Prescribing errors intercepted by pharmacist intervention in care of patients hospitalised with breast and gynaecological cancer at a Brazilian teaching hospital.

Oncologic inpatients often require multiple drug therapy. They may be at higher risk of experiencing prescribing errors, which pharmacist interventions may help to avoid. This study aimed to evaluate the types of prescribing errors, pharmaceutical interventions and differences in clinical significance, in prescriptions for hospitalised patients with breast and gynaecological cancer. A cross-sectional, prospective study was conducted at the oncology ward of a clinic specialised in breast and gynaecology cancer. A clinical pharmacist analysed prescriptions, identified errors, performed interventions and classified clinical significance. A total of 1,874 prescriptions of 248 patients were evaluated; 11.5% prescriptions were involved at least in one prescribing error, totalising 283 errors. The most common error was unsafe medication due to drug interaction (89[31.4%]). Drugs for the alimentary tract and metabolism, and nervous system were the most involved in errors with statistical association (p = .0246 and p = .0002 respectively). Of the 294 interventions, 73.5% were accepted. The clinical significance of prescribing errors and interventions were classified as significant and very significant respectively. The pharmacist interventions obtained a good acceptance rate and impact significantly, avoiding prescribing errors classified as significant.

Ex vivo expansion of CD56+ NK and NKT-like lymphocytes from peripheral blood mononuclear cells of patients with ovarian neoplasia.

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 CellGro 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-γ, TNF-α 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.

Self-sampling for human papillomavirus (HPV) testing as cervical cancer screening option. Experience from the LAMS study.

PURPOSE: To compare Hybrid Capture II (HC2) in detecting high-risk (HR) HPV in patient-collected vaginal samples with those obtained using gynaecologist collected samples. METHODS: Patients were submitted to Pap smears, visual inspection with acetic acid (VIA) and HC2 for hr-HPV. RESULTS: A total of 1,081 HC2 tests for HR-HPV were performed: 770 (71.2%) samples were collected by a physician and 311 (28.8%) were self-collected by the patients. In detecting any cervical lesion, the sensitivity of HC2 collected by a physician was higher (92.86%) than that (37.5%) in the self-sampling group. Negative predictive value (NPV) was high for both, 99.69% and 93.75%, respectively. Using the CIN2 cutoff, performance of HC2 was significantly improved: 92.9% and 62.5%, respectively. HC2 specificity for any cervical lesion and for CIN2 or higher were close to 90% in both groups. CONCLUSIONS: Self-sampled HPV testing is a powerful option to increase the detection of cervical lesions in women segregated from prevention programs.

Safety of screening with Human papillomavirus testing for cervical cancer at three-year intervals in a high-risk population: experience from the LAMS study.

OBJECTIVES: To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)-/HPV- women in low-income settings. METHODS: Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2- or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors. RESULTS: Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70-3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40-3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV- women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1-11.7). CONCLUSION: These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV-/Pap-women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).

Endocervical glandular cell abnormalities in conventional cervical smears: evaluation of the performance of cytomorphological criteria and HPV testing in predicting neoplasia.

OBJECTIVE: To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia. METHODS: A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection. RESULTS: Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status. CONCLUSIONS: Feathering was the best criterion for predicting glandular neoplasia.

Cell proliferation activity unrelated to COX-2 expression in ovarian tumors.

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.

Prediction of high-grade cervical disease with human papillomavirus detection in women with glandular and squamous cytologic abnormalities.

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.

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] = 1.31; 95% CI 1.1-1.6), in women with two or more lifetime sexual partners (OR = 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 = 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= 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.

Atypical glandular cells: criteria to discriminate benign from neoplastic lesions and squamous from glandular neoplasia.

OBJECTIVE: To evaluate the presence of some criteria in cervical smears with atypical glandular cells and their correlation with histological patterns to identify pre-neoplastic and neoplastic lesions. METHODS: Seventy-three women referred with an atypical glandular cell smear, who had undergone conization or hysterectomy, were included in this study. Referral Pap smears were reviewed using the set of 27 cyto-morphological criteria that was correlated with the histological diagnosis. RESULTS: Histological results showed intraepithelial or invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After logistic regression and decision tree analysis an increased nuclear/cytoplasmic ratio and the presence of dyskeratotic cells were strongly associated with intraepithelial or invasive neoplasia and the differential cyto-morphological criteria for glandular lesions were decreased cytoplasm, irregular nuclear membranes and the presence of nucleoli. CONCLUSION: The analysis of individual cyto-morphological criteria can better predict intraepithelial or invasive neoplasia and differentiate glandular from squamous lesions.

Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America. This report refers to partial results from the LAMS (Latin AMerican Screening) study.

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.

Aided visual inspection with acetic acid (VIA) and HPV detection as optional screening tools for cervical cancer and its precursor lesions.

PURPOSE OF INVESTIGATION: To assess the contribution of visual inspection with acetic acid (VIA) and Hybrid Capture II (HCII) as adjunct methods to the Pap test in detecting cervical neoplasia. SUBJECTS AND METHODS: This was a cross-sectional study with 809 women who consecutively attended gynecological consultations at Campinas University, Brazil, from January 2002 to July 2003. Pap test, HCII, VIA, and colposcopy were offered to all patients. Performance of tests (alone or in combination) in detecting histologically confirmed lesions was evaluated. RESULTS: Of the 40 patients with CIN, 69% had CIN1, 26% CIN2 or CIN3 and one patient had invasive carcinoma. VIA had the best performance in detecting CIN, yielding 72% sensitivity and 91% specificity. Considering only CIN2 or worse as significant lesions, HCII had the best sensitivity (73%), while the Pap test was the most specific (93%). Combining the three exams, 92% of the CIN1 or worse were detected. When CIN1 was excluded from the analysis, Pap smear plus HCII delivered 82% sensitivity and 79% specificity. However, this combination yielded a very low (5%) PPV. CONCLUSION: VIA and HCII contributed to the screening of cervical neoplasia in a group of Brazilian women, but the cost-effectiveness of conjoint screening modalities is still debatable.

P53 and Bcl-2 as prognostic predictors in epithelial ovarian cancer.

The study was designed to evaluate the prognostic importance of clinical and pathologic variables with p53 and Bcl-2 in epithelial ovarian cancer using multivariate analysis. Tumor tissues from 90 patients were analyzed immunohistochemically for p53 and Bcl-2 expression. Hazard ratios were calculated in univariate and multivariate survival analyses. Forty-two (47%) were considered positive for p53 expression and 18 (20%) were positive for Bcl-2. Positive expression for p53 was less frequent in patients in FIGO stage I (22%). Positive staining for Bcl-2 correlated significantly with the histologic type (P < 0.01). No direct correlations could be demonstrated between p53 and Bcl-2 expression and age or histologic grade. In univariate analysis, p53 and Bcl-2 expression were not significantly correlated with overall survival, disease-free survival, or progression time. FIGO stage III and IV and residual disease > or =2 cm3 after first surgery were significantly correlated with poor outcome in univariate analysis. FIGO stage retained their independent prognostic value in multivariate analysis. Neither p53 nor Bcl-2 had any significant influence on outcome in multivariate survival analysis. FIGO stage proved to be the only significant independent prognostic factor in epithelial ovarian cancer, although residual disease remains correlated with disease-free survival.

Value of morphological criteria in diagnosing cervical HPV lesions confirmed by in situ hybridization and hybrid capture assay.

The present study evaluated the value of morphological criteria (binucleation, multinucleation, koilocytosis, spindle koilocytes, abnormal mitosis and dyskeratosis) in the diagnosis of cervical human papillomavirus (HPV) lesions confirmed by in situ hybridization (ISH) and hybrid capture (HC) assay. Colposcopic punch biopsies from a series of 138 women with abnormal Pap smears were examined on light microscopy and in situ hybridization (DAKO widespectrum cocktail probe) for HPV-induced morphological changes and HPV DNA, respectively. Cervical swabs were analyzed for HPV DNA of the oncogenic types using Hybrid Capture. CIN 2 and CIN 3 were found in 44 biopsies, CIN 1 in 62, and no evidence of HPV in 32 cases. HPV was detected by ISH in 51/138 (37%) cases and by HC in 66/138 (48%) lesions. With both tests, HPV DNA detection increased parallel with lesion severity, up to 70% and 59% in CIN 2/3 by HC and ISH, respectively OR 4.6 (1.7-12.1) and 10.1 (3.0-33.8). Among the histological criteria, multinucleation, binucleation and abnormal mitoses were significantly associated with HPV DNA detection. Multinucleation proved to be the strongest predictor of HPV DNA-positivity. Binucleation, abnormal mitosis, koilocytosis and spindle koilocytes were also reliable criteria of HPV lesions. Minor nuclear atypia, and "mild koilocytosis" were of no value in making this diagnosis.

Morphological diagnosis of HPV lesions and cervical intraepithelial neoplasia (CIN) is highly reproducible.

PURPOSE: to assess the value of individual histological criteria in the diagnosis of cervical HPV lesions. METHODS: 138 women referred for colposcopic evaluation (due to abnormal PAP smears) were subjected to cervical punch biopsy. The biopsies were classified as no HPV lesion, CIN 1, or CIN 2-3 by two observers independently. Kappa tests were used for interobserver agreement of the diagnosis. The presence of binucleation, multinucleation, abnormal mitosis. koilocytosis, spindle koilocytosis and dyskeratosis was similarly assessed. RESULTS: the Kappa statistic was 0.638 (CI 95% 0.533-0.743), showing substantial inter-observer agreement. Abnormal mitosis and multi-nucleation were the two most powerful discriminators between CIN 2-3 and CIN 1. Koilocytosis proved to be the single most powerful discriminator between CIN 1 lesions and non-HPV lesions. CONCLUSION: the results advocate the use of histology as the gold standard in diagnosing cervical precancerous lesions. The classical criteria can be also used to differentiate low-grade lesions, which has practical implications by avoiding the unnecessary treatment of minor abnormalities.

Accuracy of intraoperative frozen section diagnosis of ovarian tumors.

OBJECTIVE: The goal of this work was to evaluate retrospectively, as quality control, the accuracy of frozen section diagnosis in ovarian tumors. METHOD: We compared 243 frozen section results with the final diagnosis in paraffin sections, from cases studied from January 1994 to April 1999. RESULTS: Results with the two methods were analyzed on two parameters: (a) malignant potential and (b) histological type. As for malignant potential, frozen section diagnosis agreed with the paraffin diagnosis in 94% of all cases (98.5% for malignant tumors, 94% for benign tumors, and 78.6% for borderline tumors). There was one false-positive and 13 false-negative cases. Sensitivity and specificity values for malignant tumors were 93 and 99%; for borderline tumors, 61 and 99%; and for benign tumors, 98 and 93%. With respect to histological type, in 203 cases (84%) the pathologists had no doubt in the diagnosis; in 40 cases (16%) diagnosis was given as "compatible with." In 35 of these (87.5%) the initial diagnosis was confirmed by paraffin. CONCLUSION: Frozen section diagnosis seems to be a reliable method for ovarian tumors, with high sensitivity for malignant neoplasms and a low false-positive rate which allow the best choice of treatment. The most frequent problems arise with borderline and granulosa cell tumors.

High risk HPV and p53 protein expression in cervical intraepithelial neoplasia.

INTRODUCTION: Cervical intraepithelial lesions due to HPV infection are common in Brazil. An understanding of the mechanisms of the interaction between HPV and host factors is still incomplete. In spite of the high incidence of cervical cancer in Brazil, such studies with Brazilian patients are scarce. The purpose of this study was to correlate the presence of high-risk types of HPV and expression of p53 protein, grade of cervical lesion, age, high-risk sexual behaviors and smoking. It was also intended to establish whether p53 expression might be useful as a marker for CIN progression. METHODS: HPV detection was performed on paraffin sections using biotin-labeled probes by in situ hybridization. p53 protein expression was evaluated by immunohistochemistry. RESULTS: Seventy-eight patients with cervical dysplasia were included in the study. CIN 1 was diagnosed in 38 cases, and CIN 2+3 in 40 cases. High-risk HPV was detected in 42 patients. No correlation was found between the grade of cervical lesion or the presence of HPV and smoking, and high-risk sexual behavior. Expression of p53 was significantly higher in CIN 1, as compared with CIN 2+3, but did not correlate with HPV status. CONCLUSION: Higher expression of p53 protein in early lesions supports the hypothesis of a partially protective role of the wild-type p53 in early stages of cervical lesions.

[Comparison between reference oncologic colpocytology and severity of intraepithelial cervical lesions]. / Comparação entre a colpocitologia oncológica de encaminhamento e a da gravidade das lesões cervicais intra-epiteliais.

OBJECTIVE: The study was designed to compare the Pap smear results, performed on the public health service, with: the results of Pap smear collected on the reference service; the colposcopy and punch biopsy results. METHODS: The total of 213 women assisted at the women's hospital from January 1989 to April 1991, and followed until July 1998 were selected. Ninety were referred because a Pap smears suggestive of Human Papillomavirus (HPV) induced lesion or cervical intraepithelial neoplasia (CIN) grade 1, and 123, CIN 2 or 3. RESULTS: Among the 90 women referred because of HPV/CIN 1.49% presented CIN 2 or 3 in the Pap smears performed at this service. At the colposcopy, 16/90 women did not present suspicious lesions, and in 10 women, the squamous columnar junction was not observed. At biopsy, 42 (46%) presented CIN 2 or 3. Out of the 123 women referred with Pap smear of CIN 2 or 3.54% presented CIN 2 or 3 at this service. At the colposcopy, 24 women did not present suspicious lesions and the squamous columnar junction was not observed in 12. About biopsy, 61 (49%) presented CIN 2 or 3. CONCLUSIONS: The expectant conduct in cases of Pap smear with HPV/CIN 1, should follow a criterion, involving qualified professionals to collect the Pap smear, and should provide people awareness as to control follow-up.

Ovarian germ cell cancer: clinicopathologic analysis and outcome of 31 cases.

AIMS: The aim of the study was to evaluate some clinicopathologic characteristics and the outcome of patients with ovarian germ cell cancer (OGCC) treated with cisplatin-based chemotherapy. METHODS: It was a clinical retrospective study. The clinical charts of 31 patients with OGCC assisted at the Department of Obstetrics and Gynecology of the State University of Campinas, Brazil, from January 1986 to June 1997 were reviewed. RESULTS: Ten patients had dysgerminoma and 21 patients nondysgerminomatous tumors. Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding surgical staging, age, ascites or residual tumor after the initial surgery. Frozen section, performed in 16 patients, showed some discrepancy with paraffin histology diagnosis in 8 patients. Platinum-based chemotherapy was used in 5/10 patients with dysgerminoma and in 17/21 patients with nondysgerminomatous tumors, with a 5-year survival of 100% for the dysgerminoma and 53% for the nondysgerminomatous group. CONCLUSIONS: Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding clinicopathologic characteristics. The prognosis for patients with dysgerminoma was better than for those with nondysgerminomatous tumors. Frozen section had a high error rate in diagnosing OGCC intraoperatively.

Cigarette smoking and high-risk HPV DNA as predisposing factors for high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women.

BACKGROUND: This cross-sectional study was designed to evaluate the role of cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in young, sexually active Brazilian women. MATERIALS AND METHOD: A series of 100 consecutive women with abnormal Pap smears were recruited, subjected to colposcopy, punch biopsy, and questionnaire for their social, sexual and reproductive factors. Of these, 77 women between 20 and 35 years of age (median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were enrolled in this study. Representative samples from the exocervix and endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA assay, including the probes for the oncogenic HPV types (16, 18, 31, 33, 35, 45, 51, 52 and 56). RESULTS: The overall rate of CIN 2 and 3 was 23/77 (29.8%). The women with CIN 1, 2 and 3 did not differ from each other with regard to their age, race, schooling, marital status, lifetime number of sexual partners, age at first intercourse, use of oral contraceptives, or parity. However, current cigarette smoking was strongly associated with CIN 2 and 3 (p<0.001), and among smokers, the risk of high-grade CIN increased in parallel with the time of exposure (years of smoking) (p=0.07). HPV-DNA of the oncogenic types was detected in 43 (56%) women, the risk of being HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with CIN 1 (p=0.037). Importantly, the prevalence of high-risk HPV types was significantly higher in cigarette smokers than in non-smokers (p=0.046). CONCLUSIONS: The results indicate that the severity of CIN lesions was clearly related to two fundamental risk factors: 1) high-risk HPV types, and 2) current cigarette smoking. These two risk factors were closely interrelated in that the high-risk HPV types were significantly more frequent in current smokers than in non-smokers, suggesting the possibility of a synergistic action between these two risk factors in cervical carcinogenesis.