Aim: The aim of this thesis was to investigate experiences of receiving notification of an abnormal Pap smear result and its impact on women’s health-related quality of life as well as to investigate women’s awareness of human papillomavirus.   Methods: In total, 176 women and 20 healthcare professionals participated. Data were collected through individual interviews (I, II) and a questionnaire (IV) including the instrument Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD) and Hospital Anxiety and Depression Scale (HADS). For the translation and cross-cultural adaptation of the FACIT-CD, and for evaluation of its linguistic validity and reliability, cognitive debriefing interviews and a questionnaire consisting of the Swedish instrument FACIT-CD was used. Data were analysed by content analysis (I, II) and by using statistical analysis (III, IV), while one part (III) was analysed according to FACIT translation methodology.     Results: Women receiving notification of an abnormal Pap smear result have good overall HRQoL; they become anxious but not depressed. Reasons for anxiety were mainly that women misinterpreted the result as cancer, which could lead to lower attendance for further investigation, treatment and follow-up. To cope with the anxiety, women sought emotional support and information. They primarily used the Internet for information but also turned to healthcare professionals for information needs. Moreover, women had low awareness of HPV, its sexually transmitted nature, and its relationship to abnormal Pap smear results and cervical cancer. An awareness of HPV as a sexually transmitted infection did not lead to higher level of anxiety or more depression symptoms or worse HRQoL, compared to not being aware. Finally, the Swedish FACIT-CD is equivalent to the English version and linguistically valid and exhibited good internal consistency reliability.   Conclusion: Women have low awareness of HPV and abnormal Pap smear results, whereupon they misinterpret their test result as cancer. It is of importance that women understand their test result, in order to minimise anxiety as well as to maintain high attendance for investigation, treatment and follow-up of abnormalities.

Human papillomavirus (HPV) is widespread in the population and an important concern for public health. HPV-associated benign and cancerous disease is vaccine preventable yet vaccine uptake has been suboptimal. Adolescents are the primary target for vaccination yet their perspective has been inadequately examined. Ontario provides population-based preventive HPV vaccination to adolescent girls yet in the program’s first 2 years only approximately half of eligible girls received it. Effective strategies to improve vaccine uptake are needed. This thesis proposes a theory and ethics-based model to guide health promotion planning for HPV vaccination. Adopting an adolescent perspective, the model is applied and comprises: 1) a systematic review to identify barriers and facilitators to HPV vaccination from the viewpoint of young females; 2) GIS uses for communicating geospatial health information regarding vaccination; and 3) a roadmap for the future including recommendations for guiding principles, research, intervention development, and health policy.

Mathematical models provide unique insights to real-world problems. Within the context of infectious diseases, models are used to explore the dynamics of infections and control mechanisms. Human papillomavirus (HPV) globally infects about 630 million people, many of these infections develop into cancers and genital warts. Vaccines are available to protect against the most prevalent and devastating strains of HPV. The introduction of this vaccine as part of a national immunization program in Canada is a complex decision for policy-makers in which mathematical models can play a key role. We use the current recommendations provided by the World Health Organization to explore the integral role mathematical models have in the decision to incorporate the HPV vaccine within a national immunization program. We then provide a review of the literature discussing the role of mathematical models in the decision to include a vaccine in a national immunization program within the context of the HPV vaccine. Next, we evaluate the current standing of mathematical models used within the context of HPV immunization, to highlight the types of models used, underlying assumptions and general recommendations made about these immunization programs. Then, we create and analyze a model to explore the possibility of bettering the current HPV vaccine strategy in Canada. We focus on the effects of the grade of vaccination and the number of doses required to eradicate the targeted strains of HPV.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-12T15:20:04Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Tese_Elyda Gonçalves_PPGG_2016.pdf: 2873444 bytes, checksum: a341f8fc45a442c022975db79d659268 (MD5) / Made available in DSpace on 2017-07-12T15:20:04Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Tese_Elyda Gonçalves_PPGG_2016.pdf: 2873444 bytes, checksum: a341f8fc45a442c022975db79d659268 (MD5) Previous issue date: 2016-03-11 / CAPES / O câncer da mama é o tipo de câncer que mais acomete mulheres em todo o mundo. Diversos fatores estãoassociados ao desenvolvimento desta neoplasia, dentre elas as infecções virais. Entre os três vírus mais estudados como causa de carcinogênese mamária está oPapillomavirus humano (HPV). Assim, oobjetivo foi detectar e analisar o HPV emcarcinomasmamáriosde mulheres do Nordeste do Brasil. A detecção do DNA viral foi realizada PCR, as amostras positivasforam tipificadas por sequenciamento. A quantificação da carga viral e a determinação do status físico por qPCR, e a detecção as oncoproteínas de E6 e E7 de HPV por imunohistoquímica. O DNA de HPV foi detectado em 46,7% dos carcinomas de mama HPV-positivos. O HPV16foi omais prevalente, 92% dos casos. A carga viral do HPV apresentou uma média de 14,2 cópias em 104 células, noscarcinomas de mama. Além disso, em 57,2% dos carcinomas mamáriosHPV-positivas apresentaram o DNA viral integrado ao genoma do hospedeiro. Altas taxas de detecção das oncoproteínas E6(89,5%) e E7(90%) foram identificadas nos carcinomas de mama HPV-positivos. Já as proteínas supressoras de tumor, p53 e p16INK4A, apresentaram taxas menores 95,7% e 92,3% respectivamente. Os resultados deste estudo sugerem que o vírus esteja em atividade nas células tumorais e provavelmente desempenhem papel na carcinogênese mamária. / Breast cancer is the type of cancer that affects more women around the world. Several factors are associated with the development of cancer, among which viral infections. Of the three most-studied virus as a cause of mammary carcinogenesis is the Human papillomavirus (HPV). The objective was to detect and analyze HPV in breast carcinomas of women in northeastern Brazil. The detection of viral DNA was performed PCR positive samples were typed by sequencing. The quantification of viral load and to determine the physical status by qPCR, and detection of the oncoproteins E6 and HPV E7 by immunohistochemistry. HPV DNA was detected in 46.7% of HPV-positive breast carcinomas. HPV16 was the most prevalent, 92% of cases. The HPV viral load averaged 14.2 copies in 104 cells in breast carcinomas. Furthermore, 57.2% of HPV-positive breast carcinomas showed the integrated viral DNA into the host genome. High rates of detection of E6 (89.5%) and E7 (90%) were identified in HPV-positive breast tumors. Already the tumor suppressor protein p53 and p16INK4a, had lower rates 95.7% and 92.3% respectively. The results of this study suggests that the virus is active in tumor cells and probably play role in breast carcinogenesis.

Indiana University Purdue University Indianapolis / Human papillomaviruses (HPV) are the etiologic agents of most cervical dysplasia and all cervical carcinoma. Integration of high risk HPV into the human genome is thought to be a critical event in the progression from cervical dysplasia to invasive cervical carcinoma. The ability to use molecular assays in the detection and evaluation of HPV integration is essential in informing clinical models for early intervention and therapies. We therefore sought to determine the feasibility of real time-PCR (RT-PCR) as a molecular tool in detecting the physical state, episomal versus integration of HPV 16 and 18 DNA in cervical cancers. Tyramide amplified fluorescent DNA in situ hybridization (FISH) was used to look for evidence of HPV 16/18 integration using formalin-fixed, paraffin-embedded sections of cervical carcinomas. RT-PCR used the ratio of the E2 and E6 genes as a surrogate for determining the physical state of HPV 16 and 18 in 35 infected tissues. Results of RT-PCR showed that 16 cervical specimens (45.7%) contained episomal HPV, 17 cervical samples (48.6%) harbored the integrated form of HPV DNA, and 2 samples (5.7 %) contained both integrated and episomal forms of HPV. Results of the two assays were compared in 25 cervical carcinomas. For 13 of the 25 cervical samples there was an agreement in determining the physical state of HPV. RT-PCR, using the E2/E6 ratio as an assay for HPV integration appears to be promising and may prove to be an essential clinical method in the future.

No description available.

La dynamique de l’infection par le virus du papillome humain (VPH) chez l’enfant et les facteurs de risques associés à la transmission périnatale sont peu connus. À partir des 422 femmes enceintes infectées par le VPH dans la cohorte HERITAGE, le but était de décrire le risque de transmission périnatale, de récurrence et de persistance chez l’enfant et de mesurer l’association entre la charge virale du VPH durant la grossesse et la transmission périnatale. Des tests VPH ont été effectués sur des prélèvements vaginaux et placentaires collectés chez les femmes, et sur des prélèvements conjonctivaux, oraux, pharyngés et génitaux collectés chez les enfants aux 3-6 mois de la naissance jusqu’à 2 ans. Des analyses descriptives et des modèles de régression logistique ajustés ont été utilisés. La transmission périnatale du VPH a été de 7,3% (IC95%: 5,0%-10,4%), mais peu d’infections récurrentes et persistantes ont été observées chez l’enfant. La charge virale durant la grossesse a été fortement associée au risque de transmission périnatale (ratio de cotes ajusté = 7,01; IC95%:1,89-25,98) pour les femmes ayant une charge virale moyenne aux deux trimestres au-dessus d’une copie/cellule comparativement à celles en dessous de ce seuil. Cette étude suggère que la détection du VPH chez l’enfant n’est pas rare quoique le risque de persistance et de récurrence reste faible. La charge virale durant la grossesse a été fortement associée à la transmission périnatale. Cette étude permet de mieux comprendre la dynamique du VPH chez l’enfant et les facteurs de risque associés à la transmission périnatale. / The dynamics of human papillomavirus (HPV) infection in children and the risk factors associated with perinatal transmission remain poorly understood. From the 422 HPV-positive pregnant women in the HERITAGE cohort, the aim was to describe the risk of perinatal transmission, recurrence and persistence of HPV in children and to measure the association between viral load during pregnancy and perinatal transmission. HPV testing was done on vaginal samples collected during pregnancy, on placental samples and on conjunctival, oral, pharyngeal and genital samples collected in children every 3-6 months from birth to 2 years of age. Descriptive analyses and adjusted logistic regression models were used. Perinatal transmission was 7.3% (95%CI: 5.0%-10.4%) but few cases of recurrent and persistent infections were observed among children. HPV viral load during pregnancy was strongly associated with perinatal transmission (adjusted odd ratio= 7.01; 95%CI: 1.89-25.98), for women with a mean viral load measured at both trimesters of at least one copy per cell of HPV (compared to those with less than one copy per cell). This study suggests that the detection of HPV in children is not rare, although the risk of persistence and recurrence during childhood remains low. Viral load during pregnancy is strongly associated with perinatal transmission. This study provides a more comprehensive insight into the dynamics of HPV infection in children, and the risk factors associated with perinatal transmission.

<p dir="ltr"><a href="" target="_blank">Almost every case of cervical cancer in the United States is medically preventable with vaccination and proper screening, yet many Americans are insufficiently screened. Over 12 thousand American women suffered from cervical cancer in 2018</a>¹ causing 4 thousand deaths, with over a third in women who had never received a routine screening test².</p><p dir="ltr">New, sensitive testing techniques for cervical cancer screening are facilitating HPV testing without evaluating the cells collected in the sample by eye. This opens the door to new, accessible methods of screening such as rapid testing in clinic and at home, self-sampling, and mail-in testing. As cervical cancer morbidity and mortality is largely a result of healthcare inequities, these methods may have a significant impact on cervical cancer outcomes.</p><p dir="ltr">The goal of this project is to create a proof-of-concept, sample-to-answer rapid test to be used for cervical cancer screening in Indiana outpatient clinics. We began the project by conducting interviews and a survey to explore Indiana clinician perspectives on cervical screening methods such as self-sampling, rapid testing, and home-based screening. Clinicians preferred in-clinic testing with same-visit results, in the hopes that face-to-face explanation of results and scheduling follow-up care in person would improve patient retention for these important follow-up tests. To create such a test, we augmented an isothermal nucleic acid amplification method that copies 13 of the 14 high-risk human papillomavirus (hrHPV) types with an endogenous b-globin sample control and a simple colorimetric lateral flow strip (LFS) readout. When tested with HPV 16 the assay achieved a limit of detection of 1000 HPV copies per reaction, which would detect endocervical samples deemed ‘sufficient’ by clinical guidelines. It also performs in endocervical cells using methods and equipment that could be implemented in an outpatient clinic. The final test accepts swabs or brushes of endocervical cells, lyses them in 5 minutes, copies the target DNA and a sample adequacy control, and delivers the readout within 40 minutes on an LFS readout. Future directions for this assay include soliciting feedback from clinicians and other stakeholders about the prototype developed, adapting the assay to interferents of clinical endocervical samples, and adding probes for other HPV types, such as HPV 18 and eventually the other hrHPV types.</p>

Neuartige Vakzinierungsstrategien zur Aktivierung einer Tumor-spezifischen zellulären Immunantwort sind vielversprechende Ansätze zur Therapie von Tumoren, insbesondere Human Papillomvirus (HPV)-assoziierte Tumore. Bisherige HPV-Impfstudien zeigen zwar die Aktivierung einer spezifischen zellulären Immunantwort, eine Tumorreduktion bleibt jedoch aus. Um diesen Effekt auf Immunzellebene zu definieren, wurde die Wirkung der HPV-Vakzine Ad p14 im Mausmodell und an Untersuchungsmaterial humaner Tumore analysiert. In Mäusen bildeten sich HPV+ TC1-Tumore einer frühen Entwicklungsphase nach Vakzinierung zurück. Tumore einer späten Entwicklungsphase wuchsen dagegen in zwei Intervallen aus. Immunologische Eigenschaften der Tumorzellen blieben dabei unverändert. Unterschiede zeigten sich in den Frequenzen Tumor-infiltrierender Lymphozyten; in progressiven Phasen wurden nur CD4+ T Zellen nachgewiesen, in Regressionsphasen zusätzlich zytotoxische CD8+ T Zellen. Immunmodulatoren, wie Interferon alpha oder DTA-1, einem Antikörper für den Glucocorticoid-induzierten Tumornekrosefaktor-Rezeptor, unterstützten die Wirkung der Vakzine; letzterer erhöhte die Anzahl zytotoxischer CD8+ T Zellen und führte zur Abstoßung der TC1-Tumore. HPV+ Tumorgewebe des Menschen, wie auch ihre Vorstufen, zeigten im Vergleich zu anderen Tumoren, wie Bronchial oder Kolonkarzinomen einen signifikant höheren Anteil an CD4+ und CD8+ T Zellen und an Forkhead Box P3+ regulatorischen T Zellen. Die Ergebnisse deuten darauf hin, dass die immunologischen Abläufe bei der Entwicklung HPV-assoziierter Tumore mit denen vorangeschrittener chronischer Erkrankungen vergleichbar sind, in denen sich CD4+ und CD8+ T Zellantworten erschöpfen während sich gleichzeitig immunsuppressive Mechanismen verstärken. Um die Entwicklung von Impfstoffen zur Therapie HPV-assoziierter Tumore zu verbessern sollten diese Mechanismen ausführlicher betrachtet werden. / Novel vaccination strategies, activating cellular tumour specific immune responses represent a promising approach for the treatment of cancer. Especially featured for these treatments are tumours evolving from chronic human papillomavirus (HPV) infections. But current strategies have not yet proved efficacious for complete tumour regression. Addressing cellular immunological aspects of tumour vaccination, this work focused on effects of HPV vaccine Ad p14 in mice and in samples of human tumours. In mice vaccination resulted in complete regression of early stage murine HPV+ TC1 tumours. Late stage TC1 tumours increased discontinuously. During that process, TC1 cells preserved their immunological characteristics. But frequencies of tumour-infiltrating lymphocytes varied; in progressing tumours only CD4+ T cells occurred, in temporary regressing tumours also CD8+ T cells were detected. Immune modulators, like interferon alpha or glucocorticoid-induced tumour necrosis factor receptor targeting antibody DTA-1 aggravated the effects of vaccination; latter raised cytotoxic CD8+ T cell numbers and resulted in complete tumour regression. Human HPV+ tumours as well as HPV+ precancerous stages revealed numbers of CD4+ and CD8+ T cells and especially of forkhead box P3+ regulatory T cells that were significantly increased compared to melanoma, bronchial or colon carcinoma. To assist further analysis of human HPV-associated cervical cancer and facilitate studies on therapeutic approaches, a humanized mouse model was established. The present work points to immunological exhaustion in the development of HPV-related tumours comparable to chronic diseases where CD4+ and CD8+ T cells exhaust and immunosuppression by regulatory T cells increases at the same time. For the development of appropriate strategies to enhance efficacy in HPV-associated tumour therapy, further knowledge of mechanisms involved in specific T cell activation, T cell exhaustion and immunosuppression is necessary.

The aim of the study was to gain an in-depth understanding of the girl children’s parents perceptions regarding the papillomavirus vaccine roll-out programme at schools in Tshwane District, Gauteng Province. The researcher used a qualitative exploratory research design to address the research objective of the study as the qualitative method enables the researcher to explore and describe the study phenomenon. Data were collected from 12 parents of girl children who received the papillomavirus vaccine at one of the schools in Soshanguve township, which is one of the biggest townships in the Tshwane District. Data was analysed manually using content analysis. The following four superordinate themes emerged from data analysis: a) Communication of the programme, b) Motivation for allowing their children to be immunized. c) Response to immunisation, d) Suggested ways of enhancing the programme. These themes were discussed in relation to existing literature. Recommendations were made based on the findings to enhance the papillomavirus vaccination programme and for future research. / Health Studies / M.A. (Nursing Science)