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PubMed1988

[Clinical effect of combination chemotherapy with peplomycin and mitomycin C (PM therapy) in recurrent uterine cervical cancer].

Seventeen patients with recurrent uterine cervical cancer were treated with combination chemotherapy consisting of consecutive intravenous drip infusion of PEP 5 mg for 6 days and intravenous infusion of MMC 10 mg on the 6th day. Of twelve evaluable cases, 2 complete responses and 6 partial responses were obtained and the response rate was 67%. The median survival for responders was 61.3 weeks as compared with 28.0 weeks for non-responders. The initial clinical effect appeared after at least two courses. Pulmonary toxicity in the form of interstitial pneumonitis occurred in 8 cases (50%) including 2 cases of pulmonary fibrosis. This result suggests that PM therapy is a very useful treatment method for recurrent uterine cervical cancer which can be performed safely.

Aged↗

PubMed1993

Combination chemotherapy with 254-S, ifosfamide, and peplomycin for advanced or recurrent cervical cancer.

BACKGROUND: Based on the fact that combination chemotherapy with cisplatin, ifosfamide, and bleomycin generated a 69% response rate in patients with recurrent cervical cancer; that 254-S (a cisplatin analogue) monotherapy generated a 46.3% response rate for cervical cancer, which was higher than those generated by cisplatin and carboplatin in historic comparison; and that peplomycin is a bleomycin analogue with improved pulmonary toxic effects, a combination regimen with 254-S, ifosfamide, and peplomycin was evaluated in an animal experiment and a clinical study in patients with advanced or recurrent cervical cancer with an expectation that the regimen might show a higher efficacy than 254-S monotherapy and the combination regimen including cisplatin. METHODS: In the clinical testing, 254-S was administered intravenously (IV) at 80-100 mg/m2, ifosfamide was administered IV at 1500 mg/patient for 5 days, and peplomycin was administered intramuscularly at 5 mg/patient for 6 days. This treatment was repeated every 4 weeks. RESULTS: As a result, this regimen showed additive or synergistic antitumor effects in mice receiving B16 melanoma transplants. In the clinical study, 83.8% and 60.9% response rates were obtained in 37 previously untreated patients with Stage III or IV cervical cancer and 23 with recurrent cervical cancer, respectively. The dose-limiting factor was bone marrow toxic effects, which were tolerable. The other toxic effects were mild, and there were no deaths. CONCLUSIONS: From these results, this combination regimen was thought worthy of evaluation in a Phase III comparative study in patients with advanced or recurrent cervical cancer.

Adult↗

PubMed1999

Risk of cervical cancer after a negative Pap smear.

OBJECTIVE: To evaluate whether five years is an appropriate screening interval for cervical cancer for the improvement of public health. SETTING: Finland. METHODS: 45,572 women with a cytological class I smear attending the mass screening programme organised every five years in Finland during 1971 to 1976 and followed up until the end of 1994. The data from the Nationwide Mass Screening Registry were linked to the Finnish Cancer Registry. Standardised incidence ratios of preinvasive and invasive cervical cancer with 95% confidence intervals (CI) were estimated, with rates for the total Finnish population as reference. RESULTS: The standardised incidence ratio estimates were low initially after screening and then gradually increased up to the time of the next smear five years later. This pattern was repeated after each screening. The risk was persistently low for invasive cervical cancer even after 10 years of follow up, whereas the low risk for preinvasive lesions was of a shorter duration. The low risk associated with a negative smear became even lower with advancing age. CONCLUSIONS: Women who attend organised screening programmes and have a negative smear have a low risk of cervical cancer for over 10 years. Also, the relative risk of a preinvasive lesion after an initial negative smear is decreased for more than five years. Therefore, the five year screening interval in Finland is appropriate and effective in reducing the risk of invasive cervical cancer.

Adult↗

PubMedDate not supplied

TP53 codon 72 polymorphism does not affect risk of cervical cancer in patients from The Gambia.

AIMS: A case-control study was performed to investigate the relationship between cervical cancer and TP53 polymorphism at codon 72 in young black African women from The Gambia. MATERIALS AND METHODS: The TP53 polymorphism at codon 72 was examined by PCR amplification and SSCP analysis in 40 patients with primary cervical cancer and in 20 healthy women of the same age and from the same geographical area. The occurrence of TP53 polymorphism in combination with the HPV-16 E6 genotype (assayed by PCR) was evaluated. RESULTS: The distribution of TP53 genotypes in cervical cancer patients and in the control group was not statistically different (p = 0.45) and homozygosity for argine at residue 72 was not associated with cervical cancer (odds ratio: 1.24; 95% confidence interval 0.21-9.16). Similarly, a different genotype distribution, cervical cancer and presence of HPV-16 E6 were not observed. CONCLUSIONS: These results cannot rule out an association between TP53 polymorphism at codon 72, HPV infection and the etiology of cervical cancer in this population sample.

Amino Acid Substitution↗

PubMed1997

International incidence rates of invasive cervical cancer before cytological screening.

Huge differences in incidence rates of invasive cervical cancer occur among populations. These differences reflect the influences of both etiological environmental factors and removal of precursor lesions detected upon screening. The purposes of this article are (i) to describe similarities and differences in the shapes and magnitudes of age-specific incidence rates of invasive cervical cancer before screening had an effect, (ii) to provide baseline data for further global study of screening effects, and (iii) to provide baseline incidence data for the design of optimal screening programs. To eliminate the impact of screening effects, we have selected age-specific incidence rates from times when and from populations in which screening was insignificant. The selected rates were suitably scaled and compared regarding age at onset of increase in incidence, age at peak incidence, and rate of subsequent decline. Despite a 16-fold difference in incidence rates, all curves had the same basic structure, with an increase to a peak followed by a decline or a plateau. Although all populations but one had an onset around age 25, 7 European countries showed an earlier peak age (mean = 46 vs. 59) and a more rapid decline after the peak than most other populations. The common basic shape of the age-specific incidence curve, overall, suggests a relatively similar development of invasive cervical cancer in different populations. These results illustrate the underlying similarities in the markedly different age-specific incidence rates of invasive cervical cancer. They also provide a basis for studying screening effects and for optimizing screening programs in specific geographic areas.

Africa↗

PubMed2005

Clinical audit of patients with cervical cancer in Slovenia--data analysis for the year 2003.

PURPOSE OF INVESTIGATION: The data gathered in 2003 on the patients with cervical cancer who regularly attended their gynecologist were analyzed with the purpose of clinical audit. METHODS: The data on newly detected patients with cervical cancer in 2003 who regularly attended their gynecologist were gathered simultaneously at three Advisory Boards for Gynecology in Slovenia. RESULTS: Of 149 patients in whom, according to our data, invasive cervical cancer had been diagnosed, 92 (61.7%) patients were examined by a gynecologist in the previous five years. In the majority of these patients, cervical cancer was diagnosed in early, localized disease stage. In the periods of 13-24 and of seven to 12 months before the diagnosis of cervical cancer, almost half the patients had Pap II, and three to six months before diagnosis, 67.6% of patients had Pap II. CONCLUSION: These results encourage us to proceed with clinical audits to analyze individual cervical cancer cases, including another independent reevaluation of cervical smears in the five-year period before diagnosis. A suitable calendar of refresher training courses on colposcopy, which should be obligatory for all performing this examination method, also needs to be set up.

Adult↗

PubMed1996

Trends in the incidence of female breast and cervical cancers in Miyagi Prefecture, Japan, 1959-1987.

Trends in the incidence of female breast and cervical cancers were examined, using the cancer registry data in Miyagi Prefecture, Japan, during 1959-1987. The age-standardized incidence rate of breast cancer has been increasing, while that of cervical cancer has been decreasing. Age-period-cohort models were applied to clarify the trends in incidence. For breast cancer incidence, the age-period model adequately represented the data, and demonstrated that the risk of developing breast cancer has been increasing in recent time periods. The effect of cohort on breast cancer incidence was insignificant and the full model containing age, period and cohort showed irregularities in the cohort effect. For cervical cancer incidence, the effect of period was significant, while the effect of cohort was marginal. The full model containing age, period and cohort showed that cervical cancer risk has been decreasing in recent time periods and younger birth cohorts. Using published reports, we investigated the trends in the prevalence of various risk factors and compared them with the trends in the incidence at both sites. It is suggested that the effects of period and cohort might be related to the changes in the prevalence of these risk factors as well as to improvements of the diagnostic procedures.

Adult↗

PubMed1996

Perceptions of cervical cancer and Pap smear screening behavior by women's sexual orientation.

This study examined 330 adult females' perceptions and practices regarding cervical cancer by sexual orientation. Ninety-four percent of respondents were unable to correctly identify all 5 risk factors associated with increased risk for cervical cancer (smoking, sexual intercourse with men, multiple male sexual partners, sexual intercourse before age 16, and having genital warts) regardless of sexual orientation. Furthermore, 20% were not able to identify any of the 5 risk factors for cervical cancer. Lesbians perceived themselves to be less susceptible to cervical cancer than heterosexuals or bisexuals even though 79% of lesbians had sexual intercourse with a male. Eight percent of the respondents believed that most women who develop cervical cancer die from the disease. The main barriers identified by non-regular Pap screeners (N = 127) were: no health insurance (33%), forgetting to get a pap test (32%), and not liking to get a Pap test (31%). Three-fourths (75%) have had a Pap test within the last 2 years and planned to continue having them on a regular basis. The results of this survey indicate that there is considerable room for improvement in knowledge, perceptions, and practices of all women, regardless of sexual orientation, regarding cervical cancer.

Adolescent↗

PubMed1990

In situ hybridization analysis of HPV DNA in cervical precancer and cervical cancers from China.

A series of 103 cervical biopsies derived from 103 women during July 1958 to September 1963 from Beijing, China were investigated with in situ hybridization for the presence of HPV6, 11, 16, 18, 31 and 33 DNA. The mean age of the patients was 46.1 + 10.6 years with a range of 24-74 years. Morphological features of HPV infection were found in 80 (77.7%) biopsies. Invasive cervical cancer was diagnosed in 43 biopsies and cervical intraepithelial neoplasia CIN I, CIN II and CIN III in 9, 9, and 27 cases, respectively. A total of 63.1% (65/103) of the lesions had morphological features of HPV infections associated with CIN or invasive carcinomas. Altogether, 31.1% (32/103) of the biopsies were shown to contain HPV DNA. Of the cases showing HPV morphology, 43.1% were HPV DNA positive. HPV16 (30/32) was the most frequent type, followed by HPV11 and 18, whereas no lesions with HPV6, 31 or 33 were found. A total of 19/43 (44.2%) of the invasive carcinomas contained HPV DNA. HPV DNA positivity and the grade of CIN showed a statistically significant correlation (P = 0.0011). Our study demonstrated the presence of HPV in cervical lesions among Chinese women in the late 1950's and early 1960's when a single sexual partner was the rule and also supports the concept that HPV has as an important etiological role in cervical cancer, the highest risk being associated with HPV type 16. The applicability of in situ hybridization in retrospective assessment is emphasized.

Adult↗

PubMed2006

Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines.

PURPOSE: The phosphatidylinositol 3-kinase (PI3K) catalytic subunit is amplified in cervical cancers, implicating PI3K in cervical carcinogenesis. We evaluated the radiosensitizing effect of PI3K inhibition by LY294002 on clonogenic survival, growth characteristics, and gene expression in cervical cancer cell lines (HeLa and CaSki). EXPERIMENTAL DESIGN: Cervical cancer cells were treated separately and concurrently with the PI3K inhibitor LY294002 (10 micromol/L) and radiation (2 Gy) with serial analysis of cell count, apoptosis, and flow cytometry. PI3K inhibition was assessed by protein analysis of phosphorylated Akt. Clonogenic assays were done with varying doses of radiation and LY294002 and varied time points of administration of LY294002 proximate to the radiation dose. Surviving fractions and dose modification factors (DMF) were calculated. Each experiment was done in triplicate and analyzed using ANOVA regression analysis and Dunnett's t Test. Microarray gene expression analysis was done on the HeLa cell line. RESULTS: PI3K inhibition with LY294002 alone did not decrease cell survival. However, treatment with LY294002 significantly radiosensitized HeLa and CaSki cell lines with DMFs (1 log cell kill) of 1.95 and 1.37, respectively. Compared with post-irradiation, pretreatment produced more radiosensitization (P < 0.0001). DMFs were 2.2, 2.0, 2.0, and 1.2 for LY294002 added at 6, 2, and 0.5 hours before irradiation and 6 hours after irradiation, respectively. LY294002 pretreatment in irradiated HeLa cells led to altered gene expression. CONCLUSIONS: Although LY294002 alone did not produce cytotoxic effects, PI3K inhibition with LY294002 produced significant radiosensitization, showed significant time-dependent effects, increased apoptosis, and altered gene expression. These findings support future investigation of PI3K inhibitors in combination with radiation therapy for carcinoma of the cervix.

Apoptosis↗

PubMed2000

Sociodemographic predictors of adherence to annual cervical cancer screening in minority women.

The Papanicolaou (Pap) test is an effective screening mechanism for reducing morbidity and mortality from cervical cancer. Nevertheless, Pennsylvania ranks fifth in national cervical cancer incidence and fourth in national cervical cancer mortality, with a significant number of cases contributed by Philadelphia. Substantial subgroups of American women, specifically ethnic minorities, the elderly, the uninsured, and the poor, have not been screened or are not screened at regular intervals. A secondary data analysis was conducted to test whether age, income, insurance coverage, marital status, level of education, and number of persons living at home could predict whether a woman among convenience sample of 204 black and Hispanic women adhered to annual Pap testing. A woman was considered adherent to annual Pap testing if she reported undergoing a Pap smear in the 14 months preceding her enrollment in the study. African American woman who were high school graduates and had insurance coverage were more likely to be adherent to annual Pap testing. Hispanic women older than 50 years and born outside the mainland United States were less likely to be adherent to annual Pap testing. Findings suggest that cancer nurses working to promote cervical cancer screening in Philadelphia should continue to target at-risk populations, specifically uninsured and less-educated black and Hispanic women older than 50 years who were born outside the mainland United States.

Adolescent↗

PubMed2002

[Neoadjuvant chemotherapy in the treatment of advanced cervical cancer].

UNLABELLED: Neoadjuvant chemotherapy (NAC) has been used for treatment of advanced cervical cancer by some institutions for several years. PURPOSE: We investigated the value of NAC for patients with IIb cervical cancer. MATERIALS AND METHODS: Eight patients treated at the 2nd Department of Obstetrics and Gynecology Medical University of Gdansk between 1999 and 2000 for stage IIb cervical cancer were enrolled into the study. The drugs infused were: cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days, for three cycles. NAC was followed by radical Wertheim-Meigs hysterectomy. All patients were evaluated for response and toxicity. RESULTS: In all eight patients partial responses were obtained. Despite previous data there was no severe toxicity in our study group. Hematological toxicity was mild and there was no need for modifying chemotherapy due to side effect of NAC. CONCLUSION: NAC followed by radical Wertheim-Meigs hysterectomy is an effective approach to stage IIB cervical cancer. Further larger prospective study is necessary. Preoperative imaging studies (CT and/or MR) might be consider as selection criteria for future study.

Adult↗

PubMed2001

Community-based cancer screening for underserved women: design and baseline findings from the Breast and Cervical Cancer Intervention Study.

BACKGROUND: Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival. METHODS: The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach; (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75. RESULTS: Seventy-six percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-speaking Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior. CONCLUSIONS: These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated.

Adult↗

PubMed2004

Chemoradiation with gemcitabine for cervical cancer in patients with renal failure.

The prognosis of cervical cancer patients with renal failure secondary to obstructive uropathy is poor. Our objective was to analyze our experience in the management with chemoradiation of untreated cervical cancer patients complicated by obstructive nephropathy and kidney dysfunction. Untreated patients with cervical cancer and renal failure as manifested by raised serum creatinine were treated with pelvic radiotherapy concurrently with weekly gemcitabine at 300 mg/m2. Response, toxicity and renal function pre- and post-therapy were evaluated. Eight FIGO stage IIIB and one IVB patients were treated. Pre-treatment serum creatinine ranged from 1.6 to 18.5 mg/100 ml (median 3.3, mean 6.8) and creatinine clearance varied from 4 to 57 mg/ml/min (median 17, mean 22.1). Four patients had a percutaneous nephrostomy placed and four patients had symptoms from kidney failure. All patient completed chemoradiation. Most patients had grade 3 leukopenia and neutropenia. Dermatitis, colitis and proctitis were common. All patients had improvement in creatinine clearance (pre-therapy 22.78, post-therapy 54.3 mg/ml/min) (p=0.0058) and all but one normalized serum creatinine. Eight (89%) of nine patients achieved complete response and one patient had persistence. At a median follow-up of 11 months (range 6-14), all patients are alive, one with pelvic and another with systemic disease. Ureteral obstruction causing any degree of renal insufficiency should not be a contraindication to receive chemoradiation to attempt cure. In this setting where cisplatin-based therapy is contraindicated, the use of gemcitabine may be considered.

Brachytherapy↗

PubMed2005

A strategic assessment of cervical cancer prevention and treatment services in 3 districts of Uttar Pradesh, India.

BACKGROUND: Despite being a preventable disease, cervical cancer claims the lives of almost half a million women worldwide each year. India bears one-fifth of the global burden of the disease, with approximately 130,000 new cases a year. In an effort to assess the need and potential for improving the quality of cervical cancer prevention and treatment services in Uttar Pradesh, a strategic assessment was conducted in three of the state's districts: Agra, Lucknow, and Saharanpur. METHODS: Using an adaptation of stage one of the World Health Organization's Strategic Approach to Improving Reproductive Health Policies and Programmes, an assessment of the quality of cervical cancer services was carried out by a multidisciplinary team of stakeholders. The assessment included a review of the available literature, observations of services, collection of hospital statistics and the conduct of qualitative research (in-depth interviews and focus group discussions) to assess the perspectives of women, providers, policy makers and community members. RESULTS: There were gaps in provider knowledge and practices, potentially attributable to limited provider training and professional development opportunities. In the absence of a state policy on cervical cancer, screening of asymptomatic women was practically absent, except in the military sector. Cytology-based cancer screening tests (i.e. pap smears) were often used to help diagnose women with symptoms of reproductive tract infections but not routinely screen asymptomatic women. Access to appropriate treatment of precancerous lesions was limited and often inappropriately managed by hysterectomy in many urban centers. Cancer treatment facilities were well equipped but mostly inaccessible for women in need. Finally, policy makers, community members and clients were mostly unaware about cervical cancer and its preventable nature, although with information, expressed a strong interest in having services available to women in their communities. CONCLUSION: To address gaps in services and unmet needs, state policies and integrated interventions have the potential to improve the quality of services for prevention of cervical cancer in Uttar Pradesh.

Journal Article↗

PubMed2004

Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer.

Patients with advanced stage invasive cervical cancer (CC) exhibit highly complex genomic alterations and respond poorly to conventional treatment protocols. In our efforts to understand the molecular genetic basis of CC, we examined the role of Fanconi Anemia (FA)-BRCA pathway. Here, we show that FANCF gene is disrupted by either promoter hypermethylation and/or deregulated gene expression in a majority of CC. Inhibition of DNA methylation and histone deacetylases induces FANCF gene re-expression in CC cell lines. FANCF-deregulated CC cell lines also exhibit a chromosomal hypersensitivity phenotype after exposure to an alkylating agent, a characteristic of FA patients. We also show the involvement of BRCA1 gene by promoter hypermethylation or down-regulated expression in a small subset of CC patients. Thus, we have found inactivation of genes in the FA-BRCA pathway by epigenetic alterations in a high proportion of CC patients, suggesting a major role for this pathway in the development of cervical cancer. Thus, these results have important implications in understanding the molecular basis of CC tumorigenesis and clinical management in designing targeted experimental therapeutic protocols.

Alkylating Agents↗

PubMed1995

Can a test for E6/E7 transcripts of human papillomavirus type 16 serve as a diagnostic tool for the detection of micrometastasis in cervical cancer?

Tissue from 11 cases of cervical cancer positive for human papillomavirus (HPV) type 16 DNA and 69 pelvic lymph nodes from the same patients were examined for HPV 16 DNA and mRNA from the E6/E7 genes. Five of the tumors were squamous, 3 adeno- and 3 adenosquamous carcinoma. From the primary tumors and the extirpated lymph nodes DNA and RNA or mRNA was subjected to PCR and RT-PCR. Three transcription profiles (only E6*I, E6*I and E6*II or full-length E6-E7 plus both of the spliced transcripts) were found in all of the 11 HPV 16 DNA-positive primary tumors. From the total of 69 lymph nodes analyzed 28 were positive for mRNA. HPV 16 DNA was found in 7 additional samples. Cytokeratin was found in 19 of these lymph nodes, indicating epithelial origin of tumor cells. Only 1 patient had 2 metastases evidenced by histology. These were both positive for HPV DNA and mRNA. The finding of HPV DNA, mRNA and cytokeratin in lymph nodes of patients with cervical cancer should be an indication of lymphogenically driven micrometastases of the tumor. The HPV mRNA assay should offer higher specificity than the DNA test since mRNA can be found in live cells only, while HPV DNA also can originate from dead cell material sequestered in the lymph nodes.

Adult↗

PubMed2005

[Assessment of cervical cancer screening in the Health Service of Valdivia, Chile].

BACKGROUND: One of the best Public Health achievements in Chile has been the coverage of the program for detection and treatment or cervical cancer. AIM: To evaluate the results of the Cervical Cancer Screening Program in Valdivia Health Service (Southern Chile) between 1993 and 2003. MATERIAL AND METHODS: Retrospective review of the number of women in whom a Papanicolau smear was obtained in the last three years. The incidence of the disease was calculated using pathological diagnoses of precursor or invasive lesions. Mortality for cervical cancer was calculated using data from death certificates. RESULTS: During 2003, 79% of women age 25 to 64 years, and 77% of women aged 35 to 63 years (considered the highest risk group) were screened. We confirmed that the number of precursor lesions detected were increased along with the increasing screening coverage. The diagnosis of carcinoma in situ increased almost three times when compared with 1990 figures. Likewise, the diagnosis of early invasive cervical cancer behaved similarly. Mortality by cervical cancer also experienced a decrease, reaching 4.6 per 100.000 women over 15 years old in the Health Service of Valdivia. CONCLUSIONS: The sustained increase in cervical cancer screening coverage has had a favorable impact in the morbidity and mortality caused by the disease.

Adolescent↗