L’intégration du génome du virus papilloma humain (VPH) a été reconnu jusqu’`a récemment comme étant un événnement fréquent mais pourtant tardif dans la progression de la maladie du col de l’utérus. La perspective temporelle vient, pourtant, d’être mise au défi par la détection de formes intégrées de VPH dans les tissus normaux et dans les lésions prénéoplasiques. Notre objectif était de déterminer la charge virale de VPH-16 et son état physique dans une série de 220 échantillons provenant de cols uterins normaux et avec des lésions de bas-grade. La technique quantitative de PCR en temps réel, méthode Taqman, nous a permis de quantifier le nombre de copies des gènes E6, E2, et de la B-globine, permettant ainsi l’évaluation de la charge virale et le ratio de E6/E2 pour chaque spécimen. Le ratio E6/E2 de 1.2 ou plus était suggestif d’intégration. Par la suite, le site d’intégration du VPH dans le génome humain a été déterminé par la téchnique de RS-PCR. La charge virale moyenne était de 57.5±324.6 copies d'ADN par cellule et le ratio E6/E2 a évalué neuf échantillons avec des formes d’HPV intégrées. Ces intégrants ont été amplifiés par RS-PCR, suivi de séquençage, et l’homologie des amplicons a été déterminée par le programme BLAST de NCBI afin d’identifier les jonctions virales-humaines. On a réussi `a identifier les jonctions humaines-virales pour le contrôle positif, c'est-à-dire les cellules SiHa, pourtant nous n’avons pas detecté d’intégration par la technique de RS-PCR dans les échantillons de cellules cervicales exfoliées provenant de tissus normaux et de lésions de bas-grade. Le VPH-16 est rarement intégré dans les spécimens de jeunes patientes. / Integration of human papillomavirus (HPV) has, until recently, been a frequent but late event in cervical carcinogenesis. The temporal view has, however, been challenged lately as integrated forms of HPV have been detected even in normal and preneoplastic lesions. Our objective was to describe HPV 16 load and physical state in a series of 220 normal and low grade cervical samples. We used quantitative real-time PCR, Taqman method, targeting E6, E2 and B-globin to calculate the HPV 16 load and the E6/E2 ratio in each sample. An E6/E2 ratio of 1.2 was used as a surrogate marker of integration. The site of integration was determined by restriction site PCR. Results show that the average viral load was 57.5±324.6 copies of DNA per cell, while E6/E2 ratio identified 9 samples with integrants. These integrants underwent amplification by restriction site PCR, followed by sequencing and nucleotide blast to identify the human-viral junctions. In conclusion, although it was possible to identify viral-host junctions with the integration positive control, that is, the SiHa cell line, the exfoliated cells of normal and low grade cervical lesions were negative for integration site by RS-PCR. HPV-16 is seldom integrated in specimens from young patients.

The present study was to diagnose and classify the Human Papilloma Virus (HPV) in pregnant and non-pregnant adolescents, as study the risk factors related to the infection, identify the multiples oncogenics types presents in the study people and associate the differents types of HPV with cytology and colposcopy findings. Methodologic design: the type of study was prospective, descriptive and transversal coorte. Was study 111 sexually active adolescents, between 10 and 19 years old, patients of the Gynecology Service of the Professor Alberto Antunes University Hospital of the Federal University of Alagoas (HUPAA-UFAL). Was utilized the polymerase chain reaction / restriction fragment length polymorphism - sequencing (PCR/RFLPs) to identification of the virus. Results: the viral percentual in the inferior genital tract was 27% of the cases. The molecular genotyping revealed high risk viral genetic material - HPV 16, 33, 51, 58, 66, 1S39, CP8304 and LVX100, in 28,5% of the cases, low oncogenic risk - HPV 6, 11, 53, 61 e CP141, in 40% and, the other 31,4%, considered the indeterminate type, include high and low risk virus. This more incident type is found isolated or associated to other viral types and appears in 40% of the positive cases. The viral infection rate among the pregnant adolescents was 11,7%. The HPV genital infection was associated with a past of sexually transmitted diseases and the consumption of alcohol by the adolescent. The frequency of adolescents infected by HPV, associated to low grade intraepithelial lesion, was 5,0%. No associations were observed between the specific types of HPV and the cytology and colposcopy findings among the studied adolescents. / O objetivo do presente estudo foi para diagnosticar e classificar o papilomavírus humano (HPV) em adolescentes grávidas e não grávidas, bem como estudar os fatores de risco para a infecção, identificar os diversos tipos oncogênicos presentes na população estudada e associar os diferentes tipos de HPV com achados da citologia e colposcopia. Desenho metodológico: o tipo de estudo foi prospectivo, descritivo e de coorte transversal. Foram estudadas 111 adolescentes sexualmente ativas, entre 10 e 19 anos, atendidas no Serviço de Ginecologia do Hospital Universitário Prof. Alberto Antunes da Universidade Federal de Alagoas (HUPAA-UFAL). Utilizou-se a reação de polimerase em cadeia/polimorfismo de comprimento de fragmentos de restrição - sequenciamento (PCR/RFLPs), para a identificação do vírus. Resultados: o percentual do vírus no trato genital inferior foi de 27%. A genotipagem molecular revelou material genético viral de alto risco - HPV 16, 33, 51, 58, 66, 1S39, CP8304 e LVX100, em 28.5% dos casos, enquanto que os de baixo risco oncogênico - HPV 6b, 11, 53, 61 e CP141, em 40%. Os demais 31,4%, foram do tipo considerado indeterminado, que incluem vírus de alto e baixo risco. Esse tipo mais incidente encontra-se isolado ou associado a outros tipos virais e aparece em 40% do total dos casos positivos. A taxa de infecção viral entre as gestantes foi de 11,7%. A infecção genital pelo HPV teve associação com o passado de doenças sexualmente transmissíveis e com o consumo de álcool pela adolescente. A freqüência de adolescentes infectadas pelo HPV, associada à lesão intra-epitelial de baixo grau foi de 5,0%. Não foram observadas associações tipo-específicas do HPV com os achados da citologia e da colposcopia entre as adolescentes estudadas.

Background: Cervical cancer is the second most common cause of death from cancer among women in Kenya. Various international studies indicate that the knowledge level of cervical cancer and its predisposing and preventive measures is low among the nurses as well as general population. This study aimed to assess knowledge, practices and attitudes of nurses with regards to cervical cancer screening and preventive measures at two Nairobi hospitals in Kenya. Across-sectional quantitative descriptive study design was used. Convenience sampling method was applied and data were collected from respondents using self-administered questionnaire. About 114 nurses aged 18 years and above participated in the study. The study revealed that nurses have the information about cervical cancer, available screening tests and the purpose of screening. Nurses have the knowledge that cancer screening could detect this cancer at an early stage; however, uptake is low. Cervical screening services were hampered by barriers relating to health care institutions, nurses perception and fear of screening technique, embarrassment, stigma, social influence, financial costs and available sources of information / Health Studies / M.A. (Nursing Science)

Background Cervical cancer is one of the common cancers worldwide. Despite the available screening services, the uptake of cancer of the cervix is very low. The incidence and mortality in western countries has reduced greatly due to the introduction of cervical cancer screening programmes. However, this is not the same in Africa where cervical cancer is more prevalent in lower resource countries to lack of access to effective screening and services that enhances early detection and treatment. Purpose/Aim of the study The purpose of this research is to determine knowledge of cervical cancer and the level of awareness of screening regimes/routines among HIV positive women in Swaziland. The study was conducted at one hospital specifically at the HIV Care Unit and Public Health Unit between January and June 2015. Methods The questionnaire was administered to collect data and consisted both open and close-ended questions. The questionnaire comprises of three sections: Section A: Socio-demographic data and Section B: Awareness on Cervical Cancer. Section C: Awareness/knowledge on cervical cancer screening. The sample consisted of 123 HIV positive who are on antiretroviral therapy (ART) or ART naive. The mean age for the respondents was 35 years. Results From this study, N=28 (23%) out of 123 (77%) reported to have received annual Pap smear for cervical cancer screening. A low proportion of the respondents (45%) had knowledge on cervical cancer screening. In addition, 63% of those who got information about cervical cancer screening through the radio perceived themselves to be at risk of getting cervical cancer. Only 4% heard about cervical cancer at the ART clinic, despite having been followed up for their care at the HIV clinic. Those who screened for cervical cancer were younger in age 25-34 years (80%). This study also revealed that education increased the changes of a woman to be screened for cervical cancer. If a woman had a university or high school education, she perceived herself to be at risk of getting cervical cancer. Conclusion Knowledge is power, cervical cancer campaigns should be conducted at national level in order to promote prevention through screening. Cervical cancer screening should be fully integrated into HIV services / Health Studies / M.A. (Public Health)

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.

Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos. / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T17:32:08Z (GMT). No. of bitstreams: 1 CastroSobrinho_JucaraMariade_D.pdf: 1214452 bytes, checksum: db87fc4f5e35e2d9e1091af5b48fc8cf (MD5) Previous issue date: 2012 / Resumo: Objetivo: Analisar a associação entre a coinfecção por papilomavírus humano (HPV), Chlamydia trachomatis (CT), vaginose bacteriana (VB) e resposta inflamatória (RI) com a gravidade da neoplasia cervical. Sujeitos e métodos: Estudo experimental, de corte transversal, realizado em Campinas, São Paulo e em Goiânia, Goiás, Brasil. A casuística incluiu amostras biológicas de 290 mulheres consecutivas submetidas à excisão da zona de transformação (EZT) ou conização. Para o estudo que avaliou a coinfecção entre HPV e CT e a associação com gravidade da neoplasia cervical foram selecionadas 251 (86,6%) mulheres infectadas por HPV de alto risco (HR-HPV). A detecção de HPV foi realizada utilizando os primers PGMY09/11 e a genotipagem através de hibridização reversa em pontos. A detecção da CT foi realizada por polimerase chain reaction (PCR) empregando primers cujo alvo é uma região de plasmídio críptico, gerando um fragmento de aproximadamente 512 pares de base. Para o estudo que avaliou a VB e resposta inflamatória e a associação destas condições com a gravidade da neoplasia cervical foram selecionadas 211 mulheres infectadas por HR-HPV, com esfregaços cervicais disponíveis para as análises. A presença de 20% ou mais de células indicadoras no esfregaço cervical corado pelo método de Papanicolau foi considerada positiva para VB. A resposta inflamatória nos esfregaços cervicais foi avaliada pela contagem do número de neutrófilos. O encontro de 30 ou mais neutrófilos por campo microscópico, observado sob o aumento de 1000x, foi considerado como presença de resposta inflamatória. Resultados: A prevalência de CT em mulheres HPV positivas foi de 15,1% (38/251). Foi observada uma associação significativa em mulheres CT negativas, com 30 anos ou mais, e NIC 2 ou pior diagnóstico, mas esta associação não foi observada em mulheres CT positivas. Infecções por HPV 16 e/ou 18 foram detectadas em 50% das mulheres CT negativas com menos de 29 anos e que apresentavam NIC 2 ou pior diagnóstico, e em 19,5% das mulheres CT negativas com NIC 1 ou não neoplásico. Nestas mulheres, a associação entre HPV 16 e/ou 18 e NIC 2 ou pior diagnóstico foi significativa, mas esta associação não foi observada no grupo CT positivo. Resposta inflamatória e VB foram observadas em 43,5% e 46,2% dos esfregaços cervicais de mulheres com NIC 2. Resposta inflamatória e VB foram observados em 64,2% e 32,6% dos esfregaços cervicais de mulheres com diagnóstico histológico de NIC 3. Nestas mulheres, quando infectadas pelos tipos de HPV 16 e/ou 18, foram observadas resposta inflamatória e VB, respectivamente, em 43,1% e 20% dos casos. Resposta inflamatória apresentou associação estatisticamente significante com NIC 2 ou pior diagnóstico em mulheres infectadas pelos tipos de HPV 16 e/ou 18 (OR= 6,70; 95%IC:2,32-19,31) e por outros tipos de HPV (OR=4,90; 95%IC: 1,86-12,89). Associações significativas foram observadas em mulheres com VB e NIC 2 ou pior diagnóstico, infectadas pelos tipos de HPV 16 e/ou 18 (OR= 3,38; 95% IC :1,07-10,64) e por outros tipos de HPV (OR= 3,38; 95%IC: 1,15-10,01). Conclusões: A infecção por CT detectada por PCR não mostrou associação com o aumento do risco para NIC 2 ou pior diagnóstico em mulheres HPV positivas. Em mulheres CT negativas e com menos de 30 anos de idade, os tipos de HPV 16 e/ou 18 estão associados à NIC 2 ou pior diagnóstico, resultado não observado para as mulheres CT positivas. A VB e resposta inflamatória estão associadas à NIC 2 ou pior diagnóstico em mulheres HR-HPV positivas / Abstract: Objective: To analyze the association between co-infection Human Papillomavirus (HPV) and Chlamydia trachomatis (CT), bacterial vaginosis (BV) and inflammatory response with the severity of the cervical neoplasia. Subjects and methods: This is cross-sectional experimental study carried through in Campinas, São Paulo and in Goiânia, Goiás, Brazil. The casuistic included 290 consecutive women submitted a the Excision of the Transformation Zone or conization due CIN 2 and CIN 3. For the study that evaluated the association between HPV and CT and severity of cervical neoplasia were selected 251 women who were infected with high-risk HPV (HR-HPV). HPV detection .was performed by PCR using primers PGMY09/11 and genotyping by reverse lineblot hybridization assay. The detection of CT was performed by PCR. For the study that evaluated the association between BV and inflammatory response with the severity of cervical neoplasia were selected 211 women infected with HR-HPV with cervical smears available for analysis. The presence of 20% or more clue cells in cervical smears stained by the Papanicolaou method was considered positive for VB. Inflammatory response was assessed by counting the number of neutrophils. The finding of 30 or more neutrophils per field observed under 1000x magnification was taken as presence of inflammatory response. Results: The prevalence of CT in HPV positive women was 15.1% (38/251). Significant association was observed between women with 30 years or older and CIN 2 or worse diagnosis for those CT negative, but this association was not observed for those CT positive. HPV 16 and/or HPV 18 were detected in 50% of the women ? 29 years age with CIN 2 or worse diagnosis who were CT negative, and in 19.5% for those women with CIN 1 or no neoplastic in histological diagnostic. In these women the association between HPV 16 and/or 18 and CIN 2 or worse diagnosis was significative, but this association also was not observed considering the CT positive group. Inflammatory response and BV were observed in 5.5% and 16.7% of cervical smear of women with no neoplastic diagnosis and were observed in 22.9% and 12.5% of cervical smears of women with CIN 1 in histological diagnosis. Inflammatory response and BV were observed in 43.5% and 46.2% of cervical smears of women with CIN 2 in histological diagnosis. The BV prevalence was higher in cervical smears of women infected by the types 16 and/or 18 (25.6%) and inflammatory response was more observed in cervical smears of women infected by other HPV types (25.6%). Inflammatory response and BV were observed in 64.2% and 32.6% of cervical smears of women with CIN 3 in histological diagnosis and were more observed in cervical smears of women infected types 16 and/or 18 representing respectively 43.1% and 20.0% of cases. Inflammatory response and BV were more observed in cervical smears of women infected types 16 and/or 18 in women with invasive carcinoma, representing 27.2% and 18.2% of cases respectively. Inflammatory response was significantly associated with CIN 2 or worse diagnosis in women infeted by HPV16 and/or HPV 18 (OR= 6.70; 95%CI : 2.32-19.31) and HPV other types than HPV16 and/or18 (OR=4.90; 95%CI: 1.86-12.89). Significant associations with BV and CIN 2 or worse diagnosis were observed in women infected by HPV 16 and/or 18 (OR= 3.38; 95%C1:07-10.64) and HPV types other than HPV16 and/or 18 (OR=3.38; 95%CI: 1.15-10.01). Conclusions: CT infection detected by PCR, does not increase the risk for CIN 2 or worse diagnosis in HPV positive women. HPV 16 and/or HPV 18 types in young women are associated with CIN 2 or worse diagnosis, but without obvious association with CT. BV and inflammatory response are associated with CIN 2 or worse diagnosis in women HR-HPV positives women / Doutorado / Ciencias Biomedicas / Doutora em Tocoginecologia

MCur / Department of Advanced Nursing Science / Cervical cancer remains one of the major public health problems globally, despite the fact that it is preventable and curable if identified at an early stage. Currently, cervical cancer is the leading cause of death among women in Sub-Saharan Africa where the knowledge about the disease is scarce among the affected population. Methods A quantitative cross-sectional survey was conducted in Thulamela Municipality of Limpopo Province. The purpose of the study was to assess the knowledge of cervical cancer prevention among women in four villages in Thulamela Municipality. The population of the study was composed of all women aged above 30 in the villages Malamulele, Mhinga, Muledane and Phiphidi. A sample of one thousand five hundred and forty-six (1546) was drawn using random sampling. Quantitative data were collected using a twenty-six-item questionnaire. The data were coded and then processed using the Statistical Package for Social Sciences to produce frequency tables and descriptive statistics such as chi-square and correlation. Results A number of findings were made in this study. The majority of the women in this study had little or no knowledge about cervical cancer, human papilloma virus and vaccines. The majority of the women had little or no knowledge on cervical cancer risk factors and how the disease is spread. These findings were confirmed by chi-squared values at p<0.05 and showed significant association between variables: that young women were likely to be aware of cervical cancer compared to elderly women, educated women were more likely to be knowledgeable about cervical cancer than those with low education attainment, elderly women were more likely to be not worried about cervical cancer compared to young women. Correlation, Pearson rho scores at p<0.05 showed significant correlations knowledge of cervical cancer and age (negative), knowledge and education (positive). The findings signified the need for cervical cancer prevention education in Vhembe District, and the need for primary health care nurses to promote access to such services through robust health education. vi Recommendations The study made a number of practical recommendations likely to educate women about cervical cancer, human papilloma virus and its prevention. These include: The possibility of large hospitals having their own small broadcasting stations that will frequently disseminate information throughout the local municipalities, road shows and use of informal sector like politicians and traditional healers in disseminating information.

Introducción: El virus del papiloma humano (VPH) es la causa esencial, pero no indispensable para el progreso de cáncer cervicouterino (CCU). Objetivo: Analizar la relación entre la incidencia y la mortalidad de cáncer de cuello uterino de los países de América Latina y el Caribe con el Índice de Desarrollo Humano, el Índice de Coherencia de Políticas para el Desarrollo Sostenible, en el año 2019. Métodos: Es un estudio ecológico de los grupos poblacionales de mujeres de los países de América Latina y el Caribe, durante el año 2019. Resultados: Se exhibió un promedio de incidencia de 18,33 casos/100.000 habitantes en América latina y el Caribe; una mortalidad de 10,35 casos/100.000 habitantes. Asimismo, se evidenció que la incidencia de CCU presenta un valor inferior al nivel de significancia (0,05), mientras que, la mortalidad presenta uno superior. Por otro lado, se obtuvo un IDH promedio de 0,75, lo cual describe inconsistencias en Honduras, Nicaragua, Guatemala, entre otros, los cuales manifiestan un IDH inferior. Por último, el Índice de Pobreza y Pobreza extrema, promediaron de 29,44 y 10,91 respectivamente. Conclusiones: La incidencia del CCU se aprecia en Belice, Honduras, Trinidad y Tobago, Nicaragua, Jamaica, Perú, Venezuela, Guyana, Paraguay y Bolivia convirtiéndolos en países vulnerables y a la mortalidad se incorpora a Republica dominicana. Por otra parte, la incidencia de CCU afecta principalmente a países subdesarrollados o en vías de desarrollo; Bolivia Paraguay y Guayana, son países que, a pesar ello no cursa con un IDH moderado, por lo cual mantendrán dichas naciones una relación inversa. / Introducción: El virus del papiloma humano (VPH) es la causa esencial, pero no indispensable para el progreso de cáncer cervicouterino (CCU). Objetivo: Analizar la relación entre la incidencia y la mortalidad de cáncer de cuello uterino de los países de América Latina y el Caribe con el Índice de Desarrollo Humano, el Índice de Coherencia de Políticas para el Desarrollo Sostenible, en el año 2019. Métodos: Es un estudio ecológico de los grupos poblacionales de mujeres de los países de América Latina y el Caribe, durante el año 2019. Resultados: Se exhibió un promedio de incidencia de 18,33 casos/100.000 habitantes en América latina y el Caribe; una mortalidad de 10,35 casos/100.000 habitantes. Asimismo, se evidenció que la incidencia de CCU presenta un valor inferior al nivel de significancia (0,05), mientras que, la mortalidad presenta uno superior. Por otro lado, se obtuvo un IDH promedio de 0,75, lo cual describe inconsistencias en Honduras, Nicaragua, Guatemala, entre otros, los cuales manifiestan un IDH inferior. Por último, el Índice de Pobreza y Pobreza extrema, promediaron de 29,44 y 10,91 respectivamente. Conclusiones: La incidencia del CCU se aprecia en Belice, Honduras, Trinidad y Tobago, Nicaragua, Jamaica, Perú, Venezuela, Guyana, Paraguay y Bolivia convirtiéndolos en países vulnerables y a la mortalidad se incorpora a Republica dominicana. Por otra parte, la incidencia de CCU afecta principalmente a países subdesarrollados o en vías de desarrollo; Bolivia Paraguay y Guayana, son países que, a pesar ello no cursa con un IDH moderado, por lo cual mantendrán dichas naciones una relación inversa. / Tesis

Solicitud de envio de manuscrito como artículo científico. / Propósito: La presente investigación busca describir las conductas sexuales (antes, durante y después del diagnóstico) de mujeres adultas jóvenes peruanas diagnosticadas con el virus del papiloma humano (VPH). Método: Se desarrolló un estudio cualitativo aplicando la técnica de la entrevista semiestructurada a 8 mujeres peruanas, cuyas edades oscilaron entre los 21 y los 28 años. A partir de lo manifestado por las participantes, se realizó el análisis de los datos utilizando elementos de la teoría fundamentada y el software Atlas.ti v. 7.0. Resultados: Los principales hallazgos revelaron que las participantes, al contar con escasa información sobre salud sexual, tuvieron relaciones sexuales sin preservativo; exponiéndose al contagio del VPH. Durante el diagnóstico, sintieron miedo, enojo e incertidumbre por las relaciones sexuales. Luego, señalaron que obtuvieron más información sobre salud sexual, retomaron sus relaciones sexuales, recuperaron la confianza en sí mismas y fueron capaces de disfrutar su sexualidad. Actualmente, son conscientes de su diagnóstico y conocen las consecuencias del VPH en su salud; sin embargo, relataron conductas de riesgo como no usar preservativo en sus relaciones sexuales. Conclusiones: Las mujeres adultas jóvenes peruanas diagnosticadas con el VPH cambiaron sus conductas sexuales. Antes, no utilizaban preservativos ya que utilizaban otros métodos para evitar el embarazo y no el contagio de ITS. Durante el diagnóstico, la mayoría decidió abstenerse sexualmente. Más de un año después del diagnóstico, las participantes cuentan con más información sobre salud sexual y han aprendido a disfrutar de su sexualidad. / Objective: This research is aimed at describing the sexual behavior (before, during, and after diagnosis) of young peruvian adult women diagnosed with human papillomavirus (HPV). Method: A qualitative study was conducted and the semi-structured interview technique was applied to 8 women living in Lima (Peru), whose ages ranged from 21 to 28 years. Based on what was stated by the participants, the data collected were analyzed by using the elements of grounded theory and with the support of Atlas.ti v. 7.0 software. Results: The main findings show that participants, having little information on sexual health, had sex without using a condom. This exposed them to HPV infection, and, at the time of diagnosis, they felt fear, anger, and uncertainty about sex. Participants point out that they then obtained information about sexual health, resumed their sexual relations, regained self-confidence, and now are able to enjoy their sexuality. While they are now aware of their diagnosis, they know how to take care of themselves and the health consequences of HPV. However, they report risky behaviors, such as not using a condom or other barrier methods in their sexual relations. Conclusions: Women diagnosed with HPV have changed their sexual behaviors. Previously, they used methods to prevent pregnancy but not the spread of a STI. During the diagnosis, most of them decided to abstain from sex. More than one year after diagnosis, participants report that they have information on sexual health and that they have learned to enjoy their sexuality. / Tesis

Für die Entstehung nicht-melanozytärer Hauttumore sind mehrere Risikofaktoren verantwortlich: UV-Exposition, Pigmentierung, Alter, Immunsuppression und möglicherweise Humane Papillomviren (HPV). Die molekularen Mechanismen der Tumorgenese des kutanen Plattenepithelkarzinoms (SCC) sowie der Präkanzerose Aktinische Keratose (AK) sind nur lückenhaft bekannt. Fokus dieser Arbeit ist die Untersuchung von SCC-Genexpressionsprofilen sowie der Einfluss kutaner HPV-Typen während der Karzinogenese bei immunkompetenten und immunsupprimierten, organtransplantierten Patienten. Durch Genexpressionsanalyse kutaner SCC, AK und normaler Haut konnten 118 differenziell exprimierte Gene in SCC mittels cDNA-Microarrays identifiziert werden. Bestätigt wurde die Expression von 11 aus 13 ausgewählten Genen (85%) mittels quantitativer real-time RT-PCR (qPCR), dabei konnte eine Korrelation der Genexpression mit der Progression der AK zum SCC für 3 Gene nachgewiesen werden. Dazu zählen das Gen Metalloproteinase-1, kodierend für ein Enzym, das in den Umbau von extrazellulärer Matrix involviert ist, das Protoonkogen RAB31 und das Tenascin-C (Tn-C) kodierende Gen Tn-C. Tn-C war im SCC-Gewebe an der Invasionsfront in Basalzellen sowie Keratinozyten im Stratum papillare und retikulare als Protein nachweisbar, nicht aber in normaler Haut. Die im Rahmen dieser Arbeit erstmalig nachgewiesene 2243 bp-Spleißvariante von Tn-C könnte aufgrund der primären Expression in SCC–Gewebe als diagnostischer Marker für SCC dienen. Diese Daten zeigen, dass simultane, multifaktorielle Dysregulationen von Genexpression und DNA-Reparatur, Zellzyklus und Proliferation, proteolytischen Enzymen und Adhäsionsmolekülen in SCC vorliegen. Ferner wurde die Expression von HPV in SCC und damit der kausale Zusammenhang einer HPV-Infektion mit der Hauttumorgenese untersucht. Das Infektionsmuster von SCC-Gewebe und normaler Haut mit spezifischen HPV-Typen erfolgte durch den Nachweis typenspezifischer HPV-DNA. Virale E6/E7-mRNA-Transkripte der kutanen HPV-Typen 8, 9 und 15 wurden in AK und SCC nachgewiesen. Dagegen konnten in HPV-DNA positiver, gesunder Haut oder Warzen keine HPV-Transkripte gefunden werden. Die Variantenanalyse des offenen Leserahmens von E6 identifizierte eine einzelne, bislang nicht beschriebene Punktmutation mit nicht bekannter Veränderung der Proteinstruktur. Die virale Aktivität der Onkogene E6 und E7 einiger kutaner Typen in AK und SCC weisen auf eine mögliche Rolle von HPV bei der kutanen Hautkarzinogenese hin. / During development of non-melanoma skin cancer, several risk factors are involved: UV-exposition, pigmentation, age, and potentially human papilloma virus (HPV). The molecular mechanisms underlying tumourgenesis in squamous cell carcinoma (SCC) and its pre-cancerosis actinic keratosis (AK) are not fully understood. In this study, the gene expression profile and HPV-infection status were analysed in SCC from immunocompetent and organ transplanted, immunocompromised patients.By global transcriptome analysis from cutaneous SCC, AK and healthy skin, 118 genes were identified differentially expressed in a cDNA-microarray. The expression of 11 out of 13 selected genes (85%) was investigated by real-time RT-PCR (qPCR) and the expression of three genes remarkably induced in SCC correlated with the progression to AK until SCC. These genes encoded for Metalloproteinase-1, which is involved in the remodelling of extracellular matrix, and the protooncogene RAB31 and Tenascin-C (Tn-C). Tn-C protein is expressed in SCC-tissue at the invasion front in basal cells and in keratinocytes in the Stratum papillare and retikulare, but not in healthy skin. This study, the 2243 bp Tn-C-specific splice-variant has for the first time detected in SCC, but not in normal skin. Thus it might serve as diagnostic marker of SCC progression. The data of the transcriptome analysis indicates that a simultaneous dysregulation of oncogene expression and DNA-repair, cell-cycle and proliferation, proteolysis and adhesion molecules exists in SCC. Additionally, the expression of HPV in SCC and thus the causal relationship between HPV-infection and tumourgenesis of SCC in immunocompromised patients was investigated. The HPV-infection pattern in SCC-tissue and normal skin was assessed by detection of DNA from cutaneous HPV-types. Viral E6/E7-mRNA-transcripts of the cutaneous HPV-types 8, 9, 15 were expressed selectively in AK and SCC. In contrast, no HPV-specific mRNA was present in HPV-DNA positive normal skin. The analysis of the open reading frame from the respective E6-protein genes unravelled one single pointmutation, which is not been characterized so far in terms of e.g. its impact on protein structure. The viral activity of the oncogenes E6 and E7 of cutaneous HPV-types indicates a potential function of HPV in the tumourgenesis of SCC in immunocompromised individuals.