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Three-dimensional power Doppler imaging of early-stage cervical cancer.

OBJECTIVES: To characterize intratumoral vascularization in early-stage cervical cancer by three-dimensional (3D) power Doppler ultrasound. METHODS: One hundred and forty-one patients with carcinoma of the uterine cervix and 30 normal controls were studied by transvaginal 3D power Doppler ultrasound. The tumor volume of the cervical cancer was determined. The blood flow within the tumor or normal cervix was measured and expressed as the vascularization index (VI), flow index (FI) and vascularization flow index (VFI). RESULTS: Of the 141 patients with cervical cancer, 44 patients had undergone prior cervical conization. Eighty-seven patients had measurable cervical tumors, of whom five had had prior conization. Abundant intratumoral power Doppler signals could be detected, and the VI, FI and VFI were significantly elevated in cervical cancer patients compared with women with a normal cervix and patients in whom no cervical tumor could be detected (P < 0.05, one-way ANOVA). We observed four types of intratumoral vascularity patterns, which did not significantly differ in VI, FI and VFI: localized, peripheral, scattered and single-vessel types. Cervical tumor volume was positively correlated with FI (linear regression, r = 0.373, P = 0.001), but not with VI or VFI. CONCLUSIONS: 3D power Doppler ultrasound provides a useful tool to investigate intratumoral vascularization and volume of cervical cancer.

Adult↗

Dietary vitamin A and the risk of invasive cervical cancer.

The relation between dietary vitamin A and the risk of invasive cervical cancer was evaluated using data from a hospital-based case-control study of 191 women with cervical cancer and 191 age-matched controls. There was no association between dietary retinoids and cervical cancer risk. Intake of dietary beta-carotene, on the other hand, was inversely and strongly related to the risk of cervical cancer. Compared to risks for women reporting a monthly intake of 150,000 or more international units (IU) of beta-carotene, the estimated relative risks for those with 100,000 to 149,000 and those with less than 100,000 IU per month were 2.8 and 6.1 respectively. The inverse association was not explained by any of the major identified risk factors for cervical cancer (including indicators of socio-economic status or sexual habits), or by differences in general characteristics and other lifestyle habits between cases and controls. Thus, although the uncertainties of the vitamin A measurements used are substantial, these findings support the hypothesis that dietary beta-carotene-or some related aspect of a vegetable-rich diet-is protective against invasive cervical cancer.

Animals↗

[DNA content in dysplasias and early invasive forms of cervical cancer].

Cytological preparations of normal cervical epithelium and in different forms of the epithelial dysplasia and in early cervical cancer were studied in 8 healthy females and in 35 patients. To determine the content of DNA in these cells a fluorescent variant of the Feulgen reaction was employed, using the national drug rivanol as fluorochromium in the Shiff reagent. The amount of DNA in cell nuclei of the normal epithelium and in moderate dysplasia is shown to correspond to diploid, while in marked dysplasia the content of DNA varies from di-to tetraploid values. But there are some cases when in marked dysplasia the DNA content in cells is diploid, i. e. it is characteristic of moderate dysplasia, or considerably exceeds tetraploid level, and it is in such cases that histological assays reveal early forms of cancer. Invasive cancer is charcterized by a sharp increase in the DNA content in most cells and by a considerable number of polyploid cells. Fluorescence-microscopy may serve as a valuable diagnostic adjunct to recognize early forms of cervical cancer and be used clinically.

Carcinoma, Squamous Cell↗

Cervical cancer.

The overall incidence of and mortality from cervical cancer has declined in western countries and in most developing countries. In women under 40 years of age, however, mortality rates are levelling off or increasing in most countries. The earliest and most marked increases in young women occurred in England and Wales, Scotland, Ireland, New Zealand and Australia. Mortality rates in young women from eastern European countries began to increase later than in the UK, but the increases are of concern because baseline mortality rates are high in these countries. The reasons for the overall decline in cervical cancer are largely unknown but appear to be linked to improvements in the general standard of living. The increases in young women may well be due to the increasing prevalence of HPV infection. Screening for cervical cancer has undoubtedly led to a decline in cervical cancer incidence and mortality in many countries, but its contribution to the trends is difficult to assess without further information.

Adult↗

Use of process evaluation to guide health education in Forsyth County's project to prevent cervical cancer.

The Forsyth County, NC, Cervical Cancer Prevention Project is a 5-year public health education program designed to increase the proportion of black women in the county who are appropriately screened for cervical cancer. In this paper, the authors report on process evaluation--the procedures used to monitor the intervention and to insure that the target population was reached with a high quality, community-based health education program. A system that encompasses documentation of program activities, interviews with women in waiting rooms of primary care providers, semiannual interviews with a panel of approximately 100 women from the target population, and telephone followup with participants in direct education workshops was designed and implemented. Through October 1990, more than 2,100 interviews had been conducted. Data from these activities have facilitated continued development and refinement of educational materials, provided guidance for developing new strategies for reaching the target population, and provided continuous feedback to program managers to allow monitoring the impact of all program activities.

Black or African American↗

Screening for breast and cervical cancers: the importance of knowledge and perceived cancer survivability.

INTRODUCTION: This study examines the association between recent screening for breast and cervical cancers, knowledge of cancer risk factors, and perceptions of surviving cancer. METHODS: Data were from the Cancer Control Supplement to the 1992 National Health Interview Survey (NHIS-CCS). The dependent variable combined breast and cervical cancer screening practices into a single composite index. Two independent variables combined women's knowledge about breast and cervical cancers into single indicators--one representing risk factor knowledge, the other representing perceived likelihood of surviving breast and cervical cancers following early detection. RESULTS: Multivariate analysis showed that recency of screening for both breast and cervical cancers was associated with knowledge of cancer risk factors and perceptions of surviving cancer. Education, household income, and smoking status also were correlates of comprehensive screening. Significant interactions between income and perceived survivability, and between education and perceived survivability suggested that the effects of income and education on comprehensive screening varied with perceptions about surviving cancer. CONCLUSION: The study suggests that knowledge and attitudinal questions can be combined for two diseases to enhance understanding of who is most likely to be screened comprehensively for breast and cervical cancers. Although national trends show that large percentages of women over age 50 are having mammograms and Pap tests, this progress is not likely to be sustained unless existing barriers are eliminated. Limited knowledge about breast and cervical cancer risk factors and misperceptions about survival from cancer represent two of these barriers.

Aged↗

[Expression, purification, and serum antibody detection of HPV16 E6 in cervical cancer patients].

BACKGROUND & OBJECTIVE: Human papillomavirus type 16 (HPV16) is the predominant high-risk type of HPV in cervical cancer tissues. Serum antibody responded to HPV16-related proteins is associated with the development of cervical cancer. This study was to construct and purify recombinant HPV16 E6 protein, detect its corresponding serum antibody among different populations, and explore the correlation of HPV16 E6 serum antibody reaction to cervical cancer. METHODS: HPV16 E6 early gene was constructed into pRSET-A expression vector. The plasmids were transfected into BL21 (DE3) cells, which were induced to express HPV16 E6 protein by isopropylthio-beta-D-galactoside (IPTG). E6 inclusions were denatured, purified through Ni column, and renatured. After the activity of HPV16 E6 protein being identified, the antibodies against HPV16 E6 in serum samples from 80 healthy women, 46 chronic cervicitis patients, and 32 cervical cancer patients were determined by ELISA using the fusion protein as antigen. HPV DNA genotype was estimated in cervical cancer tissues by fluorescence polarization. RESULTS: HPV16 E6 fusion protein of Mr 24x10(3) was expressed in pRSET-16E6 after induction of IPTG. The fusion protein was accounted for 22.3% of total bacterial proteins, and expressed as inclusive body. After purification with Ni-NTA agarose resin, the purity of the recombinant protein was over 95%, and its activity was identified by ELISA. The antibody-positive rate was significantly higher in cervical cancer patients than in healthy women and chronic cervicitis patients (31.2% vs. 5.0% and 6.5%, P<0.01). In the 32 cervical cancer patients, the positive rates of HPVs DNA and HPV16 DNA in cancer tissues were 90.61% and 46.88%. The antibody-positive rate of HPV16 E6 was higher in HPV16 DNA-positive cervical cancer patients than in HPV16 DNA-negative patients (46.7% vs. 17.6%), but the difference was not significant. CONCLUSIONS: HPV16 E6 fusion protein obtained from pRSET-A/BL21 can be used in serologic studies on cervical cancer-related HPV infection. Serum antibody against HPV16 E6 is more common in cervical cancer patients than in healthy women and chronic cervicitis patients.

Adult↗

Transcriptional activation of H- and N-ras oncogenes in human cervical cancer.

OBJECTIVE: Overexpression of p21 protein has been detected in human cervical cancer. However, to date, there are no data on the differential activation of the three ras genes at the transcriptional level in cervical lesions. The purpose of this study was to evaluate the quantitative and qualitative changes of expression of the ras family genes in the development of human cervical cancer. METHODS: The expression of ras mRNA levels in 35 human cervical specimens [11 normal cervix, 15 cervical intraepithelial neoplasia (CIN), 9 cervical cancer] was examined using the RT-PCR technique. In addition, we studied the incidence of point mutations in codon 12 of each ras gene using RFLP analysis and human papilloma virus (HPV) status. RESULTS: The transcript levels for H-ras and N-ras were significantly higher in cancer cases compared to normal cervical tissues (P=0.0002 and P=0.001, respectively) and CIN lesions (P<0.0001 and P=0.002, respectively). The transcript levels for K-ras were similar in normal cervical tissue, CIN and cervical cancer. A strong positive correlation was found between H- and N-ras expression (P=0.001) and no correlation between H- and K- or N- and K-ras expression. Point mutations were detected only in three samples, located in codon 12 of K-ras gene. No relationship was found between expression levels of each ras gene and the presence of HPV. CONCLUSION: Our findings indicate the expression pattern of the three ras genes in cervical tissue and the involvement of H- and N-ras up-regulation in the pathogenesis of cervical cancer independent of HPV infection.

Adenocarcinoma↗

[Cervical cancer: recent trends of incidence and mortality in Lithuania].

Time trends of the cervical cancer in Lithuanian population were analysed. Changes in age standardised cancer incidence rates (World standard) in Lithuania were analysed between 1978 and 1999. Incidence rates were calculated by periods--1978-1982, 1983-1987, 1988-1992, 1993-1997 and 1998-1999. Incidence was analysed among 15-34, 35-49, 50-64, 65-74 and 75+ age groups. From 1978-1982 cervical cancer incidence decreased from 15.4 to 12.9 per 100,000 in 1993-1997. Increase was observed from 1993-1997 up to 17.4 per 100,000 in 1998-1999. In 1998-1999 only 49.2 of all cervical cancer cases were diagnosed at stages I and II. During 1978-1992 cervical cancer mortality rates were not decreasing despite the reduction of incidence (6.8, 7.0 and 6.8 cases per 100,000 in 1978-1982, 1983-1987 and 1988-1992 respectively). Starting from 1993 the increasing number of new incidence cases is being registered, but mortality rates are not subjected to changes (7.6 and 7.7 cases per 100,000 in 1993-1997 and 1998-1999 metais respectively). The higher increasing rates in incidence and mortality were observed among women below 50 years. The causes of increase of cervical cancer incidence are demanding detailed studies. The incidence and mortality of cervical cancer can be reduced by the implementation of national-wide screening program for cervical cancer.

Adolescent↗

Surgical management of early stage cervical cancer: ten years experience from one Greek health region.

PURPOSE OF INVESTIGATION: Cervical cancer is the second most common malignancy in women, in both incidence and mortality. In the present study, we report our results of treating 93 consecutive patients with early invasive cervical cancers (Stages I-IIA). METHODS: The patients of this study comprised all women recognized with stage I-IIA cervical cancer during 1991-2000. Patients with stage IA1 cervical cancer without lymphvascular space involvement underwent either conservative management by means of large loop conization or simple hysterectomy. The remaining patients underwent radical hysterectomy and lymphadenectomy or radiation therapy. Mean (+/- SD) duration of follow-up was 6 (+/- 1.7) years. RESULTS: The mean (+/- SD) age of patients with stage I-IIA cervical cancer was 41.3 (+/- 9.1) year. Thirty-five patients with stage [A1 disease were managed conservatively with loop excision and 19 patients subsequently became pregnant. Fifty-two patients with stage IA2, IB and IIA cervical carcinoma underwent radical hysterectomy and lymphadenectomy. CONCLUSION: Young women with stage IA1 cervical carcinoma wishing future fertility who undergo loop excision have a 100% cure rate. Women with stage IA2, IB, and IIA cervical cancer should undergo radical hysterectomy and lymphadenectomy or radiation therapy.

Adult↗

Cervical cancer: prevention, diagnosis, and therapeutics.

Cervical cancer is a leading cause of cancer deaths in women worldwide. Because of its association with human papilloma virus infection, as well as the ability to screen for premalignant stages of the disease, it is now largely a preventable disease. This article describes the molecular basis for cervical cancer, and presents a clinical overview of current treatment approaches and technological advances, emphasizing the unique aspects of this viral disease as it relates to the immune system and vaccination or other immunotherapeutic strategies.

Female↗

Correlation of cervical cancer mortality with reproductive and dietary factors, and serum markers in China.

BACKGROUND: Cervical cancer is the second leading cause of cancer death among Chinese women. Within China, a considerable geographical variation in mortality rates has been observed, but the reasons are not well understood. METHODS: Cervical cancer rates were examined in relation to indices of reproductive factors, dietary habits, and selected serum biomedical markers in 65 rural Chinese counties. RESULTS: Cervical cancer mortality rates correlated positively and significantly with antibodies to herpes simplex virus type 2 (HSV-2) (r = 0.40, P < 0.01), serum levels of ferritin (r = 0.33, P < 0.01), body mass index (BMI) (r = 0.42, P < 0.01) and cigarette smoking (r = 0.51, P < 0.05) and negatively and significantly with age at first birth (r = -0.51, P < 0.01), consumption of green vegetables (r = -0.40, P < 0.01) and animal foods (r = -0.40, P < 0.01), and serum levels of selenium (r = -0.26, P < 0.05). When these variables were considered in the multiple regression analysis, early age at first birth and higher BMI were positively associated with cervical cancer mortality, while consumption of green vegetables and animal foods were negatively correlated. In the serum model, infection with HSV-2 and low levels of sex hormone binding globulin (SHBG) were positively related to cervical cancer mortality. No relation was found for consumption of fruits. CONCLUSIONS: Although limitations of these ecologic data preclude causal inferences, findings in this study, including associations with HSV-2 infection, early age at first birth, consumption of green vegetables and animal foods, may provide clues to cervical cancer aetiology.

Adult↗

Combined low-dose-rate brachytherapy and external beam radiation for cervical cancer: experience over ten years.

Cervical cancer was treated with a combination of external beam and intracavitary radiation during a 10-year period at Wayne State University. Data were collected for 216 patients treated radically with external beam radiation (EBRT) and low-dose-rate brachytherapy for cervical cancer between 1980 and 1991 at Wayne State University. Patient distribution by stage was IB, 20.8%; IIA, 7.4%; IIB, 26.9%; IIIA, 1.8%; IIIB, 40.7%; and IVA, 2.3 %. Survival curves were constructed using Kaplan-Meier methods and differences between groups were tested for significance using the log-rank test. Multivariate analysis was done using the Cox proportional hazards model. With a median follow-up of 114 months, actuarial disease-free survival for all patients was 60% at 5 years and 55% at 10 years. Actuarial 5-year survival for Stage IB was 79%; for Stage II, 59%; and for Stage III, 53%. There were 14/216 (6%) of patients with severe late complications. On univariate analysis, race was found to be statistically significant, with Caucasian patients having better survival than African American (P = 0.03). The survival for patients treated in shorter overall times was significantly higher (P<0.001), especially with treatment completion in under 58 days. The stepwise Cox multivariate analysis provided the following significant results: race (African American vs. Caucasian; P = 0.04, RR = 1.6), Stage (II vs. I, P = 0.004, RR = 2.6), Stage (III vs. I; P = 0.004, RR = 2.5), and overall treatment time (P = 0.006, RR = 1.62). Rates of local control, survival, and complications among women treated with combined external beam and intracavitary radiation for cervix cancer were similar to those of prior retrospective studies.

Actuarial Analysis↗

Human papillomavirus vaccines for the treatment of cervical cancer.

Human papillomavirus (HPV) infection is a major cause of cervical cancer, the second most common cancer in women worldwide. Currently, a HPV L1-based virus-like particle has been approved as a prophylactic vaccine against HPV infection, which will probably lead to a reduction in cervical cancer incidence within a few decades. Therapeutic vaccines, however, are expected to have an impact on cervical cancer or its precursor lesions, by taking advantage of the fact that the regulatory proteins (E6 and E7) of HPV are expressed constantly in HPV-associated cervical cancer cells. Vaccine types targeting these regulatory proteins include the recombinant protein and DNA vaccines, peptide vaccines, dendritic-cell vaccines, and viral and bacterial vector deliveries of vaccines, and these may provide an opportunity to control cervical cancer. Further approaches incorporating these vaccine types with either conventional therapy modalities or the modulation of CD4(+) regulatory T cells appear to be more promising in achieving increased therapeutic efficacy. In this review, we summarize current and future therapeutic vaccine strategies against HPV-associated malignancies at the animal and clinical levels.

Cancer Vaccines↗

Risk factors for progression of cervical intraepithelial neoplasm grade III to invasive cervical cancer.

Data from four case-control studies on invasive cervical cancer and on cervical intraepithelial neoplasia grade III (CIN III) that were concurrently conducted in Spain and Colombia were used to look for factors that might favor the progression from CIN III to the invasive stage. These studies were compared in two ways; a case-case comparison and an estimation of the ratio of odds ratios with the use of of special logistic regression model that took into account the different design of each study and possible confounding factors. Variables studied were human papillomavirus status, viral load, viral types, sexual behavior, sexually transmitted diseases, reproductive patterns, oral contraceptives, and smoking. Both CIN III and invasive cervical cancer have a very similar profile of risk factors and none of them was different in a consistent way to suggest a role in the progression from CIN III to invasive cervical cancer. Some methodological problems such as cohort-specific differences and some selection biases could be adjusted for with a careful statistical analysis. Other problems derived from the cross-sectional nature of the design are unavoidable and should be considered in the interpretation of the results.

Adult↗

Social inequities along the cervical cancer continuum: a structured review.

OBJECTIVE: To reveal areas of research/knowledge related to social inequities and cervical cancer. METHODS: A Medline search was performed looking for US based research on cervical cancer and social inequities since 1990. The papers found were organized into cells defined by a "cancer disparities grid." RESULTS: The majority of research published about cervical cancer and social inequities in the US, lies within the social domains of: race/ethnicity and socioeconomic position. Conflicting information exists as to whether race/ethnicity is a good predictor of screening and survival. Some research implied that differentials based on race/ethnicity are likely secondary to differentials in socioeconomic position. Some research about age, insurance status, and immigrant status and cervical cancer was found. Scarce information was found relating to sexuality, language, disability and geography and cervical cancer. DISCUSSION: The "cancer disparities grid" facilitated a systematic and visual review of existing literature on social inequities and cervical cancer. The grid helped to elucidate uncontested existing social inequities, conflicting social inequities, and areas where social inequity data does not exist. The cancer disparities grid can be used as a research tool to help identify areas for future research, clinical programs, and political action related to cervical cancer and social inequities.

Adult↗

Regulation of cell growth and HPV genes by exogenous estrogen in cervical cancer cells.

Human papillomavirus (HPV) infection is known as the major cause of the development of cervical cancer. The E6 and E7 proteins of oncogenic HPV can play critical roles in immortalization and malignant transformation of cervical epithelial cells. From the previous epidemiologic data, it has been determined that long-term use of oral contraceptives may be a risk factor for cervical cancer. Investigation of the estrogenic and antiestrogenic effects on the proliferation of cervical cancer cells and the gene expression of HPV would help to explain the role of estrogen in the HPV-associated pathogenesis of cervical cancer. In this study, cervical cancer cells (HeLa, CaSki, and C33A) were cultured in vitro in the presence of 17beta-estradiol or tamoxifen to observe their regulatory growth effect and HPV E6/E7 gene expression. The estrogenic effect on the promoter activity of HPV URR was further confirmed by transient transfection assay, which was conducted in C33A cells using the HPV-18 URR-CAT reporter plasmid. The supplemental effect of estrogen receptors on URR promoter activity was also evaluated. The proliferation of HeLa and CaSki cells was stimulated by estradiol at physiologic concentration levels (</=1 x 10-6 M). At a low concentration (0.1 x 10-6 M), tamoxifen also stimulated the proliferation of HeLa and CaSki cells. In contrast to HPV-positive cervical cells, the proliferation of C33A was not influenced by exogenous estradiol or tamoxifen, indicating that HPV might play a role in the hormonal stimulation of cell growth. Interestingly, the proliferation of HeLa was markedly suppressed at high concentrations of estradiol and tamoxifen (5 and 10 x 10-6 M). The levels of HPV-18 E6 and E7 mRNA were significantly increased by estradiol at a concentration of 0.5 x 10-6 M. Transient transfection experiments using the HPV URR-CAT reporter plasmid in C33A cells indicated that the expression of HPV E6/E7 genes was increased by the treatment of estradiol and tamoxifen. Co-transfection of estrogen receptors (ER) and URR-CAT leads to a fourfold increase in CAT activity by estradiol or tamoxifen at physiologic concentrations. When estradiol or tamoxifen was administered at high concentrations (5 x 10-6 M), a DNA ladder, typically indicative of apoptosis, was observed in HeLa cells. In conclusion, estradiol stimulated the growth of HPV-positive cervical cancer cells, as did tamoxifen at low concentrations (0.1 x 10-6 M). The growth stimulation of HPV-positive cervical cancer cells by estrogen appeared to be related to the increased expression of HPV E6/E7. Growth suppression observed at high concentrations of estradiol and tamoxifen in HeLa cells might be a result of apoptosis. Taken together, these data suggested that exogenous estradiol might be a risk factor in HPV-mediated cervical carcinogenesis.

Journal Article↗

Trend of cervical cancer mortality in Belgium (1954-1994): tentative solution for the certification problem of unspecified uterine cancer.

We investigated the evolution of mortality from cervical cancer in Belgium between 1954 and 1994 in terms of absolute number of deaths, and standardised and age-specific mortality rates. Changes over generations were summarised using the standardised cohort mortality ratio. Trend studies of cervical cancer mortality were hampered by certification problems. The number of deaths due to cancer of the uterine cervix is not known exactly since a substantial proportion of death causes are coded as cancer of the uterus without specifying the anatomic site: cervix or corpus uteri. This inaccuracy in codification has been corrected using distribution tables derived from countries where this certification problem is minimal. Trends in mortality from certified and corrected cervical cancers were compared. The corrected age-standardised mortality rate decreased continuously over the last 4 decades, from over 14 to 5 per 100,000 woman-years (slope -0.26/100,000 woman-years, 95% CI -0.28 to -0.24). Its slope is 3.1 times (95% CI 2.9-3.5) more important than for the rate of mortality from certified cervical cancer. In addition to the almost linear decrease, substantial nonlinear cohort influences were observed in certified and corrected mortality rates. The tendency of increasing mortality in women born after 1935 required particular attention. Nevertheless, the slope of the corrected recent cohort effect remained limited in Belgium, probably as a consequence of screening.

Adult↗