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PubMed2001

[Can human papillomavirus testing and vaccination prevent cervical cancer?].

BACKGROUND: Cervical cancer is the third most frequent cancer among women worldwide. Human papillomavirus (HPV) infection is a necessary risk factor and the first step in cervical carcinogenesis. MATERIAL AND METHODS: This article reviews the current literature concerning the possibility of preventing cervical cancer by HPV testing and vaccination. RESULTS: HPV testing cannot replace cytology, but will reduce false negative cytology and may improve the screening programme for cervical neoplasia. It has not yet been incorporated in any national cervical cancer screening program, but trials are ongoing in Scandinavia and in the Netherlands. The cost-effectiveness of HPV testing in screening has to be proven and whether it can affect the recommended screening-intervals. Therapeutic and prophylactic vaccines for HPV associated disease are in progress. Evaluating the clinical trials that are ongoing will take several years. Several anti-HPV vaccines are now in clinical trials; Norway will also participate. Therapeutic vaccines against cervical cancer have so far not been successful, but anogenital dysplasias and condylomas may be more susceptible. Prophylactic vaccines against HPV 6, 11, 16 and 18 have been evaluated in clinical phase I and II trials, and phase III trials are in progress. INTERPRETATION: HPV testing improves the specificity and sensitivity of cervical cytology and it can be used to clarify cases with atypical cells of undetermined significance (ASCUS) and low-grade intraepithelial neoplasia. In the near future it may also be included in the cervical cancer screening programme for women above the age of 30. The first results in clinical vaccine trials are encouraging, and final conclusions about the effectiveness of these vaccines may be achieved in five years' time.

Female↗
PubMed1994

3-Aminobenzamide delays rejoining of DNA strand breaks in gamma-irradiated lymphocytes from patients with breast cancer and not cervical cancer.

An inhibitor of poly(ADP-ribose) polymerase is 3-aminobenzamide (3AB), treatment by which normally results in the decreased levels of rejoining of DNA single strand breaks. We have studied the effect of 3AB in gamma-irradiation induced damage and the subsequent repair of DNA along with the corresponding changes in poly (ADP-ribose) polymerase activity in lymphocytes of patients with the cancer of breast and uterine cervix. The presence or absence of 3AB prior to gamma-irradiation did not influence the extent of DNA damage. On the other hand, single strand breaks rejoining in breast cancer cases was found to be slower as compared to that of cervical cancer cases and normal individuals. The relative ADP-ribosylation in the presence of 3AB was much lower in the breast cancer cases as compared to normal but there was no significant change in the cervical cancer cases. Overall the maximum relative ADP-ribosylation was slower in the presence of 3AB. This suggests that the lower activity of poly (ADP-ribose) polymerase in breast cancer cases might delay the first phase of single strand breaks (SSBs) rejoining.

Adenosine Diphosphate↗
PubMed1991

Clinical implications of screening for cervical cancer under Medicare. The natural history of cervical cancer in the elderly: what do we know? What do we need to know?

Despite the recent passage of coverage for Papanicolaou test screening under Medicare, several aspects of the natural history of cervical cancer in the elderly remain uncertain. This article reviews what we know about cervical cancer in elderly women to provide clinicians with the background necessary for assessments of screening recommendations, integration of new data into practice, and development of consensus approaches to screening in the elderly. Two central questions that affect a screening program for the elderly are how long the neoplastic process takes from preinvasive disease to the development of invasive cancer, and how likely is it that a given neoplastic state observed in an elderly woman will, in fact, progress to a more severe state. The ultimate success of the new Medicare benefit will also be affected by the use of Papanicolaou testing, the technique of obtaining the smear, and the adequacy of reporting and follow-up. The expansion of Medicare benefits to include early cervical cancer detection has the potential to improve the quality and the duration of older women's lives.

Aged↗
PubMed2006

The German cervical cancer screening model: development and validation of a decision-analytic model for cervical cancer screening in Germany.

BACKGROUND: We sought to develop and validate a decision-analytic model for the natural history of cervical cancer for the German health care context and to apply it to cervical cancer screening. METHODS: We developed a Markov model for the natural history of cervical cancer and cervical cancer screening in the German health care context. The model reflects current German practice standards for screening, diagnostic follow-up and treatment regarding cervical cancer and its precursors. Data for disease progression and cervical cancer survival were obtained from the literature and German cancer registries. Accuracy of Papanicolaou (Pap) testing was based on meta-analyses. We performed internal and external model validation using observed epidemiological data for unscreened women from different German cancer registries. The model predicts life expectancy, incidence of detected cervical cancer cases, lifetime cervical cancer risks and mortality. RESULTS: The model predicted a lifetime cervical cancer risk of 3.0% and a lifetime cervical cancer mortality of 1.0%, with a peak cancer incidence of 84/100,000 at age 51 years. These results were similar to observed data from German cancer registries, German literature data and results from other international models. Based on our model, annual Pap screening could prevent 98.7% of diagnosed cancer cases and 99.6% of deaths due to cervical cancer in women completely adherent to screening and compliant to treatment. Extending the screening interval from 1 year to 2, 3 or 5 years resulted in reduced screening effectiveness. CONCLUSIONS: This model provides a tool for evaluating the long-term effectiveness of different cervical cancer screening tests and strategies.

Adolescent↗
PubMed2005

Rel/Nuclear factor-kappa B apoptosis pathways in human cervical cancer cells.

Cervical cancer is considered a common yet preventable cause of death in women. It has been estimated that about 420 women out of the 1400 women diagnosed with cervical cancer will die during 5 years from diagnosis. This review addresses the pathogenesis of cervical cancer in humans with a special emphasis on the human papilloma virus as a predominant cause of cervical cancer in humans. The current understanding of apoptosis and regulators of apoptosis as well as their implication in carcinogenesis will follow. A special focus will be given to the role of Rel/NF-kappaB family of genes in the growth and chemotherapeutic treatment of the malignant HeLa cervical cells emphasizing on Xrel3, a cRel homologue.

Journal Article↗
PubMed2005

Advocating for cervical cancer prevention.

Cervical cancer is a significant health problem among women in developing countries. Contributing to the cervical cancer health burden in many countries is a lack of understanding and political will to address the problem. Broad-based advocacy efforts that draw on research and program findings from developing-country settings are key to gaining program and policy support, as are cost-effectiveness analyses based on these findings. The Alliance for Cervical Cancer Prevention (ACCP) has undertaken advocacy efforts at the international, regional, national, and local levels to raise awareness and understanding of the problem (and workable solutions), galvanize funders and governments to take action, and engage local stakeholders in ensuring program success. ACCP experience demonstrates the role that evidence-based advocacy efforts play in the ultimate success of cervical cancer prevention programs, particularly when new screening and treatment approaches-and, ultimately, radically new approaches such as a human papillomavirus vaccine-are available.

Cost-Benefit Analysis↗
PubMed2004

Protein profiling of cervical cancer by protein-biochips: proteomic scoring to discriminate cervical cancer from normal cervix.

Analysis of multiple proteins is thought to be essential for establishment of signature proteomic patterns that may distinguish cancer from non-cancer. Surface-enhanced laser desorption/ionization (SELDI) is an affinity-based mass spectrometric method in which proteins of interest are selectively absorbed to a chemically modified surface on a biochip. This technology may provide protein profiling of a variety of biological specimens. In this study, we explored whether the protein biochip SELDI approach could differentiate cervical cancer from non-cancer cohorts. We screened protein profiles generated by SELDI in 62 cervical epithelial cell samples microdissected from 35 invasive cervical cancer and 27 age-matched normal cervix tissue specimens, respectively. The cell lysates of pure populations of cervical cells were applied onto Ciphergen ProteinChip WCX2 Arrays. Proteins bound to the chips were analyzed on a ProteinChip Reader Model PBS II. Derived proteomic patterns were converted to a simple proteomic scoring for distinguishing cancer from non-cancer cohorts. SELDI protein profiles of cell lysates from 20 cervical cancer and 15 normal cervix tissue specimens were used to train and develop a classification scoring system that used a seven-protein mass pattern. The training samples could be correctly discriminated. When a test set of 27 samples was used for evaluation of this scoring system to distinguish cervical cancer from non-cancer, a sensitivity of 87%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 86% for the test population were obtained. All seven proteins appeared to be down regulated in cervical cancer. The results from this study indicate that the proteomics approach of SELDI mass spectrometry, in combination with a simple scoring system, may distinguish cervical cancer from its normal counterpart. If this approach is also workable in the analysis of cervical exfoliated cell lysate, it might potentially be used in the early diagnosis of invasive cervical cancer. In addition, the identification of these specific proteins in cervical cancer may also facilitate the discovery of new cervical tumor marker(s).

Adult↗
PubMed2003

Chemopersistent early recurrence in the perineal tear scar of an intrapartally diagnosed cervical cancer.

BACKGROUND: Cervical cancer is the most frequent cancer occurring in pregnancy. Apart from some general recommendations, there is no standardized consensus for the management of this cancer during pregnancy. Individual case reports do exist on intrapartal cancer diagnosis and risks. CASE: We describe the case of an early recurrence in the perineal tear scar of an intrapartally diagnosed cervical cancer, which had developed despite combined neoadjuvant and adjuvant chemotherapy. CONCLUSIONS: Although iatrogenic tumor cell spreading in the vagina is rare, this oncological risk is easy to avoid. It should be considered in the peripartal management of patients suffering from cervical cancer. Our case report underlines the limits of chemotherapy in the treatment of tumor residue and points out the problem of cervical cancer cell spreading during invasive procedures.

Adult↗
PubMed1996

Expression and mutation of H-ras in uterine cervical cancer.

In cervical cancer, abnormalities of ras genes have not been fully investigated. We studied the expression and mutation of H-ras oncogene in cervical cancer to investigate their relationship and usefulness as an independent prognostic indicator. Twenty-seven paraffin-embedded resection specimens of cervical cancer (21 squamous, 3 adeno, 2 adenosquamous, and 1 small cell) were examined by immunohistochemistry using a mAb H-ras p21 and by PCR and allele-specific oligonucleotide hybridization using H-ras codon 12 and 61 amplimers and oligonucleotide probes. A strong immunoreaction was noted in 10 cases (37%) and weak immunoreaction in an additional 6 cases (22%). H-ras codon 12 mutations were detected in 6 of 27 cases (22%) and all of the mutations were guanine to adenine transitions. There was no mutation in codon 61. Cases with codon 12 mutations included all 3 squamous, 2 adeno, and I adenosquamous carcinoma. Only 3 of 16 (19%) cases with positive staining and 3 of 11 (27%) cases with negative staining showed mutations. No correlation was found between ras gene alterations and patient survival time. Our findings indicate that expression and mutation of H-ras oncogene occur in cervical cancer but their determination adds no useful prognostic information.

Adult↗
PubMedDate not supplied

Telomerase-A molecular marker for cervical cancer screening.

Cervical cancer is one of the most common cancers in women and can be routinely screened for by the Papanicolaou smear. Screening for HPV high-risk types 16 and 18 has augmented the sensitivity of this test, but still some cases remain undetected. We have investigated the utility of assaying telomerase activity as a possible screening marker for cervical cancer. Telomerase activity was studied in relation to HPV 16/18 infection, Papanicolaou smear cytopathology, and biopsy histopathology in a total of 88 subjects, consisting of 29 cervical cancer cases, 19 control hysterectomy samples, 16 precancerous cervical scrapes, 6 cervical samples from other gynecological malignancies, and 18 normal healthy cervical scrapings. Telomerase activity was detected in 96.5% of cervical tumor samples and in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples and in cervical scrapings of normal healthy controls. Telomerase assay had a diagnostic accuracy of 95.8 in tissue samples, 79.1 in scrapings and 91.2 in all. Whereas HPV-16/18 subtyping had a diagnostic accuracy of 89.5% in tissue samples, 70.5% in scrapings, and 82.1% in all. There was also 71% agreement between telomerase activity and HPV-16/18 infection. The absence of telomerase activity in cervical scrapes from healthy women indicated the potential of telomerase to serve as a good screening marker for the early diagnosis of cervical cancer. For the first time we have also shown the ability of telomerase to detect micro and probably occult metastasis in gynecological malignancies.

Adult↗
PubMed2006

Cervical cancer.

Worldwide, cervical cancer is the second most common malignancy in women and a major cause of morbidity and mortality. Until recently, the greatest strides in reducing cervical cancer mortality have occurred with the advent and implementation of screening programs. Many important advances have also taken place in the diagnosis and treatment of cervical cancer. This review article will highlight diagnostic and staging considerations with an emphasis on newer imaging modalities and how they might augment approved FIGO clinical staging. Management alternatives for patients with early-stage disease, locally advanced (stage IIB-IVA) disease, and metastatic cervical cancer will be discussed. Whenever possible, these discussions will unfold through an overview of pertinent clinical trials and current controversies.

Biopsy↗
PubMed2002

Perceptions of risk of cervical cancer and attitudes towards cervical screening: a comparison of smokers and non-smokers.

OBJECTIVES: The aim of this study was to compare smokers' and non-smokers' perceptions of risks of cervical cancer and attitudes towards cervical screening. METHODS: A cross-sectional descriptive study was carried out in 722 women aged between 20 and 64 years. RESULTS: While smokers perceived their relative risk of heart disease to be greater than that of non-smokers, they did not perceive their risks of cervical cancer to be greater. Smokers held less positive attitudes towards cervical screening than did non-smokers. Smokers and non-smokers did not differ in their intentions to attend for cervical screening: for both groups, intentions were very high. Using logistic regression analysis, both attitudes towards cervical screening [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.7-2.2] and perceived relative risk of developing cervical cancer (OR 1.5; 95% CI 1.0-2.1) were predictive of intentions to attend for screening, as well as educational level (OR 3.8; 95% CI 1.2-11.3) and marital status (OR 0.6; 95% CI 0.3-0.9). CONCLUSIONS: Smokers seem unaware of their increased risks of cervical cancer and hence the increased value for them of regular smears. Evaluations are needed to determine the effectiveness of interventions delivered in the context of cervical screening aimed at (i) raising smokers' awareness of their increased risk of cervical cancer and (ii) stopping smoking.

Adult↗
PubMedDate not supplied

Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer.

BACKGROUND: Cervical cancer constitutes the second most common cancer in women. Estrogen promotes development of cervical cancer in cells infected with high risk human papillomaviruses (HPVs). We asked whether the phytochemical indole-3-carbinol (I3C) has anti-estrogenic activities in cervical cells with the goal of preventing cancer in HPV infected cells. MATERIALS AND METHODS: Using the cervical cancer cell line CaSki, we evaluated expression of HPV and cytochrome p450 (CYP) enzymes by Northern, RNase protection or quantitative RT-PCR. I3C binding to estrogen receptor was measured by competition with estradiol. Estrogen metabolites were measured by gas chromarography-mass spectrometry (GC-MS). RESULTS: Estradiol increased expression of HPV oncogenes whereas I3C and the estrogen metabolite 2-hydroxyestrone (2-OHE) abrogated the estrogen-increased expression of HPV oncogenes. Both I3C and 2-OHE competed with estradiol for estrogen receptor binding. I3C enhanced gene expression of CYP enzymes responsible for 2-hydroxylation of estrogen, and induced the formation of 2-OHE. CONCLUSION: I3C has anti-estrogenic activities which should prevent cancer in cervical cells.

Anticarcinogenic Agents↗
PubMed2002

Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.

PURPOSE: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs. We have conducted a study in patients with early-stage cervical cancer to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins. EXPERIMENTAL DESIGN: Twenty-nine patients with clinical International Federation of Gynecologists and Obstetricians (FIGO) stage Ib or IIa cervical cancer were given two vaccinations with TA-HPV at least 4 weeks apart, starting 2 weeks before radical hysterectomy. Patients were monitored closely for side effects of the vaccination. Serial blood samples were examined for HPV-specific CTLs or changes in levels of antibodies to HPV-16 or -18 E6 and E7 proteins and to vaccinia virus. RESULTS: Vaccination with recombinant vaccinia was well tolerated in all patients with only mild to moderate local toxicity, and no serious adverse events were attributable to the vaccine. After a single vaccination, HPV-specific CTLs were found in four patients (HLA A1, A3, three patients; HLA A1, A24, one patient). Eight patients developed HPV-specific serological responses. CONCLUSIONS: This study confirmed the safety and immunogenicity of the vaccine in a proportion of those patients vaccinated. Additional clinical studies using TA-HPV in combination with an additional experimental vaccine for HPV-16 are currently under way.

Adenocarcinoma↗
PubMed2000

Interventions for encouraging sexual lifestyles and behaviours intended to prevent cervical cancer.

BACKGROUND: Cervical cancer is one of the most common cancers affecting women world-wide. Prevention falls into two main categories - primary and secondary. Primary prevention is characterised by health promotion to promote lifestyles and behaviours minimising risk of cervical cancer. Interventions to promote the use of condoms for sexual intercourse (especially early intercourse amongst young women), sexual partner reduction, and negotiated safer sex strategies has been recommended as one approach to limit the spread of Human Papilloma Virus (HPV), one of the major risk factors for cervical cancer. OBJECTIVES: To determine the effectiveness of health education interventions to promote sexual risk reduction behaviours amongst women in order to reduce transmission of HPV. SEARCH STRATEGY: Electronic searching of EMBASE, ERIC, MEDLINE, PsycLIT, Social Science Citation Index and the CCTR were undertaken using a highly sensitive search strategy. Hand-searching took place of selected journals and reference lists. SELECTION CRITERIA: Studies were included if they evaluated educational interventions targeting women only, and measured the impact on : either a behavioural outcome such as condom use for sexual intercourse, partner reduction, or abstinence; or a clinical outcome such as incidence of a sexually transmitted disease (STD). DATA COLLECTION AND ANALYSIS: Data were extracted and methodological quality was assessed independently by two reviewers and any discrepancies were resolved between them. Ten per cent of the total number of studies were reviewed additionally by a third reviewer as a quality check and differences in judgement were resolved accordingly. MAIN RESULTS: Thirty trials met the inclusion criteria for the review. All of them had the primary aim of preventing HIV and other STDs rather than cervical cancer. Four core methodological qualities were present in 10 of the 30 studies and constitute the subset from which potentially reliable conclusions may be drawn. Each of the 10 studies showed a statistically significant positive effect on sexual risk reduction, typically with increased use of condoms for vaginal intercourse. This positive effect was generally sustained up to three months after intervention. REVIEWER'S CONCLUSIONS: Educational interventions targeting socially and economically disadvantaged women in which information provision is complemented by sexual negotiation skill development can encourage at least short-term sexual risk reduction behaviour. This has the potential to reduce the transmission of HPV, thus possibly reduce the incidence of cervical carcinoma.

Female↗
PubMed2004

Dual apoptotic effect of Xrel3 c-Rel/NF-kappaB homolog in human cervical cancer cells.

Cervical cancer is one of the most common cancers affecting a woman's reproductive organs. Despite its frequency and recurrence, the death rate has been declining over the past 40 years, due to early detection and treatment. In a previous report [Shehata Marlene, Shehata Marian, Shehata Fady, Pater Alan. Apoptosis effects of Xrel3 c-Rel/Nuclear factor-kappa B homolog in human cervical cancer cells. Cell Biology International, in press], we studied the role of the NF-kappaB gene family in HeLa human cervical cancer cells, using the Xrel3 c-Rel homologue of Xenopus laevis. These results showed that the expression of Xrel3/c-Rel slowed cell growth, consistent with an upregulated expression of the cell cycle inhibitor p21 and the activated poly(ADP-ribose) polymerase (PARP) apoptosis effector. However, in this report, we examined more apoptotic and anti-apoptotic factors acting upstream and downstream in apoptosis pathways after cisplatin treatment of HeLa cervical cancer cells. After 1 microM cisplatin treatment, Xrel3 had an anti-apoptotic effect, based on significantly lower levels of apoptotic proteins, including caspase-8, caspase-3 and p21. Anti-apoptotic BAG-1 isoforms were upregulated. After 5 microM cisplatin treatment, expression of HeLa Xrel3 had an apoptotic effect, based on significantly increased expression of the cell cycle inhibitor p21 and apoptotic proteins, including cleaved PARP, caspase-8, and caspase-3. However, anti-apoptotic Bcl-2 and Bcl-X(L) were elevated and the cell cycle regulator cyclin D1 was slightly upregulated with both 1 and 5 microM cisplatin treatment. The HPV E6 oncoprotein showed no significant changes. These results support previous conclusions on the potential anti-apoptotic effects of c-Rel/NF-kappaB in mild stress environments, as opposed to the apoptotic effects associated with high stress conditions [Lake BB, Ford R, Kao KR. Xrel3 is required for head development in Xenopus laevis. Development 2001; 128(2), 263-73.]. Thus, c-Rel/NF-kappaB may potentially be of clinical significance in chemotherapy.

Antineoplastic Agents↗
PubMed2002

Detection of human papillomavirus DNA by PCR/microfluorometry for screening of cervical cancer.

BACKGROUND: Cervical cancer screening is conducted by a cytological Papanicolaou (Pap) test. For screening, it is becoming increasingly important to introduce a more objective result, based on human papillomavirus (HPV) DNA test. We describe here a practical method allowing the mass detection of HPV-DNA by PCR followed by fluorogenic DNA intercalation. METHODS: Samples used were cervical scrapes or biopsy specimens obtained from women who had undergone cytological testing for cervical cancer. Crude DNAs were extracted by a simplified proteinase K-boil method. Common and type-specific primers were newly designed for major types of high-risk HPVs. A fluorogenic DNA intercalator, SYBR Green I was directly added to the specific PCR products. The resultant fluorescence was measured by a conventional fluorometric microplate reader. RESULTS: The proposed PCR/microfluorometry (MFL) allowed a simple, rapid and economical detection of HPV-DNA without any use of labeling primers or probes. HPV-DNAs were found in 48.2% (123/255) of the cervical scrapes. The detection rate of HPV in cervical cancer biopsy specimen was 92.4% (61/66). CONCLUSIONS: PCR/MFL detection of HPV-DNA, followed by combined type-specific PCR, is expected to be an extremely useful tool in cervical cancer screening.

Benzothiazoles↗
PubMed1999

Effect of organised screening on cervical cancer incidence and mortality in Finland, 1963-1995: recent increase in cervical cancer incidence.

A nation-wide screening programme for cervical cancer started in Finland gradually from 1963 onwards. By the beginning of the 1990s, there had been a decrease of 80% both in the age-adjusted incidence of and mortality from cervical cancer. To describe the recent patterns in cervical cancer incidence and mortality and evaluate their differentials in relation with the organised screening activities, we have updated the material on the cervical cancer incidence and mortality as well as mass-screening activities up to the year 1995. Based on the files of the Finnish Cancer Registry, there is a striking increase of about 60% in the incidence of cervical cancer during the last 4 years of the study period among women below 55 years of age. The mortality rates are still decreasing. There is no overall decrease over recent years in the coverage of the programme invitations or smears taken. Incidence of invasive cancer and of moderate and severe dysplasia as detected in mass screening have increased. As to the interpretation, changes in the risk factors, such as in sexual behaviour and smoking habits, over the decades might partly explain increasing trends in cervical cancer incidence. As the change in incidence was relatively abrupt, inadequacies or changes in the effectiveness in the screening programme, particularly among young women, may also have contributed. Expanding the coverage of and attendance in the pap-screening programme among women in young target ages would still be effective. Increasing emphasis on quality assessment in screening is also needed.

Adult↗