SAMMANFATTNING Bakgrund: Varje år dör ungefär 150 kvinnor i Sverige på grund av cervixcancer. Ändå har dödsfallen minskat sedan cellprovtagning infördes som svensk prevention. Trots detta är det endast 80 % av de kvinnor som blir erbjudna cellprovtagning som deltar i denna typ av kontroll. Kvinnors kunskapsnivå om hur cervixcancer kan förebyggas genom att gå på regelbundna cellprovtagningar påverkade deltagandet i dessa undersökningar. Syfte: Syftet med studien är att beskriva kvinnors kunskap om cervixcancer. Metod: En litteraturstudie med kvantitativ ansats baserad på 9 vetenskapliga originalartiklar.  Texten analyserades enligt Forsberg och Wengström (2008) och Fribergs (2006) riktlinjer för analys av artiklar vid en modifierad systematisk litteraturstudie. Resultat: Studien tar upp kunskapsläget hos kvinnor om cervixcancer under kategorierna, HPV och sambandet med livmoderhalscancer, prevention och faktorer som har samband med kunskapsnivån av cervixcancer. I stort sågs brister hos kvinnor i alla dessa kategorier, dock varierade hur stort andelen kvinnor var som hade bristande kunskap. Slutsatser: Enligt författaren är det inte möjligt för kvinnorna som har en mycket bristfällig kunskap om cervixcancer att medvetet inneha ett förebyggande beteende gentemot denna typ av cancer. Därmed ses sjuksköterskans ansvar att informera som en viktig faktor för att förbättra preventionen.

Bromodomain protein 4 (Brd4) plays critical roles in development, cancer progression and virus-host pathogenesis. Papillomaviruses (PV) E2 protein associates with Brd4 and this interaction is important for transcriptional regulation of the viral oncogenes by E2 as well as viral genome maintenance in host cells for some of the PV. Brd4 is causally linked to a rare, aggressive cancer, NUT Midline Carcinoma (NMC), which is typically defined by chromosomal translocation fusing the NUT gene to the Brd4 gene. The molecular mechanism behind Brd4-NUT oncogenesis remains largely unknown. To gain mechanistic insight into the biological functions of Brd4, we performed a proteomic analysis to identify and characterize Brd4 associated cellular proteins. We discovered binding partners of the Brd4 ET domain and show that interaction of these proteins with Brd4 is conserved across the human BET proteins. The Brd4 ET interactors, NSD3, JMJD6 and GLTSCR1, were found to be important for Brd4 transcriptional activation function and are recruited to the promoters they regulate in a Brd4 dependent manner. Moreover, depletion of Brd4 or NSD3 reduced H3K36 methylation demonstrating that the Brd4/NSD3 complex regulates the chromatin microenvironment. We thus identified the ET domain as an important transcription regulatory domain for Brd4. Since the ET domain is preserved in the Brd-NUT proteins, we also investigated its contribution to Brd-NUT pathogenesis. Expression of the ET domain, which competes off the ET domain interactors from Brd4-NUT, induced squamous differentiation. More specifically, depletion of the ET domain interactor, NSD3 induced squamous differentiation by Brd4-NUT while loss of JMJD6 markedly reduced proliferation of the NMC cells. Lastly, we investigated the effect of the recently developed small molecule inhibitors of BET bromodomains on PV E2 functions and papilloma virus mediated pathogenesis. BET inhibitors blocked association of Brd4 and E2 with mitotic chromosomes without affecting Brd4 dependent E2 transcription regulation of viral promoters. This finding suggests that Brd4 affects viral genome maintenance and viral transcription regulation via different mechanisms. Overall, these studies have shed new insight into the molecular mechanism of Brd4 functions and their role in human diseases.

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.

Purpose: To assess awareness and attitudes regarding HPV, HPV-vaccines, use of condom and participation in pap-smear screening among high-school students in Uppsala County. The intention was also to investigate if there were any differences between students at theoretical programmes and vocational programmes. Methods: 608 students from seven high-schools in Uppsala County answered a questionnaire covering demographics, awareness and attitudes regarding HPV, HPV-vaccine, use of condoms and pap-smear tests. Results: A majority of the students had never heard of HPV (86 %, n=521), HPV-vaccine (94 %, n=537) or the link between HPV and cervical cancer (88 %, n=563). Most respondents had a positive attitude towards HPV-vaccine (84 %, n=508), but the biggest obstacle was the high cost (37 %, n=227). The students believed that it was less likely that they would use a condom with a new partner if vaccinated (mean=78, SD=26, p<0.001), or if they or their partner used contraceptive pills (mean=62, SD=32, p<0.001) compared to how likely it was that they would use a condom in general with a new partner. The girls rated the probability that they would participate in a pap-smear screening as relatively low if vaccinated (mean=59 SD=27). Students at theoretical programmes had better knowledge about HPV and HPV-vaccines. They were also more positive to the use of condoms and participation in pap-smear screening. Furthermore, more students at theoretical programmes (11%, n=46) than at vocational programmes (9%, n=16) planned to be vaccinated (p=0.048). Conclusion: The awareness regarding HPV and HPV-vaccine was low among high school students in Uppsala County, especially among students at vocational programmes. More information is required to increase the awareness and motivation to use condoms and participate in pap-smear screening.

BACKGROUND: Nova Scotia has the highest rate of cervical cancer, predominantly attributed to the Human Papillomavirus (HPV). In 2007, the HPV vaccine was approved and a successful school-based program was implemented. Little is known however, which strategies used by public health nurses (PHNs) helps improve vaccine uptake. METHODS: A retrospective, exploratory correlation study examined the relationship between school-based PHN strategies, and uptake of HPV vaccine. RESULTS: HPV vaccine initiation was significantly associated with PHNs providing reminder calls for: consent return (p = .017) and missed school clinic (p = .004); HPV education to teachers (p < .001), and a thank-you to teachers (p < .001). Completion of the HPV series was associated with consents being returned to the students' teacher (p = .003), and a PHN being assigned to a school (p = .025). CONCLUSIONS: These findings will help guide PHN’s best practice for optimal uptake of the HPV vaccine.

Human papillomavirus (HPV) infections of the genital tract are now recognized to be among the most prevalent sexually transmitted diseases and also a contributing factor to some cancers of the lower genital tract of women and men. Presence of HPV in a clinical specimen is confined to detection of the HPV genome by DNA hybridization techniques. In this thesis, the commonly used DNA hybridization techniques Southern blot and filter in situ hybridization (FISH), were first used for detection of genital HPV infection. In order to increase and simplify the detection of HPV in clinical specimens a more sensitive technique, the polymerase chain reaction (PCR) was subsequently utilized. For type-specific amplificaiton of HPV 6, 16, 18 and 33 by PCR, oligonucleotide primers located in the E6 and E7 regions of the HPV genome were selected. They were found to specifically amplify the four types. To be able to amplify a broad spectrum of genital HPV types, general primers located in the E7 and El region of the HPV genome, were designed and evaluated. They were found to amplify a wide range of genital HPV types. To further increase the sensitivity and specificity, a two-step PCR using general primers, was assembled and evaluated against a one-step PCR on cervical scrapes from young women in a population-based study. The two-step PCR increased the sensitivity about three-fold compared to the one-step PCR. By Southern blot and FISH, 46% of women with abnormal Papanicolaou (Pap) smears were shown to carry HPV DNA. Of the women analysed by Southern blot, 39 % harboured HPV DNA and 25 % proved HPV 16 positive. Of the samples analysed with FISH, 27 % contained HPV DNA, compared to 11 % of samples from a group of reference women with normal cytology. With the Southern blot technique, HPV DNA was detected in 66% of women with cervical intraepithelial neoplasia grade III (CIN III) lesions. Fifty-four percent of the women with CIN III lesions were positive for HPV 16 DNA. By type-specific PCR, 12 out of 13 women with cervical squamous carcinoma were shown to carry HPV 16 and/or 18. Among women with adenosquamous carcinoma of the cervix, HPV 18 was the most prevalent type (26%) but HPV 16 was also found in a proportion of the women(15 %). Nine of 13 premenopausal cases with cervical adenocarcinoma were HPV positive compared to only 2 of 13 postmenopausal cases (p&lt; 0.015). HPV 16 DNA was detected in 48%of women with cervical intraepithelial neoplasia (CIN), by the use of type-specific PCR. Three different groups of women with normal cytology were studied. Among women attending a family planning clinic in Kenya, 19% were shown to carry HPV virus, by the use of general primers. HPV 16 was found in 5.2% of these women and HPV 18 in 3.9%. In anothergroup of women, attending the gynecological department in Umeå, HPV 16 DNA was detected in 21 % by type-specific PCR. However, if consideration was taken to the medical status of the women, only 10% of women without any medical history were HPV 16 DNA positive, versus 54% of women with diseases and women with a relative progesterone dominance. Finally, by use of a two-step PCR using general primers, 20% of young women from Umeå taking part in a population-based study were demonstrated to carry HPV DNA. The most prevalent types were HPV 6 (2.0%) and HPV 16(2.7%). Among the women in this study with normal cytology, 19%were HPV positive. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1991, härtill 9 uppsatser.</p> / digitalisering@umu

While most Human papillomavirus (HPV) infections are asymptomatic and self-resolved, high-risk types, such as HPV-16 and HPV-18 are responsible for 99% of cervical cancers worldwide, whereas low-risk types, such as HPV-6 and HPV-11, are responsible for 90% of genital warts. While the different types of HPV and their varying oncogenicities have been studied extensively, it is still not clear what features of a HPV type make it more oncogenic than another. Two aspects which could affect the oncogenicity of HPV were studied: HPV variants and the E6 protein’s interaction with membrane associated guanylate kinase (MAGUK) proteins. Previous studies have shown that some HPV-16 variants may be more oncogenic than others. The first goal of this work was to characterise the HPV-16 variants in a Manitoba cervical cancer sample population to possibly identify mutations which could be associated with an increased risk of developing cervical cancer. Seventy-five samples from different individuals were sequenced in three distinct regions: the long control region and the E6 and E7 open reading frames. The DNA sequences obtained from these genomic regions were then compared between HPV-16 cervical cancer samples and Manitoba HPV-16 non cancer samples to identify any mutations that were exclusive to the cervical cancer samples. No specific mutations in any of the regions could be associated with cervical cancer. It is also proposed that HPV16 E6 protein’s interaction with MAGUK proteins contributes to its oncogenicity since low-risk E6 proteins lack this ability. The second goal of this work was to investigate which regions of high-risk HPV E6 proteins are needed in order to achieve MAGUK protein degradation, more specifically MAGI-1 degradation. Wild-type high-risk HPV16E6, low-risk HPV6E6, as well as mutants, were synthesized and cloned into vectors. In vitro translated proteins were used in MAGI-1 degradation assays. The ability of both wild-type HPV6 and HPV16 E6 proteins to degrade MAGI-1 was confirmed. Based on the performance of the different mutants in these degradation assays, it was determined that the PDZ-binding domain is necessary but not sufficient to induce E6-induced MAGI-1 degradation. In conclusion, it was determined that the entire HPV16 E6 protein is needed for the induction of MAGI-1 degradation.

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).

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Antropologia, Programa de Pós-Graduação em Antropologia Social, 2017. / Submitted by Raquel Almeida (raquel.df13@gmail.com) on 2017-05-31T20:26:44Z No. of bitstreams: 1 2017_NatáliaAlmeidaBezerra.pdf: 2717098 bytes, checksum: 2980354b170099e0519f689b783bfe16 (MD5) / Approved for entry into archive by Raquel Viana (raquelviana@bce.unb.br) on 2017-06-23T18:30:18Z (GMT) No. of bitstreams: 1 2017_NatáliaAlmeidaBezerra.pdf: 2717098 bytes, checksum: 2980354b170099e0519f689b783bfe16 (MD5) / Made available in DSpace on 2017-06-23T18:30:18Z (GMT). No. of bitstreams: 1 2017_NatáliaAlmeidaBezerra.pdf: 2717098 bytes, checksum: 2980354b170099e0519f689b783bfe16 (MD5) / O presente trabalho é resultado de um estudo etnográfico sobre a vacinação do HPV, realizado em uma escola pública do Distrito Federal. O objetivo desta pesquisa é conhecer o mundo social que envolveu a vacina dentro da escola, a partir da construção que os atores envolvidos - profissionais da educação e da saúde, mães e pais, meninas e meninos, fizeram ou possuíam sobre a vacinação do HPV. As vacinas têm-se revelado, diria historicamente, uma fonte de prevenção, de fortalecimento do corpo. Mas como um processo apropriado, tanto pelo Estado como pelo ser humano, sofreu e sofre vários tipos de interpretações e apropriações, extrapolando o mundo biomédico e ganhando diferentes contornos sociais e culturais. Tudo isso releva diversos posicionamentos, sejam com o próprio corpo, para com/ou da família, com os poderes institucionais. Quando nos deparamos com uma vacina que chegou ao Brasil há pouco, realizada apenas em corpos femininos muito jovens, esses ainda representados por seus pais, e que recebem a dose fora de seu campo jurisdicional “natural” – as unidades médicas – mas sim, dentro de uma instituição de ensino, este contexto vacinal se torna ainda mais interessante. É sobre a trajetória da vacina HPV e seus desdobramentos que esta pesquisa se debruçou. / The present work is the result of an ethnographic study on HPV vaccination, carried out in a public school in the Federal District. The objective of this research is to know the social world that involved the vaccine within the school, from the construction that the actors involved - professionals of education and health, mothers and fathers, girls and boys, did or had on this one. The vaccine has been, I would say historically, a source of prevention, of strengthening the body. But as an appropriate process, both by the State and by the human being, it suffered and undergoes various types of interpretations and appropriations, extracting the biomedical world and gaining different social and cultural contours. All of this relies on several maneuvers, be it with the body itself, towards the family, with institutional powers. When we are faced with a vaccine that has recently arrived in Brazil, carried out only on very young female bodies, those still represented by their parents, and receiving the dose outside their "natural" jurisdictional field - the medical units - but within Of an educational institution, this vaccine context becomes even more interesting. It is about the trajectory of the HPV vaccine in a school and the social world that it involved, this research looked at.

Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-01-28Bitstream added on 2014-06-13T20:36:36Z : No. of bitstreams: 1 marcolino_ld_me_botfm.pdf: 338414 bytes, checksum: 40e16603836e81203318aa6441533bf6 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A infecção por Papilomavírus Humano (HPV) oncogênico é o fator de risco mais importante para desenvolvimento de lesões intraepiteliais bem como para o carcinoma epidermóide invasor. A resposta imune tem um papel importante na história natural da infecção pelo HPV na cérvice uterina estando envolvida na persistência viral e na progressão das lesões. As citocinas são moléculas reguladoras da transcrição do HPV, sendo que o padrão Th1 contribui para o desenvolvimento da imunidade celular contra a neoplasia e infecção pelo HPV, e está relacionado com clearance dessa infecção. O padrão Th2 está associado com a persistência da infecção viral e com a progressão das lesões. Avaliar a concentração de IL-2, IL-4, IL-6, IL-10, IL-12, IFN-g e TNF-a na secreção cervical e no soro de mulheres portadoras de lesão intraepitelial de baixo grau (LIEBG), lesão intraepitelial de alto grau (LIEAG) e carcinoma epidermóide invasor (CE). Foram incluídas no estudo 109 mulheres com diagnóstico histopatológico de LIEBG (n=16), LIEAG (n=40), CE (n=13) e 40 mulheres com suspeita de doença HPV induzida, mas sem alterações histopatológicas na biópsia do colo do útero (grupo controle), atendidas no Ambulatório de Colposcopia da Faculdade de Medicina de Botucatu (UNESP) e no Ambulatório de Ginecologia Preventiva do Hospital Amaral Carvalho, Jaú, SP. Durante o exame especular foi coletada a secreção cervical com cytobrush para determinação do perfil de citocinas. O sangue periférico das mulheres incluídas no estudo foi colhido por punção venosa, em volume de 10mL e os padrões de citocinas no soro e na secreção cervical foram avaliados por ensaio imunoenzimático (ELISA). A pesquisa de HPV nas biópsias foi realizada empregando-se a técnica da reação em cadeia da polimerase (PCR) utilizando os primers específicos (MY9/11 e GP5+/GP6+) e a genotipagem foi realizada... / Infection with oncogenic types of human papillomavirus (HPV) is the most important factor for development of intraepithelial lesions and invasive squamous cell carcinoma. The immune response has an important role in the natural history of HPV infection in uterine cervix is involved in viral persistence and progression of lesions. Cytokines are molecules that regulate the transcription of HPV; the Th1 cytokine profile contributes to the development of cellular immunity against HPV infection and neoplasia, and is related to clearance of infection. The Th2 cytokine profile is associated with persistence of viral infection and the progression of lesions. Objectve: To evaluate the concentration of IL-2, IL-4, IL-6, IL- 10, IL-12, IFN-g and TNF-a in cervical secretion and serum of women with low-grade squamous intraepithelial lesions (LSIL), high-grade intraepithelial lesion (HSIL) and invasive squamous cell carcinoma (EC). The study included 109 women with histological diagnosis of LSIL (n = 16), HSIL (n = 40), EC (n = 13) and 40 women with suspected of HPVinduced disease, but no pathological changes on cervix biopsy (control group) attending in the Colposcopy Clinic of the Botucatu Medical School (UNESP) and in the Preventive Gynecology, Hospital Amaral Carvalho, Jaú, SP. During speculum examination cervical secretion was collected with cytobrush to determining the profile of cytokines. The peripheral blood of women enrolled in the study was collected by venipuncture in 10 mL volume and patterns of cytokines in serum and cervical secretion were assessed by enzyme immunoassay (ELISA). The search for HPV in the fragments of the biopsies were performed using the technique of polymerase chain reaction (PCR) using specific primers (MY9/11 and GP5+/GP6+) and genotyping was performed using the technique of PCR primers specific and confirmed by the analysis of restriction fragment polymorphism... (Complete abstract click electronic access below)