National Cancer Institute®
Last Modified: February 1, 2002
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
UI - 11753880
AU - Shirata NK; Gomes NS; Garcia EA; Longatto Filho A
TI - Nuclear DNA content analysis by static cytometry in cervical intraepithelial lesions using retrospective series of previously stained PAP smears.
SO - Adv Clin Path 2001 Jul;5(3):87-91
AD - Istituto Adolfo Lutz, Divisione di Patologia, Avenida Dr. Arnaldo, 355 - Cerqueira Cezar. 01246-902, San Paulo, SP, Brasile.
AIMS: To evaluate the nuclear DNA content in cytological smears of uterine cervix previously stained with Papanicolaou method, focusing the potential of the method in retrospective series. METHODS: Consecutive cases of Pap smears examined at the Adolfo Lutz Institute, a Public Health Laboratory of Sao Paulo State were selected. The diagnosis were: CIN 1 (n=20), CIN 2 (n=24), CIN 3 (n=20). Slides were previously stained with Papanicolaou method. The stain was removed with 5% hydrochloric alcohol-acid solution and the slides were stained with Thionin-Feulgen using a Becton & Dickinson kit. Ploidy evaluation was performed using the DNA Quantitative Measurement software 3.0 (version 8.1) from Becton & Dickinson and the CAS 200 system of image analysis. Cell ploidy was evaluated after analysis of atypical nuclei found in the selected cases. The DNA index was obtained using histograms for interpretation. MAIN RESULTS: CIN 1 cases showed the following DNA profile: 55% of diploid, 5% of tetraploid and 40% of aneuploid. CIN 2 cases showed 45.8% of diploid, 8.3% of tetraploid and 45.8% of aneuploid cells. CIN 3 cases showed 10% diploid, 15% of tetraploid and 75% of aneuploid cells. CONCLUSION: DNA analysis was useful to distinguish CIN 3 to CIN 1 and 2, but did not discriminate CIN 1 and 2 in these series. Aneuploidy was strongly associated to the CIN 3 cases.
UI - 11584480
AU - Morin C; Bairati I; Bouchard C; Fortier M; Roy M; Moore L; Meisels A
TI - Managing atypical squamous cells of undetermined significance in Papanicolaou smears.
SO - J Reprod Med 2001 Sep;46(9):799-805
AD - Departments of Pathology, Social and Preventive Medicine, and of Gynecology and Obstetrics, Laval University, Quebec, Canada. email@example.com
OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.
UI - 11769697
AU - Zhao F; Li N; Ma J
TI - [Study of the association between human papillomavirus infection and cervical cancer in Xianguan county, Shanxi province]
SO - Zhonghua Liu Xing Bing Xue Za Zhi 2001 Oct;22(5):375-8
AD - Department of Epidemiology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China.
OBJECTIVE: To investigate human papillomavirus (HPV) prevalence in the high incidence areas of cervical cancer in Shanxi and to study the association between HPV infection and cervical cancer. METHODS: Cells exfoliated from cervix (collected by clinician) and from vagina (collected by subject herself) of 1997 women aged 35-45 from Xiangyuan county, Shanxi province were analyzed blindly by Hybrid Capture Assay (HC-II), which could detect 13 HPV types of high-risk. Unconditional logistics regression model was used to analyze the relation between HPV and cervical cancer/cervical intraepithelial neoplasia (CIN). Kappa coefficient was used to compare the agreement of the two tests. RESULTS: HPV DNA detection rate in the population was 20.8% while HPV infection rates increased with the seriousness of cervical lesions (chi 2 = 444.04, P = 0.000). Rates of the two groups (35-39 and 40-45) had no significant difference (20.9%: 20.6%, chi 2 = 0.03, P = 0.86). Unconditional logistic regression analysis showed, when comparing with the normal subjects, the risk odds ratio of HPV infection with cervical cancer/high grade CIN and low grade CIN were 254.2 and 26.4 respectively, with attributable risk proportions (ARP) 98.1% and 83.6% respectively. The sensitivity of self-collected vaginal swabs assayed for HPV DNA was lower than that of clinician-collected cervical samples assayed for HPV DNA (84%: 98%, chi 2 = 5.92, P = 0.015). No significant difference in specificity was seen between them (86%: 85%, chi 2 = 0.00, P = 0.997) and there was fair agreement between the two tests (kappa = 0.74). CONCLUSION: High-risk HPV infection in female genital tract was the major risk factor of cervical cancer and CIN in the areas. Prevention and control of cervical cancer should be focused on avoiding HPV infection, screening women for HPV infection and monitoring population infected by high-risk HPV. Self-collected vaginal swabs assayed for HPV DNA seemed a more practical method in primary screening for cervical cancer.
UI - 11775218
AU - Deng Y; Lin C; Zheng J; Fu M; Liang X; Chen J; Xiao P; Wu M
TI - Overexpression of Bcl-2 partly inhibits apoptosis of human cervical cancer SiHa cells induced by arsenic trioxide.
SO - Chin Med J (Engl) 2000 Jan;113(1):84-8
AD - Institute of Medicinal Plants, CAMS & PUMC, Beijing 100094, China.
OBJECTIVE: To study the biological effect of arsenic trioxide (As2O3) on human cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. METHODS: SiHa cells with overexpression of Bcl-2 (SiHa-Bcl2 cells) were established by transfecting SiHa cells with Bcl-2 expression vector. The sensitivities of SiHa and SiHa-Bcl2 cells to As2O3 were determined using MTT (Thiazolyl blue) reduction and colony forming ability assay, morphological analysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ cell death detection (TUNEL), Northern blot, RT-PCR and Western blot. RESULTS: As2O3 inhibited the growth of SiHa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As2O3 induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that SiHa-Bcl2 cells partly resisted As2O3 induced apoptosis, which might be related to the prevention of the down-regulation of HPV16 E7 and c-myc gene expression. Nevertheless, As2O3 at a high concentration could still induce apoptosis of SiHa-Bcl2 cells mainly via decreasing Bcl-2 expression and slightly inhibiting viral gene expression. CONCLUSION: As2O3 is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing Bcl-2 can partly resist As2O3 induced apoptosis, but the exact mechanism is unclear.
UI - 10935311
AU - Ayoubi JM; Cayrol MH; Meddoun M; Benevent JB; Degoy J; Pons JC
TI - [Role of endocervical curettage in the screening for cervical cancer: apropos of a series of 31 cases]
SO - Gynecol Obstet Fertil 2000 Jun;28(6):455-9
AD - Departement de gynecologie-obstetrique, CHU de Grenoble, France.
We present a study of 31 cases of pathologic cervical smear with an inconclusive colposcopy. The aim of this study was to compare the results of the cervical smear, colposcopy, cervical biopsy, endocervical curettage and conization. The endocervical curettage is a valuable complement to the colposcopy, especially in the case of an inconclusive colposcopy.
UI - 11075508
AU - Morice P
TI - [In response to the article of Ayoubi JM, et al. Role of endocervical curettage in the diagnosis of cervical cancer: apropos of a series of 31 cases. Gynecol Obstet Fertil 2000;28:455-9]
SO - Gynecol Obstet Fertil 2000 Sep;28(9):691
UI - 11577533
AU - Wright VC
TI - When to suspect squamous cancer at colposcopy.
SO - Nurse Pract 2001 Sep;26(9):50-6, 59-61
AD - Department of Obstetrics and Gynaecology, University of Western Ontario, London, Ontario, Canada.
Advanced practice nurses are increasingly using colposcopy to investigate abnormal cervical cytology. Specific colposcopic features can lead the clinician to suspect squamous cancer. This article discusses vascular pattern study, examination evaluation, lesion grading, and correlating colposcopy with histology and cytology to aid in identifying squamous cancer.
UI - 11769670
AU - Wang M; Wang B; Wang X
TI - [A novel antiapoptosis gene, survivin, bcl-2, p53 expression in cervical carcinomas]
SO - Zhonghua Fu Chan Ke Za Zhi 2001 Sep;36(9):546-8
AD - Department of Oncology, First Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
OBJECTIVE: To study the expression of a novel inhibitor gene of apoptosis, survivin, in cervical carcinoma and its relationship with the expression of bcl-2, p53 genes. METHODS: Using streptavidin-biotin peroxidase (SP) method, we examined the expression of survivin, bcl-2 and p53 genes in 10 normal cervical tissues and 59 cervical carcinoma tissues. RESULTS: Survivin was expressed in 41 of 59 (69.5%) cases of cervical carcinomas. In contrast, normal cervical epithelium did not express survivin. Overexpression of survivin was related to the tumor grade and clinical stage. Survivin positive cases were strongly associated with bcl-2 expression (36/45, 80.0% versus 5 of 14 cases, P < 0.005) and p53 expression (33/43, 76.7% versus 8 of 16 cases, P < 0.05). CONCLUSIONS: Apoptosis inhibition by survivin, alone or in cooperation with bcl-2 and p53 may participate in the onset and progression of cervical carcinoma. Survivin could be a new diagnostic/therapeutic target in cervical cancer.
UI - 10644829
AU - van Duin M; Snijders PJ; Vossen MT; Klaassen E; Voorhorst F; Verheijen
TI - RH; Helmerhorst TJ; Meijer CJ; Walboomers JM Analysis of human papillomavirus type 16 E6 variants in relation to p53 codon 72 polymorphism genotypes in cervical carcinogenesis.
SO - J Gen Virol 2000 Feb;81(Pt 2):317-25
AD - Department of Pathology, University Hospital Vrije Universiteit, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
This study aimed to assess the role of specific human papillomavirus type 16 (HPV-16) variants, in combination with p53 codon 72 polymorphism genotypes, in cervical carcinogenesis. An initial sequence analysis of HPV-16 long control, E6 and E7 regions of 53 well-defined cervical samples containing HPV-16 revealed that a T to G transition at nucleotide position 350 within the E6 open reading frame was the most common variation, the frequency of which seemed to decrease with increasing severity of the lesion. Therefore, a total of 246 cervical samples of residents of The Netherlands was specifically analysed for HPV-16 350G/T variants and/or p53 codon 72 genotypes. These comprised HPV-negative normal cervical scrapes (n=40), normal cervical scrapes containing HPV-16 (n=46), scrapes containing HPV-16 from women with abnormal cervical cytology participating in a non-intervention follow-up study without (n=38) and with (n=51) a histologically proven cervical intraepithelial neoplasia (CIN) III lesion at the end of the study, and cervical squamous cell carcinomas (n=71). Neither specific HPV-16 350G/T variants nor specific p53 genotypes were associated with a higher risk of developing CIN III or cervical cancer. However, HPV-16 350T variants were significantly over-represented in p53 Arg homozygous women with cervical cancer. This suggests that, in p53 Arg/Arg women, infection with HPV-16 350T variants confers a higher risk of cervical cancer.
UI - 11731569
AU - Shen MR; Chou CY; Browning JA; Wilkins RJ; Ellory JC
TI - Human cervical cancer cells use Ca2+ signalling, protein tyrosine phosphorylation and MAP kinase in regulatory volume decrease.
SO - J Physiol 2001 Dec 1;537(Pt 2):347-62
AD - University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
1. This study was aimed at identifying the signalling pathways involved in the activation of volume-regulatory mechanisms of human cervical cancer cells. 2. Osmotic swelling of human cervical cancer cells induced a substantial increase in intracellular Ca2+ ([Ca2+]i) by the activation of Ca2+ entry across the cell membrane, as well as Ca2+ release from intracellular stores. This Ca2+ signalling was critical for the normal regulatory volume decrease (RVD) response. 3. The activation of swelling-activated ion and taurine transport was significantly inhibited by tyrosine kinase inhibitors (genistein and tyrphostin AG 1478) and potentiated by the tyrosine phosphatase inhibitor Na3VO4. However, the Src family of tyrosine kinases was not involved in regulation of the swelling-activated Cl- channel. 4. Cell swelling triggered mitogen-activated protein (MAP) kinase cascades leading to the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2) and p38 kinase. The volume-responsive ERK1/ERK2 signalling pathway linked with the activation of K+ and Cl- channels, and taurine transport. However, the volume-regulatory mechanism was independent of the activation of p38 MAP kinase. 5. The phosphorylated ERK1/ERK2 expression following a hypotonic shock was up-regulated by protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and down-regulated by PKC inhibitor staurosporine. The response of ERK activation to hypotonicity also required Ca2+ entry and depended on tyrosine kinase and mitogen-activated/ERK-activating kinase (MEK) activity. 6. Considering the results overall, osmotic swelling promotes the activation of tyrosine kinase and ERK1/ERK2 and raises intracellular Ca2+, all of which play a crucial role in the volume-regulatory mechanism of human cervical cancer cells.
UI - 11813698
AU - Wartenberg D; Siegel Scott C
TI - Carcinogenicity of trichloroethylene.
SO - Environ Health Perspect 2002 Jan;110(1):A13-4
UI - 11802219
AU - Velema JP; Ferrera A; Figueroa M; Bulnes R; Toro LA; de Barahona O;
TI - Claros JM; Melchers WJ Burning wood in the kitchen increases the risk of cervical neoplasia in HPV-infected women in Honduras.
SO - Int J Cancer 2002 Feb 1;97(4):536-41
AD - Department of Public Health, Erasmus University Rotterdam, The Netherlands. firstname.lastname@example.org
There is suggestive evidence that the use of wood for cooking increases the risk of invasive cervical cancer. We investigated this association in women with cervical neoplasia in Honduras. Women aged 20-64 years with cervical intraepithelial neoplasia (CIN) grade I (n = 44), CIN II (n = 36) or CIN III (n = 45) were recruited from screening programs in Tegucigalpa City and each was matched by age and clinic to 2 controls (241 total) without cervical abnormalities. The clinics selected women of low socioeconomic status. Cervical scrapes were tested for the presence of human papillomavirus (HPV) DNA using a general primer set directed against the L1 open reading frame, and HPV genotyping was performed. Odds ratios (ORs) were computed through conditional logistic regression; p-values were from tests for linear trend of risk with increasing exposure. HPV DNA was detected in 48% of women with CIN I, 67% with CIN II and 89% with CIN III. The ORs were 1.5, 2.5 and 38.3 respectively. At univariate analysis, age at first intercourse was consistently lower among cases than controls. Risk was reduced by 50% or more in all 3 CIN classes when initiation of sexual activity at age 20 years or older was compared with initiation before age 16 years (p = 0.013 for CIN I). No effect was observed for smoking, oral contraceptives or previous cytologic screening. Effects for number of sexual partners, parity, age at first pregnancy and education were in the expected directions but never persisted after adjustment for HPV. Chronic exposure to wood smoke significantly increased the risk of CIN III (p = 0.022). However, women who said "No" when asked if they ever used wood in the kitchen had a higher risk than those with low or intermediate exposure. This was taken as evidence that the initial screening question had either been misunderstood or that answers were biased. Restricting the analysis to women who reported exposure yielded positive associations in all CIN classes with for CIN III ORs of 2.3 for 25-34 and 9.5 for 35+ years compared with women who had 1-14 years of exposure (p = 0.017). A multivariate analysis of the complete dataset (n = 366) allowed for separate ORs for HPV in each CIN class. Inclusion of age at first intercourse significantly improved this model (p = 0.021). Adding exposure to wood smoke further improved the model only if an interaction between woodsmoke and HPV was allowed for. If, as the data suggest, it was assumed that wood smoke had its effect among HPV-positives only, there was a significant linear dose-response relationship between exposure to woodsmoke and risk of CIN (p = 0.026). This association was independent of other risk factors including education, parity and number of sexual partners. ORs in the final model were 0.37 for age at first intercourse 20 years or higher and 5.69 for more than 35 years of exposure to wood burning in the kitchen. The present study suggests that the use of wood for cooking is a risk factor for cervical neoplasia that deserves further study, given its high prevalence in developing countries. Copyright 2001 Wiley-Liss, Inc.
UI - 11826455
AU - Skjeldestad FE
TI - [A new strategy for prevention of cervical cancer approaching?]
SO - Tidsskr Nor Laegeforen 2001 Nov 20;121(28):3263
UI - 11810080
AU - Petry KU; Bohmer G; Iftner T; Davies P; Brummer O; Kuhnle H
TI - Factors associated with an increased risk of prevalent and incident grade III cervical intraepithelial neoplasia and invasive cervical cancer among women with Papanicolaou tests classified as grades I or II cervical intraepithelial neoplasia.
SO - Am J Obstet Gynecol 2002 Jan;186(1):28-34
AD - Department of Gynecologic Oncology, Medizinische Hochschule Hannover, Germany. email@example.com
OBJECTIVE: Women with Papanicolaou tests classified as cervical intraepithelial neoplasia grade I or II are treated conservatively in many countries. However, these women are at an increased risk of having underlying prevalent and incident grade III cervical intraepithelial neoplasia and invasive cancer. This study was undertaken to identify factors that could predict these clinically important disease states. STUDY DESIGN: Five hundred women with Papanicolaou tests classified as persistent grade I or II cervical intraepithelial neoplasia underwent a repeat test, human papillomavirus testing with Hybrid Capture assay (Digene, Silver Spring, Md) and polymerase chain reaction, and colposcopy with histologic assessment. One hundred fifty-seven women with histologically proven grade I or II cervical intraepithelial neoplasia were monitored conservatively for a minimum of 9 months to assess predictors of incident grade III cervical intraepithelial neoplasia. RESULTS: One hundred fifty-one women with prevalent grade III cervical intraepithelial neoplasia and 5 women with prevalent invasive cancer were identified at the first colposcopy. A repeated Papanicolaou test classified as higher than grade II cervical intraepithelial neoplasia and detection of oncogenic human papillomavirus types were significant predictors of underlying grade III cervical intraepithelial neoplasia and cancer in the multivariate analysis. Seventeen of 157 women (10.8%) with grade I or II cervical intraepithelial neoplasia progressed to grade III cervical intraepithelial neoplasia. Age >30 years and detection of oncogenic human papillomavirus were significantly correlated with progression in the multivariate analysis. No progression was observed in women who were negative for human papillomavirus. CONCLUSION: The high rate of underlying prevalent grade III cervical intraepithelial neoplasia and cancer found in our study (31.2%) indicates that conservative management of women with persistent grade I or II cervical intraepithelial neoplasia should be discouraged. Colposcopy with histologic assessment should be recommended as the standard of care. However, for women with histologically proven grade I or II cervical intraepithelial neoplasia, subsequent conservative management was safe in our study for those who were negative for human papillomavirus by type-specific polymerase chain reaction.
UI - 11831082
AU - Lynge E
TI - [Cervical cancer screening]
SO - Ugeskr Laeger 2002 Jan 7;164(2):171-3
AD - Institut for Folkesundhedsvidenskab, Panum Instituttet, Kobenhavns Universitet, Blegdamsvej 3, DK-2200 Kobenhavn N.
UI - 11714112
AU - Hatch EE; Herbst AL; Hoover RN; Noller KL; Adam E; Kaufman RH; Palmer
TI - JR; Titus-Ernstoff L; Hyer M; Hartge P; Robboy SJ Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States).
SO - Cancer Causes Control 2001 Nov;12(9):837-45
AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. firstname.lastname@example.org
OBJECTIVES: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. METHODS: A cohort comprising 3,899 DES-exposed and 1,374 unexposed daughters was followed for 13 years (1982 1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. CONCLUSIONS: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.
UI - 11781657
AU - Liu Y; Chiriva-Internati M; Grizzi F; Salati E; Roman JJ; Lim S;
TI - Hermonat PL Rapid induction of cytotoxic T-cell response against cervical cancer cells by human papillomavirus type 16 E6 antigen gene delivery into human dendritic cells by an adeno-associated virus vector.
SO - Cancer Gene Ther 2001 Dec;8(12):948-57
AD - Departments of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
We have shown that the pulsing of dendritic cells (DCs) with human papillomavirus type 16 (HPV-16) antigen proteins by lipofection stimulates class I-restricted cytotoxic T lymphocyte (CTL) response against primary cervical cancer cells. Also, we have shown that adeno-associated virus (AAV) was able to effectively deliver a cytokine gene into DCs. It has been our hypothesis that the delivery of antigen genes into DCs, resulting in endogenous and continuous antigen protein expression, may result in an improvement in T-cell priming by DCs. Here, DCs are pulsed (infected) with an AAV vector containing the HPV-16 E6 gene. After infection, transduced E6 gene mRNA expression and vector chromosomal integration could be identified in infected DCs. Furthermore, priming rosettes formed at early times when the AAV/E6 vector was used. Most importantly, AAV/E6 vector pulsing of DCs induced, after only 7 days of priming, a strong CTL response against primary cervical cancer cell lines, compared to bacterial E6 protein lipofection. Killing was significantly blocked by the addition of anti-MHC class I antibodies. Fluorescence-activated cell sorter (FACS) analysis of resulting primed cell populations revealed higher levels of CD8+ T cells by AAV-based pulsing, with little evidence of CD56 (NK). FACS analysis of the DC populations revealed that AAV/E6 vector-pulsed DCs had higher levels of CD80 and lower levels of CD86 than protein-pulsed DCs. These data suggest that rAAV may be appropriate for antigen pulsing of DCs for immunotherapy protocols. Finally, our protocol represents an advance in regards to the time needed for generating a CTL response compared to other techniques.
UI - 11811276
AU - Ljubojevic N; Babic S; Audy-Jurkovic S; Ovanin-Rakic A; Jukic S; Babic
TI - D; Grubisic G; Radakovic B; Ljubojevic-Grgec D Improved national Croatian diagnostic and therapeutic guidelines for premalignant lesions of the uterine cervix with some cost-benefit aspects.
SO - Coll Antropol 2001 Dec;25(2):467-74
AD - University Hospital for Gynaecology and Obstetrics, School of Medicine, University of Zagreb, Croatia.
The national Croatian improved diagnostic and therapeutic guidelines for premalignant lesions of the uterine cervix are presented: for atypical squamous cells of undetermined significance (ASCUS), for cervical intraepithelial neoplasia (CIN I, CIN II CIN III) and for microcarcinoma (FIGO grade Ia1). Separately are presented the guidelines for abnormal glandular epithelium: atypical glandular cells of undetermined significance (AGCUS) and cervical glandular intraepithelial neoplasia (CGIN). The guidelines are created according to the guidelines of the FIGO. Improved diagnostic and therapeutic guidelines was presented and accepted at the Symposium of the Croatian Society for Colposcopy and Cervical Pathology and of the Croatian Society of Gynecologists and Obstetricians of the Croatian Medical Association, held on November 25th 2000. There are presented the chief differences and the some cost-benefit aspects between the guidelines before and the new one.
UI - 11569923
AU - Stenzel A; Semczuk A; Rozynskal K; Jakowicki J; Wojcierowski J
TI - "Low-risk" and "high-risk" HPV-infection and K-ras gene point mutations in human cervical cancer: a study of 31 cases.
SO - Pathol Res Pract 2001;197(9):597-603
AD - Department of Human Genetics, Lublin University School of Medicine, Poland.
To analyze the coexistence of human papilloma virus (HPV) infection and K-ras gene activation in cervical neoplasia, we investigated 31 (seven pre-invasive and 24 invasive) cervical carcinomas for "low-risk" (types 6 and 11) and "high-risk" (types 16 and 18) HPVs and K-ras point mutations using PCR-based technology. "Low-risk" HPVs were not detected in the group investigated; however, 20 of 31 (64%) cases were HPV 16 positive, while HPV 18 was found in only three (9.7%) samples (HPV 6/11 v. HPV 16/18, p < 0.0001; HPV 16 v. HPV 18, p < 0.0001; Fisher's exact test). There was a K-ras codon 12 point mutation in two of 31 (6.4%) neoplasms, with none of the cases showing a K-ras codon 13 point mutation. Two moderately differentiated squamous carcinomas showed K-ras exon 2 gene alterations. Interestingly, none of the pre-invasive cervical carcinomas displayed K-ras gene point mutations. The mean patient age did not differ significantly in the number of HPV-positive and -negative cases. A coexistence of "high-risk" human papillomavirus DNA with K-ras gene alterations was observed in three of 31 (9.7%) neoplasms (one IIA and two IB moderately differentiated cervical carcinomas). Our results suggest that "high-risk" HPVs coexist with K-ras gene alterations in a subset of moderately differentiated carcinomas of the cervix uteri.
UI - 11720201
AU - Siddiqui G; Kurzel RB; Lampley EC; Kang HS; Blankstein J
TI - Cervical dysplasia in pregnancy: progression versus regression post-partum.
SO - Int J Fertil Womens Med 2001 Sep-Oct;46(5):278-80
AD - Department of Obstetrics and Gynecology, Mount Sinai Hospital Medical Center, Chicago, Illinois, USA.
OBJECTIVE: To assess the natural history of cervical dysplasia during pregnancy and determine the rates for progression or regression post-partum by the severity of the lesion. METHOD: This was a retrospective study of 100 patients screened by PAP smear. Lesions were graded by colposcopy and biopsy, and followed post-partum. RESULTS: Lesions were graded as ASCUS, LGSIL, and HGSIL. The majority of lesions showed a tendency to regress post-partum (approximately 64%), a trend that was statistically significant (P < .003). A substantial minority (approximately 34%) showed no change in severity of the lesion. The tendency for lesions to progress in severity was very low (approximately 3%). No patient had microinvasive disease. Of patients who had CIS, persistence of this lesion post-partum was present in 67%. CONCLUSION: Patients with cervical dysplasia in pregnancy may be followed conservatively with colposcopy and biopsy.
UI - 11809252
AU - Conley LJ; Ellerbrock TV; Bush TJ; Chiasson MA; Sawo D; Wright TC
TI - HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study.
SO - Lancet 2002 Jan 12;359(9301):108-13
AD - Division of HIV/AIDS Prevention, Surveillance, and Epidemiology, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, GA, USA.
BACKGROUND: Information about vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia in women infected with HIV-1 is needed to develop guidelines for clinical care. Our aim was to investigate the incidence of these lesions in HIV-1-positive and HIV-1-negative women and to examine risk factors for disease. METHODS:In a prospective cohort study, 925 women had a gynaecological examination twice yearly-including colposcopy and tests for human papillomavirus DNA in cervicovaginal lavage-for a median follow-up of 3.2 years (IQR 0.98-4.87). FINDINGS: Vulvovaginal and perianal condylomata acuminata or intraepithelial neoplasia were present in 30 (6%) of 481 HIV-1-positive and four (1%) of 437 HIV-1-negative women (p<0.0001) at enrollment. Women without lesions at enrollment were included in an incidence analysis. 33 (9%) of 385 HIV-1-positive and two (1%) of 341 HIV-1-negative women developed vulvovaginal or perianal lesions, resulting in an incidence of 2.6 and 0.16 cases per 100 person-years, respectively (relative risk 16, 95% CI 12.9-20.5; p < 0.0001). Risk factors for incident lesions included HIV-1 infection (p = 0.013), human papillomavirus infection (p=0.0013), lower CD4 T lymphocyte count (p = 0.0395), and history of frequent injection of drugs (p=0.0199). INTERPRETATION: Our results suggest that HIV-1-positive women are at increased risk of development of invasive vulvar carcinoma. Thus, we recommend that, as part of every gynaecological examination, HIV-1-positive women should have a thorough inspection of the vulva and perianal region, and women with abnormalities-except for typical, exophytic condylomata acuminata-should undergo colposcopy and biopsy.
UI - 11825929
AU - Salmon HA; Smith JH; Balsitis M
TI - Is microscopic assessment of macroscopically normal hysterectomy specimens necessary?
SO - J Clin Pathol 2002 Jan;55(1):67-8
AD - Department of Histopathology, Northern General Hospital NHS Trust, Sheffield S5 7AU, UK.
AIM: To determine whether microscopic examination of macroscopically normal hysterectomy specimens yields findings that could alter subsequent clinical management. METHODS: All pathology reports on hysterectomy specimens submitted to the department of histopathology at reviewed. Cases were included for further assessment if the hysterectomy specimen was regarded as macroscopically normal by a consultant pathologist and if the patient had no history of, or suspicion of, neoplastic disease. The subsequent microscopic findings from these cases were assessed to determine whether any lesions of clinical importance were identified. RESULTS: Eight hundred and fifty four specimens were reviewed, of which 139 were suitable for inclusion. Only one of the 139 cases harboured a microscopic abnormality that necessitated specific clinical follow up; this was a focus of cervical intraepithelial neoplasia 2 (CIN 2). On follow up of that patient, no further neoplastic disease was identified. CONCLUSION: Microscopic assessment of macroscopically normal hysterectomy specimens does not contribute to patient management and is unnecessary in an era of manpower shortage and cost containment.
UI - 11801914
AU - Okuno K; Joja I; Miyagi Y; Sakaguchi Y; Notohara K; Kudo T; Hiraki Y
TI - Cervical carcinoma with full-thickness stromal invasion: relationship between tumor size on T2-weighted images and parametrial involvement.
SO - J Comput Assist Tomogr 2002 Jan-Feb;26(1):119-25
AD - Department of Radiology, Faculty of Health Sciences, Okayama University Medical School, Okayama, Japan.
PURPOSE: The purpose of this work was to investigate the relationship between tumor size on T2-weighted images and parametrial involvement by cervical carcinoma with full-thickness stromal invasion and to evaluate whether the size of the tumor on T2-weighted images is a useful index of parametrial involvement. METHOD: T2-weighted images of 33 patients with cervical carcinoma showed full-thickness stromal invasion. Three-dimensional diameters (transverse, anteroposterior, and craniocaudal) of the primary tumor were measured on T2-weighted images. The area and volume of the tumor were also calculated. RESULTS: There were statistically significant differences between the patients with parametrial involvement and those without parametrial involvement for each tumor size. The criteria that showed the best accuracy for each tumor size were determined. CONCLUSION: The tumor size on T2-weighted images is considered to be a useful index for evaluating parametrial involvement by cervical carcinoma with full-thickness stromal invasion.
UI - 10554949
AU - Mitchell H
TI - Outcome after a Pap smear report of low-grade abnormality: a longitudinal comparative study.
SO - Aust N Z J Obstet Gynaecol 1999 Aug;39(3):345-8
AD - Victorian Cervical Cytology Registry, Melbourne.
The rate of subsequent diagnosis of high-grade cervical abnormality was studied among women whose first Pap smear in 1994 was reported as being negative or from the category of low-grade abnormality (excluding CIN 1). Regardless of the degree of low-grade abnormality reported on the entry smear, the rate of subsequent high-grade disease was 3.3 cases per 100 years of follow-up. The rate of subsequent high-grade disease among women with negative Pap smear reports was 0.23 to 0.45 cases per 100 years of follow-up. Within each cohort, a small number of cases of invasive cervical cancer were diagnosed in the 2 years after the entry smear. These data indicate that Pap smear reports which are coded to the registry squamous cell code of 'mild atypia' (with or without evidence of human papillomavirus effect) have a significantly higher risk of emerging high-grade cervical disease than negative Pap smear reports (including those with minor reactive and/or inflammatory change). It is suggested that the former have a uniform recommendation of repeating the smear in 1 year and the latter in 2 years.
UI - 11706814
AU - Ishii K; Kumagai T; Tozuka M; Ota H; Katsuyama T; Kurihara M; Shiozawa
TI - T; Noguchi H A new diagnostic method for adenoma malignum and related lesions: latex agglutination test with a new monoclonal antibody, HIK1083.
SO - Clin Chim Acta 2001 Oct;312(1-2):231-3
UI - 11805997
AU - Adeniji KA
TI - Analysis of the histopathological pattern of carcinoma of the cervix in Ilorin, Nigeria.
SO - Niger J Med 2001 Oct-Dec;10(4):165-8
AD - Department of Pathology, Faculty of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Kwara State, Nigeria.
This study was carried out to determine the histopathological pattern and age distribution of the 253 patients with carcinoma of the cervix whose specimens were processed and histological diagnosis made between University of Ilorin Teaching Hospital, Ilorin, Nigeria. Well differentiated squamous cell carcinoma was the commonest tumour and constituted 60.1% while adenocarcinoma was the least and accounted for 2.4% of cases. The ages of patients ranged between 23 and 85 years with an average of 51.8 years. The frequency distribution of carcinoma of the cervix appears to have bimodal pattern with a peak age at the fifth and seventh decades of life. Yearly pattern of new cases shows a very slow rate of decline in the number of cases. It is necessary to establish many screening centres and educate the populace in order to raise the level of awareness. This will enable early detection of the preinvasive lesions and thereby reduce the incidence of the frank carcinoma.
UI - 11833970
AU - Gregg J
TI - Mixed blessings: cervical cancer screening in Recife, Brazil.
SO - Med Anthropol 2000 Jul;19(1):41-63
AD - Oregon Health Sciences University, Department of Medicine, Portland 97201, USA. GreggJ@USWest.net
This study examines the effects of a large-scale cervical cancer prevention campaign in Recife, Brazil between 1994 and 1995. It suggests that while this program effectively motivated women to get pap smears, it reinforced local understandings of the pap smear that ultimately had unintended negative consequences for women's health. It argues that because the campaign connected female sexual activity directly with cervical cancer, the program's message was interpreted by many women to mean that cervical cancer was a sexually transmitted disease and that it would behave like one. Women who were no longer sexually active believed that they did not need to be screened. In addition, women who were sexually active believed that they could use pap smears to diagnose and cure sexually transmitted diseases.
UI - 11782077
AU - Clark SB; Dawson AE
TI - Invasive squamous-cell carcinoma in ThinPrep specimens: diagnostic clues in the cellular pattern.
SO - Diagn Cytopathol 2002 Jan;26(1):1-4
AD - Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Despite the increasing utilization of the ThinPrep Pap Test (TP), limited data exist regarding the cytomorphologic features and patterns of invasive squamous-cell carcinoma in TP specimens. We analyzed a series of TP specimens from patients with histologically confirmed invasive squamous carcinomas of the cervix. Patients with biopsy-proven invasive squamous-cell carcinoma of the cervix with a TP cervical cytologic specimen within the previous 2 mo were identified. The TP slides were analyzed for overall cellularity (percent circle coverage by epithelial cells), tumor cellularity, tumor diathesis, inflammation, coexistent dysplasia, and keratinization. Tumor cellularity was defined as <5%, 5-50%, and >50% of slide cellularity. In all 13 cases that were identified, a cytologic diagnosis of either invasive squamous-cell carcinoma or suspicious for invasive squamous-cell carcinoma was made. In 7/13 cases (54%), epithelial cells covered <40% of the slide circle. Epithelial cells covered >40% of the slide circle in 6/13 cases (46%). Tumor cellularity covered <5% of the slide circle in 4/13 cases (31%), 5-50% in 7/13 cases (54%), and >50% in 2/13 cases (15%). A tumor diathesis was present in 12/13 cases (92%). Inflammation was absent in 1/13 cases (8%), mild in 8/13 cases (62%), moderate in 2/13 cases (15%), and severe in 1/13 cases (8%). Coexistent dysplasia was identified in 12/13 cases (92%). Keratinization was identified in 9/13 specimens (69%). In the vast majority of patients, a diagnosis of squamous-cell carcinoma was rendered on the TP cervical specimen, despite a pattern of decreased cell coverage. It could be hypothesized that tumor diathesis and inflammation may be the etiology for decreased cellularity by blocking filter coverage by epithelial cells. This cellular pattern with diathesis in the ThinPrep smear may be a useful clue to look carefully for diagnostic cells of squamous-cell carcinoma. Copyright 2002 Wiley-Liss, Inc.
UI - 11782079
AU - Khunamornpong S; Siriaunkgul S; Suprasert P
TI - Well-differentiated villoglandular adenocarcinoma of the uterine cervix: cytomorphologic observation of five cases.
SO - Diagn Cytopathol 2002 Jan;26(1):10-4
AD - Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. email@example.com
We retrospectively examined the cytologic findings of well-differentiated villoglandular adenocarcinoma (VGA) treated in our hospital. Cervical smears of four cases and a touch preparation of another case of VGA formed the materials for the study. The cytologic features were correlated with the histomorphology of VGA. Architecturally, long slender papillae and cohesive branching epithelial sheets with smooth borders and a lack of feathery edge were observed. Crowding and overlapping of nuclei were noted. The nuclei were uniform, small, and round to oval-shaped, with evenly distributed granular chromatin. Nucleoli were absent or inconspicuous. Mitoses were occasionally seen in all but one case. As the features of VGA are distinctive, the diagnosis could be possible on cytological grounds. Examination of cervical smears would be helpful for an early diagnosis of VGA or to suggest the coexistence of other neoplastic components. Copyright 2002 Wiley-Liss, Inc.
UI - 11782080
AU - Pinto AP AP; Tuon FF; Torres LF; Collaco LM
TI - Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.
SO - Diagn Cytopathol 2002 Jan;26(1):15-8
AD - Department of Pathology, Hospital de Clinicas, Universidade Federal do Parana, Curitiba, Parana, Brazil. firstname.lastname@example.org
The present study sought possible factors leading to the cytological diagnosis of atypical squam