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PubMed1996

[Transvaginal color-Doppler sonography for monitoring the response to neoadjuvant chemotherapy in patients with locally advanced cervical cancer].

Changes in blood flow characteristics, observed with transvaginal color-Doppler ultrasonography have recently been reported in patients with advanced cervical cancer. In order to evaluate the reliability of TVCDUS in monitoring the response to neoadjuvant chemotherapy in patients with locally advanced cervical cancer, a prospective study was undertaken on the blood flow characteristics of the cervical vessels. Pulsatility Index (PI) and Resistance Index (RI) of the uterine and cervical arteries of 12 patients with histologically proven advanced cervical cancer, scheduled for neoadjuvant chemotherapy were evaluated at diagnosis, during every cycle of chemotherapy and before surgery. A significantly lower value of mean PI and RI between cervical and uterine arteries was observed in patients with cervical cancer (PI = 1.671 +/- 0.18 vs 2.159 +/- 0.24)-(RI = 0.43 +/- 0.17 vs 0.72 +/- 0.22). Mean RI and mean PI of the descending branches of the uterine arteries were significantly lower in patients with cervical cancer, compared to healthy control women. No difference in blood flow parameters could be detected between stage I vs stage II-III, and between left and right cervical artery in patients with cervical cancer. Both RI and PI values appeared strictly related to the tumor response to chemotherapy. In fact in 8 patients in which treatment resulted in tumor regression, evaluated by pelvic examination and MR imaging, a significant (p < 0.01) increase of resistance indices was observed (PI = 1.671 +/- 0.18 vs 2.158 +/- 0.22)-(RI = 0.43 +/- 0.17 vs 0.79 +/- 0.16). On the other side 4 patients not responding to chemotherapy, had stable values of both PI and RI. Transvaginal color-Doppler ultrasonography might be useful in monitoring the response to neoadjuvant chemotherapy in patients with locally advanced cervical carcinoma.

Aged↗
PubMed1986

Transforming activity of human papillomavirus type 16 DNA sequence in a cervical cancer.

A genomic DNA sample from cervical cancer tissue, containing human papillomavirus (HPV) type 16, was found to induce malignant transformation of NIH 3T3 cells when it was tested by transfection assays using the calcium phosphate coprecipitation technique. The primary and secondary transformants contained the HPV type 16 DNA sequences and human specific Alu family sequences. To the best of our knowledge, it has not been reported previously that HPV type 16 DNA sequences in total genomic DNA from a cervical cancer have transforming activity.

Adenocarcinoma↗
PubMed2005

Identification of human papillomavirus 16-E6 protein-derived peptides with the potential to generate cytotoxic T-lymphocytes toward human leukocyte antigen-A24+ cervical cancer.

Human papillomavirus 16 (HPV16)-E6 and -E7 proteins are considered to be appropriate targets in specific immunotherapy for cervical cancer. In this study, we attempted to identify epitope peptides from the HPV16-E6 protein that have the potential to generate cytotoxic T-lymphocytes (CTLs) toward human leukocyte antigen (HLA)-A24+ cervical cancer. Two HPV16-E6 peptides at positions 75-83 and 91-100 effectively induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24+ cervical cancer patients. These HPV16-E6 peptide-induced CTLs showed cytotoxicity against HLA-A24+ and HPV16-E6 protein-expressing cervical cancer cells. Experiments with blocking antibodies and cold inhibition targets revealed that the cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. In addition, based on our observation that induction of immunoglobulin G (IgG) reactive to administered CTL-directed peptides is correlated with clinical responses, we attempted to detect IgG reactive to HPV16-E6 peptides in the plasma of cancer patients. As a result, IgGs reactive to the HPV16-E691-100 peptide were detected in 4 of 12 cervical cancer patients. These results indicate that these HPV16-E6-derived peptides are good candidates in peptide-based immunotherapy for HLA-A24+ cervical cancer patients.

Female↗
PubMed1994

The Forsyth County Cervical Cancer Prevention Project--II. Compliance with screening follow-up of abnormal cervical smears.

The Forsyth County Cervical Cancer Prevention Project was a community-wide cancer education program to address the problem of cervical cancer incidence and mortality among minority women in Forsyth County, North Carolina. This paper reports program results with regard to increasing compliance with follow-up for abnormal cervical smears. An analysis of trends prior to and after implementation of the educational program was conducted in one private and two public health primary care clinics to provide an assessment of impact of the project in improving compliance with follow-up among black women. A similar analysis also was conducted for white women. The results of medical record reviews of follow-up procedures for 878 abnormal cervical smears suggested a modest program effect among black women. The percentage of black women who returned for follow-up and treatment of an abnormal cervical smear significantly increased during the time the program was in effect. The trend analysis further indicated that the decline did not begin prior to the intervention period and was maintained throughout the duration of the intervention. No significant change in the percentage who returned for follow-up was found for white women.

Adolescent↗
PubMed2003

Acute and long-term toxicity following radiotherapy alone or in combination with chemotherapy for locally advanced cervical cancer.

Randomised studies in locally advanced cervical cancer patients showed that cisplatin should be given concurrently with radiotherapy, because of a better long-term survival compared to radiotherapy alone. This increases the relevance of treatment related toxicity. This review summarises the acute and long-term toxicity of radiotherapy given with or without chemotherapy for cervical cancer. Acute toxicity (all grades) of radiotherapy is reported in 61% of the patients in the rectosigmoid, in 27% as urological, in 27% as skin and in 20% as gynaecological toxicity. Moderate and severe morbidity consists of 5% to 7% gastrointestinal and 1% to 4% genitourinary toxicity. Adding chemotherapy to radiotherapy increases acute haematological toxicity to 5% to 37% of the patients and nausea and vomiting in 12% to 14%. Late effects of radiotherapy include gastrointestinal, urological, female reproductive tract, skeletal and vascular toxicity, secondary malignancies and quality of life issues. For at least 20 years after treatment, new side effects may develop. Gastrointestinal toxicity usually occurs in the first 2 years after treatment in about 10% of the patients. The incidence of moderate and severe urological toxicity can increase up to 10% and rises over time. Gynaecological toxicity usually occurs shortly after treatment while skeletal and vascular toxicity can occur years to decades later. Thus far, no increase in late toxicity has been observed after the addition of cisplatin to radiotherapy. Finally, methods to prevent or decrease late toxicity and therapeutical options are discussed. However, most randomised studies still have a limited follow-up period.

Antineoplastic Agents↗
PubMed2001

TP53 polymorphism, HPV infection, and risk of cervical cancer.

The role of a polymorphism at position 72 of the tumor suppressor gene TP53 in the development of cervical cancer is not well established. The arginine variant of the p53 protein could be more susceptible to degradation by human papillomavirus (HPV) E6 protein than the protein containing proline. Recent studies show controversial results. We investigated a possible association between TP53 polymorphism and cervical cancer in a Peruvian population with high prevalence of HPV infection. HPV status and TP53 polymorphism were determined for 119 cases of invasive cervical cancer and 127 control women from Peru. HPV infection was detected by PCR of cervical cells or tumor biopsies. For determination of TP53 polymorphism, exon 4 of the TP53 gene was amplified by PCR, and DNA was subsequently subjected to restriction enzyme digest. Associations between TP53 polymorphism, HPV infection, and cervical cancer were assessed using logistic regression. Women homozygotes for arginine had a 2.2-fold increased risk (95% confidence interval: 0.6-7.6) for cervical cancer. The odds ratio for women heterozygotes for Arg/Pro was 3.5 (95% confidence interval: 0.9-14). Similarly increased risks were found when restricting analysis to HPV-positive women only. The distribution of TP53 genotypes in this Peruvian population was comparable with that found in Caucasians. Our results cannot rule out an association between the TP53 polymorphism at codon 72, HPV infection, and the etiology of cervical cancer.

Adult↗
PubMed2005

Epigenetics of cervical cancer. An overview and therapeutic perspectives.

Cervical cancer remains one of the greatest killers of women worldwide. It is difficult to foresee a dramatic increase in cure rate even with the most optimal combination of cytotoxic drugs, surgery, and radiation; therefore, testing of molecular targeted therapies against this malignancy is highly desirable. A number of epigenetic alterations occur during all stages of cervical carcinogenesis in both human papillomavirus and host cellular genomes, which include global DNA hypomethylation, hypermetylation of key tumor suppressor genes, and histone modifications. The reversible nature of epigenetic changes constitutes a target for transcriptional therapies, namely DNA methylation and histone deacetylase inhibitors. To date, studies in patients with cervical cancer have demonstrated the feasibility of reactivating the expression of hypermethylated and silenced tumor suppressor genes as well as the hyperacetylating and inhibitory effect upon histone deacetylase activity in tumor tissues after treatment with demethylating and histone deacetylase inhibitors. In addition, detection of epigenetic changes in cytological smears, serum DNA, and peripheral blood are of potential interest for development of novel biomolecular markers for early detection, prediction of response, and prognosis.

Animals↗
PubMed2003

Cervical cancer rates and the supply of primary care physicians in Florida.

BACKGROUND AND OBJECTIVES: This study's aim was to determine if an increased supply of primary care physicians is associated with lower incidence and mortality rates for cervical cancer. METHODS: We determined cervical cancer incidence and mortality rates for each of Florida's 67 counties over the 3-year period of 1993-1995 using data from Florida's population-based tumor registry. Data on physician supply were obtained from the 1994 American Medical Association Physician Masterfile. We used multiple linear regression analysis to examine the relationship between physician supply and cervical cancer incidence and mortality rates, adjusting for other county-level characteristics. RESULTS: In regression analysis that adjusted for other county-level characteristics, each increase in the supply of family physicians of one physician/10,000 persons was associated with a corresponding drop in the incidence rate of 1.5 cases/100,000 persons and a corresponding drop in mortality rate of .65 cases/100,000 persons. CONCLUSIONS: Our results indicate that a greater supply of primary care physicians is likely associated with a lower incidence of cervical cancer and a lower cervical cancer mortality rate. More studies are needed at the individual patient level to confirm this association.

Confidence Intervals↗
PubMed2001

Cytokine profile of cervical cancer cells.

OBJECTIVE: In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine profile of cervical carcinoma cells. In addition, we have measured whether differences in cytokine profiles between normal and malignant cervical epithelial cells are present. METHODS: For this purpose we have determined the mRNA expression patterns of 20 relevant cytokines by RT-PCR and Southern blotting in 3 normal primary cervical epithelial cell cultures (NPE) and 10 cervical cancer cell lines (CCCL). RESULTS: TGF-beta(1), IL-4, IL-12p35, and IL-15 were produced by all CCCL and NPE. TNF-alpha, IL-10, IL-5, and RANTES were present in most NPE, but not in any of the CCCL. MCP-1 was expressed in all CCCL but in only one NPE. The presence of the anti-inflammatory cytokine TGF-beta(1) in cervical carcinomas was confirmed by RNA in situ hybridization on tissue sections of carcinomas from which the CCCL originated. CONCLUSIONS: Our results suggest that cervical carcinoma cells produce immunomodulatory cytokines and that cytokine expression patterns change after malignant transformation. The implications of locally produced cytokines by cervical cancer cells are further discussed.

Blotting, Southern↗
PubMed2005

Natural history and screening model for high-risk human papillomavirus infection, neoplasia and cervical cancer in the Netherlands.

A simulation model is presented that assumes that persistent infection with high-risk human papillomavirus (hrHPV) is a necessary cause of cervical cancer. For the estimation of the model parameters, data of recent Dutch follow-up studies were reanalyzed. The predicted incidences of cervical cancer, cervical intraepithelial neoplasia (CIN1, CIN2 and CIN3) and abnormal cytology were validated with nationwide figures and population-based screening results. The model predicted a lifetime risk for cervical cancer of 2.9% with a peak at age 48 years. The predicted lifetime risk dropped to 0.4% when attending cervical screening. For women who were not hrHPV infected at 30 years, the lifetime risk was 1.6%. Sensitivity analyses were performed to check natural history assumptions that were only weakly identified from available data sets. The incidence of CIN3 observed with screening appeared a useful clinical end point as the predicted incidence was robust against changes in the sensitivity of cervical cytology and the duration to CIN3. The model can be used to study the health-economic benefits that can be achieved in nationwide screening when including an hrHPV test.

Adolescent↗
PubMed1995

Age at marriage and cervical cancer incidence.

Cancer of the uterine cervix is the commonest cancer among Indian women accounting for 1/5 of the total cancer incidence. It is the estimated that by the turn of century 139,000 women in India would be developing cervical cancer. Age at marriage has been recognised as a major risk factor associated with cervical cancer. Over the past 8 decades there has been a rise in age at marriage varying from 14 years in 1901 to 18 years in 1981. Consequently the proportion of women married in the age group 15-19 years has fallen from 88% in 1941 to 45% in 1981. The present paper has attempted to study the effect of change in proportion married below 17 years on cervical cancer incidence for the year 1985 in India. The proportion of married women in the age group 15-19 years was constant around 88% from 1901-41 and from 1951 onwards the reduction in the proportion married has been observed. During the last 35 years, after the start of reduction in the proportion married in the age group (15-19) years, a reduction of 2097 cervical cancer cases or 6.3 percent reduction in the incidence of invasive cervical cancer is observed. It may be postulated that it will take a long time to expect a significant reduction in the incidence of cervical cancer if the primary prevention of rising the age at marriage above 18 years is adopted as a strategy for control of cervical cancer.

Adolescent↗
PubMed2002

Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis.

PURPOSE: To evaluate the role of concurrent cisplatin plus radiotherapy in the treatment of cervical cancer. METHODS: A systematic review of randomized trials of cisplatin administered concurrently with external beam radiotherapy versus radiotherapy without cisplatin for cervical cancer was combined with a meta-analysis of results abstracted from published reports of the trials. RESULTS: Pooled survival rates from eight randomized trials that evaluated the role of cisplatin, alone or in combination with other chemotherapy agents, administered concurrently with external beam radiotherapy to patients with cervical cancer demonstrated a statistically significant effect in favour of cisplatin-based chemotherapy plus radiotherapy compared with radiotherapy without cisplatin (relative risk [RR] of death, 0.74; 95% confidence interval [CI], 0.64 to 0.86). The pooled RR of death among the six trials that enrolled only women with locally advanced cervical cancer was 0.78 (95% CI, 0.67 to 0.90). The pooled relative risk for the two trials in high-risk early-stage disease also demonstrated a statistically significant benefit for the addition of cisplatin-based chemotherapy to radiotherapy (RR=0.56; 95% CI, 0.41 to 0.77). CONCLUSION: This meta-analysis confirms that treatment with concurrent cisplatin-based chemotherapy plus radiotherapy improves overall survival over various controls in women with locally advanced cervical cancer, large stage IB tumours (prior to surgery) and high-risk early-stage disease (following surgery). The variation in control treatments and the quality of their delivery among the randomized trials makes interpretation difficult. Nonetheless, the meta-analysis supports the use of concurrent cisplatin with radical radiotherapy in the treatment of cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Prognostic significance of human papillomavirus detected with polymerase chain reaction in cervical cancer.

In order to investigate the prognostic factors of cervical cancer and its association with human papillomavirus (HPV), we analyzed 50 specimens of cervical cancer with a DNA polymerase chain reaction (PCR) mainly to detect HPV types 16 (HPV 16) and 18 (HPV 18). The result showed that at least 74% (37/50) of the specimens had HPV DNA. Among them, 54% (20/37) of the cases were HPV 16 and 32% (12/37) were HPV 18. These HPV DNA positive patients had poorer differentiation in histology than the HPV DNA negative patients. We draw no conclusion about the prognostic significance of HPV DNA in cervical cancer. Perhaps more cases should be analyzed.

Adult↗
PubMed1991

[Phase II study of 5'-DFUR in uterine cervical cancer and ovarian cancer].

A phase II study of 5'-DFUR was conducted in uterine cervical cancer and ovarian cancer by the cooperative study group consisting of 26 institutions. Forty-four cases with uterine cervical cancer and 40 cases with ovarian cancer were enrolled. A daily dose of 800-1,200 mg was administered orally for more than 8 weeks. In 34 evaluable cases with uterine cervical cancer, the overall efficacy rate was 20.6%: CR was shown in 2 cases, PR in 5 cases, MR in 2 cases, NC in 17 cases and PD in 8 cases. Histologically, the response rate was 27.3% in large cell non-keratinizing type, 20.0% in small cell non-keratinizing type and 15.4% in keratinizing type of squamous cell carcinoma. The overall response rate was 20.7% in squamous cell carcinoma, while 25.0% in adenocarcinoma. In 31 evaluable cases with ovarian cancer, the overall efficacy rate was 16.1%: PR was shown in 5 cases, MR in 3 cases, NC in 11 cases and PD in 12 cases. Histologically, the response rate was 16.7% in serous cystadenocarcinoma, 25.0% in endometrioid adenocarcinoma and 33.3% in undifferentiated carcinoma. No responses were observed in cases with mucinous cystadenocarcinoma, clear cell adenocarcinoma, mature cystic teratoma with malignant transformation and mesodermal mixed tumor. Some adverse effects were observed in 43.2% (32 out of 74 cases evaluated for adverse effects), but those of grade 4 were not observed. Most of them were gastro-intestinal disturbances such as diarrhea and anorexia. Diarrhea of grade 3 was observed in 12.2% and anorexia of grade 3 in 5.4%. Severe myelosuppression or hepatic toxicity was not observed. These results suggested that 5'-DFUR is a useful anticancer drug against uterine cervical cancer and ovarian cancer.

Adenocarcinoma↗
PubMed2003

In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA.

Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers, encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for malignant transformation and maintenance of malignant phenotypes. In the hope of developing a gene-specific therapy for HPV-related cancer, we examined the effects of E6 short-interfering RNA (siRNA) on the expression of these oncogenes and on the cell growth of HPV16-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA encoding E6 as well as that encoding E7 protein and also induced nuclear accumulation of p53, the most important target of E6. E6 siRNA suppressed monolayer and anchorage-independent growth of SiHa cells, which was associated with p21(CIP1/WAF1) induction and hypophosphorylation of retinoblastoma protein. Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA. Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.

Animals↗
PubMed2003

Preventable but not prevented: the reality of cervical cancer.

INTRODUCTION: The incidence of invasive cervical cancer has decreased in the last 50 years in the developed countries substantially due to the use of routine pap smears. However, in the Asia-Oceanic region it continues to be high as screening programs are not established. Credit for starting cytology services in India goes to Professor P.N. Wahi of Agra. He became Founder President when about 34 cytologists got together in 1970 to form the Indian Academy of Cytologists. Since then cytology has spread through all parts of India. The Cytology Clinic in Cama & Albless Hospital was started in the same year. Since then over 100000 women have been screened. Approximately 1200 cases of pre- and early cancers have been detected and treated. Since 1982 we are aware of the important role of human papillomavirus infection. We diagnose it by cytology and colposcopy and histology. Facilities for polymerase chain reaction, in-situ hybridization and other virology studies are not available to us. CO2 laser treatment is found particularly useful in multicentric human papillomavirus disease. SCREENING FOR THE STATE OF MAHARASHTRA: Since 1984 we have planned for a screening program for our State. We have a population of 78.9 million. Approximately 15 million women in the age group of 35-64 years have to be screened. The health care infrastructure is good with 36 medical colleges and over 35 district hospitals. Screening is planned in phases. Trained personnel are the key to a successful program. In the final analysis, cervical cancer is not just a biomedical disease. It has socio-cultural and economic implications.

Colposcopy↗
PubMed1997

A comparison of intracavitary versus interstitial irradiation in the treatment of cervical cancer.

OBJECTIVE: Management of locally advanced cervical cancer consists primarily of combination external and internal radiation. In order to investigate the impact of intracavitary brachytherapy versus interstitial brachytherapy on local tumor control, survival, and complications, we retrospectively reviewed the concomitant experience of two institutions, each of which practice exclusively one of these radiotherapeutic techniques. METHODS: Between 1979 and 1989, 61 patients with bulky stage II, III, or IVA cervical cancer were treated using a combination of teletherapy and intracavitary brachytherapy at one institution, while 70 similar patients were treated with teletherapy and interstitial brachytherapy at another institution. Patients in both groups were similar with respect to age, FIGO stage, tumor size, surgical stage, and histologic subtype. Patients treated with intracavitary therapy received a mean cumulative dose of 7706 cGy to point A and 5523 cGy to point B using standard Fletcher-Suit techniques. Those who received interstitial irradiation were treated with a mean external dose of 5050 cGy and 2 interstitial implants using a transperineal Syed-Neblett template with a mean tumor dose of 2239 and 1,942 cGy with each application, respectively. Patients treated with chemoradiation were excluded from this review. RESULTS: Although initial rates of local control were not different, prolonged 5-year disease-free survival (50% vs 21%, P = 0.01) and improved 5-year local control (61% vs 32%, P = 0.01) were observed among patients with stage II disease treated with intracavitary irradiation. No statistical differences in survival could be detected among stage III and IVA patients. Women treated with intracavitary irradiation received a larger dose of brachytherapy than those treated with interstitial therapy (4608 vs 3504 radium milligram hours equivalent, P < 0.0001) because a tandem was only used in 17 (24%) interstitial implants. Major complications occurred in 21% of patients in each group. CONCLUSION: When a tandem is infrequently used during interstitial brachytherapy, the toxicity is similar to that of intracavitary techniques. However, more relapses are observed among patients with stage II lesions treated with interstitial irradiation.

Adult↗
PubMed2003

[Laparoscopic-vaginal radical hysterectomy in surgical treatment of cervical cancer].

Radical vaginal hysterectomy has been performed in surgical treatment of cervical cancer for over one hundred years. After the term of decrease of popularity of this operation, nowadays we can observe gradual come back to the idea of radical vaginal hysterectomy. Possibility of association of advanced laparoscopic techniques/lymphadenectomy/with vaginal operation have changed the approach to the surgical treatment of cervical cancer. The aim of the study is to present the method of laparoscopic-vaginal radical hysterectomy based on Schauta-Amreich technique. The 51 year old women was admitted to the hospital and cervical cancer FIGO stage IIA was diagnosed according to clinical and histopathological examination. We performed laparoscopic-vaginal radical hysterectomy in general anaesthesia. First after cutting of ligamentum teres uteri and infundibulo-pelvicum, laparoscopic pelvic lymphadenectomy was done. Subsequently vaginal stage of operation was performed. Then we did laparoscopy and controlled operation field again. Combining Schauta operation with laparoscopy allows us to estimate lymph nodes as well as make vaginal phase of operation easier because of mobilization of uterus. We consider that laparoscopic-vaginal radical hysterectomy could be a valuable element in broadening the spectrum of many kinds of operations used in treatment of cervical cancer.

Carcinoma, Squamous Cell↗