Sinus floor elevation with platelet-rich fibrin alone : a clinical retrospective study of 1-7 years

Several sinus floor elevation procedures for implant placement have been introduced. The present study aimed to evaluate the implants placed with Platelet-rich fibrin (PRF) alone in atrophic posterior maxillae and survival rates and the potential factors associated with implant loss. This retrospective study evaluated 71 implants in 34 patients after 1-7 years? follow-up time. Statistical models were used to determine the implant survival and the potential factors associated with loss. Overall, 7 implants were lost, and the cumulative survival rate at 7 years by implant-based and patient-bases analyses were 85.5% and 85.7%, respectively. The mean residual bone height (RBH) was 4.26 mm. The implant survival rate was significantly lower at RBH < 4 mm than RBH ? 4 mm. This retrospective study showed that sinus floor elevation with PRF alone could be applied in cases of lower RBH. However, it should be carefully performed in cases of RBH < 4 mm before surgery

A morphological protocol and guide-list on uterine cervix cytology associated to papillomavirus infection

The present study was designed to further assess the validity of the cytological description of morphological lesions said to be related to Papillomavirus (HPV) infections in senior women. The casuistic comprised 196 cervical smears from a group of women with no clinical or morphological evidence of neoplasia, collected simultaneously with samples submitted to detection of HPV DNA by PCR in a previous study. Three experienced cytologists studied each slide in two different conditions, with an interval of 20 months between them. The first approach was performed under routine laboratory standards, whereas the second was guided by a list of 16 well-defined parameters indicative of HPV-related cytological lesions. When suspicious cases of HPV-related alterations were grouped with positive cases, they showed on average: sensitivity of 25.5%, specificity of 84.4% and positive predictive value (PPV) of 26.8%. When suspicious cases were grouped with negative cases, sensitivity decreased, whereas specificity and PPV increased, as expected. In the second reading, which followed a “guide-list”, a decrease in sensitivity was observed, contrasting with a sharp increase of positive predictive value. Among the 16 cytomorphological criteria tested, “koilocytosis”, “mild koilocytosis” and “condylomatous parabasal cells” yielded the best predictive value for HPV DNA detection by PCR. In conclusion, despite the low sensitivity, cytopathologic assessment of cervico-vaginal smears leads to a highly specific diagnosis of HPV infection in menopausal women, with PPV of 91.0% when directed by a guide-list of well-defined morphologic criteria.O presente estudo analisou aspectos relacionados ao valor da citologia cervical na identificação de alterações cito-morfológicas relacionadas à infecção por Papilomavírus humano (HPV) em mulheres com idades avançadas. A casuística compreendeu 196 amostras cérvico-vaginais provenientes de uma população de mulheres sem evidências clínicas ou citológicas de neoplasia cervical. As amostras foram coletadas simultaneamente para pesquisas para DNA-HPV por Reação de Polimerização em Cadeia (PCR) e citologia. Três observadores experientes efetuaram análise das lâminas em duas etapas com intervalo de 20 meses: a primeira em condições de rotina laboratorial e a segunda dirigida por um roteiro de critérios pré-estabelecidos. Quando os casos suspeitos para alterações relacionadas ao HPV foram agrupados com os casos positivos, eles mostraram em média: 25,5% de sensibilidade, 84,4% de especificidade e valor preditivo positivo (VPP) de 26,8%. Quando os casos suspeitos foram agrupados com os negativos, a sensibilidade diminuiu, e a especificidade e o VPP aumentaram. Na segunda leitura, a sensibilidade diminuiu, contrastando com o aumento do VPP. Entre os 16 critérios cito-morfológicos avaliados, coilocitose, coilocitose leve e célula parabasal coilocitótica foram os que apresentaram melhor VPP para HPV em comparação ao PCR. Concluímos que, apesar da baixa sensibilidade, o painel de critérios cito-morfológicos poderá elevar a especificidade do teste de Papanicolaou para triagem das alterações relacionadas à infecção por HPV em pacientes de mais idade

Padronização da análise de critérios citomorfológicos de lesões associadas à infecção pelo HPV

The present study was designed to further assess the validity of the cytological description of morphological lesions said to be related to Papillomavirus (HPV) infections in senior women. The casuistic comprised 196 cervical smears from a group of women with no clinical or morphological evidence of neoplasia, collected simultaneously with samples submitted to detection of HPV DNA by PCR in a previous study. Three experienced cytologists studied each slide in two different conditions, with an interval of 20 months between them. The first approach was performed under routine laboratory standards, whereas the second was guided by a list of 16 well-defined parameters indicative of HPV-related cytological lesions. When suspicious cases of HPV-related alterations were grouped with positive cases, they showed on average: sensitivity of 25.5%, specificity of 84.4% and positive predictive value (PPV) of 26.8%. When suspicious cases were grouped with negative cases, sensitivity decreased, whereas specificity and PPV increased, as expected. In the second reading, which followed a "guide-list", a decrease in sensitivity was observed, contrasting with a sharp increase of positive predictive value. Among the 16 cytomorphological criteria tested, "koilocytosis", "mild koilocytosis" and "condylomatous parabasal cells" yielded the best predictive value for HPV DNA detection by PCR. In conclusion, despite the low sensitivity, cytopathologic assessment of cervico-vaginal smears leads to a highly specific diagnosis of HPV infection in menopausal women, with PPV of 91.0% when directed by a guide-list of well-defined morphologic criteria.O presente estudo analisou aspectos relacionados ao valor da citologia cervical na identificação de alterações cito-morfológicas relacionadas à infecção por Papilomavírus humano (HPV) em mulheres com idades avançadas. A casuística compreendeu 196 amostras cérvico-vaginais provenientes de uma população de mulheres sem evidências clínicas ou citológicas de neoplasia cervical. As amostras foram coletadas simultaneamente para pesquisas para DNA-HPV por Reação de Polimerização em Cadeia (PCR) e citologia. Três observadores experientes efetuaram análise das lâminas em duas etapas com intervalo de 20 meses: a primeira em condições de rotina laboratorial e a segunda dirigida por um roteiro de critérios pré-estabelecidos. Quando os casos suspeitos para alterações relacionadas ao HPV foram agrupados com os casos positivos, eles mostraram em média: 25,5% de sensibilidade, 84,4% de especificidade e valor preditivo positivo (VPP) de 26,8%. Quando os casos suspeitos foram agrupados com os negativos, a sensibilidade diminuiu, e a especificidade e o VPP aumentaram. Na segunda leitura, a sensibilidade diminuiu, contrastando com o aumento do VPP. Entre os 16 critérios cito-morfológicos avaliados, coilocitose, coilocitose leve e célula parabasal coilocitótica foram os que apresentaram melhor VPP para HPV em comparação ao PCR. Concluímos que, apesar da baixa sensibilidade, o painel de critérios cito-morfológicos poderá elevar a especificidade do teste de Papanicolaou para triagem das alterações relacionadas à infecção por HPV em pacientes de mais idade

Association between age at first sexual intercourse and subsequent human papillomavirus infection: results of a Brazilian screening program

Objetivo: descrever a idade de início da atividade sexual (sexarca) e a sua associação com a idade das mulheres com a infecção por papilomavírus humano (HPV) e com as alterações citológicas no exame de papanicolaou. Métodos: mulheres da população geral foram recrutadas para participar de um estudo de rastreamento de câncer cervical e lesões pré-malignas. Após a aplicação de questionário comportamental, foram submetidas ao rastreamento com gia cervical e teste para DNA de HPV de alto risco, por meio de Captura Híbrida 2. Este projeto faz parte do Latin American Screening Study, que envolve mulheres do Brasil e da Argentina, e os dados aqui apresentados referem-se aos centros brasileiros nas cidades de Porto Alegre, São Paulo e Campinas. Resultados: de 8.649 mulheres entrevistadas, 8.641 relataram atividade sexual prévia e foram incluídas na análise. A média de idade no momento da entrevista foi de 38,1±11,04 anos, com início da atividade sexual em média aos 18,5±4,0 anos. Identificamos que a idade do início da atividade sexual aumenta de acordo com o aumento da faixa etária no momento da entrevista, isto é, mulheres mais novas relataram sexarca mais precoce que mulheres mais velhas (p<0,001). Em relação à infecção por HPV de alto risco, do total de mulheres que haviam iniciado as relações sexuais, 3.463 foram testadas, com 17,3% de positividade para HPV. Notadamente, em todos os centros, as mulheres com idade ao início da atividade sexual abaixo da média da população entrevistada apresentaram positividade maior para HPV (20,2%) do que as mulheres com sexarca em idade acima da média (12,5%) – Odds Ratio (OR)=1,8 (IC95%=1,5-2,2; p<0,001). Em relação à citologia, mulheres com sexarca abaixo da média de idade apresentaram também maior percentual de citologia alterada ≥ ASC-US (6,7%) do que mulheres com sexarca em idade maior que a média (4,3%) – OR=1,6 (IC95%=1,3-2,0; p<0,001). Conclusões: a infecção por HPV e a presença de alterações citológicas identificadas no rastreio de lesões cervicais em uma população assintomática estiveram significativamente associadas à idade mais precoce no início das relações sexuais. Ademais, identificamos também que as mulheres desta amostra apresentaram diminuição da idade ao início da atividade sexual, nas últimas décadas, sugerindo importante causa para o acréscimo da prevalência de HPV e as lesões decorrentes desta infecção.Purpose: to investigate women’s age at their first sexual intercourse and its correlation with their present age, human papillomavirus (HPV) infection and cytological abnormalities at Pap smear. Methods: women from the general population were invited to be screened for cervical cancer and pre-malignant lesions. After answering a behavior questionnaire, they were submitted to screening with cervical cytology and high-risk HPV testing with Hybrid Capture 2 (HC2). This report is part of the Latin American Screening (LAMS) study, that comprises centers from Brazil and Argentina, and the data presented herein refer to the Brazilian women evaluated at the cities of Porto Alegre, São Paulo and Campinas. Results: from 8,649 women that answered the questionnaire, 8,641 reported previous sexual activity and were included in this analysis. The mean age at the interview was 38.1±11.0 years and the mean age at the first sexual intercourse was 18.5±4.0 years. The age at the first sexual intercourse increased along with the age at the interview, i.e., younger women reported they had begun their sexual life earlier than older women (p<0.001). From the total of women who had already begun having sexual intercourse, 3,643 patients were tested for high-risk HPV infection and 17.3% of them had positive results. In all the centers, it became clear that the women with the first sexual intercourse at ages below the mean age of all the population interviewed presented higher rates of HPV infection (20.2%) than the women with the first sexual intercourse at ages above the mean (12.5%) – Odds Ratio (OR) 1.8 (IC95% 1.5-2.2;p<0,001). According to the cytology, the women with first sexual intercourse at ages under the mean, presented higher percentage of abnormal cytology ≥ ASC-US (6.7%) than the women with the first sexual intercourse at ages above the mean (4.3%) – OR 1.6 (IC95% 1.3-2.;p<0.001). ConclusionS: the high-risk HPV infection and cytological abnormalities identified during the asymptomatic population screening were significantly associated to the women’s age at the first sexual intercourse. Additionally, we have also identified that the women’s age at the first sexual intercourse has decreased during the last decades, suggesting an important contribution to the increase of HPV infection and the subsequent cervical lesions.Comissão Europeia - programa INCO-DEV (International Cooperation Development) Contrato #ICA4-2001-10013

O impacto do diagnóstico citológico de atipiasi indeterminadas no sistema público de saúde

As alterações citológicas de significado indeterminado representam uma importante limitação diagnóstica nos programas de escrutíneo de lesões cérvico-vaginais. A introdução de métodos biomoleculares, como o sistema de captura híbrida para detecção de HPV de alto risco contribui para a otimização da conduta clínica dessas pacientes, indicando colposcopia com precisão. Objetivo: avaliar o significado de lesões de significado indeterminado com relação à infecção pelo HPV, com o uso do teste de DNA para HPV com o método da captura de híbridos II. Métodos: foram estudadas amostras de 236 casos consecutivos examinados no laboratório da DIGENE-BRASIL, de pacientes com diagnóstico citológico prévio de ASCUS. As amostras foram submetidas ao teste de captura híbrida para identificação de DNA-HPV de alto e baixo riscos. Resultados: dos 236 casos analisados, 183 (77,5%) foram negativos para o teste de captura híbrida, seis (2,6%) foram positivos para HPV de baixo risco e 47 (19,9%) foram positivos para HPV de alto risco. Conclusão : as amostras positivas para HPV de baixo risco representam uma pequena e não- onsiderável minoria de casos, provavelmente, transientes. Cerca de 20% dos casos foram positivos para HPV de alto risco e deverão ser encaminhados à colposcopia e biopsia, se necessário. Esses casos representam um grande potencial de progressão para lesões cervicais.In order to optimize the morphological analysis of the cases with uncertain diagnosis, we critically analyzed the cases with Atypia of Squamous Cells of Undertemined Significance (ASCUS) in cytological samples of uterine cervix collected in conventional smears (CS) and liquidbased preparations (LBC) an to correlate the findings with Hybrid Capture II (HC2) assay and biopsy. Objective: to evaluate the meanig of undetermined cytological atypia in relation to HPV infection detected by hybrid capture II test. Methods: 97 cases taken from women examined at Perola Byignton Hospital, São Paulo, Brazil, during the year of 2002. The conventional smears were taken previously than LBC. The residual sample was placed in liquid-medium and LBC preparation with DNA-Citoliq system was performed. If at least one of the paired samples were classified as ASCUS, the pair was submitted to a guided revision in order to evaluate the type of alteration taken in account to categorized ASCUS. Results: from 97 cases studied, 14 were categorized as ASCUS by the two methods simultaneously. The others had different classification under or hyper estimated. Six cases diagnosed as squamous intraepithelial lesion (SIL) by CS were ASCUS by LBC; in contrary, 19 ASCUS by CS were SIL by LBC. Eleven ASCUS by CS were diagnosed as negative by LBC, but CS categorized 47 LBC ASCUS as negative. From the morphological parameters nuclear enlargement and coarse chromatin were regarded as ASCUS. From 68 ASCUS by LBC, 36 were HC2 positive for high risk HPV (hr-HPV) : ten of them with biopsy proven lesion. From 42 CS ASCUS, 23 were hr-HPV positive, but only 7 with histological lesion. Conclusion: our results reinforced the hypothesis that ASCUS is poorly reproducible by morphological examination by CS or LBC preparations. To add HC2 as adjunct method to ASCUS cytology can improve the routine diagnosed of the uncertain atypies

Hormonal contraceptives and the length of their use are not independent risk factors for high-risk HPV infections or high-grade CIN

AIMS: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. METHODS: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. RESULTS: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. CONCLUSIONS: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort.This study is a part of the ongoing LAMS (Latin American Screening) study, entitled: Improving Health Systems Towards Equality-Based Control of Cervical Cancer in Latin America, and is supported by the INCO-DEV Program of the European Commission (Project No. ICA4-CT-2001-10013). The generous contribution of Digene Corporation (USA) who donated the HCII tests at our disposal is gratefully acknowledged

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] ¼ 1.31; 95% CI 1.1–1.6), in women with two or more lifetime sexual partners (OR ¼ 1.9; 95% CI 1.6–2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR ¼ 1.6; 95% CI 1.2–2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P ¼ 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9–86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease

Evaluation of visual inspection with acetic acid (VIA), Lugol’s iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America

Objectives: To assess the performance indicators of visual inspection with acetic acid (VIA) and visual inspection with Lugol’s iodine (VILI) in four Latin American centres participating in the ongoing Latin AMerican Screening (LAMS) study, in settings with moderate incidence of cervical disease and with poorly to moderately well-organized cervical cancer screening. Setting: Three Brazilian centres (São Paulo, Campinas and Porto Alegre) and one Argentine centre (Buenos Aires) recruited a total of 11,834 healthy women to undergo VIA, VILI, conventional Pap smear and Hybrid Capture II (HCII). Methods: Women who had a positive result from any of these tests were subjected to colposcopy and biopsies (if necessary), and women with high-grade cervical intraepithelial neoplasia (CIN) were properly treated. To control for verification bias, 5% of women with normal tests were referred for colposcopy, as were 20% of HCII-negative women. Results: Data on VIA (n = 11,834), VILI (n = 2994), conventional Pap smear (n = 10,138) and HCII (n = 4195) were available for test comparisons, calculating sensitivity, specificity, and positive and negative predictive values. Overall test positivity was 11.6% for VIA, 23.0% for VILI, 2.2% for Pap smear (LSIL threshold), 1.1% for Pap smear (HSIL threshold) and 17.1% for HCII. VIA was positive in 61.8% of the women with CIN 1, 57.0% of those with CIN 2, 35.0% of women with CIN 3 and in 21 of 28 (75%) of women with cancer. Approximately 10% of women with no detectable disease had an abnormal VIA. Regarding VILI, 83.3% of women diagnosed with CIN 1 and 62.5% of those with CIN 3 had an abnormal test. VILI failed to detect one of three cases of cancer. Both the sensitivity, specificity and positive predictive value of VIA and VILI in detecting CIN 2 or CIN 3 could be significantly improved depending on the combination with Pap smear or HCII (sensitivity up to 100.0% and specificity up to 99.8%). Conclusions: The LAMS study failed to reproduce the performance figures obtained with VIA and VILI (as stand-alone tests) in some other settings, where the prevalence of cervical disease was higher. However, a combined use of VIA or VILI with the Pap test or HCII allowed specific detection of cervical abnormalities.European Union (EU) - INCO-DEV Programme - Contract# ICA4-CT-2001-10013

Screening for cervical Cancer in high-risk populations: DNA pap test or hybrid capture II test alone?

This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system. Women with suspected cervical disease were included in this crosssectional study at a tertiary center in São Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as ‘‘gold standard’’ and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy

The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls

Systemic infection with Streptococcus pneumoniae is associated with a vigorous pro-inflammatory response to structurally complex cell wall fragments (PnCW) that are shed during cell growth and antibiotic-induced autolysis. Consistent with previous studies, inflammatory cytokine production induced by PnCW was dependent on TLR2 but independent of NOD2, a cytoplasmic NLR protein. However, in parallel with the pro-inflammatory response, we found that PnCW also induced prodigious secretion of anti-inflammatory IL-10 from macrophages. This response was dependent on TLR2, but also involved NOD2 as absence of NOD2-reduced IL-10 secretion in response to cell wall and translated into diminished downstream effects on IL-10-regulated target gene expression. PnCW-mediated production of IL-10 via TLR2 required RIPK2 a kinase required for NOD2 function, and MyD88 but differed from that known for zymosan in that ERK pathway activation was not detected. As mutations in NOD2 are linked to aberrant immune responses, the temporal and quantitative effects of activation of the TLR2-NOD2-RIPK2 pathway on IL-10 secretion may affect the balance between pro- and anti-inflammatory responses to Gram-positive bacteria.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74582/1/j.1462-5822.2008.01189.x.pd