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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Cervical Cancer - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11544696
AU - Nieminen P
TI -
[How to read a PAP report?]
SO - Duodecim 1998;114(11):1138-43
AD - HYKS:n naistenklinikka PL 140, 00029 HYKS. pekka.nieminen@huch.fi
2
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.
3
UI - 11818195
AU - Miller AB
TI -
The (in)efficiency of cervical screening in Europe.
SO - Eur J Cancer 2002 Feb;38(3):321-6
4
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.
5
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.
hornl@medizin.uni-leipzig.de
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.
6
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).
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.
8
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. ccyuan@vghtpe.gov.tw
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.
9
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.
10
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. tsimonar@ulb.ac.be
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.
11
UI - 11973975
AU - Makinen J
TI -
[Maryland--Greece--Finland?]
SO - Duodecim 1999;115(22):2506-7
12
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. bernd.hamm@charite.de
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.
13
UI - 11865599
AU - Anonymous
TI -
New way to detect cervical cancer.
SO - Can Nurse 2001 May;97(5):10
14
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.
15
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.
16
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.
17
UI - 11973875
AU - Vuopala S
TI -
[A comment to Docent Pekka Nieminen]
SO - Duodecim 1999;115(21):2410
18
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. mandelbj@georgetown.edu
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.
19
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.
20
UI - 11988064
AU - Mark DH
TI -
Visualizing cost-effectiveness analysis.
SO - JAMA 2002 May 8;287(18):2428-9
21
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.
22
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.
23
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
24
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
25
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. kari.hemminki@cnt.ki.se
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.
26
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.
27
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. sselvaggi@facstaff.wisc.edu
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.
28
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.
jfnasuti@mail.med.upenn.edu
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.
29
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. vtaylor@fhcrc.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.
30
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. dchhieng@path.uab.edu
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.
31
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.
32
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.
33
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.
34
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.
35
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.
36
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.
37
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
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