Women infected with the human immunodeficiency virus are at increased risk for developing cervical cancer. Current guidelines reflect that Pap smears should be performed twice during the first year after diagnosis with HIV and annually thereafter. However, women with HIV are not obtaining Pap smears per the current guidelines. The purpose of this study was to evaluate HIV-infected women's attitudes toward cervical cancer and cervical cancer screening. The research design is an exploratory, cross-sectional, quantitative design. The sample of convenience consisted of participants recruited from two ambulatory HIV clinics in Florida. Attitudes were assessed using Champion's Health Belief Model and Self-efficacy scales. Knowledge was evaluated with an updated HPV/Cervical Cancer Knowledge scale. Sociodemographic variables were assessed using a Demographic Data form. The results indicate that HIV-infected women in the study were not knowledgeable about HPV or cervical cancer. They did not perceive that cervical cancer was serious, nor did they feel that they were susceptible to cervical cancer. Overall, HIV-infected women were confident in their ability to request a Pap smear, and they perceived fewer barriers and more benefits to Pap smears. Despite, perceptions of fewer barriers and more benefits a chart review revealed that approximately 43% of the study participants received a Pap smear during the past year. Perceived barriers was a significant predictor of Pap smear adherence (OR = 0.93, CI: 0.90 to 0.96, p < .01). Findings from the exploratory study provide important information to clinicians and researchers that will assist in the development of effective interventions to increase Pap test adherence. Additional research is needed to further understand factors that influence cervical cancer screening in this at-risk population.

There is an urgent need for the development of an effective therapeutic vaccine against cancer caused by human papilloma virus (HPV). We focused on HPV-induced malignancies because of their high worldwide prevalence (e.g., cervical carcinoma and head & neck cancer). A successful therapeutic vaccine could prevent the 250 000 deaths/year worldwide and the 2.25 billion dollars that are expended in related care in the US. We used an HPV-induced mouse cancer model to test vaccines composed of a CD8 T cell peptide epitope administered with potent adjuvants designed to generate vast numbers of high avidity cytotoxic T lymphocytes specific for the HPV16-E7 antigen. One vaccination strategy (TriVax) consists of intravenous administration of synthetic peptide HPV16-E749-57 administered together with a Poly-IC (a TLR3 agonist) and anti-CD40 monoclonal antibody(αCD40 mAb) while the second more simple strategy (BiVax) comprises solely of peptide plus Poly-IC. We used an E7 peptide as antigen in the vaccination strategies because expression of the viral E6 and E7 proteins is required to maintain oncogenic phenotype and because normal cells do not express E6/E7, therefore a therapeutic vaccine targeting these proteins has several advantages: a) a strong immune response can be induced since immune tolerance to these foreign antigens does not exist and b) the strong immune response should not inflict damage to normal cells. TriVax and BiVax generate a high number of antigen specific CD8 T cells capable clear subcutaneous tumors and prevent recurrences, both vaccines are efficient through the i.v. and i.m. route. TriVax (prime-boost) clears tumor in 100% of mice while BiVax clears tumor in 50% of mice, this differential effect is due to the number of antigen specific CD8 T cells and increasing the number of booster shot makes BiVax as immunogenic and efficient in clearing tumors. In the absence of type-I IFN signaling (in IFNαΒR KO mice), TriVax is less effective in generating sufficient numbers of CD8 T cells that could be necessary for total disease eradication. We observed a significant anti-tumor effect of TriVax in the absence of interferon gamma, however the cytokine may play some role in the overall effectiveness of TriVax to completely reject the tumors. Immune responses produced by BiVax are highly dependent on the simultaneous administration of peptide and Poly-IC, on the peptide composition, vaccine formulation and route of administration. The magnitude of the response is dependent on the expression of the Poly-IC receptors TLR3 and melanoma differentiation-associated protein 5 (MDA5). Interestingly, the magnitude and duration of the CD8 T cell responses generated by peptide and Poly-IC mixtures does not rely on the presence of CD4 T cells, scavenger receptor-A (SR-A) or type-I IFN signals and was minimally affected by the absence of CD40 signaling. The present findings could facilitate the development of simple and effective subunit vaccines for diseases where CD8 T cells may hold a therapeutic benefit.

No description available.

To significantly improve the early detection of cervical precancers and cancers, LightTouch™ is under development by SpectRx Inc.. LightTouch™ identifies cancers and precancers quickly by using a spectrometer to analyze light reflected from the cervix. Data from the spectrometer is then used to create an image of the cervix that highlights the location and severity of disease. Our research is conducted to find the appropriate models that can be used to generate map-like image showing disease tissue from normal and further diagnose the cervical cancerous conditions. Through large work of explanatory variable search and reduction, logistic regression and Partial Least Square Regression successfully applied to our modeling process. These models were validated by 60/40 cross validation and 10 folder cross validation. Further examination of model performance, such as AUC, sensitivity and specificity, threshold had been conducted.

The overall aim of this thesis is to provide a better understanding of knowledge, attitudes, consent, and decision-making regarding Human papillomavirus (HPV) vaccination, seen from the perspectives of concerned parties – high school students, school nurses, and parents. Two quantitative studies were performed: one descriptive cross-sectional study and one quasi-experimental intervention study. Qualitative studies using focus group interviews and individual interviews were also performed. High school students’ knowledge about HPV and HPV prevention was low but their attitudes toward HPV vaccination were positive. An educational intervention significantly increased the students’ knowledge regarding HPV and HPV prevention. Their already positive attitudes toward condom use and HPV vaccination remained unchanged. The students wanted to receive more information about HPV from school nurses. The school nurses were also positive to HPV vaccination but identified many challenges concerning e.g. priorities, obtaining informed consent, culture, and gender. They saw an ethical dilemma in conflicting values such as the child’s right to self-determination, the parents’ right to make autonomous choices on behalf of their children, and the nurse’s obligation to promote health. They were also unsure of how, what, and to whom information about HPV should be given. Parents, who had consented to vaccination of their young daughters, reasoned as follows: A vaccine recommended by the authorities is likely to be safe and effective, and the parents were willing to do what they could to decrease the risk of a serious disease for their daughter. Fear of unknown adverse events was overweighed by the benefits of vaccination. Parents also saw the school nurse as an important source of HPV information. Conclusions: Positive attitudes toward HPV vaccination despite limited knowledge about HPV, are overarching themes in this thesis. School nurses have a crucial role to inform about HPV prevention. It is important that the concerned parties are adequately informed about HPV and its preventive methods, so that they can make an informed decision about vaccination. A short school-based intervention can increase knowledge about HPV among students. From a public health perspective, high vaccination coverage is important as it can lead to a reduced number of HPV-related disease cases.

Cervical cancer is the forth most commonly diagnosed cancer among women worldwide. It is caused by persistent infection with an oncogenic type of Human Papillomavirus (HPV). The HPV is a necessary but not sufficient cause of cervical cancer. Environmental factors such as smoking, high parity and long-term use of oral contraceptives increases the risk of cervical cancer. Genetic factors also affect the risk of developing the disease. The aim of this thesis is to search for and evaluate genetic risk factors for cervical cancer using both a candidate gene approach and a genome-wide association study (GWAS). Paper I examined the association of genetic variation in three Fanconi Anemia (FA) genes (FANCA, FANCC and FANCL), involved in DNA repair, with cervical cancer susceptibility in the Swedish population. No association was observed. Paper II evaluated the association of genetic variation in the TMC6 and TMC8 genes with susceptibility to cervical cancer in the Swedish population and an association of two SNPs (rs2290907 and rs16970849) with cervical cancer was observed.  In paper III the first GWAS performed in cervical cancer was reported. Three independent loci in the major histocompatibility complex (MHC) region at 6p21.3 were found to affect the susceptibility to cervical cancer. Paper IV examined the sequence variation in the TMC6 and TMC8 region and its association with cervical cancer. A highly polymorphic 21 bp sequence was identified and found to be repeated 5 to 42 times in both cases and controls. Lack of this repeat was associated with increased risk of cervical cancer. An intronic SNP (rs2926778) located in between the TNRC6C and TMC6 genes was also found to be associated with cervical cancer. The thesis provides evidence for the importance of genes in the immune system for cervical cancer susceptibility. The genetic risk factors identified explain only a part of the genetic susceptibility, implying that other risk factors remains to be identified

Cervical cancer is the second most common cancer, with about 500 000 new cases per year among women worldwide. With a well-organized screening programme the number of cases can be reduced by more than 50%. In spite of having such a screening programme there are still around 450 new cases yearly in Sweden. The majority of these cases occur in non-attendees. There is thus a need to improve the Swedish cervical cancer screening programme in order to further reduce the number of cases of cervical cancer. Cervical cancer and high-grade cervical dysplasia are caused by sexually transferred high-risk human papillomaviruses (HR-HPVs). In cases of persistent HR-HPV infection there is a risk of development of dysplasia and in some cases subsequent progress to cervical cancer. HR-HPV testing shows high sensitivity as regards the detection of cervical dysplasia. Self-sampling of vaginal fluid for the analysis of HR-HPV has many advantages, since a woman can perform the sampling herself in a private setting, whenever suitable, without the need to travel to a clinic. Our studies have shown that sensitivity in the detection of precancerous lesions is about twice as great with the HR-HPV self-test compared with cytology-based tests.  If a woman was HR-HPV-positive in two consecutive tests, the specificity of the HR-HPV test increased to about 98%. Among women with short-term persistent HR-HPV infection, the prevalence of CIN 2+ was over 40%. There was good concordance in sensitivity as regards the detection of CIN 2+ between self-obtained and physician-obtained samples, although self-sampling was associated with slightly lower specificity. The prevalence of HR-HPV from day to day in premenopausal women was not influenced by hormonal changes during the menstrual cycle. Neither were there significant day-to-day changes in postmenopausal women. A single self-test thus provides reliable information on whether or not a woman has an HR-HPV infection. In conclusion, self-sampling combined with the analysis of HR-HPV appears to be a powerful alternative as a primary screening method for the prevention of cervical cancer. Self-sampling for HR-HPV testing is a suitable, safe and accepted strategy for cervical cancer prevention among women.

Cervical cancer is a disease that annually claims the lives of over a quarter of a million women. A substantial number of these deaths could be prevented if population wide cancer screening, based on the Papanicolaou test, were globally available. The Papanicolaou test involves a visual review of cellular material obtained from the uterine cervix. While being relatively inexpensive from a material standpoint, the test requires highly trained cytology specialists to conduct the analysis. There is a great shortage of such specialists in developing countries, causing these to be grossly overrepresented in the mortality statistics. For the last 60 years, numerous attempts at constructing an automated system, able to perform the screening, have been made. Unfortunately, a cost-effective, automated system has yet to be produced. In this thesis, a set of methods, aimed to be used in the development of an automated screening system, are presented. These have been produced as part of an international cooperative effort to create a low-cost cervical cancer screening system. The contributions are linked to a number of key problems associated with the screening: Deciding which areas of a specimen that warrant analysis, delineating cervical cell nuclei, rejecting artefacts to make sure that only cells of diagnostic value are included when drawing conclusions regarding the final diagnosis of the specimen. Also, to facilitate efficient method development, two methods for creating synthetic images that mimic images acquired from specimen are described.

Cervical cancer is the third most common cancer among women worldwide, and the fourth leading cause of cancer mortality. Despite significant declines in the incidence and mortality rates of cervical cancer in Canada, it remains the 4th most common cancer in women aged 20-29 years. In order to gain novel insights into cervical cancer tumourigenesis and clinical outcome, we investigated and characterized the alterations in microRNA (miRNA) expression in this disease. Firstly, we performed global miRNA expression profiling of cervical cancer cell lines (n=3), and patient specimens (n=79). From this analysis, we identified miR-196b to be significantly down-regulated in cervical cancer, and characterized its role in regulating the HOXB7~VEGF axis. The global miRNA expression data also led to the development of a candidate 9-miRNA signature that was prognostic for disease-free survival in patients with cervical cancer, although we were unable to validate this signature in an independent cohort. This report describes important considerations concerning the development and validation of microRNA signatures for cervical cancer. Our investigations also led us to a comparison of three methods for measuring miRNA abundance: the TaqMan Low Density Array, the NanoString nCounter assay, and single-well quantitative real-time PCR. Our findings demonstrated limited concordance between the TLDA and NanoString platforms, although each platform correlated well with PCR, which is considered the gold standard for nucleic acid quantification. Furthermore, we examined biases created by amplification protocols for microarray studies. Our analysis demonstrated that performing a correction using the LTR-method (linear transformation of replicates) could help mitigate, but not completely eliminate such biases. Overall, this report presents insights into the role of miRNAs in cervical cancer, as well as an evaluation of technical considerations concerning miRNA and mRNA expression profiling studies.

Bakgrund: Antalet drabbade kvinnor av livmoderhalscancer i Sverige är cirka 450 per år. Cirka en tredjedel av kvinnorna är under 40 år. I Sverige har insjuknandet av livmoderhalscancer minskat, troligen efter att regelbunden populations screening infördes på 1960-talet. Symtomen är få och diffusa och är därför svåra att upptäcka. Screening är en viktig undersökning för att upptäcka cancern tidigt. Tidigare forskning visade att kvinnor med livmoderhalscancer förändrade värderingar och synen på livet. Den begränsade forskningen inom området gör det relevant att studera kvinnors upplevelser av att leva med livmoderhalscancer. I studien användes livsvärldsteorin för att ge perspektiv på kvinnors upplevelser av att leva med livmoderhalscancer. Syfte: Är att analysera och beskriva kvinnors upplevelser av att leva med livmoderhalscancer. Metod: Studien har en kvalitativ ansats och en kvalitativ innehållsanalys används för att analysera bloggarna. Datamaterialet består av fem bloggar publicerade på internet. Resultat: Presenteras under kategorier, Förändrad identitet, En ständig kamp och Yttre påverkande faktorer. Slutsats:Livmoderhalscancer medför många psykiska och fysiska förändringar hos kvinnorna. Vilket bidrar till kvinnornas svårigheter att bevara sin identitet och självkänsla. / Background: The number of suffering women of cervical cancer in Sweden is approximately 450 per year. About a third of the women are under 40 years. In Sweden has the onset of cervical cancer reduced, probably after that regular population screening was introduced in the 1960s. The symptoms are few and diffuse and therefore difficult to detect. Screening is an important survey to detect the cancer early. Previous research showed that women with cervical cancer changing values and views on life. The limited research in this area makes it relevant to study women's experiences of living with cervical cancer. The study used the life-world theory to provide perspective on women's experiences of living with cervical cancer. Aim: The study aims are to describe the women´s experiences of living with cervical cancer. Method: the study has a qualitative approach and a qualitative analysis is used to analyze blogs. Data involve five blogs published on the Internet. Results: Presented in categories, Changed identity, a constant struggle and External influencing factors. Conclusion: Cervical cancer causes many physical and psychological changes in women. This contributes to women’s difficulties to preserve their identity and self-esteem.