Associação dos tipos e variantes de HPV com o diagnostico histologico em mulheres com anormalidades em celulas glandulares do colo uterino

Orientadores: Luiz Carlos Zeferino, Sophie Françoise Mauricette DerchainTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Objetivo: Analisar a associação do tipo de HPV e das variantes dos HPV 16 e 18 com lesão neoplásica do colo uterino em mulheres cujo exame citológico apresenta anormalidades em células glandulares endocervicais. Métodos: Este estudo de corte transversal analítico incluiu 160 mulheres com citologia cervical de rastreamento, sendo 93 mulheres com células glandulares atípicas sem outras especificações (AGC-SOE), 18 com células glandulares atípicas provavelmente neoplásicas (AGC-NEO), 35 com por AGC associado a lesões intra-epitelias escamosas de alto grau (HSIL) e 14 com adenocarcinoma in situ (AIS). No primeiro atendimento foi colhido material cervicovaginal para pesquisa de DNA de HPV, segundo esfregaço cervical, e foi realizada colposcopia em todas as mulheres. Biópsias e/ou conizações foram realizadas em 129 pacientes. Trinta e uma mulheres encaminhadas por diagnóstico citológico de AGC-SOE com colposcopia normal e segunda citologia com resultado negativo foram seguidas a cada quatro meses com exames citológicos e colposcópicos. Todas as mulheres incluídas foram submetidas a ecografia pélvica. A pesquisa de DNA-HPV foi feita por PCR, utilizando os primers PGMY09 e PGMY11, e a genotipagem foi realizada através de hibridização reversa em pontos. A determinação das variantes de HPV 16 e HPV 18 foi realizada através de sequenciamento. Resultados: Dos 129 casos com avaliação histológica, 75 (58%%) mostraram diagnósticos neoplásicos (intra-epiteliais e invasivos). A maioria dos diagnósticos neoplásicos foi categorizada como de origem escamosa (77%). A prevalência total de HPV foi de 43%. O HPV 16 foi o mais prevalente e esteve significantemente associado a neoplasias escamosas (NIC 2 ou lesão mais grave) e neoplasias glandulares (AIS ou lesão mais grave). O HPV 18 foi o segundo tipo mais prevalente e esteve significativamente associado a neoplasias glandulares. Maior diversidade na distribuição dos tipos foi observada nos diagnósticos histológicos de NIC 2 e NIC 3. As neoplasias glandulares foram exclusivamente relacionadas aos tipos 16 e 18. O estudo de variantes incluiu 24 casos HPV 16 positivos e 6 casos HPV 18 positivos. Variantes Européias e Não Européias (Ásia-Americanas) foram detectadas, respectivamente, em 62% e 38% dos casos HPV 16 positivos. Variantes Européias de HPV 18 também foram mais prevalentes (3/6). Neoplasias glandulares foram mais prevalentes e significativamente associadas a Variantes Ásia-Americas de HPV 16. Variantes Européias de HPV 16 foram mais prevalentes em neoplasias escamosas. Neoplasias glandulares também foram associadas aos HPV 18, mas a análise de suas variantes não foi conclusiva, devido ao pequeno número de casos. Conclusão: Os HPV estão associados ao tipo histológico de neoplasia cervical detectada em mulheres com anormalidades em células glandulares endocervicais, contudo a identificação dos tipos não é suficiente para explicar o padrão histológico, uma vez que o HPV 16 pode estar associado com neoplasias escamosas e glandulares. A associação do HPV 16 com neoplasias escamosas e glandulares é explicada por suas variantes. Variantes Ásia-Americanas associam-se às neoplasias glandulares, enquanto variantes européias associam-se às neoplasias escamosasAbstract: Objective: To analyze the association between the different genotypes of oncogenic human papillomavirus (HPV) and HPV 16 and HPV 18 variants with histological diagnosis in women referred for glandular endocervical abnormalities in their cervical smear. Methods: This cross sectional study included a series of 160 women. Atypical Glandular Cells (AGC) not otherwise specification (NOS), AGC favor neoplastic (FN) were the only diagnosis in 93 and 18 women respectively. Thirty five patients had both AGC and high grade squamous intraepithelial lesion (HSIL). Fourteen women were diagnosed as adenocarcinoma in situ (AIS). All women were subjected a collection of sample for HPV-DNA testing and second cervical smear and underwent a colposcopic examination. Biopsies or conizations were done in 129 due to colposcopically abnormal area or second abnormal cervical smear result. In 31 women, referred due to AGC-NOS at screening cervical smear with adequate and normal colposcopy and second cervical smear results, follow up each 4 months with new cytology and colposcopy were done and the final diagnosis was considered as non-neoplastic. All women had pelvic ultrasound examination. The HPV-DNA testing was done by PCR using the set of PGMY09 e PGMY11 with genotyping by linear array hybridization. The molecular variants of HPV 16 and 18 were tested using PCR sequencing. Results: Among 129 women with histologic evaluation, 75 (58%) revealed neoplastic diagnoses (intraepithelial and invasive); of them the majority (77%) were of squamous cell origin. The overall prevalence of HPV was 43%. HPV 16 was the most prevalent genotype and was significantly associated with squamous neoplasias (CIN 2 or worse) and glandular neoplasias (AIS or worse). HPV 18 was the second most prevalent and was significantly associated with glandular neoplasias. Major diversity on HPV distribution was observed in Cervical Intraepithelial Neoplasia (CIN) 2 and CIN 3 histologic diagnosis. The variants study included 24 cases HPV 16 positives and 6 cases HPV 18 positives. European Variants and Asian-American Variants were detected in 62% and 38% of HPV positives cases. European variants of HPV 18 also were more prevalent (3/6). Asian-American HPV 16 variants were significantly associated with glandular neoplasia and European variants were more prevalent in squamous neoplasias. Glandular neoplasias also were associated with HPV18 but in this study the analysis of its variants was not conclusive. Conclusion: The HPV genotypes are associated with histological type of the cervical neoplasia, but HPV genotypes is not enough to explain at whole, since the HPV 16 were associated with squamous and glandular neoplasia. The association of HPV 16 with squamous or glandular neoplasia is explained by its variants. Squamous neoplasias were nearly related to HPV 16 European variants and glandular neoplasias were related to HPV 16 Asian-AmericanDoutoradoCiencias BiomedicasDoutor em Tocoginecologi

Human Papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalinfixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/ 58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Factors Associated With Hpv Persistence After Treatment For High-grade Cervical Intra-epithelial Neoplasia With Large Loop Excision Of The Transformation Zone (lletz).

Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). For this cohort study, a total of 94 women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook Pap smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27 (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were strongly associated with positive HPV during follow-up. HPV persistence following LLETZ was associated with smoking and with the interaction between age and conization margins.31270-

Increased Detection Of Clue Cells In Smears From Cervical Intraepithelial Lesions With Reduced Expression Of Cox-2.

The relation between the detection of clue cells in cervical smears of women with CIN and the expression of COX-2 in these lesions were determined. Samples from 228 women, treated due to CIN and who underwent cervical conization, were obtained. Hybrid Capture II and Pap smear samples were collected immediately before performing conization. Pathological diagnoses were 11 (5%) normal cervix, 35 (15%) CIN1, 31 (14%) CIN2, and 151 (66%) CIN3. COX-2 immunoreactivity grading on the pathological specimens was based on the German ImmunoReactive score. In cervical smears, 20 fields (40x) were examined, each of them with a minimum count of 10 epithelial cells. When 20% or more of clue cells were detected the sample was considered positive for clue cells. The prevalence of clue cells was similar across histological strata (P = 0.42). Although the expression of COX-2 did not differ in lesions with varying severities (P = 0.24), there was a negative association between the expression of COX-2 and the presence of clue cells in Pap smear (OR = 0.4; 95% CI = 0.2-0.9): only 12% of women with moderate and strong expression of COX-2 had clue cells in their smears, contrasted to 22% of those with negative and weak expression of COX-2. HPV infection was associated in a borderline manner to the expression of COX-2 (P = 0.04; OR = 2.3 95% CI = 1.0-5.4). The reduced expression of COX-2 in CIN specimens may suggest that clue cells interfere with the inflammatory component of the carcinogenic process that lead to CIN.36705-