Background: Several studies have shown there has been significant lack of knowledge about women who have sex with women cross infect each other with STIs. It has been less likely that women who have sex with women visit health care than heterosexuals, they often felt badly treated, invisible and did not always know where to turn in case of an STI. Objective: The objective was to examine if STI information from Kalmar and Växjö county websites and GCK-summit, targeted women who have sex with women. Method: With a queer theoretical perspective a critical discourse analysis was made by STI information on the internet. Results: Women who have sex with women have been excluded in the STI information currently available through Kalmar and Växjö county websites. The public notices for screening tests have not been designed in such way it includes women who have sex with women. Women who have sex with women have been an obscure group. Conclusion: The conclusion was that women who have sex with women have not been included in the STI information available on the internet within the county councils of Kalmar and Kronoberg.

<p>The ability to determine nucleic acid sequences is one ofthe most important platforms for the detailed study ofbiological systems. Pyrosequencing technology is a relativelynovel DNA sequencing technique with multifaceted uniquecharacteristics, adjustable to different strategies, formatsand instrumentations. The aims of this thesis were to improvethe chemistry of the Pyrosequencing technique for increasedread-length, enhance the general sequence quality and improvethe sequencing performance for challenging templates. Improvedchemistry would enable Pyrosequencing technique to be used fornumerous applications with inherent advantages in accuracy,flexibility and parallel processing.</p><p>Pyrosequencing technology, at its advent, was restricted tosequencing short stretches of DNA. The major limiting factorwas presence of an isomer of dATPaS, a substitute for thenatural dATP, which inhibited enzyme activity in thePyrosequencing chemistry. By removing this non-functionalnucleotide, we were able to achieve DNA read-lengths of up toone hundred bases, which has been a substantial accomplishmentfor performance of different applications. Furthermore, the useof a new polymerase, called Sequenase, has enabled sequencingof homopolymeric T-regions, which are challenging for thetraditional Klenow polymerase. Sequenase has markedly madepossible sequencing of such templates with synchronizedextension.</p><p>The improved read-length and chemistry has enabledadditional applications, which were not possible previously.DNA sequencing is the gold standard method for microbial andvial typing. We have utilized Pyrosequencing technology foraccurate typing ofhuman papillomaviruses, and bacterial andfungal identification with promising results.</p><p>Furthermore, DNA sequencing technologies are not capable oftyping of a sample harboring a multitude of species/types orunspecific amplification products. We have addressed theproblem of multiple infections/variants present in a clinicalsample by a new versatile method. The multiple sequencingprimer method is suited for detection and typing of samplesharboring different clinically important types/species(multiple infections) and unspecific amplifications, whicheliminates the need for nested PCR, stringent PCR conditionsand cloning. Furthermore, the method has proved to be usefulfor samples containing subdominant types/species, and sampleswith low PCR yield, which avoids reperforming unsuccessfulPCRs. We also introduce the sequence pattern recognition whenthere is a plurality of genotypes in the sample, whichfacilitates typing of more than one target DNA in the sample.Moreover, target specific sequencing primers could be easilytailored and adapted according to the desired applications orclinical settings based on regional prevalence ofmicroorganisms and viruses.</p><p>Pyrosequencing technology has also been used forclone-checking by using preprogrammed nucleotide additionorder, EST sequencing and SNP analysis, yielding accurate andreliable results.</p><p><b>Keywords:</b>apyrase, bacterial identification, dATPaS, ESTsequencing, fungal identification, human papillomavirus (HPV),microbial and viral typing, multiple sequencing primer method,Pyrosequencing technology, Sequenase, single-strandedDNA-binding protein (SSB), SNP analysis</p>

Non-melanoma skin cancer (NMSC), comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for both BCC and SCC development. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. It has been hypothesized that intermittent patterns and childhood sunlight exposure are important for BCC while continuous (chronic) and lifelong (i.e. childhood and adulthood) sunlight exposure is important for SCC. Epidemiologic studies have demonstrated that cutaneous human papillomavirus (HPV) infection may also be a risk factor for developing NMSC. However, the pathway by which cutaneous HPV is associated with NMSC remains unclear. It is hypothesized that UVR exposure may interact synergistically with cutaneous HPV in NMSC development. The goal of the research study was to evaluate the relationship between levels of sunlight exposure and BCC and SCC and to investigate differences in sunlight-associated BCC and SCC risk by genus-specific cutaneous HPV serostatus. To address these goals, we conducted a clinic based case-control study of histologically confirmed BCC and SCC cases recruited from a university dermatology clinic and controls with no history of cancer and screened negative for current skin cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between measures of sunlight exposure and BCC and SCC. Multiplicative interactions were tested by placing an interaction term for the product of genus-specific HPV seroreactivity and sunlight related factors in the logistic regression models. Measures of both intermittent and continuous patterns of sunlight exposure were associated with both types of skin cancer (i.e. BCC and SCC). Specifically, history of blistering sunburn (a marker of intermittent sunlight exposure) and occupational sunlight exposure (i.e. having a job in the sun for at least 3 months for >10 years) were both associated with BCC and SCC. The major differences in patterns of sunlight exposure between BCC and SCC were observed for sunlight exposure in one's thirties. Additionally, sunlight exposure in one's twenties was associated with SCC, regardless of pattern of exposure; similar associations were not observed for BCC. Measures of timing of sunlight exposure consistently demonstrated that childhood/adolescent sunlight exposure was more important for SCC than BCC. These included number of moles on the forearms and entire body (measure of increased childhood sunlight exposure), and younger age at first and tanning bed use. Younger age at first blistering sunburn was statistically significantly associated with both BCC and SCC. NMSC cases were more likely to be seropositive for cutaneous HPV antibodies compared to controls. Compared to tanning, having a propensity to sun burn (p=0.006), or poor tanning ability (p=0.003) were significantly associated with a higher seroprevalence to genus beta HPV types within SCC cases. Statistically significant interactions were observed between poor tanning ability and genus-specific seropositivity with NMSC. Specifically, the associations between poor tanning ability and BCC (p interaction=0.02) and SCC (p interaction=0.01) were significantly stronger among individuals that were seropositive for antibodies to genus alpha HPV types. Similarly, the association between poor tanning ability and SCC was stronger among those seropositive for genus beta HPV types (p interaction=0.001). No additional significant interactions were observed for BCC or SCC between cutaneous sensitivity, history of blistering sunburn, or cumulative sunlight exposure and genus-specific seroreactivity. In conclusion, associations with patterns of sunlight exposure appeared to be similar between BCC and SCC cases. With the exception of age at first blistering sunburn, factors measuring timing of sunlight exposure demonstrated stronger and statistically significant relationships with SCC. Additionally, of the sunlight related factors measured, only the associations between poor tanning ability and BCC and SCC were significantly modified by HPV seropositivity to types in genera alpha or beta.

The overall aim of this thesis was to examine beliefs about human papillomavirus (HPV) prevention, especially vaccination, among parents, immigrant women, adolescents and school nurses, and to promote primary prevention among adolescents. The methods used in the thesis were focus group interviews, individual interviews, a web-based questionnaire, and finally, a randomised controlled intervention study. The immigrant women were largely in favour of HPV prevention, although barriers, such as logistic difficulties, and cultural or gender norms were found. Parents’ decision concerning vaccination of their daughters depended on several factors. Regardless of their final choice, they made the decision they believed was in the best interest of their daughter. The benefits outweighed the risks for parents choosing to vaccinate while parents declining made the opposite judgement. The majority of the school nurses reported that the governmental financial support given because of the vaccination programme had not been used for the intended purpose. Three out of four nurses had been contacted by parents who raised questions regarding the vaccine; most were related to side effects. The educational intervention had favourable effects on the adolescents’ beliefs regarding HPV prevention, especially among those with an immigrant background. Furthermore, the intention to use condom as well as actual vaccination rates among girls was slightly increased by the intervention. Trust in the governmental recommendations and the amounts of information given are important factors in the complex decision about HPV vaccination. Attention given to specific needs and cultural norms, as well as the possibility to discuss HPV vaccination with the school nurse and provision of extra vaccination opportunities at a later time are all strategies that might facilitate participation in the school-based HPV vaccination programme. School nurses need sufficient resources, knowledge and time to meet parents’ questions and concerns. The vaccinations are time-consuming and the governmental financial support needs to be used as intended, for managing the vaccination programme. A school-based intervention can have favourable effects on the beliefs and actual actions of young people and may possibly thus, in the long term, decrease the risk for HPV-related cancer.

Le VPH-16 de même que certains VPH, dont le VPH-18, causent le cancer du col utérin. Son intégration dans le génome humain pourrait être un marqueur de progression de l’infection. Les charges virales totale et intégrée sont présentement mesurées en quantifiant par PCR en temps réel les gènes E6 (RT-E6) et E2 (RT-E2-1) du VPH-16. Nous avons évalué l’impact du polymorphisme du gène E2 sur la quantification de l’ADN du VPH-16 dans des spécimens cliniques. Dans un premier temps, le gène E2 de 135 isolats de VPH-16 (123 appartenaient au clade Européen et 12 à des clades non- Européens) fut séquencé. Ensuite, un test de PCR en temps réel ciblant les séquences conservées dans E2 (RT-E2-2) fut développé et optimisé. Cent trente-neuf spécimens (lavages cervicaux et vaginaux) provenant de 74 participantes (58 séropositives pour le VIH, 16 séronégatives pour le VIH) ont été étudiés avec les trois tests E2 (RT-E2-2), E6 (RT-E6) et E2 (RT-E2-1). Les ratios de la quantité d’ADN de VPH-16 mesuré avec RT-E2-2 et RT-E2-1 dans les isolats Européens (médiane, 1.02; intervalle, 0.64-1.80) et Africains 1 (médiane, 0.80; intervalle, 0.53-1.09) sont similaires (P=0.08). Par contre, les ratios mesurés avec les isolats Africains 2 (médiane, 3.23; intervalle, 1.92-3.49) ou Asiatique- Américains (médiane, 3.78; intervalle, 1.47-37) sont nettement supérieurs à ceux obtenus avec les isolats Européens (P<0.02 pour chaque comparaison). Les distributions des quantités de E2 contenues dans les 139 échantillons mesurées avec RT-E2-2 (médiane, 6150) et RT-E2-1 (médiane, 8960) étaient statistiquement différentes (P<0.0001). Nous avons observé que les charges virales totale (odds ratio (OR) OR, 2.16 95% intervalle de confiance (IC) 1.11-4.19), et épisomale du VPH-16 (OR, 2.14 95% IC 1.09-4.19), mais pas la présence de formes intégrées (OR, 3.72 95% IC 1.03-13.4), sont associées aux néoplasies intraepitheliales cervicales de haut grade (CIN-2,3), et ce, en contrôlant pour des facteurs confondants tels que l’âge, le taux de CD4 sanguin, l’infection au VIH, et le polymorphisme de VPH-16. La proportion des échantillons ayant un ratio E6/E2 > 2 pour les femmes sans lésion intraépithéliale (7 de 35) est similaire à celle des femmes avec CIN-2,3 (5 de 11, p=0.24) ou avec CIN- 1 (4 de14, P=0.65). Le polymorphisme du gène E2 est un facteur qui influence la quantification des charges intégrées de VPH-16. / Episomal and integrated HPV-16 loads are currently estimated by quantitation with real-time PCR of HPV-16 E6 (RT-E6) and E2 (RT-E2-1) DNA. We assessed the impact of HPV-16 E2 polymorphism on quantitation of integrated HPV-16 DNA in clinical specimens. First, HPV-16 E2 was sequenced from 135 isolates (123 from European and 12 from non-European lineages). A novel assay targeting conserved HPV-16 E2 sequences (RT-E2-2) was optimized and applied with RT-E6 and RTE2- 1 on 139 HPV-16-positive cervicovaginal lavages collected from 74 women (58 HIV-seropositive, 16 HIV-seronegative). Ratios of HPV-16 DNA copies measured with RT-E2-2 and RT-E2-1 with European (median, 1.02; range, 0.64-1.80) and African 1 (median, 0.80; range, 0.53-1.09) isolates were similar (P=0.08). Ratios obtained with African 2 (median, 3.23; range, 1.92-3.49) or Asian-American (median, 3.78; range, 1.47-37) isolates were greater than those with European isolates (P<0.02 for each comparison). Distributions of HPV-16 E2 copies measured in 139 samples with RT-E2-2 (median, 6150) and RT-E2-1 (median, 8960) were different (P<0.0001). HPV-16 total (odds ratio (OR) OR, 2.16 95% confidence interval (CI) 1.11-4.19), episomal (OR, 2.14 95% CI 1.09-4.19) but not integrated (OR, 3.72 95% CI 1.03-13.4) load, were associated with high-grade cervical intraepithelial neoplasia (CIN-2,3) after controlling for age, CD4 count and HIV, and HPV-16 polymorphism. The proportion of samples with an E6/E2 ratio >2 in women without SIL (7 of 35) was similar to that of women with CIN-2,3 (5 of 11, P=0.24) or CIN-1 (4 of 14, P=0.65). E2 polymorphism was a factor that influenced measures of HPV-16 integrated load.

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.

Problématique : Bien que le tabac et l’alcool soient les facteurs causaux principaux des cancers épidermoïdes de l’oropharynx, le virus du papillome humain (VPH) serait responsable de l’augmentation récente de l’incidence de ces cancers, particulièrement chez les patients jeunes et/ou non-fumeurs. La prévalence du VPH à haut risque, essentiellement de type 16, est passée de 20% à plus de 60% au cours des vingt dernières années. Certaines études indiquent que les cancers VPH-positifs ont un meilleur pronostic que les VPH- négatifs, mais des données prospectives à cet égard sont rares dans la littérature, surtout pour les études de phase III avec stratification basée sur les risques. Hypothèses et objectifs : Il est présumé que la présence du VPH est un facteur de bon pronostic. L’étude vise à documenter la prévalence du VPH dans les cancers de l’oropharynx, et à établir son impact sur le pronostic, chez des patients traités avec un schéma thérapeutique incluant la chimio-radiothérapie. Méthodologie : Les tumeurs proviennent de cas traités au CHUM pour des cancers épidermoïdes de la sphère ORL à un stade localement avancé (III, IVA et IVB). Elles sont conservées dans une banque tumorale, et les données cliniques sur l’efficacité du traitement et les effets secondaires, recueillies prospectivement. La présence du VPH est établie par biologie moléculaire déterminant la présence du génome VPH et son génotype. Résultats: 255 spécimens ont été soumis au test de génotypage Linear Array HPV. Après amplification par PCR, de l’ADN viral a été détecté dans 175 (68.6%) échantillons tumoraux ; le VPH de type 16 était impliqué dans 133 cas (52.25 %). Conclusion: Une proportion grandissante de cancers ORL est liée au VPH. Notre étude confirme que la présence du VPH est fortement associée à une amélioration du pronostic chez les patients atteints de cancers ORL traités par chimio-radiothérapie, et devrait être un facteur de stratification dans les essais cliniques comprenant des cas de cancers ORL. / Background: HPV is recognised as a good prognostic factor in head and neck (H&N) cancer. However, most of the data is derived from randomised trials with different treatment options or small heterogeneous cohorts. This trial aims to determine the prevalence and prognostic impact of HPV on overall survival (OS), disease-free survival (DFS), local regional control (LRC) and treatment toxicity, in patients with locally advanced SCCHN treated with concomitant platinum-based chemoradiation therapy (CRT) and followed prospectively. Methods: Prospective data on efficacy and toxicity was available for 560 patients treated with CRT. Of these, 270 fixed and paraffin embedded specimens were collected. DNA was extracted from specimens and HPV detection was performed as previously described (Coutlée, J Clin Microbiol, 2006). Analysis was performed using Kaplan-Meier survival curves, Fisher's test for categorical data and log-rank statistics for failure times. Results: Median follow-up was 4.7 years. DNA extraction was successful in 255 cases. HPV prevalence was 68.6%, and 53.3% for HPV-16 specifically. For HPV+ and HPV- respectively, median LRC were 8.9 and 2.2 years (log-rank p = 0.0002), median DFS were 8.9 and 2.1 years (log-rank p=0.0014) and median OS were 8.9 and 3.1 years (log-rank p=0.0002). Survival was statistically significantly different based on HPV genotype, stage, treatment period and chemotherapy regimen. COX adjusted analysis for T, N, age, and treatment remained significant (HR 0.45, p=0.004). Subgroup analysis for genotype, TNM, primary site and chemotherapy regimen will be presented at the meeting. Conclusions: An increasing proportion of oropharyngeal cancer is linked to HPV. This large study with confirms that HPV status is strongly associated with improved prognosis among H&N cancer patients receiving CRT, and should be a stratification factor for clinical trials including H&N cases. Toxicity of CRT is not modified for the HPV population.

O câncer de colo de útero (CCU) é um dos mais danosos que afetam as mulheres, especialmente em países em desenvolvimento, onde os programas de prevenção (baseados no exame de Papanicolaou) não se mostram efetivos. Vacinas contra o HPV foram disponibilizadas em 2007 como prevenção primária do CCU. Apresentam boa eficácia e segurança, porém um elevado custo para sua incorporação. O objetivo desta dissertação é avaliar a incidência de câncer de colo de útero no estado de Roraima, seu impacto econômico, e o perfil sócio-econômico das portadoras de CCU tratada no SUS, além de realizar análises de custo-efetividade e custo-utilidade da inclusão da vacinação para o HPV aos programas preventivos vigentes. A dissertação é composta por 2 ensaios cujo tema unificador é a análise econômica de estratégias de combate ao CCU. No primeiro ensaio, todos os exames histopatológicos e citológicos emitidos em Roraima em 2009 foram revisados, juntamente com os prontuários médicos de todas as pacientes portadoras de CCU. Todos os procedimentos terapêuticos e diagnósticos realizados em 2009 em portadoras de CCU foram registrados. Prospectivamente foram entrevistadas as pacientes portadoras de CCU abordando tópicos sócio-econômicos. Foram registrados 90 casos de CCU em Roraima em 2009. A incidência correspondeu a 46,2 casos novos por 100.000 mulheres, a maior do Brasil. As portadoras do CCU demonstram perfil econômico desfavorável, exclusão social, e baixo conhecimento e adesão precária aos programas preventivos de saúde feminina. O impacto anual do CCU para gestão em saúde de Roraima é superior a R$8 mil por caso. Este ensaio ressalta a inequidade de acesso aos programas preventivos em Roraima, excluindo da cobertura de rastreio o subgrupo que mais se beneficiaria, e gerando custos elevados. O segundo ensaio realiza avaliações econômicas da incorporação da vacina para o HPV para o estado de Roraima. Foi desenvolvido um modelo de coorte de Markov como instrumento analítico de simulação da história natural do HPV até a progressão para CCU, levando em consideração os programas preventivos. As probabilidades de transição foram baseadas preferencialmente em dados empíricos locais e nacionais. Após calibração satisfatória e considerando valores de caso-base, a adição a vacinação para HPV reduziria em 35% a incidência de CCU, em cenário de realização de 3 testes de Papanicolaou ao longo da vida. A razão incremental de custo-efetividade foi de R$ 2.556 para cada ano de vida ajustado pela qualidade (AVAQ) poupado. As análises de sensibilidade confirmam a robustez deste resultado. A vacinação possui perfil favorável do ponto de vista de custo-utilidade, e sua inclusão no calendário vacinal resultaria em redução substancial da incidência e mortalidade por CCU em Roraima. / Invasive cervical cancer (ICC) is one of the most damaging that affect women, especially in developing countries, where preventive programs (based on the Pap smear) haven’t achieved effectiveness. HPV vaccines have recently been proposed as primary prevention of ICC. They show good efficacy and safety, but a high cost for its acquisition. Objectives: The objective of this dissertation is to evaluate the incidence of ICC in Roraima, its economic impact, and the socioeconomic profile of ICC carriers assisted in the public health system, and to perform a costeffectiveness and cost-utility analysis of adding HPV vaccination to current preventive programs. In the first essay, all histopathologic and cytologic reports issued in Roraima in 2009 were reviewed, along with the medical records of all patients diagnosed with ICC. All therapeutic and diagnostic procedures performed in 2009 in women with ICC cervix carcinoma were recorded. These patients were argued prospectively, addressing socio-economic topics. We registered 90 cases of cervical cancer in Roraima in 2009. The incidence corresponded to 46.2 new cases per 100,000 women. Carriers of the ICC showed unfavorable economic profile, social exclusion, deficient knowledge on ICC prevention and low adherence to the screening preventive programs. The annual impact of the ICC in Roraima is over R$ 8,000 per case. This essay highlights the inequity of access to preventive programs in Roraima, that excludes the subgroup of the population who would mostly benefit from screening, resulting in elevated costs. The second essay conducted economic evaluations of the incorporation of HPV vaccine to preventive programs in Roraima. A Markov cohort model was developed as an analytic tool to simulate the natural history of HPV and its progress to ICC, considering the current preventive programs. Transition probabilities were based mainly on empirical data of local and national studies. After satisfactory calibration values and considering the base case, the addition of HPV vaccination would reduce by 35% the incidence of ICC, in a scenario of three Pap tests throughout life. The incremental ratio of cost-effectiveness was R$ 2,556 for each year of quality-adjusted life (QALY) saved. The sensitivity analysis confirms the robustness of this result. Vaccination has a favorable profile in terms of cost-utility, and its inclusion in the immunization schedule would result in substantial reduction in incidence and mortality of ICC in Roraima.

Analisamos uma coorte de mulheres no sul do Brasil, com objetivo de identificar associações epidemiológicas para persistência e cura da infecção pelo HPV e realizamos uma metanálise para determinar a acurácia da telomerase nas lesões precursoras do câncer cervical. Métodos: O estudo de coorte foi iniciado em fevereiro de 2003. Foram coletados espécimes cervicais para citologia oncótica e para detecção do DNA HPV na entrada do estudo e no seguimento. O desfecho foi dividido em quatro categorias: (1) persistência, (2) conversão (3) cura. A quarta categoria (referência) eram mulheres negativas no início que permaneceram negativas. Foram usados o teste χ2 de Pearson, regressão logística multinomial e Kaplan- Meier para análise estatística. Para a metanálise foram incluídos estudos que comparavam o teste de telomerase (TRAP) e anatomopatológicos, obtidos por biópsias cervicais para diagnóstico de lesões cervicais. Resultados: A Incidência de HPV foi 12,3%. O HPV16 foi o tipo mais encontrado (18,6%), entre as 501 mulheres do estudo.Trinta e quatro mulheres (6,78%) ficaram persistentemente infectadas pelo HPV, estando essa categoria associada à idade da sexarca inferior a 21 anos (OR = 3,14, IC 95%, 1,43-6,87) e a quatro ou mais parceiros durante a vida (OR = 2,48 IC 95%, 1,14-5,41). No período mediano de 19 meses, 80,7 % das mulheres tinham curado o HPV, a cura foi significativamente associado à cor preta (OR= 3,44 IC 95%, 1,55-7,65), co-infecção com C. trachomatis no arrolamento (OR= 3,26, IC 95%, 1,85-5,76) e história de já ter realizado exame de Papanicolaou (OR= 3,48, IC 95%, 1,51- 8,00). Na metanálise dez estudos foram analisados, os quais incluíram 1069 mulheres. Para lesões intraepiteliais de baixo grau (LIEBG) vs. normal ou lesões benignas, encontrou-se uma positividade do teste da telomerase, sendo que o resultado da odds ratio para diagnóstico (DOR) foi de (DOR = 3,2, IC 95%,1,9-5,6). Nas lesões intraepiteliais de alto grau (LIEAG) vs LIEBG, normal ou benigna: (DOR = 5,8, IC 95%, 3.1-10). )]. Encontrou-se uma DORelevada de 8,1 (IC 95%: 3,2-20) nas lesões de câncer cervical vs LIEAG. Da mesma forma, nas lesões de câncer cervical vs. LIEBG, a razão de chance foi elevada, com uma DOR de 40,9 (IC 95%: 18,2-91). Conclusões: A persistência da infecção pelo HPV foi associada com a sexarca precoce e ao número de parceiros sexuais na vida, sugerindo que estratégias de orientação sexual podem modificar as taxas de persistência do HPV. A associação da cura do HPV com história prévia de realização de Papanicolaou salienta a importância de aprimorar os programas de rastreamento de câncer cervical. Futuros estudos da associação de infecções ginecológicas com cura da infecção pelo HPV são necessários. Na metanálise nossos dados suportam a corrente hipótese da atividade da telomerase como um evento precoce na carcinogênese e que poderia estar associado ao início e à progressão de lesões cervicais. / We analysed a cohort of women in Southern Brazil with the aim to identify epidemiological correlates for persistence and clearance of cervical HPV infection. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Methods: A cohort study was started on February 2003. Cervical smears were collected to perform Pap cytology and HPV DNA detection at baseline and during the follow up. The outcome was constructed in four categories (1) persistence of HPV DNA; (2) conversion; (3) clearance of HPV. Pearson’s χ2 test, multinomial logistic regression and univariate analysis using the log-rank test were performed. Meta-analysis studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Results: Incidence of HPV DNA: 12.3%. HPV16 was the most frequent type (18.6%) among 501 women in the study. Thirty-four women were persistently infected with HPV, which was associated with age below 21 years at first intercourse (OR 3.14, 95% CI, 1.43-6.87) and ≥ 4 sexual partners during lifetime (OR 2.48, 95% CI, 1.14-5.41). In a median period of 19 months, 80.7% of women had clearance of HPV, which was associated with black race (OR 3.44, 95% CI, 1.55-7.65), co-infection with C. trachomatis at baseline (OR 3.26, 95% CI, 1.85-5.76) and history of previous Pap smear (OR 3.48, 95% CI, 1.51-8.00). In meta-analysis ten studies were analyzed, which included 1,069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for Lo-SIL vs. normal or benign lesions was 3.2 (95% CI, 1.9-5.6). The DOR for a positive telomerase test for Hi-SIL vs. Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1-10). For cervix cancer vs. Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs. Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2-91). Conclusions: Persistence of HPV infection wasassociated with early age at first intercourse and number of sexual partners during lifetime, suggesting that strategies for sexual orientation may modify the rates of HPV persistence. The association of HPV clearance with a history of previous Pap smear screening highlights the importance of improving cervical screening programs. Further studies on the association of gynaecological infections with HPV clearance are needed. In meta-analysis our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis, that could be associated with the initiation and progression of cervical lesions.

Cervical cancer represents an enormous health, psychological and social stress for every woman. The most important risk factor in the development of cervical carcinoma, which the second most common malignant cancer in women, is infection with a high-risk strain of human papillomavirus - a very frequent sexually transmitted disease. More than 100 types of HPV are acknowledged to exist, with HPV 16 and 18 being classified as high-risk types in particular. Worldwide, 500,000 new cases of cervical cancer are diagnosed every year. In the Czech Republic, there are 1,000 new cases of cervical cancer each year, out of which up to 400 women die. It is estimated that there will be up to 1,000,000 new cases of cervical cancer by 2050 unless the prevention is improved. Every woman is at risk of developing cervical cancer. HPV is sexually transmitted, however not only by sexual intercourse but also by skin-to-skin-contact with infected areas. Other risk factors in the development of the disease are: first sexual intercourse at early age, the number of sexual partners, smoking, other sexually transmitted diseases and a long term use of hormonal contraception. Use of condoms, which protects against sexually transmitted diseases, reduces the transmission of HPV by up to 70%. Having regular gynaecological check-ups with Pap smears is crucial for cervical cancer screening, as the screening suggests the presence of cytological abnormalities and pre-cancer. However, it cannot detect all types of premalignant changes and early stages of the carcinoma. Two vaccines have recently been developed, effective against the most frequent oncogenic strains of HPV (16 and 18), which currently cause about 70% of cervical cancer cases. Active immunisation against human papillomavirus is the first vaccination against carcinoma. Together with screening, it represents the best prevention method against cervical carcinoma. Based on the research of technical literature, the first part of the dissertation gives an overall view of the issue of cervical carcinoma. The second part of the dissertation deals with the research, eliciting the knowledge and attitude of women from Southern Bohemian towns in the field of cervical carcinoma prevention in the period of December 2008 - March 2009 and comparing it to technical literature.