Background: The qHPV vaccine has the potential to significantly reduce the burden of HPV-related diseases, including cervical cancer. However, a recent systematic review of clinical trials has suggested that the risk of bronchospasm may be increased by this vaccine, and a large observational study has reported an increased risk of anaphylaxis. Objectives: To determine whether qHPV vaccination increases the risk of incident asthma, asthma exacerbation, and anaphylaxis. Methods: A population-based retrospective cohort of grade 8 girls eligible for Ontario’s HPV immunization program between 2007 and 2011 was identified using the province’s administrative health and immunization databases. Cohort members were followed from September 1st of their grade 8 year until their date of death or end of study (March 31st, 2012). The self-controlled case series method, a self-matched, case-based analysis was used to assess the effect of qHPV vaccination on the risk of SRREs, and rate ratios (RRs) and 95% confidence intervals for each outcome was estimated using conditional Poisson regression. Results: The cohort consisted of 125,575 girls with a mean age of 13.2 years, 57.7% of whom received at least one dose of the qHPV vaccine. During an average of 2.5 years of follow-up, 1473 cases of incident asthma, 901 of asthma exacerbation and 38 of anaphylaxis were identified. HPV vaccination was not associated with an increased risk of incident asthma or asthma exacerbation (RRadj 0.76, 95% CI 0.37-1.54 and RRadj 0.74, 95% CI 0.27-2.00, respectively), and these associations were unchanged by the presence of risk factors and time since vaccination. There was also no evidence of an increased risk of anaphylaxis following qHPV vaccination as demonstrated by an absence of cases of anaphylaxis occurring on the day of vaccination. Conclusions: This large, population-based study provides strong evidence that the qHPV vaccine does not increase the risk of developing or exacerbating asthma, and additional evidence for the lack of an increased risk of anaphylaxis in the younger populations targeted by HPV immunization programs. These findings add to the growing body of evidence on the safety of the qHPV vaccine. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2014-04-16 19:20:41.019

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.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 3 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 4 uppsatser.

Persistent infection of the cervix with high risk (HR) types of Human Papilloma Virus (HPV) (HR-HPV) can result in precancerous lesions and cancers. However, most HPV infections can be cleared naturally by the immune response without causing disease. Although genetic variations have long been considered as the main explanation for individual heterogeneity in cancer susceptibility, the underlying mechanisms remain unclear. In this project, a panel of routinely taken clinical samples was assessed for 32 rationally selected SNPs with allele frequency related to disease outcome using the Taqman® OpenArray® system. The panel incorporated 475 HR-HPV negative, cytologically-normal cervical samples, 413 HR-HPV positive cervical high grade squamous intraepithelial lesion (HSIL) cases and 62 HR-HPV positive cervical cancers. Two SNPs, rs2234671 and rs2623047, were found with significant differences between HR-HPV negative, cytologically-normal samples and HR-HPV positive cervical HSIL cases. In the validation step, these two SNPs were further genotyped in the same set of samples using TaqMan® SNP genotyping assay and/or LightSNiP assay and in additional samples including 83 HR-HPV positive, cytologically-normal cervical samples, 21 HR-HPV positive cervical cancer cases, 129 HR-HPV positive vulval intraepithelial neoplasia cases and 23 HR-HPV positive vulval cancer cases. Statistical analysis was then performed based on pooled and re-grouped genotyping data of the above-mentioned samples under different genetic models so as to evaluate the associations with different stages in the disease process. After validation, SULF1 rs2623047 revealed a strong significant association with the susceptibility to HR-HPV infection but not with the development of high-grade squamous intraepithelial lesion and the progression to cervical cancer. CXCR1 rs2234671, by contrast, was associated with the progression of HR-HPV-related cancers and the minor allele CXCR1 827C was significantly enriched in HPV16 positive cancers. CXCR1 is a receptor for the chemokine CXCL8/IL-8 and CXCR1 rs2234671 leads to a serine to threonine change in an extracellular loop of the receptor. Functionally, the CXCR1 827C allele was shown to enhance cell motility in response to IL-8 stimulation in a chemotaxis assay with transiently transfected fibroblasts (HEK293 cells) and also in a wound healing assay with stably transduced cervical cancer (CaSki) cells. In addition, significantly increased cell proliferation upon IL-8 treatment was observed in two cervical cancer derived cell lines, CaSki and SiHa, transduced with CXCR1-827C allele, but not in their CXCR1 827G transduced counterparts. These findings suggest that SULF1 rs2623047 and CXCR1 rs2234671 may be genetic risk factors for HR-HPV-related cervical disease and CXCR1 rs2234671 might affect HR-HPV-related cancer susceptibility by functionally altering IL-8-CXCR1 signalling. This information has potential for use in the risk stratification of HR-HPV infected women and may also suggest new therapeutic targets to be exploited for treatment of cervical cancer patients.

Combating HPV infection in males is a significant public health issue. In addition to the number of HPV-related cancers that develop each year, Palefsky (2007) reported that "HPV infection of men is of great importance given that sexual transmission is the primary mode of spread to women" (p. 261). In recent years, the development of the HPV vaccine has spurred controversy over whether or not males as well as females should obtain the vaccine against this disease. The purpose of this study was to examine male college students' intention to be HPV vaccinated and their HPV knowledge, attitudes, subjective norms, and perceived behavioral control towards the vaccination. A descriptive, correlational, cross-sectioned research design was employed. Two hundred and eight (208) male college students at a mid-sized public university participated in the study and completed an in-class questionnaire. The results of the descriptive statistics showed that, on average, the sample of 208 male college students had correct responses on only half of the 15 questions regarding knowledge about HPV based on the mean scores. Respondents had positive attitudes towards HPV vaccination, greater sense of control over being HPV vaccinated, and favorable intention to be HPV vaccinated. Subjective norms and perceived behavioral control were significant predictors of male college students' behavioral intention to be HPV vaccinated. Subjective norms and perceived behavioral control had a positive influence on male college students' behavioral intention to be HPV vaccinated. Lastly, male college students' level of HPV knowledge was not significantly correlated to their behavioral intention to be HPV vaccinated

Orientadores: Sophie Françoise Mauricette Derchain, Luis Otavio Sarian / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T00:16:06Z (GMT). No. of bitstreams: 1 Moraes_DenisedaRochaPittaLimade_M.pdf: 959384 bytes, checksum: dcd7eaa366994d0d3d606ecc04a19503 (MD5) Previous issue date: 2008 / Resumo: Introdução: Este estudo faz parte de uma linha de pesquisa cuja finalidade é avaliar testes de detecção de papilomavírus humano (HPV) envolvidos na carcinogênese e rastreamento de câncer cervical. Até recentemente, a captura híbrida 2 (HC2) para detecção de um pool de HPV de alto risco oncogênico foi o método clínico mais estudado por este grupo. Entretanto, frente à evidente diferença no risco de evolução das lesões cervicais, a genotipagem do HPV através de análise do ácido nucléico passou a ser relevante. Objetivo: Avaliar a distribuição de infecções simples e múltiplas de diferentes tipos de HPV em mulheres com neoplasia intra-epitelial cervical de alto grau (NIC2 e NIC3). Sujeitos e Métodos: Foram avaliados os genótipos específicos de HPV da amostra cervical de 106 mulheres utilizando Roche Linear Array® human papillomavirus (LA-HPV) genotyping assay (Roche Diagnostics,USA). O material foi coletado antes da conização cervical. Foram comparadas as proporções de NIC2 e NIC3 em grupos de mulheres infectadas com tipos de HPV dos grupos filogenéticos Alfa7 (A7) e Alfa9 (A9). Três situações foram consideradas: mulheres com 1) infeccão simples; 2) infecção múltipla; 3) infecção simples e múltipla. Foram comparadas as proporções de diferentes combinações de tipos de HPV em grupos de mulheres com NIC2 e NIC3. Resultados: Pelo menos um tipo de HPV foi detectado em 99% das amostras. Infecções múltiplas foram detectadas em 68 (64,7%) das amostras. Os genótipos de alto risco mais freqüentemente detectados em infecção simples ou múltipla foram HPV16 (57,1%), HPV58 (24,7%), HPV33 (15,2%), HPV52 (13,3%), HPV31 (10,4%) e HPV51 (7,6%) e HPV18 (6,6%). A probabilidade de mulheres com NIC3 serem infectadas com HPV da espécie A9 foi maior. Os HPV 16 e ou 18, associados ou não com outros tipos virais foram mais frequentemente encontrados nas mulheres com NIC3 do que naquelas com NIC2. Conclusão: A severidade da NIC esteve associada com a presença de tipos de HPV incluídos na classificação filogenética A9 e por infecções que incluem HPV16 e 18 combinados ou não com outros genótipos de HPV / Abstract: Objective: To evaluate the distribution of single and multiple infections of different human papillomavirus (HPV) types in women with high grade cervical intraepithelial neoplasia (CIN2 and CIN3) and to assess the relation of the various combinations of virus with the severity of CIN. Subject and methods: Cervical samples from 106 women treated due to CIN2 (18) or CIN3 (88) were examined for specific HPV genotypes using Roche Linear Array® Human Papillomavirus (LA-HPV)(Roche Diagnostics, USA). The material was collected immediately before cervical conization. The proportion of CIN2 and CIN3 in groups of women infected with varying HPV phylogenetic groups Alpha7 (A7) and Alpha9 (A9) was compared. Three situations were considered: women with 1) single infection; 2) multiple infections; 3) the whole sample. The proportions of CIN2 and CIN3 in groups of women with different combinations of HPV types were compared. Results: At least one HPV type was detected in 99% of the whole series. Multiple infections were detected in 68 (64.7%) samples. The most frequent high-risk genotypes detected (single/multiple) were HPV16 (57.1%), HPV58 (24.7%), HPV33 (15.2%), HPV52 (13.3%), HPV31 (10.4%), HPV51 (7.6%) and HPV18 (6.6%). Women with CIN3 were more infected with HPV of species A9. HPV16 and/or HPV18, associated or not with other viral types, were more frequently found in specimens of women with CIN3 than in those of women with CIN2. Conclusions: the severity of high-grade CIN may be associated by the presence of HPV types included in the A9 phylogenetic classification and by infections including HPV16 and 18 combined or not with other HPV genotypes / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

A infecção genital pelo Papilomavírus Humano (HPV) é considerada a doença sexualmente transmissível mais freqüente em todo o mundo, representando importante problema de saúde pública devido à sua alta prevalência e transmissibilidade. Estima-se que cerca de 75% da população sexualmente ativa entre em contato com um ou mais tipos de HPV durante sua vida, com prevalência mais elevada entre mulheres jovens. Estudos epidemiológicos têm demonstrado que a infecção pelo vírus da imunodeficiência humana (HIV) está associada a elevadas prevalências da infecção pelo HPV. A literatura acerca da infecção pelo HPV em gestantes é escassa e controversa. O objetivo do trabalho foi identificar a prevalência da infecção pelo HPV em gestantes e identificar a possível influência da infecção pelo HIV-1 nesta prevalência. Foi realizada amostragem de pacientes do Ambulatório de Pré-natal do Setor de Moléstias Infecto-contagiosas e do Pré-natal de Baixo Risco do Departamento de Ginecologia e Obstetrícia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Todas as pacientes foram informadas sobre o estudo e assinaram o termo de consentimento livre e esclarecido. Foram coletados lavados cérvico-vaginais, que foram submetidos à extração do DNA utilizando a técnica de salting out. Realizou-se a detecção do HPV nas amostras de DNA através da técnica de reação em cadeia de polimerase (PCR), e as amostras positivas para o HPV foram testadas para os tipos 6, 11, 16 e 18. Foram arroladas ao todo 97 pacientes, sendo 44 portadoras do HIV e 53 sem esta infecção. Do total de pacientes avaliadas, 66 foram positivas para o HPV. A prevalência para a infecção pelo HPV foi de 79,5% e 58,5% nas pacientes portadoras ou não do HIV, respectivamente. A infecção pelo HIV aumentou o risco de ser portadora do HPV, principalmente do tipo oncogênico. Contagem de linfócitos T CD4+ abaixo de 200 células/mm3 e carga viral do HIV maior que 10000 cópias aumentaram o risco de infecção pelo HPV. Este estudo mostrou haver maior prevalência da infecção pelo HPV em grávidas portadoras do HIV, permitindo inferir que a infecção por esse retrovírus seja um fator de risco significativo para o aumento da infecção pelo HPV em gestantes. / Genital infection with human papillomavirus (HPV) is considered to be the most frequent sexually transmitted disease around the world, representing an important public health problem due to its high prevalence and transmissibility. It is estimated that 75% of the sexually active population gets in contact with one or more HPV types during their lives, with higher prevalence among younger women. Epidemiologic studies have demonstrated that human immunodeficiency virus (HIV) infection is associated with a high prevalence of HPV infection. The literature about HPV infection during pregnancy is scarce and controversial. The aim of this study was to estimate the prevalence of HPV infection in pregnant women and identify the possible influence of HIV-1 infection on this prevalence. Patients were selected from the Prenatal Outpatient Clinic of the Infectious Diseases Sector and from the Low-risk Prenatal Outpatient Clinic of the Obstetrics and Gynecology Department of the University Hospital, Medical School of Ribeirão Preto, São Paulo University. All patients were informed about the study and signed an informed consent term. Cervical-vaginal washes were collected and submitted to DNA extraction by the salting-out technique. HPV was detected in the DNA samples by the polymerase chain reaction (PCR) technique and the HPV-positive samples were tested for types 6, 11, 16 and 18. Ninety-seven patients were included in the study, 44 of them being HIV-positive and 53 HIV-negative. Of the patients evaluated, 66 were positive for HPV. The prevalence of HPV infection was 79.5% and 58.5% in HIV-positive and -negative women, respectively. HIV infection increased the risk of harboring HPV, mainly oncogenic types. A CD4+ T-cell count below 200 cells/mm3 and HIV viral load above 10000 copies/mL increased the risk of HPV infection. This study showed a higher prevalence of HPV infection in HIV-positive pregnant women, suggesting that this retrovirus infection is a significant risk factor for the increase of HPV infection in pregnant women.

PROJECT ONE Introduction HPV is detected in about 99.7% of cervical cancers. However, the HPV type distribution in South African women is unknown. Objectives To determine HPV-type distribution among women with cervical dysplasia in relation to oral contraceptive usage. Methods Prospective cross-sectional study of four groups of patients according to oral contraceptive usage: non-users, users of less than five years duration, users of between five years and ten years and users of more than ten years duration. Swabs of the cervix were analysed for HPV DNA using polymerase chain reaction method. Results A total of 124 women were recruited for the study. There were 75 HIV-infected patients (seroprevalence 61%). Of the 102(82%) HPV-positive patients, 79 patients had high-risk HPV DNA (78%). In terms of the four oral contraceptive groups, high-risk HPV DNA was detected in 70% (n=21), 79% (n=22), 90% (n=21) and 71% (n=15) of patients, respectively. The odds of having HPV DNA was six times higher for the combination of contraceptive users of less than 5 years duration/non-users (OR 5.9, 95% CI: 1.87 - 18.77). There was no change when adjustment was made for age (OR 6.1, 95% CI: 1.9 - 19.4). HPV DNA types 16 and or 18 was present in a total of 21 patients (49%) (non-contraceptive users and users < 5years duration) versus 15 patients (42%) who used oral contraceptives of more than 5 years duration (p=0.524). HPV type 16 was the commonest HPV type detected (20.2%) and HPV type 58 was the next commonest high-risk HPV type (16.1%). HPV types 58 and 33 was detected in a much greater percentage of our population and HPV 16 in a much smaller percentage of our population compared with a non-South African population. Conclusion The findings of this study demonstrate an interesting distribution of HPV types in a South African population. PROJECT TWO Introduction Various risk factors have been implicated in the causation of cervical cancer including human papillomavirus (HPV), the early genes (E6 and E7) of which encode the main transforming proteins. Studies have suggested that steroid hormones may enhance the expression of these genes leading to loss of p53 gene-mediated cell apoptosis. Methods A total of 120 cervical tissue samples were obtained from patients with proven cervical cancer. Patients who used depo-medroxyprogesterone acetate steroid contraception were recruited as part of the study arm. Only HPV DNA type 16 samples were used for the study. Controls included three cell lines (CaSki, SiHa,&C33A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients, there were 111 patients with HPV type 16 identified. Of this number, RNA was present in 63 samples. There were 30 women (30/63) who used steroid contraception. In relation to patients who used contraception, HPV 16 E6 gene expression was present in 79% (n = 23) and 88% (n = 30) of steroid users compared to nonusers, respectively. In total there were 25 patients (40%) with expression of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. There were 57% of steroid users (n = 17) who had expression of the E6*I/E6*II gene, compared to 52% (n = 17) of nonusers (P = 0.800). Conclusion From a molecular level, this study reflects almost similar distribution of the HPV 16 E6/E6*1 and E6*11 and does not confirm the role of injectable progesterones in cervical carcinogenesis. Further studies with larger patient numbers are needed. / Thesis (PhD)--University of Pretoria, 2011. / Obstetrics and Gynaecology / unrestricted

This thesis examined the evidence, policy decision-making, and implementation of HPV vaccination in Canada as a case study to explore normalization versus individualized decision making in public health programs. Mixed methods were used: a systematic review, content analyses and policy document analysis. Overall, the scientific evidence supported an effect of vaccination against HPV infection and precancerous cervical lesions, but evidence regarding cervical cancer incidence or mortality is lacking. Scientific and medical communities appeared optimistic about the vaccine, but cautious about its readiness for routine implementation. Policy decision-making was initially cautious, but shifted towards active program implementation, possibly related to the availability of federal funding. The educational materials and media coverage both sent clearly normalizing messages about HPV vaccination. The discussion suggests that HPV vaccination might be more suited to an individualized than population approach, but many factors coincided to promote its implementation, in Canada, within a traditional public health model.