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[A case of immunohistochemically carcinoembryonic antigen producing cervical cancer--the evaluation of plasma CEA levels in 201 patients with uterine cancer].

A case of a cervical cancer in a 40-year-old woman with a plasma carcinoembryonic antigen (CEA) level of 29.4 ng/ml was investigated using light and electron microscopy. In addition, the plasma CEA levels before treatment were determined in 168 patients with cervical cancer and in 33 patients with endometrial cancer. CEA was found to be elevated in the plasma of 19% of those with cervical cancer and in 6% of those with endometrial cancer. Effective serial plasma CEA determinations following therapy, in patients whose plasma or tumors initially contain elevated amounts of antigen, might be useful as an adjunctive method in the earlier detection of a recurrent cancer.

Adult↗

Incidence and mortality of cervical cancer in Latin America.

Cervical cancer incidence and mortality estimates for 2000 are presented for the 21 Latin American countries, using estimates from the statistical package GLOBOCAN 2000. Additional data on time-trends are also presented, using the WHO mortality database. By the year 2000, some 76,000 cervical cancer and almost 30,000 deaths were estimated for the whole region, which represent 16% and 13% of the world burden, respectively. Thus, Latin American countries are among those with highest incidence rates in the world, together with countries from Sub-Saharan Africa, South and South East Asia. Variation in incidence among countries is large. Very high rates are found in Haiti (ASR 93.9 per 100,000), Nicaragua (ASR 61.1 per 100,000) and Bolivia (ASR 58.1 per 100,000). It seems unlikely that differences in risks in the region can be explained as the result of screening activities. Several descriptive studies carried out to evaluate the screening programmes in Latin America have pointed out problems related to insufficient coverage and frequency of screening. Other related problems include inadequate collection and reading of cytological samplings as well as incomplete follow-up of women after the test. The main challenge for Latin America countries remains on how to organize effective screening programmes, and for this, a real and urgent commitment from public health services and decision-makers in the region is needed. This paper is available too at: http://www.insp.mx/salud/index.html.

Adolescent↗

The apoptotic effect of intercalating agents on HPV-negative cervical cancer C-33A cells.

Cervical cancer is one of the leading causes of female cancer death worldwide with about 500,000 deaths per year. Both mitomycin C and cisplatin are alkylating agents, which bind and intercalate DNA, and thus used as anti-cancer drugs. In these studies, we focused on investigating the apoptotic effects of intercalating agents on HPV-negative cervical cancer C-33A cells. Accordingly, C-33A cells were treated with carboplatin, mitomycin C or cisplatin. Cell cycle analysis revealed that treatment with mitomycin C and cisplatin but not with carboplatin resulted in apoptosis. Both mitomycin C and cisplatin induced apoptosis in C-33A cells via caspase-8 and -3 processing in a Fas/FasL-dependent manner and also suppressed IL-18 expression, while they down-regulated IkappaB expression and up-regulated p65 expression. These results suggest that both mitomycin C and cisplatin induce apoptosis, not only via the caspase-8 and -3 dependent Fas/FasL pathway, but also via the regulation of NF-kappaB activity and IL-18 expression in HPV-negative cervical cancer C-33A cells.

Apoptosis↗

Cervical cancer.

Behavioral and psychosocial factors affect all aspects of cervical cancer control, from prevention to posttreatment rehabilitation. Behavioral scientists gathered at the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002) reviewed selected studies of behavioral factors related to cervical cancer, including women's receptivity to emerging cervical cancer screening and diagnostic technologies, factors that influence adherence to follow-up colposcopy recommendations, and cervical cancer survivors' quality of life. Researchers reported that reduced distress during examinations with new technology may improve adherence to cervical cancer screening recommendations. Until new technology becomes mainstream, research shows that distress is reduced and adherence improves when health care providers match interventions to patients' informational processing styles. Investigations of survivors' quality of life report conflicting findings, but studies indicate that survivors experience anger over reproductive loss, loss of interest in sex, and perhaps a greater vulnerability to sexual dysfunction compared with survivors of other cancers. Survivors also report a need for posttherapy support programs. Primary prevention of cervical cancer should remain a priority as research in behavioral interventions and barriers to screening, especially among vulnerable populations, moves forward.

Behavior↗

Cervical cancer and microchimerism.

OBJECTIVE: To determine whether microchimerism is involved in the pathogenesis or progression of cervical cancer. METHODS: Cervical tissue was obtained from eight women who had at least one live-born son and who underwent radical hysterectomy after a diagnosis of cervical cancer. Control tissue was obtained from four women without cervical cancer who had at least one live-born son and from three women with cervical cancer and no male births. Tissue sections were analyzed with fluorescence in situ hybridization for the presence of fetal cells, defined by an X and Y chromosome. Immunolabeling was used to determine the phenotype of the presumed fetal cells. RESULTS: Male cells were found in cervical tissue from all four patients for whom large sections (approximately 1.5 x 2 cm) were analyzed. Only one male cell was found in two of the four patients for whom small biopsy specimens (approximately 0.1 x 0.5 cm) were analyzed. No male cells were found in tissue specimens from controls, whether they were small or large sections. In immunolabeling studies, eight of 18 male cells from one patient were CD45-positive and nine of 37 male cells from two patients were cytokeratin-positive. No cells were positive for both markers. CONCLUSION: Cervical cancer might be associated with microchimerism, possibly from fetomaternal cell trafficking. These results further expand the potential relationship between microchimerism and disease in women.

Adult↗

Characteristics of women with AIDS and invasive cervical cancer.

OBJECTIVE: To characterize women reported with AIDS and invasive cervical cancer in the first year of the expanded AIDS surveillance case definition. METHODS: Using X2 testing and logistic regression, we compared women with invasive cervical cancer with those having other AIDS-defining illnesses. RESULTS: Of the 16,794 women 13 years old or older and reported with AIDS in 1993, 217 (1.3%) had invasive cervical cancer and 9113 (54.3%) had other opportunistic illnesses; the remaining 7464 (44.4%) had no opportunistic illnesses and were reported based on immunologic criteria. Women with invasive cervical cancer were more likely to have had AIDS diagnosed before 1993 (73 and 56%, respectively; P < .01), to be younger (median age 33 and 35 years; P < .001), to be white (31 and 21%; P < .01), and to reside in the south (41 and 34%; P < .05). Among women reported with CD4+ counts, the median value was higher in 149 women with invasive cervical cancer than in the 5993 with other opportunistic illnesses (153 and 50 cells/microL, respectively). Women with invasive cervical cancer were more likely to report injection drug use (57 and 48%; P < .05). In multivariate analysis, Hispanic women were 0.6 times less likely to be reported with invasive cervical cancer than were white women (P < .05). Among women infected through injecting drug use, black women were 0.5 times less likely to be reported with invasive cervical cancer (P < .001). CONCLUSION: Hispanic and black women infected with HIV were less likely to be reported with invasive cervical cancer, a finding that may be associated with inadequate access to health care services. Women with invasive cervical cancer were less severely immunosuppressed than women with other AIDS opportunistic illnesses.

Acquired Immunodeficiency Syndrome↗

Knowledge, attitudes and practices on cervical cancer screening among the medical workers of Mulago Hospital, Uganda.

BACKGROUND: Cervical cancer is the commonest cancer of women in Uganda. Over 80% of women diagnosed in Mulago national referral and teaching hospital, the biggest hospital in Uganda, have advanced disease. Pap smear screening, on opportunistic rather than systematic basis, is offered free in the gynaecological outpatients clinic and the postnatal/family planning clinics. Medical students in the third and final clerkships are expected to learn the techniques of screening. Objectives of this study were to describe knowledge on cervical cancer, attitudes and practices towards cervical cancer screening among the medical workers of Mulago hospital. METHODS: In a descriptive cross-sectional study, a weighted sample of 310 medical workers including nurses, doctors and final year medical students were interviewed using a self-administered questionnaire. We measured knowledge about cervical cancer: (risk factors, eligibility for screening and screening techniques), attitudes towards cervical cancer screening and practices regarding screening. RESULTS: Response rate was 92% (285). Of these, 93% considered cancer of the cervix a public health problem and knowledge about Pap smear was 83% among respondents. Less than 40% knew risk factors for cervical cancer, eligibility for and screening interval. Of the female respondents, 65% didn't feel susceptible to cervical cancer and 81% had never been screened. Of the male respondents, only 26% had partners who had ever been screened. Only 14% of the final year medical students felt skilled enough to use a vaginal speculum and 87% had never performed a pap smear. CONCLUSION: Despite knowledge of the gravity of cervical cancer and prevention by screening using a Pap smear, attitudes and practices towards screening were negative. The medical workers who should be responsible for opportunistic screening of women they care for are not keen on getting screened themselves. There is need to explain/understand the cause of these attitudes and practices and identify possible interventions to change them. Medical students leave medical school without adequate skills to be able to effectively screen women for cervical cancer wherever they go to practice. Medical students and nurses training curricula needs review to incorporate practical skills on cervical cancer screening.

Adult↗

Contribution of epigenetic risk factors but not p53 codon 72 polymorphism to the development of cervical cancer in Northeastern Thailand.

Relationships between cervical cancer and risk factors were investigated in Northeastern Thailand. Cases (n = 90) with squamous cell cervical cancer (SCCA) and age matched healthy controls (n = 100) were recruited. The p53 codon 72 polymorphism, proline and arginine allele, was studied by the polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference in the allele and the genotype distribution between the SCCA and the control groups (P > 0.05). Significant difference was observed in the number of sexual partners (P < 0.003) age at the first sexual intercourse (P < 0.03) and number of parities ( P< 0.006). After adjusted by age and p53 genotype, significant difference was still observed in the number of sexual partners (P = 0.017) The partners' smoking increased the risk to develop SCCA. Increased odds ratios were observed when the partner had smoking history both at present (3.31; P < 0.003) and in the past (3.36; P < 0.003). The p53 polymorphism itself may not be a risk factor for cervical cancer in Northeastern Thailand. Much attention should be paid to the presence of other risk factors such as sexual behaviors and smoking habits in the prevention of cervical cancer in this region.

Adult↗

Optimizing radiation parameters for cervical cancer.

The treatment of cervical cancer has become increasingly sophisticated with evidence-based guidelines generated from randomized trials directing combined modality programs. The radiotherapeutic guidelines have been derived largely from single institutional experiences coupled with data from the Patterns of Care Studies. The design of external-beam fields has improved because of a better understanding of the anatomy of the cervix, uterus, parametrium, and draining lymph nodes from surgical, lymphangiogram, computed tomography scan, and magnetic resonance imaging series. An improvement in survival and local control with dose intensity (a reduction in overall treatment time and increase in overall dose) has been shown for cervical cancer, especially for locally advanced disease, and these series are highlighted. The use of intracavitary radiation, which is technically accurate, dramatically improves outcome and allows for dose intensity. Alternative brachytherapy techniques, such as high-dose-rate, and interstitial, are discussed. Ways to improve the therapeutic ratio for radiation, including biological factors, are reviewed. More research is necessary to understand the complex dose distribution of external-beam and intracavitary brachytherapy and its relationship to tumor control.

Brachytherapy↗

Duration of relative protection of screening for cervical cancer.

The reduction in cervical cancer among women with at least one previous negative Pap smear can be assessed in terms of the time elapsed since the last smear was taken. One indicator of the utility of screening is the duration of relative protection, commonly calculated as the inverse of the disease odds ratio. Most investigations of the extent of relative protection provided by Pap testing have relied on data from centrally organized screening programs or case-control studies. For geographic areas without mass screening programs or tumor registries, reliance on subject recall of Pap tests is required. We conducted a case-control investigation of cervical cancer and interviewed 153 Maryland women with invasive disease and two control groups: 153 case-nominated controls and 392 randomly selected controls. The duration of relative protection of screening for disease was 4-6 years for both control groups [relative protection (RP) = 4.30, 95% confidence interval (CI) = 1.5-12.7 for neighborhood controls, RP = 3.63, 95% CI = 1.4-9.6 for random controls]. These findings held after adjusting for education, ever treated for a sexually transmitted disease, smoking, age at menarche and at first sexual intercourse, number of pregnancies, lifetime contraceptive use, and utilization of obstetrician-gynecologist services; the RPs increased upon adjustment. However, there was a decline in the RP with increased duration. Our findings are directly comparable to reports where smears have been verified, suggesting that self-reports of previous tests may be reliable as a method to evaluate the utility of screening.

Adult↗

Binding and growth-stimulation of cervical cancer cell lines by prolactin.

Two cervical cancer cell lines CC7-T and Si-Ha were employed to observe the relationship between cervical cancer and prolactin. By immunocytochemical and indirect immunofluorescent assays using two prolactin monoclonal antibodies PRL-149 and PRL-151, both cell lines with added prolactin (10 ng/mL) were noted to be positive for PRL-151, but negative for PRL-149. The control cell lines from ovarian cancer and the myeloma lines were both stained negative. By using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, it was noted that CC7-T and Si-Ha grew better in the presence of various added concentrations of prolactin, ranging from 0.1 to 1,000 ng/mL, suggesting that prolactin may enhance the growth of cervical cancer. The degree of stimulation appears to depend on cell differentiation. However, prolactin levels in the cultured supernatant were undetectable by the enzyme immunoassay (EIA) method. We postulate that prolactin can bind and stimulate the growth of some cervical cancer cell lines, probably through the prolactin receptor rather than by autocrine regulation.

Animals↗

Squamous cell cancer of the cervix, immune senescence and HPV: is cervical cancer an age-related neoplasm?

Relationships between cancer and aging will assume greater scientific importance over the coming decades as the number and proportion of elderly increase. Contrary to popular belief, cervical cancer remains an important disease into old age. This paper will briefly review what is known about immune senescence, cervical cancer and immune function, and the relationship between human papilloma virus and immunity, to support the hypothesis that these factors may contribute to the continued occurrence of invasive cervical cancer in the elderly.

Adolescent↗

Searching for pathogenic gene functions to cervical cancer.

OBJECTIVES: Molecular pathology of cervical cancers associated with human papillomavirus (HPV) infection is presently unclear. In an effort to clarify this issue, we investigated gene expression profiles and pathogenic cellular processes of cervical cancer lesions. METHODS: Tissues of 11 patients (invasive cancer stages Ib-IIIa) were investigated by a cDNA microarray of 4700 genes, hierarchical clustering and the Gene Ontology (GO). RESULTS: We identified 74 genes showing a more than 2-fold difference in their expression in at least 8 out of 11 patients. Among these, 33 genes were up-regulated, in contrast, 41 genes were down-regulated. The gene expression profiles were classified into mutually dependent 345 function sets, resulting in 611 cellular processes according to the GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis, and nucleic acid metabolism. Also, genes belonging to nucleic acid binding and structural molecule activity were significantly down-regulated. In contrast, significant up-regulation was shown in skeletal development, immune response, and extracellular activity. CONCLUSIONS: These data suggest that the regulated genes and cellular processes could be further used for predicting prognosis and diagnosis of cervical cancer patients, and further investigation and functional characterization of the identified genes is warranted.

Down-Regulation↗

Cervical cancer screening. Past success and future challenge.

Population screening for cervical cancer resulted in significant reduction in the morbidity and mortality from cervical cancer. An increased understanding of the relationship of HPV infection with cervical cancer and the natural history of cervical cancer precursor lesions further solidifies and expands the biological basis for cervical cancer screening. Pap tests in asymptomatic women remain the cornerstone of cervical cancer screening. Clinicians should be cognizant of the significant false-negative rate of Pap smears. Meticulous attention to proper Pap smear technique is necessary to maximize the sensitivity of the test. Further research is needed to establish the role of cervicography and HPV DNA hybridization techniques in cervical cancer screening.

Adult↗

Cervical cancer in Australia and the United Kingdom: comparison of screening policy and uptake, and cancer incidence and mortality.

OBJECTIVE: To compare cervical screening policy, screening uptake, and changes in cervical cancer incidence and mortality between Australia and the United Kingdom. DESIGN: Analysis of screening registry data and national cancer statistics. SETTING: In Australia, organised cervical screening was initiated in 1991 for sexually active women aged 18-69 years, with a recommended 2-yearly interval. In the UK, organised screening began in 1988 for women aged 20-64 years, with a recommended 3-yearly interval in most regions. RESULTS: Estimated lifetime screening participation rates in 2001 were similar in the two countries, at 88% in Australia and 90% in the UK. For women who were screened and had a negative result, the median time to the next screen was 27 months in Australia and 38 months in the UK. At 39 months, equivalent proportions (74%) had been re-screened in the two countries, and by 60 months the re-screened proportions were 81% in Australia and 94% in the UK. From 1991-1993 to 1998-2000, the incidence of cervical cancer in women aged 20-69 years fell by 33% in Australia and 33% in the UK, and mortality from cervical cancer fell by 36% in both countries. CONCLUSIONS: After the introduction of organised screening, similar reductions in cervical cancer incidence and mortality were achieved in Australia and the UK. Therefore, the 2-yearly screening policy in Australia and the predominantly 3-yearly screening policy in the UK appear to have been of broadly similar effectiveness.

Adolescent↗

Cervical cancer screening: state of the art.

PURPOSE OF REVIEW: The objective of cervical cancer screening is to prevent the occurrence of and death from cervical cancer by detecting and treating high-grade squamous intraepithelial lesions. A significant decline in occurrence and mortality from cervical cancer in developed countries has been associated with the application of organized cervical screening programs. The use of the available local health methods in cervical cancer screening can be adjusted in different countries. This review discusses the recent results in traditional and alternative cervical cancer screening. RECENT FINDINGS: The current recommendations of both the American Cancer Society and the American College of Obstetricians and Gynecologists concerning clinical practice guidelines for cervical cancer screening are commented upon. New methods and new technology for cervical cancer screening are described. Attributable failure factors in the screening process, particularly in the coverage, are analyzed. A critical assessment of the suitability of local cervical cancer screening resources is discussed. SUMMARY: Screening is clearly a complex multifactorial process, not a test. Nowadays, with the human papillomavirus vaccine on the horizon, screening is the best strategy for cervical cancer control. Good screening programs, with high coverage, quality control and follow-up included, are the basis of obtaining better results. The Papanicolaou test and its variants are the best methods of cervical cancer screening in high-resource settings. Alternative visual inspection using cervical dyes could be the most useful method in low-resource settings. The challenge for the future may be less of a technical nature and more dependent on local finances and screening policies.

Female↗

[Progress in the treatment of cervical cancer].

The cure rate of cervical cancer is undoubtedly improved by early detection accomplished by mass-screening programs. Improvements in surgical technique have also reduced the incidence of complications. Conization or laser vaporization for stage 0 and extended hysterectomy for stage Ia are demonstrated to be appropriate treatment modalities. Extended surgery, such as total pelvic exenteration, is applied for advanced cancer. For radiation treatment, fast-neutron irradiation, intraoperative irradiation and interstitial irradiation have been tested. Hyperthermia combined with irradiation is one of the most attractive methods, which deserves further investigation. Irradiation of the para-aortic lymph nodes has been started by many institutions. Great progress has been achieved in chemotherapy for cervical cancer. Multi-drug combination chemotherapy including cis-platinum has yielded promising results, and intra-arterial infusion and long-term maintenance chemotherapy have been tried with the expectation of favorable outcome. It is concluded that individualized multi-disciplinary treatment will be the best approach for cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Radiation-sparing managements for cervical cancer: a developing countries perspective.

Cervical cancer is the seventh most frequent cancer worldwide but more than 80% of cases occur in developing countries. Till date, radiation therapy with external beam and brachytherapy remains as the core treatment for most stages of cervical cancer. However, radiation treatment protocols and equipment modelled on the best developed countries can be seldom applied directly to developing countries owing to financial constraints and lack of qualified personnel, thus, a substantial proportion of patients do not have access to even palliative radiation therapy. Treatment options when the standard therapy is either not available or difficult to reproduce in particular settings is highly desirable with the potential to save lives that otherwise could be lost by the lack of adequate treatment. These options of treatment ideally had to have show, 1) that these are not inferior to the "standard" in terms of either survival or quality of life; 2) that these can be delivered in settings were the "standard" is not available or if available its quality is poor; and 3) that the treatment option be accepted by the population to be treated. Based on these considerations, it is obvious that cervical cancer patients, particularly those who live in countries with limited resources and therefore may not have sufficient radiation therapy resources are in need of newer therapeutical options. There is now a considerable amount of information emanating from clinical studies where surgery has a major role in treating this disease. These forms of "radiation-sparing" treatments include total mesometrial resection that could make unnecessary the use of adjuvant radiation; neoadjuvant chemotherapy that could avoid the use of adjuvant radiation in around 85% of patients and preoperative chemoradiation that could make brachytherapy dispensable. The feasibility and therapeutical value of these potential forms of management need to be prospectively evaluated.

Journal Article↗