La Bolivie a des taux d’incidence et de mortalité associés au cancer du col de l’utérus qui setrouvent parmi les plus élevés de l’Amérique. Le programme national de prévention du cancerdu col de l’utérus est basé sur le test Papanicolaou et l’inspection visuelle avec acide acétiquepour la détection de lésions précancéreuses. Cependant, divers types de barrières (économique,socio-culturelle et géographique) empêchent que ce programme ne parvienne à réduireefficacement l’incidence du cancer du col de l’utérus en Bolivie.Le principal facteur étiologique associé au développement du cancer du col de l’utérus estl’infection persistante par les papillomavirus humains à haut-risque (HPV-HR). L’introductionde tests qui permettent la détection du matériel génétique des HPV-HR a donc le potentiel deréduire l’incidence et la mortalité associées à ce cancer dans le monde. De plus, ce test peut êtreréalisé sur des échantillons auto-prélevés. Ceci permettrait une augmentation du taux departicipation des femmes dans les programmes de dépistage primaire.Dans ce travail de thèse, nous proposons une stratégie de faible coût pour la détection des HPVHR.Cette stratégie commence par l’auto-prélèvement de cellules cervico-vaginales avec uncoton-tige et le transport des échantillons à sec sur une lame de verre. Ensuite, l’ADN estrécupéré avec un protocole simple utilisant la résine Chelex-100 et la protéinase K. Un contrôlede qualité de l’extraction d’ADN est réalisé avec une PCR amplifiant un fragment du gène dela b-globine humaine. Finalement, la détection des HPV-HR est faite avec une combinaison dedeux techniques :PCR BSGP-EIA et PCR pU. Toutes les étapes de cette stratégie ont été validéanalytiquement en utilisant des dispositifs et techniques standards comme référence. Dans cetravail nous montrons aussi le bon degré d’acceptabilité envers l’auto-prélèvement par lapopulation féminine locale de Cochabamba. Les différentes études ont été réalisées dans ledépartement de Cochabamba entre août 2014 et mai 2018.Notre stratégie a le potentiel d’améliorer le programme de dépistage du cancer du col de l’utérusen Bolivie étant donné que les femmes préfèrent faire un auto-prélèvement et que nostechniques sont plus sensibles analytiquement pour la détection des HPV-HR. Cependant, il estimpératif que le système de santé public bolivien améliore le suivi clinique des femmes à risqueafin de réduire efficacement l’incidence et la mortalité provoquées par le cancer du col del’utérus. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

abstract: Every year, 3 million older people are treated for fall injuries, and nearly 800,000 are hospitalized, many of which due to head injuries or hip fractures. In 2015 alone, Medicare and Medicaid paid nearly 75% of the $50 Billion in medical costs generated by falls. As the US population continues to age, more adults are beginning to deal with movement related disorders, and the need to be able to detect and mitigate these risks is becoming more necessary. Classical metrics of fall risk can capture static stability, but recent advancements have yielded new metrics to analyze balance and stability during movement, such as the Maximum Lyapunov Exponent (MLE). Much work has been devoted to characterizing gait, but little has explored novel way to reduce fall risk with interventional therapy. Targeting certain cranial nerves using electrical stimulation has shown potential for treatment of movement disorders such as Parkinson’s Disease (PD) in certain animal models. For human models, based on ease of access, connection to afferents leading to the lower lumber region and key brain regions, as well as general parasympathetic response, targeting the cervical nerves may have a more significant effect on balance and posture. This project explored the effects of transcutaneous Cervical Nerve Stimulation (CNS) on posture stability and gait with the practical application of ultimately applying this treatment to fall risk populations. Data was collected on each of the 31 healthy adults (22.3 ± 6.3 yrs) both pre and post stimulation for metrics representative of fall risk such as postural stability both eyes open and closed, Timed-Up-and-Go (TUG) time, gait velocity, and MLE. Significant differences manifested in the postural stability sub-metric of sway area with subject eyes open in the active stimulation group. The additional 8 metrics and sub-metrics did not show statistically significant differences among the active or sham groups. It is reasonable to conclude that transcutaneous CNS does not significantly affect fall risk metrics in healthy adults. This can potentially be attributed to either the stimulation method chosen, internal brain control mechanisms of posture and balance, analysis methods, and the Yerkes-Dodson law of optimal arousal. However, no adverse events were reported in the active group and thus is a safe therapy option for future experimentation. / Dissertation/Thesis / Masters Thesis Biomedical Engineering 2019

This cross-sectional, mixed-methods study examined the nature of, and association between, causal attributions and current smoking behavior in cervical cancer survivors who were smokers at cancer diagnosis (n=50). As a whole, participants’ beliefs about smoking as a risk factor or cause of cervical cancer in general (i.e., global attribution) and/or their own cervical cancer (i.e., personal attribution) reflected far greater endorsement of global than personal attributions. Data collection involved a quantitative survey and an optional semi-structured interview to assess key variables (i.e., smoking behavior and causal attributions). Data were analyzed via descriptive statistics and inferential tests, all of which illustrated greater endorsement of global smoking-related causal attributions versus personal attributions within the sample. In conclusion, the results of this formative study highlights the potential role of causal attributions in understanding the smoking behavior of cervical cancer survivors, the results of which aids understanding of how cancer survivors think about, and make changes in, their smoking behavior.

Introduction: Over 74,000 US women are diagnosed annually with endometrial or cervical cancers and experience significant treatment-related difficulties with body image, sexuality, and sexuality. The aims of the research were to examine relationships among body image, sexuality, and sexual functioning, and understand women’s views of these concepts. A novel theoretical framework encompassing these three concepts and contextual variables guided the research. Methods: A non-experimental cross-sectional pilot study was conducted with pre-menopausal women in an academic medical center who had stages I-III cervical or endometrial cancer, were 3-36 months post-treatment, and had no mental health diagnoses. Participants completed the Body Image Scale, Female Sexual Function Index, Female Sexuality Questionnaire, a demographic questionnaire, and open-ended questions and the researchers collected clinical data from the medical record. Results: Twenty women participated, and most reported disruption in body image, sexuality, and sexual functioning. Significant relationships were found between body image and sexuality (p = 0.0244) and sexuality and sexual functioning (p <0.0003). Stages II-III disease were significantly (p= 0.0371) associated with worse body image. Women reported issues with body image, sexuality, sexual functioning, psychosocial areas, reproduction, and communication with healthcare providers and personal caregivers. Discussion: This study is one of the first to examine relationships among body image, sexuality, and sexual functioning simultaneously, highlighting the importance of this approach. Despite design and sample limitations, results demonstrate a need for longitudinal studies using larger samples to further examine relationships among these concepts and selected contextual variables, explore communication issues, and refine the theoretical framework.

Hispanic and African American women are infected with sexually transmitted diseases more often than are Caucasian women. This racial disparity is also seen in the incidence of human papillomavirus (HPV) and cervical cancer. The medical connection between HPV and cervical cancer is often unknown or misunderstood among women. This study addressed the beliefs and subsequent health decisions of minority parents regarding whether to get their daughters vaccinated against HPV. The theoretical framework for this study was Rosenstock's health belief model (HBM). The specific study design used was Husserl and Heidegher's theory on Phenomenology. This qualitative study utilized focus groups containing mothers of young girls ages 9 to 12 years, who were recruited from local churches in San Antonio, TX. Twenty-seven mothers, African American (9), Hispanic (7), and Caucasian (11), participated in one of two focus groups for each racial group. Each focus group session was audiotaped and NVivo for Mac was used to perform a content analysis and to identify the themes present. Minority parents held stronger cultural and spiritual beliefs against vaccinating their daughters for a sexually transmitted disease more so than believing that their daughters were at risk for being exposed to STDs such as HPV. These beliefs presented as barriers to initiating the desired HPV prevention and screening practices. Gaps in the current knowledge of all parents exist and must be thoroughly addressed for all racial/ ethnic groups. Future educational programs need to not only address the gaps in knowledge but also shape and package public health messages with sensitivity to cultural and spiritual concerns.

Cervical cancer is a major public health problem in developing countries. In Guyana, factors associated with increasing cervical cancer cases among Indigenous Amerindian women (IAW), Afro- women (AGW), and Indo-Guyanese women (IGW) have not been fully examined. In this comparative cross-sectional study, 5,800 cervical cancer cases were selected from Guyanese women age 13 and above for ethnicity (Indigenous Amerindian, Afro- and Indo Guyanese women), geographical region, marital status, and year and stage at diagnosis. Secondary data from Guyana Cancer Registry for the 2000-2012 study periods were analyzed using chi-square test, multinomial logistic regression, poisson regression, and relative risk. Geographical region was a strong predictor of cervical cancer cases for all three ethnic groups (p < 0.05). The relative risk for cervical cancer for IAW in Regions 2 (RR = 1.2) and 6 (RR = 1.07) was greater than for IAW in Region 4, the reference group for the study period. Comparatively, the relative risk for cervical cancer for AGW in Region 4 was greater than AGW in all other regions except Region 3 (RR = 1.05). Additionally, the relative risk for cervical cancer for IGW in Region 3 (RR = 1.03) was greater than that of IGW in all other regions. Single IAW (1.05) have a higher risk of getting cervical cancer than their married counterparts as compared to AGW (0.96) and IGW (1.00). Implications for social change include development of tailored programs which utilize a socio-ecological model to address cervical cancer issues at the individual, interpersonal, cultural, and community levels. Future research should focus on understanding the epidemiology of cervical cancer and the social factors among the ethnic groups of women.

Cervical cancer is the single most common cancer in India, affecting an estimated 134,420 women in 2008. With access to early detection and basic treatments, most cases of cervical cancer are preventable. Moreover, if treatment is administered during the earliest stages of cervical cancer, 5-year survival rates can be increased to higher than 90 percent. Unfortunately, despite the availability of methods for prevention, more than 95 percent of women in India have never been screened for cervical cancer. Consequently, women in India are most often diagnosed during later stages of cervical cancer, significantly reducing survival prognosis. The objective of this study was to explore the role of awareness and knowledge of cervical cancer as a barrier to screening participation among urban women in Tamil Nadu; and further to identify the potential impact of increased cervical cancer awareness and knowledge on screening attitude. Quantitative and qualitative methods were used to characterize existing levels of awareness and knowledge of cervical cancer and screening among 207 women from the metropolitan area of Chennai. The results suggest that the majority of women (69.6%) were not aware of cervical cancer and very few (16.4%) were aware of screening. Demographically, women with secondary levels of education or higher were significantly more likely to have heard of cervical cancer and screening. Of the women that were aware of cervical cancer screening, most reported receiving information through television (33%) or a healthcare provider (28.6%). To describe the potential benefit of providing women with basic information about the secondary prevention of cervical cancer, levels of knowledge, measured before and after an educational session, were compared. This study further explored changes in associations between awareness, knowledge, perceived susceptibility, and screening attitude. It was observed that an overwhelming majority of women were receptive to participating in free cervical cancer screening, independent of previous knowledge of cervical cancer. Results also suggest that although lack of awareness appears to be a major barrier to participation in cervical cancer screening, providing women with information about cervical cancer has the potential to change the attitude of a significant proportion (58.3%) of women who were previously unreceptive to screening. Further, perceived susceptibility to cervical cancer appeared to be strongly associated with a positive screening attitude before and after receiving information. Finally, we examined and compared the socio-demographic characteristics of three subgroups of women: those who were receptive to screening without information, those who were receptive to screening after receiving information, and those who were not receptive to screening at either point. We found that younger, more educated women were receptive to screening without information. In addition, previously unscreened women who were less educated and illiterate in Tamil were most likely to acquire a positive attitude toward screening after receiving information. It also appeared that women who were most likely to be unreceptive to cost-free cervical cancer screening were more likely to be older and previously screened. These findings from our exploratory research with insights from additional comments made by several participants who were unreceptive to cost-free screening suggest that perceptions of free versus private healthcare may have influenced responses in this study.

Human Papillomavirus (HPV) is one of the most common causes of sexually transmitted disease worldwide. Infections by high-risk HPVs, such as HPV-18, have been associated etiologically with cervical cancer. The successful development of HPV vaccines may be beneficial to the HPV-na??ve population, but women that have already been exposed to the virus are still at risk of developing HPV-associated malignancies. A need for a systemic cure for HPV-infection therefore still exists. Gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers; however, few studies have explored this possibility for cervical cancer. The aim of this project is to construct a gene expression vector that can specifically target HPV-infected cervical cancer cells, by making use of the activity and selectivity of the P105 promoter which is determined by transcription control elements within the HPV-18 long control region (LCR). The first part of this study involved the construction of LCR deletion plasmids, and examining the subsequent level of gene expression induced within different mammalian cell lines. The results suggest the LCR to be capable in achieving cervical cancer-specific gene expression. The 3′-end of the viral L1 gene upstream of the LCR appeared to have a repressive effect on the promoter and therefore should be excluded for maximum LCR promoter activity. The second part of the project involved site-directed mutagenesis studies performed on selected transcription factor binding sites with an attempt to further increase the level of LCR promoter activity and specificity towards HPV-infected cervical cancer cells. The results suggest that a GRE/YY1 mutation may significantly enhance promoter activity. In terms of promoter regulation, the E2BSs appeared to be responsible for promoter activation in the absence of viral E2 proteins. The findings of this study suggest a possible gene therapy approach towards the treatment of cervical cancer. By making use of the activity and specificity of the HPV-18 P105 promoter to induce cervical carcinoma-specific expression of appropriate therapeutic genes, suicidal phenotypes can be introduced selectively within HPV-positive cervical cancer cells while normal HPV-negative cells are unaffected.

Human papillomavirus (HPV) is a double-stranded DNA virus, typically infecting mucosal or cutaneous epithelial keratinocytes. Today, more than 118 different HPV types have been formally described. Sexual transmission of mucosal HPVs is very common and generally asymptomatic, but HPV infection can be associated with benign lesions such as condylomata acuminata or, in rare cases, with malignant lesions such as cervical cancer. Two prophylactic vaccines are currently available in Europe, protecting against HPV-16 and HPV-18 (Cervarix) or against HPV-6, HPV-11, HPV-16 and HPV-18 (Gardasil). In order to assess the impact of the vaccination program, it is mandatory to obtain geographically widespread date on the baseline HPV prevalence and type distribution in cervical samples from women, presenting or not, normal or abnormal cytologic or histologic results. We undertook an epidemiological study in the Capital Region of Brussels to determine the HPV prevalence and type-distribution in 1526 cervical samples of women presenting a cytology within normal limits (WINL), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intra-epithelial lesions (LSIL), high-grade squamous intra-epithelial lesions (HSIL) or invasive cervical cancer (ICC). The HPV prevalence was 10.8% (95%CI: 8.8-12.8) for NILM, 34.5% (95%CI: 28.3-40.8) for ASC-US, 54.0% (95%CI: 47.4-60.6) for LSIL and 100% for HSIL and ICC. With an HPV-16 and HPV-18 prevalence of 63.3% (95%CI: 44.1-67.7) and 73.5% (95%CI: 63.0-84.0) in mono-infected HSIL and ICC, respectively, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the management and treatment of women suffering from HSIL and ICC in the Capital Region of Brussels. We also detected HPV-30, HPV-53, HPV-66 and HPV-68 in mono-infected HSIL and ICC samples, possibly providing arguments for the reconsideration of the carcinogenicity of these types. Vertical transmission of HPV was also previously reported, but in most cases one could not exclude a placental contamination by HPV positive cells from an infected birth canal. In order to confirm that the placenta can be infected with HPV, we analysed residual cells from 35 transabdominally obtained placental samples from pregnant women undergoing chorionic villous sampling for screening of suspected foetal abnormalities and found that two samples were positive for HPV-16 and HPV-62, respectively. The clinical importance of these results remains to be elucidated, but the previously observed association between placental HPV infection and pregnancy loss might gain further in importance. HPV gene regulation in placental trophoblastic cells has not been studied so far. We studied the HPV-16 early gene expression regulation in transiently transfected monolayer cultured trophoblastic cells with an HPV-16 long control region (LCR) driven reporter plasmid. We observed important differences in constitutive HPV-16 LCR activities between trophoblastic cell lines and could identify progesterone as an important inducer of HPV-16 early gene expression. Steroid hormones are induced during pregnancy and could therefore lead to an enhanced expression of the E5, E6 and E7 proteins upon placental HPV infection. Since these proteins were previously shown to affect trophoblast adhesion, survival, migration and invasion, their enhanced expression might eventually contribute to pregnancy loss. We furthermore found that the transcription of episomally maintained HPV-16 is not regulated by E2 or E1, but by E5, E6 and/or E7.

Injuries to the neck, or cervical region, are very importantsince there is a potential risk of damage to the spinal cord.Any neck injury can have devastating if not life threateningconsequences. High-speed transportation as well as leisure-timeadventures have increased the number of serious neck injuriesand made us increasingly aware of its consequences.Surveillance systems and epidemiological studies are importantprerequisites in defining the scope of the problem. Thedevelopment of mechanical and clinical tools is important forprimary prevention of neck injuries. Thus, the main objectives of the present doctoral thesisare:- To illustrate the dimension of cervical injuries inSweden,- To develop a Finite Element (FE) model of the uppercervical spine, and- To study spinal stability for cervical injuries. The incidence studies were undertaken with data from theinjury surveillance program at the Swedish National Board ofHealth and Welfare. All in-patient data from Swedish hospitals,ranging over thirteen years from 1987 to 1999, were analyzed.During this period 14,310 nonfatal and 782 fatal cervicalinjuries occurred. The lower cervical spine is the mostfrequent location for spinal trauma, although, this changeswith age so that the upper cervical spine is the most frequentlocation for the population over 65 years of age. The incidencefor cervical fractures for the Swedish population decreased forall age groups, except for those older than 65 years of age.The male population, in all age groups, has a higher incidencefor neck fractures than females. Transportation relatedcervical fractures have dropped since 1991, leaving fallaccidents as the sole largest cause of cervical trauma. An anatomically detailed FE model of the human uppercervical spine was developed. The model was validated to ensurerealistic motions of the joints, with significant correlationfor flexion, extension, lateral bending, axial rotation, andtension. It was shown that an FE-model could simulate thecomplex anatomy and mechanism of the upper cervical spine withgood correlation to experimental data. Three studies wereconducted with the FE model. Firstly, the model of the uppercervical spine was combined with an FE model of the lowercervical spine and a head model. The complete model was used toinvestigate a new car roof structure. Secondly, the FE modelwas used for a parameter study of the ligament materialcharacteristics. The kinematics of the upper cervical spine iscontrolled by the ligamentous structures. The ligaments have tomaintain spinal stability while enabling for large rotations ofthe joints. Thirdly, the FE-model was used to study spinalinjuries and their effect on cervical spinal stability inflexion, extension, and lateral bending. To do this, the intactupper cervical spine FE model was modified to implementruptures of the various spinal ligaments. Transection of theposterior atlantooccipital membrane, the ligametum flavum andthe capsular ligament had the most impact on flexion, while theanterior longitudinal ligament and the apical ligamentinfluenced extension. It is concluded that neck injuries in Sweden is a problemthat needs to be address with new preventive strategies. It isespecially important that results from the research on fallaccidents among the elderly are implemented in preventiveprograms. Secondly, it is concluded that an FE model of thecervical region is a powerful tool for development andevaluation of preventive systems. Such models will be importantin defining preventive strategies for the future. Lastly, it isconcluded that the FE model of the cervical spine can increasethe biomechanical understanding of the spine and contribute inanalyses of spinal stability.