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PubMed1981

Estimated cervical cancer disease state incidence and transition rates.

Cervical cancer was modeled as a disease of four states: disease-free (DF), carcinoma in situ (CIS), occult invasive (OI), and clinically invasive (CI). This model allowed transitions from DF to CIS, CIS to DF, CIS to OI, OI to CI, and DF to OI. Cases transiting from DF to OI after less than a year in the CIS state were included in the last category, which was called rapid-onset invasive disease. With the data from the British Columbia Cervical Cancer Screening Program (1955 through 1971) the disease-state transition-rate parameters for this model were estimated by least squares, and the fitted model was found to be in good agreement with the data. The estimates for parameters of particular interest were: average annual transition rate from CIS to OI, 3.7% +/- 0.6%/year; average annual transition rate from OI to CI, 48% +/- 1%/year; average annual transition rate from DF to CIS (after 1963), 1.1 +/- 0.1/1,000 person-years/year (= incidence rate of CIS); and average annual transition rate from DF to OI, 7.4 +/- 2/100,000 person-years/year (= incidence rate of rapid-onset invasive disease). Each year between 1.7 and 9.7% of all new cervical cancers and about one-third of all new OI cases were estimated to be of the rapid-onset variety.

Carcinoma↗
PubMed2003

The role of the French-Italian glossary of complications in the outcome evaluation of cervical cancer treatment: an Italian multicentric study.

UNLABELLED: The optimal treatment for cervical cancer is still a controversial matter: in the last two decades a lot of different modalities combining surgery, radiotherapy (RT) and chemotherapy (CHT) have been suggested and analysed in clinical trials. Nevertheless, analysis of treatment in cancer patients should be directed not only to survival, but also to the cost of complications and quality of life. In June 1988, a French-Italian co-operative group set up a glossary in which the complications of the treatment of cervical cancer are described and ranked. Nowadays, this is the only international system based upon an accurate description of symptoms and signs of complications following multidisciplinary treatment. The glossary was based on our previous experience in treating patients by surgery alone, RT or their combinations. Recently multimodality treatment includes also CHT. The aim of the present study was to verify whether the glossary is still a useful clinical instrument in outcome evaluation of cervical cancer treatment. MATERIALS AND METHODS: The analysis has been done on a retrospective consecutive series of 579 patients affected by cervical cancer, treated in five Italian institutions. A minimum of 12 months follow up was required. All medical records of the patients enrolled, were examined by two independent reviewers in order to classify the complications according to the glossary. RESULTS: Out of 579 patients 319 (55.1%) were free of complications and 260 (44.9%) experienced at least one complication. We found 436 complications. The distribution by Grade was: G1 58.9%, G2 27.5%, G3 13.5%. We had no fatal complication (G4). The glossary included all observed complications, except for pulmonary fibrosis. CONCLUSION: The glossary is still a useful instrument in evaluating the outcome of cervical cancer treatment, whatever the therapy, and should be considered in quality of life assessment.

Female↗
PubMed2003

[Metastatic cancer in transposed ovaries after radical Wertheim-Meigs hysterectomy for a stage I B and II A cervical cancer].

In this research work we show our and foreign experience in preserving the ovarian function in young women and cervical cancer stage I B and II A. 6 cases are quoted for the period of time from 1987 till 2003 (4 patients with ovarian metastases from our experience and 2 patients with ovarian metastases found from the greek colleagues). Histologically 3 patients were with adenosquamous metastatic cervical cancers and 3 patients with squamous metastatic cervical cancers in the region of the transposed ovaries. The metastases occurred mostly 2 to 3 years after the radical hysterectomies a modo Wertheim-Meigs. Nevertheless our experience which is connected with radical hysterectomies a modeo W. Meigs including both ovaries, we have also experience in transposing ovaries /one or both of them/. In some of them we found metastases. In our research work we found 4 cases with metastases in transposed ovaries. In these cases a chemotherapy was applied: mitomicin C, etoposide, and cysplatinum. The greek colleagues also have applied such schemes of chemotherapy. 3 from the patients had a very good effect from the chemotherapy, in 2 the recurrences have appeared 2 years after the chemotherapy, and in one case there was a very big progression of the disease, nevertheless the chemotherapy. IT is very important for the oncogynaecologist to clear up if the transposition of the ovaries is safe and effective, especially in young patients with early cervical cancer receiving postoperative radiotherapy. That is why we did this research work in order to give more light on this problem.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Breast and cervical cancer screening activities among family physicians in Nigeria.

Breast and cervical cancers are the two commonest malignancies among Nigerian women; where they constitute about 50% of female cancers. A total of 63 out of 82 family physicians from 4 out of the 6 health zones in Nigeria and the Federal Capital Territory, Abuja, Nigeria completed a self-administered questionnaire to determine their knowledge and screening practices for breast and cervical cancers. Forty nine percent (49%) of family physicians perceived cancer as one of the serious health problem facing women in Nigeria. Although 93.7% of responding physicians have heard of breast cancer screening facilities and 96.8% of cervical screening facilities, only 74.6% and 55.6% of these respondents offered screening services for breast and cervical cancers respectively. Breast examination was carried out monthly by 48.9% of the physicians on their regular patients. A comprehensive programme of continuing medical education and training in view of setting up facilities and offering service are recommended for family physicians. These stand to bridge the gap between the knowledge and the practice of breast and cervical cancer screening activities. The umbrella Association for Family Physicians and other regulating bodies should facilitate access to screening facilities and initiate training of willing physicians with a view to setting up services.

Adult↗
PubMedDate not supplied

Histologic and clinical characteristics associated with rapidly progressive invasive cervical cancer: a preliminary report from the Yale Cancer Control Research Unit.

Histologic and clinical characteristics associated with rapidly progressive invasive cervical cancer are presented in this preliminary report from a population-based study involving all patients in Connecticut diagnosed with cervical cancer from March 1, 1985. Rapidly progressive invasive cervical cancer, i.e., invasive cancer diagnosed within three years of a true negative Pap smear, is more likely to occur in younger women with high annual incomes (61 percent greater than $40,000) who report a greater frequency of benign gynecologic conditions (uterine leiomyomata, vaginitis) compared to a control cervical cancer group. These preliminary data suggest that as many as 35 percent of the rapidly progressive cervical cancers are likely to be adenocarcinomas. Because they are mostly endocervical in origin, they may not be detected cytologically if scrapers or cotton swabs are used to sample the endocervical canal. New cytologic screening techniques using brushes may identify these lesions earlier and should routinely be employed in cytologic screening for cervical neoplasia. The difficulty in early detection of this form of the disease requires that physicians rapidly assess patients with unexplained pelvic and lower abdominal pain, vaginal discharge, or abnormal vaginal bleeding since early recognition is the only chance for cure. Further analyses of this population of women will be made to identify additional risk factors when the study data are complete.

Adenocarcinoma↗
PubMed1990

Cervical cancer as a natural phenomenon.

Recognizing cervical cancer as a natural stochastic phenomenon, that is in the first stage of its self-organization into a new biological dissipative structure (initiation) and sustaining its development in the second stage (promotion), is a basic requirement in conquering cancer and preventing neoplastic disease, i.e., the third stage of neogenesis (progression). A dissipathogenic state inside an organism is the only common primary cause of neoplasia. Thus, medical thermodynamics clarifies why so many non-specific factors enable the origin of cervical cancer, that is, can cause cervical dissipathogenic states. This thermodynamical theory abolishes opposition and unites the heretofore cellular neoplastic theories by bringing them to an atomic level. Diagnosis and treatment of dissipathogenic processes implies true causal prophylaxis of cancer, therapy of which always has to encompass its environment.

Female↗
PubMed1997

Case-control study of oestrogen replacement therapy and risk of cervical cancer.

OBJECTIVE: To examine the relation between use of oestrogen replacement therapy and risk of cervical cancer. DESIGN: Case-control study. SETTING: Northern Italy. SUBJECTS: 645 women aged 40-75 years with cervical cancer admitted between 1981 and 1993 to university and general hospitals. The control group consisted of 749 women aged 40-75 years admitted to the same hospitals with acute conditions judged to be unrelated to any of the known or suspected risk factors for cervical cancer. MAIN OUTCOME MEASURES: Use of oestrogen replacement therapy and risk of cervical cancer. RESULTS: 40 cases versus 86 controls had ever used oestrogens, and the corresponding multivariate odds ratio was 0.5 (95% confidence interval 0.3 to 0.8). The odds ratios of cervical cancer decreased with duration of use, being 0.6 (0.4 to 1.1) for less than 12 months' use and 0.5 (0.2 to 1.0) for use for 12 months or more compared with never users. The protection tended to be somewhat stronger for women reporting first oestrogen use before age 50. The odds ratio was 0.9 (0.5 to 1.7) for women who had taken oestrogens within the past 10 years and 0.4 (0.2 to 0.7) for those who had taken them 10 or more years ago. CONCLUSION: These findings suggest that exogenous oestrogens do not increase the risk of cervical cancer and may decrease the risk.

Adenocarcinoma↗
PubMed2000

The screening history of women with cervical cancer in the Rotterdam area.

OBJECTIVE: In order to gain insight into the diagnostic effectiveness of the screening program on cervical cancer in the Rotterdam area, the history of women with cervical cancer was studied. Three questions were asked: (1) What percentage of women were invited to the screening program, and what percentage participated. (2) What percentage of women had had a negative smear within 3 years before cancer was diagnosed, and (3) What percentage of women encountered inadequate follow-up. METHODS: All the cytological and histological results of women who were diagnosed with cervical carcinoma between 1992-1994 were studied. RESULTS: Within 3 years of the diagnosis, 42% of the 165 women with cervical cancer were invited for the cervical screening program. A total of 47% were too old to be invited and 10% were too young. A total of 37% of the women who were invited participated in the screening program. A total of 33 (20%) of 165 women with cervical carcinoma had had a negative smear within three years preceding the diagnosis. For women under 34 years of age this was 41% (n = 7), and for women over 56 years 8% (n = 6). A total of 7% of all women with cervical cancer encountered inadequate follow-up. CONCLUSION: Many women with a diagnosis of cervical cancer are too old to be invited for the cervical screening program. Relatively few of the women with cervical cancer who were invited for the screening program actually participated in this program.

Adenocarcinoma↗
PubMed1997

Treatment of pre-invasive conditions during opportunistic screening and its effectiveness on cervical cancer incidence in one Norwegian county.

Norway had until recently no organized screening programme for cervical cancer, but opportunistic screening was common. This study focuses on the effectiveness of treatment of pre-malignant cervical conditions (CIN III) on cervical-cancer incidence in the county of Sør-Trøndelag in Norway, prior to the introduction of organized mass screening. The study is based on cervical-cancer incidence rates during the years 1965-92 and treatment data for CIN III. The expected number of cervical-cancer cases prevented due to early intervention was expressed in a regression model with 2 unknown parameters: the probability, p, of cancer development in case of CIN III, and the time lag, t, between treatment and when clinical cancer would otherwise have been diagnosed. The estimated probability that a patient treated for CIN III would have developed cervical cancer if not treated was found to be approximately 20%, and the mean time delay was around 16 years. In the last period of study (1988-92), the incidence was reduced by nearly 40% of what would have been expected without early intervention. Based on equal treatment rates as in 1990, parameter estimates were used to predict future incidence reduction. Maximum effectiveness will be achieved around the year 2005, with a nearly 70% reduction. Opportunistic screening and treatment of CIN III seems to have had considerable influence on cervical-cancer incidence. The costs, however, are substantial over-treatment, since our results indicate that 4 of 5 women treated for CIN III would not progress into the invasive state.

Adult↗
PubMed1999

Expression of vascular endothelial growth factor (VEGF) and its mRNA in uterine cervical cancers.

To know the potential of growth, invasion and metastasis of uterine cervical cancer associated with neovascularization, localization of vascular endothelial growth factor (VEGF) and microvessel density in tumours were determined by immunohistochemical staining, the levels of VEGF subtypes were determined by Western blot analysis and by a sandwich enzyme immunoassay, and the levels of VEGF subtype mRNAs were determined by reverse transcription polymerase chain reaction (RT-PCR)-Southern blot analysis in uterine cervical cancers. The relation between VEGF subtype expressions and microvessel density, histological types and clinical stages of uterine cervical cancers was analysed. The expression of VEGF was seen dominantly in the cancer cells, and correlated with microvessel density in uterine cervical cancers. Among the four subtypes of VEGF, the populations of VEGF165 and VEGF121 were dominant in normal uterine cervices and uterine cervical cancers. The levels of VEGF and VEGF165 and VEGF121 mRNAs were remarkably higher in some stage II and III/IV adenocarcinomas of the cervix than in other cases, including normal cervices. Therefore, the elevation of VEGF165 and VEGF121 might contribute to the relatively late advancing via angiogenic activity in some adenocarcinomas of the cervix.

Adult↗
PubMed2005

Screening for cervical cancer--an evidence-based approach.

INTRODUCTION: The Papanicolau (Pap) smear is widely accepted by both the public and health authorities as a useful tool for detection of cervical cancer and its precursors. In Israel only opportunistic screening exists and still the incidence of invasive cervical cancer is among the lowest in the world. OBJECTIVES: To examine the existing evidence for the effectiveness of cervical cancer screening by Pap smears; to apply the findings to Israeli data, and to assess the implications for the current cervical cancer screening policy. METHODS: Search of Medline (1966-June 2003) and the Cochrane Library for relevant systematic reviews, controlled trials and cohort studies. RESULTS: There have been no trials of screening for cervical cancer and its precursors and therefore, no direct evidence that screening improves outcomes. A single retrospective cohort study estimated the age-adjusted RR for invasive cervical cancer in women with at least one Pap smear, whether normal or abnormal, compared to women with no smear at 0.4 (95% CI 0.2-0.9). In Israel some 27,800 (range: 20,800-167,000) women need to be screened in order to prevent one case of cervical cancer. The cost of preventing a single case of invasive cervical is approximately 1.288 million NIS (range: 1.643-13.193 million NIS). CONCLUSIONS: An evidence-based approach to the question of the effectiveness of cervical cancer screening using Pap smears has yielded weak evidence. Based on this weak evidence and rough estimations of the effectiveness and cost of mass screening for cervical cancer in Israel, we conclude that the current policy should be maintained.

Adult↗
PubMed2003

The influence of depth of marker administration on sentinel node detection in cervical cancer.

BACKGROUND: Regional lymph node surgical management is an integral part of cervical cancer therapy. In gynaecological oncology, recent studies have confirmed the utility of the sentinel node concept in vulvar and cervical cancer. The method of the marker's administration is considered to play an important role in sentinel node detection. MATERIAL AND METHODS: 60 patients with cervical cancer (stage IB-IIA) underwent SLN detection during radical abdominal hysterectomy. The patients were randomly divided into two groups: the first group of 30 patients with 0.5-1cm deep marker injection, the second with sub-epithelial marker injection. Gamma-camera scanning, as well as hand-held probe detection was applied. RESULTS: All hot nodes visualised on lymphoscintigraphy were "hot" when using the hand-held gamma probe. Deep marker injection revealed a sentinel node in 27 patients (90%) on both sides, in 3 patients (10%) only on one side. Only 40 (67%) sentinel nodes were blue-stained. Sub-epithelial marker administration revealed a sentinel node on both sides in all 30 patients (100%). In 28 patients (93.3%) the sentinel nodes were radioactive and blue-stained, in one case not-blue stained on either side, in one case blue stained only on one side. CONCLUSIONS: The sentinel node detection rate in cervical cancer is relatively high and depends on the applied technique. The superficial administration of radiocolloid and the blue dye into the cervix provides a higher sentinel node detection rate than deep administration in cervical cancer patients.

Adult↗
PubMed1993

[A study of intercellular adhesion molecule-1 (ICAM-1) in cervical cancer].

Intercellular adhesion molecule-1(ICAM-1), one of the adhesion molecules, plays an important role in target-cell lysis by immune cells. In this study we examined the expression of ICAM-1 in 15 cases of cervical cancer. We also examined ICAM-1 expression on cervical cancer cell lines in response to cytokines. Immunohistochemistry revealed expression (4 positive among 15 cases) of ICAM-1 in cervical cancer. Furthermore, the expression of ICAM-1 on cervical cancer was correlated with the degree of mononuclear cell infiltration, bearing CD3. On the other hand, the expression of ICAM-1 was not correlated with Class I or Class II antigens in cervical cancer. The expression of ICAM-1 on cervical cancer cell lines was augmented by in vitro treatment with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. These results suggest that the expression of ICAM-1 on cervical cancer might be modified by cytokines, and ICAM-1 expression on cervical cancer might augment the host immune reaction. So it will be possible to use cytokines in immunotherapy.

Cell Adhesion Molecules↗
PubMed2001

Low serum and red blood cell folate are moderately, but nonsignificantly associated with increased risk of invasive cervical cancer in U.S. women.

Previous observational epidemiologic studies of folate and cervical cancer, as well as folate supplementation trials for cervical dysplasia, have produced mixed results. We examined the relationship between serum and RBC folate and incident invasive cervical cancer in a large, multicenter, community-based case-control study. Detailed in-person interviews were conducted, and blood was drawn at least 6 mo after completion of cancer treatment from 51% of cases and 68% of controls who were interviewed. Blood folate was measured with both microbiologic and radiobinding assays. Included in the final analyses were 183 cases and 540 controls. Logistic regression was used to control for all accepted risk factors, including age, sexual behavior, smoking, oral contraceptive use, Papanicolaou smear history and human papillomavirus (HPV)-16 serology. For all four folate measures, the geometric mean in cases was lower than in controls (e.g., 11.6 vs. 13.0 nmol/L, P < 0.01 for the serum radiobinding assay). Folate measures using microbiologic and radiobinding assays were correlated (serum: r = 0.90; RBC: r = 0.77). For serum folate, multivariate-adjusted odds ratios (OR) in the lowest vs. highest quartile were 1.3 [95% confidence interval (CI) = 0.8--2.9] and 1.6 (0.9--2.9), using the microbiologic and radiobinding assays, respectively. For RBC folate, comparable OR were 1.2 (0.6--2.2) and 1.5 (0.8--2.7). Similar risks were obtained when restricting analyses to subjects with a history of HPV infection. Thus, low serum and RBC folate were each moderately, but nonsignificantly, associated with increased invasive cervical cancer risk. These findings support a role for one-carbon metabolism in the etiology of cervical cancer.

Adenocarcinoma↗
PubMed1997

Detection of HPV-16 DNA by PCR in histologically cancer free lymph nodes from patients with cervical cancer.

The prognostic value of detection of human papillomavirus (HPV) type 16 DNA in histologically cancer free lymph nodes was assessed in left obturator lymph nodes from cervical cancer patients with HPV-16 positive primary tumours. HPV-16 DNA was detected by polymerase chain reaction in 12 of 35 patients with histologically cancer free lymph nodes. Of these 12 patients, only one developed a recurrence, suggesting HPV-16 DNA detection in cancer free lymph nodes has no prognostic value.

Carcinoma, Squamous Cell↗
PubMed2005

Up-regulation of vascular endothelial growth factor-C by nicotine in cervical cancer cell lines.

PROBLEM: Smoking and infection with human papilloma virus (HPV) are major risk factors for cervical cancer. Our earlier work shows that nicotine enhances cellular proliferation of cervical cancer cell lines by up-regulating epidermal growth factor (EGF) and its receptor EGF-R, which leads to increased insulin-like growth factor II in vitro. We found that the vascular endothelial growth factor (VEGF)-C, one of the five isoforms of VEGF, may be specifically involved in lymphogenic metastasis of cervical cancer. This has prompted us to study if in vitro nicotine treatment will up-regulate VEGF-C alongside EGF-R levels, while down regulating the anti-proliferative transforming growth factor (TGF)-beta levels in HPV positive cervical cancer cell lines. METHOD OF STUDY: Cervical cancer cell lines CaSki, HeLa and ME-180, were cultured in serum free DMEM medium for 24-hr, and treated with 10 ng/mL nicotine in the medium supplemented with 10% fetal bovine serum. A group of untreated cells served as controls. The cells were cultured in chamber slides (for immunofluorescent antibody assay) as well as microtiter plate wells (for BrdU cell proliferation assay). The cellular levels of VEGF-C, TGF-beta, EGF-R and HPV-E6 (early protein 6) were measured by a semi-quantitative immunofluorescent antibody assay. The cell proliferation and immunofluorescent assay data were analyzed by a Student's t-test. RESULTS: Cell proliferation was significantly increased after nicotine treatment in all the cell lines. The VEGF-C levels were significantly increased, while TGF-beta levels were decreased by nicotine in all the cell lines (P < 0.00001). EGF-R levels were also significantly increased after nicotine treatment in HeLa and ME-180, while HPV-E6 levels remained unchanged in all three. CONCLUSIONS: Nicotine up regulates expression of cell proliferative VEGF-C and EGF-R, while down-regulating anti-proliferative TGF-beta. Our data suggest that nicotine in circulation and in cervical squamous epithelial cells may promote not only rapid tumor growth but its lympho-angiogenic spread (VEGF-C) as well. It appears that nicotine does not promote HPV spread in the cervical cancer cells.

Cell Proliferation↗
PubMed1982

Second cancers following radiotherapy for cervical cancer.

Incidence of second primary cancers was evaluated in 7,127 women with invasive cancer of the cervix uteri, diagnosed between 1935 and 1978, and followed up to 38 years (average, 8.9 yr) in Connecticut. Among 5,997 women treated with radiation, 449 developed second primary cancers compared with 313 expected (relative risk = 1.4) on the basis of rates from the Connecticut Tumor Registry. Excess incidence was noticeable 15 years or more after radiotherapy and attributed mostly to cancers of sites in or near the radiation field, especially the bladder, kidneys, rectum, corpus uteri, and ovaries. No excess was found for these sites among the 1,130 nonirradiated women. The ratio of observed to expected cancers for these sites did not vary appreciably by age at irradiation. The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer.

Adult↗
PubMed2005

Detection and quantitation of human papillomavirus type 16, 18 and 52 DNA in the peripheral blood of cervical cancer patients.

OBJECTIVE: To prospectively evaluate the feasibility of detecting human papillomavirus (HPV) type 16, 18 and 52 DNA in the peripheral blood of patients with cervical cancer using real-time polymerase chain reaction (PCR) and to determine its prognostic importance. METHODS: Blood and cervical swab specimens from 135 consecutive patients with 60 invasive cervical cancers, 10 microinvasions, 20 cervical intraepithelial neoplasias (CIN) III, 10 CIN II, 10 CIN I and 25 controls were collected and examined for HPV type 16, 18 and 52 DNA using real-time PCR to investigate the prevalence and viral load of HPV DNA at the time of diagnosis and during follow-up in patients with positive blood samples. RESULTS: Of the 60 patients with invasive cervical cancer, 27% had positive test results for HPV DNA in blood samples in contrast to 0% of patients with microinvasions, CIN III, CIN II, CIN I and normal controls. The DNA detection rates of viral subtypes in blood samples of cervical cancer patients were 5% for HPV-16, 16.7% for HPV-18, 8.3% for HPV-52, 1.7% for both HPV-16 and HPV-18 and 1.7% for both HPV-18 and HPV-52, while the detection rates in cervical swab specimens were 36.2% for HPV-16, 15.5% for HPV-18 and 17.2% for HPV-52. During follow-up, 8 of 10 cervical cancer patients with viral DNA detected in blood within 3 months after treatment had recurrence, and a high percentage (87.5%, 7/8) of this recurrence involved distant metastases. CONCLUSIONS: In this study, real-time PCR detected HPV-16, -18 or -52 DNA in the peripheral blood of more than one-fourth of invasive cervical cancer patients. The association between risk of cancer recurrence and the amount of viral DNA detected in blood among cervical cancer patients after treatment is intriguing and deserves further investigation.

Adult↗