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PubMed1990

Opioid-like immunoreactants in human cervical cancer.

Cervical carcinoma cell lines produce several polypeptide hormones. While screening human cervical cancers for such factors we have found many tumors to be immunoreactive for opioid peptides. The tumors were collected at surgery or prior to actinotherapy, fixed in buffered formalin, paraffin-embedded, and immunocytochemically stained using the PAP method. The localization of opioid-like immunoreactivity was investigated using a primary antiserum recognizing the Tyr-Gly-Gly-Phe sequence common to all known opioid peptides. The presence of neuropeptide Y (NPY) and peptide histidine methionine (PHM), both known to be present in normal human cervical tissue, was also investigated using specific antisera. Controls included staining controls and absorption controls, using Sepharose-coupled antigen and were all negative. Out of 40 cervical carcinomas, 27 displayed varying numbers of opioid-immunoreactive cells. In 12 normal cervical specimens no specific staining was observed. None of the tumors displayed any NPY-like or PHM-like immunoreactivity. The growth of cervical carcinoma seems therefore to be accompanied by a destruction of the local peptidergic innervation of blood vessels and smooth muscle cells. The demonstration of opioid-like immunoreactants and the known immunoregulatory properties of these peptides, indicate that opioid peptides may be important in the regulation of growth of human cervical carcinoma.

Adult↗
PubMed2003

Prevention of cervical cancer.

Cervical screening in Australia is a successful public health initiative. Since the introduction of the National Cervical Screening Program in 1991, there has been a significant fall in incidence of and mortality from cervical cancer. Laboratory quality procedures are critical to ensuring optimal outcomes. Laboratory accreditation procedures are being reviewed in line with recent government recommendations. For a sustainable program, cost-containment issues need to be considered; screening interval, management of screen-detected abnormalities, and new technologies are the critical drivers of cost.

Accreditation↗
PubMed2002

Transforming growth factor-beta1 induces tumor stroma and reduces tumor infiltrate in cervical cancer.

Cervical carcinomas consist of tumor cell nests surrounded by varying amounts of intratumoral stroma containing different quantities and types of immune cells. Besides controlling (epithelial) cell growth, the multifunctional cytokine transforming growth factor-beta(1) (TGF-beta(1)) is involved in the formation of stroma and extracellular matrix (ECM) and in immunosuppression. Several malignancies are known to be associated with enhanced production of TGF-beta(1), repression or mutation of TGF-beta transmembrane receptors, or mutations at the postreceptor intracellular signaling pathway. The aim of our study was to investigate the role of tumor cell-derived TGF-beta(1) on the amount of intratumoral stroma; the deposition of collagen IV, fibronectin, and laminin; and the tumor infiltrate in cervical carcinoma. The expression of TGF-beta(1) mRNA in 108 paraffin-embedded cervical carcinomas was detected by mRNA in situ hybridization. Immunohistochemistry was used to investigate the amount of tumor stroma and ECM proteins and the extent of the tumor infiltrate. Plasminogen activator inhibitor-1 (PAI-1) protein expression in tumor cells was determined to verify the biological activity of TGF-beta(1.) Cytoplasmatic TGF-beta(1) mRNA expression in tumor cells was significantly correlated with the amount of intratumoral stroma and the deposition of collagen IV. TGF-beta(1) mRNA expression in every tumor was accompanied by PAI-1 expression, indicating biological activity of TGF-beta(1). An inverse relationship between TGF-beta(1) mRNA expression in tumor cells and the extent of the tumor infiltrate was demonstrated. Our results indicate that cervical cancer cells affect the amount and the composition of the intratumoral stroma and the tumor infiltrate by the production and secretion of TGF-beta(1).

Collagen Type IV↗
PubMed2006

Environmental risk factors for prevention and molecular intervention of cervical cancer.

Cervical cancer (CC) is potentially the most preventable and treatable cancer in human but it is a leading cause for cancer morbidity and mortality in women around the world. Therefore, more innovative prevention and treatment protocols need to be developed and implemented. With better understanding of the etiology of the disease, specific prevention protocols that involve life-style modifications to minimize the impact of environmental risk factors can be developed. It may be necessary to implement unique modification protocols for different countries. In addition, antiviral vaccine is a highly promising prevention approach. With respect to therapy, the development of more specific protocols that have fewer side effects is needed. With the availability of sophisticated molecular techniques, a new generation of targeted approach that has the potential to generate outstanding efficacy is being tested. Using the siRNA technology against the expression of human papillomavirus oncogenes, specific biological pathways that are essential to the growth and survival of the CC cells can be interrupted. Another promising approach is the molecular intervention of the estrogen pathway by blocking the expression of estrogen receptors. These molecular techniques may work by reactivating endogenous regulatory processes, e.g., the core apoptotic machinery, that can cause self-destruction of the CC cells, thus providing potentially effective molecular therapy. These topics are discussed in this review.

Environment↗
PubMed1995

Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain.

A human papillomavirus (HPV) type 16 virus-like particle-based ELISA was used to assess antivirion immune responses in 300 women participating in cervical cancer case-control studies in Colombia and Spain. Virion IgG antibodies were detected in the sera of 51% and 59% of women with HPV-16 DNA-positive invasive cervical cancer and 81% and 73% of women with HPV-16 DNA-positive cervical intraepithelial neoplasia grade III (CIN III) in Colombia and Spain, respectively. Capsid antibodies were detected in 22% and 3% of cancer controls (P < .001) and in 43% and 10% of CIN III controls (P = .010) from Colombia and Spain, respectively. Since Colombia has an 8-fold higher incidence of cervical cancer, these results demonstrate an association between ELISA positivity and cancer risk. Capsid antibody responses did not correlate with humoral responses of the same women to HPV-16 E6 and E7 oncoproteins.

Antibodies, Viral↗
PubMed1981

Screening strategies for cervical cancer and cervical intraepithelial neoplasia.

Exfoliative cytology is a highly sensitive and inexpensive screening technique for cervical cancer and its precursors. The detection and eradication of the precursors have led to a significant fall in cervical cancer incidence rates and death rates in those areas in which there has been widespread and prolonged use. Recently, however, the utility and cost-effectiveness of cytology has been questioned, and it has been suggested that screening strategies be altered. A consideration of the effect of the transit times of cervical intraepithelial neoplasia on screening intervals and the impact of the changing patterns of cervix cancer epidemiology on screening strategy suggests that a significant change in screening intervals may be counterproductive.

Adult↗
PubMed1998

Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia.

Both p16 and retinoblastoma (Rb) proteins are important tumor suppressors that regulate the cell cycle. The status of both proteins in invasive cervical cancer and cervical intraepithelial neoplasia (CIN) has not yet been examined. The aim of this study was to investigate the expression of p16 and Rb proteins by immunohistochemistry using 98 formalin-fixed and paraffin-embedded samples of various cervical neoplastic lesions. Strong immunoreactivity for the p16 protein was observed in both the nuclei and cytoplasm of all CIN and invasive cancer cases except several low-grade CIN lesions. Expression of Rb protein was also demonstrated in the scattered nuclei of neoplastic and normal cells in all cases investigated. The results suggest that the deletion or mutational inactivity of both p16 and Rb proteins may be a rare event in cervical carcinogenesis. Moreover, overexpression of the p16 protein may be a useful diagnostic marker for cervical neoplastic lesions on routine laboratory screening.

Adenocarcinoma↗
PubMed1998

Immunoglobulin-A and -G responses against virus-like particles (VLP) of human papillomavirus type 16 in women with cervical cancer and cervical intra-epithelial lesions.

Immunoglobulin-A and -G (IgA and IgG) responses against HPV-16-like particles (VLP) were tested by ELISA in 104 women with cervical abnormalities, 26 atypical cells of undetermined significance (ASCUS) and 14 cytologically normal women with HPV DNA. As controls, 130 age-matched cytologically normal women with no HPV DNA were selected from the population in which the cases were generated. The existence of HPV DNA in cervical samples was tested by a PCR-based method. The normal women positive with HPV-16 DNA were followed up at 4- to 7-month intervals for 16 to 24 months. IgA and IgG antibodies against HPV-16 VLP were frequently detected in these women repeatedly positive with HPV-16 DNA, suggesting that persistent HPV infection is crucial for effective antibody responses against the viruses. IgA response appears earlier and persists longer than IgG response. Women with HPV DNA of types 16, 31/33/35, 58 and unknown types showed significantly higher seropositivity for both IgA and IgG antibodies than the controls (p < 0.05 for both). No significant seropositivity for IgA or IgG was detected in the HPV-18/45-DNA-positive group. HPV 31/33/35, 58 appear to be types close to HPV 16, whereas HPV 18/45 appears to be distinct from HPV 16 in antigenicity. IgA and IgG responses against HPV-16 VLP were more frequently observed in women with normal cervices with HPV DNA, ASCUS, HSIL and cervical cancer than in the controls. Strong IgA and IgG responses depended on HPV-16 infection in HSIL and cervical cancer, but there was no correlation between the serological responses and the status of HPV DNA in ASCUS and LSIL. Antibody positivity reflects persistent viral infection that may increase the risk for malignant progression of the cervix. This serological assay using HPV-16 VLP may therefore be useful as a new diagnostic tool supplementing cervical cytological tests.

Adult↗
PubMed1985

Diagnosis analysis in breast cancer and cervical cancer screening.

Assessment of the accuracy of diagnostic procedures has been made independent of the diagnostic criteria used by means of Relative Operating Characteristics (ROC) analysis. A ROC curve describes the mutual relationship between the sensitivity and specificity of a diagnostic decision on the basis of various diagnostic criteria. The construction of such ROC curves is made possible if diagnoses are graded into levels of certainty. The curve enables the choice of an operating point with predetermined sensitivity and specificity values for the diagnosis decision. The population-based breast-cancer and cervical cancer screening projects carried out in Utrecht demonstrated an excellent fit between actual data and the calculated ROC curves. Analysis of the accuracy or performance of cytological diagnosis uncovered a problem arising from the similarly graded histopathological reference criteria used to determine the 'truth' of the cytological diagnosis decisions. The proposed solution is a serial calculation of ROC curves, one for each level differentiating between the histopathological categories. The ensuing three-dimensional ROC hill may reveal a summit marking numerically advantageous diagnosis criterion levels for both the test and the disease to be detected, or a depression signalling locally below-standard detection performance.

Adult↗
PubMed1997

Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions.

PURPOSE: Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. PATIENTS AND METHODS: Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. RESULTS: Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. CONCLUSION: The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.

Carcinoma in Situ↗
PubMed2006

Effectiveness of cervical cancer screening over cervical cancer mortality among Japanese women.

BACKGROUND: Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study. METHODS: Baseline survey of the Japan Collaborative Cohort Study for the enrollment of subjects was completed during 1988-90 and followed until 2003. This study only analyzed 63,541 women, aged 30-79 years, who were free from any cancer history at enrollment. RESULTS: During the follow-up period, 38 CC deaths were identified. The mean age at mortality was 67.0 years, with a mortality rate of 4.2 per 100,000 person-years. Participation rate in CC screening was 46.9%. Age-adjusted Cox model indicated significantly lower CC mortality [hazard ratio (HR) = 0.30, 95% confidence interval (CI) = 0.12-0.74] due to CC screening. Protectiveness remained almost the same (HR = 0.30, 95% CI = 0.12-0.76) when adjusted for age, body mass index and number of deliveries. The results also revealed that CC screening could reduce at least 50% of CC deaths even after excluding the effect of possible self-selection bias. CONCLUSIONS: CC screening in Japan may reduce CC mortality significantly for women aged 30-79 years. However, further studies with more CC deaths and increased statistical power are needed to validate the findings.

Adult↗
PubMed1994

The Forsyth County Cervical Cancer Prevention Project--I. Cervical cancer screening for black women.

The Forsyth County Cervical Cancer Prevention Project was a 5 year National Cancer Institute-funded community-based public health education program implemented to address the problem of excess mortality from cervical cancer among black women in Forsyth County, North Carolina. The intervention was a community-based public health education program that included mass media, direct education workshops, and provision of education on cervical cancer and screening to health care providers. The intervention was implemented from November 1988 to September 1991. Evaluation of the community intervention used a quasi-experimental design, with Forsyth County, North Carolina, receiving the program and Durham County, North Carolina, serving as the control. Comparison of pre- and post-intervention telephone survey data revealed that, overall, awareness of cervical cancer and the Pap smear increased. Knowledge, attitudes and behaviors showed little change, considering those interviewed in aggregate. Among women defined as high-risk (elderly, low socioeconomic status, public health clinic patients and/or those who do not receive regular care), a significant trend toward greater participation in screening was detected for the 6 month period following the intervention. These results suggest that awareness of cervical cancer can be increased by public health education, but that the additional attention coming to patients through the actions of health care providers and health care delivery systems may supply the additional input needed to produce behavior change.

Adolescent↗
PubMed1999

The psychosocial burden of caring for some Nigerian women with breast cancer and cervical cancer.

In Nigeria, the rising incidence of cancer and the paucity of institutional facilities and specialist man-power implies that the burden of care rests largely on relatives. We assessed the severity of indices of psycho-social and economic burden among relatives of women with breast and cervical cancer; and its relationship with patients' psychosocial distress. Using a burden questionnaire, relatives of 73 women with cancer (41 cervical and 32 breast, mean age of caregivers 35.6 years) were interviewed, in out-patient clinics. While the caregivers admitted high frequency of all indices of 'objective' burden, emotional ties at home and social relationships in the neighbourhood seemed intact, indicating tolerance and lack of social stigma. The financial burden was more problematic than the effect of caring on family routines; and these two factors significantly predicted global rating of burden. The severity of patient's worries and psychopathological symptoms were not significantly correlated with care-giver global rating of burden. The tolerance shown by this group of relatives implies that they have strong potentials for playing useful roles in community care of patients.

Breast Neoplasms↗
PubMed1984

[Epidemiological studies on multiple primary cancers--observations on the second primary cancers among cervical cancer and laryngeal cancer cases].

Two epidemiological studies on multiple primary cancers were conducted. The first one was 7-9 years' follow up among cervical cancer cases (1,767 radiotherapy and 1,377 non-radiotherapy cases) registered in the Osaka Cancer Registry. The number of observed second primaries was significantly higher than the expected numbers at the rectum, bladder, lung and all sites in the radiotherapy group only. The other was a 7 years' follow up study on 532 laryngeal cancer cases. Higher incidence than expected second primaries were observed at the mouth and pharynx, esophagus and lung and all sites. The factors associated with these results were analyzed in relation to radiotherapy and smoking. Through these studies, the authors proved the usefulness of the data accumulated in a population-based cancer registry, especially in finding the multiple primaries, surveying prognosis of subjects and controls, and calculating expected numbers using the incidence data from the general population.

Adult↗
PubMed2000

Chlamydia trachomatis infection as a risk factor for invasive cervical cancer.

Cervical carcinoma is a sexually transmitted disease most strongly linked with human-papillomavirus (HPV) infection. We conducted a prospective sero-epidemiologic study to evaluate the role of Chlamydia trachomatis infection in the development of cervical carcinoma, with invasive cancer as an end point. A nested case-control study within a cohort of 530000 Nordic women was performed. Linking data files of 3 Nordic serum banks and the cancer registries of Finland, Norway and Sweden identified 182 women with invasive cervical carcinoma diagnosed during a mean follow-up of 5 years after serum sampling. The serum samples of the cases and matched cancer-free controls were analyzed for IgG antibodies to C. trachomatis, C. pneumoniae (a control microbe) and HPV types 16, 18 and 33, as well as for serum cotinine (an indicator of tobacco smoking). Serum antibodies to C. trachomatis were associated with an increased risk for cervical squamous-cell carcinoma (HPV- and smoking-adjusted OR, 2.2; 95% CI, 1.3-3.5). The association remained also after adjustment for smoking both in HPV16-seronegative and -seropositive cases (OR, 3.0; 95% CI, 1.8-5.1; OR, 2.3, 95% CI, 0. 8-7.0 respectively). No such association was found for C. pneumoniae. Our prospective study provides sero-epidemiologic evidence that infection with C. trachomatis confers an increased risk for subsequent development of invasive squamous-cell carcinoma of the uterine cervix.

Adenocarcinoma↗
PubMedDate not supplied

Outreach to multiethnic, multicultural, and multilingual women for breast cancer and cervical cancer education and screening: a model using professional and volunteer staffing.

Reaching low-income women from diverse ethnic and cultural communities for the purpose of breast and cervical cancer education and screening is a challenge. This article describes an approach used by Center for Healthy Aging in Santa Monica, California, to implement three projects aimed at Hispanic and African American women to encourage early intervention behaviors. Hispanic and African American volunteers and professional staff work together to establish trusting relationships, join forces with community leaders and develop collaborative approaches to achieve the goal of screening about 1,000 underserved women annually and providing education for an additional 5,000 women. Incorporated in the article are lessons learned about working with this population, the communities in which they live and the use of volunteers for these and other projects.

Black People↗
PubMed1980

Association of breast cancer and cervical cancer incidence with income and education among whites and blacks.

Data from the 1969-71 Third National Cancer Survey were used to study the association of cancer incidence with income and education as indicated by census tract of residence. Also considered was the effect of adjustment for differences in socioeconomic distribution on the observed excess risk of cervial cancer and lower risk of breast cancer among black women compared to white women. Strong positive associations with both income and education were found, with the rates based on 19,344 breast cancer cases among white women. These observations were noted in most geographic areas studied. The relative risk showed little apparent relationship to age. The rates based on 1,570 cases among black women indicated a strong positive association with education but not with income. Socioeconomic adjustment reduced by almost one-half the black-white difference in breast cancer rates, and education had a stronger effect than did income. White women continued to have a significantly higher rate after such adjustment. Conversely, the incidence of cancer of the cervix showed strong negative associations with each of the two variables among both the 3,802 cases in white women and 954 cases in black women. The negative gradient decreased with age and was apparent in almost all the areas. The excess risk among black women was reduced by two-thirds with socioeconomic adjustment, though the rates remained significantly different. Income had a stronger association than did education with cervical cancer incidence.

Adult↗
PubMed1998

Telomerase activity and human papillomavirus (HPV) infection in human uterine cervical cancers and cervical smears.

Telomerase activity and human papillomavirus (HPV) infection were investigated in uterine cervical samples using molecular biology techniques. Thirteen cervical carcinomas and corresponding normal tissue from the same patient, and 102 cervical swabs were examined. Telomerase activity was detected in 12 of 13 cervical cancer tissues (92%). Of the 12 cases that showed telomerase activity, all were HPV positive, and the one case that did not show telomerase activity was HPV negative. A telomeric repeat amplification protocol assay detected telomerase activity in one out of seven normal cervical tissues (14%), and this one case was HPV positive. In cervical smear samples, telomerase activity was detected in two out of 36 normal smears (6%; both HPV positive), in 10 of 32 (31%) CIN1 (cervical intra-epithelial neoplasia) cases (three HPV positive), in four of five (80%) CIN2 cases (two HPV positive), in 15 of 21 (71%) CIN3 cases, (seven HPV positive) and in seven of eight (88%) squamous cell carcinoma cases (six HPV positive). These results suggest that telomerase activity may play some role in cervical carcinogenesis, and telomerase activity is associated with HPV infection in uterine cervical lesions.

Carcinoma, Squamous Cell↗