A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current research and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the development, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, optimization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.

Introduction Cervical cancer is the fourth most common cancer in women worldwide. An estimated 62,000 cases of cervical cancer occur annually in China, accounting for 12% of global incidence. Virtually all cervical cancers are related to infection by Human Papilloma Virus (HPV): effective HPV vaccines have been developed and vaccination programmes introduced in many countries over the last decade. Given the burden of cervical cancer in China, it is imperative that effective primary and secondary prevention strategies are introduced. Effective introduction of HPV vaccination programmes will require education and information strategies that are informed by a comprehensive understanding of the knowledge, attitudes and beliefs about HPV infection and its relationship to cervical cancer in the Chinese population. Aims and objectives The aims of my thesis are: 1) to systematically review the evidence from the Chineselanguage literature in relation to knowledge of and attitude towards HPV infection and HPV vaccination, and 2) to explore knowledge and attitudes about HPV infection, HPV vaccination and cervical screening amongst teenagers in Heilongjiang province in China. Methods I undertook a systematic literature review using two electronic Chinese databases – the ‘Chinese National Knowledge Infrastructure’ (CNKI) database and the ‘Wanfang’ database. These were searched from inception through November 30th 2012: MeSH terms were applied to both Chinese databases. Manual searching of relevant online journals was also undertaken. Following selection of papers based on pre-determined inclusion and exclusion criteria, quality assessment was carried out using a modified quality assessment checklist, and included studies were classified as good, fair or poor quality. Due to heterogeneity of populations and survey instruments a narrative approach was adopted for data synthesis. I also undertook a questionnaire survey of high-school students in China. Questions were designed based on the Health Belief Model, informed by findings from my systematic review, and refined through cognitive interviews prior to field work in early 2014. The survey targeted students in five public high schools in one middle-income city (Mudanjiang city) and two small counties (Ning’an and Hailin) of Heilongjiang province; 3788 young people aged 14-22 years participated. Descriptive statistical analysis was used to summarise demographic characteristics; initially differences were identified using the chi-square test. Factor analysis was applied to identify attitude patterns and logistic regression analysis models were applied to determine the association between attitude (potential predictors) and acceptability, attitude and levels of knowledge. Results Forty seven articles met my inclusion criteria and were included in the systematic review. All included studies were published between 2006 and 2011; all were cross-sectional questionnaire surveys with sample sizes ranging from 100 – 9,865. The quality of included studies varied considerably. Included populations ranged from the general public, to young people, and health professionals. Awareness of HPV and knowledge of the relationship between HPV and cervical cancer, and of the sexually transmitted nature of HPV, were the main issues examined. Awareness of HPV was low among all non-health professionals groups. Similarly, understanding of the relationship between HPV infection and cervical cancer and of the sexually transmitted nature of HPV was low. However, significant differences in awareness and knowledge were found, based on urban/rural status, ethnicity and age. Uighur women had the lowest awareness and knowledge levels, followed by rural women adults, and teenagers. Acceptability of HPV vaccination varied in terms of the vaccine target recipients (whether adult women, or for their daughters), and between health professionals and the general public). Reported levels of HPV vaccine acceptability (for women adults themselves and for their daughters) were higher in North China compared to South China. Health professionals were less willing to accept the vaccine for their daughters than they were to receiving it themselves. The cost, source and appropriate age for HPV vaccination were also frequently examined issues. Importantly, a high proportion of the health professionals believed that the appropriate age for vaccine was over 18 years old for girls. 3788 participants aged 14-22 years were included in the questionnaire survey, with 54% females and 20% urban students. Overall awareness of HPV was 13.2% and acceptability of the HPV vaccine was 68%. Knowledge levels varied in different content areas; for example 74% of respondents knew that HPV vaccination is not 100% effective against cervical cancer while only 6% knew that poor personal hygiene did not increase the risk of contracting HPV infection. Attitudes towards HPV infection and vaccination were also interesting and novel; the greatest concern about HPV vaccination was minor side effects (72%). The highest-rated source of recommendations about HPV vaccination was parents (66%), while there were concerns expressed about ‘gossip’ in relation to HPV vaccination (51%). No urban/rural differences were found in knowledge and attitudes - gender differences existed, but depended on specific circumstances. Participants who were willing to accept HPV vaccination were more likely to be influenced by others, to report high perceived severity of HPV and cervical cancer, to perceive benefits of HPV vaccination and to score well on knowledge questions. Participants with high knowledge scores for HPV infection and vaccination were more likely to consider HPV infection and cervical cancer to be serious, and were less likely to associate HPV infection with stigma. Participants who had high levels of awareness of HPV infection were more likely to be influenced by others in relation to accepting HPV vaccination. Discussion My thesis has produced new and novel findings in relation to HPV vaccination knowledge, attitudes and beliefs in China. Low levels of awareness and knowledge amongst Chinese people may be influenced by traditional Chinese culture, which perhaps makes people more reluctant to consider issues related to sexual practices. Another possible explanation is that people tended to under-report knowledge of HPV when answering the questions in the survey in order to conform to social norms in China - these topics are highly sensitive in China. High levels of acceptability of HPV vaccines may have also been influenced by ‘ways of thinking’ among Chinese people; their natural inclination is to accept all recommendations for vaccination from government agencies – so they may not have thought hard about this choice. There is optimism in the Chinese population that cancer can be prevented by vaccination – indeed, they are inclined to believe it will prevent disease that can generate serious health impacts in the future. Nevertheless, some Chinese people have conservative attitudes towards the effectiveness of HPV vaccination and some suspicion of the drug companies which produce these vaccines. There were significant methodological issues in my comparisons of Western and Chinese literature. Western literature is more likely to comprise good quality studies – typically there are better-defined sampling frames, more valid and reliable instruments and robust theoretical frameworks. The difference in quality between Chinese and Western literature arises from the stricter rules for reporting and evaluation in western publications and the relatively low publishing standards in Chinese literature. / My thesis also details a number of methodological issues which arose in conducting my questionnaire survey – ideally, I would like to follow up the work I have done with a multi-centre population-based study among teenagers in China (an idea which I will pursue once I return to China). This would hopefully provide better quality information on the influences of factors such as socio-economic status and family background in determining acceptability of HPV vaccination. Nevertheless, my relatively modest, school-based study has, I believe, produced results which add to the information available to health care planners and policy makers in the field of HPV vaccination in China. Conclusion My systematic review is, to my knowledge, the first to identify and synthesise findings about knowledge of and attitude towards HPV infection and vaccination in the Chinese literature – as such, it addresses a gap in currently available evidence. Although there are methodological limitations in Chinese literature (with more poor quality studies), the results still have implications for further health education intervention programmes and health policy. My questionnaire survey was also a ‘first’ in many ways – it explored attitudes towards HPV vaccines based on Health Belief Model among Chinese teenagers and examined HPV related stigma among mainland Chinese teenagers. Low levels of awareness and knowledge and conservative attitudes towards sexually related infections suggest the impact of Chinese traditional culture and a range of other social and financial constraints in China. Hence, there is a great deal to be done before HPV vaccination can be implemented in China – there are educational needs, and in many areas societal and cultural attitudes need to be challenged. Significant changes are also need in government policy and investment – these are major challenges for health care in China, and I sincerely hope my thesis will contribute to these important debates.

Orientador: Paulo Cesar Giraldo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T21:42:54Z (GMT). No. of bitstreams: 1 EleuterioJunior_Jose_D.pdf: 17867889 bytes, checksum: 0d9e1c3f2399c5be86d6fbf719dc98c4 (MD5) Previous issue date: 2007 / Resumo: Objetivos: Estudar a importância de determinados marcadores de diagnóstico e prognóstico de lesões escamosas genitais, com ênfase nos estudos de p16INK4a e HPV de alto risco. Material e Métodos: Marcadores tumorais foram revisados em 21 estudos publicados entre 1994 e 2005, no sentido de identificar aqueles que teriam melhor valor diagnóstico e/ou prognóstico das lesões intra-epiteliais escamosas. Revisão mais apurada avaliou os marcadores p16INK4a e HPV de alto risco em lesões do colo uterino (36 publicações entre 1994 e 2006). Estudou-se a associação do p16INK4a e HPV de alto risco em 96 amostras de colo utenno (13 casos de lesão intra-epitelial escamosa de alto grau (HSIL), 26 casos de lesão intra-epitelial escamosa de baixo grau (LSIL) e 57 biópsias normais. O p16INK4a foi identificado por imuno-histoquímica, usando-se o p16INK4a kit (E6H4 clone, DakoCytomation, Carpinteria, CA) e o DNA-HPV foi classificado por captura híbrida (Digene®). Associações foram avaliadas pelo índice KAPPA. No artigo foram envolvidos 54 homens, parceiros sexuais assintomáticos de mulheres com lesão intra-epitelial escamosa de baixo grau associada com HPV de alto risco, com a finalidade de verificar se a presença do HPV de alto risco poderia ajudar a identificar os casos com maior risco de ter lesões intra-epiteliais penianas, devendo submeter-se à biópsia. O DNA-HPV foi testado por captura híbrida (Digene®) em raspados do pênis. Peniscopia identificou lesões suspeitas que resultaram em biópsias. Resultados: As revisões demonstraram uma clara potencialidade clínica no uso da associação do p16INK4a e do HPV de alto risco no diagnóstico das SIL do colo uterino, e um possível uso como fator prognóstico. O p16INK4a foi detectado em 92,3% das HSIL, em 15,4% das LSIL e em nenhum caso de histologia normal. Encontrou-se respectivamente sensibilidade, especificadade, valor preditivo positivo e valor preditivo negativo de 92,3%, 100%, 100% e 98,3%, de p16INK4a para HSIL e 100%, 70,42%, 43,3% e 100% do HPV de alto risco para HSIL. No segundo estudo o HPV de alto risco estava presente em 25,9% dos parceiros. A peniscopia levou a 13 biópsias (24,07%) com os seguintes diagnósticos: condiloma (2 casos), PIN I (2 casos), PIN II (1 caso) e histologia normal (8 casos). O teste de HPV de alto risco revelou 80% de sensibilidade, 100% de especificidade, 100% de valor preditivo positivo e 88,9% de valor preditivo negativo para identificação de lesões penianas, mostrando que homens com HPV de alto risco positivo têm maior chancer de ter lesões escamosas penianas em biópsias guiadas pela peniscopia que aqueles com lesões aceto-brancas com teste de HPV negativo, (p = 0.007); OR = 51 (Cl 1.7-1527.1). Conclusões: Marcadores como o HPV de alto risco têm um potencial muito grande para aumentar o poder diagnóstico das HSIL e, principalmente, supor o prognóstico da evolução destas lesões, principalmente quando associado ao p16INK4a / Abstract: Objectives: To study the importance of the diagnostic and prognostic markers of genital squamous lesions, meanly p16INK4a and high risk HPV. Material And Methods: Squamous intra-epithelial lesion tumoral markers were revised in 21 publications between 1994 and 2005 to identify those with diagnostic and prognostic value. More accurate revision assessed the markers p16INK4a and high risk HPV (36 publications between 1994 and 2006). The p16INK4a and high-risk Human papillomavirus were investigated in 96 samples of the cervix (13 cases of high grade squamous intraepithelial lesions, 26 cases of low grade intraepithelial lesions and 57 normal tissues). The p16INK4a was identified by immunohistochemistry using the p16INK4a kit (E6H4 clone, DakoCytomation, Carpinteria, CA). and Human papillomavirus DNA was classified by hybrid capture (Digene®). Associations were evaluated by the KAPPA index. In the other report fifty four asymptomatic male sexual partners of women with low grade squamous intraepithelial lesions (LSIL) associated to high risk HPV were examined, between April 2003 and June 2005, to verify if the high risk HPV could help to identify those with more risk to have a squamous penile lesion. The DNA-HPV was tested by second generation Hybrid Capture (Digene ®) in penile scraped samples. Peniscopy identified suspicious lesions leading to biopsy. Results: The revisions showed the clinical potentiality of the concomitant use of high risk HPV and p16INK4a in diagnosis of cervical SIL and a possible utility in prognosis of genital squamous intra-epithelial. In 96 cervical biopsies, p16INK4a was detected in 92.3% of the high-grade squamous intraepithelial lesions, in 15.4% of the low-grade and in none of the normal tissues. The sensitivity, specificity, positive predictive value and negative predictive value for high-grade lesion were 92.3%, 100%, 100%, and 98.3%, respectively when considering p16INK4a expression, and 100%, 70.2%, 43.3% and 100%, respectively when considering high-risk HPV. In the male partner study high risk HPV was present in 25.9% (14/54) of the cases. Peniscopy led to 13 biopsies (24.07%). Condyloma (2 cases), PIN I (2 cases), PIN II (1 case) and normal tissue (8 cases) were found. The high risk HPV test presented 80% sensitivity, 100% specificity, 100% positive predictive value and 88.9% negative predictive value for the identification of penile lesions. So, there was a greater chance in finding HPV lesions in the biopsy in the positive cases for high risk HPV with abnormal peniscopy than in the negative cases for high risk HPV with anormal peniscopy (p = 0.007); OR = 51 (CI 1.7-1527.1). Conclusions: Markers as high risk HPV have a potential to increase the diagnostic of HPV induced lesions and maybe indicate the evolution, meanly associated with p16INK4a / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

Master of Science / Division of Biology / Nicholas A. Wallace / Cancer is not a single story, but rather numerous often interwoven tales, each with its own characters and progression. In the case of human papillomavirus (HPV) induced cervical cancer (CaCx), the narrative is about the relationship between virus and host, with the consequences of evolution’s shortsightedness driving the plot. Along with the increased proliferative state characteristic of cancer, cells experience frequent, inaccurate replication and replication stresses (ex. DNA damage and nucleotide starvation). To prevent replication fork stall and collapse generated by these stresses, the cell employs translesion synthesis (TLS). Notably, most of the genes in this pathway are upregulated in CaCx; however, the key protein polymerase eta is not. We have observed that upregulation in this pathway is complicated. It occurs at numerous levels, increasing both mRNA and protein abundance. This research further dissects how TLS upregulation occurs. Data shows that in CaCx-derived cell lines, the stability of some TLS proteins is increased, while the stability of other TLS proteins is unchanged. The increased proliferation, typical of these cell lines, cannot account for the enhanced stability. Despite increased TLS protein stability, these cells fail to adequately activate TLS increasing the risk of DNA damage. Genomic instability is a driving factor in HPV genome integration that prevents viral propagation and leads to cell transformation. It also raises mutagenesis rates, likely creating a selective pressure for tolerating failed TLS. The elevated mutation rate known to be associated with failed TLS could also provide a mechanism for acquired resistance to the drugs commonly used to treat CaCx. Changes in protein abundance are routinely used as biomarkers that can lead to the improved outcomes associated with early cancer detection. Elevated TLS protein could be leveraged to ensure cervical cancers are detected during Stage 1, when the 5-year survival rate is 80-90%, rather than at Stage IV, when the rate dips to around 15%.

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2011 / Introduction: A prospective study was conducted across the spectrum of cervical aberrancies with the aim of assessing the distribution of HPV relating to the degree of cervical abnormalities using polymerase chain reaction (PCR) and P16INK4A assay as a marker for cervical disease progression. Patient demographics including their sexual, contraceptive and screening history were evaluated to determine whether subsidiary risk factors contribute towards the development of cervical lesions among Namibian women. Methods: From Feb 2006 to March 2007, 187 women with abnormal cervical cytology were examined. Cervical smears were immunostained using the P16INK4A assay (Dakocytomation, Heidelberg, Germany). Brown discolourisation of the nucleus and/or cytoplasm of abnormal cells were considered positive for P16 immunoexpression. Absence of brown decolourisation in the nucleus or cytoplasm of abnormal cells was considered negative for P16 immunoexpression. DNA was successfully extracted from 182 specimens, and the respective samples were subjected to PCR using GP5+/6+ primers. Type-specific (HPV types 16 and 18) PCR were also applied. Patients’ sociodemographics, sexual and reproductive history, HIV status, contraceptive use and Pap smear history were all recorded.

De récents essais cliniques ont montré les bénéfices thérapeutiques des nouvelles immunothérapies (Sipoleucel T pour le cancer de la prostate…). Mais jusqu’ici la majorité des essais cliniques de vaccins contre le cancer n’ont montré que de faibles effets sur les patients, ce qui contraste avec les résultats obtenus dans les modèles pré cliniques. Ceux-ci, comprennent la greffe sous cutanée de cellules tumorales ce qui ne mime pas la vrai localisation anatomique de la lésion tumorale. De plus, dans la plupart des cas les vaccins anti-cancéreux sont administrés par voie systémique et induisent une réponse antitumorale avec un effet thérapeutique au niveau du compartiment systémique. La réponse antitumorale induite par ces vaccins au niveau du microenvironnement tumoral et ses effets antitumoraux sur des modèles orthotopiques n’ont jamais été décrits sur des modèles pré cliniques. Comme la majorité des tumeurs humaines se développe dans des localisations muqueuses, nous avons étudié l’effet de la voie d’immunisation dans l’induction des réponses antitumorales au niveau du site anatomique de la tumeur en comparant l’induction de LT CD8+ spécifiques de l’antigène tumoral après une vaccination par voie systémique (intramusculaire) ou muqueuse (intranasale). Cette stratégie de vaccination repose sur l’utilisation d’un vecteur non réplicatif qui cible les antigènes in vivo aux cellules dendritiques et qui a été développé au sein de notre unité. Il s’agit de la sous unité B de la toxine de Shiga (STxB) associée à un antigène tumoral (protéine E7 de l’HPV16) nous avons également analysé l’effet antitumoral de cette vaccination sur deux modèles de tumeurs orthotopiques à localisations ORL et pulmonaires exprimant l’antigène E7. Nous avons montré que la vaccination i.n. induisait une plus forte réponse LT-CD8+ spécifique et des effets antitumoraux au niveau des localisations muqueuses que la vaccination par voie systémique, et que cette immunisation par voie i.n. induisait un phénotype particulier sur ces LT-CD8+ spécifiques et en particulier une augmentation de l’expression des intégrines CD103 et CD49a en opposition à la voie systémique. L’inhibition de CD49a réduit l’effet thérapeutique de la vaccination par voie i.n. et le nombre de LT-CD8+ infiltrant les tumeurs orthotopiques. Nos résultats montrent que la réponse LT-CD8+ systémique ne sert pas comme marqueur prédictif de la qualité de la réponse immunitaire antitumorale au niveau local. Nos observations mettent en évidence l’existence d’une compartimentalisation de la réponse muqueuse antitumorale, une découverte capitale pour le développement rationnel des vaccins anti cancer / Recent clinical trials have shown the therapeutic benefits of new promising immunotherapies (Sipoleucel T for prostate cancer, Ipilimumab in melanoma…). But by far, the majority of cancer vaccine clinical trials have shown modest clinical effects on cancer patients, contrasting with results found in preclinical models. Those preclinical models of cancer rely on subcutaneous grafts of tumor cells which do not mimic the true anatomic location of tumor lesions. In addition, in most cases cancer vaccines are administrated by systemic route, eliciting systemic antitumor responses and therapeutic effects. The antitumor response elicited by those vaccine strategies at the local environment of tumor location and their antitumor effect on orthotopic tumor models has not yet been addressed in preclinical cancer models. Since the majority of human tumors develop at mucosal surfaces, we addressed the question of the effect of the immunization route in the induction of local mucosal antitumor CD8+T cell responses by comparing a systemic intramuscular (i.m.) and intranasal (i.n.) route of administration of cancer vaccine. This vaccine consists of a non-replicative vaccine strategy that targets tumor antigen in vivo to dendritic cells developed at our laboratory and composed of the B subunit of the Shiga toxin (STxB) associated to a tumor antigen (E7 protein of HPV16). We also analyzed the antitumor effect of these vaccinations on two mucosal orthotopic tumor models of head and neck and lung cancer expressing the E7 antigen. We found that intranasal vaccination induced stronger specific CD8+T cell responses and antitumor effects at mucosal sites than systemic immunization, and, that mucosal vaccination induced a mucosal imprinting phenotype on mucosal derived antigen specific T cells as they expressed the mucosal integrins CD103 and CD49a, as opposed to systemic specific CD8+T cells or tumor infiltrating T cells in subcutaneous tumors. Inhibition of CD49a reduced the antitumor efficacy of the nasal vaccine and the number of tumor infiltrating CD8+T cells on orthotopic mucosal tumors. Our results showed that systemic antigen-specific T cell responses as typically assessed did not predict the quality of local mucosal immune response. Our observations provide direct evidence for the compartmentalization of mucosal tumor immunity, a critical finding for the rational design of better cancer vaccines

Alkaline glutaraldehyde (GTA) has been used as a high level chemical disinfectant and sterilant for many years and is known to kill a broad spectrum of organisms ranging from vegetative eukaryotes to bacterial endospores. Although the mechanism of sporicidal action has been studied on numerous occasions, GTA's exact mechanism(s) of action are still debated. In addition to the uncertainty of GTA's mechanism(s) of action, GTA has also shown significant variability in the time required to kill endospores and naked viruses. A better knowledge of the lethal mechanism(s) of GTA is needed to understand this discrepancy in kill times for GTA against spores of different species. Similar trends have been observed in GTA's activity against non-enveloped viruses. Based on previous work, one proposed major mechanism of GTA's sporicidal activity is related to the number of available primary amines located on the surface of microbes. In this study, we have compared the efficacy of GTA on spores from 5 Bacillus species. We have also developed a method for staining these spores with amine reactive dyes to create fluorescent profiles correlating to the abundance of free amino groups on each spore type. We also describe a method for staining non-enveloped viruses to identify exposed primary amino groups on capsid proteins that may act as targets for GTA, using amine reactive Gold nanoparticles. We found that GTA 6-Log10 reduction times for various spore types varied at both the batch and species level. Spore coat thickness and fluorescence were useful tools in predicting the susceptibility of spores to GTA. Amine reactive gold particles (AuNPs) also proved useful in identifying virus susceptibility to GTA. Ultimately, more reliable disinfection testing methods are needed, and caution should be used when trying to extrapolate data generated from surrogate organisms to other species.

No description available.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / To systematically review all studies examining HPV vaccination acceptability among immigrant and ethnic minority parents and eligible individuals for cervical cancer prevention in the Unites states. MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Cochrane database searches were conducted searching for English language, US‐based studies to examine immigrant and ethnic minority population’s acceptability of HPV vaccination. Thirteen of more than 3,098 potentially relevant articles were included in the final analysis. Results. Latinos were statistically more likely to accept vaccination for both their daughters and sons. Foreign‐born adult Latinas were more accepting of the vaccine than U.S.‐born Latinas after controlling for other variables. Overall African American and Asian American parents were less likely to accept HPV vaccination for their daughters than Hispanic and White parents. Of the African American parents who intended to vaccinate their children the majority were significantly non‐Baptist and had higher levels of education. The majority of Haitian immigrants intended to vaccinate daughters and the rest agreed that they would most likely have their daughters vaccinated if their daughters’ physicians recommended it. More research is needed, particularly in the context of health care provider HPV vaccination recommendation to immigrant and ethnic‐minority populations. Acceptance figures so far suggest that the vaccine is generally well received among Hispanic/Latin and Haitian immigrants, but details of ethnic variations among these groups and a qualitative understanding of lower rates of acceptability among African American and Asian American communities are still being awaited. Despite advances in cervical cancer screening rates in the US, cervical cancer remains disproportionately high among low‐income immigrant and minority women, making this subgroup particularly vulnerable to disparities in screening and its detection. The purpose of this study is to examine the qualitative aspects of institutional and community level interventions of Cervical Intraepithelial Neoplasia (CIN) within the immigrant and refugee populations and the use of HPV vaccination as a prevention method. Combinations of the following keywords/phrases will be used: CIN‐ Cervical Intraepithelial Neoplasia, Cervical diseases, Cervical dysplasia, Refugees, Pap smear, Cervical Cancer Screening, HPV‐ Human Papillomavirus, HPV vaccination, Ethnic minorities, Immigrants. Independent reviews of each article will be conducted to assess the study quality and confirm the accuracy, completeness, and consistency of the abstracted data.

Introdução: A endoscopia de contato (EC) foi um exame descrito inicialmente como método de analise da histologia uterina e das cordas vocais. Os primeiros estudos utilizando a EC nas cavidades nasais mostraram resultados promissores na diferenciação de lesões benignas, considerando que a biópsia tradicional pode trazer algumas complicações. Objetivo: Descrever e comparar os achados da EC no papiloma schneideriano invertido e no carcinoma espinocelular nasossinusal e testar a efetividade do exame como método não invasivo in vivo para diferenciação entre esses tumores. Métodos: Os pacientes inclusos no estudo foram divididos em grupo A, com diagnóstico de papiloma invertido e grupo B, com diagnóstico de carcinoma espinocelular. Os resultados da EC de cada lesão foram comparados entre si. As imagens gravadas dos exames foram apresentadas à examinadores sem experiência com a EC. Resultados: Um total de vinte e dois pacientes foram examinados, treze no grupo A e nove no grupo B. As principais diferenças nos achados da EC entre os dois grupos foram: presença de vasos espiralados, mitoses, queratinização e pleomorfismo nuclear no carcinoma e presença de células vacuolizadas no papiloma. Os examinadores, mesmo não habituados a este novo método, tiveram um bom índice de acerto no diagnóstico diferencial das duas lesões nasais, baseados apenas nas imagens da EC. Conclusão: A EC pode ser um exame não invasivo e in vivo útil para o diagnóstico diferencial entre o papiloma invertido e o carcinoma espinocelular nasossinusal, principalmente quando usado no planejamento pré-operatório do paciente. / Background: Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. Objective: Describe and compare the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma and test the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. Methods: The patients included in this study were divided into Group A, whose diagnosis was inverted papilloma, and Group B, whose diagnosis was squamous cell carcinoma. CE results were compared amongst themselves. CE images were presented to examiners not experienced with the method. Results: Twenty-two patients were examined, thirteen in Group A and nine in Group B. The main relevant differences in CE findings between those two groups were: corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. Conclusion: CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal squamous cell carcinoma, which may enable better preoperative planning.