Cervical cancer in the developing world

In developed countries, systematic screening programmes have reduced the morbidity and mortality resulting from cervical cancer. Cytological methods of screening have been the mainstay in these countries. Nevertheless, there is scant evidence that cytology-based screening has had any effect in reducing cervical cancer mortality in less-developed countries. In fact, the challenge in less-developed countries is surpassed by the complex array of problems that go far beyond the introduction of simplified technologies. Currently, there are two main issues on this subject: the assessment of simpler screening methods, and the evaluation of different strategies regarding which women to target and the screening interval. Achieving high rates of coverage and compliance of the target population through high-quality procedures has remained the most difficult goal to achieve. Nevertheless, it is believed that creativity, flexibility and well-focused use of resources can reduce the inequitable burden of cervical cancer borne by women in poor countries.20333935

Ex vivo Expansion of CD56(+) NK and NKT-like Lymphocytes from Peripheral Blood Mononuclear Cells of Patients with Ovarian Neoplasia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Methods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in Cell-Gro medium supplemented with anti-CD3 (9-10 initial days), IL-2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56(+) lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 +/- 63.4 and 82.7 +/- 25.3-fold, respectively, being the largest lymphocyte subtype among CD56(+) population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF-gamma, TNF-alpha and higher IL-4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56(+) effector cell fractions compared with CD56-deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56(+) lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56(+) population and the main variable among the final effector cell preparation affecting target cell killing.743244252Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2006/04600-2

Expression of cyclooxygenase-2 (COX-2) and Ki67 as related to disease severity and HPV detection in squamous lesions of the cervix

Objectives. To assess the expression of cyclooxygenase (COX-2) and Ki67 in cervical squamous lesions in relation to disease severity and human papillomavirus (HPV) detection. Subjects and methods. For this cross-sectional study, 223 women subjected to diathermic conization of the cervix have been enrolled, between February 2001 and April 2004. All patients undertook pelvic examination, including colposcopy and collection of samples for Hybrid Capture II (HCII). Pathological assessment disclosed: 9 cases of normal epithelium/cervicitis, 33 CIN1, 28 CIN2, 146 CIN3 and 7 invasive squamous cell carcinomas. COX-2 and Ki67 protein expression was determined with immunohistochemistry. COX-2 immunoreactivity grading was based on the German ImmonoReactive score. The continuum percentage of positive cells was used for the assessment of nuclear Ki67 expression. Results. Expression of COX-2 did not correlate with disease severity and with Ki67 expression. The HPV detection rates did not differ significantly across COX-2 protein expression strata, ranging from negative to strong expression. Ki67 expression, however, was higher in the CIN3 group (P = 0.001) as compared to the specimens rendered as normal/cervicitis. Conclusions. COX-2 protein expression did not correlate with disease severity or Ki67 expression. (c) 2006 Elsevier Inc. All rights reserved.102353754

Cytomorphological Criteria, Subclassifications of Endocervical Glandular Cell Abnormalities, and Histopathological Outcome: A Frequency Study

The objective of this study was to evaluate the frequency and the significance of cytomorphological criteria defined in studies as being predictive of neoplasia in cervical smears of women with a cytological diagnosis of atypical glandular cells (AGC) or adenocarcinoma in situ (AIS). Women (n = 103) with cytological findings suggestive of AGC or AIS, whose diagnoses were later established by histopathology, were included in the study. The criteria analyzed and classified as present or absent in cervical smears previously classified as AGC-NOS (not otherwise specified), AGC-FN (favor neoplasia), or AIS were as follows: irregular nuclear membranes; scanty cytoplasm; dyskeratotic cells; increased nuclear/cytoplasmic ratio; nucleoli; overlapping; papillary clusters, feathering; loss of polarity; nuclear enlargement; coarsely granular chromatin; and pseudostratified strips. Histopathology resulted in neoplastic diagnoses in 55 cases (53.3%) and nonneoplastic diagnoses in 48 cases (46.6%). Coarsely granular chromatin was observed in 62.5% of cases with a diagnosis of neoplasia. Feathering was present in 80% of cases of histopathological AIS. Loss of polarity and coarsely granular chromatin were significantly associated with neoplastic diagnosis considering all subcategories of glandular abnormalities diagnosis. In AGC-SOE subclassification. coarsely granular chromatin was significantly associated with neoplastic diagnosis. The presence of nucleoli was significantly associated with neoplastic diagnosis in cervical smears qualified as AGC-FN and AIS. Nuclear enlargement, increased nuclear/cytoplasmic ratio, coarsely granular chromatin and overlapping cells were found in all the subclassifications of glandular cell abnormalities irrespective of the histopathological results. Chromatin aspects, polarity, and presence of nucleoli can predict neoplasia. Diagn. Cytopathol. 2010;38:806-810. (C) 2010 Wiley-Liss, Inc.381180681

Variants of human papillomavirus types 16 and 18: Histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in cervical smear

Human papillomavitus (HPV) genotypes cannot fully explain the histological diagnosis of women with glandular abnormalities detected by cervical smear. Thus, this study was designed to analyze the distribution of HPV-16 and HPV-18 variants in women referred because of atypical glandular cells and adenocarcinoma in situ in their cervical smears and its association with histological results. Twenty-four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical smears suggestive of glandular abnormalities, were included. Histological results showed cervicitis (I case), squamous neoplasia (18 cases), glandular neoplasia (7 cases), and glandular neoplasia associated with a squamous component (4 cases). Among the 24 cases presenting HPV-16, the European variant was detected in 15 (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive adenocarcinoma. Asian-American HPV-16 variants were significantly. associated with histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2]) or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]). Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had the European variant, 1 had the Asian Amerindian variant, and 1 had the African variant. The association of HPV-16 with squamous or glandular neoplasia is explained by its variants. In this study, squamous neoplasia Was related to the European variant of HPV-16, whereas glandular neoplasia was related to the Asian-American variant. Glandular neoplasia is associated with HPV-18, but the results of our analysis of its variants were inconclusive.25439339