National Cancer Institute®
Last Modified: March 1, 2002
UI - 11817921
AU - Coughlin SS; Uhler RJ
TI - Breast and cervical cancer screening practices among Hispanic women in the United States and Puerto Rico, 1998-1999.
SO - Prev Med 2002 Feb;34(2):242-51
AD - Epidemiology and Health Services Research Branch, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Atlanta, GA 30341, USA. SIC9@cdc.gov
BACKGROUND: Results from recent studies suggest that Hispanic women in the United States may underuse cancer screening tests and face important barriers to screening. METHODS: We examined the breast and cervical cancer screening practices of Hispanic women in 50 states, the District of Columbia, and Puerto Rico from 1998 through 1999 by using data from the Behavioral Risk Factor Surveillance System. RESULTS: About 68.2% (95% confidence interval [CI] = 66.3 to 70.1%) of 7,253 women in this sample aged 40 years or older had received a mammogram in the past 2 years. About 81.4% (95% CI = 80.3 to 82.5%) of 12,350 women aged 18 years or older who had not undergone a hysterectomy had received a Papanicolaou test in the past 3 years. Women with lower incomes and those with less education were less likely to be screened. Women who had seen a physician in the past year and those with health insurance coverage were much more likely to have been screened. For example, among those Hispanic women aged 40 years or older who had any health insurance coverage (n = 6,063), 72.7% (95% CI 70.7-74.6%) had had a mammogram in the past 2 years compared with only 54.8% (95% CI 48.7-61.0%) of women without health insurance coverage (n = 1,184). CONCLUSIONS: These results underscore the need for continued efforts to ensure that Hispanic women who are medically underserved have access to cancer screening services. Copyright 2002 American Health Foundation and Elsevier Science (USA).
UI - 11544829
AU - Zorin AV; Tsodikov AD; Khanin LG; Zharinov GM; Zaikin GV; Iakovlev AIu
TI - [Parametric survival analysis in patients with cervical cancer following fractionated radiotherapy: a new procedures and results]
SO - Vopr Onkol 2001;47(3):307-11
AD - Central Research Institute of Roentgeno-Radiology, Ministry of Health of the RF, St. Petersburg.
A recent theoretical result of Kendal (1998) enabled us to develop a survival model which allows for proliferation of tumor clonogenic cells in the course of fractionated radiotherapy. We explored this model during an analysis of clinical data on survival of 982 patients with cancer of the cervix uteri. The model provided a good description of survival patterns in different groups of patients. The estimated cure probability did not correlate with the rates of cell proliferation between exposures to radiation. Also, our results showed that this parameter cannot be estimated from survival data. Some light has been thrown on the relationship of cell proliferations taking place between exposures, on the one hand, and end-results of treatment for cancer of the cervix uteri, on the other.
UI - 11544831
AU - Rozenko LIa; Nepomniashchaia EM; Rubtsov VR; Gudtskova TN; Tartanova TM
TI - [Pathologic morphology of cervical carcinoma with endolymphatic infusion of immuno-modulating drugs]
SO - Vopr Onkol 2001;47(3):315-20
AD - Research Institute of Oncology, Ministry of Health of the RF, Rostov-on-Don.
Prior to standard therapy, an immunomodulator was administered by endolymphic infusion to 85 patients with cervical carcinoma (T3NxMo), with a view to reinforce treatment. The drug was fed to lymph collectors which were regional and aregional with respect to tumor. Also, the treatment was supplemented with regional infusion of considerable doses of cytostatic mixes. Our morphological evidence pointed to the stimulation of cytostatic effect by immunomodulation.
UI - 11544838
AU - Vishnevskaia EE; Okeanova NI; Shelkovich SE; Matylevich OP
TI - [Evaluation of combined treatment in stage-II cervical cancer in terms of morphologic structure of the tumor]
SO - Vopr Onkol 2001;47(3):355-9
AD - N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
The efficacy of stage II cervical cancer (CC) treatment was evaluated in two groups: squamous cell carcinoma--151, cervical adenocarcinoma (CAC)--49. All the patients received combined treatment (preoperative large-fraction brachytherapy + surgery + postoperative radiation). A comparison of the results highlighted the role of morphological pattern of tumor as a factor of cure. Five-year survival rates for CAC stage II patients were lower by 12.4% while the incidence of distant lymphogenous metastases and those to organs, responsible for failed therapy, was 2.7 times as high.
UI - 11564482
AU - Green JA; Kirwan JM; Tierney JF; Symonds P; Fresco L; Collingwood M;
TI - Williams CJ Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis.
SO - Lancet 2001 Sep 8;358(9284):781-6
AD - Department of Medicine, University of Liverpool, L69 3GA, Liverpool, UK. J.A.Green@liverpool.ac.uk
BACKGROUND: The US National Cancer Institute alert in February, 1999, stated that concomitant chemotherapy and radiotherapy should be considered for all patients with cervical cancer. Our aim was to review the effects of chemoradiotherapy on overall and progression-free survival, local and distant control, and acute and late toxicity in patients with cervical cancer. METHODS: With the methodology of the Cochrane Collaboration, we did a systematic review of all known randomised controlled trials done between 1981 and 2000 (17 published, two unpublished) of chemoradiation for cervical cancer. FINDINGS: The trials included 4580 randomised patients, and 2865-3611 patients (62-78%) were available for analysis. Cisplatin was the most common agent used. The findings suggest that chemoradiation improves overall survival (hazard ratio 0.71, p<0.0001), whether platinum was used (0.70, p<0.0001) or not (0.81, p=0.20). A greater beneficial effect was seen in trials that included a high proportion of stage I and II patients (p=0.009). An improvement in progression-free survival was also seen with chemoradiation (0.61, p<0.0001). Thus, the absolute benefit in progression-free and overall survival was 16% (95% CI 13-19) and 12% (8-16), respectively. A significant benefit of chemoradiation on both local (odds ratio 0.61, p<0.0001) and distant recurrence (0.57, p<0.0001) was also recorded. Grade 3 or 4 haematological (odds ratio 1.49-8.60) and gastrointestinal (2.22) toxicities were significantly greater in the concomitant chemoradiation group than the control group. There was insufficient data to establish whether late toxicity was increased in the concomitant chemoradiation group. INTERPRETATION: Concomitant chemotherapy and radiotherapy improves overall and progression-free survival and reduces local and distant recurrence in selected patients with cervical cancer, which may give a cytotoxic and sensitisation effect.
UI - 11748359
AU - Kang GH; Min K; Shim YH; Kim KR
TI - Papillary immature metaplasia of the uterine cervix: a report of 5 cases with an emphasis on the differential diagnosis from reactive squamous metaplasia, high-grade squamous intraepithelial lesion and papillary squamous cell carcinoma.
SO - J Korean Med Sci 2001 Dec;16(6):762-8
AD - Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. firstname.lastname@example.org
Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.
UI - 11481905
AU - Szentirmay Z; Cseh J; Pulay T; Kasler M
TI - [Human papillomavirus and cervical cancer: genetic background of the neoplastic process]
SO - Orv Hetil 2001 Jul 8;142(27):1429-36
AD - Orszagos Onkologiai Intezet, Budapest.
In a 2-year period, 136 HPV positive cytological samples of the cervix uteri were analyzed at the Department of Molecular Pathology, National Institute of Oncology, Hungary. Comparison with the international data obtained from the literature revealed that the Hungarian epidemiological data bore closest resemblance to the European ones except some differences. The HPV18 is rather seldom encountered in this country. Similarly low occurrence was noted only in Japan. However, the 14.1% occurrence rate of HPV58 in Hungary is by far higher than that in any other country in this analysis except Japan where this virus is of similarly high frequency. In Hungary, the incidence of HPV59 is relatively high just like in Central and South America. HPV33 and HPV66 infections occur in a significantly higher number with Hungary than in any of the countries studied. In our study The European type variant of HPV16 (E-V-350G) occurred in 2/10 CIN II-III cases. The authors also compared the various clinico-pathological grouping of HPV types published, and identified several inconsistencies. Viruses considered to have high risk occurred in intact epithelium, CIN I-II-III and carcinoma alike. The general tendency was, however, that certain viruses correlated with specific clinico-pathological entities. At present there is no reason to include the PCR-based HPV typing in the mass screening of cervical cancers. HPV typing and physical state of the virus can reasonable be determined if the cervical cytology is suspect for HPV infection or even control examination after "loop" conisation. Negative cytology completed with negative HPV-DNA test means the lack of cancer risk even in the case of a previously removed CIN or carcinoma. However, a positive HPV test detected after conisation associated with negative cytology finding indicates a risk of 70% of the development of CIN within 2 years.
UI - 11843937
AU - McGahan CE; Blanks RG; Moss SM
TI - Reasons for variation in coverage in the NHS cervical screening programme.
SO - Cytopathology 2001 Dec;12(6):354-66
AD - Cancer Screening Evaluation Unit, Institute of Cancer Research, Section of Epidemiology, Sutton, UK.
In order to investigate reasons for variation in coverage of cervical screening, data from standard Department of Health returns were obtained for all Health Authorities for 1998/1999. Approximately 80% of the variation between health authorities is explained by differences in age distribution and area classification. Considerable differences between Health Authority and Office of National Statistics (ONS) population figures in City and Urban (London) areas for the age group 25-29 years and for City (London) for age group 30-34 years, suggest an effect of list inflation in these groups. Coverage as a performance indicator may be more accurately represented using the age range 35-64 years. Using this narrower age range, the percentage of health authorities meeting the 80% 5-year coverage target increases from 87% to 90%.
UI - 11843939
AU - Migliore G; Rossi E; Aldovini A; Mudu P; Alderisio M; Giovagnoli MR;
TI - Fabiano A; Morosini PL; Branca M Variation in the assessment of adequacy in cervical smears.
SO - Cytopathology 2001 Dec;12(6):377-82
AD - Laboratory of Epidemiology and Biostatistics, Cytopathology Unit, National Institute of Health, Rome, Italy.
OBJECTIVE: To assess the interobserver reproducibility of the diagnosis of 'adequacy' of cervical smears according to the Bethesda System criteria in cervical smears. STUDY DESIGN: 358 cervical smears were obtained from three Italian cytopathological centres in 1998-99. All centres provided consecutively collected smears. The cervical smears were independently and blindly assessed by four cytologists.The screening was performed using a 10x objective and an additional evaluation of the percentage of cellularity was performed using a 4x objective. RESULTS: The proportion of smears assessed by the four cytologists as 'adequate' ranged from 60% to 70%, the proportion of 'satisfactory for evaluation but limited by' ranged from 27% to 38%, and the proportion of 'inadequate smears' ranged from 2% to 4%. Full agreement in the assessment of smear adequacy was observed in 311 slides and disagreement was observed only in 47. The category 'inadequate smear' was less reliable than the other two; however, the kappa value observed was acceptable. CONCLUSION: The present study shows that it is possible to achieve a high reproducibility in the assessment of smear adequacy, at least among expert cytologists who follow the Bethesda System criteria strictly.
UI - 11843940
AU - Herbert A; Johnson J
TI - Personal view. Is it reality or an illusion that liquid-based cytology is better than conventional cervical smears?
SO - Cytopathology 2001 Dec;12(6):383-9
AD - Histopathology Department, Guy's and St Thomas' Hospitals NHS Trust, London, UK.
Liquid-based cytology (LBC) has been heralded as the way forward for cervical screening, and as the answer to many of its problems. It is already used as a sole method of cell preparation in many private clinics in the UK. It is being used for colposcopy smears in many NHS clinics and is now being piloted for primary screening in three screening centres in England, as well as one in Scotland and one in Wales. LBC has been welcomed as a new technology because it deals with the problem of specimen adequacy at source, removing responsibility for slide preparation and fixation from the clinician or nurse. It provides uniformly well-fixed preparations that are free of inflammatory exudate and blood, and seem easier to screen than conventional smears. There are many articles in the world literature suggesting that LBC is more accurate than conventional screening, and it is thought likely to reduce the number of false negative tests. The main reasons for piloting LBC in the NHS Cervical Screening Programme (NHSCSP) lie in its potential for reducing screening times and for reducing the numbers of repeats for inadequate tests. LBC is expensive in terms of equipment, capital costs, maintenance, consumables, training, technical preparation time, transportation and disposal of liquid media. Its costs could be justified if they were offset by the money saved from reduced screening time and repeat tests, but only if its accuracy in terms of sensitivity and specificity were proven to be equal to or better than conventional cytology. Although that is generally held to be true by the public and medical profession alike, there is very little hard evidence to support it.
UI - 11857315
AU - Acevedo CM; Henriquez M; Emmert-Buck MR; Chuaqui RF
TI - Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ.
SO - Cancer 2002 Feb 1;94(3):793-802
AD - Department of Pathology, Catholic University, Santiago, Chile.
BACKGROUND: Despite the increasing frequency of adenocarcinomas of the uterine cervix, little is known regarding inactivation of tumor suppressor genes (TSGs) in this tumor type. The authors analyzed loss of heterozygosity (LOH) in 36 carcinomas of the cervix with glandular differentiation, and 5 adenocarcinoma in situ in 40 patients. METHODS: The authors analyzed samples using laser capture microdissection from archival material and DNA amplified with microsatellite markers on the following loci: 3p14.2 (D3S1234, D3S1300), 3p21.3 (D3S1029, D3S1447), 3p22-24 (D3S1537, D3S1351), 6q21-23.3 (D6S250), 6q25.1 (ESR), 6q25.2 (D6S255), 8p21 (D8S136, D8S1820), 13q12.3 (D13S220, D13S267), 17q21 (D17S579, D17S855). Eight additional markers spanning the short arm of chromosome 3 (3p12-p25) and six spanning the long arm of chromosome 6 (6q11-q27) were studied in the cases showing LOH to further define the deletion intervals. RESULTS: The frequency of allelic loss in cancers was chromosome 3p: 49% (p14.2: 35%, p21.3: 23%, p22-24: 41%), 6q: 48% (q21-23.1: 39%, q25.1: 45%, q25.2: 7%), 13q: 22%, 17q: 6%, and 8p: 18%. On chromosome arm 3p, the authors' data suggest at least two discrete areas of deletion: a proximal area between markers D3S1234 (p12) and D3S1766 (p14.2-14.3), and a second distal interval, telomeric from marker D3S4623 (p21.3). On chromosome 6q, the deletion area is between marker D6S300 (q22) and D6S255 (q25.2). Two of five preneoplastic lesions showed LOH on chromosome arm 3p, and two five showed allelic loss on chromosome arm on 6q, suggesting the genes might be inactivated early in cervical tumorigenesis. CONCLUSIONS: The authors have identified three chromosomal regions that may harbor TSGs involved in the development/progression of adenocarcinomas of the uterine cervix, 3p12-14.2, 3p21.3-pter, and 6q22-25.2. Deletions also were detected in adenocarcinoma in situ, suggesting the genes may be inactivated early in cervical tumorigenesis. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10275
UI - 11859985
AU - Mogren I; Stenlund H; Hogberg U
TI - Long-term impact of reproductive factors on the risk of cervical, endometrial, ovarian and breast cancer.
SO - Acta Oncol 2001;40(7):849-54
AD - Department of Clinical Science, Umea University, Sweden. email@example.com
The influence of maternal age, parity, low or high birthweight, multiple births, and pre-eclampsia on the risk of cervical, endometrial, ovarian and breast cancers was studied. Data on 40951 women and the outcomes of their deliveries between 1955 and 1995 were obtained from birth registers. For the mothers, data from the Swedish Cancer Registry and the Cause of Death Register were added. The sample was evaluated using Cox's regression in univariate and bivariate analyses where the relative risk and its 95% confidence interval were calculated. Increasing maternal age at first birth was associated with an increasing relative risk of endometrial, ovarian, and breast cancers, and with a decreased risk of cervical cancer. Multiparity was a protective factor for all gynaecological cancers, including cervical and breast cancers. Multiple births were associated with an increased risk of endometrial cancer.
UI - 11850794
AU - Jarboe EA; Liaw KL; Thompson LC; Heinz DE; Baker PL; McGregor JA; Dunn
TI - T; Woods JE; Shroyer KR Analysis of telomerase as a diagnostic biomarker of cervical dysplasia and carcinoma.
SO - Oncogene 2002 Jan 21;21(4):664-73
AD - Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado, CO 80262, USA.
Telomerase expression is a potentially important marker of high-grade cervical dysplasia and squamous cell carcinoma (SCC). The routine practice of cervical cytology is limited by problems of false negative diagnoses as well as by poor specificity for clinically significant lesions in patients with low-grade cytologic abnormalities. Telomerase is widely expressed in most SCCs as well as in a high proportion of high-grade squamous intraepithelial lesions. Histochemical studies have confirmed that telomerase is expressed in the lower portions of normal or metaplastic squamous mucosa but that telomerase positive cells extend into the upper epithelial layers in cases of high-grade dysplasia. Since the cervical smear samples the uppermost cell layers of the cervical mucosa, but does not normally include cells derived from the lower layers of the squamous mucosa, the detection of telomerase in exfoliated cells of the cervical smear may have specificity for clinically significant lesions. The analysis of hTR, hTERT, and telomerase activity are complicated by a number of technical factors that may lead to either false negative or false positive test results. Thus, the practical application of telomerase analysis as a diagnostic adjunct for cervical cytopathology may depend on the development of more reliable and sensitive assay systems, possibly formatted for cytochemical applications.
UI - 11606114
AU - Belinson J; Qiao YL; Pretorius R; Zhang WH; Elson P; Li L; Pan QJ;
TI - Fischer C; Lorincz A; Zahniser D Shanxi Province Cervical Cancer Screening Study: a cross-sectional comparative trial of multiple techniques to detect cervical neoplasia.
SO - Gynecol Oncol 2001 Nov;83(2):439-44
AD - Department of Gynecology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. firstname.lastname@example.org
OBJECTIVE: The aim of this study was to design a cervical cancer screening algorithm for the developing world that is highly sensitive for cervical intraepithelial neoplasia (CIN) II, III, and cancer and highly specific for CIN II and III, making it possible to ablate the transformation zone without histologic confirmation. METHODS: In rural Shanxi Province, China, we examined 1997 women ages 35-45. Each subject underwent a self-test for intermediate and high-risk HPV (by HC-II assay), fluorescence spectroscopy, a liquid-based Pap (read manually and by computer and used as a direct test for HPV), a visual inspection (VIA) diagnosis, and colposcopy with multiple cervical biopsies. RESULTS: Mean age was 39.1 +/- 3.16 years, mean number of births was 2.6 +/- 0.93. Based on tests administered, 4.3% subjects had > or =CIN II. All subjects with > or =CIN II had either a ThinPrep Pap (> or =ASCUS) or a positive HPV direct test. The sensitivity and specificity for the detection of > or =CIN II were, respectively, 83 and 86% for the HPV self-test, 95 and 85% for the HPV direct test, 94 and 78% for the ThinPrep Pap (> or =ASCUS), 77 and 98% for the ThinPrep Pap (> or =HGSIL), 94 and 9% for fluorescence spectroscopy, 71 and 74% for VIA, and 81 and 77% for colposcopy. CONCLUSION: Based on these data and the existing healthcare infrastructure in China, we believe that further refinement of primary HPV screening using centralized labs is indicated. Self-testing in the local villages may be effective with improvements in the devices and techniques. Copyright 2001 Academic Press.
UI - 11792748
AU - Sherman ME; Schiffman M; Cox JT; Atypical Squamous Cells of Undetermined
TI - Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study Group Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS).
SO - J Natl Cancer Inst 2002 Jan 16;94(2):102-7
AD - Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7374, USA. email@example.com
BACKGROUND: Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (ASCUS), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage. METHODS: We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thin-layer cytopathology in 2198 women with ASCUS and in 848 women with LSIL enrolled in ALTS from two thresholds for HPV load and repeat cytopathology. RESULTS: For ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with ASCUS, referral for repeat cytopathology of ASCUS had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity. CONCLUSION: For women with ASCUS, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL.
UI - 11812077
AU - Li H; Huang CJ; Choo KB
TI - Expression of homeobox genes in cervical cancer.
SO - Gynecol Oncol 2002 Feb;84(2):216-21
AD - Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan.
OBJECTIVE: Members of the homeobox (HB) gene superfamily encode transcription factors crucial for development and may be associated with tumorigenesis. In this study, we aimed to develop a procedure to survey the expression of the dispersed-type HB genes in cervical cancer cells. METHODS: Nineteen sets of degenerate primers were designed based on conserved homeodomains of known dispersed-type HB genes. A cDNA library derived from HeLa, a cervical cancer cell line, was used. Two successive rounds of PCR were performed using a combination of the HB degenerate primers and a primer recognizing the flanking sequence of the vector used in the cDNA library construction. RESULTS: On cloning and sequence analysis of the PCR fragments generated, 10 known and 3 putative novel HB genes were detected in HeLa. RT-PCR expression analysis further showed that HOXD9 and ATBF1 were differentially expressed in cancer cells and not in normal cervix. CONCLUSIONS: Our data demonstrate the feasibility of using degenerate primers in PCR experiments in a collective analysis of complex gene families. Our data indicate that HOXD9 and ATBF1 are expressed in cervical cancer, but not in normal cervix. B)2002 Elsevier Science.
UI - 11812078
AU - Brummer O; Bohmer G; Hollwitz B; Flemming P; Petry KU; Kuhnle H
TI - MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation--an immunohistochemical study.
SO - Gynecol Oncol 2002 Feb;84(2):222-7
AD - Department of Gynecologic Oncology, Medizinische Hochschule Hannover, Germany. firstname.lastname@example.org
OBJECTIVES: Enzymatic degradation of the extracellular matrix (ECM) represents a key element in the multistage process of tumor invasion and metastasis. This process requires extensive degradation of ECM components such as basement membrane collagen (type IV) and interstitial collagen (type I, II, III). Matrix metalloproteinase-2 (MMP-2) specifically cleaves collagen type IV, the major collagen of the basement membrane. MMP-1 digests interstitial collagen type I and III, the main collagen types of the stromal extracellular matrix. We investigated protein levels of MMP-1 and MMP-2 in different stages of malignant transformation. METHODS: Using the APAAP method we analyzed 10 normal cervical tissues, 11 cervical intraepithelial neoplasia 1 (CIN 1), 8 CIN 2 and 10 CIN 3 lesions, and 15 invasive squamous cell carcinomas. These data were compared with the HPV DNA status tested by hybrid capture II. RESULTS: Only a few isolated epithelial cells stained positively for MMP-1 and MMP-2 in normal cervical tissue and CIN 1 lesions. The CIN 2 and CIN 3 group displayed a heterogeneous distribution of MMP expression. 3 CIN 2 and 8 CIN 3 lesions showed strong MMP-2 and weak MMP-1 expression in the dysplastic epithelial cells. 5 CIN 2 and 2 CIN 3 lesions stained negatively. Invasive carcinomas showed a coexpression for MMP-1 and MMP-2 in malignant epithelial cells and peritumoral stroma cells. All MMP-2-positive cases tested positive for the HPV high-risk group. CONCLUSIONS: The expression of MMP-2 protein in preinvasive lesions of the cervix uteri and a consecutive coexpression of MMP-1 and MMP-2 in invasive cancer suggest a gradually increasing invasive potential. MMP-2 expression, when focally observed in high-grade squamous intraepithelial lesions of the cervix, may indicate tumor areas with an increased risk for invasive growth. B)2002 Elsevier Science.
UI - 11812083
AU - Winter R; Haas J; Reich O; Koemetter R; Tamussino K; Lahousen M; Petru
TI - E; Pickel H Parametrial spread of cervical cancer in patients with negative pelvic lymph nodes.
SO - Gynecol Oncol 2002 Feb;84(2):252-7
AD - Department of Obstetrics and Gynecology, University of Graz, Graz, Austria. email@example.com
OBJECTIVE: We studied the incidence and prognostic implications of parametrial involvement according to tumor volume in a series of cervical cancer patients with negative pelvic lymph nodes. METHODS: We reviewed a series of 351 node-negative patients with stage IB, IIA, or IIB cervical cancer treated with class III radical hysterectomy. The surgical specimens were processed as step-serial giant sections and tumor volume was calculated. Overall, 180 patients had tumors <5 mL, 120 had tumors of 5-20 mL, and 51 had tumors >20 mL. Parametrial involvement was classified as continuous, discontinuous, or involvement of blood vessels or lymph nodes and according to location as medial or lateral. A total of 302 patients had squamous cell tumors and 49 had adenocarcinomas. The mean duration of follow-up was 9.3 years. RESULTS: Overall, 44 of 351 patients (12.5%) had parametrial involvement. The rate of parametrial involvement in patients with tumors <5, 5-20, and >20 mL was 6.7, 12.5, and 33%, respectively. Isolated involvement of the medial parametrium increased with tumor size (3.8, 8.3, and 27.5%, respectively), whereas isolated involvement of the lateral parametrium was seen in 2.2, 1.6, and 0% of the cases. Involvement of both the medial and the lateral portions of the parametrium was seen in 0.5, 2.5, and 5.9% of the specimens, respectively. There were no differences in the rate of parametrial involvement between squamous cell carcinomas and adenocarcinomas. The 5-year disease-free survival rates in patients without or with parametrial involvement were 90.2% vs 90%, 91.7% vs 92.9%, and 84.7% vs 67%, respectively. CONCLUSION: The lateral portion of the parametrium can be involved in patients with cervical cancer and negative pelvic lymph nodes, but this is uncommon. In this series of patients treated with type III radical hysterectomy, parametrial involvement had no influence on disease-free survival. (c)2001 Elservier Science
UI - 11812089
AU - Nakamoto Y; Eisbruch A; Achtyes ED; Sugawara Y; Reynolds KR; Johnston
TI - CM; Wahl RL Prognostic value of positron emission tomography using F-18-fluorodeoxyglucose in patients with cervical cancer undergoing radiotherapy.
SO - Gynecol Oncol 2002 Feb;84(2):289-95
AD - Division of Nuclear Medicine, Johns Hopkins University, Baltimore, Maryland 21287-0817, USA.
OBJECTIVE: The purpose of this study was to determine whether positron emission tomography (PET) using F-18-fluorodeoxyglucose (FDG) before and after radiotherapy would predict whether local control of cervical cancer had been achieved. METHODS: FDG-PET scans were performed prior to therapy and at a mean of 4.6 months after radiation in 20 patients (pts) with histologically proven uterine cervical cancer who were undergoing a "curative" course of radiation therapy. FDG uptake was interpreted visually by two readers using a 5-point grading system (0 = normal, 1 = probably normal, 2 = equivocal, 3 = probably abnormal, and 4 = definitely abnormal). The standardized uptake values corrected by lean body mass (SUL) were calculated for suspicious areas. The percentage of residual activity (%RA) for the posttherapy SUL was also evaluated as a percentage of the pretherapy SUL. RESULTS: At baseline before irradiation, 17 of 20 (85.0%) primary tumors were detected. Following irradiation, no or low (grade 0-2) uptake was observed in 9 pts, and none of these had local recurrence. Among the remaining 11 pts with grade 3 or 4 uptake, the correct diagnosis was made for 5 pts with active tumor; SULs (mean +/- SD = 4.17 +/- 2.52) and %RAs (57.9 +/- 16.8). Six patients without active tumor showed relatively low SULs (2.67 +/- 0.69) and %RAs (43.0 +/- 18.3). No significant differences were observed between the recurrent and nonrecurrent groups for these parameters. Overall, sensitivity, specificity, and accuracy were 100, 60, and 70%, respectively. CONCLUSION: These preliminary data indicate that FDG-PET is a sensitive tool for detecting active cervical cancer after radiation, however, the method, without anatomic correlation had suboptimal specificity. B)2002 Elsevier Science.
UI - 11812091
AU - Robison SW; Dietrich CS; Person DA; Farley JH
TI - Ethnic differences in survival among Pacific Island patients diagnosed with cervical cancer.
SO - Gynecol Oncol 2002 Feb;84(2):303-8
AD - Department of Obstetrics and Gynecology, Tripler Army Medical Center, 1 Jarrett White Road, TAMC, Hawaii 96859-5000, USA.
BACKGROUND: It was the purpose of this study to investigate whether Pacific Island (PI) ethnicity, Micronesian and Polynesian, is an independent prognostic factor in the survival of cervical cancer in a health care system with minimal racial bias and few barriers to access to care. METHODS: Records from 1988 to 1999 were reviewed for the U.S. Military Health Care System. The medical records of women with the diagnosis of invasive cervical cancer were abstracted and clinical data recorded. A cohort analysis based on Pacific Island ethnicity was also performed on all patients treated at Tripler Army Medical Center (TAMC) during this time period. Significant differences in distribution of clinical factors were determined by Wilcoxon rank-sum test and survival analyses were performed using Kaplan-Meier actuarial statistics. RESULTS: A total of 153 patients were identified who were treated at TAMC; 74 were of PI ethnicity. An additional 1400 patients were identified throughout the military health care system during this time. Forty-eight percent of non-PI TAMC patients were Caucasian, 14% Filipino, and 13% Korean. The mean age of PI was 45 versus 40 years for their non-PI counterparts. There was no difference in the distribution of the grade of tumors among cohorts analyzed. Seventy-five percent of non-PI patients presented at an early stage while 74% of PI women presented at an advanced stage. Twenty-three percent of PI patients had positive lymph nodes, versus 7% of non-PI patients. There was no difference in the radiation dosages among patients treated with primary radiation therapy. PI patients had a significantly decreased 5-year survival, 32% versus 71%, compared to their cervical cancer patient counterparts, P < 0.001. Multivariate analysis revealed PI ethnicity to be a significant independent predictor of decreased survival, P < 0.001. CONCLUSION: PI women diagnosed with cervical cancer tend to present at an advanced age and stage with metastatic disease. They have a decreased survival that remains present after adjusting for age, stage, and grade. The poor prognosis is likely due to lack of uniform screening among this population; however, molecular etiologies and human papillomavirus could also contribute to decreased survival. B)2002 Elsevier Science.
UI - 11848503
AU - Schoppmann SF; Schindl M; Breiteneder-Geleff S; Soleima A; Breitenecker
TI - G; Karner B; Birner P Inflammatory stromal reaction correlates with lymphatic microvessel density in early-stage cervival cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3419-23
AD - Institute of Clinical Pathology, University of Vienna, Austria.
BACKGROUND: In early-stage cervical cancer, high lymphatic microvessel density (LMVD) indicates favorable prognosis. This unexpected finding was thought to be an effect of local immunological response, although no data supported this thesis. MATERIALS AND METHODS: LMVD and lymphovascular invasion (LVI) were assessed in 85 specimens of cervical cancer stage pT1b by immunostaining for podoplanin, a marker for lymphatic endothelia. Local immunological response, evident by inflammatory stromal reaction (ISR), was determined in H&E-stained slides and rated from grade 1 (absent or weak) to 3 (strong) RESULTS: A good correlation of LMVD and ISR was found (p=0.002). While a strong correlation between LMVD and the presence of LVI was found (p<0.001), no association between LMVD and pelvic lymph node involvement (p=0.732) was observed. ISR indicated favourable prognosis of patients (p=0.0247, log-rank test). CONCLUSION: Our findings suggest that ISR might play a role in the induction of lymphangiogenesis in early stage cervical cancer.
UI - 11870517
AU - Brooks LA; Sullivan A; O'Nions J; Bell A; Dunne B; Tidy JA; Evans DJ;
TI - Osin P; Vousden KH; Gusterson B; Farrell PJ; Storey A; Gasco M; Sakai T; Crook T E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia.
SO - Br J Cancer 2002 Jan 21;86(2):263-8
AD - Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG, UK.
In common with other E2F1 responsive genes such as p14(ARF) and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Delta2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Delta2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium. Copyright 2002 The Cancer Research Campaign
UI - 11870518
AU - Kammer C; Tommasino M; Syrjanen S; Delius H; Hebling U; Warthorst U;
TI - Pfister H; Zehbe I Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease.
SO - Br J Cancer 2002 Jan 21;86(2):269-73
AD - Institute of Virology, University of Cologne, Furst-Puckler-Strasse 56, D-50935 Cologne, Germany.
High-risk human papillomavirus types, especially type 16, are risk factors for cervical cancer. Preliminary studies suggest that HPV16 polymorphisms in the long control region or in the E6 gene may alter the oncogenic potential of the virus. This could partially explain why some lesions progress to cancer while others do not. A systematic study combining the long control region and E6 has not been undertaken. This prompted us to investigate the long control region and the E6 in northern European women infected with human papillomavirus 16. We identified the sequence variations of both regions and investigated the long control region promoter activity among various isolates. In addition, we correlated the distribution of long control region and E6 polymorphisms with disease status. We analyzed 45 samples from Swedish and Finnish women. The long control region and the E6 gene were sequenced after polymerase chain reaction long control region fragments of six European isolates covering the majority of polymorphisms in this region were ligated into the pALuc vector and used for luciferase assays. In European HPV16 isolates, polymorphisms in the long control region are more frequent than in the E6 gene. Nevertheless, the promoter function was slightly increased in only one of the tested European long control region variants. In addition, we found a specific European E6 variant, L83V, to be enriched in high-grade lesions and cancer rather than a specific European long control region variant. The difference in oncogenicity between European HPV16 genotypes is more probably due to an altered property of the corresponding E6 proteins rather than to an altered activity of the P97 promoter. Copyright 2002 The Cancer Research Campaign
UI - 11870519
AU - Cheng Q; Lau WM; Chew SH; Ho TH; Tay SK; Hui KM
TI - Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix.
SO - Br J Cancer 2002 Jan 21;86(2):274-81
AD - Laboratory of Gene Structure & Expression, Division of Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, 169610 Singapore.
To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT--PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA--RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials. Copyright 2002 The Cancer Research Campaign
UI - 11168078
AU - Gopalkrishna V; Aggarwal N; Malhotra VL; Koranne RV; Mohan VP; Mittal A;
TI - Das BC Chlamydia trachomatis and human papillomavirus infection in Indian women with sexually transmitted diseases and cervical precancerous and cancerous lesions.
SO - Clin Microbiol Infect 2000 Feb;6(2):88-93
AD - Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (Indian Council of Medical Research), New Delhi, India.
OBJECTIVES: Sexually transmitted diseases (STDs) and anogenital cance