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Generation and characterization of monoclonal antibodies directed against the surface antigens of cervical cancer cells.

In this report, we describe the development and characterization of monoclonal antibodies against the surface antigens of cervical cancer cells. Using HeLa cervical carcinoma cells as the immunogen, we have developed a number of antibodies that specifically label cervical cancer cells but not normal cervical epithelial cells. These antibodies displayed differential reactivity towards various cervical cancer cell lines as determined by immunofluorescence labeling and western blotting analyses. One of these antibodies, 13G4, which showed the strongest labeling to HeLa cells and has the widest range of reactivity to other cervical cancer cell lines, was extensively characterized. By immunoaffinity chromatography, we purified a 90-kDa protein that appears to be the principal target recognized by this antibody. This protein was subsequently identified as decay accelerating factor (DAF) or CD55 by the mass spec sequencing analysis of the tryptic peptides derived from this protein. Digestion of HeLa DAF with glycosidases that removed its N- and O-linked carbohydrates has revealed that the 13G4 antibody binds to the peptide portion of this glycoprotein. Overall, our approach of generating and characterizing monoclonal antibodies directed against the surface antigens of cervical cancer cells serves as a stepping stone towards the eventual development of a unique panel of monoclonal antibodies that could potentially be used for the detection and therapeutic treatment of cervical cancer.

Animals↗

Efficacy of screening for cervical cancer: a review.

Cytologic screening for cervical cancer currently enjoys wide acceptance, but there remains controversy in the literature concerning its efficacy in prolonging life. On the basis of a literature review, several conclusions are reached: 1) Cervical screening can identify women who are at greater-than-average risk of developing invasive cervical cancer by detecting asymptomatic lesions that would frequently progress to invasion if left untreated; 2) Therapy based on confirmed positive smears can reduce the incidence and mortality rates of invasive cervical cancer, as shown by declining rates in many centers that had constant or increasing rates before screening began, lower rates for geographic areas and occupational groups having less screening, and lower rates among screened women than unscreened women; and 3) Attempts to estimate the amount of life prolongation attributable to cervical screening have not yet yielded reliable figures, because of difficulties with the models or data used. However, in view of the available evidence, it is suggested that incomplete data should not prevent a vigorous continuation of screening where it is already extensive, and an escalation where it is not.

Adolescent↗

[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers].

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.

Adult↗

Implementing recommendations for the early detection of breast and cervical cancer among low-income women.

SCOPE OF THE PROBLEM: Among U.S. women, breast cancer is the most commonly diagnosed cancer and remains second only to lung cancer as a cause of cancer-related mortality. The American Cancer Society (ACS) estimates that 182,800 new cases of female breast cancer and 41,200 deaths from breast cancer will occur in 2000. Since the 1950s, the incidence of invasive cervical cancer and mortality from this disease have decreased substantially; much of the decline is attributed to widespread use of the Papanicolaou (Pap) test. ACS estimates that 12,800 new cases of invasive cervical cancer will be diagnosed, and 4,600 deaths from this disease will occur in the United States in 2000. ETIOLOGIC FACTORS: The risk for breast cancer increases with advancing age; other risk factors include personal or family history of breast cancer, certain benign breast diseases, early age at menarche, late age at menopause, white race, nulliparity, and igher socioeconomic status. Risk factors for cervical cancer include certain human papilloma virus infections, early age at first intercourse, multiple male sex partners, a history of sexually transmitted diseases, and low socioeconomic status. Black, Hispanic, or American Indian racial/ethnic background is considered a risk factor because cervical cancer detection and death rates are higher among these women. RECOMMENDATIONS FOR PREVENTION: Because studies of the etiology of breast cancer have failed to identify feasible primary prevention strategies suitable for use in the general population, reducing mortality from breast cancer through early detection has become a high priority. The potential for reducing death rates from breast cancer is contingent on increasing mammography screening rates and subsequently detecting the disease at an early stage--when more treatment options are available and survival rates are higher. Effective control of cervical cancer depends primarily on early detection of precancerous lesions through use of the Papanicolaou test, followed by timely evaluation and treatment. Thus, the intended outcome of cervical cancer screening differs from that of breast cancer screening. In 1991, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) was implemented to increase breast and cervical cancer screening among uninsured, low-income women. RESEARCH AGENDA: To support recommended priority activities for NBCCEDP, CDC has developed a research agenda comprising six priorities. These six priorities are a) determining effective strategies to communicate changes in NBCCEDP policy to cancer screening providers and women enrolled in the program; b) identifying effective strategies to increase the proportion of enrolled women who complete routine breast and cervical cancer rescreening according to NBCCEDP policy; c) identifying effective strategies to increase NBCCEDP enrollment among eligible women who have never received breast or cervical cancerscreening; d) evaluating variations in clinical practice patterns among providers of NBCCEDP screening services; e) determining optimal models for providing case-management services to women in NBCCEDP who have an abnormal screening result, precancerous breast or cervical lesion, or a diagnosis of cancer; and f) conducting economic analyses to determine costs of providing screening services in NBCCEDP. CONCLUSION: The NBCCEDP, through federal, state, territorial, and tribal governments, in collaboration with national and community-based organizations, has increased access to breast and cervical cancer screening among low-income and uninsured women. This initiative enabled the United States to make substantial progress toward achieving the Healthy People 2000 objectives for breast and cervical cancer control among racial/ethnic minorities and persons who are medically underserved. A continuing challenge for the future is to increase national commitment to providing screening services for all eligible uninsured women to ultimately reduce morbidity and mortality from breast and cervical cancer.

Breast Neoplasms↗

Cervical cancer: issues of sexuality and fertility.

Cervical cancer rates have fallen in the United States; regardless, the disease remains a significant concern for women, especially those who are premenopausal. The management of cervical cancer is dependent on stage of disease at diagnosis, and specific needs emerge for patients both during and following treatment. Over the past decade, the focus has been to maintain adequate tumor control while reducing long-term negative consequences. However, problems with sexuality and fertility persist for women treated for cervical cancer despite these advances. Sexual dysfunction following treatment for gynecologic cancer has been well documented in the literature, and recent studies demonstrate the success of brief psychosexual interventions. Treatment of sexual difficulties in cancer patients can be achieved through the provision of information, support, and symptom management, ideally as part of a sexual health program. Resources are not always available to develop such a program. However, medical professionals can identify individuals and organizations with expertise in treating sexual and fertility concerns, which can be provided to their patients, making help with these problems more accessible as needs arise.

Female↗

American Indian women's talking circle. A cervical cancer screening and prevention project.

BACKGROUND: Cervical cancer is important to American Indian women due to high mortality and low survival rates compared with other ethnic groups. This article describes the development and implementation of a culturally acceptable cervical cancer screening program in urban and rural American Indian health clinics in California. METHODS: A team of researchers used social learning theory, research data, and focus groups to design a cervical cancer screening program. The major component of the program was the adaptation of a culturally acceptable mode of communication called Talking Circles. The American Indian Talking Circle project used the Talking Circle format, coupled with traditional Indian stories, as a vehicle to provide cancer education and to improve adherence to cancer screening. Eight American Indian clinics were randomly assigned into intervention and control sites (n = 400 women). The intervention was administered to 200 Indian women 18 years and older in four American Indian clinics; four additional American Indian clinics (n = 200 women) served as control sites. RESULTS: Preliminary results from the research show that American Indian women responded favorably to a culturally framed education project. Initial reports indicate that health-related information is accepted and acted on when it is coupled with cultural information that is presented in a sensitive manner. Final evaluation of the project is forthcoming. CONCLUSIONS: Utilizing a culturally acceptable intervention has the potential to improve the health status of American Indian Women.

Attitude to Health↗

Knowledge and practice about cervical cancer and Pap smear testing among patients at Kenyatta National Hospital, Nairobi, Kenya.

Invasive cervical cancer (ICC) is the leading cause of cancer-related death among women in developing countries. Population-based cytologic screening and early treatment does reduce morbidity and mortality associated with cervical cancer. Some of the factors related to the success of such a program include awareness about cervical cancer and its screening. The objective of this study was to assess knowledge and practice about cervical cancer and Pap smear testing among cervical cancer and noncancer patients using a structured questionnaire to obtain information. Fifty-one percent of the respondents were aware of cervical cancer while 32% knew about Pap smear testing. There were no significant differences in knowledge between cervical cancer and noncancer patients. Health care providers were the principal source of information about Pap testing (82%). Only 22% of all patients had had a Pap smear test in the past. Patients aware of cervical cancer were more likely to have had a Pap smear test in the past. The level of knowledge is low among ICC and noncancer patients. There is need to increase the level of knowledge and awareness about ICC and screening among Kenyan women to increase uptake of the currently available hospital screening facilities.

Adult↗

Sexual health in women treated for cervical cancer: characteristics and correlates.

OBJECTIVE: A large proportion of women with a history of cervical cancer experience sexual problems as a result of treatment. The present study examined whether differences in sexual health between cervical cancer survivors and women with no history of cervical cancer could be explained by selected demographic, clinical, and psychosocial and physical factors. METHODS: Women treated between 1 and 5 years previously for stage 0 to II cervical cancer and age- and education-matched women with no history of cancer undergoing routine cervical cancer screening were recruited to participate. All participants had a partner with whom they had ever been sexually active. Women completed measures of sexual health, vaginal changes, partner relationship quality, perceived physical appearance, and sexual self-concept. RESULTS: Cervical cancer survivors reported significantly (p<.05) less sexual interest, more sexual dysfunction, and lower sexual satisfaction. The most consistent predictors of sexual health after treatment among survivors were time since diagnosis, receipt of radiotherapy, partner relations, and perceived physical appearance, as well as vaginal changes. These variables accounted for about 50% of the variance in sexual health outcomes. CONCLUSION: The findings suggest that efforts to improve sexual health in women with a history of cervical cancer must move beyond the direct effects of cancer treatment on vaginal anatomy and physiology. Sexual rehabilitation interventions should consider partner relationships, perceived physical appearance, and women's attitudes toward themselves as sexual beings, in addition to vaginal changes. Future research should use prospective longitudinal research designs incorporating appropriate comparison groups to further explore this issue.

Adult↗

Influence of age on cervical cancer survival in Japan.

BACKGROUND: Relative 5-year survival for cervical cancer has been reported to be lower in older women in Japan. A population-based study was carried out to clarify why increased age is associated with decreased survival in spite of a nationwide cervical cancer screening program having been carried out since 1982 in Japan. METHODS: The Osaka Cancer Registry's data were used to investigate associations between age groups and survival for cervical cancer patients. Survival analysis was restricted to the reported 8966 cases diagnosed in 1975-1996 who lived in Osaka Prefecture (except for Osaka City), or resided in Osaka City in 1993-1996, since active follow-up data on vital status 5 years after the diagnosis were available. RESULTS: Relative 5-year survival for cervical cancer cases was lower in older age groups (88.6% in <30 years, 78.1% in 30-54 years, 67.7% in 55-64 years and 54.4% in 65+ years), as was the proportion of the detection by screening (6.3, 9.8, 9.2 and 6.0%), the proportion of the localized stage (83.0, 67.3, 51.0 and 42.7%) and the proportion of women who underwent surgery (79.2, 83.2, 65.6 and 35.2%). Among localized cases detected with screening, the survival in those > or =55 years old was >92% and almost comparable with that in 30 to 54 year olds, but significantly lower among those detected without screening. CONCLUSION: Lower survival among older women was caused mainly by the presence of more advanced disease at diagnosis. Further extension of the nationwide cervical cancer screening program should result in improved diagnosis of earlier stage disease, which might improve differences of cervical cancer survival among these age groups.

Adult↗

Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers.

Loss of heterozygosity (LOH) at chromosome 3p21 is frequent in cervical cancers. The candidate tumor suppressor gene, RASSF1A located at 3p21.3, is found to be inactivated in several major human cancers, implicating its significance in carcinogenesis. We aimed to investigate the status of RASSF1A in cervical cancers. The mutation and methylation status of RASSF1A were analysed in 4 cervical cancer cell lines, 50 primary cervical cancers including 33 squamous cell carcinoma (SCC), 17 adenocarcinoma (AC) and 11 normal controls. The primary cancer samples were also detected for LOH at 3p21 and human papillomavirus (HPV). Hypermethylation of RASSF1A was detected in 30% of SCC, 12% of AC and in 1 of the 4 cancer cell lines but was absent in all normal cases. Methylation of the cancer cell line was associated with loss of gene expression, which was restored by demethylation. About 67% (8 of 12) of hypermethylated primary cancers showed concomitant LOH at 3p21. No somatic mutation was found in all primary cancer samples or cell lines but 2 cases showed germline polymorphism at codon 133. Oncogenic HPV DNAs were found in most cancer samples. No correlation was detected between RASSF1A-hypermethylation or LOH at 3p21 and age of patient, HPV genotype, tumor grade and stage. Hypermethylation of RASSF1A occurs in a subset of cervical cancers, among which concomitant LOH at 3p21 is common. The results supported that RASSF1A may be one of the cervical cancer-related tumor suppressor genes located at 3p21 regions.

Adenocarcinoma↗

Risk factors for cervical cancer in Colombia and Spain.

A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.

Age Factors↗

Determinants of risk of invasive cervical cancer in young women.

We analysed determinants of risk of cervical cancer in women aged less than 45 years using data from a case-control study conducted in Italy. Cases were 261 women aged < 45 years with histologically confirmed invasive cervical cancer. Controls were 257 women aged < 45 years, with acute, non-neoplastic conditions, judged to be unrelated to any of the known or suspected risk factors for cervical cancer. In comparison with women reporting one or no sexual partner, the multivariate odds ratio (OR) of cervical cancer was 2.4 (95% confidence interval, CI, 1.3-4.6), for women reporting two or more sexual partners, and, in comparison with women reporting their first intercourse at 17 years of age or before, the multivariate OR was 0.5 (95% CI 0.3-0.9) in women aged > or =23 years at first intercourse. The risk of cervical cancer was higher in parous women and increased with number of births (OR = 8.1 for three or more births). Among parous women the risk tended to increase with later age at last birth; in comparison with parous women reporting their last birth before age 25, the OR was 1.9 in those reporting their last birth at > or =35 years. No clear association emerged between oral contraceptive use, smoking, education, social class and risk of cervical cancer.

Acute Disease↗

Prospects for primary prevention of cervical cancer in developing countries.

The HPV types that cause cervical cancer are sexually transmitted, but there is little evidence that infection can be avoided by behavioural changes, such as condom use. In contrast, prophylactic vaccines against HPV infection are likely to have high efficacy. In principle, the effectiveness of HPV vaccination as a strategy for cervical cancer control can be measured either by monitoring secular trends in cervical cancer incidence or by conducting randomized trials. The former approach is unlikely to provide convincing evidence of effectiveness, since cervical cancer rates are subject to strong secular trends that are independent of intervention measures. A few phase III trials of HPV prophylactic vaccines are now being started. Such trials are very expensive studies involving frequent and complicated investigations. It is important, however, to start as soon as possible simpler trials designed to demonstrate the effectiveness of HPV vaccine in field conditions, i.e. in developing or intermediate countries which suffer the major burden of mortality from cervical cancer. Such trials may capture a difference in the most severe, and rarest, preinvasive cervical lesions (i.e., the real target of any HPV vaccine) over a prolonged follow-up (20 years at least). The design of such studies is briefly considered for two areas: Southern India and South Korea. This paper is available at: http://www.insp.mx/salud/index.html.

Clinical Trials as Topic↗

Time costs associated with cervical cancer screening.

OBJECTIVES: Time costs borne by women when undergoing cervical cancer screening have rarely been elucidated, although such costs may pose substantial barriers to care. The purpose of this project was to quantify the opportunity costs associated with cervical cancer screening in young women attending Planned Parenthood Clinics. METHODS: We conducted a self-report survey of 105 women from six clinics to measure travel, waiting, and exam times associated with cervical cancer screening. Respondents recorded their time of arrival and departure, length of time in the waiting room, age, income level, and hours per week they worked outside of the home. Time costs were valued three ways: through self-reported hourly wage, age- and gender-adjusted minimum earnings, and national age- and gender-adjusted hourly wages. RESULTS: Respondents were on average 24 years old, worked 29 hours per week outside the home, and earned less than $20,000 per year. Mean time for one-way travel was 18.7 minutes; waiting room time was 16.9 minutes; and exam time was 50.8 minutes. Time costs were estimated to be $14.08 per visit based upon the self-reported hourly wage; $16.46 per visit based upon age- and gender-adjusted minimum earnings; and $19.63 per visit based upon age- and gender-adjusted national wage rates. CONCLUSIONS: Time costs associated with cervical cancer screening represent an important opportunity cost and should be considered in studies attempting to identify barriers to screening adherence. Our results indicate that time costs accounted for up to 25% of cervical cancer screening costs. Time costs should be identified, measured, valued, and included in cost-effectiveness analyses of cervical cancer screening.

Adult↗

Cervical cancers in Greenlandic women diagnosed after negative results on cervical cytology: perspectives in a high-risk population.

A total of 160 indigenous Greenlandic women had incident cervical cancer diagnosed during 1976-1991, and 41 of these women (27%) had had at least one negative smear reported during the 10 years preceding the diagnosis of cancer. Thirteen patients had previously had abnormalities of the cervix. Of the remaining 28 patients, 17 had so-called interval cancer diagnosed within three years after a negative smear result. In seven of these cases, representing 4% of all incident cancers during the period, there had previously been two or more negative smears. Suboptimal sampling of negative smears was suggested in roughly one out of two interval cancers. The results suggest that rapid biological development of cervical cancer is infrequent among Greenlandic females and that efforts should be aimed at increasing the smear test's sensitivity and providing a better follow-up of women with cervical abnormalities rather than shortening the three-year rescreening interval.

Adenocarcinoma↗

Geographic & age variations in invasive cervical cancer in Kentucky, 1995-1999.

The incidence rate of invasive cervical cancer in Kentucky is among the highest in the United States. Data from the Kentucky Cancer Registry and the National Cancer Institute (NCI) show that in 1998, Kentucky's invasive cervical cancer incidence rate was 49% higher than the national rate (11.2 per 100,000 women versus 7.5 per 100,000 women). As with most diseases, the incidence of invasive cervical cancer varies by both time and geographic location. As noted in a previous article by Wyatt et al, this variation is tied to the prevalence of established risk factors for cervical cancer over time and place. To document Kentucky's invasive cervical cancer incidence patterns, incident cases over a five-year period (1995-1999) were analyzed by place (Area Development District, ADD) and age.

Adolescent↗

[Radiotherapy for cervical cancer: a multi-institutional comparison].

Radiotherapy has long been recognized as a successful treatment modality for all stages of carcinoma of the uterine cervix. In Japan, however, radiotherapists mainly have had to treat patients with far advanced cancer. Recently, however, the incidence of patients with early-stage cervical cancer who undergo surgery has increased, whereas that of patients with advanced disease has decreased significantly. As a result, the number of cervical cancer patients who visit radiotherapy departments has decreased significantly. Radiotherapy is useful for early cervical cancer, and radiotherapists need to make every effort to treat patients with early-stage cancer. Radiotherapy alone for cervical cancer consists mainly of external irradiation and intracavitary brachytherapy. Two modalities are used for brachytherapy, low dose rate and high dose rate. The latter modality, which was developed about three decades ago, spread rapidly and was improved in Japan and Europe. In 1983, the standard method of treating cervical cancer with Co-60 RALS was proposed by Arai et al. in Japan. Most institutes accepted this method with some modifications and have reported treatment results based on it. Currently, several modalities of radiotherapy are available for cervical cancer. JASTRO organized a study group to reconsider the treatment proposed by Arai et al. and reviewed the outcomes from nine institutions in Japan. Chemotherapy combined with radiotherapy previously was considered ineffective for cervical cancer. However, this February NCI suggested concomitant chemoradiotherapy was effective for improving the survival rates of most cervical cancer patients. This suggestion is introduced.

Antineoplastic Combined Chemotherapy Protocols↗

Chapter 30: HPV vaccines and screening in the prevention of cervical cancer; conclusions from a 2006 workshop of international experts.

The finding that cervical cancer only occurs in women infected with specific, "high-risk" types of the human papillomavirus (HPV) has led to the development of novel, non-cytology-based cervical cancer prevention strategies. We now have sensitive molecular methods for detecting HPV that dramatically improve our ability to detect high-grade cervical cancer precursor lesions. Perhaps more importantly, prophylactic HPV vaccines have been developed that are protective against cervical cancer precursors caused by HPV 16 and 18. In the Spring of 2006, over 100 experts in HPV, cervical cancer screening, and vaccination worked together to define how best to incorporate HPV DNA testing and the HPV vaccines into cervical cancer prevention efforts. In this summary, we summarize the opinions of this expert group on how these advances can be introduced to provide the maximum benefit to women and to reduce the global burden of cervical cancer.

Female↗