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[Cost effectiveness of cervical cancer screening strategies in Tunisia].

Cervical cancer is a public health problem in developing countries and is the first cancer among women in several of these countries. Screening using the Pap test is the principle control strategy for this cancer. The aim of this study is to identify the highest cost-effectiveness strategy of Pap test screening, according to age group (20-64 years, 35-64 years and 40-64 years) and the frequency of this test (every 3 years or every 5 years). Number of cases avoid by screening and mean cost to prevent one case were used to compare these screening strategies. The principles results showed that the number of cervical cancer cases avoid increase with the coverage level of the screening and age group size, and decrease with the frequency of the Pap tests. The screening strategy interesting age group "40-64 years" every 5 years observed the highest cost-effectiveness ratio (19 MD); however cost is 23 MD for age grovy 35-64 years. These results lead to choice a frequency of Pap tests every 5 years. However, for determination of age group, other factors, as psycho-social ones, should be taken into account besides economic criterias.

Age Distribution↗

Low risk of cervical cancer during a long period after negative screening in the Netherlands.

A condition for effective cervical cancer screening is a low incidence of cervical cancer after negative screening compared to that in the absence of screening. This relative risk was studied for the period 1994-1997 in the Netherlands and compared with previous studies. All cases of invasive cervical cancer diagnosed from 1994 to 1997 in the Netherlands were related to woman-years at risk, stratified by age, number of preceding negative screenings and time since the preceding negative screening. These incidence rates were compared with that before screening started in the Netherlands. The relative risk increases from 0.13 in the first year after screening to 0.24 after more than 6 years after screening for women with one previous negative screening. These figures reduce to 0.06 and 0.18, respectively, for women with two or more previous screenings. However, these estimates are less favourable when account is taken of the likely decrease in risk for cervical cancer in the period studied. Our data show a low relative risk of cervical cancer for several years following the last negative Pap smear. However, the denominator of the relative risk, that is, the incidence without screening, may have been overestimated. This applies also to the IARC multicountry study, and may have caused too optimistic expectations about the effectiveness of cervical cancer screening.

Adult↗

Invasive cervical cancer in human immunodeficiency virus-infected and uninfected hospital patients.

OBJECTIVE: To compare the prevalence of invasive cervical cancer in women with, and in women without, human immunodeficiency virus (HIV) infection, so as to evaluate the inclusion of invasive cervical cancer in the AIDS surveillance case definition. METHODS: The Sentinel Hospital Surveillance System for HIV Infection collected data and serum specimens that remained after clinical testing of persons who received inpatient or outpatient care at 14 hospitals with high HIV prevalence. We analyzed data on invasive cervical cancer obtained from medical record review and HIV serostatus from white, black, and Hispanic women in the age groups 20-34, 35-44, and 45-54 years. RESULTS: In 1994 and 1995, 2684 (6.6%) of the 40,524 women sampled were HIV infected. Of the HIV-positive women, 28 had invasive cervical cancer (10.4 per 1000 women) and of the HIV-negative women, 236 had invasive cervical cancer (6.2 per 1000 women, relative risk [RR] 1.7, 95% confidence interval [CI] 1.1, 2.5). The prevalence of invasive cervical cancer was higher for HIV-positive than for HIV-negative black women aged 20-34 (RR 3.8; CI 1.7, 8.5) and Hispanic women aged 20-34 (RR 7.3; CI 1.4, 37.1) and 35-44 (RR 3.9; CI 1.1, 14.7) years. Twenty-six of the 28 cases of invasive cervical cancer in HIV-positive women were in women known to be HIV-positive during admission. CONCLUSION: The prevalence of invasive cervical cancer was higher for women who were HIV positive than for women who were HIV negative. This lends support to the inclusion of invasive cervical cancer in the revision of the surveillance case definition for AIDS in 1993.

Adult↗

Reproductive and infectious risk factors for invasive cervical cancer in Taiwan.

A community-based case-control study was carried out to assess multiple risk factors for invasive cervical cancer in Taiwan. All of 183 cases of pathologically confirmed cervical cancer cases and 293 healthy neighborhood controls were recruited from Taipei metropolitus. Healthy controls were matched with cervical cancer cases for age and residence. Multiple risk factors for cervical cancer were obtained from study subjects through standardized interviews according to a structured questionnaire. Serotiters of antibodies to Chlamydia trachomatis (CLT), human cytomegalovirus (HCMV) and human herpes simplex virus type 2 (HSV-2) were determined by enzyme-linked immunosorbent assay. Multiple logistic regression analysis were used to derive maximum likelihood estimates of multivariate-adjusted odds ratios (AOR) and confidence intervals (CI). After adjustment for potential risk factors, parity and number of vaginal delivery were associated with an increased risk of invasive cervical cancer. The higher the number of vaginal delivery, the higher the risk of developing cervical cancer (AOR = 6.2, 95% CI = 1.7-22.6 for 7 or more deliveries compared with 0-2 deliveries as the referent group). Increased cervical cancer risk was also significantly associated with the history of chronic cervicitis (AOR = 2.1, 95% CI = 1.1-3.8) and elevated serotiters of CLT (AOR = 7.0, 95% CI = 1.7-28.9), HCMV (AOR = 4.1, 95% CI = 1.5-11.3) and HSV-2 (AOR = 2.3, 95% CI = 1.1-4.6). The use of diaphragm for contraception was found to be associated with a decreased risk of cervical cancer (AOR = 0.4, 95% CI = 0.1-1.0).

Adenocarcinoma↗

Screening for cervical cancer in the developing world.

Cervical cancer remains the most common malignancy amongst females in countries of low income, mainly due to a lack of screening. Responsible factors are centred around inadequacies of the Pap smear: high cost; low sensitivity; the need of a laboratory with high human expertise; and a demanding logistic system for mass screening. No alternative screening method seems to be clearly advantageous. Although combinations of tests have higher sensitivities, they are complex, costly and associated with low specificities. Adding the problem of effective treatment, it seems that mass screening with adequate coverage of the population is an unreachable goal for many developing countries. The most promising development in the control of cervical cancer seems to be vaccination against the human papillomavirus, either as a preventative measure or for stimulating immunity in infected women.

Acetic Acid↗

Epidemiology of cervical cancer--overview.

Numerous studies of the epidemiology of cervical cancer have shown strong associations with religious, marital and sexual patterns. Although it is well established that women with multiple partners and early ages at first intercourse are at high risk, less is known about how these factors interact or how risk is affected by specific sexual characteristics. Recent studies indicate that number of steady partners and frequent intercourse at early ages may further enhance risk, supporting hypotheses regarding a vulnerable period of the cervix and a need for repeated exposure to an infectious agent. It is now widely accepted that HPV is the major infectious etiological agent, but whether other infectious agents play supportive or interactive roles is unclear. Of specific interest is the independent effect of HSV 2 on risk, especially given some evidence that this viral agent may interact with HPV. Other speculative risk factors for cervical cancer include cigarette smoking, oral contraceptive usage and certain nutritional deficiencies, but again it is not clear whether these factors operate independently from HPV. Although cervical cancer incidence trends correlate with the population prevalence of various venereally transmitted agents, it is not certain how disease rates are affected by other potential risk factors which have changed during recent time (e.g., exposure to HPV, sexual behaviour, cigarette smoking). In addition, a number of recent studies highlight the need for considering not only female influences on risk of cervical cancer, but also male factors, since the sexual behaviour of the male consort appears to play an important role.

Europe↗

Metastatic cervical cancer and pelvic inflammatory disease in an AIDS patient.

The Center for Disease Control (CDC) recently added invasive cervical cancer to its list of surveillance case-defining diseases, and also included cervical dysplasia, carcinoma in situ, and pelvic inflammatory disease (PID) in the classification system. There are several reported cases of cervical cancer in AIDS patients that behaved in an unusually aggressive fashion and responded poorly to therapy. In light of the above-reported cases, it may be expected that cervical cancer may manifest itself in unusual ways in HIV-positive women. A case of aggressive cervical cancer in an AIDS patient with PID is reported. She was admitted with PID and newly diagnosed cervical cancer with recurrent fever spikes despite adequate antibiotic coverage. An aspiration of a presumed psoas abscess revealed metastatic squamous cell carcinoma. These data suggest that not only are HIV-infected women at risk for aggressive and unusual presentations of cervical cancer, but also that coexistent pelvic infection may contribute to development and spread of the disease. Immunosuppression from the virus may increase the incidence and severity of neoplasia. Data suggest that cervical cancer in HIV-infected women is often of advanced stage and responds poorly to treatment. Unique treatment approaches may need to be developed as conventional strategies do not seem to be adequate. More research is required to determine what these strategies should be. Lastly, universal HIV screening of women with either PID or cervical cancer seems prudent.

Acquired Immunodeficiency Syndrome↗

[Transposition of ovaries during radical hysterectomy for cervical cancer].

INTRODUCTION: 422 radical hysterectomies were performed for cervical cancer between 1st July 1990. and 31st December 2000. in the 1st Department of Obstetrics and Gynecology, Semmelweis Medical University. At least one of the ovaries was conservated and suspended in 21 cases. AIM(S): The aim of this study is to preserve ovaries guaranteeing natural oestrogen production for young patients suffering in early stage cervical cancer, and to prove appropriate efficacy of their method. PATIENTS/METHOD(S): According to present examinations transposition of ovary (21 patients) and radiotherapy made as a part of the protocol can only slightly influence the endocrine function of ovary. RESULTS: Only in one case of 21 a hormonal substitution was needed for treating menopausal syndrome. Studying histopathologically ovaries removed during 422 radical hysterectomies the authors could not find any metastasis given by early stage (I/A2 or I/B) cervical cancer. Following and controlling their patients after ovarial transpositions for a long period they could not observe any pathological ovarial disorder (cyst). CONCLUSION(S): According to the data of international literature the authors conclude, that transposition of ovaries during radical hysterectomy for well-selected, younger aged, early staged cervical cancer cases can result only a low risk, but much better quality of life for the patients.

Adult↗

Expression of Pin1 and Ki67 in cervical cancer and their significance.

In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P < 0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P < 0.05). No significant difference in the Pin1 expression was found between disease stages (FIGO), pathological grades or pelvic lymph node metastasis status (P > 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.

Biomarkers, Tumor↗

Women's Health Lotería: a new cervical cancer education tool for Hispanic females.

PURPOSE/OBJECTIVES: An innovative public education tool, called Women's Health Lotería (WHL), was created to promote cervical cancer awareness among Hispanic females. The tool covers the risk factors for cervical cancer, the American Cancer Society (ACS) cervical cancer screening guidelines, and the invasive cervical cancer incidence rate in the Hispanic population. DATA SOURCES: Professional journals and books; ACS and National Cancer Institute literature. DATA SYNTHESIS: Scientific evidence strongly suggests that cervical cancer mortality descreases with regular Pap test screening for sexually active women or those who have reached age 18. Many Hispanic women, however, do not know about the importance of Pap testing. WHL was developed to meet this learning need. CONCLUSIONS: After attending the educational program, 87% of the respondents achieved the learning objectives. IMPLICATIONS FOR NURSING PRACTICE: This educational program can be used to educate Hispanic women about cervical cancer. The content and principles also can be applied to other groups of women.

Adult↗

Hypoxia-inducible factor-1&#x3b1; promotes the malignant progression of cervical cancer cells by regulating lactate dehydrogenase A-mediated glycolysis.

BACKGROUND: Enhanced glycolysis is a hallmark of metabolic reprogramming in cervical cancer and plays a key role in tumor progression. Hypoxia-inducible factor-1&#x3b1; (HIF-1&#x3b1;), a core regulator of glycolytic metabolism, remains incompletely characterized in cervical cancer. This study aimed to investigate the expression pattern and clinical significance of HIF-1&#x3b1; in cervical cancer, and to explore its association with malignant biological behavior and lactate dehydrogenase A (LDHA)-related glycolytic metabolism in cervical cancer cells. METHODS: The expression level, clinicopathological features, immune infiltration correlation, and prognostic value of HIF-1&#x3b1; in cervical cancer were analyzed based on the The Cancer Genome Atlas (TCGA) database. HIF-1&#x3b1; overexpression and knockdown models were established in HeLa and Caski cells. Cell viability and invasive ability were assessed by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect changes in LDHA expression. Lactate production was measured using a lactate assay kit, and intracellular reactive oxygen species (ROS) levels were determined by flow cytometry. RESULTS: Bioinformatics analysis showed that HIF-1&#x3b1; was highly expressed in cervical cancer and was closely associated with patient age, menopausal status, immune cell infiltration, and poor prognosis. Kaplan-Meier survival analysis demonstrated that patients with high HIF-1&#x3b1; expression had significantly worse overall survival (OS) than those with low expression. In vitro functional experiments further confirmed that HIF-1&#x3b1; overexpression significantly enhanced the viability and invasive ability of HeLa and Caski cells, whereas HIF-1&#x3b1; knockdown produced the opposite effects. HIF-1&#x3b1; overexpression was associated with increased messenger RNA (mRNA) and protein expression levels of LDHA, a key glycolytic molecule, along with increased lactate production and elevated intracellular ROS levels. CONCLUSIONS: HIF-1&#x3b1; is aberrantly highly expressed in cervical cancer and may enhance glycolytic activity by upregulating LDHA expression, thereby promoting the proliferation and invasion of cervical cancer cells. These findings suggest that HIF-1&#x3b1; could serve as a potential diagnostic, prognostic, and therapeutic target biomarker for cervical cancer.

Hypoxia-inducible factor-1&#x3b1; (HIF-1&#x3b1;)↗

Epidemiology of cervical cancer in Taiwan.

Because the prevalence of several risk factors for cervical cancer, including sexual behavior, reproductive patterns, contraceptive use, and cigarette smoking, has changed significantly over time among Taiwanese women, it is of interest to analyze the impact of these trends on the incidence and mortality rates for this cancer during the decades between 1970 and 1990. The number of deaths from cervical cancer was obtained from the Taiwan Provincial Department of Health during the period from 1974 to 1992. Data of all incident cervical cancer cases from 1979 through 1990 obtained from the Taiwan Cancer Registry were also used for the analyses. The trends in the age-adjusted and age-specific rates were examined. Age, period, and cohort effects on the incidence and mortality rates were also examined, using age-period-cohort (APC) models. The age-adjusted mortality rate has been increasing since the 1970s, particularly in both the youngest group (20-29 years) and the oldest group (65 years and over). While the age-adjusted incidence rate decreased from 1979 to 1990, and decreases were apparent across all broad age groups, nevertheless, the incidence of adenocarcinoma was moderating during the same time period. The APC models disclosed a decreasing cohort effect for the mortality and incidence rates among women born after 1936. Decreasing incidence rates after menopause were more consistent with a hormonal effect than a cohort effect. Declining trends in cervical cancer incidence may be related to the screening practices which may have counteracted the increasing prevalence of several risk factors, although poor survival influenced the incidence/mortality differentials for cervical cancer. Continued surveillance is warranted; however, attention might be directed to the trends in cervical adenocarcinoma.

Adult↗

The public health breast and cervical cancer program. Our role as physicians.

Through a federally funded breast and cervical cancer control program, women who have breast or cervical cancer should be identified at earlier stages of their disease. Working together, community physicians and local health departments can ensure that the highest quality breast and cervical cancer control services are available to all women in their communities. This public/private partnership will help ensure the survival of these crucial members of our families and communities--our mothers, grandmothers, wives, sisters, daughters, friends, and co-workers. For information about the location of participating local health departments, please call the Michigan Department of Public Health Mammogram Hotline at 1-800-922-MAMM (1-800-922-6266). For media materials or for more information about becoming involved as a provider of services for community breast and cervical cancer screening programs, call (517) 335-9161. All women are at risk of developing breast and cervical cancer. Please do what you can to encourage all women to obtain screening according to the schedule recommended by the American Cancer Society and the National Cancer Institute. And please cooperate with your local health department when your community initiates this program. References available upon request.

Adult↗

Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients.

Human papillomaviruses (HPVs), particularly HPV-16/18, are linked to cervical cancer development. Full-length, recombinant HPV-16/18 E7 oncoproteins were used in a new streptavidin-biotin capture ELISA method to investigate anti-HPV E7 antibody prevalence in serum. Sera from 99 healthy women, 70 cervical cancer patients, and 30 patients with cervical pre-invasive neoplasia were analyzed. Anti-HPV-16/18 E7 positivity was found in 53% of cervical cancer patients, in 40% with cervical pre-invasive neoplasia, and in 8% of healthy women. Serum samples from 12 cervical cancer patients were obtained at different time intervals during the treatment. Eleven out of 12 showed a correspondence between HPV-E7 antibody levels (decreasing versus increasing) and the type of response (clinically complete or partial response versus progression or stable disease) at each serological evaluation. Five patients with recurrent HPV-16/18-positive cervical carcinoma were analyzed before and after vaccination with HPV-16/18 E7-pulsed autologous dendritic cells; anti-HPV-16/18 E7 positivity was found in 3 out of 5 women. In conclusion, this assay could potentially be used as an adjunctive tool to monitor the type of response to treatment and possibly to detect antibody induction in cervical cancer patients after vaccination, as a potential marker to evaluate its efficacy.

Antibodies, Viral↗

[A case-control study on the association between folate and cervical cancer].

OBJECTIVE: To evaluate the possible effects of folate on cervical carcinogenesis and the interaction of folate and human papillomaviruses 16 (HPV16). METHODS: A hospital-based case-control study was conducted. 111 hospitalized cases who were pathologically diagnosed of having cervical cancer and 111 controls identified with hysteromyoma that frequency-matched to cases on age, birth place and residential area. A 60-item food-frequency questionnaire (FFQ) were administered to estimate the consumption of dietary folate. HPV16 DNA in exfoliated cervical cell and serum folate were detected by special PCR and radioimmunoassay respectively. RESULTS: HPV16 infection rate in cases (61.26%) was significantly higher than that in controls (28.83%), with adjusted OR of 4.95(95% CI:2.49-9.83).The levels of dietary folate in cases (5.00 microg/kcal +/- 0.41 microg/kcal) were significantly lower than that in controls (5.14 microg/kcal +/- 0.35 microg/kcal), but the adjusted OR showing no statistical significance. However, serum folate in cases (1.79 ng/ml +/- 1.42 ng/ml) was significantly lower than that in controls(2.59 ng/ml +/- 2.81 ng/ml),and there were significantly increasing trend in the risk of cervical cancer with reducing level of serum folate (chi-squared trend test of P = 0.000). Meanwhile, low-level of serum folate and HPV16-infection showed significant interaction in the development of cervical cancer, with likelihood ratio test of G = 5.56, P = 0.02. CONCLUSION: Results indicated that low levels of folate might increase the risk of cervical cancer, and potential synergistic action might exist between low level of serum folate and HPV16 in the development of cervical cancer.

Case-Control Studies↗

Chapter 1: Human papillomavirus and cervical cancer--burden and assessment of causality.

Cervical cancer remains the second most common cancer in women worldwide and the most frequent in developing countries. Pre-neoplasic cervical lesions represent an additional burden in countries where screening is widespread. The human papillomavirus (HPV) prevalence and type distribution in normal smears and in cancer specimens are being described and show relatively small international variation. State-of-the-art detection techniques have unequivocally shown that HPV-DNA can be detected in 95% to 100% of adequate specimens of cervical cancer, supporting the claim that HPV is the necessary cause. The odds ratios for cervical cancer related to a cross sectional detection of HPV-DNA range from 50 to several hundred in all studies. The risk for any of 15 high-risk types is not statistically different from the risk reported for HPV16. The estimates of the attributable fraction range from 90% to 98%. Additional work should be done in providing information on incidence of cervical cancer and on HPV infection in areas where the disease is common. Theoretical work including modeling of the incidence could be of potential use in the evaluation of the existing and novel preventive strategies. Research is currently being conducted on the mechanisms of HPV carcinogenesis. These include the determinants of the systemic and cellular immune response to the viral infection, the interaction between the host and the virus and the relevance of the different strains and variants of the HPV viral types. Technology developments in this area suitable for epidemiological studies are needed.

Age Distribution↗

Cervical cancer screening knowledge, behaviors, and beliefs of Vietnamese women.

PURPOSE/OBJECTIVES: To describe the knowledge, beliefs, and practices of cervical cancer screening of Vietnamese women who have migrated to the United States. DESIGN: Exploratory, descriptive. SETTING: Five Vietnamese churches in southeastern Louisiana. SAMPLE: Nonprobability sample of 96 adult Vietnamese migrant women. METHODS: Data were collected by a bilingual nurse during face-to-face interviews conducted in the language preferred by the subjects (English or Vietnamese). MAIN RESEARCH VARIABLES: Cervical cancer screening knowledge, behaviors, and beliefs. FINDINGS: Three fourths of the Vietnamese women interviewed could not correctly explain what a Pap test is used for, and few were aware that the most commonly occurring cancer in Vietnamese females in the United States is cervical cancer. Most believed that their risk of cervical cancer was low. Less than half reported ever having had a Pap test and cited not having a gynecologist, cost, and fear of the test as reasons for not ever having had the test done. CONCLUSIONS: The number of Vietnamese women who adhere to cervical cancer screening guidelines is low. Cultural beliefs and structural barriers influence the choices that Vietnamese women make regarding Pap test utilization. IMPLICATIONS FOR NURSING PRACTICE: When planning programs to promote cervical cancer screening, nurses must target those at greatest risk--Vietnamese women. Culturally sensitive educational interventions and cervical cancer screening programs for Vietnamese women are needed to increase Pap test utilization and the early detection of cervical cancer.

Adolescent↗

Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence.

PURPOSE: Cervical cancer is the second most frequently diagnosed cancer in women worldwide. About one-third of patients experience recurrent disease. A better chance of survival might be achieved by the early detection of recurrent cervical cancer. [(18)F]fluoro-2-deoxy-D-glucose (FDG) PET could be a promising imaging modality for this purpose, given that FDG PET has high diagnostic efficacy. Ideally, pre-selection of patients should be performed before considering FDG PET. The purpose of this study was to investigate parameters of primary cervical cancer associated with recurrence as a basis for pre-selection of patients in whom FDG PET should be performed. METHODS: Thirty-eight cervical cancer patients, clinically suspected of having recurrent disease, underwent FDG PET. Tissue from primary tumours and nine histologically confirmed metastases was analysed for biomarkers possibly related to glucose metabolism and prognosis (vascular endothelial growth factor, CD31 for microvessel density, glucose transporter-1, hexokinases I, II and III, Ki67, p53, hypoxia-inducible factor 1alpha, and degree of infiltration by lymphocytes and macrophages). RESULTS: Based on clinical outcome, sensitivity and specificity of FDG PET were 96% and 100%, respectively. Cox regression revealed microvessel density and p53 (tumour suppressor protein) to be the two most important biomarkers for prediction of recurrence (hazard ratios 2.54 and 2.28, respectively). By combining these two biomarkers in a parallel test, sensitivity and specificity in predicting recurrence were 87% and 71%, respectively. Leave-one-out cross-validation demonstrated predictive validity of a model based on microvessel density and p53. CONCLUSION: In this first study of its kind, we have demonstrated that microvessel density and p53 profiles could be important in pre-selecting cervical cancer patients for detection of recurrence by FDG PET.

Adult↗