Bakgrund: Livmoderhalscancer är en av de vanligaste cancerrelaterade dödsorsakerna i utvecklingsländer. Humant papillomvirus (HPV) är ett sexuellt överförbart virus som kan, vid bestående infektioner, orsaka livmoderhalscancer. I Sveriges infördes år 2010 ett vaccin till flickor som skydd mot de typer av HPV som orsakar livmoderhalscancer med 70%. I Sverige erbjuds kvinnor mellan 23 till 50 år cellprov vart tredje år, vilket minskar risken att utveckla livmoderhalscancer med 90 %. Majoriteten av kvinnorna deltar dock inte i de erbjudna cellprovskontrollerna. Eftersom HPV är ett sexuellt överförbart virus kan det hos vissa vara stigmatiserat och leda till en känsla av skam. Människans syn på den sexuella hälsan och kroppen präglas av människans kulturella bakgrund och erfarenheter vilket påverkar människans värderingar och val. Syfte: Syftet var att belysa kvinnors erfarenheter av HPV-förebyggande åtgärder. Metod: Denna studie baserades på en litteraturöversikt av elva vetenskapliga artiklar som samlades in via noggrann analys och som ligger till grund för resultatet. Dessa artiklar bestod av vetenskapliga originalartiklar som samlades in från tre olika databaser. Analysen redovisades med två huvudteman och ett undertema. Resultat: Resultat framkom i två teman; Cellprov och HPV-vaccin. Under Cellprov tillfogades ett undertema; Självtest. Resultatet visade att kvinnors erfarenheter influerades av deras kulturella bakgrund och det i sig påverkade deras attityder mot preventiva åtgärder. Det visade sig även att den kulturella bakgrunden och mödrars erfarenhet av livmoderhalscancer påverkade mödrars attityd gentemot vaccin för sina döttrar. Deltagandet av cellprovstagning påverkades av kvinnors tidigare erfarenheter och skam/skuldkänslor gällande cellprov. Kvinnors erfarenhet av självtest var positivt då det ökade integriteten och därmed minskade känslan av skam. Diskussion: Kvinnors attityd till cellprov och HPV-vaccin präglades av kunskapsbrist och kulturell påverkan. Kvinnors önskan av en mer individanpassad information både språkligt och skriftligt ansågs som ett positivt och välbehövt inslag i vården. Mer vikt bör läggas på att öka deltagandet och kunskapen hos kvinnor genom att anpassa informationen som ges ut till individen. Madeleine Leiningers teori om transkulturell omvårdnad är ett hjälpfullt stöd för sjuksköterskor att anpassa vården utifrån individens kulturella bakgrund. Det gäller både den information som lämnas och omvårdnaden av patienter. / Background: Cervical cancer is one of the most common cancer-related causes of death in developing countries. Human papillomavirus (HPV) is a sexually transmitted virus that, in case of permanent infections, causes cervical cancer. In Sweden, a vaccine for girls was introduced in 2010 to protect against the types of HPV causing 70% of cervical cancer. In Sweden, women between 23 and 50 years of age are offered cell samples every three years, which reduces the risk of developing cervical cancer by 90%. However, the majority of women do not participate in the offered cell sample checks. Because HPV is a sexually transmitted virus, it may in some cases be stigmatized and lead to a sense of shame. Human views of sexual health and the body is characterized by human cultural background and experiences, which affects human values and choices. Aim: The purpose was to highlight women's experiences of HPV prevention. Method: This study was based on a literature review of eleven scientific articles collected through careful analysis and is the basis for the outcome. These articles consisted of scientific original articles as they were collected from three different databases. The analysis was presented with two main themes and one sub theme. Results: Results emerged in two themes; Cell sample and HPV vaccine. Self-test was added as a subtheme under Cell sample. The results showed that women's experiences were influenced by their cultural background and in turn influenced their attitudes toward preventive measures. It also turned out that the cultural background and mothers' experience of cervical cancer affected mothers' attitude towards vaccines for their daughters. The participation of cell sampling was influenced by the women's previous experiences and shame/guilty feelings regarding cell samples. Women's self-test experience was positive as it increased integrity and thus reduced the sense of shame. Discussion: Women’s attitude towards Cell sample and HPV vaccine were characterized by lack of knowledge and cultural impact. Women's desire for more personalized information was considered a positive and well-needed feature in health care. More emphasis should be placed on increasing the participation and knowledge of women by adapting the information given to the individual. Madeleine Leininger's theory of transcultural care can help nurses to adapt their care based on the individual's cultural background. This applies to both the information provided and the care of patients.

MSc (Microbiology) / Department of Microbiology

Head and neck squamous cell carcinoma encompasses a complex and heterogeneous group of malignant diseases. Originally, this tumor type was associated with tobacco and alcohol consumption. However, a significantly expanding subset of tumors associated with oncogenic human papillomavirus infection arising in deep tonsillar crypts was identified within the last decades. Due to the essential role of the immune system in antiviral and anticancer immune response, the prognosis of patients is significantly influenced by the volume, composition and functional capacity of the immune infiltrate. The immunosuppressive landscape of head and neck cancer leads to unfavorable outcome of patients and decreased efficacy of immunotherapy. The response rate to standard treatment is high, however, standard therapy is accompanied by considerable toxicity influencing the quality of life. In 2016, the first immunotherapeutics for the treatment of patients with recurrent squamous cell carcinoma of the head and neck were approved - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab. This type of therapy, based on mitigation of immunosuppression, shows strong efficacy and less toxicity in combination with other therapies. Therefore, anti-PD-1 immunotherapy was recently approved in the first-line...

Indiana University-Purdue University Indianapolis (IUPUI) / Human papillomavirus (HPV) infection results in serious health issues including cervical, anal, vulvar, penile and oropharyngeal cancers. There are three vaccines against HPV but vaccination rates in the United States remain low. One barrier to uptake is a concern that individuals who are vaccinated may increase their risky sexual behaviors or decrease their use of cervical cancer screenings, an adjustment in perceived level of risk for HPV that can be studied using risk compensation theory. Methods Three distinct studies examined risk compensation after HPV vaccination. A systematic review examined literature from January 1, 2008-June 30, 2015, using three databases. A qualitative study using semi-structured interviews of 22 healthcare providers that assessed their beliefs regarding sexual disinhibition and cervical cancer screening following vaccination. A cross-sectional survey that assessed cervical cancer screening practices, awareness and comfort with recommendations, and knowledge regarding the purpose of a Papanicolaou (Pap) test. Results Twenty articles were included in the systematic review. None of the studies of sexual behaviors and/or biological outcomes found evidence of riskier behaviors after HPV vaccination. Instead, the studies found vaccinated individuals were less likely to report risky sexual behaviors, sexually transmitted infections (STIs), and pregnancy. Qualitative interviews found no healthcare providers believed the HPV vaccine would result in increased risky sexual behavior or decreased cervical cancer screening, and these concerns would not influence their vaccination recommendations. The survey included 291 women 21-35 years old; 62% were non-Hispanic black, 84% had a Pap test in the last three years, and 33% had at least one HPV vaccine. Logistic regression showed that vaccinated women did not have greater odds of having a Pap test in the past three years (OR=1.32; 95% CI=0.66-2.65; p=0.427). However, this odds ratio was significant when controlling for age and race (AOR=3.06; 95% CI=1.37-6.83; p=0.006). Conclusion These studies found no evidence of increased risky sexual behaviors or decreased cervical cancer screening rates after HPV vaccination. Furthermore, vaccinated women showed less evidence of risk compensation. These results should alleviate concerns about administering the HPV vaccination among parents and providers.

Contexte : La littérature suggère que le virus du papillome humain (VPH) puisse être transmis verticalement. Or, le mécanisme exact de transmission verticale demeure inconnu et les données ne permettent pas de savoir dans quelle mesure la transmission verticale est affectée par le mode d’accouchement. L’objectif de l’étude était de mesurer l’association entre le mode d’accouchement et la détection d’ADN du VPH chez les bébés. Méthode : Nous avons utilisé les données de 1052 femmes enceintes de la cohorte HERITAGE. Des échantillons vaginaux auto-collectés ont été obtenus chez les mères durant la grossesse, et des échantillons des muqueuses de la bouche, la gorge, les yeux et de la région anogénitale ont été collectés chez les bébés à la naissance et à 3 mois. Nous avons inclus les 282 femmes ayant eu un test VPH positif au premier et troisième trimestre de grossesse. Tous les échantillons ont été analysés pour la détection d’ADN du VPH par la méthode de réaction de polymérase en chaîne (PCR) avec le test Linear ArrayMC. Les informations sur l’accouchement ont été collectées dans les dossiers médicaux. L’association entre le mode d’accouchement et la transmission verticale du VPH a été mesurée par régressions logistiques. Résultats : La probabilité de transmission verticale du VPH a été de 8,9% (25/282), soit 3,7% (3/81) pour les césariennes et 10,9% (22/201) pour les accouchements vaginaux. Chez 21 des 25 enfants positifs au VPH (84%), il y avait au moins un génotype concordant avec leur mère, et tous sont nés par accouchement vaginal. Une augmentation significative du risque de transmission verticale du VPH a été observée pour l’accouchement vaginal, en comparaison avec la césarienne (OR ajusté: 3,63, intervalles de confiance à 95% (IC 95%): 1,03-12,82). Nous n’avons pas observé d’association significative entre la césarienne suivant la rupture des membranes et le risque de transmission, lorsque comparé avec la césarienne avec membranes intactes (OR ajusté : 1,31, IC 95% : 0,10-17,76). Il n’y a pas eu d’association entre la durée écoulée entre la rupture des membranes et la naissance (en heures continues) et le risque de transmission verticale (OR : 1,00, IC 95% : 0,97-1,02). Conclusion : L’accouchement par césarienne a été associé à un risque significativement plus faible de transmission du VPH chez les bébés. La transmission verticale du VPH surviendrait principalement lors du passage dans le canal vaginal car très peu d’enfants nés par césarienne ont été infectés au VPH. Puisque la rupture des membranes avant la césarienne et la durée entre la rupture des membranes et la naissance n’ont pas été associées à un risque de transmission du VPH plus élevé, nos résultats suggèrent que la transmission par infection ascendante après rupture des membranes est probablement rare. / Background: The literature suggests that human papillomavirus (HPV) can be transmitted vertically. However, the exact mechanism of vertical transmission remains unknown and the data do not allow us to know to what extent vertical transmission is affected by the mode of delivery. The aim of the study was to measure the association between mode of delivery and the detection of HPV DNA in infants. Method: We used data from 1052 pregnant women from the HERITAGE cohort. Self-collected vaginal samples were obtained from mothers during pregnancy, and specimens from the mucous membranes of the mouth, throat, eyes and anogenital region were collected from infants at birth and at 3 months. We included 282 women who had both positive HPV tests in the first and third trimester of pregnancy. All samples were analyzed for detection of HPV DNA by the polymerase chain reaction (PCR) method with the Linear ArrayTM assay. Information about the delivery was collected from medical records. The association between the mode of delivery and HPV detection in infants was measured using logistic regressions. Results: The probability of transmission of HPV was 8.9% (25/282); 3.7% (3/81) for caesarean sections and 10.9% (22/201) for vaginal deliveries. In 21 of 25 HPV positive infants (84%), there was at least one genotype concordant with their mother, and all were born vaginally. A significant increase in the risk of transmission of HPV was observed for vaginal delivery, compared to caesarean section (adjusted OR: 3.63, 95% confidence intervals (95% CI): 1.03-12.82). We found no significant increase in the risk of HPV transmission for caesarean section following rupture of membranes, compared to caesarean section with intact membranes (adjusted OR: 1.31, 95% CI: 0.10-17.76). There was no association between the time between rupture of membranes and birth (in continuous hours) and the risk of vertical transmission (OR: 1.00, 95% CI: 0.97-1.02). Conclusion: Caesarean delivery is associated with a significantly lower risk of HPV vertical transmission. Vertical transmission is thought to occur mainly during passage through the vaginal canal, because very few infants born by caesarean section have been infected with HPV. Since rupture of membranes before caesarean section and the time between ruptured membranes and birth have not been associated with a higher risk of HPV transmission, our results suggest that transmission by ascending infection after rupture of membranes is unlikely.

Detection of p16 through immunohistochemistry (IHC) is the standard for determining the HPV status of the tumor according the TNM eighth edition released in 2017 and has become crucial for determining the HPV status of oropharyngeal squamous cell carcinomas (OPSCC) with direct impact on staging and prognostication. In recent years, detection of HPV DNA in mouthwashes has been proposed as a noninvasive alternative, both for OPSCCs and for other head and neck squamous cell carcinomas (HNSCCs). However, the prospect of using the mouthwashes to monitor the response to therapy is unclear. To evaluate the effect of curative therapy on the detection of HPV DNA, we performed a prospective study comparing the detection frequency of high-risk HPV DNA (HR-HPV-DNA) in pre- and post-therapy mouthwashes. We collected 137 mouthwashes from 88 pathologically confirmed HNSCC patients for DNA isolation and HPV genotyping with the Inno- LiPA assay. We show that HPV DNA in pretherapeutic mouthwashes can detect HPV-driven HNSCCs with a sensitivity of 50.0% and specificity of 85.4%, alongside a high negative predictive value of 79.5% and an accuracy of 74.5%. Furthermore, we observed a notable decrease in the detection frequency of HR-HPV-DNA after successful treatment (pre-therapy 50.0% (9/18) versus post-therapy 9.7% (3/28)). However, the comparatively low sensitivity regarding detection of HPV-driven OPSCC argues against its use in clinical routine.

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Made available in DSpace on 2011-05-04T12:36:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2009 / O desenvolvimento de vacina contra o Papilomavirus humano (HPV), que se apresenta revolucionária, pelo potencial de prevenção primária do câncer de colo uterino tem suscitado polêmica quanto à incorporação em programas de saúde pública. As evidências de eficácia da vacina se limitam a lesões invasivas pelos principais genótipos doHPV e a vacina tem custo muito mais alto do que outras vacinas do calendário vacinal do Programa Nacional de Imunização do SUS. Este trabalho analisa as possibilidades de utilização da vacina contra o HPV, considerando a efetividade do Programa de Rastreamento do Câncer de Colo Uterino do Brasil e a eficácia da vacina contra o HPV registrada. O estudo foi realizado a partir de revisão das evidências obtidas de dados empíricos, e disponíveis em relatórios, publicações e páginas eletrônicas. A vacina apresentou resultados muito favoráveis para a eficácia e segurança, porém com lacunas importantes no conhecimento sobre seu efeito a longo prazo e correlato sorológico de proteção. Os dados indicam que o programa de prevenção do câncer de colo do Brasil tem baixa efetividade, com grande heterogeneidade de cobertura e qualidade. Foi observada também uma variação muito grande com relação à acurácia do Papanicolaou, com implicações no desempenho do programa. Considerando que o controle de câncer de colo uterino continuará dependendo de rastreamento com o Papanicolaou, e que a efetividade do programa em outras partes do mundo permitiu reduzir a mortalidade, parece mais indicado concentrar esforços e recursos na melhoria do programa de rastreamento e aguardar os resultados de médio prazo da vacinação. / The development of a vaccine against human papillomavirus (HPV), which presents itself revolutionary due to its potential for primary prevention of cervical cancer, has raised controversy over the incorporation into public health programs. Evidence of effectiveness of the vaccine are limited to invasive lesions of the major genotypes of HPV and the vaccine cost is much higher than other vaccines in the immunization calendar of the National Program on Immunization of the Unified Health System (SUS). This study analyzes the potential use of the vaccine against HPV, considering the effectiveness of the Program for Cervical Cancer Control in Brazil and the efficacy of the vaccine against HPV registered. The study was carried out from reviewing the evidence obtained from empirical data, and available in reports, publications and websites. The vaccine showed very favorable safety and efficacy results, but with important gaps in knowledge about their effect in the long term and serological correlate of protection. The data indicate that the program for the prevention of cervical cancer in Brazil has low effectiveness, with great diversity of coverage and quality. There was also a very large variation with respect to the accuracy of Papanicolaou, with implications for the performance of the program. Considering that the control of cervical cancer will continue depending on the Papanicolaou screening, and that the effectiveness of the program in other parts of the world has reduced mortality, it seems more appropriate to concentrate efforts and resources in improving the tracking program and wait for the results medium-term vaccination.

Made available in DSpace on 2014-07-29T15:30:36Z (GMT). No. of bitstreams: 1 Dissertacao Andrea Alves Ribeiro.pdf: 1577076 bytes, checksum: 24bc7ace843786b03ff879da0df4f7aa (MD5) Previous issue date: 2009-12-15 / Human papillomavirus (HPV) is considered the central etiological agent involved in the genesis of cervical cancer. The HPV viruses are classified according to their biological niche, oncogenic potential and phylogenetic position. According to the criteria established by the International Committee on Taxonomy of Viruses (ICTV), the various groups of human papillomaviruses that infect the female genital tract are classified phylogenetically in the Alphapapillomavirus genus, including species classified among phylogenetic species 1 and species 15. The main high risk HPV are classified in species 9 (HPV 16, 31, 33, 35, 52, 58, 67), and in species 7 (18, 39, 45, 59, 56, 66, 68 and 70). HPV 16 is the most prevalent type irrespective of diagnosis, principally in more severe lesions. Coinfection with multiple-types HPV is a common finding of many molecular studies. Some HPV types might interact or act synergistically to induce progression. Few studies have investigated the interactions of viral genotypes or species in multiple-type HPV infections. Therefore, the objective of this study was to evaluate the effect of single or multiple-types HPV infections considering also the phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) among women undergoing colposcopy following a abnormal cervical smear. Methodology: In this analysis, 198 women attending at the colposcopic clinic, because of an abnormal cervical smear were included. Colposcopy was carried out in all cases and biopsies were done in 193 of 198 women included. All specimens were tested for 27 HPV genotypes by Roche s polymerase chain reaction reverse line blot assay. Results: The overall prevalence of HPV in women with an abnormal cervical smear was 86% (171/198). Of the total of HPV-positive women, 45% (77/171) were infected with HPV 16 as a single or multiple-type infections. HPV 31 and 35 were, respectively, the second and third most prevalent types. The prevalence of HPV 16 in high grade cervical intraepithelial neoplasia (CIN2/3) was 52% (40/76) and it was detected in 88.8% (8/9) in cases of invasive carcinoma. The prevalence of type 31 and 35 in high grade CIN was respectively 10.5% (8/76) and 6.6% (5/76). Single HPV infection for any type was significantly associated with neoplastic diagnosis. High grade neoplastic diagnosis (≥ CIN2) was significantly associated with HPV 16 in single or multiple infections. Also, there was significantly association between HPV 16 and others types of specie 9 and high grade neoplastic diagnosis, but no association was observed considering the HPV 16 and other of groups of species 7 or others types. Conclusion: These results indicated that the type 16 is the most important predictor of high grade cervical neoplasia. Multiple-type infections are predictors of high grade cervical neoplasia when the type 16 is present. / O Papilomavírus humano (HPV) é considerado o agente etiológico central envolvido na gênese do câncer cervical. O vírus HPV é classificado de acordo com seu nicho biológico, potencial oncogênico e classificação filogenética. De acordo com os critérios estabelecidos pelo Comitê Internacional de Taxonomia dos Vírus (ICTV), os diversos tipos de HPV que infectam o trato genital feminino são classificados filogeneticamente no gênero Alphapapillomavirus. Esta classificação inclui espécies filogenéticas classificadas entre a espécie 1 e a espécie 15, dentre as quais, as de maior interesse em relação ao potencial carcinogênico são a espécie 9 (HPV 16, 31, 33, 35, 52, 58, 67) e a espécie 7 (18, 39, 45, 56, 59, 66, 68, 70). O HPV 16 é tipo o mais predominante, independente do diagnóstico, presente principalmente nas lesões cervicais mais graves. A co-infecção com múltiplos tipos de HPV é um achado comum em muitos estudos moleculares, contudo, as interações dos genótipos virais ou espécies envolvidas nas infecções por múltiplos tipos de HPV têm sido pouco analisadas. Portanto, o objetivo deste estudo foi avaliar o efeito das infecções simples ou por múltiplos tipos de HPV, considerando também os grupos filogenéticos, sobre a prevalência e a gravidade das neoplasias cervicais. Metodologia: Este estudo de corte transversal incluiu 198 mulheres encaminhadas ao Ambulatório de Colposcopia da Santa Casa de Misericórdia de Goiânia por exame citopatológico anormal. Todas as mulheres foram esclarecidas quanto aos objetivos de estudo e assinaram o termo de consentimento livre e esclarecido. A colposcopia foi realizada em todos os casos e a biópsia em 193 das 198 mulheres incluídas. As amostras foram testadas para 27 genótipos de HPV, por reação em cadeia da polimerase (PCR); em seguida foi realizada a hibridização reversa em pontos da Roche Diagnósticos. Resultados: A prevalência de HPV em mulheres encaminhadas por exame citopatológico anormal foi de 86% (171/198). Do total de mulheres HPV-positivas, 45% (77/171) estavam infectadas por HPV 16 em infecções simples e múltiplas. Os tipos de HPV 31 e 35 foram respectivamente, o segundo e o terceiro mais prevalentes. A prevalência do HPV 16 foi de 52% (40/76) nas neoplasias intra-epiteliais cervicais de alto grau (NIC 2/3) e de 88,8% (8/9) nos casos de carcinomas invasivos. As prevalências dos tipos 31 e 35 em neoplasias intra-epiteliais cervicais de alto grau (NIC 2/3) foram de 10,5% (8/76) e 6,6% (5/76), respectivamente. A infecção simples por qualquer tipo de HPV foi significativamente associada com diagnósticos neoplásicos de alto grau (≥ NIC 2). Os diagnósticos neoplásicos de alto grau (≥ NIC 2) foram significativamente associados com o HPV 16 em infecções simples ou múltiplas, mesmo depois de ajustado pela positividade para DNA de HPV. Houve significativa associação entre o HPV 16 e outros tipos da espécie 9 e os diagnósticos neoplásicos de alto grau (≥ NIC 2), mas não foi observada associação, considerando o HPV 16 e outros tipos da espécies 7 ou outros tipos de HPV. Conclusão: Estes resultados indicam que o HPV 16 parece ser o mais importante preditor de diagnósticos neoplásicos de alto grau. As infecções múltiplas são preditoras das neoplasias cervicais de alto grau quando o HPV 16 está presente.