The research described in this thesis reviewed previous uses of Interactive Voice Response (IVR), developed appropriate software, and employed IVR to obtain self-report of sensitive issues in surveys and conduct brief public health interventions. Chapter 1 introduces IVR and describes a systematic critical review of the use of IVR. IVR is a telephone interviewing technique where the human speaker is replaced by a high quality recorded interactive script to which the respondent provides answers by pressing the keys of a touch-telephone (touchphone). IVR has numerous advantages, including: economy, autonomy, confidentiality, access to certain population groups, improved data quality, standardised interviewing, multi-lingual interfaces, and detailed longitudinal assessments. Despite this, there have been few survey applications of IVR compared to alternative methods such as Computer-Assisted Telephone Interview (CATI). There has not been any evaluation of the use of IVR for asking sensitive questions in surveys or as a tool for health promotion at the community level. A literature review, described in Chapter 2, was conducted to identify other methods of asking sensitive questions. The literature review identified 19 different methods. Those methods that were most successful were those that provided the greatest degree of anonymity to the respondent. It was suggested that IVR may be a suitable method for community surveys. As described in Chapter 3, a custom software called Generalized Electronic Interviewing System (GEIS) was developed. This provided both CATI and IVR interviewing modes. As described in Chapter 4, it was found that the response rate obtained using IVR was unacceptably low, and an alternative interviewing method, the Hybrid method was developed. In the Hybrid method the interview was initiated by the interviewer but completed using IVR with GEIS. As described in Chapter 5, the IVR, CATI and Hybrid methods were used to investigate self-reported rates of alcohol and drug consumption within a telephone household survey of 2880 households. The self-report rates were compared to the National Drug Strategy Household Survey (NDSHS). Response rates did not differ significantly between the CATI and Hybrid methods, however the response rate for IVR was significantly less than the other methods. The Hybrid and IVR methods obtained significantly higher self-report consumption rates for alcohol and marijuana, and significantly higher hazardous drinking scores using Alcohol Use Disorders Identification Test (AUDIT). In Chapter 6 a pilot of an IVR cervical screening brief advice interface is described. A total of 5000 households were contacted by the IVR system. The system randomly selected an eligible woman aged 18-69 per household and determined her cervical screening status. A total of 661 women listened to the IVR message. The IVR call was shown to be acceptable and inexpensive compared to a mail pamphlet intervention. In Chapter 7 a randomized controlled trial of an IVR cervical screening brief advice involving 17,008 households is described. Cervical screening rate data were obtained from the Health Insurance Commission (HIC) for a period spanning six months before and following the intervention. The cervical screening rate was increased in the intervention postcodes by 0.43% compared to the control postcodes, and the increase was greater for older women at 1.34%. This was a desirable outcome since this group is considered to be an at-risk group. The overall conclusion was that IVR technology could be feasibly used to contact women to deliver brief interventions aimed at increasing cervical screening rates, but the cost per screen was likely to be high. It is suggested that an IVR system could be linked to cervical screening registers to more directly and economically contact women, and provide an efficacious complementary approach to the existing letter reminder system. / PhD Doctorate

<p>The study aimed to describe the knowledge and awareness of HPV infection and vaccine of female university students and to determine the predictors of vaccine acceptability.&nbsp / The study found that 70% of the participants were sexually active. Awareness and knowledge on HPV/vaccine were poor / with only 22% being aware of HPV and that a HPV vaccine was available in South Africa. A greater proportion (80%) reported willingness to be vaccinated. Being aware of the existence of a pap smear, higher knowledge about HPV, higher perceived vaccine effectiveness and higher perceived severity of HPV infection were significantly associated with increased willingness to be vaccinated.</p>

Cervical cancer is the second most common malignancy in women worldwide and one of the leading causes of cancer mortality globally. In patients with invasive cervical cancer prognostic factors are of value for the choice of treatment, monitoring of treatment and follow-up. The most important clinical prognostic factors are stage, tumor volume, parametrial infiltration, vascular invasion, lymph node metastases, and distant metastases. An improved estimation of the prognosis of cervical cancer is desirable, especially in early cancer stages. The aim of this research was to study possible associations between tumor markers, female sex steroids, smoking, S-phase fraction (SPF), and prognosis in invasive squamous cell cervical cancer (SCC). The study comprised 190 patients with SCC, stages IB-IV, admitted to the Department of Gynecologic Oncology at Norrland University Hospital in Umeå between September 1984 and October1990. Ten year mortality was estimated. In study I, of a total of 103 patients, it was found that increased tumor growth, measured by the DNA SPF, was associated with elevated serum progesterone and smoking in the premenopasual patients and with aneuploidy in the whole group. In study II, comprising 128 patients, survival length related to hormone levels and SPF was evaluated in women who died of cervical cancer. In both pre- and postmenopausal women, who died of cervical cancer, SPF at or above 12% was correlated with reduced survival. There was significant positive correlation between a low serum estradiol/progesterone ratio and short survival in those premenopausal women who died of cancer (p=0.02). In study III, ten-year follow-up results in 128 women were compared with the expression of ten relevant tumor markers, assessed by immunohistochemistry. The overall ten-year survival rate in patients with low COX-2 and high CD4+ expression was 76%, versus 53% in the remaining women. The survival rate with absent p53 and high COX-2 expression in the tumors was 42%, versus 71%, while the corresponding figure for the combination of high COX-2 intensity and expression of c-myc was 27%, versus 62%. None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did. Study IV addressed possible associations between selected tumor markers and cofactors in SCC. Ten tumor markers were examined in 128 patients. Smoking habits and previous oral contraceptive use were recorded. Serum estradiol and progesterone levels were evaluated in 80 women. Highly significant associations were found between strong c-myc staining and increased progesterone, low EGFR staining and high serum estradiol, and absence of p53 staining and smoking. There was an association between absence of p53 and high serum progesterone. In study V, LRIG1 expression was studied in 128 patients and was compared with expression of nine other tumor markers, smoking history, hormone levels, and prognosis. LRIG1 appears to be a significant prognostic predictor in early stage SCC, independent of the other tumor markers that were studied.  Diminished expression in advanced cancer stages and the inverse correlation to serum progesterone and smoking indicate that LRIG1 is a tumor suppressor in squamous cell cervical cancer. Conclusion: The results of these studies support a role of progesterone as a promoter of cervical cancer and indicate that smoking is associated with tumor progression. A combination of tumor markers might be of help in prognostic prediction. LRIG1 acts as a tumor suppressor. These findings might contribute towards greater understanding of prognostic prediction of squamous cell cervical cancer.

The purpose of this Thesis is to present a Bayesian analysis of oncological data sets with particular focus on cervical carcinomas and ovarian cancers. Bayesian methods of data analysis have a very long history, and have been used with great success in many disciplines, from Physics to Econometrics. Nonetheless, they remain very controversial among statisticians who belong to the orthodox - i.e, frequentist school, and are not well known by the medical community. To help in that direction, we reviewed in the introductory chapter the basic philosophical and practical differences between the two schools, and in the second chapter, we briefly reviewed the history of Bayesian methodology, from the early efforts of Thomas Bayes and of Pierre Simon de Laplace to the modern contributions of Harold Jeffreys, Richard Cox, and Edwin Jaynes. In many aspects of medical research, we deal with experimental data from which a certain proposition or hypothesis is validated. Unlike in physics, where we have strong and solid foundations such as Newton's law of motion, Snell's optical laws, Kirchoff's laws, Einstein's relativity theory, and many more, we do not have such privileges in medical research. Hence, many hypotheses are constantly tested as new evidence becomes available. One of the actively-researched medical areas is cancer research about which our understanding is still in its infancy. Numerous experiments (both in vivo and in vitro) and clinical trials have been conducted to further our knowledge; thus, Bayesian methodology finds its place to aid us in obtaining scientific inferences about certain propositions or hypotheses from available data and resources. In this work, we use data given to us by our medical collaborators at the Princess Margaret Hospital (PMH) in Toronto to carry out two main projects: Firstly, to make an inference about the oxygenation status (oxygen partial pressure, pO$_2$) within human cervical carcinomas and secondly, an inference about the effectiveness of various molecularly-targeted agents (MTAs) in phase II clinical trials of relapsed ovarian cancer patients. In the first problem, we address the challenges of tumor hypoxia - a state of oxygen deprivation in tumors. Currently, there are two methods to obtain tumor oxygen status, namely the direct Eppendorf needle electrode and the indirect immunohistochemical assay of a protein marker, Carbonic Anhydrase IX (CAIX). In this project, we introduce Bayesian probability theory to obtain inferences about tumor oxygenation from each technique and the concordance between the two techniques. From this study, we conclude that under certain conditions, two biopsies are sufficient to infer the tumor oxygenation level based on the immunohistochemical assays of CAIX. Additionally, there is a fair concordance between the direct and the indirect measurements of tumor oxygenation. In the latter problem, ovarian cancer is the topic of study. Ovarian cancer has the highest mortality rate among gynecological cancers and one that is known to relapse. CA-125 is still the most inexpensive biomarker for monitoring ovarian cancers. From the phase II clinical trial data, we demonstrate the survival advantage of CA-125 responsive group of patients by means of a non-parametric Kaplan-Meier statistic.

SAMMANFATTNING Bakgrund: Livmoderhalscancer orsakas av humant papillomvirus (HPV). De flesta fallen inträffar bland kvinnor som inte deltar i preventionsprogram mot livmoderhalscancer. Syfte: Att undersöka invandrarkvinnors inställning till prevention av livmoderhalscancer. Metod: En explorativ kvalitativ studie. The Health Belief Model har använts som teoretisk modell. Fem fokusgruppintervjuer med 32 kvinnor ålder 18-54 år, som studerade svenska för invandrare. Data analyserades med latent innehållsanalys. Resultat: De temata som kunde urskiljas var svårigheterna med kommunikation med sjukvården, positiva till hälso- kontroll, behov av information för att fatta beslut samt ojämlikhet mellan könen. Kvinnorna i studien var mycket positiva till prevention av livmoderhalscancer och hade hög tilltro till det svenska sjukvårdssystemet. De poängterade i synnerhet kontakten med barnmorska. Deltagarna hade överlag svårigheter med information från sjukvården och saknade kunskap och information om HPV för att kunna fatta beslut om prevention av livmoderhalscancer med HPV- vaccin. Det framkom även att kulturella skillnader och ojämlikhet mellan könen påverkade inställning till prevention av livmoderhalscancer. Slutsats: Informanterna var positiva till prevention av livmoderhalscancer och vill få adekvat kunskap och information om sjukdomen men de har svårigheter med kontakten med sjukvården. Sjukvårdspersonal behöver beakta att kulturella normer påverkar kvinnors inställning till deltagande i det nationella preventionsprogrammet av livmoderhalscancer. / ABSTRACT Background: Cervical cancer is caused by Human papillomavirus (HPV). Most cases occur among women who don’t attend prevention programs. Objective: To explore immigrant women’s attitude towards prevention of cervical cancer. Method: An exploratory qualitative study. The Health Belief Model (HBM) has been used as a theoretical model. Five focus groups interviews with 32 women age 18-54, who studied Swedish for immigrants. Data was analyzed with content analysis. Results: Four main themes were found: difficulties to communicate with healthcare, positive to health control, the need of information to make a decision and inequalities among genders. The informants were positive to prevention of cervical cancer and had high confidence in the Swedish health care system. They appreciated in particular the meeting with the midwife. They had difficulty understanding the information from health care and had inadequate knowledge about HPV to make decisions about prevention of cervical cancer. Cultural differences and inequalities among genders were also related to prevention of cervical cancer. Conclusion: The informants were positive to prevention of cervical cancer and want to have adequate information about the disease. Healthcare professionals should consider that difficulties in contact with healthcare as well as inequalities in gender and cultural aspects have an impact on immigrant women’s attitude to prevention of cervical cancer. / HPV-projektet

The purpose of this Thesis is to present a Bayesian analysis of oncological data sets with particular focus on cervical carcinomas and ovarian cancers. Bayesian methods of data analysis have a very long history, and have been used with great success in many disciplines, from Physics to Econometrics. Nonetheless, they remain very controversial among statisticians who belong to the orthodox - i.e, frequentist school, and are not well known by the medical community. To help in that direction, we reviewed in the introductory chapter the basic philosophical and practical differences between the two schools, and in the second chapter, we briefly reviewed the history of Bayesian methodology, from the early efforts of Thomas Bayes and of Pierre Simon de Laplace to the modern contributions of Harold Jeffreys, Richard Cox, and Edwin Jaynes. In many aspects of medical research, we deal with experimental data from which a certain proposition or hypothesis is validated. Unlike in physics, where we have strong and solid foundations such as Newton's law of motion, Snell's optical laws, Kirchoff's laws, Einstein's relativity theory, and many more, we do not have such privileges in medical research. Hence, many hypotheses are constantly tested as new evidence becomes available. One of the actively-researched medical areas is cancer research about which our understanding is still in its infancy. Numerous experiments (both in vivo and in vitro) and clinical trials have been conducted to further our knowledge; thus, Bayesian methodology finds its place to aid us in obtaining scientific inferences about certain propositions or hypotheses from available data and resources. In this work, we use data given to us by our medical collaborators at the Princess Margaret Hospital (PMH) in Toronto to carry out two main projects: Firstly, to make an inference about the oxygenation status (oxygen partial pressure, pO$_2$) within human cervical carcinomas and secondly, an inference about the effectiveness of various molecularly-targeted agents (MTAs) in phase II clinical trials of relapsed ovarian cancer patients. In the first problem, we address the challenges of tumor hypoxia - a state of oxygen deprivation in tumors. Currently, there are two methods to obtain tumor oxygen status, namely the direct Eppendorf needle electrode and the indirect immunohistochemical assay of a protein marker, Carbonic Anhydrase IX (CAIX). In this project, we introduce Bayesian probability theory to obtain inferences about tumor oxygenation from each technique and the concordance between the two techniques. From this study, we conclude that under certain conditions, two biopsies are sufficient to infer the tumor oxygenation level based on the immunohistochemical assays of CAIX. Additionally, there is a fair concordance between the direct and the indirect measurements of tumor oxygenation. In the latter problem, ovarian cancer is the topic of study. Ovarian cancer has the highest mortality rate among gynecological cancers and one that is known to relapse. CA-125 is still the most inexpensive biomarker for monitoring ovarian cancers. From the phase II clinical trial data, we demonstrate the survival advantage of CA-125 responsive group of patients by means of a non-parametric Kaplan-Meier statistic.

<p>The study aimed to describe the knowledge and awareness of HPV infection and vaccine of female university students and to determine the predictors of vaccine acceptability.&nbsp / The study found that 70% of the participants were sexually active. Awareness and knowledge on HPV/vaccine were poor / with only 22% being aware of HPV and that a HPV vaccine was available in South Africa. A greater proportion (80%) reported willingness to be vaccinated. Being aware of the existence of a pap smear, higher knowledge about HPV, higher perceived vaccine effectiveness and higher perceived severity of HPV infection were significantly associated with increased willingness to be vaccinated.</p>

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Magnetinio rezonanso tomografija (MRT) yra optimalus diagnostikos metodas vertinant gimdos kaklelio vėžio išplitimą. Pasaulyje pastaraisiais metais atlikta nedaug mokslinių tyrimų, kuriuose vertinamas gimdos kaklelio vėžys difuzinės MRT metodu. Daugumoje jų dalyvavo nedidelis tiriamųjų skaičius. Šis klinikinis tyrimas yra pirmasis Lietuvoje, kuriuo vertinamas gimdos kaklelio vėžys minėtu metodu, todėl jis turi nemažą mokslinę vertę optimizuojant MRT panaudojimo galimybes gimdos kaklelio vėžio diagnostikoje. Darbo tikslas – nustatyti konvencinės ir difuzinės MRT reikšmę vertinant gimdos kaklelio vėžio išplitimą ir chemospindulinio gydymo efektyvumą. Darbo uždaviniai: 1. Įvertinti konvencinės MRT metodu nustatytų gimdos kaklelio vėžio prognozės veiksnių tarpusavio ryšį su klinikinio ir histologinio tyrimų duomenimis. 2. Apskaičiuoti konvencinės MRT diagnostinės vertės parametrus gimdos kaklelio piktybiniam augliui ir liekamajam po chemospindulinio gydymo naviko audiniui. 3. Palyginti tariamojo difuzijos koeficiento (ADC) skaitinės reikšmės vidurkį sveikame gimdos kaklelyje, vėžio pažeistame ir po chemospindulinio gydymo. Nustatyti gimdos kaklelio vėžiui būdingą ADC skaitinės reikšmės ribą. Įvertinti ADC skaitinės reikšmės tarpusavio ryšį su įvairiais klinikinio ir histologinio tyrimų duomenimis. 4. Apskaičiuoti konvencinės ir difuzinės MRT derinio diagnostinės vertės parametrus gimdos kaklelio piktybiniam augliui ir liekamajam po chemospindulinio gydymo naviko audiniui. / Magnetic resonance imaging (MRI) is the optimal method for evaluation of spread of cervical cancer. Only a few diffusion–weighted (DW) MRI studies in the field of cervical cancer have been accomplished around the world. Most of them included a small number of subjects. This is the first clinical study in Lithuania that assesses the cervical cancer by DW–MRI and it has the scientific value in optimizing the use of MRI potential in the evaluation of the diagnostics and treatment efficiency of the mentioned illness. The aim – to identify the significance of conventional and DW–MRI in the assessment of the outspread of cervical cancer and of the efficiency of chemoradiation therapy. The objectives: 1. To assess the interrelationship of prognostic factors of cervical cancer detected by conventional MRI with clinical and histological findings. 2. To calculate the diagnostic value parameters of conventional MRI for the malignant cervical tumor and for the residual tumor tissue after chemoradiation therapy. 3. To compare the mean value of apparent diffusion coefficient (ADC) in a healthy, cancer affected cervix and the cervix after chemoradiation therapy. To identify the value range of ADC typical for cervical cancer. To evaluate the correlation of ADC with the various clinical and histological findings. 4. To calculate the diagnostic value parameters of conventional and DW–MRI combination for the malignant cervical tumor and for the residual tumor tissue after chemoradiation therapy... [to full text]

O câncer cervical é uma neoplasia muito prevalente na população feminina e está associado à infecção pelo papilomavírus humano (HPV). As oncoproteínas E6 e E7 de HPV de alto risco são as principais responsáveis pelas alterações celulares que levam ao desenvolvimento deste tipo tumoral. A dipeptidil peptidase IV (DPPIV/CD26) é uma enzima que exerce importantes funções relacionadas à progressão tumoral. Diversos estudos demonstram alterações na expressão e atividade desta proteína em diferentes tipos de câncer. Tendo em vista a relação entre a DPPIV/CD26 e o câncer, e que ainda não existem estudos relacionando esta proteína ao câncer cervical, neste estudo inicialmente investigamos a expressão e atividade da DPPIV/CD26 em linhagens celulares de carcinoma cervical humano (SiHa, HeLa e C33A) e em queratinócitos imortalizados (HaCaT). Nossos resultados demonstram uma baixa expressão da DPPIV/CD26 nas linhagens celulares estudadas, sendo praticamente indetectável na linhagem HeLa. Foi verificada a atividade enzimática dipeptidilpeptidásica tanto ligada à membrana quanto solúvel em todas as linhagens. Na presença do inibidor de DPPIV/CD26 (fosfato de sitagliptina) observamos que a linhagem SiHa apresentou um aumento na migração celular, e assim sugerimos que ao menos em parte a migração nesta linhagem é regulada pela atividade enzimática da DPPIV/CD26. A fim de investigar a relação da expressão da DPPIV/CD26 com as oncoproteínas E6 e E7 do HPV, avaliamos sua expressão em queratinócitos normais e transduzidos com estas oncoproteínas. Verificamos que queratinócitos expressando E6 de HPV de alto risco apresentam uma redução na expressão da DPPIV/CD26, e esta regulação parece ser dependente da degradação da p53. Considerando que as linhagens celulares estudadas apresentam baixa expressão e atividade da DPPIV/CD26, para melhor compreender a importância da expressão desta proteína, nós induzimos a superexpressão da DPPIV/CD26 em linhagem de câncer cervical (HeLa) para posterior avaliação dos efeitos em diferentes mecanismos tumorais. Os resultados demonstram uma redução no crescimento de células expressando DPPIV/CD26, sendo este efeito independente da atividade enzimática. Além disso, foi demonstrado que a indução da expressão de DPPIV/CD26 não afeta os mecanismos de migração e adesão celular na linhagem HeLa. Sendo assim, acreditamos que o esclarecimento do papel da DPPIV/CD26 no contexto do câncer cervical possibilita que novas abordagens diagnósticas e terapêuticas sejam implementadas no futuro. / Cervical cancer is a very prevalent neoplasm in female population and is associated with human papillomavirus (HPV) infection. The high risk HPV E6 and E7 oncoproteins are responsible for cellular alterations that lead to the development of this tumor type. The dipeptidyl peptidase IV (DPPIV/CD26) is an enzyme that exerts important functions related to tumor progression. Several studies have shown changes in the expression and activity of this protein in different types of cancer. Considering the relationship between DPPIV/CD26 and cancer, and that there are still no studies relating this protein to cervical cancer, in the present study we first investigated the DPPIV/CD26 expression and activity in human cervical carcinoma cell lines (SiHa, HeLa and C33A) and in immortalized keratinocytes (HaCaT). Our results demonstrate a low DPPIV/CD26 expression in the studied cell lines, being almost undetectable in HeLa cell line. The dipeptidylpeptidasic enzymatic activity was verified both membrane bound and in the soluble form in all cell lines. In the presence of the DPPIV/CD26 inhibitor (sitagliptin phosphate) we observed that SiHa cell line showed an increase in cell migration, thus we suggest that at least in part cell migration in this cell line is regulated by DPPIV/CD26 enzymatic activity. In order to investigate the relationship between DPPIV/CD26 expression and HPV E6 and E7 oncoproteins, we evaluated the expression of this protein in normal keratinocytes or transduced with these oncoproteins. We have found that keratinocytes expressing high-risk HPV E6 present a reduction in DPPIV/CD26 expression, and this regulation appears to be dependent on p53 degradation. Considering that the cell lines studied have low DPPIV/CD26 expression and activity, in order to better understand the importance of the expression of this protein, we induced the DPPIV/CD26 overexpression in a cervical cancer cell line (HeLa) for further evaluation of the effects on different tumor mechanisms. The results demonstrate a reduction in cell growth of DPPIV/CD26 expressing cells, being this effect independent of the enzymatic activity. In addition, it has been demonstrated that the induction of DPPIV/CD26 expression does not affect the cell migration and adhesion mechanisms in the HeLa cell line. Thus, we believe that the elucidation of the DPPIV/CD26 role in the context of cervical cancer enables new diagnostic and therapeutic approaches to be implemented in the future.