Attitudes and beliefs on HPV infection and vaccination II Veronika Regnerová, PharmDr. Eva Zimčíková, Ph.D. Background: Cervical cancer is the second most common type of cancer in women. The majority of cervical cancer cases are caused by human papillomavirus (HPV). Three vaccines have been approved to prevent HPV infection and related diseases. Objectives: The study aimed to analyse the knowledge and attitudes regarding HPV, cervical cancer and HPV vaccination in secondary school students in the Czech Republic. Methods: The study was carried out in May 2017 at four secondary schools. A questionnaire used for data collection comprised 15 items including questions on demographic characteristics, knowledge about cervical cancer and HPV, vaccination coverage, HPV perceived susceptibility and seriousness, and beliefs on HVP vaccination. Results: A total of 667 students participated (mean age: 16.8 y ± 1.18; 63% female); 20.5% were smokers, 24.7% God believers. Most of the students (97.0%) heard about cervical cancer and penile cancer, significant proportion (68.3%) knew HPV was the causative factor. Half of the respondents (49.9%) have heard about vaccination against HPV. Among cervical cancer risk factors HPV infection was reported in 58.1% cases followed by promiscuity (14.5%), irregular...

ATTITUDES AND KNOWLEDGE OF HPV INFECTION AND VACCINATION Author: Dominika Blašková Supervisor: PharmDr. Eva Zimčíková, Ph.D. INTRODUCTION Human papillomavirus (HPV) is a DNA virus. The virus causes benign and malignant diseases of men and women such as laryngeal papillomatosis, genital warts, oropharyngeal carcinoma, cervical cancer, penile cancer and anus cancer. HPV can be prevented by appropriate precautionary measures. The main preventative method is vaccination against HPV. Besides vaccination, regular screening is necessary to detect premalignant changes on time. AIMS The aim of the theoretical part of the diploma thesis was to summarize the information about HPV, the diseases caused by human papillomavirus and vaccination against HPV, the main preventive measure. The primary aim of the practical part was to find out the level of HPV awareness among girls and boys and diseases caused by HPV. The secondary aim of the practical part was to find out opinions on HPV vaccination and determine the rate of vaccination against HPV among young people in Slovakia. METHODS The method of quantitative research taken in the form of a questionnaire was used in the diploma thesis. The survey was realized at two secondary schools in Svidník, Slovakia. The age range of respondents was 15-20 years. The data...

The aim of this research was to study the correlation between tissue tumor marker expression and HR-HPV infection, smoking, hormonal contraceptive use and sex steroids in women with cervical intraepithelial neoplasia or normal epithelium. The study investigated the expression of 11 tumor markers in cervical biopsies obtained from 228 women with different diagnoses ranging from normal cervical epithelium to various stages of CIN. 188 women were recruited at our colposcopy clinic (out-patient surgery, Department of Obstetrics and Gynecology, Falun Hospital) for laser cervical conization or a directed punch biopsy, either because of a vaginal smear (Pap smear) that showed cytological findings suggesting CIN, or because of repeated findings showing atypical squamous cells of undetermined significance (ASCUS). For 40 volunteers, punch biopsies were taken from the normal cervical epithelium. The time period for this study was 2005-2007. Study I :  228 women, of whom 116 were tested, 64 were positive to HR-HPV. The results showed that Ki67 tumor cell proliferation index was the only marker that independently correlated to both the presence of HR-HPV and the severity of cervical lesions. Study II:  228 women, of whom 83 were smokers (36, 9%). Smokers showed lower expression of p53, FHIT (tumor suppressor markers) and interleukin-10 .Higher expression of Cox-2 and Ki-67 (tumor proliferation markers). Study III:  195 women who were premenopausal. There was increased p53 expression (tumor suppressor) in the progestin-IUD users compared to non-users. Decreased IL-10 expression (immunological marker) was observed in both COC users and any progestin-only users. Study IV: Serum from 80 premenopausal women was available. The main finding was that the increased levels of serum progesterone and estradiol were associated with increased Cox-2 expression (proliferation marker). Serum progesterone and estradiol levels influence cellular and extracellular proteins which have been associated with neoplastic development in normal epithelium and CIN. Conclusion: The results of these studies support previous epidemiological findings on the role of smoking, contraceptive use and sex steroids as co-factors in development of CIN and that tumor marker expression varies in different grades of CIN.

Orientador: Márcia Guimarães da Silva / Resumo: Objetivo: O objetivo do presente estudo foi identificar determinantes do clearance da infecção pelo Papilomavírus Humano (HPV) em mulheres brasileiras em idade reprodutiva. Métodos: Trata-se de estudo de coorte denominado HPV-UNESP, no qual 1638 mulheres em idade reprodutiva foram recrutadas no período de setembro de 2012 e janeiro de 2013. Desse total, 544 mulheres positivas para a infecção pelo HPV participaram do seguimento longitudinal durante 30 meses, em mais 4 visitas. A infecção por HPV foi definida como detecção de qualquer um dos 36 genótipos testados pelo Linear Array Genotyping Test (Roche Molecular Systems, Inc.) e o desfecho de interesse foi o clearance da infecção, definido como a eliminação da infecção pelo HPV por, pelo menos, duas visitas consecutivas. Um questionário estruturado com 58 questões relativas à dados sociodemográficos, características comportamentais e ginecológicas foi aplicado em cada visita. Imediatamente após a entrevista, todas as mulheres realizaram exame ginecológico, no qual, após inserção de espéculo de Collins, não lubrificado, foi aferido o pH vaginal com fita (pH 4.0-7.0, Merck, Germany) no terço médio da parede vaginal. Para avaliação da microbiota vaginal, amostras foram coletadas com swab da parede vaginal e o padrão de microbiota foi classificado de acordo com os critérios de Nugent et al. (1991). O whiff test realizado por adição de solução de 10% de KOH ao conteúdo vaginal foi interpretado como positivo, negativo ou duvidoso. A... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: The objective of the present study was to identify determinants of Human Papillomavirus (HPV) infection clearance in Brazilian women of reproductive age. Methods: This is a cohort study called HPV-UNESP, in which 1638 women of reproductive age were recruited from September 2012 to January 2013. Of this total, 544 women positive for HPV infection participated in longitudinal follow-up for 30 months, in 4 more visits. HPV infection was defined as detection of any of the 36 genotypes tested by the Linear Array Genotyping Test (Roche Molecular Systems, Inc.) and the outcome of interest was infection clearance, defined as the elimination of HPV infection by least two consecutive visits. A structured questionnaire with 58 questions regarding sociodemographic data, behavioral and gynecological characteristics was applied at each visit. Immediately after the interview, all women underwent a gynecological exam, in which, after insertion of the non-lubricated Collins speculum, the vaginal pH with tape (pH 4.0-7.0, Merck, Germany) was measured in the middle third of the vaginal wall. For vaginal microbiota evaluation, samples were collected with vaginal wall swab and the microbiota pattern was classified according to the criteria of Nugent et al. (1991). The whiff test performed by adding 10% KOH solution to the vaginal content was interpreted as positive, negative or doubtful. Endocervical samples were collected with cytobrush for molecular analysis of HPV, Chlamydia trachom... (Complete abstract click electronic access below) / Doutor

Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2016-03-04T17:16:30Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) MICHELINE OLIVEIRA LOBO PEREIRA DA COSTA- TESE DOUTORADO -23-10-2015.pdf: 15371820 bytes, checksum: 4afd4b560150641ba2dc59721bbb563e (MD5) / Made available in DSpace on 2016-03-04T17:16:30Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) MICHELINE OLIVEIRA LOBO PEREIRA DA COSTA- TESE DOUTORADO -23-10-2015.pdf: 15371820 bytes, checksum: 4afd4b560150641ba2dc59721bbb563e (MD5) Previous issue date: 2015-01-23 / CAPES / O presente estudo avaliou o desempenho da metodologia citológica de base líquida (ThinPrep-TP) com o da citologia convencional de Papanicolaou (CC) no diagnóstico de alterações citopatológicas e de resultados insatisfatórios, sob a visão de um serviço público no estado de Pernambuco (LACEN-PE) e da Fundação Oncocentro de São Paulo (FOSP-SP). Também foram avaliadas as associações entre a presença de coinfecções genitais dos subtipos de Human papillomavirus (HPV) com Chlamydia trachomatis (CT) e/ou outras microfloras, com os diferentes estágios de alterações cervicais das pacientes. A população do estudo foi de 525 mulheres na faixa etária dos 18-65 anos, atendidas por demanda espontânea, pelas Unidades Básicas de Saúde no Estado de Pernambuco, no período de abril a novembro de 2011. Um questionário padronizado com informações sobre características sociodemográficas, sexuais, reprodutivas e de hábitos (tabagismo, consumo de bebidas alcoólicas e uso de drogas) foram obtidos de todas as pacientes do estudo. A presença de DNA do HPV e da CT foram diagnósticadas através da reação em cadeia da polimerase (PCR) e o exame citológico foi realizado para detecção das demais infecções. Para avaliar a relação das infecções genitais com a presença de alterações intraepiteliais cervicais, foi utilizado o teste exato de Fisher. Os resultados mostraram que 11,05% das pacientes tinham menos de 25 anos, 30,86% eram solteiras, 6,86% tiveram mais de 5 parceiros sexuais, 44% não faziam uso de métodos contraceptivos, 38,85% eram usuárias de álcool, 24,38% eram fumantes e 3,24% haviam consumido drogas. Além disso, 42,01% tinham queixas ginecológicas; e 12,19% história pregressa de doenças sexualmente transmissíveis (DST). Quando comparadas a eficiência das técnicas TP e CC sob a visão do LACEN-PE, observou-se que as duas metodologias avaliadas apresentaram fraca concordância entre os métodos (k=0,19;95%IC(0,11-0,26); p<<0,001). A metodologia TP reduziu a taxa de resultados insatisfatórios de 4,38% para 1,71% (×2= 5,28; p=0,02), e o número de alterações citopatológicas diagnosticadas aumentaram de 2,47% para 3,04%. Porém sob a avaliação da FOSP-SP, as duas metodologias apresentaram concordância (k=0,39;95%IC(0,29-0,50); p<<0,001). A metodologia TP apresentou taxas insatisfatórias e praticamente semelhantes de 3,20% para 3,60% (×2= 5,00; p=0,17), e de alterações citopatológicas de 5,60% para 4,20%. Em 87 casos, foram observadas alterações cervicais por uma das metodologias utilizadas; destas, em 83,91% foram detectados CT e 82,76% foram positivas para HPV, ocorrendo coinfecção em 65 casos (74,7%). Em 93,1% dos casos houveram alterações colposcópicas, observando-se uma associação estatisticamente significativa entre coinfecção HPV-CT e presença de lesão (p=0.037). Outras microfloras encontradas foram Gardnerella vaginalis (35,6%), cocos (18,4%), Candida sp (9,2%), Trichomonas vaginalis (6,9%), Lactobacillus sp (4,6%) e herpesvírus (1,15%). Flora mista (coinfecção por várias microfloras – com exceção de CT simultaneamente) ocorreram em 41,38% dos casos. No entanto, nenhuma associação da presença desses microrganismos não-virais e os herpesvírus com a gravidade das lesões intraepiteliais foram encontradas. Os subtipos de HPV mais frequentes foram 16 e 31 (34,3% e 17,15%, respectivamente). Porém nas lesões de maior gravidade, os mais prevalentes foram 16 e 18. Desta forma, concluimos que este estudo demonstra a superioridade da metodologia TP no diagnóstico citológico das amostras cervicais o que poderá contribuir na diminuição de possíveis perdas por repetição citológica e seguimento das pacientes. É importante chamar atenção para as infecções genitais, em especial a CT, que devem sem investigadas e tratadas adequadamente, haja vista, que coinfecções com o HPV estão associadas ao favorecimento de lesões cervicais, e podem evoluir a graus mais avançados. / This study evaluated the performance of cytological methodology net basis (ThinPrep-TP) with the conventional Pap cytology (CC) in the diagnosis of cytopathological findings and unsatisfactory results under the vision of a public service in the state of Pernambuco (LACEN -PE) and Oncocentro Foundation of São Paulo (FOSP-SP). We also evaluated whether there is an association between the presence of genital co-infections of human papillomavirus subtypes (HPV) with Chlamydia trachomatis (CT) and or other microflora, with the different stages of cervical abnormalities of patients. The study population of 525 women between the ages of 18-65 years, assisted by spontaneous demand, the Basic Health Units in the State of Pernambuco, in the period from April to November 2011. A standardized questionnaire with information on sociodemographic characteristics, sexual, reproductive habits (such as smoking, alcohol consumption and drug use) were obtained from all study patients. The presence of HPV DNA and CT were both diagnosed by polymerase chain reaction (PCR) and cytological examination was performed to detect other infections. To evaluate the relationship of genital infections with the presence of cervical intraepithelial changes, Fisher's exact test was used. The results showed that 11.05% of patients were under 25yrs, 30.86% were single, 6.86% had more than five sexual partners, 44% did not use contraception, 38.85% were users of alcohol, 24.38% smokers and 3.24% had used drugs before. Moreover, gynecological complaints were 42.01%; and 12.19% history of STD. When comparing the efficiency of two techniques used in diagóstico of cervical abnormalities in the view of LACEN-PE, it was observed that the two methodologies evaluated showed poor agreement between the methods (k = 0.19; 95% CI (0,11- 0.26), p << 0.001). TP method reduced the rate of unsatisfactory 4.38% to 1.71% (5.28 = 2 × p = 0.02) and the number of cytopathological changes diagnosed increased 2.47% to 3 04%. But in the assessment of FOSP-SP, the two methodologies showed reasonable agreement (k = 0.39; 95% CI (0.29 to 0.50); p << 0.001) .The TP methodology showed unsatisfactory results virtually rates similar 3.20% to 3.60% (× 2 = 5.00; p = 0.17), and cytological changes from 5.60% to 4.20%. In 87 cases, cervical abnormalities were observed by any of the methods used, and of these, 83.91% were detected CT, and 82.76% were positive for HPV, occurring co-infection in 65 cases (74.7%). In 93.1% of cases there were colposcopic changes, observing a statistically significant association between co-infection HPV-CT and presence of lesions (p = 0.037). Other microflora were found Gardnerella vaginalis (35.6%), coconut (18.4%), Candida sp (9.2%), Trichomonas vaginalis (6.9%), Lactobacillus sp (4.6%) and herpesviruses (1.15%). Mixed flora (co-infection with various microflora - CT exception with both) occurred in 41.38% of cases. However, no association between the presence of non-viral organisms and herpesviruses with the severity of intraepithelial lesions were found. The most common HPV subtypes there were 16 and 31 (34.3% and 17.15%, respectively). But in more severe injuries, the most prevalent were 16 and 18. Thus, we conclude that this study demonstrates the superiority of TP methodology in the cytological diagnosis of cervical samples which could contribute to decrease possible losses by repetition and cytologic follow-up of patients . It is important to draw attention to the genital infections, especially CT, which are not investigated and dealt with appropriately, given that co-infections with HPV are associated with the favoring of cervical lesions, and can progress to more advanced degrees.

O câncer de colo do útero é o terceiro tipo de câncer mais frequente em mulheres no mundo, e a infecção persistente pelo papilomavirus humano (HPV) oncogênico é condição necessária, mas não suficiente para seu desenvolvimento. As oncoproteínas virais E6 e E7 interferem direta ou indiretamente na ação de várias proteínas celulares. Entretanto, as variantes proteicas, resultantes de polimorfismos genéticos, podem apresentar comportamento distinto mediante a infecção pelo HPV. O objetivo deste estudo foi avaliar possíveis associações entre polimorfismos nos genes TP53 (p53 PIN3, p53 72C>G) e p21 (p21 31C>A) e o desenvolvimento de neoplasias cervicais, considerando os níveis de expressão das proteínas p53, p21, p16 e ciclina D1, e fatores de risco clássicos para o câncer cervical. Foram selecionadas 466 mulheres residentes no Rio de Janeiro, 281 com diagnóstico histopatológico de neoplasia cervical de baixo (LSIL) e alto grau (HSIL) e câncer (grupo de casos) e 185 sem história atual ou pregressa de alteração citológica do colo uterino (grupo controle). A técnica de PCR-RFLP (reação em cadeia da polimerase - polimorfismo de comprimento de fragmento de restrição), foi empregada na análise dos polimorfismos p53 72C>G e p21 31C>A, usando as enzimas de restrição BstUI e BsmaI, respectivamente. A avaliação do polimorfismo p53 PIN3 (duplicação de 16 pb) foi feita por meio da análise eletroforética direta dos produtos de PCR. A expressão das proteínas p53, p21, p16, ciclina D1 e Ki-67 e a pesquisa de anticorpos anti-HPV 16 e HPV pool foram avaliadas por imunohistoquímica (Tissue Microarray - TMA) em 196 biópsias do grupo de casos. O grupo controle se mostrou em equilíbrio de Hardy-Weinberg em relação aos três polimorfismos avaliados. As distribuições genotípicas e alélicas relativas a p53 PIN3 e p53 72C>G nos grupos controles e de casos não apresentaram diferenças significativas, embora o genótipo p53 72CC tenha aumentado o risco atribuído ao uso de contraceptivos das pacientes apresentarem lesões mais severas (OR=4,33; IC 95%=1,19-15,83). O genótipo p21 31CA(Ser/Arg) conferiu proteção ao desenvolvimento de HSIL ou câncer (OR=0,61, IC 95%=0,39-0,97), e modificou o efeito de fatores de risco associados à severidade das lesões. A interação multiplicativa de alelos mostrou que a combinação p53 PIN3A1, p53 72C(Pro) e p21 31C(Ser), representou risco (OR=1,67, IC95%=1,03-2,72) e a combinação p53 PIN3A1, p53 72C(Pro) e p21 31A(Arg) conferiu efeito protetor (OR=0,26, IC95%=0,08-0,78) para o desenvolvimento de HSIL e câncer cervical. Observou-se correlação positiva da expressão de p16 e p21 e negativa da ciclina D1 com o grau da lesão. A distribuição epitelial de p16, Ki-67, p21 e p53 se mostrou associada à severidade da lesão. Os polimorfismos analisados não apresentaram associação com a expressão dos biomarcadores ou positividade para HPV. Nossos resultados sugerem a importância do polimorfismo p21 31C>A para o desenvolvimento das neoplasias cervicais e ausência de correlação dos polimorfismos p53 PIN3 e p53 72C>G com a carcinogênese cervical, embora alguns genótipos tenham se comportado como modificadores de risco. Nossos resultados de TMA corroboram o potencial de uso de biomarcadores do ciclo celular para diferenciar as lesões precursoras do câncer cervical. / Cervical cancer is the third most common female cancer worldwide, and persistent infection by the Human Papillomavirus (HPV) is a necessary but not sufficient condition to cause it. The viral oncoproteins E6 and E7 interfere directly or indirectly with the action of various cellular proteins. However, the protein variants, resulting from genetic polymorphisms, may act differently when encountering HPV infection. The aim of this study was to evaluate possible associations between polymorphisms in the TP53 (p53 PIN3, p53 72C>G) and p21 (p21 31C>A) genes, and the development of cervical neoplasia, considering the expression levels of p53, p21, p16 and cyclin D1 proteins, together with classic risk factors for cervical cancer. A total of 466 women resident in Rio de Janeiro were selected, being 281 with histopathological diagnosis of low (LSIL) or high grade (HSIL) cervical neoplasia or cancer (test group), and 185 with no current or previous history of alteration of cervical cytology (control group). The PCR-RFLP technique (polymerase chain reaction restriction fragment length polymorphism) was used to analyze the p53 72C>G and p21 31C>A polymorphisms, using BstUI and BsmaI restriction enzymes, respectively. Genotyping of the p53 PIN3 (duplication of 16 pb) polymorphism was performed by direct electrophoretic analysis of the PCR products. The expression of p53, p21, p16, cyclin D1 and Ki-67 proteins and the study of anti-HPV 16 and anti-HPV pool positivities were evaluated by immunohistochemisty (Tissue Microarray - TMA) in 196 biopsies of cases. The control group obeyed the Hardy-Weinberg principle in relation to the three polymorphisms analysed. The genotypic and allelic frequencies regarding p53 PIN3 and p53 72C>G in the control and test groups were not significantly different, although the p53 72CC genotype has increased the risk of more severe lesions attributed to the use of contraceptives (OR=4.33; IC 95%=1.19-15.83). The p21 31CA(Ser/Arg) genotype showed to protect against the development of HSIL or cancer (OR=0,61, IC 95%=0,39-0,97), and modified the effect of risk factors associated to the lesion severity. The multiplicative interaction of alleles showed that the combination p53 PIN3A1, p53 72C(Pro) and p21 31C(Ser) represented risk (OR=1,67, IC95%=1,03-2,72) and the combination p53 PIN3A1, p53 72C(Pro) and p21 31A(Arg) conferred protection (OR=0,26, IC95%=0,08-0,78) against the development of HSIL and cervical cancer. It was observed positive and negative correlations of, respectively, p16 and p21, and cyclin D1 expression with the cervical lesion grade. The epithelial distribution of p16, Ki-67, p21 and p53 was associated with the lesion severity. The polymorphisms analyzed showed neither association with the expression of the biomarkers nor positivity for HPV. Our results suggest the importance of polymorphism p21 31C>A in the development of cervical neoplasia and the lack of correlation between the polymorphisms p53 PIN3 and p53 72C>G with cervical carcinogenesis, although some genotypes acted as risk modifiers. Our TMA results corroborated the potential use of cell cycle biomarkers as an adjunctive tool to differentiate cervical precursor lesions.

O câncer de colo do útero é o terceiro tipo de câncer mais frequente em mulheres no mundo, e a infecção persistente pelo papilomavirus humano (HPV) oncogênico é condição necessária, mas não suficiente para seu desenvolvimento. As oncoproteínas virais E6 e E7 interferem direta ou indiretamente na ação de várias proteínas celulares. Entretanto, as variantes proteicas, resultantes de polimorfismos genéticos, podem apresentar comportamento distinto mediante a infecção pelo HPV. O objetivo deste estudo foi avaliar possíveis associações entre polimorfismos nos genes TP53 (p53 PIN3, p53 72C>G) e p21 (p21 31C>A) e o desenvolvimento de neoplasias cervicais, considerando os níveis de expressão das proteínas p53, p21, p16 e ciclina D1, e fatores de risco clássicos para o câncer cervical. Foram selecionadas 466 mulheres residentes no Rio de Janeiro, 281 com diagnóstico histopatológico de neoplasia cervical de baixo (LSIL) e alto grau (HSIL) e câncer (grupo de casos) e 185 sem história atual ou pregressa de alteração citológica do colo uterino (grupo controle). A técnica de PCR-RFLP (reação em cadeia da polimerase - polimorfismo de comprimento de fragmento de restrição), foi empregada na análise dos polimorfismos p53 72C>G e p21 31C>A, usando as enzimas de restrição BstUI e BsmaI, respectivamente. A avaliação do polimorfismo p53 PIN3 (duplicação de 16 pb) foi feita por meio da análise eletroforética direta dos produtos de PCR. A expressão das proteínas p53, p21, p16, ciclina D1 e Ki-67 e a pesquisa de anticorpos anti-HPV 16 e HPV pool foram avaliadas por imunohistoquímica (Tissue Microarray - TMA) em 196 biópsias do grupo de casos. O grupo controle se mostrou em equilíbrio de Hardy-Weinberg em relação aos três polimorfismos avaliados. As distribuições genotípicas e alélicas relativas a p53 PIN3 e p53 72C>G nos grupos controles e de casos não apresentaram diferenças significativas, embora o genótipo p53 72CC tenha aumentado o risco atribuído ao uso de contraceptivos das pacientes apresentarem lesões mais severas (OR=4,33; IC 95%=1,19-15,83). O genótipo p21 31CA(Ser/Arg) conferiu proteção ao desenvolvimento de HSIL ou câncer (OR=0,61, IC 95%=0,39-0,97), e modificou o efeito de fatores de risco associados à severidade das lesões. A interação multiplicativa de alelos mostrou que a combinação p53 PIN3A1, p53 72C(Pro) e p21 31C(Ser), representou risco (OR=1,67, IC95%=1,03-2,72) e a combinação p53 PIN3A1, p53 72C(Pro) e p21 31A(Arg) conferiu efeito protetor (OR=0,26, IC95%=0,08-0,78) para o desenvolvimento de HSIL e câncer cervical. Observou-se correlação positiva da expressão de p16 e p21 e negativa da ciclina D1 com o grau da lesão. A distribuição epitelial de p16, Ki-67, p21 e p53 se mostrou associada à severidade da lesão. Os polimorfismos analisados não apresentaram associação com a expressão dos biomarcadores ou positividade para HPV. Nossos resultados sugerem a importância do polimorfismo p21 31C>A para o desenvolvimento das neoplasias cervicais e ausência de correlação dos polimorfismos p53 PIN3 e p53 72C>G com a carcinogênese cervical, embora alguns genótipos tenham se comportado como modificadores de risco. Nossos resultados de TMA corroboram o potencial de uso de biomarcadores do ciclo celular para diferenciar as lesões precursoras do câncer cervical. / Cervical cancer is the third most common female cancer worldwide, and persistent infection by the Human Papillomavirus (HPV) is a necessary but not sufficient condition to cause it. The viral oncoproteins E6 and E7 interfere directly or indirectly with the action of various cellular proteins. However, the protein variants, resulting from genetic polymorphisms, may act differently when encountering HPV infection. The aim of this study was to evaluate possible associations between polymorphisms in the TP53 (p53 PIN3, p53 72C>G) and p21 (p21 31C>A) genes, and the development of cervical neoplasia, considering the expression levels of p53, p21, p16 and cyclin D1 proteins, together with classic risk factors for cervical cancer. A total of 466 women resident in Rio de Janeiro were selected, being 281 with histopathological diagnosis of low (LSIL) or high grade (HSIL) cervical neoplasia or cancer (test group), and 185 with no current or previous history of alteration of cervical cytology (control group). The PCR-RFLP technique (polymerase chain reaction restriction fragment length polymorphism) was used to analyze the p53 72C>G and p21 31C>A polymorphisms, using BstUI and BsmaI restriction enzymes, respectively. Genotyping of the p53 PIN3 (duplication of 16 pb) polymorphism was performed by direct electrophoretic analysis of the PCR products. The expression of p53, p21, p16, cyclin D1 and Ki-67 proteins and the study of anti-HPV 16 and anti-HPV pool positivities were evaluated by immunohistochemisty (Tissue Microarray - TMA) in 196 biopsies of cases. The control group obeyed the Hardy-Weinberg principle in relation to the three polymorphisms analysed. The genotypic and allelic frequencies regarding p53 PIN3 and p53 72C>G in the control and test groups were not significantly different, although the p53 72CC genotype has increased the risk of more severe lesions attributed to the use of contraceptives (OR=4.33; IC 95%=1.19-15.83). The p21 31CA(Ser/Arg) genotype showed to protect against the development of HSIL or cancer (OR=0,61, IC 95%=0,39-0,97), and modified the effect of risk factors associated to the lesion severity. The multiplicative interaction of alleles showed that the combination p53 PIN3A1, p53 72C(Pro) and p21 31C(Ser) represented risk (OR=1,67, IC95%=1,03-2,72) and the combination p53 PIN3A1, p53 72C(Pro) and p21 31A(Arg) conferred protection (OR=0,26, IC95%=0,08-0,78) against the development of HSIL and cervical cancer. It was observed positive and negative correlations of, respectively, p16 and p21, and cyclin D1 expression with the cervical lesion grade. The epithelial distribution of p16, Ki-67, p21 and p53 was associated with the lesion severity. The polymorphisms analyzed showed neither association with the expression of the biomarkers nor positivity for HPV. Our results suggest the importance of polymorphism p21 31C>A in the development of cervical neoplasia and the lack of correlation between the polymorphisms p53 PIN3 and p53 72C>G with cervical carcinogenesis, although some genotypes acted as risk modifiers. Our TMA results corroborated the potential use of cell cycle biomarkers as an adjunctive tool to differentiate cervical precursor lesions.