The topic of my thesis is cervical cancer and its prevention with emergence on vaccination against cervical cancer. The aim of my diploma thesis is to use analyzation of the campaign against cervical cancer, All I can, and analyzation of interviews with mothers who have decided to vaccinate their daughters to find out how the responsibility of mothers for health of daughters is constructed in the connection with cervical cancer. I am interested in how campaign promoting a vaccination articulates what is good or bad motherhood and how mothers construct a good motherhood. I am also interested in gender consequences of campaign that it brings and how mothers prevent health of their daughters. The thesis shows that health is our project and is as good as we care about it. In the connection with reproductive health there is mainly appear a theme of considering risks which participate on creation of good parenthood. The thesis talks about different medicalization of child body that is set up and reproduce by interviewed mothers and by campaign. It brings gender inequalities and stereotypical gender constructions and questions of who is responsible for reproductive health.

<p>This dissertation aimed at examining the predictors of HPV vaccination intentions of college students in a Kenyan university and those in a Midwest university in the United States of America (USA). Using the theory of planned behavior (TPB), the dissertation investigated the most salient factors that predict the vaccination intentions of college male and female students in Kenya and the USA. A mixed method approach was utilized to collect data from the participants. Specifically, interviews with 43 students (22 from Kenya and 21 from USA) were used to collect the qualitative data from the students. The quantitative data were collected using closed-ended surveys with 512 Kenyan students at a large university in Uasin Gishu County and 522 students at the Midwestern university, USA. The qualitative findings revealed that identification had a major influence on how students sought health, ate, and related with their peers. In particular, identification through religiosity influenced the students’ attitudes toward sex and perception of oneself. Thus, many respondents reported viewing their bodies as the temple of God and sex as an activity for married couples. Thus, when they engaged in premarital sex, they often felt disconnected with God and they resulted to seeking forgiveness, minimizing their actions, and normalizing their actions.</p><p>Overall, the quantitative results suggested that college students in Kenya and the USA converged in certain health trends but differed in several others. For example, the Kenyan participants depicted a low understanding of HPV and HPV vaccine compared to the participants at the Midwestern university. The country of the participant also moderated the relationships between subjective norms and intentions, sex attitudes, vaccine attitudes, and intention to get vaccinated. The participants from the USA, for example, reported a stronger relationship between subjective norms and the intention to be vaccinated compared to the participants from Kenya. The results of this study also showed that the gender of the participant had an influence on the attitudes of students toward sex, with male participants having more favorable attitudes toward sex compared to female participants. Overall, subjective norms and cancer worry were the only common vaccine predictors among both female and male participants from Kenya and the USA. Surprisingly, although religiosity was correlated with other variables under consideration, it did not emerge as a direct predictor of the intention to get vaccinated. This might suggest it as a probable indirect predictor.</p><p>Being a comparative study of students in two countries, this dissertation offers unique insights that can inform theory, research, practice, and policy development. Specifically, the results point to the need for health practitioners designing health campaigns to consider the unique differences that exist among male and female students in Kenya and the USA. Some of the weaknesses of the study include use of self-report measures, which are limited to the memory of participants. This study suggests that researchers continue to explore the role of religiosity in influencing health-seeking behaviors among college students.</p>

Cervical cancer rates in Sub-Saharan Africa (SSA) are amongst the highest in the world. The World Health Organization currently estimates that worldwide, cervical cancer will kill more than 443,000 women per year by 2030, of which 90% of deaths are predicted to occur in SSA. The Human Papillomavirus (HPV) vaccine provides primary protection against the most common cancer-causing strains of HPV that are responsible for cervical cancer. Over the last five years, there has been a slow increase in the number of African countries that have introduced the HPV vaccine via demonstration and pilot projects, and a minority of African countries that have incorporated the HPV vaccine into their National Immunisation Programmes. As part of this systematic review, a literature review was conducted and revealed that research has been conducted on top-down barriers and facilitators to HPV vaccine uptake and have found that poor health system capabilities, inaccessibility to medical care, low cervical cancer screening levels, inadequate infrastructure, finances, and health worker training are significant systemic barriers to HPV vaccination success in SSA. Little research has been conducted on demand-side or end-user perspectives of, and decisions around, the HPV vaccine. In order to complement existing research, and inform current and future implementation approaches, this qualitative systematic review explored stakeholder understandings of the HPV vaccine in SSA. This review searched the following databases: Embase (via Scopus), Scopus, MEDLINE (via PubMed), PubMed, EBSCOhost, Academic Search Premier, Africa-Wide Information, CINAHL, PsycARTICLES, PsycINFO, SocINDEX, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) and found a total of 259 articles. Of these, 31 articles met the inclusion and exclusion criteria and were included in the review. Braun and Clarke’s six step process for conducting a thematic analysis was used for analysis and studies were assessed for quality using the Critical Appraisal Skills Programme (CASP) checklist. Three major themes emerged from the thematic analysis: knowledge is intertwined with misinformation; fear shapes contradictory perceptions about the HPV vaccine; and social norms and gender dynamics are relevant factors in how stakeholders understand the HPV vaccine in SSA. This review iterates the importance of first working with communities to gauge understandings of the HPV vaccine, before trying to implement change through education, sensitization and behavior change.

No description available.

No description available.

Le gène L1 encode pour la protéine majeure de la capside des papillomavirus humains (VPH). L’information relative au polymorphisme de L1 pour les types autres que VPH- 16 est jusqu’ici limitée. Cet ouvrage explore le polymorphisme de L1 en comparant les séquences des types phylogénétiquement apparentés VPH-31, -33, -35 à VPH-16. Des spécimens génitaux recueillis de 732 femmes VIH-séropositives et 323 VIHséronégatives ont été criblés à le recherche d’ADN de VPH par PCR consensus au niveau du gène L1. Les échantillons positifs pour VPH-16 (n=74), -31 (n=74), -33 (n=37) et -35 (n=58) étaient analysés par PCR-séquençage pour la totalité du gène L1. Le nombre de nucléotides substitués pour L1 variait de 19 pour VPH-33 à 52 pour VPH-31. Le rapport du nombre de variantes sur le nombre d’isolats testés était plus élevé pour VPH-31 (56.4%, p=0.05) et VPH-35 (60.3%, p=0.04) comparativement à VPH-16 (40.5%), alors que ce ratio était inférieur pour VPH-33 mais sans différence statistiquement significative (24.3%, p=0.14). La distance entre les variantes était plus grande à l’intérieur des cinq boucles présumément exposées à la surface de la protéine L1 que dans la séquence à l’extérieur (p<0.01) Des variations synonymes étaient observées chez 1.7% (95% CI 1.1- 2.3) des nucléotides intra-boucles et 2.4% (95% CI 1.2-3.7) de ceux extra-boucles. Les variations non-synonymes étaient rencontrées pour 1.8% (95% CI 1.1-2.5) des nucléotides intra-boucles et 0.2% (95% CI 0-0.4) pour les nucléotides extra-boucles. Les ratios dN/dS étaient inférieurs à 1.0 pour les régions extra-boucles et encore davantage pour les régions intra-boucles. Ces résultats suggèrent que les séquences des régions hypervariables de L1 ont été sélectionnées positivement. / The L1 gene encodes for the major capsid protein of human papillomaviruses (HPV). There is limited information on the polymorphism of L1 for types related to HPV-16. This report explores the polymorphism of L1 in phylogenetically-related types 31, 33, and 35 compared to HPV-16. Genital specimens collected from 732 HIV-seropositive and 323 HIV-seronegative women were screened for HPV DNA with consensus L1 PCR. Cervical samples positive for HPV-16 (n=74), -31 (n=78), -33 (n=37), and -35 (n=58) were further characterized by PCR-sequencing of the complete L1 gene. The number of nucleotide substitutions within L1 ranged from 19 for HPV-33 to 52 for HPV-31. The ratio of the number of variants/number of isolates tested was higher for HPV31 (56.4%, p=0.05) and HPV-35 (60.3%, p=0.04) compared to HPV-16 (40.5%), while this ratio was lower for HPV-33 (24.3%), although not significantly (p=0.14). The maximal distance between HPV variants was greater in the five putative surface-exposed loops of L1 than in sequences outside the loops (p<0.01). Synonymous variations were encountered in 1.7% (95% CI 1.1-2.3) of nucleotides inside the L1 loops and 2.4% (95% CI 1.2-3.7) of nucleotides outside the L1 loops. Non-synonymous variations were encountered in 1.8% (95% CI 1.1-2.5) of nucleotides within the L1 loops and 0.2% (95% CI 0-0.4) of nucleotides outside the loops. dN/dS ratios were below 1.0 in extra-loop and intra-loop regions, but they were lower in extra-loop regions. These results suggest that sequences within and outside the hypervariable loops of L1 were under selective constraint.

The aim of this thesis was to track the impact of selected herpesviruses, polyomaviruses, Chlamydia trachomatis and methylation of tumor supressor genes at the development and progression of high grade- lesion in HPV - positive patients by means of molecular-genetic techniques. Confirmation of these markers presence in women with severe lesions of cervix would help to raise necessary specificity of molecular genetics HPV testing and recommend it as a primary screening test for cervical carcinoma prevention. HPV testing could thus replace currently prevailing cytology which has relatively low sensitivity and therefore the number of false negative results. The analyzed samples consisted of cytological cervical smears of 51 HPV positive women, with histologically confirmed presence of severe lesions, collected in liquid medium. Samplings from 51 women without infection were used as a control. The possible effect on disease progress was confirmed only in the case of gene promoters' methylation whose presence was detected in up to 26 patients. It is, however, very unlikely that cancer would develop in all these women. This marker could thus help to stratify patients at risk but only to some extent. Although the individual effect of remaining markers has not been established in the carcinogenesis of cervical...

L’infection au papillomavirus humain (HPV) est connue pour être le principal facteur causal d’une série de maladies aussi bien bénignes (condylomatose ano-génitale, papillomatose lyringée, et autres) que malignes (cancer du col de l’utérus, certains cancers ORL, et autres). Deux vaccins prophylactiques (Gardasil® et Cervarix®) sont sur la marché depuis à peu près quatre ans pour prévenir cette infection. Le présent travail de thèse comportait trois objectifs principaux : i) étudier in-silico l’immunogénicité du vaccin Gardasil® ; ii) étudier in-silico l’histoire naturelle d’une infection à HPV et iii) évaluer in-silico le potentiel de l’hypothèse thérapeutique suivante : l’administration intramusculaire du vaccin Gardasil® chez des patients atteints d’une papillomatose laryngée induirait un effet bénéfique car l’arrivée des immunoglobulines au tissu affecté empêcherait l’HPV de compléter son cycle de vie et, par conséquent, la maladie de se propager. Les principales conclusions sont : i) pour qu’une papillomatose laryngée ne s’étende pas il faudrait, d’après nos simulations, que le taux d’IgGs sériques soit maintenu au-dessus de 200 mMU/mL ; ii) pour rester, sur une période de 10 ans, le plus longtemps possible au-dessus de ce seuil (d´effet thérapeutique), en administrant la quantité minimale de vaccin, il faudrait, d’après nos simulations, suivre le protocole suivant : l’immunisation de base (à 0, 2 et 6 mois), suivie de trois rappels successifs tous les six mois jusqu’au 24ème mois, suivis d’un rappel 18 mois plus tard ; iii) par ailleurs, il semble inutile (voire contreproductif), d’après nos simulations, de modifier le schéma traditionnel de base (0-2-6 mois) / Two prophylactic vaccines have demonstrated to prevent infections with the human papillomavirus (HPV). Thus, they have been in the market for the last four years, or so. The three main objectives of the present project were: i) to study in-silico the immunogenicity of one of these vaccines (Gardasil®); ii) to study in-silico the natural history of an HPV infection, and iii) to assess in-silico the potential of the following therapeutic hypothesis : the intramuscular administration of Gardasil® to patients already suffering from a recurrent respiratory papillomatosis would result in a better prognosis thanks to the fact that the HPV-specific immunoglobulins that would bathe the affected tissue would impede the virus to complete its life cycle and, therefore, the disease to progress. The main conclusions are: i) according to our simulations, the minimum serum IgG titer required for hampering the progression of a recurrent respiratory papillomatosis would be 200 mMU/mL ; ii) in order to keep, within a time window of ten years, the anti-HPV IgG titer over the just-mentioned therapeutic-effect threshold, the biggest possible fraction of time and through the administration of the smallest possible number of booster doses, it would be necessary, according to our simulations, to adopt the following vaccination schedule: the basic three doses (at months 0, 2 and 6), followed by three successive booster doses, every six months, until reaching the 24th month, followed by a late final booster dose, 18 months later. iii) incidentally, it would seem to be inappropriate, according to our simulations, to modify the original initial vaccination schedule (at months 0, 2 and 6)

Introdução/Objetivos: Anualmente são estimados cerca de 16.000 novos casos de câncer de colo do útero no Brasil. As novas tecnologias podem levar a uma redução deste número, permitindo não só uma expansão da população abrangida pelo rastreio, mas também melhorando a taxa de detecção de lesões precursoras. Casuística e Métodos: Mulheres com idade entre 12 e 90 anos provenientes de duas regiões da cidade de São Paulo, rotineiramente realizando seus exames citopatológicos e histopatológicos com a FOSP, foram recrutadas para este estudo no período de dezembro de 2014 até março de 2016, totalizando 15.991 amostras. As amostras foram transportadas para a FOSP onde foram submetidas paralelamente ao teste Onclarity para DNA de HPV de alto risco (HrHPV) e citologia em base líquida (LBC), ambos produtos da empresa BD (Becton-Dickinson, EUA). O ensaio BD Onclarity® HPV detecta 14 genótipos de alto risco, com identificação individual dos tipos 16, 18, 31, 45, 51, 52 e os demais tipos em três grupos distintos: P1 (HPVs 33, 58); P2 (HPVs 56, 59, 66) e P3 (HPVs 35,39,68). Mulheres com resultado citológico ASC-US ou superior e/ou positivas para HrHPV foram encaminhadas para a colposcopia e eventual biópsia a critério médico. Resultados: Entre as 15.991 amostras analisadas, 15.945 (99,7%) foram satisfatórias para a citologia, destas 7,2% (1.152/15.945) apresentaram alguma anormalidade e foram classificadas como positivas, da seguinte forma: ASC-US 546 (3,4%); ASC-H 119 (0,7%); LSIL 392 (2,5%); HSIL 87 (0,5%), dois casos (0,01%) de CEC e seis (0,04%) de AGC. O teste molecular para a pesquisa do HrHPV mostrou 2.398 (15 %) amostras positivas. O DNA do HPV foi detectado em 12,1% das citologias classificadas como negativas, em 31,1% dos casos de ASC-US; 58,8% de ASC-H; 73,2% de LSIL; 87,4% dos casos de HSIL, nas duas amostras classificadas como CEC e em 16,7% das AGC. Os tipos de HPVs mais frequentes foram representados pelo grupo P3 em 3,8% das amostras seguidos do grupo P2 em 3,6%; HPV 16 (3,2%); HPV 52 (2,4%); grupo P1 (2,3%); HPV 31 (1,9%); HPV 51 (1,4%); HPV 18 (1,2%) e HPV 45 (0,9%). Pelo protocolo, 2.309 (14,4%) amostras foram encaminhadas para a colposcopia e destas 1.287 (55,7%) realizaram o procedimento. Trezentos e trinta e quatro foram biopsiadas, revelando 147 (44%) resultados histopatológicos alterados, distribuídos da seguinte forma: 75 (51%) casos de NIC 1; 59 (40,1%) de NIC 2; sete (4,8%) de NIC 3; dois (1,4%) de Carcinomas in situ; dois (1,4%) de Carcinomas epidermóides invasivos (CEC) e dois (1,4%) de Adenocarcinomas. O DNA do HPV foi detectado em 98,6% (71/72) dos casos de NIC 2+, destes, 18 apresentaram citologias negativas, incluindo um adenocarcinoma. Entre os casos de NIC 3+ (N=13), o HrHPV foi detectado em 100% sendo o HPV 16 o mais frequente, presente em 53,8% (7/13) enquanto a citologia foi negativa em dois destes. Conclusões: O teste de DNA do HPV detectou um número significativo de pacientes com lesões pré-malignas não detectadas por citologia. Ainda, a citologia forneceu uma classificação que de acordo com o algoritmo atual, atrasaria a detecção de NIC2 + devido a adição de um ciclo de citologia repetida em 6 meses - 1 ano. Se for adotado o rastreamento por DNA do HPV, de modo a evitar um aumento na demanda de exames colposcópicos, será muito importante adicionar um marcador de valor preditivo positivo elevado às amostras HrHPV+ antes de referir à colposcopia. O limite inferior de idade de 30 anos para o rastreamento baseado em HPV empregado na Europa provavelmente não é ideal para o Brasil, onde não é incomum observar-se mulheres jovens com NIC 2 +. As taxas de NICs verificadas permitiram uma avaliação robusta dos ensaios, algoritmos e estratégias de gestão. O uso da genotipagem 16/18 e triagem citológica para os demais HrHPVs forneceu um equilíbrio entre sensibilidade e especificidade, número de testes e colposcopias requeridas para detecção de NIC 2+, e pode ser uma alternativa de uso combinado dos dois testes. A implantação na rede pública é viável mas deve ser previamente analisada sua custo-efetividade / Background/Objectives: Every year there are approximately 16,000 new cases of cervical cancer in Brazil. New technologies may lead to a reduction of this number by allowing an expansion of the screening covered population but also by improving the detection rate of precursor lesions. Methods: Women participating in a routine CC primary screening program were invited to enroll in this study. An LBC sample was collected in SurePath medium and transported to Fundação Oncocentro where BD Totallis prepared, in parallel, slides for cytology and an aliquot for the BD Onclarity(TM) HPV Assay (HrHPV). A positive HrHPV test and/or cytology class > ASC-US referred the patient to colcoscopic examination and biopsy, if found necessary by the clinican. Results: In between December 2014 and March 2016 15,991 women joined this study. Among samples analyzed, 15,945 (99.7%) were satisfactory for cytology, of these 7.2% (1,152/ 15,945) had some abnormality and were classified as positive, as follows: ASC-US 546 (3.4 %); ASC-H 119 (0.7%); LSIL 392 (2.5%); HSIL in 87 (0.5%), two cases (0.01%) of ICC and six (0.04%) of AGC. HPV DNA testing showed 2,398 (15%) positive samples, detected in 12.1% of the samples cytology classified as NILM, in 31.1% of ASC-US cases; 58.8% ASC-H; 73.2% LSIL; 87.4% of the cases of HSIL, in 100% samples classified as ICC and in 16.7% of the AGC. The most frequent HPV types were represented by the P3 group in 3.8% of these, followed by the P2 group in 3.6%; HPV 16 (3.2%); HPV 52 (2.4%); P1 group (2.3%); HPV 31 (1.9%); HPV51 (1.4%); HPV 18 (1.2%) and HPV 45 (0.9%). By protocol, 2,309 (14.4%) were referred to colposcopic study and 1,287 (55.7%) submitted to the procedure. Of these 334 samples were biopsied, revealing 147 (44%) positive results distributed as follows: 75 (51%) cases of CIN 1; 59 (40.1%) of CIN 2; 7 (4.8%) of CIN 3; 2 (1.4%) SCC; 2 (1.4%) of ICC and 2 (1.4%) of adenocarcinomas. HrHPV was detected in 98.6% (71/72) cases of CIN 2+, of these, 18 were negative by cytology, including an adenocarcinoma and was present in 100% of the 13 cases of CIN 3+, whereas cytology missed two of them. Among CIN3+ cases HPV 16 was the most frequent type, found in 53.8% (7/13). Conclusions: HPV DNA testing detected a significant number of patients with premalignant lesions missed by cytology. In another fraction, cytology provided a classification that would, according to the current algorithm, delay the CIN2+ detection due to a loop of repeating cytology in 6 mo - 1 year. If HPV DNA screening is to be adopted, it will be a challenge to avoid an increase in the need for colposcopic examinations. Towards that, it will be very important to add one marker of high positive predictive value to HrHPV+ samples, before referral and analyzed in the same primary cervical smear. The European age cut-off of 30 yo for HPV based-screening is probably not ideal in Brazil, where is not uncommon to observe young women with CIN2+. The CIN rate allowed a thorough evaluation of the assays and management strategies. The use of 16/18 HPV genotyping and cytological triage for the other HrHPVs provided a balance between sensitivity and specificity, number of tests and colposcopies required for detection of CIN 2+. The implementation in the public health system is feasible upon a positive cost effectiveness evaluation

O desenvolvimento do câncer cervical está associado à infecção por alguns tipos de Papilomavírus Humano (HPV). Entre os mecanismos de carcinogênese associados ao HPV incluem-se alterações em moléculas que modulam a manutenção de componentes da matriz extracelular (MEC), como as metaloproteinases de matriz (MMP) e alguns de seus reguladores. A proteína RECK (reversion inducing cysteine rich protein with kazal motifs) apresenta função essencial na remodelação tecidual e na angiogênese fisiológica ou tumoral, através da regulação pós-transcricional da atividade de MMP-2, MMP-9 e MMP-14 (MT1-MMP). Resultados publicados previamente por nosso grupo apontam para a correlação entre a expressão da oncoproteína E7 de HPV16, a alta expressão e atividade de MMP-9 e a baixa expressão de seus reguladores, TIMP-2 e RECK. A expressão de RECK também é baixa em lesões do colo uterino de alto grau e em amostras de câncer cervical, quando comparadas a amostras de pacientes com cervicite. O presente estudo visa determinar o papel de RECK no processo de tumorigênese mediado por HPV. Para isto, estabelecemos linhagens derivadas de tumor de colo de útero (SiHa, SW756 e C33A) que superexpressam RECK a partir de transdução com lentivírus. Os efeitos da superexpressão de RECK sobre o potencial tumorigênico de SiHa, SW756 e C33A foram avaliados em modelos de estudo in vivo e in vitro. De maneira geral, a superexpressão de RECK foi associada com a capacidade reduzida de invasão em câmara de Matrigel® e de formação de colônia independente de ancoragem. Ainda, camundongos nude inoculados s.c. com células tumorais superexpressando RECK apresentaram atraso no estabelecimento e crescimento tumoral e sobrevida global estendida quando comparados aos controles. Ambos tumores derivados de SiHa RECK e SW756 RECK apresentaram redução na frequência de células tumorais e endoteliais, ao passo que mostrarm aumento no infiltrado inflamatório. Esta observação foi acompanhada de redução na população de neutrófilos e potenciais células mieloderivadas supressoras em tumores de ambas as linhagens. Em tempo, analisamos séries de dados de expressão de CIN e carcinomas cervicais do banco de dados GEO e verificamos que a hipermetilação do gene RECK e a inibição da expressão de mRNA de RECK são eventos precoces no desenvolvimento do câncer de colo de útero. Avaliamos que a baixa expressão de RECK foi associada a progressão de lesões CIN3+ e ao aumento de metástases em linfonodo pélvico em pacientes com câncer de colo de útero. Ademais, notamos que o tratamento com quimio radioterapia levou ao aumento dos níveis de mRNA de RECK em um outro grupo de pacientes com câncer de colo de útero. Concluímos que a superexpressão de RECK (i) reduz o potencial tumorigênico de linhagens celulares derivadas de colo de útero independente do status de infecção por HPV e que (ii) o seu efeito sobre as populações intratumorais se mostrou específico para as linhagens infectadas por HPV. Estes resultados apontam para uma possível interação entre as alterações no microambiente tumoral associadas ao HPV e a função de RECK. Finalmente, a regulação negativa da expressão de RECK é um evento precoce na história natural do câncer cervical. / Persistent infection with high-risk Human Papillomavirus (HPV) types is the main etiologic factor for the development of cervical cancer. The HPV carcinogenic mechanisms include alterations in extracellular matrix (ECM) components, as matrix metalloproteinases (MMP) and its regulators. The Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) plays a central role on tissue remodeling, tumor angiogenesis and exert inhibitory effects on the transcription, synthesis, activation and activity of MMP-2, MMP-9 e MMP-14 (MT1-MMP). As previously published by our group, it has been observed a correlation between the HPV16 E7 oncoprotein expression, the up-regulation of MMP-9 and the down-regulation of its inhibitors, RECK and tissue inhibitor of metalloproteinases 2 (TIMP-2). Also, RECK expression was downregulated in cervical intraepithelial neoplasias grades 2 and 3 (CIN2/3) and invasive carcinoma samples levels when compared with clinical samples of pacients diagnosed with cervicitis. The present study aims to determine the role of RECK in HPV mediated tumorigenesis. In order to do so, we generated cervical tumors derived cell lines (SiHa, SW756 e C33A) superexpressing RECK by lentiviral transduction followed by FACS. We assessed the effects of RECK superexpression in the tumorigenic potential of SiHa, SW756 e C33A using both in vitro and in vivo protocols. Overall, RECK superexpression is associated with reduced chamber invasion and reduced anchorage independent colony formation. Moreover, nude mice injected s.c. with RECK superexpressing tumor cells presented (i) delayed tumor establishment and (ii) increased overall survival, when compared with controls. Both SiHa and SW756 superexpressing RECK presented decreased frequency of tumor and endothelial cells, whilst showed increase in inflammatory infiltrate population. This observation was followed by a decrease in potential myeloid derived suppressor cell and neutrophil populations in both SiHa RECK and SW756 RECK tumors. Additionally, we observed hipermethylation and premature and consistent downregulation of RECK mRNA expression in CIN and cervical cancer expression datasets from GEO database. We observed that reduced RECK expression was associated with CIN3+ progression and increased pelvic lymph node metastasis in cervical cancer patients. Furthermore, we found that chemo radiotherapy treatment led to increased levels of mRNA in another set of cervical cancer patients. We conclude that RECK superexpression reduces the tumorigenic potential of cervical cancer derived cell lines regardless of HPV infection status. However, we found that the effect of RECK over the intratumoral cells populations is specific to HPV infected tumor cell lines. These results points to a possible interaction between HPV associated tumor microenvironment alterations and RECK. Finally, RECK downregulation is an early event in the natural history of cervical cancer.