e 14,0 % respectivamente. Os subgrupos de HPV de alto risco foram mais prevalentes (27,6%) do que os de baixo e mÃdio risco (18,4%) e a sua associaÃÃo mostrou-se estatisticamente significativa (p<0,05). A associaÃÃo da infecÃÃo genital por HPV de alto risco com lesÃes intraepiteliais escamosas descritas na Citologia oncÃtica convencional foi mais prevalente (8,5%) do que com HPV de baixo de mÃdio risco (5,6%) e teve significÃncia estatÃstica (p<0,05) / This work studies the prevalence (cross sectional) on infection by HPV in uterine cervical of pregnant women evaluating the subgroups of HPV more prevalents and the association in relation to the development of squamous intraepithelial lesions. The methodology was constituted of questionary applied to 272 pregnant women independent of pregnant age and of being symptomatic or not in the first medical advice of prenatal besides the collect of cervico vaginal material (vaginal walls, ectocervix and endocervix) to the achievement of conventional oncotic cytology by the method of coloration proposed by Papanicolaou and the test of Capture Hybrid IIÂ. Then it was proceeded the identification of squamous intraepithelial lesions and the presence of HPV virus of high, low and medium oncogenic risk. The results of Capture Hybrid IIÂ were correlated with the cytologic discoveries comparing the frequency of anormal results in both methods. It was also proceeded the association with biosocial aspects which could interfere in the possible development of squamous intraepithelial lesions. The analysis of univariable and bivariable correlations were accomplished with calculus of Qui-squared of Pearson and value p<0,05. The logistic regression was used to estimate the importance of associations. The prevalence of infection by HPV and anormal oncotic cytologies was about 32,3% and 14,0% respectively. The sub groups of HPV of high risk were more prevalent (27,6%) than the ones of low and medium risk. (18,4%) and their association showed to be statistically significant (p< 0,05). The association of genital infection by HPV of high risk with squamous epithelial lesions described on conventional oncotic cytology was more prevalent (8,5%) than with HPV of low and medium risk (5,6%) and had statistical importance (p< 0,05)

Neste estudo avaliamos o papel do metabolismo do triptofano (Trp) na homeostasia, na vaginose bacteriana e nas lesões cervicais associadas ao HPV. A importância do metabolismo do Trp se deve a sua ação na proliferação de microrganismos e de células do sistema imune. O consumo de triptofano tem sido identificado como uma forma de controlar o crescimento bacteriano limitando a infecção. Por outro lado, a oxidação de Trp produz quinurenina (QUIN), que tem papel chave na tolerância imunológica. A formação de QUIN se dá através das enzimas indoleamina 2,3-dioxigenase (IDO) e triptofano 2,3- dioxigenase (TDO). A mais estudada delas no âmbito das infecções/ imuno escape é a enzima IDO. Mais recentemente, tem-se dado ênfase ao papel da TDO no câncer. Nesta dissertação, o interesse foi avaliar a expressão da IDO no epitélio cervicovaginal de mulheres com vaginose bacteriana e de IDO e TDO em amostras cervicais de mulheres com diferentes graus de lesão cervical associada ao HPV. Foram incluídas 165 mulheres atendidas no CAISM/UNICAMP, as quais foram divididas em dois grupos: grupo caso composto por mulheres com lesão de baixo ou alto grau e carcinoma invasor (n=42) e grupo controle composto por mulheres com citologia oncológica normal, independente de apresentar infecção genital (n=123). IDO foi avaliada por imunocitoquímica em citologia em base líquida e IDO e TDO em biópsias cervicais. Mulheres com vaginose bacteriana apresentaram expressão aumentada de IDO em células escamosas em comparação às mulheres sem vaginose bacteriana (OR=7.41; IC 95%= 2.50 a 21.4; p <0.0001). No epitélio vaginal normal com ou sem infecção por HPV houve uma expressão leve de IDO em células escamosas. Na presença de lesões ou carcinoma, houve um aumento no número de células escamosas displásicas e de leucócitos IDO-positivos; aumento de IDO também pôde ser observada em culturas de pele organotípicas transduzidas com as oncoproteínas E6/ E7 do HPV16. Nas lesões cervicais, assim como visto para a IDO, a TDO esteve expressa em leucócitos, especialmente os infiltrados na região estromal e na parede dos vasos sanguíneos. A expressão basal de IDO no epitélio cervical normal e sua regulação positiva na infecção por HPV e lesões associadas sugerem a participação do metabolismo do Trp nos mecanismos imunossupressores envolvidos na doença. Embora o papel do IDO já tenha sido abordada anteriormente, até onde sabemos esta é a primeira evidência da expressão de TDO no epitélio vaginal, na neoplasia intraepitelial cervical e carcinoma de células escamosas. Ainda, em leucócitos, especialmente aqueles com morfologia típica de polimorfonucleares, parecem ser importantes fontes de IDO na cérvix uterina. / In this study we evaluated the role of tryptophan (Trp) metabolism in cervix homeostasis, bacterial vaginosis and HPV-associated lesions. The importance of Trp metabolism is due to its action on microorganisms and immune cells. Tryptophan consumption has been identified as a way to controlling bacterial growth limiting infection. On the other hand, the oxidation of Trp produces kynurenine (Kyn) which plays a key role in immunological tolerance. The formation of Kyn occurs through the enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). IDO is the most studied of them within the context of infections / immune escape. More recently, TDO has also been considered in studies of cancer progression. In this thesis, we were interested in cervicovaginal epithelium IDO expression in women with bacterial vaginosis and of IDO and TDO in cervical samples of women with different degrees of cervical lesion associated with HPV. A total of 165 women attended at CAISM/UNICAMP were divided into two groups: a case group composed of women with low or high grade lesions and invasive carcinoma (n = 42) and a control group composed of women with normal cytology, independent to present genital infection (n =123). IDO was evaluated by immunocytochemistry in liquid-based cytology and IDO and TDO in cervical biopsies. Women with bacterial vaginosis had increased IDO expression in squamous cells compared to women without bacterial vaginosis (OR = 7.41, 95% CI = 2.50- 21.74; p<0.0001). In normal vaginal epithelium with or without HPV infection there was a mild IDO expression in squamous cells. In the presence of cervical intraepithelial lesions or squamous cell carcinoma, there was an increase in the number of IDO-positive dysplastic squamous cells and leukocytes; increase in IDO can also be observed in organotypic skin cultures transduced with HPV-16 E6/E7 oncoproteins. In cervical lesions, as observed for IDO, TDO was expressed in leukocytes, especially infiltrates in the stromal region and in the wall of blood vessels. The basal expression of IDO in the normal cervical epithelium and its positive regulation in HPV infection and associated lesions suggests the participation of Trp metabolism in the immunosuppressive mechanisms involved in the disease. Although some previous data have already considered the role of IDO, as far as we know this is the first evidence of the participation of TDO in the vaginal epithelium, cervical intraepithelial neoplasia and squamous cell carcinoma. In addition, in leukocytes, especially those with a typical polymorphonuclear morphology, appear to be important sources of IDO in the uterine cervix.

Les papillomavirus humains (HPV) constituent l’archétype des virus à ADN oncogènes. Les HPV muqueux à haut risque (principalement HPV16) sont les principaux agents étiologiques du cancer du col utérin. Les protéines virales E6 et E7 sont des acteurs cruciaux de la cancérogenèse induite par HPV. Nous avons construit une ressource composée de 600 ADNc codant les effecteurs humains du système ubiquitine-protéasome (UPS) et identifié de nouvelles cibles potentielles des protéines E6 et E7 en utilisant une méthode basée sur la complémentation protéique de la Gaussia princeps luciférase (GPCA). HPV16 E6 lie les motifs LxxLL présents dans E6AP et IRF3. Nous avons résolu la structure cristallographique des complexes E6/LxxLL de E6AP/p53 et E6/LxxLL de IRF3. Par ailleurs, nous avons montré que les HPV ciblent une nouvelle voie suppresseur de tumeurs, la voie Hippo, avec ses deux médiateurs clef YAP et TAZ. Nous avons généré une banque d’ADNc codant 265 domaines PDZ humains et identifié de nouveaux partenaires potentiels des protéines YAP/TAZ en utilisant la méthode GPCA. Les résultats obtenus permettent de mieux comprendre la biologie des HPV et leur pouvoir oncogène. / The human papillomavirus (HPVs) are the archetype of DNA oncogenic viruses. High-risk mucosal HPVs (mainly HPV16) are the main causative agents of cervical cancer and are also involved in other cancers. HPV oncogenic properties are mainly due to the expression of E6 and E7 proteins. We built a resource composed of 600 cDNA encoding the human ubiquitin-proteasome system (UPS) effectors and identified novel E6 and E7 potential targets by using a method based on the complementation of the Gaussia princeps luciferase (GPCA). HPV16 E6 binds to specific LxxLL motifs present in E6AP and IRF3. We have solved the crystallographic structure of the E6/E6AP LxxLL/p53 and E6/IRF3 LxxLL complexes. Furthermore, HPV may target a novel tumour suppressor pathway, the Hippo signalling pathway with its two main mediators YAP and TAZ. We have built a cDNA library dedicated to the 265 human PDZ domains and identified news potential partners of YAP and TAZ proteins by using the GPCA. The results provide novel insights on HPV biology and their oncogenic property.

Bakgrund: Livmoderhalscancer är en av de vanligaste cancerrelaterade dödsorsakerna i utvecklingsländer. Humant papillomvirus (HPV) är ett sexuellt överförbart virus som kan, vid bestående infektioner, orsaka livmoderhalscancer. I Sveriges infördes år 2010 ett vaccin till flickor som skydd mot de typer av HPV som orsakar livmoderhalscancer med 70%. I Sverige erbjuds kvinnor mellan 23 till 50 år cellprov vart tredje år, vilket minskar risken att utveckla livmoderhalscancer med 90 %. Majoriteten av kvinnorna deltar dock inte i de erbjudna cellprovskontrollerna. Eftersom HPV är ett sexuellt överförbart virus kan det hos vissa vara stigmatiserat och leda till en känsla av skam. Människans syn på den sexuella hälsan och kroppen präglas av människans kulturella bakgrund och erfarenheter vilket påverkar människans värderingar och val. Syfte: Syftet var att belysa kvinnors erfarenheter av HPV-förebyggande åtgärder. Metod: Denna studie baserades på en litteraturöversikt av elva vetenskapliga artiklar som samlades in via noggrann analys och som ligger till grund för resultatet. Dessa artiklar bestod av vetenskapliga originalartiklar som samlades in från tre olika databaser. Analysen redovisades med två huvudteman och ett undertema. Resultat: Resultat framkom i två teman; Cellprov och HPV-vaccin. Under Cellprov tillfogades ett undertema; Självtest. Resultatet visade att kvinnors erfarenheter influerades av deras kulturella bakgrund och det i sig påverkade deras attityder mot preventiva åtgärder. Det visade sig även att den kulturella bakgrunden och mödrars erfarenhet av livmoderhalscancer påverkade mödrars attityd gentemot vaccin för sina döttrar. Deltagandet av cellprovstagning påverkades av kvinnors tidigare erfarenheter och skam/skuldkänslor gällande cellprov. Kvinnors erfarenhet av självtest var positivt då det ökade integriteten och därmed minskade känslan av skam. Diskussion: Kvinnors attityd till cellprov och HPV-vaccin präglades av kunskapsbrist och kulturell påverkan. Kvinnors önskan av en mer individanpassad information både språkligt och skriftligt ansågs som ett positivt och välbehövt inslag i vården. Mer vikt bör läggas på att öka deltagandet och kunskapen hos kvinnor genom att anpassa informationen som ges ut till individen. Madeleine Leiningers teori om transkulturell omvårdnad är ett hjälpfullt stöd för sjuksköterskor att anpassa vården utifrån individens kulturella bakgrund. Det gäller både den information som lämnas och omvårdnaden av patienter. / Background: Cervical cancer is one of the most common cancer-related causes of death in developing countries. Human papillomavirus (HPV) is a sexually transmitted virus that, in case of permanent infections, causes cervical cancer. In Sweden, a vaccine for girls was introduced in 2010 to protect against the types of HPV causing 70% of cervical cancer. In Sweden, women between 23 and 50 years of age are offered cell samples every three years, which reduces the risk of developing cervical cancer by 90%. However, the majority of women do not participate in the offered cell sample checks. Because HPV is a sexually transmitted virus, it may in some cases be stigmatized and lead to a sense of shame. Human views of sexual health and the body is characterized by human cultural background and experiences, which affects human values and choices. Aim: The purpose was to highlight women's experiences of HPV prevention. Method: This study was based on a literature review of eleven scientific articles collected through careful analysis and is the basis for the outcome. These articles consisted of scientific original articles as they were collected from three different databases. The analysis was presented with two main themes and one sub theme. Results: Results emerged in two themes; Cell sample and HPV vaccine. Self-test was added as a subtheme under Cell sample. The results showed that women's experiences were influenced by their cultural background and in turn influenced their attitudes toward preventive measures. It also turned out that the cultural background and mothers' experience of cervical cancer affected mothers' attitude towards vaccines for their daughters. The participation of cell sampling was influenced by the women's previous experiences and shame/guilty feelings regarding cell samples. Women's self-test experience was positive as it increased integrity and thus reduced the sense of shame. Discussion: Women’s attitude towards Cell sample and HPV vaccine were characterized by lack of knowledge and cultural impact. Women's desire for more personalized information was considered a positive and well-needed feature in health care. More emphasis should be placed on increasing the participation and knowledge of women by adapting the information given to the individual. Madeleine Leininger's theory of transcultural care can help nurses to adapt their care based on the individual's cultural background. This applies to both the information provided and the care of patients.

This study examines the accessibility and barriers that Polish immigrants face in public gynecological care in Sweden and explains their attitudes towards and frequency of gynecological visits. To understand attitudes of the research group, the study explores their knowledge about basic gynecological health topics such as Pap and HPV tests, HPV infections and vaccinations. Qualitative ethnographic methods were used in this research. Thirteen semi-structured interviews were conducted with 25 to 45-year old Polish women living in Stockholm, Sweden. Analysis was performed using descriptive and theoretical approaches. The results indicate several barriers to fully adapt to the Swedish healthcare system for Polish women. The barriers included the lack of understanding of how Swedish gynecological care works (division of specializations), problems in finding specialist care, an insufficient number of specialists, a lack of information in English or Polish, and a limited amount of knowledge among study participants about HPV tests and vaccinations. The adaptation of Polish immigrants to the Swedish system and their level of trust is influenced by their first experiences in Sweden, health literacy, experiences with the Polish private gynecological system, and the attitudes of partners and family with Swedish backgrounds or those who have long term experiences in Sweden.

Detection of p16 through immunohistochemistry (IHC) is the standard for determining the HPV status of the tumor according the TNM eighth edition released in 2017 and has become crucial for determining the HPV status of oropharyngeal squamous cell carcinomas (OPSCC) with direct impact on staging and prognostication. In recent years, detection of HPV DNA in mouthwashes has been proposed as a noninvasive alternative, both for OPSCCs and for other head and neck squamous cell carcinomas (HNSCCs). However, the prospect of using the mouthwashes to monitor the response to therapy is unclear. To evaluate the effect of curative therapy on the detection of HPV DNA, we performed a prospective study comparing the detection frequency of high-risk HPV DNA (HR-HPV-DNA) in pre- and post-therapy mouthwashes. We collected 137 mouthwashes from 88 pathologically confirmed HNSCC patients for DNA isolation and HPV genotyping with the Inno- LiPA assay. We show that HPV DNA in pretherapeutic mouthwashes can detect HPV-driven HNSCCs with a sensitivity of 50.0% and specificity of 85.4%, alongside a high negative predictive value of 79.5% and an accuracy of 74.5%. Furthermore, we observed a notable decrease in the detection frequency of HR-HPV-DNA after successful treatment (pre-therapy 50.0% (9/18) versus post-therapy 9.7% (3/28)). However, the comparatively low sensitivity regarding detection of HPV-driven OPSCC argues against its use in clinical routine.