SFRP1, Posible biomarcador en la progresión o regresión de lesiones de cérvix asociado al Virus del Papiloma Humano / SFRP1, Possible Biomarker in the Progression or Regression of Cervical Pre-neoplastic Lesions Associated with Human Papilloma Virus

Resumen Objetivo: Comparar la expresión de mRNA y proteínas de SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 y HAND1 en pacientes con lesión intra-epitelial cervical de bajo y alto grado, con posterior progresión o regresión. Material y Método: Se realizó análisis de expresión de genes mediante RT-PCR y análisis de expresión de proteínas por inmunohistoquímica. El análisis estadís tico fue realizado con las pruebas: Wilcoxon, coeficiente de correlación de Spearman e índice de concordancia. Las muestras fueron pareadas en momento 1 y momento 2. Resultados: SFRP1 mostró tendencia de mayor expresión de mRNA en lesión intra-epitelial de bajo grado (momento 2) Vs. alto grado (momento 1). La expresión de proteínas por inmunohistoquímica de SFRP1 en casos de progresión (83,3 %) mostró disminución en su graduación (p = 0,0313*); los demás genes en estudio no tuvieron cambios estadísticamente significativos. Discusión: SFRP1 mostró comportamiento ajustado a resultados de estudios previos donde se encontró hipermetilado en lesiones intra-epiteliales de alto grado; su subexpresión por hipermetilación se reportó en otros canceres, proceso que colabora con su silenciamiento y transición epitelial-mesenquimatosa del cáncer de cuello uterino. Conclusiones. SFRP1 es potencial biomarcador en lesiones preneoplásicas del cuello uterino asociadas al virus de papiloma humano.

Abstract Objective. The aim of this work was to compare the expression of mRNA and proteins of SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 and HAND1 in patients with low and high grade cervical intraepithelial lesion, with subsequent progression or regression. Material and Methods: Gene expression analysis was conducted through RT-PCR and protein expression analysis was performed by immunohistochemistry. The statistics analysis were Wilcoxon test, Spearman's correlation coefficient and concordance index. The samples were paired during moment 1 (initial patient diag nosis) and moment 2 (follow-up histological diagnosis). Results: SFRP1 showed a trend of higher mRNA expression in low-grade intra-epithelial lesions (moment 2) Vs. high-grade (moment 1). The expression of proteins by immunohistochemistry of SFRP1 in progression cases (83.3%) showed a decrease in its graduation (p = 0.0313*); the other genes under study had no statistically significant. Discussion: SFRP1 showed a biological behavior adjusted to the results of previous studies where hypermethylation was found in high-grade intra-epithelial lesions; its subexpression by hypermethylation has been reported in other cancers, a process that collaborates with its silencing and epithelial-mesenchymal tran sition of cervical. Conclusions. SFRP1 is a potential biomarker in preneoplastic lesions of the cervix associated with human papillomavirus.

Detección del virus del papiloma humano en muestras obtenidas mediante técnica de autotoma en un grupo de universitarias peruanas / Detection of the human papillomavirus in samples obtained by self-collection technique in a group of peruvian college students

RESUMEN Estudio transversal que determinó la frecuencia y genotipos del virus del papiloma humano de alto riesgo (VPH-AR) a través de la técnica de autotoma en un grupo de universitarias de Lima. Participaron 221 estudiantes y se detectó el ADN del VPH-AR con el método de reacción en cadena de la polimerasa (PCR). La frecuencia del VPH-AR en las participantes fue de 43,4%; de este grupo se encontraron los genotipos VPH 16 en el 15,6% y VPH 18 en el 4,2% y otros VPH-AR en el 80,2%. Se concluye que la frecuencia del VPH-AR es mayor en el grupo de universitarias de este estudio en comparación a investigaciones nacionales previas.

ABSTRACT Cross-sectional study that determined the frequency and the genotypes of the (HR-HPV) high-risk human papillomavirus through the self-collection technique in a group of college students of Lima. Two hundred twenty-one (221) students participated and the DNA of the HR-HPV was detected with polymerase chain reaction (PCR). The frequency of HR-HPV in participants was 43.4%; of this group, genotype HPV 16 was present in 15.6%, HPV 18 in 4.2%, and another HR-HPV in 80.2%. We can conclude that the frequency of HR-HPV is greater in the group of college students of this study in comparison with previous national investigations.

Avaliação do rastreamento do câncer do colo do útero e sua periodicidade em um município de Santa Catarina / Assessment of cervical cancer screening and its periodicity in a city of Santa Catarina state

Modelo do estudo: Estudo de Prevalência. Objetivo do estudo: Conhecer a prevalência dos resultados alterados dos exames preventivos para câncer do colo do útero e a sua regularidade na coleta. Metodologia: Estudo observacional, transversal e retrospectivo. Foram estudadas 3.425 mulheres usuárias do Sistema Único de Saúde e 9.436 exames citopatológicos de novembro de 2003 a janeiro de 2014. Resultados: A mediana da idade foi de 35 anos (25,0 - 46,0, percentil 25 a 75%). No primeiro exame citopatológico, 2,7% das mulheres apresentaram alterações em células epiteliais. As Células escamosas atípicas de significado incerto (ASC-US) (n=54; 1,7%) e as lesões intra-epiteliais de baixo grau (LIEBG) (n=24; 0,7%) foram as mais frequentes. Ao longo do período observado houveram 87 novas alterações citopatológicas, totalizando 173 exames alterados em 9.436 analisados. Quanto a regularidade, 58,5% pacientes repetiram a segunda coleta. Conclusões: Houve um perfil predominante de mulheres jovens, sendo o diagnóstico de ASC-US o mais frequente. A flora bacteriana mais frequente foi Lactobacillus principalmente em mulheres jovens. (AU)

Study Model: Prevalence Study. Study objective: To determine the prevalence of the abnormal cervical cancer screening test (PAP) and regularity in repeat it. Methods: An observational, cross-sectional and retrospective study. 3,425 women, users of the Brazilian Unified Health System, and 9,436 cytopathology, conducted from November 2003 to January 2014, were studied. Results: The median age was 35 years (25.0 to 46.0, 25 to 75% percentile). In the first PAP, 2.7% of women examined had alterations in epithelial cells. The atypical squamous cells of uncertain significance (ASC-US) (n = 54; 1.7%), and low-grade intraepithelial lesion (LSIL) (n = 24; 0.7%) were the most frequent alterations found. During the observed period, 87 new abnormal PAPs were found, totalling 173 altered tests in 9436 analysed. Regarding regularity of test, 58.5% patients repeated the second PAP. Conclusions: There was a preferential profile of young women, and the diagnosis of ASC-US was the most frequently found. Lactobacillus, especially in young women, was the main bacterial flora. (AU)

Oncogenic High-risk Human Papillomavirus Detection and Evaluation of Risk Factors in the Cervical Intraepithelial Neoplasia I / Detecção do Papilomavírus Humano de Alto Risco Oncogênico e Avaliação dos seus Fatores de Risco nas Neoplasias Intraepiteliais Cervicais Grau

The cervical intraepithelial neoplasia grade I (CIN I) shows an important percentual of spontaneous regression (80%) and there is no universal consensus if these lesions should be treated or only monitored. Lesions at risk for progression are precisely those associated with high-risk HPV. Knowing which CIN I are related to these viruses may be one of the determining factors for the decision to treat or not. Objective: To determine the prevalence of high-risk HPV in women with CIN I and to evaluate if there is an association between the presence of the virus and some risk factors. Methods : Cross-sectional descriptive study. We evaluated 55 women with histological diagnosis of CIN I. All of them were previously submitted to HPV-DNA testing. Results: 25 out of 55 (45.5%) women analyzed were positive for high-risk HPV. The virus infection was related with higher level of education, smoking and history of sexually transmitted diseases. Other risk factors like age, number of sexual partners, age at first sexual intercourse, use of hormonal contraceptives, and immunosuppression condition did not show a relation to the high-risk HPV infection. Conclusions: The prevalence of high-risk HPV in women with histological diagnosis of CIN I was 45.5%. HPV-DNA detection was associated with smoking, history of sexually transmitted diseases, and higher level of education.

As neoplasias intraepiteliais cervicais grau I (NIC I) apresentam um percentual importante de regressão espontânea (cerca de 80%) e não há um consenso universal se essas lesões devam ser tratadas ou apenas acompanhadas. As lesões que apresentam risco de progressão são justamente aquelas associadas aos HPV de alto risco oncogênico. O conhecimento de quais lesões estão relacionadas a esses vírus pode ser um dos fatores determinantes para a decisão de se tratar ou não tais lesões. Objetivo: Determinar a prevalência do papilomavírus humano (HPV) de alto risco oncogênico em mulheres com resultado histológico de NIC I e verificar a existência da associação entre a presença do vírus e alguns fatores de risco. Métodos: Trata-se de um estudo transversal, de caráter descritivo, onde foram avaliadas 55 mulheres com diagnóstico histopatológico de NIC I. Todas foram submetidas ao teste de DNA-HPV previamente. Resultados: Das 55 mulheres analisadas, 25 (45,5%) apresentaram HPV de alto risco positivo. A infecção pelo vírus foi associada às mulheres com mais anos de estudo, tabagismo e à história de alguma doença sexualmente transmissível. Outros fatores de risco, como a idade, o número de parceiros sexuais, a faixa etária em que ocorreu a coitarca, o uso de anticoncepcionais hormonais e o estado de imunossupressão, não mostraram relação com a infecção pelo HPV. Conclusão: A prevalência do HPV de alto risco oncogênico nas mulheres com diagnóstico histológico de NIC I foi de 45,5%. A detecção do vírus foi associada ao tabagismo, à história de doença sexualmente transmissível e a um grau maior de escolaridade.

Human Papillomavirus Prevalence and Genotype Distribution among HIV-Infected Women in Korea

The epidemiology on human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women in Korea is not well established. A retrospective study was conducted to determine the prevalence and genotype distribution of HPV infection among HIV-infected women in Korea. HPV DNA genotype and cervical cytology were examined in 60 HIV-positive women and 1,938 HIV-negative women. HPV genotypes were analyzed by using a HPV DNA chip. HIV-infected women had higher prevalence of high-risk HPV (hr-HPV) infection (30% vs 4.9%, adjusted odds ratio [AOR], 6.96; 95% confidence interval [CI], 3.63-13.34, P<0.001) and abnormal cervical cytology (18.3% vs 1.8%, AOR, 10.94; 95% CI, 5.18-23.1, P<0.001) compared with controls. The most common hr-HPV genotype detected in HIV-infected women was HPV 16 (10%), followed by 18 (6.7%) and 52 (5%). Prevalence of quadrivalent vaccine-preventable types (HPV 6, 11, 16, and 18) was 21.7% and 2.3% in HIV-positive women and HIV-negative women, respectively. Age was a significant risk factor for hr-HPV infection in HIV-infected women (P=0.039). The presence of hr-HPV was significantly associated with abnormal cervical cytology (P<0.001). These findings suggest that HPV testing for cervical cancer screening in HIV-infected women would be necessary, particularly among young age group.

Prevalence of HR-HPV and risk factors associated with the development of lesion cervical precousor of cervical cancer, a sample of the Curitiba metropolitan region, case-control study / Prevalência do HPV-AR e fatores de risco associados ao desenvolvimento de lesões cervicais precursoras do câncer cervical, numa amostra da região metropolitana de Curitiba, estudo caso-controle

Objective: Characterize the risk factors associated with the development of cervical intraepithelial neoplasia (CIN) and determine the prevalence of Highrisk Human Papillomavirus (HR-HPV) infection in women without cytological abnormalities and women diagnose with CIN 2 and 3, living in metropolitan region Curitiba, Parana state, Brazil. Material and Methods: Case-control study consisting of 382 women without cytological abnormalities, 233 women with high-grade intraepithelial lesions, which were subdivided in 131 women with CIN 2 and 102 women with CIN 3 diagnose by histological analysis of the cervical segment conical excision material. The age range of the women in the study was 15-45 years old, collected in the period of 2009 to 2012. The detection of HR-HPV DNA was performed by Hybrid Capture 2 test (CH2)...

Objetivo: Caracterizar os fatores de risco associados ao desenvolvimento de neoplasias intraepiteliais cervicais (NIC) e verificar a prevalência da infecçãopelo HPV de alto risco (HPV-AR) em mulheres sem anormalidade citológicas e com NIC 2 e 3, residentes na Região Metropolitana de Curitiba, Paraná,Brasil. Materiais e Métodos: Estudo caso-controle, composto por 382 mulheres sem anormalidades citológicas, 233 mulheres com lesão intraepitelial de alto grau, sendo estas subdivididas em 131 mulheres com NIC 2 e 102 com NIC 3 após a análise histológica do material da excisão cônica do segmento do colo do útero. A faixa etária das mulheres do estudo foi de 15 a 45 anos, coletadas no período de 2009 a 2012. A detecção do DNA do HPV-AR foi realizada pelo teste Captura Híbrida (CH2)...

Comparison between two methods for molecular characterization of human papillomavirus

A sensitive method of detection for Human Papillomavirus (HPV) is important to facilitate the early treatment of cervical cancer precursors.Objective: to analyze the spectrum of HPV infection and compare the sensibility of DNA HPV detection using polymerase chain reaction (PCR) and nestedPCR (nPCR) methods in a group of 251 women of Pelotas-RS. Methods: genomic DNA was extracted from the collected samples and was submitted toPCR methods with the primers MY09/11 and nPCR with the pair of primers MY09/MY11 and GP5+/6+. The results were applied to the softwares Epi-Info v.3.5.1* and STATA v.11 * for analyzes. Results: the prevalence of HPV infection was 6.8% with the use of primers MY09/11. When associated withprimers GP5/6, this result increased to 29.9% (p < 0.001). Conclusion: the increase founded in HPV DNA detection from 6.8 to 29.9% suggests that thetechnique of nPCR MY09/11 followed by GP5/6 is the most sensitive method to detect HPV DNA from cervical specimens.

Prevalence of Human Papilloma Virus DNA in HIV Positive Women in Lagos University Teaching Hospital (LUTH) Lagos, Nigeria.

Introduction: HIV-infected women have a high prevalence of Human Papilloma virus (HPV) infection and are more likely to be infected with high risk genotypes with the potential of progressing to cervical cancer. There is paucity of data regarding the prevalence of sexually transmitted HPV infection among HIV positive women in Nigeria. Aims: The objective of this cross-sectional prospective study was to determine the prevalence of high risk HPV among HIV positive and negative women in LUTH, Lagos, Nigeria and to relate HPV genotypes in the study population to commercially available HPV vaccine types that would be or not be appropriate for implementation of vaccination programs in Lagos State. Place and Duration of Study: AIDS Prevention Initiative In Nigeria (APIN) clinic as well as the Gynecologic outpatient clinic of LUTH, Lagos between August 2011 and August 2012. Methodology: A combination of PCR and flow through hybridization method was used in the genotyping of HPV from samples obtained from 98 HIV positive and 97 HIV negative women. Data was analyzed using Epi info 3.5.6. Non parametric variables were compared with chi-square or Fisher exact test as appropriate. The differences in mean for parametric variables were compared using student T test. P value <0.05 were considered significant. Results: The prevalence of HPV among HIV positive women was 44.9% while the prevalence of high risk types was 37.5%. The commonest high risk types seen were types 31, 52, 53 and 35. The prevalence of HPV among the HIV negative women was 11%. The commonest high risk types seen were types 18, 16, 52 and 56. Conclusion: In view of the high prevalence and diversity of HPV genotypes among the HIV positive women, adequate screening protocols should be put in place for screening this category of women. Studies should also be carried out to determine the efficacy of existent HPV vaccines on this group of patients.

Detección del virus del papiloma humano de alto riesgo por captura híbrida II® según hallazgos citológicos en mujeres tratadas por lesiones escamosas intraepiteliales de cuello uterino, período 2006/2010 / Detection of high risk human papillomavirus by hybrid capture II(r) according cytological findings in women treated for squamous intraepithelial lesions of the cervix, period 2006/2010

OBJETIVO: Determinar la frecuencia del virus de papiloma humano de alto riesgo oncogénico (HR-HPV) por captura híbrida II (r) (CH II(r)) según hallazgos citológicos en mujeres tratadas por lesiones escamosas intraepiteliales (SIL) de cuello uterino. MATERIAL Y MÉTODO: Estudio descriptivo de corte transverso de una serie de casos, en donde se incluyeron 122 mujeres tratadas, 79 (65%) por SIL de bajo grado (LSIL) y 43 (35%) por SIL de alto grado (HSIL) que concurrieron al Laboratorio de HPV del Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, para realizarse un control post-tratamiento, periodo 2006/2010. RESULTADOS: Se observó un total del 28% (34/122) de mujeres tratadas por SIL positivas para HR-HPV, detectándose infección viral en un 20% de las mujeres con ausencia de SIL (NSIL) (22/108), 83% de las mujeres con LSIL (10/12) y 100% de las mujeres con HSIL (2/2). De las 34 mujeres positivas para HR-HPV, 10 mujeres (29%) presentaron valores altos (100 pg/mL o más) de carga viral relativa, detectándose un aumento de casos positivos con la severidad de la lesión (28% NSIL, 30% LSIL, 50% HSIL). CONCLUSION: La detección de HR-HPV por CH II(r), así como los valores de carga viral relativa altos, en especial en mujeres con NSIL podrían ayudar a identificar mujeres tratadas con riesgo a desarrollar recidivas, contribuyendo así a fortalecer el programa de prevención de cáncer de cuello uterino. .

OBJECTIVE: To determinate the frequency of high risk human papillomavirus (HR-HPV) by hybrid capture II (r) (CH II(r)), according cytology results in women treated for squamous intraepithelial lesions of the cervix (SIL). MATERIAL AND METHODS: A descriptive cross-sectional study of a series of cases that included 122 women treated, 79 (75%) for low grade SIL (LSIL) and 43 (35%) for high grade SIL (HSIL) attending at the HPV Laboratory at the Health Sciences Research Institute (IICS), National University of Asunción (UNA), for post-treatment control during period 2006/2010. RESULTS: A total of 28% (34/122) of women treated for SIL were positive for HR-HPV, detecting viral infection in 20% of women with no SIL (NSIL) (22/108), in 83% of women with LSIL (10/12) and in 100% of women with HSIL (2/2). Of 34 women positive for HR-HPV, 10 women (29%) had high values (100 pg / mL or more) of relative viral load, detecting an increase of positive cases with severity of the lesion (28% NSIL, 30% LSIL, 50% HSIL). CONCLUSION: HR-HPV detection by CH II(r) and high relative viral load values especially in women with NSIL could help to identify treated women at risk of developing recurrence, thereby contributing to strengthening the cervical cancer prevention program. .

Prevalence and correlation of human papilloma virus and its types with prognostic markers in patients with invasive ductal carcinoma of the breast in Kuwait

This study aimed to document the association of human papilloma virus [HPV] and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied [age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status]. HPV frequency was documented using immunohistochemistry [IHC] and chromogenic in-situ hybridisation [CISH]. HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. The HPV prevalence as determined by CISH and IHC was 51 [35.4%] and 24 [16.7%] cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant [P <0.001]. HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 [3.9%] cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 [13.7%] cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 [3.9%] cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 [52.9%] and 19 [37.2%], respectively. No correlation was observed with the prognostic parameters. The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% [CISH]. Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected

Investigação das alterações moleculares nos receptores de fator de crescimento epidermal (HER-1 e HER-2) e da proteína P16 em carcinoma de células escamosas de língua e assoalho de pacientes jovens e adultos / Investigation of the molecular receptors epidermal growth factor (HER-1 and HER-2) and P16 protein in squamous cell carcinoma of the tongue and floor of young adult patients

O carcinoma de células escamosas (CCE) tem aumentado em pacientes jovens, principalmente em língua, correspondendo a 6% de todos os cânceres bucais. Sugere-se que essa neoplasia maligna seja uma doença distinta da que ocorre em pacientes mais velhos, com etiologia e progressão clínica particulares. Os receptores da família HER apresentam um importante papel na patogênese e progressão do CCE, sendo relevante a identificação de alterações no gene e na expressão das proteínas relacionadas ao CCE bucal...O CCE em pacientes jovens acomete mais a língua e não tem predileção pelo sexo masculino, estando o etilismo menos associado a esse grupo de pacientes em relação aos adultos. A imunopositividade observada para os anticorpos para HER-1 e p16 demonstra a participação dessas proteínas na carcinogênese dos CCE de língua e assoalha de boca. A presença de mutações nas regiões hot spots do gene HER-1 reforça a participação desse gene no desenvolvimento CCE de língua e assoalho em pacientes jovens. Futuras investigações são sugeridas nessa linha de pesquisa, para avaliar proteínas envolvidas na via de sinalização do HER-1, bem como nos casos p16 positivos, a presença do vírus HPV.

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

BACKGROUND: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. METHODS: We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. RESULTS: All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. CONCLUSIONS: Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Perfil citopatológico de mulheres atendidas nas unidades básicas do município de Uruguaiana, RS / Cytopathological profile of women met in the basic units of the municipality of Uruguaiana, RS

O câncer do colo de útero tem sido apontado como o terceiro tipo de câncer mais comum entre as mulheres e sua relação com a infecção por papilomavírus humano (HPV) é bem estabelecida. Objetivo: conhecer o perfil citopatológico de mulheres atendidas nas Unidades Básicas de Saúdedo município de Uruguaiana, RS. Métodos: análise retrospectiva de corte transversal e descritivo dos laudos de exames citopatológicos de pacientes querealizaram a citopatologia ginecológica (Papanicolaou) e respectivos prontuários, emitidos entre os anos de 2003 e 2011. Foram selecionadas as variáveis referentes à idade e a alteração citopatológica e classificadas segundo Bethes da, 2001. Resultados: da totalidade de laudos de exames citopatológicos analisados, 15,5% possuem alguma alteração celular e a que apresentou maior prevalência foi a atipia de células escamosas de significado indeterminado(ASC-US), com 50,28%, seguida das lesões intraepiteliais de baixo grau (LIEBG), com 35,45%. Em ambos os casos as mulheres com idade inferior a 25anos foram as que apresentaram maior prevalência. Cerca de 13% das pacientes apresentaram infecção pelo HPV e a maior prevalência foi observada nafaixa etária inferior a 25 anos (47,84%). Conclusão: a faixa etária de maior prevalência de lesões cervicais está em mulheres com idade inferior a 25 anose muitas das alterações celulares estão associadas à infecção pelo HPV. Salienta-se, portanto, a necessidade de políticas de rastreamento de lesões cervicais em mulheres nesta faixa etária, evitando assim a progressão das lesões que evoluem ao câncer.

Cancer of the cervix has been named as the third most common type of cancer among women and its relation to infection by human papillomavirus (HPV) is well established. Objective: cytopathologic know the profile of women attending the Basic Health Units in the municipality of Uruguaiana, RS. Methods: retrospective analysis of cross-sectional and descriptive the reports of cytopathology from patients who underwent gynecologic cytology (Papanicolaou) and their medical records, issued between the years 2003 and 2011. We selected the variables related to age and change and cytopathological sorted by Bethesda, 2001. Results: of all reports of reports of cytopathology analyzed, 15.5% have a cell phone and some change withthe highest prevalence was atypical squamous cells of undetermined significance (ASC-US), with 50.28%, followed by low-grade intraepithelial lesions(LSIL), with 35.45%. In both cases, women younger than 25 years showed the highest prevalence. About 13% of patients had HPV infection and the highestprevalence was observed in the age group below 25 years (47.84%). Conclusion: the age group with the highest prevalence of cervical lesions in womenis under the age of 25 years and many of the cellular changes associated with HPV infection. It is noteworthy, therefore, the need for political screening ofcervical lesions in women in this age group, thus preventing the progression of lesions that evolve to cancer.

Clinical and laboratorial study of HPV infection in men infected with HIV

OBJECTIVES: To determine the prevalence of precursor lesions of penile cancer, to establish the concordance of diagnostic techniques (PCR, Hybrid Capture (HC) and peniscopy with acetic acid 5%) in the diagnosis of Human Papilloma Virus (HPV) of the penis of men infected with HIV and to evaluate the influence of the immune status. PATIENTS, METHODS AND RESULTS: 276 men were studied, with a median age of 34.6 years. Prevalence of High Risk HPV, Low Risk HPV and infection with both, according to HC, was 43%, 32% and 22%, respectively. PCR showed 50% of positivity for HPV DNA. Peniscopy was positive in 27% of individuals. Peniscopy showed good specificity and low sensitivity for the detection of penile HPV, and low concordance with PCR. Men with white lesions had a 3.6 higher relative risk of positivity for HPV. The most common clinical lesion observed was vegetation, identified in 29% of patients. PCR and HC techniques showed high sensitivity for HPV DNA and there was an excellent correlation between them. Immunosuppressed individuals with CD4< 200 cells/mm3 had the highest prevalence of pre-malignant lesions that were observed in 10% of the studied individuals. CONCLUSIONS: Peniscopy was important for identification and treatment of subclinical lesions. PCR and HC techniques were sensitive methods for the detection of HPV DNA with high concordance. Severely immunosuppressed individuals showed a higher prevalence of pre-malignant lesions of the penis.

Células escamosas atípicas cervicais: conduta clínica / Cervical atypical squamous cells: clinical management

O diagnóstico precoce e o rastreamento das lesões precursoras do câncer do colo uterino são de extrema importância. O diagnóstico citológico ainda é a principal ferramenta para a prevenção. O uso de testes para detectar o DNA-HPV associado à citologia tem sido proposto, visto que existem evidências epidemiológicas de que o papilomavírus humanos (HPV) é causa necessária para a ocorrência do câncer cervical. De acordo com a classificação de Bethesda 2001, células escamosas atípicas (ASC) são alterações citológicas sugestivas de lesão intraepitelial, qualitativa ou quantitativamente insuficientes para uma interpretação definitiva. Elas são subdivididas em ASC-US (células escamosas atípicas de significado indeterminado possivelmente não neoplásicas) e ASC-H (células escamosas atípicas não sendo possível excluir lesão intraepitelial de alto grau). O seguimento ideal para mulheres com diagnóstico de ASC é controverso e existem dúvidas sobre como realizá-lo, bem como qual o tratamento mais apropriado. O objetivo desta revisão consiste em avaliar o seguimento e tratamento das mulheres com diagnóstico citológico de ASC. Foi realizada revisão da literatura de estudos indexados em banco de dados como MEDLINE, PubMed e LILACS.

Early diagnosis and screening of precursor lesions of cervical cancer are extremely important. The cytological diagnosis is still the main tool to prevention. The use of tests to detect DNA-HPV combined with cytology has been proposed, since there are epidemiological evidences that human papillomavirus (HPV) is a necessary cause for the occurrence of cervical cancer. According to the 2001 Bethesda classification atypical squamous cells (ASC), there are cytological changes suggestive of squamous intraepithelial lesion that are qualitatively or quantitatively insufficient for a definitive interpretation. It is subdivided into ASC-US (atypical squamous cells of undetermined significance may not neoplastic) and ASC-H (atypical squamous cells is not possible to exclude high-grade intraepithelial lesion). The ideal follow-up for women diagnosed with ASC is controversial and there are doubts about how to accomplish it and the most appropriate treatment. The objective of this review is to evaluate the monitoring and treatment of women with cytological diagnosis of ASC. We performed a literature review of studies indexed in databases such as MEDLINE, PubMed and LILACS.

Análise comparativa de biomarcadores no câncer cervical invasivo e sua correlação com o tipo de HPV / Comparative analysis of biomarkers in invasive cervical cancer and its correlation with hpv type

O câncer cervical é o terceiro tipo de câncer mais comum entre mulheres no mundo. Dentre outros cofatores, a infecção pelo HPV de alto risco, tem sido bem documentada como fator necessário ao desenvolvimento desse tipo de câncer. A principal ação do HPV envolve a expressão massiva das oncoproteínas virais E6 e E7 que podem formar complexos específicos com proteínas supressoras de tumor, sendo capazes de alterar mecanismos do ciclo celular, modificando a expressão de proteínas celulares. Um dos principais avanços na medicina clínico patológica é o uso dessas proteínas como marcadores de forma a aumentar a acurácia do prognóstico e do próprio estadiamento do câncer cervical. Assim, a fim de reforçar a hipótese de que as proteínas associadas ao ciclo celular Ki-67, MCM-2, p53 e p16INK4a se encontram superexpressas no câncer cervical, foram analisadas em 87 amostras cervicais de pacientes com câncer invasivo (CCI) e 43 cérvix normais. Verificamos também se há uma expressão diferencial que pode ajudar a avaliação do estadiamento clínico da FIGO e quais tipos virais podem induzir a uma expressão diferencial dessas proteínas. Além disso, características sociodemográficas, comportamentais e clínicas das pacientes foram obtidas dos prontuários e analisadas. Para isso, a detecção de DNA de HPV foi realizada pela técnica da PCR e hibridização in situ. A expressão das proteínas foi observada por imunohistoquímica, seguida por quantificação manual e através do software ImagePro Plus. A análise estatística foi feita utilizando o software STATA/SE 10.1 aplicando os testes: Kruskall-Wallis, Student, Fisher e Qui-Quadrado. Nossos resultados mostraram forte associação (p<0,05) do CCI e dos estágios tumorais mais avançados (III e IV) com mulheres superiores a 55 anos, com mais de quatro gestações e sem escolaridade. A prevalência de DNA de HPV por PCR na população total foi de 73,4 por cento. Nos grupos de CCI e controle foram, respectivamente, 94,3 por cento e 29,3 por cento. O tipo mais prevalente foi o HPV16 (70,8 por cento), acompanhado pelo HPV33 (11,2 por cento) e 35 (4,5 por cento). Como esperado, foi observado aumento (p<0,05) na expressão de Ki-67, MCM-2, p53 e p16INK4a no CCI, quando comparados ao controle. A proteína p16INK4a com expressão difusa, citoplasmática e nuclear esteve associada ao câncer. Ki-67 apresentou forte expressão (>50 por cento) conforme o agravamento da doença. Não foi observada associação entre a expressão de MCM-2, p53 e p16, e o estadiamento do tumor. Como conclusões, foram observadas maiores chances no desenvolvimento do CCI em mulheres com idades superiores a 55 anos, com mais de quatro gestações e sem escolaridades, estando esses fatores associados, também, à progressão tumoral. Apenas o marcador Ki-67 associouse ao estágio do CCI. Os tipos mais prevalentes encontrados, HPV16, 33, 35, 67 e 58, sugerem que novos estudos devam ser considerados para implementação de vacinação contra o HPV no Brasil.

prevalence of human papilloma virus in esophageal squamous cell carcinoma

Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus [HPV] is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma [ESCC] cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences. DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control [HPV-18 and HPV positive biopsies of uterine exocervix] and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 [CTLA4]. Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed. There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests / Métodos de triagem colposcópica para detecção de neoplasia intraepitelial cervical grau 3 após diagnóstico citopatológico de lesão intraepitelial escamosa de baixo grau: uma revisão sistemática de testes diagnósticos

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6 percent to 12 percent. The HPV-DNA positivity rate ranged from 64 percent to 83 percent; sensitivity for CIN3 detection ranged from 95.2 percent to 100 percent; and specificity was available in two studies (27 percent and 52 percent). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33 percent and 90.8 percent); and specificity was available in one study (53 percent). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

CONTEXTO E OBJETIVO: O desempenho do teste de DNA-HPV (ácido desoxirribonucleico-papilomavírus humano) oncogênico estratificado por idade para triagem de lesão intraepitelial escamosa de baixo grau (LSIL) demanda investigação. O objetivo do estudo foi avaliar e comparar o desempenho, para detecção de neoplasia intraepitelial cervical (NIC3), do teste de DNA-HPV oncogênico e da citologia de repetição estratificados por idade (ponto de corte 35 anos), para triagem de LSIL. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura. Foram identificados estudos em nove bases de dados eletrônicas e listas de referências dos artigos recuperados. MÉTODOS: Critérios de elegibilidade: citologia inicial LSIL, realização do teste de DNA-HPV oncogênico e da citologia de repetição e detecção de NIC3. A diretriz QUADAS (Quality Assessment of Diagnostic Accuracy Studies) foi utilizada para avaliação da qualidade. As informações foram sintetizadas qualitativamente. RESULTADOS: Dentre 7.776 estudos, 284 eram pertinentes ao tema e três atenderam aos critérios de elegibilidade. A prevalência de NIC3 apresentou variação entre 6 por cento e 12 por cento. A taxa de positividade do teste de DNA-HPV apresentou variação entre 64 por cento e 83 por cento; a sensibilidade para NIC3 apresentou variação entre 95,2 por cento e 100 por cento; a especificidade estava disponível em dois estudos (27 por cento e 52 por cento). A sensibilidade da citologia de repetição (ponto de corte ASCUS - células escamosas atípicas de significado indeterminado) estava disponível em dois estudos (33 por cento e 90,8 por cento); a especificidade estava disponível em um estudo (53 por cento). CONCLUSÕES: Não existem, atualmente, evidências científicas disponíveis para comprovar que, em mulheres com 35 anos ou mais e citologia LSIL, a triagem colposcópica com teste de DNA-HPV oncogênico apresenta melhor desempenho para detecção de NIC3 do que a repetição citológica.

Expression of CHOP in Squamous Tumor of the Uterine Cervix

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53. METHODS: Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I). RESULTS: CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively). CONCLUSIONS: Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.