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PubMed2002

Chemoradiotherapy for cervical cancer.

Cervical cancer remains a major health problem worldwide, despite advances in screening. For patients with locally advanced stage disease, failure to obtain local-regional control usually results in death. In an effort to improve local-regional tumour control, neoadjuvant and concurrent chemoradiation has been tested. Recently, five randomised trials performed by the Gynecologic Oncology Group (GOG), Radiation Therapy Oncology Group (RTOG) and the SouthWest Oncology Group (SWOG) studying cisplatin-based chemoradiation have demonstrated a significant survival advantage. Three of the trials compared cisplatin-based concurrent chemotherapy and radiation to radiation alone and two trials compared cisplatin-based concurrent chemotherapy and radiation to radiation with hydroxyurea. In all of the trials, cisplatin-based chemotherapy administered concurrently with radiation therapy was more effective at reducing the risk of death by 30-50%. Acute toxicities, principally neutropenia and gastrointestinal, were more common with chemoradiation, but were transient and the rates of late complications (complications that persisted or occurred for more than 60 days after the treatment) were similar. Based on the results of these five randomised trials, the National Cancer Institute (NCI) released a Clinical Announcement stating that cisplatin-based chemotherapy, as used in these trials (i.e. concurrently with radiation therapy), as the new standard of therapy for cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Second primary cancers after cervical intraepithelial neoplasia III and invasive cervical cancer in Southeast England.

OBJECTIVE: Multiple primary cancers may arise in an individual because they share a common environmental risk factor (such as smoking); genetic predisposition or immunodeficiency may predispose to both cancers, or treatment for one cancer may cause a second cancer. The objective of this analysis was to identify which, if any, cancers occur more often than would be expected in a cohort of women diagnosed with cervical intraepithelial neoplasia III (CIN III) and in women with invasive cervical cancer. METHODS: The Thames Cancer Registry was used to identify two cohorts of women diagnosed with either CIN III or invasive cervical cancer. The number of subsequent cancers at other sites was observed and compared to the expected number, based on relevant age-, sex-, and period-specific incidence rates. Standardised incidence rates (SIRs) were calculated assuming a Poisson distribution. RESULTS: The following cancer sites were significantly increased after a diagnosis of either CIN III or cervical cancer: anus (SIR 5.9 and 6.3, respectively), lung (SIR 1.8 and 2.5), vulva (SIR 4.4 and 1.9), vagina (SIR 18.5 and 8.0), and kidney (SIR 1.6 and 1.9). In addition, the incidence of cancers of the rectum, bladder, and connective tissue was significantly increased after invasive cervical cancer. Cervical cancers were seen significantly more often than expected after cancers of the anus and vagina. CONCLUSION: These results support the hypothesis that cancers of the cervix, anus, vulva, and vagina share common risk factors such as human papillomavirus and smoking.

Adult↗
PubMed2005

G-308A TNF-alpha polymorphism is associated with an increased risk of invasive cervical cancer.

Cervical cancer is initiated by high-risk human papillomaviruses (HPV-16 and HPV-18), but an effective immune response may control the progression of this disease. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, that has been implicated in several cancers. In a case-control study, we evaluated the association between the G-308A TNF-alpha promoter polymorphism and the risk for invasive cervical cancer (ICC). TNF-alpha polymorphism was analyzed by PCR-RFLP and confirmed by sequencing. DNA was obtained from blood samples of 439 individuals, including 195 patients with ICC and 244 normal healthy controls. According to our results, women carrying the A allele present a twofold increased risk of developing ICC (p=0.006; OR=1.88; 95% CI [1.20-2.94]). In conclusion, our study suggests that the presence of the high producer allele -308A in the TNF-alpha gene appears to be associated with an increased risk for the development of ICC.

Biomarkers, Tumor↗
PubMed2000

Chemoradiotherapy: the new standard care for invasive cervical cancer.

Cervical cancer remains a major health problem worldwide, despite advances in screening. For patients with locally advanced stage disease, failure to obtain local-regional control usually results in death. In an effort to improve local-regional tumour control, neoadjuvant and concurrent chemoradiation have been tested. Recently, 5 randomised trials performed by the Gynecologic Oncology Group, Radiation Therapy Oncology Group and the Southwest Oncology Group studying cisplatin-based chemoradiation have demonstrated a significant survival advantage. Three of the trials compared cisplatin-based concurrent chemotherapy and radiation to radiation alone and 2 trials compared cisplatin-based concurrent chemotherapy and radiation to radiation with hydroxyurea. In all trials, cisplatin-based chemotherapy administered concurrently with radiation therapy was the more effective therapy, reducing the risk of death by 30 to 50%. Acute toxicities, principally neutropenia and gastrointestinal, were more common with chemoradiation but were transient and rates of late complications were similar between treatment groups. Based on the results of these 5 randomised trials, the National Cancer Institute released a Clinical Announcement stating that cisplatin-based chemotherapy as used in these trials concurrently with radiation therapy should be the new standard of therapy for high risk early stage and locally advanced stage cervical cancer.

Antineoplastic Agents↗
PubMed1994

Cytological changes preceding cervical cancer.

Cervical smears were reviewed from 62 women who developed squamous carcinoma of the cervix up to 18 years later. The findings indicate that the prevention of cervical cancer by screening depends very largely on the detection of severe dyskaryosis. In this series there was no evidence that mild dyskaryosis was a forerunner of invasive disease. Cytology during the evolution of squamous carcinoma is not characterised by a dyskaryosis which progressively increases in severity. Instead the findings support new concepts that cervical cancer generally arises from an aggressive CIN 3 lesion widely present in the cervix, and in our series, established years before invasion occurs. It would be more useful to report cytology as showing either a low or high grade abnormality rather than distinguishing between different degrees of dyskaryosis.

Adult↗
PubMedDate not supplied

[Detection of breast cancer and cervical cancer. Teaching life habits].

In the United States, annual deaths from breast cancer and cervical cancer outnumber deaths caused by all other types of gynecological cancer. Although early detection and intensive treatment can save the lives of a great number of victims, many Americans often fail to follow recommended detection procedures. The nurse practitioner's global approach and advanced level of knowledge allow her to intervene at all stages of care delivery, and consequently give her a key role in preventing these ailments. She is able to evaluate a client's state of health and the quality of health care offered to the clientele. She can explain to women the risk factors for cancer, design programs for early detection and intervention, and follow up on clients' treatments. By pointing out health care needs to the members of the care team, the nurse practitioner works toward improving care quality. She is called upon to defend women's interests in discussions likely to have an impact on the detection and treatment of breast cancer and cervical cancer.

Breast Neoplasms↗
PubMedDate not supplied

Role of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in re-recurrent cervical cancer.

Cervical cancer patients with histologically documented re-recurrence after curative salvage therapy or unexplained tumor marker elevation (negative computed tomography and/or magnetic resonance imaging [CT-MRI]) proven to be a re-recurrence when a further attempt for cure (or control of cancer) appeared feasible were enrolled. Lesion status was determined from pathology or clinical follow-up for at least 12 months. Management decisions were recorded with CT-MRI alone and incorporating [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), respectively. The benefits calculated were based on clinical impact because of the FDG-PET findings. Cox proportional hazards model was used to select independent prognostic covariates. Of the 26 patients who were eligible for analysis, 12 (46.2%) patients had positive impacts due to PET. Squamous cell carcinoma (SCC, P = 0.029), re-recurrence at distant metastasis only (P = 0.012), and level of SCC antigen < or = 4 ng/mL (P = 0.005) were significantly associated with better survival. A scoring system using these covariates defined three distinct prognostic groups (P = 0.0001). Patients with score 0 had a 36-month cumulative survival rate of 80%. Using this prognostic scoring system, FDG-PET may facilitate selecting appropriate management for the individual patient with re-recurrent cervical cancer.

Adult↗
PubMedDate not supplied

Human papillomavirus and cervical cancer.

Cervical cancer is the fifth most common cancer worldwide, and is second only to breast cancer as the leading cause of cancer deaths in women. Half a million cases are diagnosed annually with the highest rates in developing countries.

Female↗
PubMed1987

The role of contraceptive use in cervical cancer: the Maryland Cervical Cancer Case-Control Study.

Recent evidence on the importance of sexual history and sexually transmissible agents in cervical cancer has been reported. Case-control studies have frequently demonstrated increased risk of cervical cancer for women using oral contraceptives, while laboratory results have shown that vaginal spermicides inactivate various sexually transmissible agents. To determine the role of contraceptive use in cervical cancer, 153 cases of Maryland women with invasive cervical cancer and age, race, and residence-matched controls were interviewed in 1985, focusing on sexual history, health care utilization patterns, screening history, contraceptive use, and smoking. Overall, lifetime use of contraceptives was protective of cervical cancer (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.2-0.7). Use of oral contraceptives (OR = 0.48), diaphragm (OR = 0.29), and vaginal spermicides (OR = 0.28) were more frequent in controls than cases. After adjustment for behavioral factors (age at first intercourse, smoking, gaps in Papanicolaou smear testing, and obstetrician-gynecologist visits), use of vaginal spermicides remained significant (OR = 0.30), although use of oral contraceptives and barrier methods of contraception failed to remain significant. The effectiveness of vaginal spermicides in preventing cervical cancer may be due to their antiviral action.

Adult↗
PubMed1997

Quantitative determination of the epidermal growth factor receptor in cervical cancer and normal cervical epithelium by 2-color flow cytometry: evidence for down-regulation in cervical cancer.

Expression of epidermal growth factor receptor (EGFR) was quantified by 2-color flow cytometry in cervical cancer (n = 73) and normal cervical epithelium (n = 11). EGFR was determined using a murine monoclonal EGFR antibody, and number of bound antibodies was quantified adding calibration beads with defined antigenic binding sites. Tumor cells were identified by simultaneous DNA staining. Epithelium of normal cervical tissue was detected by labeling for cytokeratin. Results were compared with EGFR quantification by autoradiography on cryostat sections using a radioligand binding assay. A high degree of correlation was found between the 2 methods. In cervical carcinomas 14,600 binding sites/cell (median; range, 160-283,000 binding sites/cell) were detected, considerably less compared with normal cervical squamous epithelium, which was 30,700 binding sites/cell (median; range, 19,900-44,000 binding sites/cell). This finding clearly contrasts with other reports of enhanced EGFR expression in cervical cancer. The discrepancy may be explained by contamination of tissue homogenates used for radioligand or enzyme immunosorbent assays by non-epithelial tissue elements with low or absent EGFR expression. Interference with quantitative EGFR determination in epithelial cells may result in false low estimates of EGFR expression predominantly in normal cervical tissue. This should be avoided by identifying tumor and normal epithelial cells prior to analysis. In our study, 63% of cervical cancers expressed low levels of EGFR compared with normal cervical epithelium, and only 10% showed overexpression. There is evidence that cervical carcinomas overexpressing EGFR represent a small, but biologically distinct group of cervical cancers exhibiting enhanced aggressiveness associated with poor survival of the patients.

Antibodies, Monoclonal↗
PubMed2005

Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy.

With the goal of identifying genes with a differential pattern of expression between invasive cervical carcinomas (CVX) and normal cervical keratinocytes (NCK), we used oligonucleotide microarrays to interrogate the expression of 14,500 known genes in 11 primary HPV16 and HPV18-infected stage IB-IIA cervical cancers and four primary normal cervical keratinocyte cultures. Hierarchical cluster analysis of gene expression data identified 240 and 265 genes that exhibited greater than twofold up-regulation and down-regulation, respectively, in primary CVX when compared to NCK. Cyclin-dependent kinase inhibitor 2A (CDKN2A/p16), mesoderm-specific transcript, forkhead box M1, v-myb myeloblastosis viral oncogene homolog (avian)-like2 (v-Myb), minichromosome maintenance proteins 2, 4, and 5, cyclin B1, prostaglandin E synthase (PTGES), topoisomerase II alpha (TOP2A), ubiquitin-conjugating enzyme E2C, CD97 antigen, E2F transcription factor 1, and dUTP pyrophosphatase were among the most highly overexpressed genes in CVX when compared to NCK. Down-regulated genes in CVX included transforming growth factor beta 1, transforming growth factor alpha, CFLAR, serine proteinase inhibitors (SERPING1 and SERPINF1), cadherin 13, protease inhibitor 3, keratin 16, and tissue factor pathway inhibitor-2 (TFPI-2). Differential expression of some of these genes including CDKN2A/p16, v-Myb, PTGES, and TOP2A was validated by quantitative real-time PCR. Flow cytometry on primary CVX and NCK and immunohistochemical staining of formalin fixed paraffin-embedded tumor specimens from which primary CVX cultures were derived as well as from a separate set of invasive cervical cancers confirmed differential expression of the CDKN2A/p16 and PTGES markers on CVX versus NCK. These results identify several genes that are coordinately disregulated in cervical cancer, likely representing common signaling pathways triggered by HPV transformation. Moreover, these data obtained with highly purified primary tumor cultures highlight novel molecular features of human cervical cancer and provide a foundation for the development of new type-specific diagnostic and therapeutic strategies for this disease.

Biomarkers, Tumor↗
PubMed2000

Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands.

The study aimed at probing the possible role of human papillomavirus (HPV) infection in squamous cell carcinomas of the upper aerodigestive tract, with a special reference to tonsillar cancer. We used the Swedish Family Cancer Database to analyse second cancers in the upper aerodigestive tract of women first diagnosed with in-situ or invasive cervical cancer. First cancers of their husbands were also analysed. Standardized incidence ratios (SIRs) were calculated for female and male cancers, adjusted for age at diagnosis, period, sex, socio-economic status and residential area. Among women, increases were observed at many sites, but tonsillar cancers were increased only among women aged 50 years or more at diagnosis of in-situ cervical cancer (SIR 2.58). The increases at these sites are probably ascribed to the effects HPV, smoking, alcohol or their interaction. Husbands of cervical cancer patients developed an excess (SIR over 2.00) of both tonsillar cancer (SIR 2.39 when wife with in-situ cancer and SIR 2.72 when wife with invasive cervical cancer) and cancer of the tongue. The excess of tonsillar cancer among husbands of women with HPV-associated neoplastic lesions of the cervix supports the a priori hypothesis that HPV may be involved in tonsillar carcinogenesis.

Adult↗
PubMed2002

Women's knowledge about cervical cancer and cervical screening practice: a pilot study of Hong Kong Chinese women.

Cervical cancer is the seventh leading cause of death and the fourth most common type of cancer among Hong Kong Chinese women. Despite the provision of cervical screening programs, women's attendance for screening remains low at 59%. Evidence suggests that women's knowledge about cervical cancer and preventive strategies are significant to their screening practice. A preliminary pilot study consisting of a two-phase descriptive design using quantitative and qualitative methods of data collection was undertaken to investigate the level of knowledge about cervical cancer and cervical screening among a population of Hong Kong Chinese women. From a total sample of 467 women, 242 (52%) responded to a confidential questionnaire, 18 of whom, aged between 30 and 54 years, volunteered to participate in a semistructured interview. A total of 135 (57%) women had attended screening, with those who were married with children significantly more likely to attend. Although no significant difference was found between the overall level of knowledge of attenders and nonattenders, individual items such as women's knowledge of risk factors were significant. The need for further knowledge about the preventive nature of cervical screening and regular screening was demonstrated. Other factors influencing Chinese women's attendance patterns included advice from practitioners and the significance of children to women's propensity for self-care. The implications of these findings to women's attendance patterns for screening are considered, particularly the need for culturally sensitive health promotion and intervention strategies.

Adult↗
PubMed2004

Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer.

Cervical carcinoma is a human papilloma virus (HPV)-related immunogenic type of malignancy, in which escape of the tumor from the hosts' immune response is thought to play an important role in carcinogenesis. The multifunctional cytokine transforming growth factor-beta(1) (TGF-beta(1)) is involved in immunosuppression, stroma and extracellular matrix formation and controlling (epithelial) cell growth. The plasminogen activating (PA) system plays a key role in the cascade of tumor-associated proteolysis leading to extracellular matrix degradation and stromal invasion. Changes in expression of components of this system, including plasminogen activator inhibitor-1 (PAI-1), have been associated with poor prognosis in a variety of solid tumors. The present study was undertaken to assess the role of both components on relapse, survival and other clinicopathologic parameters in cervical cancer. 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 expression of PAI-1 protein. The presence of cytoplasmatic TGF-beta(1) mRNA in tumor cells was not significantly correlated with the other clinicopathologic parameters investigated or with a worse (disease-free) survival. Expression of the PAI-1 protein in tumor cells was strongly correlated with worse overall and disease-free survival, in addition to well-known prognostic parameters such as lymph node metastasis, depth of tumor infiltration, tumor size and vasoinvasion. In the multivariate analysis, PAI-1 turned out to be a strong independent prognostic factor. In a subgroup of patients without lymph node metastases, PAI-1 was predictive for worse survival and relapse of disease, too. Our results show that the (enhanced) expression of PAI-1 by carcinoma cells is correlated with worse (overall and disease-free) survival of patients with cancer of the uterine cervix. The expression of TGF-beta(1) in itself is not associated with worse survival in these patients. Although simultaneous presence of the 2 factors was observed in all tumors, induction of PAI-1 by TGF-beta(1) could not be demonstrated in our group of cervical carcinomas.

Adult↗
PubMed2004

A population-based study on the risk of cervical cancer and cervical intraepithelial neoplasia among grand multiparous women in Finland.

Previous studies suggest that high parity increases the risk of cervical cancer. We studied the risk of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN3) in a Finnish cohort of grand multiparous (GM) women (at least five children) with low prevalence of sexually transmitted infections (STI). The Finnish Cancer Registry data revealed 220 CC and 178 CIN3 cases among 86 978 GM women. Standardised incidence ratios (SIR) were calculated from the numbers of observed and expected cases. Interval analyses by parity, age at first birth and average birth interval were done using multivariate Poisson regression. Seroprevalence of human papillomavirus (HPV) 16 and Chlamydia trachomatis was tested among 561 GM women and 5703 women with 2-4 pregnancies. The incidence among GM women was slightly above the national average for squamous cell carcinoma of cervix uteri (SIR 1.21, 95% CI 1.05-1.40) and CIN3 (1.37, 95% CI 1.17-1.58), but lower for adenocarcinoma (SIR 0.77, 95% CI 0.52-1.10). The seroprevalence of HPV16 and Chlamydia trachomatis among GM women was lower than in the reference population, except among those women who had their child under age 19. Age under 20 years at first birth increased the risk of CC and CIN3 especially in premenopausal GM women, while increasing parity had no effect. The small relative risks of CC and CIN3 among GM women in our study as compared to studies from other countries can be explained by the exceptionally low prevalence of STIs in Finnish GM women. The observed SIRs between 1.2 and 1.4 should be interpreted to represent increased risk attributable to grand multiparity. The increased incidence of CC and CIN3 among young GM women suggests causal association to HPV 16 and Chlamydia trachomatis infections.

Adenocarcinoma↗
PubMed2007

Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer.

Cervical cancer (CaC) is the third most frequent cause of death from cancer among women in the world and the first in females of developing countries. Several ion channels are upregulated in cancer, actually potassium channels have been suggested as tumor markers and therapeutic targets for CaC. Voltage-gated sodium channels (VGSC) activity is involved in proliferation, motility, and invasion of prostate and breast cancer cells; however, the participation of this type of channels in CaC has not been explored. In the present study, we identified both at the molecular and electrophysiological level VGSC in primary cultures from human cervical carcinoma biopsies. With the whole cell patch clamp technique, we isolated and identified a voltage-gated Na(+) current as the main component of the inward current in all investigated cells. Sodium current was characterized by its kinetics, voltage dependence, sensitivity to tetrodotoxin (TTX) block and dependence to [Na(+)](o). By analyzing the expression of mRNAs encoding TTX-sensitive Na(+) channel alpha subunits with standard RT-PCR and specific primers, we detected Na(v)1.2, Na(v)1.4, Na(v)1.6, and Na(v)1.7 transcripts in total RNA obtained from primary cultures and biopsies of CaC. Restriction enzyme analysis of PCR products was consistent with the molecular nature of the corresponding genes. Notably, only transcripts for Na(v)1.4 sodium channels were detected in biopsies from normal cervix. The results show for the first time the functional expression of VGSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer.

Biomarkers, Tumor↗
PubMed2001

Locally advanced cervical cancer.

Cervical cancer is a tremendous health problem as the third most frequent cancer affecting women. Locally advanced disease, which exceeds that successfully treated with surgery, is a common presentation of unscreened women. The use of concurrent chemotherapy and radiation therapy has resulted in a significant increase in patient survival. Our understanding of cervical tumor biology has the potential for further improvements.

Combined Modality Therapy↗
PubMed1996

Cervical intraepithelial neoplasia and cervical cancer.

Cervical cancer remains an important health problem for women worldwide, despite its decline in countries where organized screening programs are in place. The morbidity of treatment and the mortality for advanced lesions are high, a frustrating situation because the cervix is accessible and a good screening test, the Pap smear, exists. HPV is an important risk factor, and the molecular evidence for its role is overwhelming. Molecular markers may soon help us decide which lesions are at highest risk of progression to invasion and which invasive lesions are likely to recur. Chemoprevention of precursor lesions is promising. An HPV vaccine could be effective in eradicating this cancer.

Biomarkers, Tumor↗