Persistent infection with certain subtypes of Human papillomavirus (HPV) is a necessary cause of cervical cancer, the second most common cancer among women worldwide. Uptake of HPV vaccines in the targeted Canadian female population has been lower than anticipated. This study’s primary objective was to determine undergraduate women’s perceptions about HPV vaccination. A total of 401 female University of Ottawa undergraduate students completed a newly developed cross-sectional web survey. The prevalence of HPV vaccination was 49%. While the overall attitude towards receiving the vaccine was positive, vaccinated respondents had more favorable attitudes toward the vaccine. Lack of vaccine knowledge and cost were the primary barriers that have prevented HPV vaccination among non-vaccinated respondents. Offering HPV vaccination for women aged 18 to 25 presents a strategy for addressing suboptimal vaccination coverage in the targeted female population and may reduce health inequities demonstrated by variations in cervical cancer incidence within jurisdictions.

Au moins un cancer sur six dans le monde est causé par des agents infectieux, parmi lesquels les papillomavirus humains (HPV) qui sont responsables d'environ 600000 cas de cancer chaque année. Les HPV sont reconnus comme la cause nécessaire des cancers du col utérin, et la cause d'une fraction des cancers de l'anus, de la vulve, du vagin, du pénis, mais aussi de l'oropharynx et de la cavité buccale. Les données épidémiologiques récentes montrent une augmentation préoccupante de l'incidence des cancers HPV-induits de l'oropharynx dans certains pays développés, notamment en Amérique du Nord et en Europe du Nord. Dans le cancer du col de l'utérus, la connaissance approfondie de l'histoire naturelle de l'infection à HPV et des lésions associées a permis la mise en place du dépistage par frottis cervico-utérin, qui a donné lieu à une diminution considérable de l'incidence des cancers du col utérin. En revanche dans les cancers des voies aérodigestives supérieures (VADS) induits par l'HPV, très peu de données sur l'histoire naturelle de la maladie sont disponibles. Au- jourd'hui, le mode de transmission de l'infection à HPV et les étapes de la cancérisation des tissus des VADS restent toujours très mal compris. Si la vaccination contre l'HPV devrait avoir un impact sur l'incidence des cancers HPV-induits autres que ceux du col utérin, la couverture vaccinale reste insuffisante dans de nombreux pays pour générer une immunité de groupe, et à ce jour, aucune autre méthode de prévention des cancers des VADS HPV- induits n'est disponible. Les objectifs principaux de ce travail sont : (i) mieux définir le potentiel cancérogène des dif- férents HPV [Articles I, II et III] ; (ii) améliorer les connaissances du rôle de l'HPV dans les cancers des VADS [Articles IV et V] ; et (iii) comprendre l'histoire naturelle de l'infection à HPV et des lésions associées dans l'oropharynx [Projets I et II] / At least one out of six cancers worldwide is caused by infectious agents, of which human papillomaviruses (HPV) are responsible for around 600 000 cancer cases each year. HPV are recognized as a necessary cause of cervical cancer, and the cause of a fraction of cancers of the anus, vulva, vagina, penis, but also the oropharynx. Recent epidemiological data report an alarming increase in the incidence of HPV-induced oropharyngeal cancers in some devel- oped countries, as in North America and North Europe. In cervical cancer, extended knowledge of the natural history of HPV infection and associat- ed lesions has led to the implementation of cervical pap smear screening resulting in a sub- stantial decrease in cervical cancer incidence. Conversely, in HPV-induced head and neck cancers, very few data on the natural history of the disease are available. Today, the mode of transmission of HPV infection and the steps in cancerisation of head and neck tissues are still poorly understood. Although vaccination against HPV should impact the incidence of HPV- induced cancers other than in the cervix, vaccine coverage is insufficient in many countries to generate herd immunity, and to date no other method for prevention of HPV-induced head and neck cancers is available. The main objectives of this work are: (i) to better define the oncogenic potential of the differ- ent HPV types [Articles I, II and III]; (ii) to improve the knowledge of the role of HPV in can- cers of the head and neck [Articles IV and V]; and (iii) to understand the natural history of HPV infection and associated lesions in the oropharynx [Projects I and II]

Cervical Cancer is a preventable disease. Sadly it is a cause morbidity and mortality of women in poor socio-economic settings worldwide, largely due to avoidable factors. This amounts to a gross violation of the rights to life and access to healthcare of vulnerable populations of women. Awareness, sensitisation and mobilisation of the civil society could be crucial in influencing change in political will and healthcare policies to address the needs of HIV infected women, in particular, given their susceptibility to the development of cervical cancer. This work advocates for the South African government to further commit resources towards the prevention of cervical cancer, including hysterectomy in women at high risk of developing cervical cancer before it ensues. / Mini Dissertation (MPhil)--University of Pretoria, 2019. / Public Law / MPhil / Unrestricted

Orientador: Marilia de Freitas Calmon / Resumo: O câncer cervical é um problema de saúde pública mundial, especialmente devido à sua relação com a infecção prévia pelo papilomavírus humano (HPV). Os HPV são uma família de vírus de DNA com mais de 200 tipos e podem ser classificados em HPVs de baixo e alto risco. Os HPVs de alto risco mais relevantes são os HPV-16 e -18, que juntos são responsáveis por mais de 70% dos casos de carcinoma cervical. As modalidades atuais de tratamento para o câncer cervical são cirurgia, e a combinação de quimioterapia à base de cisplatina com radiação, porém apresentam efeitos adversos graves. Portanto, esforços contínuos são necessários para desenvolver novas drogas e estratégias terapêuticas eficazes para aumentar a eficácia da quimioterapia e diminuir esses efeitos colaterais. A emodina tem atraído grande atenção devido a seu efeito anti-inflamatório, antineoplásico e proapoptótico nos últimos anos. Além disso, a emodina pode ser utilizada como agente fotossensibilizador na terapia fotodinâmica. O interesse na terapia fotodinâmica no tratamento do câncer tem crescido exponencialmente, uma vez que é um tratamento minimamente invasivo, onde se erradica as células alvo, evitando-se a toxicidade sistêmica e os efeitos colaterais nos tecidos saudáveis. Assim, o objetivo deste estudo foi analisar o efeito da emodina associada à terapia fotodinâmica em linhagens de carcinoma cervical infectadas por HPV de alto risco (SiHa e CaSki) e queratinócitos humanos imortalizados (HaCaT). Inicialmente, as i... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Cervical cancer is a worldwide public health problem, especially due to its relation to the previous infection by human papillomavirus (HPV). The HPV is a family of DNA viruses with more than 200 types, and can be classified in low and high risk HPVs. The most important high risk HPVs are the HPV-16 and -18, which together are responsible for more than 70% cervical carcinoma cases. Current treatment modalities for cervical cancer are surgery, and the combination of cisplatin based chemotherapy with radiation, however they present severe adverse effects. Therefore, ongoing efforts are necessary to developed new drugs and effective therapeutic strategies to enhance chemotherapeutic efficacy and decrease these side effects. Emodin has attracted extensive attention due to its anti-inflammatory, antineoplastic, and proapoptotic effects in recent years. Furthermore, emodin may be used as a photosensitizing agent in photodynamic therapy. The interest in photodynamic therapy in the treatment of cancer has grown exponentially, since it is a minimally invasive treatment where eradicate target cells while avoiding systemic toxicity and side effects on healthy tissues. So, the aim of this study was to analyze the effect of emodin associated with photodynamic therapy in cervical carcinoma cell lines infected with high-risk HPV (SiHa and CaSki) and immortalized human keratinocytes (HaCaT). Initially, the investigations demonstrated that emodin presented cytotoxicity in concentration and ti... (Complete abstract click electronic access below) / Doutor

Knowledge and attitudes to HPV immunisation IV Author: Tereza Jelínková Thesis supervisor: PharmDr. Eva Zimčíková, Ph.D. Introduction HPV infection is one of the most common sexually transmitted diseases causing, apart from genital warts, other malignancies, most often cervical cancer. The most effective way of prevention is vaccination. So far, there have been 3 types of vaccines, most recent one being the nonavalent vaccine providing up to 90 % protection against cervical cancer- causing HPV, in contrast to the previously available 70 % protection from bivalent or quadrivalent vaccines. Aims The main aim of this thesis was to investigate the knowledge and attitudes towards vaccination against HPV, and knowledge about HPV in general, among secondary school students. Furthermore, to determine their vaccination status and compare the findings with data from previous theses, including a comparison of their knowledge about HPV and relevant prevention. Methodology The data was obtained by means of a questionnaire survey, which took place at three secondary schools. In December 2017 at Gymnázium in Mladá Boleslav, then during June 2018 at Gymnázium in Brandýs nad Labem, and finally in September 2018 at Gymnázium Chotěboř. The obtained data was recorded in a Microsoft Excel spreadsheet and then...

Human papillomavirus is the most frequently occurring sexually transmitted infection and has been recognized as the necessary cause of cervical cancer. Understanding the shift in public awareness caused by recent changes to cervical prevention is critical to addressing cervical cancer disparities in Appalachia. Since the human papillomavirus vaccine was approved for prevention, little data have been collected regarding human papillomavirus risk assessment and vaccine perceptions among Appalachian women. The purpose of the authors in this study was to investigate communication and cultural issues via a social scripting framework that could influence human papillomavirus vaccine uptake among southern Appalachian women; and explore participants' perceptions of human papillomavirus, cervical cancer, and the vaccine. A qualitative, descriptive design was employed to examine these issues in eight counties in northeast Tennessee and southwest Virginia. Thirty-nine women aged 18-49 years participated in a single individual interview or focus group session from October 2007 through August 2008. Interview and focus group data were audio-taped and transcribed verbatim. Two major themes emerged from the data: the human papillomavirus vaccine protection dilemma and spheres of silence surrounding the human papillomavirus vaccine protection dilemma. Study findings suggested areas for future research and may assist healthcare professionals in approaching southern Appalachian women as they make decisions regarding cervical cancer prevention.

Purpose of Review: Recent technological developments have vastly improved our ability to study the host microbiome and its role in many disease states. Numerous other reviews have contributed to our understanding of single viruses and gut microbiota or immunological outcomes. Here, we report, in aggregate, the newest data on genital microbiota interactions with the three most common viral STIs. Recent Findings: Four themes emerge: (1) the repeatability of specific community state types corresponding with infection risk, (2) a role for the microbiota as both therapeutic target and major player in treatment efficacy, (3) a need for models in which to study the mechanisms at play in microbiota/virus interactions, and (4) the impact of microbiota populating external genitalia on viral transmission. Summary: The studies reviewed herein suggest a convoluted interplay between host microbiota and viral STIs. More mechanistic studies are needed in order to leverage these interactions to improve prevention and treatment strategies.

Cancer metastasis is a highly complex process and is of great clinical importance since majority of cancer related mortality is associated with metastatic disease rather than primary tumor. The fact that cancer metastasis can develop years or even decades after primary tumor diagnosis, makes this process even more complex and therefore its understanding is of vital importance. Cervical cancer (CxC) is one of the most commonly diagnosed and cause of death among gynecologic cancers worldwide. In this chapter, our aim is to provide a broad overview of risk factors, modes of metastasis and major molecular factors and signaling pathways involved in the progression and metastasis of CxC. The understanding of these factors will enhance the knowledge of CxC pathogenesis and targeting these pathways would help combat against CxC and its metastasis.

Membres épithéliotropes de notre virome, les papillomavirus humains (HPV) causent majoritairement des infections asymptomatiques ou bénignes, contrôlées par les mécanismes de défense de l'hôte à l’échelle épithélial et immunitaire. Néanmoins, l’infection persistante par certains HPV à haut risque (hrHPV) cancérogène peut conduire au développement de cancers. Ainsi, les hrHPV à tropisme muqueux causent 98% des cancers cervicaux, et sont impliqués dans un nombre croissant de cancers ano-génitaux et oropharyngés. Les vaccins prophylactiques sont efficaces pour prévenir les lésions associées aux hrHPV à tropisme muqueux, mais à l'heure actuelle, il n'existe aucun traitement antiviral pour une infection établie. Dans cette thèse de doctorat, nous avons cherché à étudier les facteurs de l’hôte impliqués dans le cycle de vie d’HPV et sa carcinogenèse à deux niveaux : ceux du kératinocyte infecté et du système immunitaire. Des études chez certains patients immunodéficients (syndrome de WHIM, WS) présentant une susceptibilité sélective à la pathogénèse HPV ont identifié la chimiokine CXCL12 et CXCR4, son récepteur couplé aux protéines G (dont les mutations causent le WS) comme facteurs de contrôle du cycle de vie de ces virus. CXCL12/CXCR4 ainsi que ACKR3, le récepteur-leurre de CXCL12, peuvent moduler à la fois les réponses antivirales épithéliales et immunitaires. Nous avons d'abord étudié la contribution d'ACKR3 au cycle de vie d’HPV dans des cultures 3D de cellules épithéliales humaines (3D-EpC), seul modèle permettant la réplication d’HPV. Nos résultats indiquent que l'activité accrue d'ACKR3 présente un potentiel pro-oncogène puisqu'elle déplace le cycle de vie productif d’HPV vers l'oncogenèse et que le blocage d'ACKR3 pourrait être une approche thérapeutique attrayante pour favoriser la réplication d’HPV. Par la suite, nous avons étudié les conséquences fonctionnelles du cycle de vie productif d’HPV dans la communication intercellulaire, en mettant en place la technique FLIP dans les 3D-EpC. Enfin, nous avons étudié l'impact d’une mutation de CXCR4 associée au WS au niveau des cellules immunitaires cutanées dans le contexte de la carcinogenèse induite par HPV. Nous avons ainsi mis en évidence le rôle de CXCR4 dans la distribution, l’activation et la migration des cellules dendritiques dermales et des cellules de Langerhans ; leur possible dérégulation dans le contexte du WS pouvant contribuer à la sensibilité sélective des patients à la pathogenèse HPV. En conclusion, ce travail fournit des clés mécanistiques sur les interactions HPV-hôte aux niveaux épithélial et immunitaire. Il révèle le rôle central d'ACKR3 dans la réponse intrinsèque des kératinocytes envers HPV et approfondit nos connaissances sur le rôle de l’axe CXCL12/CXCR4 dans l'immunité cutanée à l’homéostasie et dans la carcinogenèse HPV. / Human papillomavirus (HPV) are part of our virome and infect cutaneous and mucosal sites. Most infections are asymptomatic or only cause benign lesions that are controlled by the host defence mechanisms, which take place both at the epithelial and the immune system levels. However, persistent infections with certain mucosal HPV types at high-risk for cancer development, cause virtually all cases of cervical cancers, a majority of anogenital cancers and an increasing proportion of oropharyngeal cancers. Prophylactic vaccines are efficient in preventing mucosal HPV types-associated lesions but currently, there is no antiviral treatment for an established HPV infection. In this doctoral thesis, we aimed at investigating host factors involved in HPV life cycle and carcinogenesis at two levels: the infected keratinocyte and the immune system. Studies in the context of certain immunodeficient patients (WHIM syndrome, WS) with selective susceptibility to HPV pathogenesis have identified the CXCL12 chemokine and its classical G protein-coupled receptor CXCR4 (whose mutations are causing the WS) as host susceptibility factors that act as gatekeepers of HPV life cycle. CXCL12/CXCR4 together with ACKR3, the second receptor of CXCL12 with an atypical decoy activity, can modulate both epithelial and immune cell anti-viral responses. Therefore, we first investigated the intrinsic contribution of ACKR3 to HPV life cycle in 3D human epithelial cell cultures (3D-EpC), the sole model allowing for HPV replication. Our results indicate that enhanced ACKR3 activity displays pro-oncogenic potential as it shifts HPV productive life cycle toward oncogenesis and that blocking ACKR3 could be an attractive therapeutic approach to favour HPV replication. In addition, we have studied the functional consequences of the productive HPV life cycle in cell-cell communication, being pioneers in setting up FLIP technique in 3D-EpC. Lastly, we investigated the impact of CXCR4 WS-mutation at the cutaneous immune cell level in the context of HPV-induced carcinogenesis. We have thus gained insights into the role of CXCR4 in dendritic cell and Langerhans cell distribution, phenotype and migration and how their deregulation in the context of the WS could account for the selective susceptibility of WS patients to HPV pathogenesis. In conclusion, this work provides new insights into HPV-host interactions at the epithelial and immune cell levels. We have unravelled the central role of ACKR3 in keratinocyte intrinsic response against HPV and deepen our knowledge on the role of CXCL12/CXCR4 in skin immunity in health and in HPV carcinogenesis.

Although the human papillomavirus (HPV) vaccine has been approved by the Federal Drug Administration (FDA) and is available for males and females, completion of the 3-shot series in Georgia remains relatively low. The purpose of this study was to examine the predictors of HPV vaccination initiation and completion for male and female adolescents, ages 13 to 17 years old, in Georgia between 2013 and 2015. The theoretical foundation of the study was the structural model of health behavior which is an ecological model. Logistic regression was performed to determine if there was any relationship between the independent variables of parental knowledge, providers' recommendation, and physical access to vaccination sites, and the dependent variables of vaccination initiation and completion while controlling for and separately testing the impact of age, race, and gender. The data sets from the Centers for Disease Control and Prevention, National Immunization Survey-Teen from 2013-2015 were used. There was no significant difference in HPV vaccination initiation or completion for any of the 3 years that were analyzed related to parental knowledge, as indicated by a p-value.