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Review of the screening history of Alberta women with invasive cervical cancer.

OBJECTIVE: To conduct a failure analysis of cervical cancer screening among women with invasive cervical cancer in Alberta. DESIGN: Descriptive study. Review of demographic, staging and treatment information from cancer registry records; generation of documented screening history from Alberta Health billing records and self-reported history from subjects who agreed to be interviewed; and comparison of findings in initial cytology reports with those from subsequent review by at least 2 pathologists of all cytology slides for each patient for the 5 years before diagnosis. Cases were assigned to 1 of 6 categories of identified screening failure. SETTING: Alberta. SUBJECTS: All women with diagnosis of invasive cervical cancer reported to a population-based provincial cancer registry from January 1990 to December 1991. OUTCOME MEASURES: Demographic, staging and treatment information; documented and self-reported screening histories; correlation of test results in initial cytology report with those generated from slide review; category of identified screening failure. RESULTS: Of the 246 women identified with invasive cancer of the cervix, 37 (15.0%) had stage IA disease; 195 (79.3%) had squamous-cell carcinoma, and 35 (14.2%) had adenocarcinoma. According to the categories of screening failure, 74 women (30.1%) had never been screened, 38 (15.4% had not been screened within 3 years before diagnosis, 42 (17.1%) had had a false-negative cytology result, and 20 (8.1%) had been managed outside of conventional protocols. Of the 23 women (9.3%) who had been screened appropriately and had true-negative results, 19 had smears that were considered technically limited. It was not possible to classify 49 (19.9%) of the cases. Agreement between the documented and the self-reported screening histories was exact for only 39 (36.1%) of the 108 women interviewed. CONCLUSIONS: Despite widespread use of opportunistic cervical screening, many women in Alberta are still not being screened adequately. In most cases women are being screened too infrequently or not at all. Self-reported screening histories are unreliable because many women may overestimate the number of smears. An organized approach to screening, as recommended by the National Workshop in Cervical Cancer Screening, may assist in reducing the incidence of invasive cervical cancer.

Adenocarcinoma↗

Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA.

Human cervical cancer is caused by high-risk types of human papillomavirus (HPV) such as HPV16 and HPV18, which possess the E6 and E7 oncogenes, whose concurrent expression is a prerequisite for cancer development and maintaining malignant phenotypes. Silencing these oncogenes is considered to be applicable in molecular therapies of human cervical cancer. However, it remains to be determined whether E6, E7, or both should be silenced to obtain most efficient antitumor activity by an HPV small-interfering RNA (siRNA). Herein, we report two types of siRNAs targeting HPV18 E6, that exerted a negative growth effect on HPV18-positive cervical cancer cells (HeLa and SW756), in part, inducing cell death. One siRNA (Ex-18E6), designed to target both E6-E7 mRNA and its splicing variant, E6*I-E7 mRNA, efficiently knocked down both E6 and E7 expression. The other (Sp-18E6), designed to specifically target E6-E7 mRNA but not E6*I-E7 mRNA, suppressed E6 to a similar level as Ex-18E6; however, it less efficiently inhibited E7 as compared to Ex-18E6. Although both siRNAs induced cell death, Sp-18E6 siRNA induced more prominent cell death than Ex-18E6. Our results suggest that E6-specific suppression may induce more potent anticancer activity than simultaneous E6 and E7 suppression, and that E6-specific targeting is a promising strategy for siRNA-based therapy for HPV-positive cervical cancer.

Animals↗

Cervical cancer screening in Korean American women: findings from focus group interviews.

PURPOSE: Korean American women have twice the rate of cervical cancer than white women and demonstrate low rates in participation in cervical cancer screening. This study was to describe the perceptions about cervical cancer and factors related to cervical cancer screening among Korean American women. METHOD: Focus group methods. RESULT: Five themes emerged. First, knowledge about cervical cancer; misconceptions about cervical cancer, its causes, reproductive anatomy and the treatment. Second, perceived meanings of having cervical cancer; most of the women felt that cervical cancer represented a loss of femininity and existential value of womanhood. Third, knowledge about cervical cancer screening ; regular medical check-ups were necessary for early detection and prevention of cervical cancer. Fourth, experiences and perceived meanings of cervical cancer screening; the participants expressed their feelings; embarrassment, fear, shame and shyness. Fifth, practices of cervical cancer screening; various intervals in participating in cervical cancer screening. But they mentioned several deterrents, language, insurance, time constraint, embarrassment, fear of the screening results, misbelief about susceptibility, lack of health prevention behavior, and lack of information written in Korean. CONCLUSION: Results emphasize the critical need for culturally appropriate health education to encourage participation of Korean American women in cervical cancer screening.

Adult↗

A critical review of patient-rated quality of life studies of long-term survivors of cervical cancer.

OBJECTIVES: Increasing survival rates of cervical cancer (CC) patients and the trend towards more toxic multimodal therapy have led to focus on the quality of life (QOL) of cervical cancer survivors (CCSs). The aim of this critical review was to summarize and discuss the research findings of QOL in CCSs based on self-report measures in terms of physical, psychosocial, and sexual well-being. METHODS: Electronic databases were used to identify studies published between 1966 and August 2005. A quality assessment using methodological and treatment-related criteria was performed to distinguish between studies with good and less good methodology. RESULTS: Twenty-three studies were included, whereof eight had a good methodology. Eight studies used at least one questionnaire that had not been validated previously, and only one of the validated questionnaires had been tested in former studies of CCSs. The studies with good methodology focused primarily on sexual and social function after treatment, and less on physical and psychological well-being. The trend is that radiotherapy is more associated with reduced QOL dimensions than surgery or chemotherapy. In earlier stages of CC and following surgery alone, there seem to be minor differences between CCSs and control groups concerning various QOL domains. CONCLUSIONS: Reviewed studies indicate that quality of life in cervical cancer survivors is reduced compared to the general female population following radiotherapy, but less so following surgery and earlier stages of cervical cancer. Shortcomings of both methodology and content of the studies reviewed preclude definite conclusions concerning QOL for the moment.

Female↗

Midwives' descriptions of their familiarity with cancer: a qualitative study of midwives working with population-based cervical cancer screening in urban Sweden.

Nurse-midwives are responsible for taking Papanicolaou (Pap) smears in Swedish population-based cervical cancer screening programs. A research project examining the screening program from the perspective of different stakeholders includes an interview study of 21 midwives working in Stockholm. This article explores the way the midwives describe cancer-related knowledge and aspects of screening, contrasting this with relevant findings from a substudy of 66 healthy women participating in screening. A semistructured interview guide with open-ended questions was used to investigate ideas about benefits and risks in the screening program, risk factors for cervical cancer, the reliability of the test itself, sources of information/knowledge relevant for cervical cancer screening, and the manner in which the midwife described her role in the screening program. The transcripts of the audiotaped interviews were analyzed thematically using a team approach. The interviewed midwives showed a great deal of consensus in their descriptions of lacking familiarity with cervical cancer and its prevention and treatment. The midwives said they lack recent education and knowledge, often avoiding use of the word "cancer" with women attending screening. It seems that the midwives experienced little professional guidance in discussing cancer-related issues with women attending the screening program. In this study, they appeared to rely on personal knowledge, values, and experience instead.

Adult↗

[The management of cervical cancer cases in pregnancy and puerperium].

UNLABELLED: Cervical cancer in women during pregnancy and puerperium is a serious diagnostic and therapeutic problem. Twelve multiparas with confirmed cervical cancer during pregnancy, delivery and puerperium were examined. The mean age of the group was 35. In two of them cervical cancer was diagnosed in the second trimester, in 5 in the third trimester and in 5 in puerperium. Clinical stage according to FIGO was as follow: Ib--9 patients, IIa--2 patients, III--1 patient. In two patients operated in the second trimester--extended hysterectomy was performed. In four women cesarean section with extended hysterectomy and lymphadenectomy was performed. Only one patient in third trimester had cesarean section and in the same time unradical hysterectomy because of bleeding. In two patients in puerperium extended hysterectomy was performed (Meigs operation). Three patients underwent only radiotherapy. All patients who were operated on underwent subsequent radiotherapy. CONCLUSIONS: Cervical cancer during pregnancy and puerperium is diagnosed very late, usually in advanced stage. It is connected with lack of clinical and cytological examination of women before pregnancy. Principles of treatment of cervical cancer in pregnancy and puerperium do not differ from those applicable in other patients.

Adult↗

A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer.

DNA of a new papillomavirus type was cloned from a cervical carcinoma biopsy. Two EcoRI clones of 7.8 and 6.9 kb in length were obtained, the latter contained a 900-bp deletion. The BamHI fragments of both clones were used to characterize the DNA. It represents a distinct type of papillomavirus as determined by its size, its cross-hybridization with DNA of other papillomavirus types under conditions of low stringency only, the co-linear alignment of its genome with HPV 6 and HPV 16 prototypes and its occasional occurrence as oligomeric episomes. We tentatively propose to designate it as HPV 18. DNA hybridizing with HPV 18 under stringent conditions was detected in 9/36 cervical carcinomas from Africa and Brazil, in 2/13 cervical tumors from Germany and 1/10 penile carcinomas. Benign tumors (17 cervical dysplasias, 29 genital warts), eight carcinomata in situ and 15 biopsies of normal cervical tissue were devoid of detectable HPV 18 DNA. HPV 18-related DNA was found, however, in cells of the HeLa, KB and C4-1 lines all derived from cervical cancer. The state of the viral DNA was investigated in four cervical cancer biopsies. The data reveal that the DNA might be integrated into the host cell genome. One tumor provided evidence for head to tail tandem repeats some of which persisted as circular episomes.

Base Sequence↗

Involving the community in cervical cancer prevention programs.

Underutilization of cervical cancer prevention services by women in the high-risk age group of 30-60 years can be attributed to health service factors (such as poor availability, poor accessibility, and poor quality of care provided), to women's lack of information, and to cultural and behavioral barriers. The Alliance for Cervical Cancer Prevention (ACCP) partners have been working to identify effective ways to increase women's voluntary participation in prevention programs by testing strategies of community involvement in developing countries. The ACCP experiences include developing community partnerships to listen to and learn from the community, thereby enhancing appropriateness of services; developing culturally appropriate messages and educational materials; making access to high-quality screening services easier; and identifying effective ways to encourage women and their partners to complete diagnosis and treatment regimens. Cervical cancer prevention programs that use these strategies are more likely to increase demand, ensure follow-through for treatment, and ultimately reduce disease burden.

Ambulatory Care↗

Efficacy and cost-effectiveness of nationwide cervical cancer screening in Taiwan.

The annual cervical screening programme using the Papanicolaou (Pap) smear test was launched for women aged 30 years and over from 1995 in Taiwan. This study aimed to evaluate the Taiwanese cervical screening policy and to make recommendations based on the empirical findings from cervical screening data between 1995 and 1998. We used a stochastic process to model the natural history of precancerous lesions and cervical cancer. Based on the estimated results, Monte-Carlo computer simulation was used to evaluate the effectiveness in terms of the reduction in incidence of and mortality from cervical cancer for screening regimes with different screening intervals. Annual Pap smear screening with 100% compliance was estimated to lead to an approximate 80% reduction in deaths from cervical cancer. With 50% compliance, around a 40% reduction was expected. Triennial screening with high compliance was as effective as annual screening with low compliance, and more cost-effective. Based on the observed Taiwan Pap smear-screening programme between 1995 and 1998, with 44.5% women attending at least once, there was an estimated reduction of 16% in deaths from cervical carcinoma. The estimated effectiveness was greater when the period was extended to 2001, in which period 61% of women attended at least once. The screening programme by 2001 was estimated to reduce cervical cancer mortality by 50% (95% confidence interval: 29-65%). The incremental cost-effectiveness was estimated as 8174 dollars per additional life-year gained. In conclusion, triennial screening targeting women aged 30-69 is recommended, along with efforts to enhance the compliance rate.

Adult↗

An overview of innovative techniques to improve cervical cancer screening.

Although current cytomorphology-based cervical cancer screening has reduced the incidence of cervical cancer, Pap-smears are associated with high false positive and false negative rates. This has spurred the search for new technologies to improve current screening. New methodologies are automation of Pap-smear analysis, addition of new biological or molecular markers to traditional cytology or using these new markers to replace the current screening method. In this overview we will summarize data on cervical cancer epidemiology and etiology and the current cervical cancer screening approach. Available data on new screening approaches, such as quantitative cytochemistry, detection of loss of heterozygosity (LOH) and hypermethylation analysis will be reviewed. We discuss the potential of these approaches to replace or augment current screening. When available, data on cost-effectiveness of certain approaches will be provided. In short, Human Papillomavirus (HPV) DNA detection stands closest to implementation in nation-wide screening programs of all markers reviewed. However, specificity is low in women aged <35 years and the psychological effects of knowledge of HPV positivity in absence of cervical (pre) malignant disease are important drawbacks. In our opinion the results of large clinical trials should be awaited before proceeding to implement HPV DNA detection. New technologies based on molecular changes associated with cervical carcinogenesis might result in comparable sensitivity, but improved specificity. Hypermethylation analysis is likely to be more objective to identify patients with high grade squamous intra-epithelial lesions (HSIL) or invasive cancer with a higher specificity than current cytomorphology based screening.

Biomarkers, Tumor↗

Holistic care of the patient with cervical cancer.

Participation by women in screening programs for cervical cancer is far from optimal, and many lives are lost because of this. Cervical cancer is common, and is easily detected and treated. It has a good prognosis for cure if detected early in its course. Effective screening has been shown to have a major role in decreasing the morbidity and mortality associated with cervical cancer. Therefore, there is a need for increased public health education and availability of screening programs for women. It is particularly important that public health efforts reach women in the lower socioeconomic groups who are less apt to exhibit health promotive behaviors. Women of Latin American heritage are at particularly high risk because of cultural barriers to the discussion of sexual practices. Until public health interventions are more successful, cervical cancer will continue to pose a major threat to women who are either too embarrassed or too misinformed to understand that prevention is an integral part of women's health care. Nurses view patients in a holistic way. It is this philosophy of care that offers women who are diagnosed with cervical cancer a means to adapt successfully to the psychologic and physiologic stresses associated with the diagnosis. Nurses need to recognize this strength and to offer holistic approaches to women in crisis. No two patients deal with a diagnosis of cancer in the same manner. A major challenge to nurses across a hospital community continuum is to provide comprehensive psychologic and physiologic assessment of a women's response to a diagnosis of cervical cancer and to provide effective and holistic intervention when necessary.

Female↗

Decision science and cervical cancer.

Mathematical modeling is an effective tool for guiding cervical cancer screening, diagnosis, and treatment decisions for patients and policymakers. This article describes the use of mathematical modeling as outlined in five presentations from the Decision Science and Cervical Cancer session of the Second International Conference on Cervical Cancer held at The University of Texas M. D. Anderson Cancer Center, April 11-14, 2002. The authors provide an overview of mathematical modeling, especially decision analysis and cost-effectiveness analysis, and examples of how it can be used for clinical decision making regarding the prevention, diagnosis, and treatment of cervical cancer. Included are applications as well as theory regarding decision science and cervical cancer. Mathematical modeling can answer such questions as the optimal frequency for screening, the optimal age to stop screening, and the optimal way to diagnose cervical cancer. Results from one mathematical model demonstrated that a vaccine against high-risk strains of human papillomavirus was a cost-effective use of resources, and discussion of another model demonstrated the importance of collecting direct non-health care costs and time costs for cost-effectiveness analysis. Research presented indicated that care must be taken when applying the results of population-wide, cost-effectiveness analyses to reduce health disparities. Mathematical modeling can encompass a variety of theoretical and applied issues regarding decision science and cervical cancer. The ultimate objective of using decision-analytic and cost-effectiveness models is to identify ways to improve women's health at an economically reasonable cost.

Cost-Benefit Analysis↗

Cervical cancer and vital statistics.

Records of cervical cancer mortality in vital statistics have been so affected by differences in diagnosis, certification, compilation and presentation that they are not suitable for time and place comparisons. Records of combined mortality charged to cervical cancer, other uterine cancer and cancer of other genital organs have been less affected. These records from different places show declines which do not appear to be correlated with control programs but, in recent years, have brought the rates from places cited into agreement. Reductions in reported cases of cervical cancer following screening for and treatment of carcinoma in situ have stimulated interest. However, the uncertainty in the mortality records and in understanding of cervical cancer and its relationship to carcinoma in situ, agreement in recent mortality rates despite diversity of sources, and other pertinent considerations cast doubt on the significance of such reductions.

Adult↗

Improved prognostic value of 18F-FDG PET using a simple visual analysis of tumor characteristics in patients with cervical cancer.

UNLABELLED: In patients with cervical cancer, it is important to estimate prognosis at the time of diagnosis. This study using PET with (18)F-FDG was undertaken to determine whether a simple and fast visual analysis of characteristics of the primary tumor before initiation of treatment could achieve this goal. METHODS: Forty-seven patients with cervical cancer who were to be treated by combined radiation therapy and chemotherapy were imaged before beginning treatment. They were then followed for up to 3 y for evidence of recurrence or death. Images of the chest, abdomen, and pelvis were obtained 40-90 min after administration of 370-555 MBq (10-15 mCi) (18)F-FDG. Three observers then independently graded the primary tumor for size (0 = small, 1 = moderate, 2 = large), shape (0 = spherical, 1 = nonspherical), heterogeneity of uptake (0 = none, 1 = moderate, 2 = marked), and presence of lymph nodes (0 = none, 1 = pelvic, 2 = paraaortic, 3 = distant). The scores were summed to achieve a total score. A statistical calculation demonstrated that a score cutoff of 4 best separated patients with a good prognosis from patients with a bad prognosis. Kaplan-Meier analysis was used to compute progression-free survival and overall survival. Evaluation of lymph nodes alone was compared with the grading of tumor characteristics. RESULTS: Observers 1 and 2 scored 26 patients as having a good prognosis and 21 as having a bad prognosis. Observer 3 scored 30 and 17, respectively, a statistically insignificant difference. Survival curves were almost identical for the 3 observers. For progression-free survival, approximately 12% of patients with a good score had disease recurrence whereas approximately 75% with a bad score had disease recurrence. For overall survival, approximately 10% (good) and 80% (bad) died. Evaluation of lymph nodes also separated the groups, but not as well as did visual analysis alone. The combination of the 2 was only slightly superior to visual assessment alone. CONCLUSION: A simple, rapid, and highly reproducible system is described for visual grading of characteristics of the primary tumor in patients with cervical cancer at the time of diagnosis. This approach separates patients with a poor prognosis from those who will do well, thus providing a new tool for accurate estimation of prognosis.

Adult↗

Spinal cord compression in metastatic cervical cancer.

Spinal cord compression secondary to metastatic cervical cancer may not be considered as a possible cause of neurologic symptoms by primary care physicians who do not often treat these patients. Delays in diagnosis and treatment may result in irreversible but potentially preventable neurologic changes. This report describes 5 cases of spinal cord compression in patients with metastatic cervical carcinoma, 2 of whom were previously undiagnosed with cervical cancer. These 2 patients represent 1.6% (2 of 121) of all new cervical cancer cases diagnosed during this time period. Two of 5 patients (40%) with spinal cord compression showed improvement following therapy by regaining the ability to walk, while none of the remaining patients had further acute deterioration of neurologic function. The mean survival of patients presenting with spinal cord compression from cervical cancer in this series was 4 months (maximum 6 months). This series illustrates the relative frequency with which spinal cord compression is seen in patients with a new diagnosis of invasive cancer. This diagnosis should be considered when evaluating neurologic complaints in known cervical cancer patients or any woman with apparent pelvic pathology. Rapid diagnosis and treatment of these lesions, while not likely to improve overall survival significantly, can improve function and alleviate symptoms.

Adult↗

Cancer prevention in primary care. Screening for cervical cancer.

Cervical screening has been shown to be effective in several countries, although not by means of randomised controlled trials. A screening programme has been in operation in the United Kingdom since 1964, but it has, in the past, been beset with problems of organisation, accountability, and commitment. The introduction in 1988 of a systematic call and recall introduction in 1988 of a systematic call and recall system and the setting up of an NHS cervical screening programme national coordinating network has brought a greater sense of coherence. Coverage of the target population in England between 1989-90 and 1992-3 increased from 61% to 83%, and there is a strong indication that cervical screening is now beginning to reach those most at risk--namely, older women from lower social classes. Primary care is central to the overall success of the cervical screening programme. General practitioners are in a unique position to invite women for a smear test, to take smears, to ensure that abnormal smear test results are followed up, and to check on reasons for non-attendance. Numerous studies have looked at the involvement of general practice in cervical screening, identifying many ways in which the programme can be improved. Many practices are now running well organised and effective programmes.

Family Practice↗

Ethical dilemmas of cervical cancer screening.

Cervical screening presents several ethical dilemmas to family physicians. The author reviews the risks associated with screening, costs versus benefits of running a screening program, and the issues surrounding patient autonomy and patient coercion. Is saving one life worthwhile, and at what cost? Cervical screening programs are imperative in family practice, but only if harm to the patient is minimized and ethical objections are addressed.

Coercion↗

[Long time survival after combination chemotherapy with cisplatin, vinblastine and peplomycin for cervical cancer].

Twenty seven patients with cervical cancer were treated with PVP therapy including cisplatin 50mg/m2, vinblastine 4mg/m2 and peplomycin 15mg/body during the period from 1984 to 1989. Fourteen patients had a primary lesion. Five of 14 patients were treated with PVP as the primary therapy because of pathological findings which suggested no radiotherapy effect. Nine patients had a radio-resistant lesion and were treated following PVP. Twelve of 14 cases responded and median survival time was 32.5 months (2-101 months). Thirteen patients were treated with PVP because of recurrent cervical cancer. Five of those which recurred after radiotherapy and other 8 cases had been treated with radical hysterectomy and radiotherapy. Two of 5 cases with previous radiotherapy responded and one of 2 patient is still alive with no evidence of disease, but the patients treated with radical hysterectomy and pelvic irradiation showed no sign of a PVP effect and all of them died within 1 year. Primary cases responded even after radiation and some are still alive after more than 5 years. But PVP had no effect on the in patients which there was recurrence. It is necessary to determine which regimen is better, how to select the dose of cisplatin and how to combine the chemotherapy and other therapy. Patients who responded survived for a long time and PVP is an effective therapy. To obtain a better prognosis for advanced cervical cancer, we need a prospective randomized study of radio-chemotherapy or chemo-radiotherapy.

Adult↗