National Cancer Institute®
Last Modified: May 1, 2002
UI - 11072200
AU - Linos A; Riza E; Ballegooijen M
TI - Introduction. Cervical cancer screening.
SO - Eur J Cancer 2000 Nov;36(17):2175-6
AD - Department of Hygiene and Epidemiology, University of Athens Medical School, 75 Mikras Asias St, GR 115 27 Goudi, Athens, Greece.
UI - 11914322
AU - Bayo S; Bosch FX; de Sanjose S; Munoz N; Combita AL; Coursaget P; Diaz
TI - M; Dolo A; van den Brule AJ; Meijer CJ Risk factors of invasive cervical cancer in Mali.
SO - Int J Epidemiol 2002 Feb;31(1):202-9
AD - Institut National de Recherche en Sante Publique, Bamako, Mali.
BACKGROUND: Cervical cancer is the most common cancer in women in Mali and the second commonest cause of cancer mortality. METHODS: As part of an international effort to evaluate the role of human papillomavirus (HPV) in the aetiology of cervical cancer, we conducted a hospital-based case-control study in three medical centres in Bamako during 1994-1995. A total of 82 cases (invasive cervical cancer patients) and 97 controls matched to the cases for age were included. Information on risk factors was collected through personal interview. Serum antibodies to HPV 16, 18 and 31 virus like particles (VLP) were detected using ELISA assays. Polymerase chain reaction was used to detect HPV DNA in frozen biopsies of cases. RESULTS: Human papillomavirus 6, 18, 31 VLP were detected in 60.4% of cases and 45.4% of controls (P = 0.03). Overall, HPV DNA was identified in 96.9% of the cervical cancer cases. Risk factors for cervical cancer were parity >10 versus <5 children ([odds ratio] OR = 4.8, 95% CI : 1.5-14.7), never having practised vaginal douching (OR = 17.6, 95% CI : 4.2-74.7), re-using home-made feminine napkins (OR = 45.9, 95% CI : 8.8-238.7) and having a husband with more than two wives (OR = 5.3, 95% CI : 1.3-21.3). CONCLUSIONS: These data provide further evidence on the role of HPV in cervical cancer and show that high parity and poor genital hygiene conditions were the main co-factors for cervical cancer in this population with prevalent HPV infection.
UI - 11865946
AU - Horn LC; Raptis G; Nenning H
TI - DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b.
SO - Anal Quant Cytol Histol 2002 Feb;24(1):23-9
AD - Institute of Pathology, Leipzig University, Germany. firstname.lastname@example.org
OBJECTIVE: To determine the utility of DNA content and DNA-related variables of proliferative activity regarding prognosis in cervical cancer. STUDY DESIGN: DNA image (ICM) andflow cytometry (FCM) were performed to determine the DNA index (DI), 5c-exceeding rate (5c-ER), S-phase fraction (SPF) and proliferation index (PI) in 163 patients with surgically staged pT1b1-pT2b squamous cell cancer of the uterine cervix and treated with primary radical hysterectomy. ICM was performed on imprint cytology, obtained from fresh tumor tissue, which was also used for FCM. Results were analyzed using the chi2 test and Cox regression analysis for risk of pelvic lymph node involvement, tumor recurrence and recurrence-free survival (RFS). RESULTS: ICM was performed on all 163 and FCM on 133 samples. One-third of the tumors showed DNA aneuploidy. Analysis demonstrated prognostic significance of a DI > or = 1.70, with a (70:30) 2.3-fold risk of recurrence (P=.024) and reduced RFS of 10 months (P=.003) in cases of DI > or = 1.70. A high 5c-ER > 11% was associated with pelvic lymph node involvement and decreased RFS (P < or = .04). Significantly more relapses were found in tumors with SPF > 12% (70.8% vs. 29.2%, P=.007). RFS was markedly reduced in tumors with high SPF (52.3 vs. 61.1 months, P=.011). Low proliferative tumors (PI<25%) were associated with lower stage (P=.036) and increased RFS (61.2 vs. 47.1 months, P=.028). In multivariate analysis of clinicopathologic variables (pT category, nodal status, lymphovascular space involvement) and DNA related variables, pelvic lymph node involvement was the only significant predictor of RFS. In patients with nodal involvement, tumors with DI >1.70 were associated with lessfavorable outcomes. CONCLUSION: DNA-related variables of cell cycle analysis were valuablefor predicting prognosis in cervical cancer patients. Tumors with DI>1.70, 5c-ER >11% and high proliferative activity (SPF>12%, PI>25%) represent a subgroup with a poor prognosis.
UI - 11883300
AU - Panek G; Bidzinski M
TI - [Adenocarcinoma of the cervix--stage IB: results of treatment and prognostic factors]
SO - Ginekol Pol 2001 Dec;72(12A):1478-84
AD - Kliniki Nowotworow Narzadow Plciowych Kobiecych Centrum Onkologii-Instytutu w Warszawie.
The study presents the results of treatment of 63 women with stage IB adenocarcinoma of the cervix. The treatment consist of radical Wertheim-Meigs hysterectomy with adjuvant brachytherapy or external beam irradiation. A statistical analysis with Kaplan-Meier and cox model was conducted to assess the influence of selected prognostic factors on survival. After 5-year long follow-up 73.4% of patients were alive without recurrence. The results of univariate analysis showed that metastatic pelvic nodes, cervical tumor size of more than 4 cm and the presence of microscopic parametrial infiltration had a statistically significant negative influence on survival. In a multivariate analysis tumor size of more than 4 cm and microscopic parametrial involvement had an independent negative impact on survival (relative risk of death--12.1 and 15.7).
UI - 11883303
AU - Kwasniewska A; Skoczynski M; Semczuk-Sikora A; Gozdzicka-Jozefiak A
TI - [PCR and Digene Hybride Capture System I in identification of human papillomavirus]
SO - Ginekol Pol 2001 Dec;72(12A):1497-500
AD - I Katedry i Kliniki Poloznictwa i Patologii Ciazy AM w Lublinie.
We have analyzed and compared two different systems used in identification of DNA HPV. 100 samples obtained from patients with I degree and II degree Papanicolaou smears and 200 from patients with cervical intraepithelial neoplasia were analyzed. The obtained data indicate higher sensitivity of the PCR method compared to Digene Hybride Capture System.
UI - 11925135
AU - Yuan CC; Wang PH; Ng HT; Li YF; Huang TS; Chen CY; Tsai LC; Shyong WY
TI - Detecting cytokeratin 19 mRNA in the peripheral blood cells of cervical cancer patients and its clinical-pathological correlation.
SO - Gynecol Oncol 2002 Apr;85(1):148-53
AD - Department of Obstetrics & Gynecology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 112, Taiwan. email@example.com
OBJECTIVE: The aim of this study was to study the presence of cytokeratin 19 (CK19)-expressing cancer cells in the blood of preoperative patients with FIGO stage Ib and IIb cervical cancers who received radical hysterectomy and to investigate the cells' clinical significance. METHODS: CK19 mRNA in the blood cells of the patients was detected preoperatively by a newly designed nested reverse transcriptase-polymerase chain reaction, which excluded pseudogenes a and b, performed on 84 patients with stage Ib and IIb cervical carcinoma. Possible correlations between clinicopathological factors were then analyzed. RESULTS: The sensitivity of this assay was 1 CK19-mRNA-positive cell per 10(6) peripheral blood mononuclear cells. Results showed that 21.4% of the 84 patients with cervical carcinoma had CK19-mRNA-positive cells in the blood, in comparison with 5.7% of the 35 patients with benign gynecological tumors and 0% of the 28 healthy controls (P = 0.037 and 0.006, respectively). The positive tests in the cervical cancer patients were not associated with prognostic factors including stage, pelvic lymph node metastasis, pathological types, bulky tumor size (> or =4 cm), differentiation, parametrial extension, lymphovascular space involvement, deep stromal invasion, or age. CONCLUSIONS: This study revealed the presence of circulating CK19-expressing cancer cells in the blood of patients with untreated early-stage cervical carcinomas, indicating that cervical cancer disseminated early. The survival effect of this phenomenon must be clarified. This detection assay provides an early checkpoint in the multistep process for developing metastasis in cervical cancer patients.
UI - 11925139
AU - Neviliappan S; Fang Kan L; Tiang Lee Walter T; Arulkumaran S; Wong PT
TI - Infrared spectral features of exfoliated cervical cells, cervical adenocarcinoma tissue, and an adenocarcinoma cell line (SiSo).
SO - Gynecol Oncol 2002 Apr;85(1):170-4
AD - Department of Obstetrics and Gynaecology, National University of Singapore, Singapore.
OBJECTIVE: The objective of the present study is to evaluate and compare the infrared spectral features of normal and malignant exfoliated cervical cells, cells from malignant tissue, and the SiSo cell line. METHODS: Infrared spectra of cervical adenocarcinoma (CA) tissue, normal and malignant exfoliated cervical cells, and a uterine cervical adenocarcinoma cell line (SiSo) were obtained. Spectral qualities in terms of band intensity ratio and band position, which reflect configurational changes in the functional groups of the above samples, were measured. RESULTS: Spectral bands of CA tissue, exfoliated cells from CA, and the cell line were similar but markedly different from that of exfoliated normal cervical cells. Significant changes in bands at 1025 cm(-1) (glycogen), 1080 cm(-1) (glycogen and nucleic acids), 1155 cm(-1) (C-OH groups of serine, threonine, and tyrosine of cell proteins, and C-O groups of carbohydrates), 1240 cm(-1) (PO(2) groups of nucleic acids), 1400 cm(-1) (methyl group of lipids and proteins), and 1450 cm(-1) (methylene group of lipids and proteins) were noted in the CA tissue, exfoliated CA cells, and adenocarcinoma cell line compared with exfoliated normal cells. Marked shifts in band positions from 1080 to 1086 cm(-1), 1153 to 1160 cm(-1), and 935 to 970 cm(-1) in CA tissue, exfoliated CA cells, and the adenocarcinoma cell line were noted. CONCLUSION: Spectral bands of the adenocarcinoma cell line matched very well with those of cervical CA tissue and exfoliated CA cells in terms of position. In contrast, spectral bands of the SiSo cell line differed greatly from those of normal exfoliated cells.
UI - 11925126
AU - Simonart T; Boelaert JR; Mosselmans R; Andrei G; Noel JC; De Clercq E;
TI - Snoeck R Antiproliferative and apoptotic effects of iron chelators on human cervical carcinoma cells.
SO - Gynecol Oncol 2002 Apr;85(1):95-102
AD - Department of Dermatology, Erasme University Hospital, Brussels, B-1070, Belgium. firstname.lastname@example.org
OBJECTIVE: Cervical carcinoma is a human papillomavirus (HPV)-associated cancer for which treatment options still mainly rely on surgical procedures, with or without adjuvant radiotherapy and chemotherapy. As iron may participate in the pathogenesis of viral infections and cancer in several ways, the present study was designed to investigate the effect of iron chelation on HPV-16- and HPV-18-positive cervical carcinoma cell lines. METHODS: Desferrioxamine and deferiprone, two chemically unrelated iron chelators, were used to investigate the effect of iron chelation on SiHa and HeLa cells. Proliferation was investigated by cells counts, by [(3)H]thymidine uptake assay, and by immunostaining with Ki-67 and proliferating cell nuclear antigen (PCNA). Apoptosis was determined by morphological analysis, by a TUNEL assay, and by flow cytometry detecting FITC-conjugated annexin-V. RESULTS: Desferrioxamine and deferiprone induced a time- and dose-dependent inhibition of SiHa and HeLa cell growth. The inhibition of cell growth was associated with a decrease in the expression of both stable and total PCNA and Ki-67, a proliferation marker whose expression may predict survival in uterine cervical carcinoma. TUNEL assay, flow cytometry with annexin-V-fluorescein, and morphological analysis indicated that iron chelation also induced a time- and dose-dependent apoptosis of both cell lines. This apoptotic effect was prevented by the addition of exogenous iron. CONCLUSION: These results show that iron chelation inhibits the growth and induces the apoptosis of HPV-positive carcinoma cells. This suggests that iron chelators may represent a potential therapeutic approach for the management of cervical carcinoma.
UI - 11873311
AU - Hamm B; Pollinger A
TI - [Cross-sectional imaging of endometrial carcinoma: MR imaging and CT]
SO - Zentralbl Gynakol 2002 Jan;124(1):27-31
AD - Institut fur Radiologie, Charite, Medizinische Fakultat der Humboldt-Universitat zu Berlin, Germany. email@example.com
Magnetic resonance (MR) imaging has superseded computed tomography (CT) in the diagnostic assessment of cancer of the uterus (endometrial and cervical carcinoma). Contrast-enhanced MR imaging is highly accurate in staging endometrial carcinoma, in particular in terms of the depth of myometrial invasion. MR imaging will in the future provide a good basis for preoperative therapeutic decision making, especially to answer the question whether or not lymphadenectomy is necessary based on myometrial infiltration depth. - This article outlines the potential of MR imaging for staging endometrial cancer, provides a brief description of the imaging strategies, and discusses the role of MR imaging in the diagnostic assessment of endometrial cancer.
UI - 11904459
AU - Dai H; Holm R; Kristensen GB; Abeler VM; Borresen-Dale AL; Helland A
TI - Fibroblast growth factor receptor 3 (FGFR3) - analyses of the S249C mutation and protein expression in primary cervical carcinomas.
SO - Anal Cell Pathol 2001;23(2):45-9
AD - Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 0slo, Norway.
Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant.This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.
UI - 11906986
AU - Mauad EC; Gomes UA; Nogueira JL; Melani AG; Lemos DL; Hidalgo GS
TI - Prevention of cervical cancer in a poor population in Brazil.
SO - Fam Pract 2002 Apr;19(2):189-92
AD - Department of Clinical Oncology, Fundacao Pio XII, Barretos and Faculdade de Medicina de Ribeirao Preto (USP), Ribeirao Preto, Sao Paulo, Brazil.
OBJECTIVE: The purpose of this study was to determine the possibility of providing a cervical screening facility to a poor population. METHODS: A Paulo and three other neighbouring cities. Performed by a nurse, the programme included door-to-door interviews and cervical screening. The Papanicolaou smears were taken either at the community centre or at home using a portable gynaecological table transportable by bicycle, developed by the Institution. RESULTS: From 1384 interviewed women, 1044 (75.4%) agreed to undergo the examination and 499 (47.8%) had never had the test or had not had it repeated within the last 3 years. Among 1044 examined women, seven cases of carcinoma 'in situ', one invasive squamous cell carcinoma (stage IB) and two polyps were found. CONCLUSIONS: This study shows that programmes of cancer prevention in poor populations can be as successful as those carried out in more developed countries by taking advantage of innovations in the delivery of care.
UI - 11975858
AU - Saraiya M; Lee NC; Blackman D; Smith MJ; Morrow B; McKenna MT
TI - Observations from the CDC. An assessment of Pap smears and hysterectomies among women in the United States.
SO - J Womens Health Gend Based Med 2002 Mar;11(2):103-9
AD - Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, and The Klemm Analysis Group, Atlanta, Georgia 30341, USA.
UI - 11988058
AU - Mandelblatt JS; Lawrence WF; Womack SM; Jacobson D; Yi B; Hwang YT; Gold
TI - K; Barter J; Shah K Benefits and costs of using HPV testing to screen for cervical cancer.
SO - JAMA 2002 May 8;287(18):2372-81
AD - Lombardi Cancer Center, 2233 Wisconsin Ave NW, Suite 317, Washington, DC 20007. firstname.lastname@example.org
CONTEXT: Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal. OBJECTIVE: To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their combination to screen for cervical cancer. DESIGN, SETTING, AND POPULATION: A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death. MAIN OUTCOME MEASURE: Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy. RESULTS: Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of $76 183 per QALY compared with Pap testing alone every 2 years. Stopping biennial screening with HPV and Pap testing at age 75 years captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test. CONCLUSIONS: Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.
UI - 11988059
AU - Kim JJ; Wright TC; Goldie SJ
TI - Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance.
SO - JAMA 2002 May 8;287(18):2382-90
AD - Department of Health Policy and Management, Harvard Center for Risk Analysis, 718 Huntington Ave, Second Floor, Boston, MA 02115, USA.
CONTEXT: Every year approximately 2 million US women are diagnosed as having a cervical cytological result of atypical squamous cells of undetermined significance (ASC-US). OBJECTIVE: To determine the most efficient and cost-effective management strategy for women in the United States diagnosed as having ASC-US. DESIGN AND SETTING: Cost-effectiveness analysis of data from clinical trials, prospective studies, and other published literature. A computer-based model was used to compare 4 management strategies for a cytological result of ASC-US: immediate colposcopy; human papillomavirus (HPV) triage, which includes colposcopy if high-risk HPV types are detected; repeat cytology, which includes follow-up cytology at 6 and 12 months and referral for colposcopy if a repeat abnormal result occurs; and reclassifying ASC-US as normal in which a cytological result of ASC-US is ignored. Reflex HPV DNA testing uses either residual liquid-based cytological specimens or samples co-collected at the time of the initial screening for conventional cytology. Another method, referred to as the 2-visit HPV DNA triage, requires a woman with an ASC-US result to return within 1 month to provide another speciman sample. MAIN OUTCOME MEASURES: Years of life saved (YLS), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: The least costly strategy for biennial screening was to reclassify ASC-US as normal, resulting in a reduction in total cancer incidence of 75% for conventional cytology and 84% for liquid-based cytology compared with no screening. The next least costly strategy was HPV DNA testing resulting in a reduction in total cancer incidence of 86% for conventional cytology and 90% for liquid-based cytology, followed by immediate colposcopy with a reduction of 87% and 91%, respectively. Compared with reflex HPV DNA testing, a strategy of repeat cervical cytology or delayed HPV testing costs more but is less effective. When all strategies were compared simultaneously, varying frequency and type of cytological test, biennial (vs every 3 years) liquid-based cytology with reflex HPV testing had a cost of $174 200 per YLS. In a similar comparison, liquid-based cytology with reflex HPV testing conducted every 3 years (vs every 5 years) had a cost of $59 600 per YLS and was more effective and less costly than a strategy of conventional cytology incorporating repeat cytology or immediate colposcopy conducted biennially. CONCLUSION: Reflex HPV DNA testing provides the same or greater life expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US.
UI - 11836622
AU - Sahu GR; Nayak BK; Patnaik S; Parija T; Das BR
TI - Rearrangement of p53 gene with overexpressed p53 protein in primary cervical cancer.
SO - Oncol Rep 2002 Mar-Apr;9(2):433-7
AD - Molecular Oncology and Medical Biotechnology Division, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar-751 023, Orissa, India.
The frequency of p53 mutations is low and there is evidence of p53 protein overexpression even without p53 mutations in cervical cancers. This suggests that alternative mechanisms other than p53 mutation could be responsible for tumourigenesis of the uterine cervix. Therefore, an attempt has been made in the present investigation to analyze mutation and rearrangement of p53 gene in primary cervical cancers. The results indicated absence of mutation and presence of rearrangement in about 35% of cervical cancer patients. However, p53 overexpression in 50% of patients was demonstrated by immunohistochemistry and Western blot analysis. Further, rearrangement of p53 has been correlated with p53 mRNA and p53 protein status. The results indicated presence of overexpressed p53 protein in the samples with rearranged p53 gene. Thus, it is presumed that rearrangement of p53 might lead to production of defective p53 protein by affecting the level of p53 protein and this might have a role in the process of tumourigenesis. This study reports for the first time rearrangement of p53 in cervical cancers.
UI - 11688467
AU - Morrison C; Catania F; Wakely P Jr; Nuovo GJ
TI - Highly differentiated keratinizing squamous cell cancer of the cervix: a rare, locally aggressive tumor not associated with human papillomavirus or squamous intraepithelial lesions.
SO - Am J Surg Pathol 2001 Oct;25(10):1310-5
AD - Department of Pathology, Ohio State University Medical Center, Columbus 43210, USA.
The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening.
UI - 11979099
AU - Rubinstein E
TI - Highly differentiated keratinizing squamous cell cancer of the cervix.
SO - Am J Surg Pathol 2002 May;26(5):676; discussion 676
UI - 11509878
AU - Gissmann L; Osen W; Muller M; Jochmus I
TI - Therapeutic vaccines for human papillomaviruses.
SO - Intervirology 2001;44(2-3):167-75
AD - DeutschesKrebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Heidelberg, Deutschland. L.Gissmann@dkfz.de
Although papillomavirus infections are not very immunogenic there is evidence that the immune system controls the spread of virus and the development of diseases associated with such infections. Certain types of human papillomaviruses (HPV) are the major cause of premalignant and malignant diseases of the anogenital tract, most notably cancer of the uterine cervix, a major health care problem worldwide. Since the viral oncoproteins E6 and E7 are constitutively expressed within the tumor cells, they are considered as suitable targets for attack by T lymphocytes. Several approaches to specifically trigger a cell-mediated immune response have been successful in experimental animals, leading to suppression of HPV-induced tumors. First clinical trials have been completed which raise hopes that a similar effect can also be achieved by therapeutic vaccination of humans. Copyright 2001 S. Karger AG, Basel
UI - 11767957
AU - Hemminki K; Li X; Mutanen P
TI - Age-incidence relationships and time trends in cervical cancer in Sweden.
SO - Eur J Epidemiol 2001;17(4):323-8
AD - Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden. email@example.com
Age-incidence relationships are informative of carcinogenic mechanisms. These have been previously assessed for cervical squamous cell carcinoma (SCC) but not for adenocarcinoma. The aim was to assess by means of age-, period- and cohort-specific analyses and Poisson regression modelling whether the two types of cervical cancer show an age-incidence maximum at a relatively young age, as shown in cross-sectional analyses. The Swedish Family-Cancer Database was used to analyse age-incidence relationships in cervical SCC and adenocarcinoma diagnosed in years 1958-1996, including a total of 15,118 and 1866 cases, respectively. Area of residence and socio-economic status were included in analyses because they were risk factors of cervical cancer. The analysis of cervical SCC confirmed an incidence maximum at ages 35-39 years. The data for adenocarcinoma also suggested a similar early age maximum but the curves differed extensively by birth cohort. The incidence of adenocarcinoma increased substantially at young age groups towards the end of follow-up. Endometrial adenocarcinoma and vaginal and vulvar SCC, which share some risk factors with cervical cancer, did not show an early age incidence maximum. The results also showed that there was a decrease in the incidence of cervical SCC around year 1960, almost 10 years before the organized population screening, probably due to introduced opportunistic pap testing. The benefits of the organized screening were observed as a further decline in the incidence rates. The unique age-incidence relationships in cervical cancer call for biological explanations.
UI - 11880111
AU - Yamaguchi A; Hashimoto N; Tsutae W; Seino K; Ebina Y; Tokino T; Sato N;
TI - Kikuchi K Detection of human papillomavirus DNA by PCR/microfluorometry for screening of cervical cancer.
SO - Clin Chim Acta 2002 Apr;318(1-2):41-9
AD - Sapporo Immunodiagnostic Laboratory, Shinkawa 2-2-12-20, Kita-ku, Sapporo 001-0922, Japan.
BACKGROUND: Cervical cancer screening is conducted by a cytological Papanicolaou (Pap) test. For screening, it is becoming increasingly important to introduce a more objective result, based on human papillomavirus (HPV) DNA test. We describe here a practical method allowing the mass detection of HPV-DNA by PCR followed by fluorogenic DNA intercalation. METHODS: Samples used were cervical scrapes or biopsy specimens obtained from women who had undergone cytological testing for cervical cancer. Crude DNAs were extracted by a simplified proteinase K-boil method. Common and type-specific primers were newly designed for major types of high-risk HPVs. A fluorogenic DNA intercalator, SYBR Green I was directly added to the specific PCR products. The resultant fluorescence was measured by a conventional fluorometric microplate reader. RESULTS: The proposed PCR/microfluorometry (MFL) allowed a simple, rapid and economical detection of HPV-DNA without any use of labeling primers or probes. HPV-DNAs were found in 48.2% (123/255) of the cervical scrapes. The detection rate of HPV in cervical cancer biopsy specimen was 92.4% (61/66). CONCLUSIONS: PCR/MFL detection of HPV-DNA, followed by combined type-specific PCR, is expected to be an extremely useful tool in cervical cancer screening.
UI - 11892025
AU - Selvaggi SM
TI - Cytologic features of high-grade squamous intraepithelial lesions involving endocervical glands on ThinPrep cytology.
SO - Diagn Cytopathol 2002 Mar;26(3):181-5
AD - Department of Pathology, Loyola University Medical Center, Maywood, Illinois, USA. firstname.lastname@example.org
Usage of liquid-based cytology has resulted in better cellular preservation with enhancement of nuclear features. The purpose of this evaluate the cellular features of endocervical gland involvement by a high-grade squamous intraepithelial lesion (HSIL) vs. endocervical adenocarcinoma in situ (AIS) on cell samples processed by the ThinPrep method as compared to conventional smears. Of the 97 cases of CIN III diagnosed on cytology, 52 (54%) showed surface endocervical gland involvement by CIN III and form the basis of this study. There were also six cases of endocervical AIS diagnosed on histology with prior cytology. The architectural features of HSIL involving endocervical glands and AIS were similar to those previously reported on conventional smears. A consistent finding of HSIL involving endocervical glands was the loss of central cell polarity and piling within cell groups, a finding not present in AIS. Central cell polarity was maintained in cellular groupings of AIS. In addition to the cellular feature present on conventional smears, micronucleoli were clearly visualized in cells of HSIL involving endocervical glands and prominent nucleoli were present in AIS. Apoptosis and mitoses were clearly visualized in both entities. Endocervical gland involvement by HSIL has characteristic cell patterns and features on liquid-based/thin-layer cytology that permit their distinction from AIS. Copyright 2002 Wiley-Liss, Inc.
UI - 11892026
AU - Nasuti JF; Fleisher SR; Gupta PK
TI - Atypical glandular cells of undetermined significance (AGUS): clinical considerations and cytohistologic correlation.
SO - Diagn Cytopathol 2002 Mar;26(3):186-90
AD - University of Pennsylvania Medical Center, Department of Pathology and Laboratory Medicine, Cytopathology and Cytometry Section, 3400 Spruce Street/6 Founders Pavilion, Philadelphia, PA 19104, USA. email@example.com
The diagnoses of atypical glandular cells of undetermined significance (AGUS) made upon evaluation of cervical/vaginal (Pap) smears is examined to ascertain salient clinical and cytologic features that may lead to better characterization of the true nature of these lesions. Prior history of squamous dysplasia, age of the patient, and the occurrence of abnormal microbiopsy tissue fragments are investigated to determine their value in the proper evaluation of AGUS specimens. Of the 86,234 Pap smears submitted to our laboratory during a period of 2 yr, 187 (0.2%) were diagnosed as AGUS. Available follow-up in 128 (69%) cases revealed 54 (42%) significant tissue proven abnormalities, the majority (55%, 30 patients) of which were diagnosed as squamous intraepithelial lesions (SIL). Squamous dysplasia is significantly more common in women younger than 40 (15/18, 83%) and in patients with prior history of SIL (29/30, 97%). In addition, all nine patients diagnosed with endometrial lesions on subsequent histology were older than 40. Age, however, was not a discriminating factor in women proven to have endocervical glandular lesions. Additionally, certain tissue fragment cytomorphologic features were significantly more often observed on follow-up in specific histologic diagnostic categories. The Pap smears of patients diagnosed with SIL were noted to contain tissue fragments composed of both dysplastic squamous and benign glandular cells in 29 of 30 (97%). The presence of two distinct populations of glandular tissue fragments (typical and atypical) was found in the Pap smears of all nine women with endometrial abnormalities and in the smears of most women subsequently diagnosed with endocervical glandular lesions (87%, 13/15). These observations suggest that a more specific and clinically useful Pap smear interpretation other than AGUS is often possible by consideration of the patient's age and prior history along with the correct identification of the type of atypical cells observed in abnormal tissue fragments. Copyright 2002 Wiley-Liss, Inc.
UI - 11983755
AU - Taylor VM; Hislop TG; Jackson JC; Tu SP; Yasui Y; Schwartz SM; Teh C;
TI - Kuniyuki A; Acorda E; Marchand A; Thompson B A randomized controlled trial of interventions to promote cervical cancer screening among Chinese women in North America.
SO - J Natl Cancer Inst 2002 May 1;94(9):670-7
AD - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98105, USA. firstname.lastname@example.org
BACKGROUND: North American Chinese women have lower levels of Papanicolaou (Pap) testing than other population subgroups. We conducted a randomized controlled trial to evaluate the effectiveness of two alternative cervical cancer screening interventions for Chinese women living in North America. METHODS: Four hundred and eighty-two Pap testing underutilizers were identified from community-based surveys of Chinese women conducted in Seattle, Washington, and Vancouver, British Columbia. These women were randomly assigned to one of two experimental arms or control status. Several Chinese-language materials were used in both experimental arms: an education-entertainment video, a motivational pamphlet, an educational brochure, and a fact sheet. Women in the first experimental group (outreach worker intervention) received the materials, as well as tailored counseling and logistic assistance, during home visits by trilingual, bicultural outreach workers. Those in the second experimental group (direct mail intervention) received the materials by mail. The control group received usual care. Follow-up surveys were completed 6 months after randomization to ascertain participants' Pap testing behavior. All statistical tests were two-sided. RESULTS: A total of 402 women responded to the follow-up survey (83% response rate). Of these women, 50 (39%) of the 129 women in the outreach group, 35 (25%) of the 139 women in the direct mail group, and 20 (15%) of the 134 women in the control group reported Pap testing in the interval between randomization and follow-up data collection (P<.001 for outreach worker versus control, P =.03 for direct mail versus control, and P =.02 for outreach worker versus direct mail). Intervention effects were greater in Vancouver than in Seattle. CONCLUSION: Culturally and linguistically appropriate interventions may improve Pap testing levels among Chinese women in North America.
UI - 11954023
AU - Chhieng DC; Talley LI; Roberson J; Gatscha RM; Jhala NC; Elgert PA
TI - Interobserver variability: comparison between liquid-based and conventional preparations in gynecologic cytology.
SO - Cancer 2002 Apr 25;96(2):67-73
AD - Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35249-6823, USA. email@example.com
BACKGROUND: Studies have shown that the ThinPrep Papanicolaou test (TP) increases the detection of epithelial cell abnormalities compared with the conventional preparation. Little is known about the interobserver variability of reporting gynecologic cytology results using the TP preparation and its comparison with results obtained using the conventional method. METHODS: To compare the interobserver variability between the TP method and the conventional method for reporting the diagnoses of gynecologic cytology, 20 pairs of conventional and TP slides (total, 40 slides) that were prepared from split samples were evaluated blindly by 19 cytotechnologists from three different laboratories. Each reviewer was asked to categorize each slide into the following five categories: within normal limits, benign cellular changes, atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). For both conventional and TP preparations, interobserver variability was analyzed using Spearman rank correlation coefficients. The mean correlation coefficients (weak, 0.0-0.4; fair, 0.4-0.7; and strong, 0.7-1.0) between the TP method and the conventional method were then compared. RESULTS: The overall interobserver agreement as well as interobserver agreement within each laboratory was good for both TP and conventional preparations. Based on the set of conventional cervical smears, only one slide that was diagnosed as HSIL had unanimous agreement; whereas, based on the set of TP slides, three slides, including two diagnosed as HSIL and one diagnosed as LSIL, had a unanimous diagnosis. The difference in the interobserver agreement between TP and conventional methods, based on comparing their mean +/- standard deviation correlation coefficients (TP method, 0.84 +/- 0.081; conventional method, 0.82 +/- 0.105; P < 0.001), was statistically significant. CONCLUSIONS: Interobserver agreement in reporting gynecologic cytology using the TP method is good, particularly for squamous intraepithelial lesions, and appears to be superior to the conventional method. Copyright 2002 American Cancer Society.
UI - 11996166
AU - Llewellyn H
TI - Observer variation, dysplasia grading, and HPV typing: a review.
SO - Am J Clin Pathol 2000 Nov;114 Suppl():S21-35
AD - Victorian Cytology Services Inc, Australia.
Squamous dysplasia of the cervix is a morphologic continuum that is divided into a number of categories. When the severity of a morphologic abnormality is assessed, whether in a biopsy sample or in an exfoliative smear, there can be significant observer variation. The statistical quantification of this variation, with particular reference to the kappa statistic and the influence of the number of categories utilized on the kappa statistic, is discussed. The contribution of information theory to the understanding of the reasons for observer variation is explored. The use of a binary (Bethesda) system of classification of squamous dysplasia and its validation by comparing consensus diagnoses with human papilloma virus type both in biopsy samples and in smears is reviewed.
UI - 11996167
AU - Demay RM
TI - Hyperchromatic crowded groups: pitfalls in pap smear diagnosis.
SO - Am J Clin Pathol 2000 Nov;114 Suppl():S36-43
AD - Department of Pathology, Cytopathology Section, University of Chicago, IL 60637, USA.
A problem in the diagnosis of Papanicolaou smears--the interpretation of "hyperchromatic crowded groups" (HCGs)--is identified and analyzed. HCGs usually represent benign entities such as endometrial cells, syncytial aggregates in severe atrophy, or fragments of endocervical tissue, the latter being seen with increasing frequency due to the use of the endocervical brush. Tubal metaplasia is another common, benign source of HCGs. However, occasionally HCGs represent serious lesions, such as carcinoma in situ, invasive squamous cell carcinoma, and glandular neoplasia, either in situ or invasive. The distinction among these various entities is not always easy, but guidelines are presented.
UI - 11996168
AU - Rotmensch J
TI - Controversies associated with cervical cytologic screening: a physician's view.
SO - Am J Clin Pathol 2000 Nov;114 Suppl():S44-7
AD - Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, IL 60637, USA.
UI - 11996169
AU - DeMay RM
TI - Should we abandon pap smear testing?
SO - Am J Clin Pathol 2000 Nov;114 Suppl():S48-51
AD - Department of Pathology, Cytopathology Section, University of Chicago, IL 60637, USA.
UI - 11996170
AU - McCoy DR
TI - Defending the pap smear: a proactive approach to the litigation threat in gynecologic cytology.
SO - Am J Clin Pathol 2000 Nov;114 Suppl():S52-8
AD - Saperston & Day, Buffalo, NY 14203, USA.
UI - 11890589
AU - Sawaya GF; Sung HY; Kearney KA; Miller M; Kinney W; Hiatt RA;
TI - Mandelblatt J Advancing age and cervical cancer screening and prognosis.
SO - J Am Geriatr Soc 2001 Nov;49(11):1499-504
AD - Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 94143, USA.
OBJECTIVES: To determine associations between advancing age and screening behavior and prognosis in long-term members of a prepaid health plan diagnosed with invasive cervical cancer (ICC). DESIGN: Case series. SETTING: Prepaid health plan. PARTICIPANTS: All women diagnosed with ICC at Kaiser Permanente Medical Care Program-Northern California health plan from 1988 to 1994. MEASUREMENTS: From medical records, we recorded participants' age, stage at diagnosis, tumor histology, and results of and reasons for all previous cervical smears. We limited our analysis to women who had been members of the health plan for at least 30 of the 36 months preceding diagnosis (n = 455). RESULTS: Women in older age groups were less likely than younger women to have been screened within the 3 years before diagnosis (P = .005 for trend). Nonadherence to follow-up of abnormal cervical smears was uncommon (17/455, 3.7%) and not age related (P = .932 for trend). The proportions of ICC that were interval cancers, defined as ICC diagnosed within 3 years of a negative screening smear, were highest in women under age 30 (P = .004 for trend). In multivariate analyses controlling for stage at diagnosis, women age 60 and older were not more likely to die of ICC within 3 years of diagnosis than were women younger than age 60 (odds ratio 1.30, 95% confidence interval 0.75-2.28). CONCLUSION: The disproportionate burden of cervical cancer observed in older women appears to be largely attributable to lack of screening within the 3 years before diagnosis.
UI - 11742605
AU - Sulik SM; Kroeger K; Schultz JK; Brown JL; Becker LA; Grant WD
TI - Are fluid-based cytologies superior to the conventional Papanicolaou test? A systematic review.
SO - J Fam Pract 2001 Dec;50(12):1040-6
AD - Department of Family Medicine, State University of New York Upstate