Diagnostic and prognostic use of DNA image cytometry in cervical squamous intraepithelial lesions and invasive carcinoma.
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In the fight against cervical malignancy and its precursors, several adjuvant diagnostic methods have been proposed to increase the accuracy of cytologic and histologic diagnoses. Because chromosomal aneuploidy has been accepted as an early key event in tumorigenesis caused by genetic instability, the cytometric equivalent of chromosomal aneuploidy detected by DNA image cytometry (DNA-ICM) may serve as a marker of neoplasia. During the last decade, the appearance of a new generation of hardware with high processing and storage capacities, together with the development of appropriate software, has facilitated the development of high-performance DNA-ICM systems. International consensus on the clinical application of DNA-ICM has been reached. According to the statements of Task Force 8 of the International Consensus Conference on the Fight Against Cervical Cancer, indications for DNA-ICM include the identification of prospectively malignant cells in squamous intraepithelial lesions (SILs) and atypical squamous cells of undetermined significance (ASCUS). The European Society of Analytical Cellular Pathology consensus reports on DNA-ICM have provided standardized technical details on performance, terms, and algorithms for diagnostic data interpretation and quality-assurance procedures. Increasing biologic evidence and clinical data have confirmed the utility of DNA-ICM as an adjuvant method suitable for determining the diagnosis and prognosis of cervical intraepithelial lesions and invasive carcinoma. Patients with ASCUS and low-grade SIL diagnoses that reveal DNA euploidy may return for normal screening intervals, whereas the detection of DNA aneuploidy indicates that these lesions should be removed. Formerly a research tool, today, standardized DNA-ICM has become a useful and low-cost laboratory method to establish objectively and reproducibly an early diagnosis of prospectively progressive cervical intraepithelial lesions at a high-quality level. DNA-ICM may further contribute to the monitoring of treatment in patients with invasive cervical malignancies. (+info)
Management of low-grade squamous intraepithelial lesions of the uterine cervix.
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Strategies of management for low-grade squamous intraepithelial lesion (SIL) vary even on a national level. We evaluated the diversity of management algorithms. This should serve as a source to find a common basis for the management of low-grade SIL. A total of 38 representatives and specialists for colposcopy and cervical pathology were contacted to provide national guidelines, recommendations or consensus for the management of patients diagnosed with the cytologic diagnosis of low-grade SIL. In all, 23 addressees (60%) responded. The algorithms provided varied considerably. Three variants of algorithms could be defined. Variant 1 was proposed in 14 countries and recommended colposcopy immediately after cytologic diagnosis of low-grade SIL or at the same time the smear is taken. If available, HPV testing was recommended as a triage option in some countries. Variant 2 is used in three countries and colposcopy is only performed after a repeated abnormal cytologic result within a 6-month interval or after an optional test positive for high-risk HPV. Variant 3, as proposed in six countries, takes into account the socio-economic status of the patient: In patients with poor compliance, 'see and treat' management is recommended; in patients where compliance can be assured, follow-up is carried out by cytology and colposcopy. Global policy of management of patients with low-grade SIL can be summarised in three algorithms. Quality standards and outcome parameters must be defined in order to improve the management of women with low-grade SIL. (+info)
Cigarette smoking, oncogenic human papillomavirus, Ki-67 antigen, and cervical intraepithelial neoplasia.
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Although cigarette smoking has been identified as a cofactor for cervical neoplasia, it is not clear whether smoking exerts an early or late effect on the evolution of human papillomavirus (HPV)-related lesions. A case-control study of Washington State women who presented for routine gynecologic care from 1997 to 2001 was conducted. All women underwent cytologic testing and HPV DNA screening. Those with abnormal cytology findings or a positive oncogenic HPV test and a random sample of women negative on both tests were referred for colposcopically directed cervical biopsy with repeated testing. Among 461 women with oncogenic HPV were 181 controls with negative histology, 137 cases with histologically confirmed cervical intraepithelial neoplasia (CIN) grade 1 (CIN1), and 143 cases with histologically confirmed CIN grades 2-3 or higher (>/= CIN2-3). Smoking information was obtained by questionnaire. Immunohistochemistry testing for Ki-67 was performed on a subset of biopsy specimens (n = 139). Smoking 10 or more cigarettes per day was associated with >/= CIN2-3 (adjusted odds ratio = 2.6, 95% confidence interval: 1.3, 5.5) and CIN1 (adjusted odds ratio = 2.5, 95% confidence interval: 1.2, 5.3). Heavy smoking was positively associated with Ki-67 but not with repeated detection of oncogenic HPV. Since smoking was associated with both CIN1 and >/= CIN2-3, cigarette by-products may affect the early evolution of HPV-related lesions, possibly by increasing the rate of cell turnover. (+info)
Visual inspection for cervical cancer screening: evaluation by doctor versus paramedical worker.
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BACKGROUND: In the absence of an effective cervical cancer screening programme, efforts are being made to explore the feasibility of using the existing infrastructure to develop effective low-cost screening methods. AIMS: To evaluate and compare test performance of visual inspection of the cervix by a doctor and a paramedical worker. SETTING AND DESIGN: Gynaecology outpatient department (OPD), All India Institute of Medical Sciences, New Delhi; cross-sectional study. MATERIAL AND METHODS: One hundred women with complaints of vaginal discharge, irregular bleeding, post coital bleeding or unhealthy cervix underwent visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) by a doctor and nurse, followed by colposcopy and biopsy. STATISTICAL ANALYSIS USED: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each test and compared. Concordance was determined by kappa statistics. RESULTS: VIA by nurse had a higher sensitivity (100% versus 87.5%), but lower specificity (53% versus 63%) when compared with the doctor, but it was not statistically significant. There was moderate agreement between their VIA findings (kappa=0.56). VILI findings were comparable to that of the VIA, both by the doctor and nurse. There was almost perfect agreement (kappa=0.89) between VILI by the doctor and nurse. CONCLUSION: Visual inspection can be performed reliably by trained paramedical workers and doctors and is an effective screening option in low resource settings. (+info)
Clinical evaluation of atypical glandular cells of undetermined significance upon cervical cytologic examination in Israeli Jewish women.
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The adjusted incidence of cervical carcinoma among Israeli Jewish women is approximately 5 out of 100 000. This retrospective study sought to determine the clinical implications of finding atypical glandular cells of undetermined significance (AGUS) in cervical cytologic specimens in this population. Cervical cytologic examinations during January 2001-June 2003 diagnosed as AGUS were identified by a computerised database. Medical records were reviewed to determine the presence or absence of associated significant pathologic conditions of the cervix and identified 45 out of 11 800 patients (0.38%) with AGUS. AGUS was the only cytologic diagnosis in 14 patients, while 31 patients had both AGUS and an additional atypical squamous cell of undetermined significance (ASCUS). All subjects underwent colposcopy, endocervical curettage, and cervical biopsy. A clinically significant diagnosis (cervical intraepithelial neoplasia (CIN) II, CIN III, or carcinoma) was made in 24 patients (53.3%), including cancer in three (6.7%): one had microinvasive adenocarcinoma and two had microinvasive squamous cell carcinoma. Squamous carcinoma coexisting with a clinically significant lesion carried a risk of 61.3%, compared with a risk of 35.7% for AGUS alone (P=0.20). Detection of AGUS during cervical cytologic screening, especially with a coexisting ASCUS, indicates the existence of serious pathologic processes; management by cervical colposcopy, endocervical curettage, and cervical biopsy is recommended. (+info)
An evaluation of liquid-based cytology and human papillomavirus testing within the UK cervical cancer screening programme.
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The aim of this study is to evaluate different options for introducing liquid-based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical cancer screening programme. These include options that incorporate HPV testing either as a triage for mild and borderline smear abnormalities or as a primary screening test. Outcomes include the predicted impact on resource use, total cost, life years and cost-effectiveness. Extensive sensitivity analysis has been carried out to explore the importance of the uncertainty associated with disease natural history and the impact of screening. Under baseline assumptions, the cost-effectiveness of different options for introducing LBC appears favourable, and these results are consistent under a range of assumptions for its impact on the diagnostic effectiveness of cytology. However, if we assume a higher marginal cost of LBC in comparison to conventional methods, primary smear testing options are predicted to be more cost-effective without LBC. Combined LBC primary smear and HPV testing with a 5-year interval is similar in both cost and effectiveness to the other 3-yearly options of primary smear testing or primary HPV testing alone. However, both primary HPV testing and combined options would give rise to a far greater risk of inappropriate colposcopy throughout a woman's lifetime. British Journal of Cancer (2004) 91, 84-91. doi:10.1038/sj.bjc.6601884 www.bjcancer.com Published online 25 May 2004 (+info)
Psychological impact of human papillomavirus testing in women with borderline or mildly dyskaryotic cervical smear test results: cross sectional questionnaire study.
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OBJECTIVE: To describe the psychological impact on women of being tested for human papillomavirus (HPV) when smear test results are borderline or mildly dyskaryotic. DESIGN: Cross sectional questionnaire study. SETTING: Two centres participating in an English pilot study of HPV testing in women with borderline or mildly dyskaryotic smear test results. PARTICIPANTS: Women receiving borderline or mildly dyskaryotic smear test results tested for HPV and found to be HPV positive (n = 536) or HPV negative (n = 331); and women not tested for HPV with borderline or mildly dyskaryotic smear results (n = 143) or normal smear results (n = 366). MAIN OUTCOME MEASURES: State anxiety, distress, and concern about test result, assessed within four weeks of receipt of results. RESULTS: Women with borderline or mildly dyskaryotic smear results who were HPV positive were more anxious, distressed, and concerned than the other three groups. Three variables independently predicted anxiety in HPV positive women: younger age (beta = -0.11, P = 0.03), higher perceived risk of cervical cancer (beta = 0.17, P < 0.001), and reporting that they did not understand the meaning of test results (beta = 0.17, P = 0.001). Testing HPV negative was not reassuring: among women with abnormal smear test results, those who were HPV negative were no less anxious than those who were not tested for HPV. CONCLUSIONS: Informing women more effectively about the meaning of borderline or mildly dyskaryotic smear test results and HPV status, in particular about the absolute risks of cervical cancer and the prevalence of HPV infection, may avoid some anxiety for those who are HPV positive while achieving some reassurance for those who test HPV negative. (+info)
Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study.
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OBJECTIVES: To evaluate symptoms and signs of genital irritation, vaginal leakage and acceptability of polystyrene sulfonate (PSS), which is being studied as a vaginal contraceptive and microbicide. METHODS: Forty-nine women applied 2.5 mL of either 5% PSS, 10% PSS, PSS vehicle, or Conceptrol (a marketed spermicidal product containing 4% nonoxynol-9) for 6 consecutive days. RESULTS: All women completed the study except one in the Conceptrol group who experienced vaginal symptoms after her first use and was discontinued. After both the first use and after all uses, irritation was seen among more women in the Conceptrol group than in the PSS groups, reaching statistical significance with regard to any evidence of irritation, signs of irritation and product-related irritation. There were no adverse events that were serious, unexpected and related to product use in any group. The 5% concentration of PSS may be preferable in terms of leakage and acceptability. CONCLUSION: The results suggest that PSS has a safety profile comparable to that of the marketed nonoxynol-9 product, Conceptrol, and appears to be associated with less genital irritation. (+info)