• Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological cervical cancer screening.

• Host genetic polymorphism analysis in cervical cancer.

• AWHONN partners with national cervical cancer campaign.

• A decade has passed...the Pap smear and cervical cancer.

• Determinants of cervical cancer rates in developing countries.

• Analysis of cervico-vaginal (Papanicolaou) smears, in girls 18 years and under.

• What do we expect from imaging?

• Imaging of cancer of the cervix.

• [Etiotropic treatment of patients with early uterine carcinoma as a basis for prevention of relapses and complications]

• [An in situ study on immunostimulatory molecules in cancer cells within the cervical carcinoma tissues]

• Criteria for organized cervical screening programs. Special emphasis on The Netherlands program.

• Task force consensus report on HPV-related changes of the lower female genital tract.

• Significance of cytologic smears in the diagnosis of small cell carcinoma of the uterine cervix.

• Modelled current distribution in cervical squamous tissue.

• Antibodies against human papillomavirus type 16 and 18 E6 and E7 proteins in cervicovaginal washings and serum of patients with cervical

• Prognostic significance of DNA cytometry in carcinoma of the uterine cervix FIGO stage IB and II.

• Confronting cervical cancer. Screening is the key to stopping this killer.

• HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India.

• Cytologic and biopsy findings leading to conization in adenocarcinoma in situ of the cervix.

• Discrepancy in the interpretation of cervical histology by gynecologic pathologists.

• Cervical cancer risk as a predictor of Pap smear use in rural North Carolina.

• Use of cell block preparation for morphological, immunocytochemistry, and ploidy analysis in ThinPrep monolayer preparations.

• HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasiveness.

• Cervical cancer screening by simple visual inspection after acetic acid.

• [HPV testing--the effect must be evaluated prior to clinical use!]

• A prospective study of the relationship between prediagnostic human papillomavirus seropositivity and HPV DNA in subsequent cervical

1
UI - 12065846
AU - Ngan HY; Cheung AN; Liu SS; Liu KL; Tsao SW
TI - Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological cervical cancer screening.
SO - Tumour Biol 2002 Mar-Apr;23(2):87-92
AD - Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. hysngan@hkucc.hku.hk
OBJECTIVE: This study aims at exploring the potential use of telomerase activity assay and typing of human papillomaviruses (HPV) 16 and 18 in improving the identification of high-grade cervical intraepithelial neoplasia (CIN). METHODS: From 86 women with normal cervical smears and from 114 patients with abnormal cervical smears cervical scrapings were collected. The telomerase activity was assayed using the Telomerase Repeat Amplification Protocol, and HPV was detected using consensus primers and specific primers for HPV 16 and HPV 18. RESULTS: HPV 16 in cervical scrapes was significantly associated with high-grade squamous epithelial lesions on cytology and with high-grade CIN, i.e., CIN 2/3 on biopsy. The detection of HPV 18 or telomerase activity had no significant association with high-grade squamous intraepithelial lesions or high-grade CIN. CONCLUSION: The use of the telomerase activity assay in cervical scrapes, unlike HPV 16 typing, did not improve the detection of high-grade CIN. Copyright 2002 S. Karger AG, Basel

2
UI - 12142377
AU - Calhoun ES; McGovern RM; Janney CA; Cerhan JR; Iturria SJ; Smith DI;
TI - Gostout BS; Persing DH Host genetic polymorphism analysis in cervical cancer.
SO - Clin Chem 2002 Aug;48(8):1218-24
AD - Mayo Foundation for Medical Education and Research, Rochester, MN 55905, USA.
BACKGROUND: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. METHODS: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. RESULTS: The tumor necrosis factor-alpha (TNFalpha) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFalpha -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3' untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. CONCLUSIONS: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFalpha single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.

3
UI - 11975131
AU - Anonymous
TI - AWHONN partners with national cervical cancer campaign.
SO - AWHONN Lifelines 2002 Apr-May;6(2):163-4

4
UI - 9353086
AU - Linder J
TI - A decade has passed...the Pap smear and cervical cancer.
SO - Am J Clin Pathol 1997 Nov;108(5):492-8

5
UI - 12115570
AU - Drain PK; Holmes KK; Hughes JP; Koutsky LA
TI - Determinants of cervical cancer rates in developing countries.
SO - Int J Cancer 2002 Jul 10;100(2):199-205
AD - International Health Program, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
Although cervical cancer (CC) is a leading cause of cancer-related deaths in developing countries, incidence rates vary considerably, ranging from 3 to 61 per 10(5) females. Identifying determinants of high vs. low rates may suggest population-level prevention strategies. CC rates for 175 countries were obtained from the IARC. Country-specific behavioral, health, economic and demographic measures were obtained from United Nations agencies and other international organizations. Regression analyses performed for 127 low or medium developed countries identified both geography and religion as independently associated with high CC rates. Among behavioral measures, high fertility rates, early age at birth of first child and high teenage birth rates were significantly associated with high CC rates. Countries with high CC rates had fewer doctors per capita, less immunization coverage, more HIV infections and shorter life expectancies. CC rates also tended to be higher in countries with more spending on health and younger, less educated populations. Patterns of CC rates suggest that programmatic approaches, such as promoting delayed childbearing and sexual monogamy, may be appropriate interventions. For countries with high CC rates and some flexibility in their health-care budgets, a once-in-a-lifetime screen of women 30-50 years of age, using Pap smears, direct visual inspection and/or HPV DNA testing, may be cost-effective. Finally, relatively low immunization rates and a shortage of health-care workers in countries with high CC rates suggest potential challenges for introducing prophylactic HPV vaccines. Copyright 2002 Wiley-Liss, Inc.

6
UI - 12089874
AU - Prussia PR; Gay GH; Bruce A
TI - Analysis of cervico-vaginal (Papanicolaou) smears, in girls 18 years and under.
SO - West Indian Med J 2002 Mar;51(1):37-9
AD - School of Clinical Medicine and Research, University of the West Indies, Queen Elizabeth Hospital, Cave Hill, Barbados. prussia@cariaccess.com
This study was conducted retrospectively at the Queen Elizabeth Hospital and a private laboratory in Barbados to determine the types of epithelial abnormalities in cervico-vaginal Papanicolaou (Pap)-stained smears, and their clinical implications in Barbadian girls, 18 years and hundred and sixty-five Pap smears from 236 patients were examined and the gynaecological history, initial and repeat Pap smear diagnoses, and histology reports of these patients were analyzed. Of the 236 first-visit smears, 94 (39.8%) were abnormal with 36 (15.3%) displaying cytologic features of squamous intra-epithelial lesions (SIL), (33 low grade and 3 high grade). A diagnosis of atypical squamous cells of undetermined significance (ASCUS) was reported in the remaining 58 (24.5%) abnormal smears, of which 35 (60.3%) were suspected to be related to human papillomavirus (HPV) infection. Twenty-two (23.4%) of these 94 patients, who had abnormal smears of either ASCUS or low grade squamous intra-epithelial lesions (LSIL) were re-evaluated within six to twelve months of the initial abnormal Pap smear diagnosis. Eight of these 22 patients (36.4%) had histological diagnosis of LSIL inclusive of cervical intra-epithelial neoplasia grade 1 (CIN 1) and condylomata. High-risk HPV DNA types were detected in two of these eight patients (25%). The study confirms that sexually active teenage girls are at risk of developing SIL and high-risk HPV infection. Screening of sexually active teenaged girls by Pap smears followed by other appropriate investigative procedures is recommended.

7
UI - 12117191
AU - Barakat RR; Hricak H
TI - What do we expect from imaging?
SO - Radiol Clin North Am 2002 May;40(3):521-6, vii
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. barakatr@mskcc.org
The objectives of imaging in gynecologic cancer include tumor detection, tumor diagnosis, staging, and follow-up. In addition, both monitoring response to treatment and differentiating tumor recurrence from post-treatment changes are important indications for imaging. In 2001 it was estimated that there would be 38,300 cases of endometrial cancer, 23,400 cases of ovarian cancer, and 12,900 cases of cervical cancer. This article reviews what information is required by the practicing gynecologist or gynecologic oncologist prior to surgery and briefly summarizes state-of-the-art imaging in answering clinically pertinent questions.

8
UI - 12117194
AU - Scheidler J; Heuck AF
TI - Imaging of cancer of the cervix.
SO - Radiol Clin North Am 2002 May;40(3):577-90, vii
AD - Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, Klinikum Grosshadern, Germany. scheidler@rzm.de
Cancer of the endometrium is the most common invasive gynecologic malignancy in North America. Although transvaginal sonography is often the initial imaging examination in women with dysfunctional uterine bleeding, MRI offers multifactorial assessment once the diagnosis of endometrial cancer has been established. Specifically, preoperative contrast-enhanced MRI alters the likelihood ratios for myometrial invasion, which in turn affects type and extent of surgery performed. This information also helps identify patients who would most benefit from referral to a tertiary care center for treatment by a gynecologic oncologist.

9
UI - 11519444
AU - Iaremchuk AIa; Vakulenko GA; Khadi D
TI - [Etiotropic treatment of patients with early uterine carcinoma as a basis for prevention of relapses and complications]
SO - Lik Sprava 2001 Mar-Apr;(2):90-3
In this paper, consideration is given to the role that etiological and pathogenetic factors have in the development of malignant tumours. Prevention of possible recurrencies and complications in patients with incipient forms of hysterocarcinoma warrant etiotropic treatment which has been shown to be effective and essential for the object to succeed in.

10
UI - 11798783
AU - Guo J; Si L; Wang Y
TI - [An in situ study on immunostimulatory molecules in cancer cells within the cervical carcinoma tissues]
SO - Zhonghua Yi Xue Za Zhi 2000 May;80(5):342-5
AD - Institute of Immunopathology, Xi'an Medical University, Xi'an 710061, China.
OBJECTIVE: To explore the immune escape mechanism by investigating the expression of B7.1, B7.2, ICAM-1 and MHCI, MHCII Ag in the cancer cells of cervical carcinoma. METHODS: The expressions of B7.1, B7.2 and ICAM-1, together with MHCI and IIAg were analyzed in tumor cells and interstitial cells of human cervical carcinoma with immunohistochemistry technique. The mRNA expressions of B7.1, B7.2 and ICAM-1 were observed by in situ hybridization. RESULTS: Out of the 42 fresh specimens analyzed with immunohistochemistry, the tumor cells expressed B7.1 Ag and ICAM-1 molecules in 22 and 27 specimens respectively, but not expressed B7.2; B7.1(+), B7.2(+) and ICAM-1(+) dendritic cells and lymphocytes were scattered more or less in the parenchyma and interstitum. Among the 37 cases studied for MHC Ag expression, the tumor cells expressed MHCI Ag and MHCIIAg in 32 and 4 cases respectively. No matter whether the tumor cells expressed MHCIIAg or not, MHCIIAg(+) dendritic cells were observed in the nests and the interstitial. When the same section staind for identifying, B7.1, B7.2 and MHCIIAg expressions was compared, by and large, the MHCIIAg(+) dendritic cells were always more numerous than B7.1, B7.1(+) or B7.2(+) ones. As for the 20 specimens inspected with in situ hybridization, the tumor cells in 11 and 12 cases expressed B7.1 mRNA and ICAM-1 mRNA respectively; Infiltrating dendritic cells and lymphocytes expressed B7.1 mRNA, B7.2 mRNA and ICAM-1 mRNA. CONCLUSION: Tumor cells in most cervical carcinomas have the necessary elements for presenting antigen and evoking T lymphocytes activation, and there are a lot of dendritic cells infiltrated in the tumor tissues. These findings indicate that the mechanism for tumor escape may be attributed to the post-antigen presentation events.

11
UI - 12146020
AU - Hanselaar AG
TI - Criteria for organized cervical screening programs. Special emphasis on The Netherlands program.
SO - Acta Cytol 2002 Jul-Aug;46(4):619-29
AD - Department of Pathology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Based on the criteria of Wilson and Jungner and experiences in the population-based organized cervical screening program in the Netherlands, conditions for efficient and effective population screening for cervical cancer are described. The purpose of this paper is to determine if these criteria are met for cervical cancer screening and to give recommendations for improvement. Cervical cancer is still an important health problem; the present incidence reflects both background risk and screening activity during previous decades. A positive effect of screening is reached because of the long development time of the disease and the ability of the Pap smear test to detect precancer and early, symptomatic disease. Considerable reduction in the incidence and mortality of cervical cancers can be reached if all women attend and all detected lesions are adequately followed up. Common terminology and classification criteria for histology and cytology should be used. Whether newly developed techniques that may improve or replace cytology can be used in screening programs should be a multidisciplinary decision after clinical trials have given evidence-based information on the performance, cost-effectiveness and need of these techniques. When cervical cancer screening is undertaken, it should be offered in organized programs at the medical level closest to the patients, the general practitioner. High compliance is the most important factor in reducing cervical cancer incidence. Quality control and assurance must be performed at all levels. In the case of limited resources, the program should use a five-year interval and concentrate on the age range 25-60 years, with special attention to women who have never been screened or were screened > 10 years previously. Evaluation of medical and organizational aspects is mandatory. Cooperation between all involved parties is a prerequisite of creating a successful screening program.

12
UI - 12146021
AU - Feichter G; Meisels A
TI - Task force consensus report on HPV-related changes of the lower female genital tract.
SO - Acta Cytol 2002 Jul-Aug;46(4):630-2

13
UI - 12146023
AU - Kim Y; Ha HJ; Kim JS; Chung JH; Koh JS; Park S; Lee SS
TI - Significance of cytologic smears in the diagnosis of small cell carcinoma of the uterine cervix.
SO - Acta Cytol 2002 Jul-Aug;46(4):637-44
AD - Department of Anatomic Pathology, Korea Cancer Center Hospital, Gongneung-Dong 215-4, Nowon-Ku, Seoul 139-706, Korea.
OBJECTIVE: To provide improved identification of small cell carcinoma (SMCC) and reevaluate the significance of cervical cytologic smears in its diagnosis. STUDY DESIGN: Analyses of histocytologic morphology and clinical data were performed by reviewing clinical records, histopathology and cervical cytology smears from 18 SMCC cases of the uterine cervix (including one recurrent case and three SMCC cases with adenocarcinoma) between 1986 and 2001. RESULTS: Most cases showed minimal cytoplasm, finely stippled ("salt and pepper") chromatin, prominent nuclear molding and smearing effect. Cytologic smears diagnosed or suggested 79% of SMCC cases before histologic confirmation. Of the cases, 89% displayed moderate to high cellularity. The tumor cells were arranged mostly in clusters of varying sizes with no typical architectural pattern. In addition, the tumors often exhibited very pleomorphic cells and recognizable nucleoli. CONCLUSION: Cytologic features of SMCC cells are characteristics enough for specific diagnosis or at least an early indication of it. Timely detection by cervical cytologic smears will allow clinicians to initiate prompt treatment of these aggressive tumors.

14
UI - 11876229
AU - Walker DC; Brown BH; Smallwood RH; Hose DR; Jones DM
TI - Modelled current distribution in cervical squamous tissue.
SO - Physiol Meas 2002 Feb;23(1):159-68
AD - Department of Medical Physics and Clinical Engineering, University of Sheffield, Royal Hallamshire Hospital, UK. mpp98dcw@sheffield.ac.uk
The electrical properties of cervical squamous epithelium have been modelled in the frequency range 100 Hz to 10 MHz. The hierarchical modelling process comprises a cellular level stage, which includes detailed models of cells typical of different depths within the epithelium and a tissue model, which utilizes electrical properties obtained from the cellular models. The fit between the modelled and measured impedance spectra and the distribution of current with depth depends on the macroscopic model structure. Both the properties of the basement membrane and the presence of a surface mucus layer are shown to have a significant effect. The best fit with measured data is obtained when a 10 microm thick, high-conductivity surface layer is included in the tissue model.

15
UI - 11792070
AU - Tjiong MY; Zumbach K; Schegget JT; van der Vange N; Out TA; Pawlita M;
TI - Struyk L Antibodies against human papillomavirus type 16 and 18 E6 and E7 proteins in cervicovaginal washings and serum of patients with cervical neoplasia.
SO - Viral Immunol 2001;14(4):415-24
AD - Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
Serum antibodies against the E6 and E7 proteins of human papillomavirus (HPV) 16 and 18 are associated with cervical cancer. The aim of this study was to investigate the presence of local antibodies against HPV in cervicovaginal washings (CWs). In this study antibodies against the native HPV16 and HPV18 E6/E7 proteins were detectable in CWs (48%) and sera (29%) from patients with cervical cancer (n = 21) utilizing a sandwich protein enzyme-linked immunosorbent assay (ELISA). In paired CWs and sera from patients with cervical intraepithelial neoplasia (n = 38) and from healthy women (n = 22) no antibodies against these proteins were found. In 10 of 11 patients, the antibody response corresponded with the HPV type in the cervical smear and/or tumor tissue, which indicates the HPV type specificity of the assay. In 7 of 11 patients with antibody reactivity against HPV16 or HPV18 E6 and/or E7 proteins a higher level of antibody reactivity in the CWs than in the paired serum samples was found at similar inputs of total IgG. This suggests that the antibodies in the CWs against the investigated HPV proteins in these patients were locally produced.

16
UI - 12082291
AU - Grote HJ; Friedrichs N; Pomjanski N; Guhde HF; Reich O; Bocking A
TI - Prognostic significance of DNA cytometry in carcinoma of the uterine cervix FIGO stage IB and II.
SO - Anal Cell Pathol 2001;23(3-4):97-105
AD - Institute of Cytopathology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Dusseldorf, Germany.
OBJECTIVE: To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. STUDY DESIGN: The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow-up was 55 months (range 1-162 months). DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin-fixed, paraffin-embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA-variables as well as various clinical and histological variables were related to survival rates. RESULTS: In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut-off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involvement were significantly correlated with survival. The synopsis of all parameters in a multivariate Cox model indicated that - with declining relevance - the number of positive pelvic lymph nodes, DNA stemline ploidy using a cut-off level at a modal value of 2.2c, largest pelvic lymph node, 5c exceeding rate, and ratio of carcinoma area to cervix area, were of predictive value for survival. CONCLUSIONS: Our results suggest that prognostic information deducted from classical staging parameters is successfully complemented by DNA image cytometry which can be applied pretherapeutically.

17
UI - 12078567
AU - Adams KL
TI - Confronting cervical cancer. Screening is the key to stopping this killer.
SO - AWHONN Lifelines 2002 Jun-Jul;6(3):216-22
AD - Lakewood Hospital, Lakewood, OH, USA.

18
UI - 12144822
AU - Saranath D; Khan Z; Tandle AT; Dedhia P; Sharma B; Contractor R;
TI - Shrivastava S; Dinshaw K HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India.
SO - Gynecol Oncol 2002 Aug;86(2):157-62
AD - Laboratory of Cancer Genes, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai, 400 012, India. dsaranath@netscape.net
OBJECTIVES: The HPV16/18 code for an oncoprotein-E6, which binds to p53 tumor suppressor protein and degrades the protein via ubiquitination. A common polymorphism of p53 in exon 4 codon 72, resulting in either proline (Pro) or arginine (Arg), affects HPV16/18 E6-mediated degradation of p53 protein in vivo. Hence, in the current study we investigated the prevalence of HPV16/18 in cervical lesions and the distribution of p53 genotypes in cervical cancers and normal healthy women. METHODS: DNA from 337 Indian women with invasive cervical cancers, 164 women with clinically normal cervix, 64 women with low-grade squamous intraepithelial lesions (LSIL), and 5 women with high-grade squamous intraepithelial lesions (HSIL) was examined for the presence of HPV16/18 using consensus primers in a polymerase chain reaction (PCR), and the specific HPV type was identified by Southern hybridization of the PCR product using HPV16/18 type-specific nucleotide sequences as probes. Further, 134 women with cervical cancers and 131 healthy women were used to determine the frequency of p53 genotypes, Pro/Pro, Arg/Arg, and Pro/Arg, using peripheral blood cell DNA to indicate the constitutional genotypes and allele-specific primers, in a PCR-based assay. RESULTS: We observed a prevalence of HPV16/18 in 77% (258/337) of cervical cancer patients, 38% (24/64) of LSILs, 4 of 5 HSILs, and 15.2% (25/164) of normal healthy women. The frequency of distribution of the three genotypes of p53 codon 72 in a subgroup of the HPV16/18-positive cervical cancer patients was Pro/Pro 0.18 and Arg/Arg 0.26, with the heterozygous Pro/Arg 0.56, differing significantly from the genotype frequency in the normal healthy women (chi(2) = 6.928, df = 2, P < 0.05). CONCLUSIONS: A high prevalence of HPV16/18 was observed in the cervical cancers. The prevalence in LSILs confirms HPV16/18 infection as an early event and further indicates a role in progression of lesions. The p53 genotype distribution indicated that women homozygous for Arg genotype were at a 2.4-fold higher risk for developing HPV16/18-associated cervical carcinomas, compared to those showing heterozygous Pro/Arg genotype (odds ratio 2.4, 95% confidence interval 1.89 to 3.04).

19
UI - 12151149
AU - Shin CH; Schorge JO; Lee KR; Sheets EE
TI - Cytologic and biopsy findings leading to conization in adenocarcinoma in situ of the cervix.
SO - Obstet Gynecol 2002 Aug;100(2):271-6
AD - Division of Gynecologic Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
OBJECTIVE: To investigate the utility of currently available screening tests in preoperatively detecting adenocarcinoma in situ of the cervix. METHODS: Patients with a cone biopsy diagnosis of adenocarcinoma in situ from 1987 to 2000 at our institution were identified. Results from Papanicolaou smears, cervical biopsies, and endocervical curettages preceding the diagnostic cone biopsy were collected from medical records and referring providers. Fisher exact test (two-tail) was used for statistical analysis. RESULTS: The preoperative screening results preceding a cone biopsy containing adenocarcinoma in situ were available in 118 patients. Among 94 Papanicolaou smears, 65 (69%) glandular lesions and 29 (31%) squamous or unspecified lesions were reported. Biopsy and/or endocervical curettage after the 29 squamous or unspecified lesions on Papanicolaou smear detected 15 additional glandular lesions, totaling 80 (85%) of 94 cases of glandular disease detected before conization. Among all 118 cases with some form of preoperative data available, glandular disease was predicted in 100 cases (85%). In cases of suspected glandular disease, 86% were treated with cold knife cone compared with 22% in cases of suspected squamous abnormalities (P <.001). CONCLUSION: The sensitivity of detecting a glandular abnormality before a cone biopsy containing adenocarcinoma in situ is 69% with the Papanicolaou smear and 85% with the addition of biopsy and endocervical curettage. This underscores the importance of using preoperative assessment to appropriately plan treatment for a suspected glandular lesion.

20
UI - 12151150
AU - Parker MF; Zahn CM; Vogel KM; Olsen CH; Miyazawa K; O'Connor DM
TI - Discrepancy in the interpretation of cervical histology by gynecologic pathologists.
SO - Obstet Gynecol 2002 Aug;100(2):277-80
AD - Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. parker@tatrc.org
OBJECTIVE: To determine if subspecialty review of cervical histology improves diagnostic consensus of cervical intraepithelial neoplasia (CIN). METHODS: After routine histologic assessment within the hospital pathology department, 119 colposcopic cervical biopsies were interpreted by two subspecialty-trained gynecologic pathologists (GYN I and GYN II) blinded to each other's interpretations and to the interpretations of the hospital general pathologists (GEN). Biopsies were classified as normal (including cervicitis), low grade (LG, including CIN I and human papillomavirus changes), and high grade (HG, including CIN II/III). The interobserver agreement rates between GEN and GYN I, between GEN and GYN II, and between GYN I and GYN II were described using the kappa statistic. The proportions of biopsies assigned to each biopsy class were compared using McNemar test. RESULTS: Interobserver agreement rates between GEN and GYN I were moderate for normal (kappa = 0.53) and LG (kappa = 0.46) and excellent for HG (kappa = 0.76). There were no significant differences in the classifications between GEN and GYN I. Interobserver agreement rates between GEN and GYN II were moderate for normal (kappa = 0.50) and LG (kappa = 0.44) and excellent for HG (kappa = 0.84). Also, GYN II was significantly more likely to classify biopsies as normal (P <.001) and less likely to classify biopsies as LG (P <.001). The interobserver agreement rates between GYN I and GYN II were moderate for normal (kappa = 0.61) and LG (kappa = 0.41) and excellent for HG (kappa = 0.84). Also, GYN II was significantly more likely to classify biopsies as normal (P <.001) and less likely to classify biopsies as LG (P =.01). CONCLUSION: Interobserver agreement between two gynecologic pathologists was no better than that observed between general and gynecologic pathologists. Subspecialty review of cervical histology does not enhance diagnostic consensus of CIN.

21
UI - 12043757
AU - Cyrus-David MS; Michielutte R; Paskett ED; D'Agostino R Jr; Goff D
TI - Cervical cancer risk as a predictor of Pap smear use in rural North Carolina.
SO - J Rural Health 2002 Winter;18(1):67-76
AD - Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. mscyrus@mdanderson.org
Risk for invasive cervical cancer is reported to be higher in rural areas than urban ones, and cervical cancer-related mortality is higher in rural women due to poorer utilization of preventive services and subsequent presentation at late stages of the disease. This cross-sectional study examined the relationship between prevalence of risk factors for cervical cancer and the degree of compliance with risk-appropriate screening guidelines for cervical cancer. Secondary data were analyzed for 614 women from Robeson County, NC, aged 40 and older, and of mainly rural and low socioeconomic status. High-risk status was determined by the presence of any of the following five risk factors: a history of more than two sexual partners, age at first sexual intercourse under 18 years, history of sexually transmitted disease, history of sexually transmitted disease in sexual partner(s), and smoking. Low-risk status was the absence of all factors. A high-risk participant was considered compliant if she had had at least three Pap smears in the 3 years prior to the interview, while a low-risk participant was considered compliant if she had had at least one Pap smear within the previous 3 years. Overall, 82% of the participants were at high risk for cervical cancer. However, only 41% of all participants were compliant with the risk-appropriate screening guidelines. Low-risk status was significantly associated with compliance with cervical cancer screening guidelines (adjusted OR = 6.7; 95% CI = 3.7 to 11.1, p = .0001). Findings in this study population suggest rural women at high risk for cervical cancer are less likely to be compliant with appropriate Pap smear screening guidelines, indicating the need to target educational programs.

22
UI - 11747241
AU - Freitas C; Milanezi F; Dias AJ; Bento MJ; Schmitt FC
TI - Use of cell block preparation for morphological, immunocytochemistry, and ploidy analysis in ThinPrep monolayer preparations.
SO - Diagn Cytopathol 2001 Dec;25(6):415-7

23
UI - 12116007
AU - Badaracco G; Venuti A; Sedati A; Marcante ML
TI - HPV16 and HPV18 in genital tumors: Significantly different levels of viral integration and correlation to tumor invasiveness.
SO - J Med Virol 2002 Aug;67(4):574-82
AD - Laboratory of Virology, Regina Elena Cancer Institute, Rome, Italy. badaracco@ifo.it
The integration of the high-risk HPV16 and HPV18 types into the cell genome is considered an important step in malignant transformation. The relationship between the physical status of the virus and clinical/pathological parameters was studied by type-specific and multiplex PCR for E6, E2, and E1 sequences in 86 genital tumors from different sites, consisting of 69 invasive carcinomas (including 5 microinvasive carcinomas), 9 carcinomas in situ, 6 severe dysplasias, and 2 moderate dysplasias. Forty tumors contained HPV16 (46.6%), 7 HPV18 (8.1%), and 39 both viruses (45.3%). HPV16 DNA was found either as pure integrant (35.4%), or pure episome (36.7%), or a mixture of both (27.8%). Conversely, all 46 lesions containing HPV18 showed pure integrated forms. The physical status of both types was not related to the tumor site, the tumor/node/metastasis stage, or the histological differentiation grade of the invasive carcinomas. HPV16 integration was significantly associated with invasiveness. Interestingly, in double infections when HPV16 coexisted with HPV18, its genome was found more frequently in episomal form than in single infections where, conversely, it was mostly integrated (P < 0.0001), suggesting a sort of competition for cell integration sites. The complete HPV18 integration, even in pre-neoplastic lesions, indicates a different behavior in genital transformation compared with HPV16 and may reflect a major aggressiveness of this viral type. In conclusion, virus typing in conjunction with the evaluation of the integration status may provide a better prognostic evaluation together with an improved diagnosis. Copyright 2002 Wiley-Liss, Inc.

24
UI - 11864690
AU - Suba EJ; Raab SS
TI - Cervical cancer screening by simple visual inspection after acetic acid.
SO - Obstet Gynecol 2002 Mar;99(3):517-8

25
UI - 12092058
AU - Persson E; Andrae B; Strander B
TI - [HPV testing--the effect must be evaluated prior to clinical use!]
SO - Lakartidningen 2002 May 30;99(22):2552
AD - elisabeth.persson@ks.se

26
UI - 12107839
AU - Sigstad E; Lie AK; Luostarinen T; Dillner J; Jellum E; Lehtinen M;
TI - Thoresen S; Abeler V A prospective study of the relationship between prediagnostic human papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas.
SO - Br J Cancer 2002 Jul 15;87(2):175-80
AD - Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway. eva.sigstad@labmed.uio.no
Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2-8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA.

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