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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Cervical Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 11817921
AU - Coughlin SS; Uhler RJ
TI -
Breast and cervical cancer screening practices among Hispanic women in
the United States and Puerto Rico, 1998-1999.
SO - Prev Med 2002 Feb;34(2):242-51
AD - Epidemiology and Health Services Research Branch, Division of Cancer
Prevention and Control, Centers for Disease Control and Prevention, 4770
Buford Highway NE, Atlanta, GA 30341, USA. SIC9@cdc.gov
BACKGROUND: Results from recent studies suggest that Hispanic women in
the United States may underuse cancer screening tests and face important
barriers to screening. METHODS: We examined the breast and cervical
cancer screening practices of Hispanic women in 50 states, the District
of Columbia, and Puerto Rico from 1998 through 1999 by using data from
the Behavioral Risk Factor Surveillance System. RESULTS: About 68.2%
(95% confidence interval [CI] = 66.3 to 70.1%) of 7,253 women in this
sample aged 40 years or older had received a mammogram in the past 2
years. About 81.4% (95% CI = 80.3 to 82.5%) of 12,350 women aged 18
years or older who had not undergone a hysterectomy had received a
Papanicolaou test in the past 3 years. Women with lower incomes and
those with less education were less likely to be screened. Women who had
seen a physician in the past year and those with health insurance
coverage were much more likely to have been screened. For example, among
those Hispanic women aged 40 years or older who had any health insurance
coverage (n = 6,063), 72.7% (95% CI 70.7-74.6%) had had a mammogram in
the past 2 years compared with only 54.8% (95% CI 48.7-61.0%) of women
without health insurance coverage (n = 1,184). CONCLUSIONS: These
results underscore the need for continued efforts to ensure that
Hispanic women who are medically underserved have access to cancer
screening services. Copyright 2002 American Health Foundation and
Elsevier Science (USA).
2
UI - 11830871
AU - Paavonen J; Saikku P
TI -
[Chlamydiaceae and cancer]
SO - Duodecim 1999;115(3):265-9
AD - HYKS:n naistenklinikka Haartmaninkatu 2 00290 Helsinki.
jorma.paavonen@helsinki.fi
3
UI - 11544829
AU - Zorin AV; Tsodikov AD; Khanin LG; Zharinov GM; Zaikin GV; Iakovlev AIu
TI -
[Parametric survival analysis in patients with cervical cancer following
fractionated radiotherapy: a new procedures and results]
SO - Vopr Onkol 2001;47(3):307-11
AD - Central Research Institute of Roentgeno-Radiology, Ministry of Health of
the RF, St. Petersburg.
A recent theoretical result of Kendal (1998) enabled us to develop a
survival model which allows for proliferation of tumor clonogenic cells
in the course of fractionated radiotherapy. We explored this model
during an analysis of clinical data on survival of 982 patients with
cancer of the cervix uteri. The model provided a good description of
survival patterns in different groups of patients. The estimated cure
probability did not correlate with the rates of cell proliferation
between exposures to radiation. Also, our results showed that this
parameter cannot be estimated from survival data. Some light has been
thrown on the relationship of cell proliferations taking place between
exposures, on the one hand, and end-results of treatment for cancer of
the cervix uteri, on the other.
4
UI - 11544831
AU - Rozenko LIa; Nepomniashchaia EM; Rubtsov VR; Gudtskova TN; Tartanova TM
TI -
[Pathologic morphology of cervical carcinoma with endolymphatic infusion
of immuno-modulating drugs]
SO - Vopr Onkol 2001;47(3):315-20
AD - Research Institute of Oncology, Ministry of Health of the RF,
Rostov-on-Don.
Prior to standard therapy, an immunomodulator was administered by
endolymphic infusion to 85 patients with cervical carcinoma (T3NxMo),
with a view to reinforce treatment. The drug was fed to lymph collectors
which were regional and aregional with respect to tumor. Also, the
treatment was supplemented with regional infusion of considerable doses
of cytostatic mixes. Our morphological evidence pointed to the
stimulation of cytostatic effect by immunomodulation.
5
UI - 11544838
AU - Vishnevskaia EE; Okeanova NI; Shelkovich SE; Matylevich OP
TI -
[Evaluation of combined treatment in stage-II cervical cancer in terms
of morphologic structure of the tumor]
SO - Vopr Onkol 2001;47(3):355-9
AD - N.N. Alexandrov Research Institute of Oncology and Medical Radiology,
Minsk, Belarus.
The efficacy of stage II cervical cancer (CC) treatment was evaluated in
two groups: squamous cell carcinoma--151, cervical adenocarcinoma
(CAC)--49. All the patients received combined treatment (preoperative
large-fraction brachytherapy + surgery + postoperative radiation). A
comparison of the results highlighted the role of morphological pattern
of tumor as a factor of cure. Five-year survival rates for CAC stage II
patients were lower by 12.4% while the incidence of distant lymphogenous
metastases and those to organs, responsible for failed therapy, was 2.7
times as high.
6
UI - 11564482
AU - Green JA; Kirwan JM; Tierney JF; Symonds P; Fresco L; Collingwood M;
TI -
Williams CJ
Survival and recurrence after concomitant chemotherapy and radiotherapy
for cancer of the uterine cervix: a systematic review and meta-analysis.
SO - Lancet 2001 Sep 8;358(9284):781-6
AD - Department of Medicine, University of Liverpool, L69 3GA, Liverpool, UK.
J.A.Green@liverpool.ac.uk
BACKGROUND: The US National Cancer Institute alert in February, 1999,
stated that concomitant chemotherapy and radiotherapy should be
considered for all patients with cervical cancer. Our aim was to review
the effects of chemoradiotherapy on overall and progression-free
survival, local and distant control, and acute and late toxicity in
patients with cervical cancer. METHODS: With the methodology of the
Cochrane Collaboration, we did a systematic review of all known
randomised controlled trials done between 1981 and 2000 (17 published,
two unpublished) of chemoradiation for cervical cancer. FINDINGS: The
trials included 4580 randomised patients, and 2865-3611 patients
(62-78%) were available for analysis. Cisplatin was the most common
agent used. The findings suggest that chemoradiation improves overall
survival (hazard ratio 0.71, p<0.0001), whether platinum was used (0.70,
p<0.0001) or not (0.81, p=0.20). A greater beneficial effect was seen in
trials that included a high proportion of stage I and II patients
(p=0.009). An improvement in progression-free survival was also seen
with chemoradiation (0.61, p<0.0001). Thus, the absolute benefit in
progression-free and overall survival was 16% (95% CI 13-19) and 12%
(8-16), respectively. A significant benefit of chemoradiation on both
local (odds ratio 0.61, p<0.0001) and distant recurrence (0.57,
p<0.0001) was also recorded. Grade 3 or 4 haematological (odds ratio
1.49-8.60) and gastrointestinal (2.22) toxicities were significantly
greater in the concomitant chemoradiation group than the control group.
There was insufficient data to establish whether late toxicity was
increased in the concomitant chemoradiation group. INTERPRETATION:
Concomitant chemotherapy and radiotherapy improves overall and
progression-free survival and reduces local and distant recurrence in
selected patients with cervical cancer, which may give a cytotoxic and
sensitisation effect.
7
UI - 11748359
AU - Kang GH; Min K; Shim YH; Kim KR
TI -
Papillary immature metaplasia of the uterine cervix: a report of 5 cases
with an emphasis on the differential diagnosis from reactive squamous
metaplasia, high-grade squamous intraepithelial lesion and papillary
squamous cell carcinoma.
SO - J Korean Med Sci 2001 Dec;16(6):762-8
AD - Department of Pathology, University of Ulsan College of Medicine, Asan
Medical Center, Seoul, Korea. krkim@www.amc.seoul.kr
Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of
the uterine cervix and shares some histologic and cytologic features
with ordinary squamous metaplasia (SM), atypical immature squamous
metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL)
and papillary squamous cell carcinoma (PSC). PIM has been suggested to
be a subset of condyloma associated with low-risk type human papilloma
virus (HPV), however, the etiologic role of HPV and biologic behavior of
the disease are still elusive. We compared the clinical and
histopathological findings, immunohistochemical expression of Ki-67 and
p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6),
and PSC (n=4) to know the helpful features for the differential
diagnosis. Histologically, all 5 cases showed a papillary proliferation
of immature metaplastic cells involving the proximal transformation zone
and endocervix. On HPV typing by polymerase chain reaction-restriction
fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV
6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16
each. Ki-67 labeling index and mitotic index of PIM were significantly
lower than those of HSIL or PSC. There were no significant differences
of Ki-67 labeling index and mitotic index between PIM and SM. The
expression of p53 varied among the groups and thus it was not helpful
for the differential diagnosis.
8
UI - 11481905
AU - Szentirmay Z; Cseh J; Pulay T; Kasler M
TI -
[Human papillomavirus and cervical cancer: genetic background of the
neoplastic process]
SO - Orv Hetil 2001 Jul 8;142(27):1429-36
AD - Orszagos Onkologiai Intezet, Budapest.
In a 2-year period, 136 HPV positive cytological samples of the cervix
uteri were analyzed at the Department of Molecular Pathology, National
Institute of Oncology, Hungary. Comparison with the international data
obtained from the literature revealed that the Hungarian epidemiological
data bore closest resemblance to the European ones except some
differences. The HPV18 is rather seldom encountered in this country.
Similarly low occurrence was noted only in Japan. However, the 14.1%
occurrence rate of HPV58 in Hungary is by far higher than that in any
other country in this analysis except Japan where this virus is of
similarly high frequency. In Hungary, the incidence of HPV59 is
relatively high just like in Central and South America. HPV33 and HPV66
infections occur in a significantly higher number with Hungary than in
any of the countries studied. In our study The European type variant of
HPV16 (E-V-350G) occurred in 2/10 CIN II-III cases. The authors also
compared the various clinico-pathological grouping of HPV types
published, and identified several inconsistencies. Viruses considered to
have high risk occurred in intact epithelium, CIN I-II-III and carcinoma
alike. The general tendency was, however, that certain viruses
correlated with specific clinico-pathological entities. At present there
is no reason to include the PCR-based HPV typing in the mass screening
of cervical cancers. HPV typing and physical state of the virus can
reasonable be determined if the cervical cytology is suspect for HPV
infection or even control examination after "loop" conisation. Negative
cytology completed with negative HPV-DNA test means the lack of cancer
risk even in the case of a previously removed CIN or carcinoma. However,
a positive HPV test detected after conisation associated with negative
cytology finding indicates a risk of 70% of the development of CIN
within 2 years.
9
UI - 11843936
AU - Cruickshank ME
TI -
Is cervical screening necessary in older women?
SO - Cytopathology 2001 Dec;12(6):351-3
10
UI - 11843937
AU - McGahan CE; Blanks RG; Moss SM
TI -
Reasons for variation in coverage in the NHS cervical screening
programme.
SO - Cytopathology 2001 Dec;12(6):354-66
AD - Cancer Screening Evaluation Unit, Institute of Cancer Research, Section
of Epidemiology, Sutton, UK.
In order to investigate reasons for variation in coverage of cervical
screening, data from standard Department of Health returns were obtained
for all Health Authorities for 1998/1999. Approximately 80% of the
variation between health authorities is explained by differences in age
distribution and area classification. Considerable differences between
Health Authority and Office of National Statistics (ONS) population
figures in City and Urban (London) areas for the age group 25-29 years
and for City (London) for age group 30-34 years, suggest an effect of
list inflation in these groups. Coverage as a performance indicator may
be more accurately represented using the age range 35-64 years. Using
this narrower age range, the percentage of health authorities meeting
the 80% 5-year coverage target increases from 87% to 90%.
11
UI - 11843939
AU - Migliore G; Rossi E; Aldovini A; Mudu P; Alderisio M; Giovagnoli MR;
TI -
Fabiano A; Morosini PL; Branca M
Variation in the assessment of adequacy in cervical smears.
SO - Cytopathology 2001 Dec;12(6):377-82
AD - Laboratory of Epidemiology and Biostatistics, Cytopathology Unit,
National Institute of Health, Rome, Italy.
OBJECTIVE: To assess the interobserver reproducibility of the diagnosis
of 'adequacy' of cervical smears according to the Bethesda System
criteria in cervical smears. STUDY DESIGN: 358 cervical smears were
obtained from three Italian cytopathological centres in 1998-99. All
centres provided consecutively collected smears. The cervical smears
were independently and blindly assessed by four cytologists.The
screening was performed using a 10x objective and an additional
evaluation of the percentage of cellularity was performed using a 4x
objective. RESULTS: The proportion of smears assessed by the four
cytologists as 'adequate' ranged from 60% to 70%, the proportion of
'satisfactory for evaluation but limited by' ranged from 27% to 38%, and
the proportion of 'inadequate smears' ranged from 2% to 4%. Full
agreement in the assessment of smear adequacy was observed in 311 slides
and disagreement was observed only in 47. The category 'inadequate
smear' was less reliable than the other two; however, the kappa value
observed was acceptable. CONCLUSION: The present study shows that it is
possible to achieve a high reproducibility in the assessment of smear
adequacy, at least among expert cytologists who follow the Bethesda
System criteria strictly.
12
UI - 11843940
AU - Herbert A; Johnson J
TI -
Personal view. Is it reality or an illusion that liquid-based cytology
is better than conventional cervical smears?
SO - Cytopathology 2001 Dec;12(6):383-9
AD - Histopathology Department, Guy's and St Thomas' Hospitals NHS Trust,
London, UK.
Liquid-based cytology (LBC) has been heralded as the way forward for
cervical screening, and as the answer to many of its problems. It is
already used as a sole method of cell preparation in many private
clinics in the UK. It is being used for colposcopy smears in many NHS
clinics and is now being piloted for primary screening in three
screening centres in England, as well as one in Scotland and one in
Wales. LBC has been welcomed as a new technology because it deals with
the problem of specimen adequacy at source, removing responsibility for
slide preparation and fixation from the clinician or nurse. It provides
uniformly well-fixed preparations that are free of inflammatory exudate
and blood, and seem easier to screen than conventional smears. There are
many articles in the world literature suggesting that LBC is more
accurate than conventional screening, and it is thought likely to reduce
the number of false negative tests. The main reasons for piloting LBC in
the NHS Cervical Screening Programme (NHSCSP) lie in its potential for
reducing screening times and for reducing the numbers of repeats for
inadequate tests. LBC is expensive in terms of equipment, capital costs,
maintenance, consumables, training, technical preparation time,
transportation and disposal of liquid media. Its costs could be
justified if they were offset by the money saved from reduced screening
time and repeat tests, but only if its accuracy in terms of sensitivity
and specificity were proven to be equal to or better than conventional
cytology. Although that is generally held to be true by the public and
medical profession alike, there is very little hard evidence to support
it.
13
UI - 11857315
AU - Acevedo CM; Henriquez M; Emmert-Buck MR; Chuaqui RF
TI -
Loss of heterozygosity on chromosome arms 3p and 6q in microdissected
adenocarcinomas of the uterine cervix and adenocarcinoma in situ.
SO - Cancer 2002 Feb 1;94(3):793-802
AD - Department of Pathology, Catholic University, Santiago, Chile.
BACKGROUND: Despite the increasing frequency of adenocarcinomas of the
uterine cervix, little is known regarding inactivation of tumor
suppressor genes (TSGs) in this tumor type. The authors analyzed loss of
heterozygosity (LOH) in 36 carcinomas of the cervix with glandular
differentiation, and 5 adenocarcinoma in situ in 40 patients. METHODS:
The authors analyzed samples using laser capture microdissection from
archival material and DNA amplified with microsatellite markers on the
following loci: 3p14.2 (D3S1234, D3S1300), 3p21.3 (D3S1029, D3S1447),
3p22-24 (D3S1537, D3S1351), 6q21-23.3 (D6S250), 6q25.1 (ESR), 6q25.2
(D6S255), 8p21 (D8S136, D8S1820), 13q12.3 (D13S220, D13S267), 17q21
(D17S579, D17S855). Eight additional markers spanning the short arm of
chromosome 3 (3p12-p25) and six spanning the long arm of chromosome 6
(6q11-q27) were studied in the cases showing LOH to further define the
deletion intervals. RESULTS: The frequency of allelic loss in cancers
was chromosome 3p: 49% (p14.2: 35%, p21.3: 23%, p22-24: 41%), 6q: 48%
(q21-23.1: 39%, q25.1: 45%, q25.2: 7%), 13q: 22%, 17q: 6%, and 8p: 18%.
On chromosome arm 3p, the authors' data suggest at least two discrete
areas of deletion: a proximal area between markers D3S1234 (p12) and
D3S1766 (p14.2-14.3), and a second distal interval, telomeric from
marker D3S4623 (p21.3). On chromosome 6q, the deletion area is between
marker D6S300 (q22) and D6S255 (q25.2). Two of five preneoplastic
lesions showed LOH on chromosome arm 3p, and two five showed allelic
loss on chromosome arm on 6q, suggesting the genes might be inactivated
early in cervical tumorigenesis. CONCLUSIONS: The authors have
identified three chromosomal regions that may harbor TSGs involved in
the development/progression of adenocarcinomas of the uterine cervix,
3p12-14.2, 3p21.3-pter, and 6q22-25.2. Deletions also were detected in
adenocarcinoma in situ, suggesting the genes may be inactivated early in
cervical tumorigenesis. Copyright 2002 American Cancer Society. DOI
10.1002/cncr.10275
14
UI - 11859985
AU - Mogren I; Stenlund H; Hogberg U
TI -
Long-term impact of reproductive factors on the risk of cervical,
endometrial, ovarian and breast cancer.
SO - Acta Oncol 2001;40(7):849-54
AD - Department of Clinical Science, Umea University, Sweden.
ingrid.mogren@obstgyn.umu.se
The influence of maternal age, parity, low or high birthweight, multiple
births, and pre-eclampsia on the risk of cervical, endometrial, ovarian
and breast cancers was studied. Data on 40951 women and the outcomes of
their deliveries between 1955 and 1995 were obtained from birth
registers. For the mothers, data from the Swedish Cancer Registry and
the Cause of Death Register were added. The sample was evaluated using
Cox's regression in univariate and bivariate analyses where the relative
risk and its 95% confidence interval were calculated. Increasing
maternal age at first birth was associated with an increasing relative
risk of endometrial, ovarian, and breast cancers, and with a decreased
risk of cervical cancer. Multiparity was a protective factor for all
gynaecological cancers, including cervical and breast cancers. Multiple
births were associated with an increased risk of endometrial cancer.
15
UI - 11284307
AU - Cortese C; American Society of Cytopathology
TI -
Cervical Cytology Practice Guidelines. American Society of
Cytopathology.
SO - Acta Cytol 2001 Mar-Apr;45(2):201-26
16
UI - 11850794
AU - Jarboe EA; Liaw KL; Thompson LC; Heinz DE; Baker PL; McGregor JA; Dunn
TI -
T; Woods JE; Shroyer KR
Analysis of telomerase as a diagnostic biomarker of cervical dysplasia
and carcinoma.
SO - Oncogene 2002 Jan 21;21(4):664-73
AD - Department of Pathology, University of Colorado Health Sciences Center,
Denver, Colorado, CO 80262, USA.
Telomerase expression is a potentially important marker of high-grade
cervical dysplasia and squamous cell carcinoma (SCC). The routine
practice of cervical cytology is limited by problems of false negative
diagnoses as well as by poor specificity for clinically significant
lesions in patients with low-grade cytologic abnormalities. Telomerase
is widely expressed in most SCCs as well as in a high proportion of
high-grade squamous intraepithelial lesions. Histochemical studies have
confirmed that telomerase is expressed in the lower portions of normal
or metaplastic squamous mucosa but that telomerase positive cells extend
into the upper epithelial layers in cases of high-grade dysplasia. Since
the cervical smear samples the uppermost cell layers of the cervical
mucosa, but does not normally include cells derived from the lower
layers of the squamous mucosa, the detection of telomerase in exfoliated
cells of the cervical smear may have specificity for clinically
significant lesions. The analysis of hTR, hTERT, and telomerase activity
are complicated by a number of technical factors that may lead to either
false negative or false positive test results. Thus, the practical
application of telomerase analysis as a diagnostic adjunct for cervical
cytopathology may depend on the development of more reliable and
sensitive assay systems, possibly formatted for cytochemical
applications.
17
UI - 11606114
AU - Belinson J; Qiao YL; Pretorius R; Zhang WH; Elson P; Li L; Pan QJ;
TI -
Fischer C; Lorincz A; Zahniser D
Shanxi Province Cervical Cancer Screening Study: a cross-sectional
comparative trial of multiple techniques to detect cervical neoplasia.
SO - Gynecol Oncol 2001 Nov;83(2):439-44
AD - Department of Gynecology, The Cleveland Clinic Foundation, Cleveland,
Ohio 44195, USA. belinsj@ccf.org
OBJECTIVE: The aim of this study was to design a cervical cancer
screening algorithm for the developing world that is highly sensitive
for cervical intraepithelial neoplasia (CIN) II, III, and cancer and
highly specific for CIN II and III, making it possible to ablate the
transformation zone without histologic confirmation. METHODS: In rural
Shanxi Province, China, we examined 1997 women ages 35-45. Each subject
underwent a self-test for intermediate and high-risk HPV (by HC-II
assay), fluorescence spectroscopy, a liquid-based Pap (read manually and
by computer and used as a direct test for HPV), a visual inspection
(VIA) diagnosis, and colposcopy with multiple cervical biopsies.
RESULTS: Mean age was 39.1 +/- 3.16 years, mean number of births was 2.6
+/- 0.93. Based on tests administered, 4.3% subjects had > or =CIN II.
All subjects with > or =CIN II had either a ThinPrep Pap (> or =ASCUS)
or a positive HPV direct test. The sensitivity and specificity for the
detection of > or =CIN II were, respectively, 83 and 86% for the HPV
self-test, 95 and 85% for the HPV direct test, 94 and 78% for the
ThinPrep Pap (> or =ASCUS), 77 and 98% for the ThinPrep Pap (> or
=HGSIL), 94 and 9% for fluorescence spectroscopy, 71 and 74% for VIA,
and 81 and 77% for colposcopy. CONCLUSION: Based on these data and the
existing healthcare infrastructure in China, we believe that further
refinement of primary HPV screening using centralized labs is indicated.
Self-testing in the local villages may be effective with improvements in
the devices and techniques. Copyright 2001 Academic Press.
18
UI - 11792748
AU - Sherman ME; Schiffman M; Cox JT; Atypical Squamous Cells of Undetermined
TI -
Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study
Group
Effects of age and human papilloma viral load on colposcopy triage: data
from the randomized Atypical Squamous Cells of Undetermined
Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study
(ALTS).
SO - J Natl Cancer Inst 2002 Jan 16;94(2):102-7
AD - Environmental Epidemiology Branch, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, Bethesda, MD 20892-7374, USA.
shermanm@mail.nih.gov
BACKGROUND: Testing for oncogenic human papillomavirus (HPV) DNA at a
1.0-pg/mL threshold represents a promising approach for colposcopy
triage of atypical squamous cells of undetermined significance (ASCUS),
but not for low-grade squamous intraepithelial lesions (LSIL).
Considering age or viral load could improve colposcopy triage. METHODS:
We determined the sensitivity for detecting Cervical Intraepithelial
Neoplasia 3 (CIN3) and cancer and the percentage of referrals for
colposcopy using HPV testing and repeat thin-layer cytopathology in 2198
women with ASCUS and in 848 women with LSIL enrolled in ALTS from
two thresholds for HPV load and repeat cytopathology. RESULTS: For
ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1%
(95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with
age (range, 93.9% to 97.8%). HPV testing at this threshold would refer
31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as
compared with more than 65% of younger women. Among women aged 29 years
or older with ASCUS, referral for repeat cytopathology of ASCUS had a
sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1%
(95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a
10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to
41.7%. More than 63% of LSIL would have been referred using any strategy
achieving 90% sensitivity. CONCLUSION: For women with ASCUS, HPV testing
was highly sensitive for detecting CIN3 and cancer with dramatically
fewer referrals of older women. Neither a single HPV test nor repeat
cytopathology provides useful triage for women with LSIL.
19
UI - 11812077
AU - Li H; Huang CJ; Choo KB
TI -
Expression of homeobox genes in cervical cancer.
SO - Gynecol Oncol 2002 Feb;84(2):216-21
AD - Institute of Molecular Biology, Academia Sinica, Nankang, Taipei,
Taiwan.
OBJECTIVE: Members of the homeobox (HB) gene superfamily encode
transcription factors crucial for development and may be associated with
tumorigenesis. In this study, we aimed to develop a procedure to survey
the expression of the dispersed-type HB genes in cervical cancer cells.
METHODS: Nineteen sets of degenerate primers were designed based on
conserved homeodomains of known dispersed-type HB genes. A cDNA library
derived from HeLa, a cervical cancer cell line, was used. Two successive
rounds of PCR were performed using a combination of the HB degenerate
primers and a primer recognizing the flanking sequence of the vector
used in the cDNA library construction. RESULTS: On cloning and sequence
analysis of the PCR fragments generated, 10 known and 3 putative novel
HB genes were detected in HeLa. RT-PCR expression analysis further
showed that HOXD9 and ATBF1 were differentially expressed in cancer
cells and not in normal cervix. CONCLUSIONS: Our data demonstrate the
feasibility of using degenerate primers in PCR experiments in a
collective analysis of complex gene families. Our data indicate that
HOXD9 and ATBF1 are expressed in cervical cancer, but not in normal
cervix. B)2002 Elsevier Science.
20
UI - 11812078
AU - Brummer O; Bohmer G; Hollwitz B; Flemming P; Petry KU; Kuhnle H
TI -
MMP-1 and MMP-2 in the cervix uteri in different steps of malignant
transformation--an immunohistochemical study.
SO - Gynecol Oncol 2002 Feb;84(2):222-7
AD - Department of Gynecologic Oncology, Medizinische Hochschule Hannover,
Germany. oliver.brummer@gmx.de
OBJECTIVES: Enzymatic degradation of the extracellular matrix (ECM)
represents a key element in the multistage process of tumor invasion and
metastasis. This process requires extensive degradation of ECM
components such as basement membrane collagen (type IV) and interstitial
collagen (type I, II, III). Matrix metalloproteinase-2 (MMP-2)
specifically cleaves collagen type IV, the major collagen of the
basement membrane. MMP-1 digests interstitial collagen type I and III,
the main collagen types of the stromal extracellular matrix. We
investigated protein levels of MMP-1 and MMP-2 in different stages of
malignant transformation. METHODS: Using the APAAP method we analyzed 10
normal cervical tissues, 11 cervical intraepithelial neoplasia 1 (CIN
1), 8 CIN 2 and 10 CIN 3 lesions, and 15 invasive squamous cell
carcinomas. These data were compared with the HPV DNA status tested by
hybrid capture II. RESULTS: Only a few isolated epithelial cells stained
positively for MMP-1 and MMP-2 in normal cervical tissue and CIN 1
lesions. The CIN 2 and CIN 3 group displayed a heterogeneous
distribution of MMP expression. 3 CIN 2 and 8 CIN 3 lesions showed
strong MMP-2 and weak MMP-1 expression in the dysplastic epithelial
cells. 5 CIN 2 and 2 CIN 3 lesions stained negatively. Invasive
carcinomas showed a coexpression for MMP-1 and MMP-2 in malignant
epithelial cells and peritumoral stroma cells. All MMP-2-positive cases
tested positive for the HPV high-risk group. CONCLUSIONS: The expression
of MMP-2 protein in preinvasive lesions of the cervix uteri and a
consecutive coexpression of MMP-1 and MMP-2 in invasive cancer suggest a
gradually increasing invasive potential. MMP-2 expression, when focally
observed in high-grade squamous intraepithelial lesions of the cervix,
may indicate tumor areas with an increased risk for invasive growth.
B)2002 Elsevier Science.
21
UI - 11812083
AU - Winter R; Haas J; Reich O; Koemetter R; Tamussino K; Lahousen M; Petru
TI -
E; Pickel H
Parametrial spread of cervical cancer in patients with negative pelvic
lymph nodes.
SO - Gynecol Oncol 2002 Feb;84(2):252-7
AD - Department of Obstetrics and Gynecology, University of Graz, Graz,
Austria. obstet.gynecol@kfunigraz.ac.at
OBJECTIVE: We studied the incidence and prognostic implications of
parametrial involvement according to tumor volume in a series of
cervical cancer patients with negative pelvic lymph nodes. METHODS: We
reviewed a series of 351 node-negative patients with stage IB, IIA, or
IIB cervical cancer treated with class III radical hysterectomy. The
surgical specimens were processed as step-serial giant sections and
tumor volume was calculated. Overall, 180 patients had tumors <5 mL, 120
had tumors of 5-20 mL, and 51 had tumors >20 mL. Parametrial involvement
was classified as continuous, discontinuous, or involvement of blood
vessels or lymph nodes and according to location as medial or lateral. A
total of 302 patients had squamous cell tumors and 49 had
adenocarcinomas. The mean duration of follow-up was 9.3 years. RESULTS:
Overall, 44 of 351 patients (12.5%) had parametrial involvement. The
rate of parametrial involvement in patients with tumors <5, 5-20, and
>20 mL was 6.7, 12.5, and 33%, respectively. Isolated involvement of the
medial parametrium increased with tumor size (3.8, 8.3, and 27.5%,
respectively), whereas isolated involvement of the lateral parametrium
was seen in 2.2, 1.6, and 0% of the cases. Involvement of both the
medial and the lateral portions of the parametrium was seen in 0.5, 2.5,
and 5.9% of the specimens, respectively. There were no differences in
the rate of parametrial involvement between squamous cell carcinomas and
adenocarcinomas. The 5-year disease-free survival rates in patients
without or with parametrial involvement were 90.2% vs 90%, 91.7% vs
92.9%, and 84.7% vs 67%, respectively. CONCLUSION: The lateral portion
of the parametrium can be involved in patients with cervical cancer and
negative pelvic lymph nodes, but this is uncommon. In this series of
patients treated with type III radical hysterectomy, parametrial
involvement had no influence on disease-free survival. (c)2001 Elservier
Science
22
UI - 11812089
AU - Nakamoto Y; Eisbruch A; Achtyes ED; Sugawara Y; Reynolds KR; Johnston
TI -
CM; Wahl RL
Prognostic value of positron emission tomography using
F-18-fluorodeoxyglucose in patients with cervical cancer undergoing
radiotherapy.
SO - Gynecol Oncol 2002 Feb;84(2):289-95
AD - Division of Nuclear Medicine, Johns Hopkins University, Baltimore,
Maryland 21287-0817, USA.
OBJECTIVE: The purpose of this study was to determine whether positron
emission tomography (PET) using F-18-fluorodeoxyglucose (FDG) before and
after radiotherapy would predict whether local control of cervical
cancer had been achieved. METHODS: FDG-PET scans were performed prior to
therapy and at a mean of 4.6 months after radiation in 20 patients (pts)
with histologically proven uterine cervical cancer who were undergoing a
"curative" course of radiation therapy. FDG uptake was interpreted
visually by two readers using a 5-point grading system (0 = normal, 1 =
probably normal, 2 = equivocal, 3 = probably abnormal, and 4 =
definitely abnormal). The standardized uptake values corrected by lean
body mass (SUL) were calculated for suspicious areas. The percentage of
residual activity (%RA) for the posttherapy SUL was also evaluated as a
percentage of the pretherapy SUL. RESULTS: At baseline before
irradiation, 17 of 20 (85.0%) primary tumors were detected. Following
irradiation, no or low (grade 0-2) uptake was observed in 9 pts, and
none of these had local recurrence. Among the remaining 11 pts with
grade 3 or 4 uptake, the correct diagnosis was made for 5 pts with
active tumor; SULs (mean +/- SD = 4.17 +/- 2.52) and %RAs (57.9 +/-
16.8). Six patients without active tumor showed relatively low SULs
(2.67 +/- 0.69) and %RAs (43.0 +/- 18.3). No significant differences
were observed between the recurrent and nonrecurrent groups for these
parameters. Overall, sensitivity, specificity, and accuracy were 100,
60, and 70%, respectively. CONCLUSION: These preliminary data indicate
that FDG-PET is a sensitive tool for detecting active cervical cancer
after radiation, however, the method, without anatomic correlation had
suboptimal specificity. B)2002 Elsevier Science.
23
UI - 11812091
AU - Robison SW; Dietrich CS; Person DA; Farley JH
TI -
Ethnic differences in survival among Pacific Island patients diagnosed
with cervical cancer.
SO - Gynecol Oncol 2002 Feb;84(2):303-8
AD - Department of Obstetrics and Gynecology, Tripler Army Medical Center, 1
Jarrett White Road, TAMC, Hawaii 96859-5000, USA.
BACKGROUND: It was the purpose of this study to investigate whether
Pacific Island (PI) ethnicity, Micronesian and Polynesian, is an
independent prognostic factor in the survival of cervical cancer in a
health care system with minimal racial bias and few barriers to access
to care. METHODS: Records from 1988 to 1999 were reviewed for the U.S.
Military Health Care System. The medical records of women with the
diagnosis of invasive cervical cancer were abstracted and clinical data
recorded. A cohort analysis based on Pacific Island ethnicity was also
performed on all patients treated at Tripler Army Medical Center (TAMC)
during this time period. Significant differences in distribution of
clinical factors were determined by Wilcoxon rank-sum test and survival
analyses were performed using Kaplan-Meier actuarial statistics.
RESULTS: A total of 153 patients were identified who were treated at
TAMC; 74 were of PI ethnicity. An additional 1400 patients were
identified throughout the military health care system during this time.
Forty-eight percent of non-PI TAMC patients were Caucasian, 14%
Filipino, and 13% Korean. The mean age of PI was 45 versus 40 years for
their non-PI counterparts. There was no difference in the distribution
of the grade of tumors among cohorts analyzed. Seventy-five percent of
non-PI patients presented at an early stage while 74% of PI women
presented at an advanced stage. Twenty-three percent of PI patients had
positive lymph nodes, versus 7% of non-PI patients. There was no
difference in the radiation dosages among patients treated with primary
radiation therapy. PI patients had a significantly decreased 5-year
survival, 32% versus 71%, compared to their cervical cancer patient
counterparts, P < 0.001. Multivariate analysis revealed PI ethnicity to
be a significant independent predictor of decreased survival, P < 0.001.
CONCLUSION: PI women diagnosed with cervical cancer tend to present at
an advanced age and stage with metastatic disease. They have a decreased
survival that remains present after adjusting for age, stage, and grade.
The poor prognosis is likely due to lack of uniform screening among this
population; however, molecular etiologies and human papillomavirus could
also contribute to decreased survival. B)2002 Elsevier Science.
24
UI - 11848503
AU - Schoppmann SF; Schindl M; Breiteneder-Geleff S; Soleima A; Breitenecker
TI -
G; Karner B; Birner P
Inflammatory stromal reaction correlates with lymphatic microvessel
density in early-stage cervival cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3419-23
AD - Institute of Clinical Pathology, University of Vienna, Austria.
BACKGROUND: In early-stage cervical cancer, high lymphatic microvessel
density (LMVD) indicates favorable prognosis. This unexpected finding
was thought to be an effect of local immunological response, although no
data supported this thesis. MATERIALS AND METHODS: LMVD and
lymphovascular invasion (LVI) were assessed in 85 specimens of cervical
cancer stage pT1b by immunostaining for podoplanin, a marker for
lymphatic endothelia. Local immunological response, evident by
inflammatory stromal reaction (ISR), was determined in H&E-stained
slides and rated from grade 1 (absent or weak) to 3 (strong) RESULTS: A
good correlation of LMVD and ISR was found (p=0.002). While a strong
correlation between LMVD and the presence of LVI was found (p<0.001), no
association between LMVD and pelvic lymph node involvement (p=0.732) was
observed. ISR indicated favourable prognosis of patients (p=0.0247,
log-rank test). CONCLUSION: Our findings suggest that ISR might play a
role in the induction of lymphangiogenesis in early stage cervical
cancer.
25
UI - 11864690
AU - Suba EJ; Raab SS
TI -
Cervical cancer screening by simple visual inspection after acetic acid.
SO - Obstet Gynecol 2002 Mar;99(3):517-8
26
UI - 11870517
AU - Brooks LA; Sullivan A; O'Nions J; Bell A; Dunne B; Tidy JA; Evans DJ;
TI -
Osin P; Vousden KH; Gusterson B; Farrell PJ; Storey A; Gasco M; Sakai T;
Crook T
E7 proteins from oncogenic human papillomavirus types transactivate p73:
role in cervical intraepithelial neoplasia.
SO - Br J Cancer 2002 Jan 21;86(2):263-8
AD - Ludwig Institute for Cancer Research, St Mary's Hospital Medical School,
Norfolk Place, London W2 1PG, UK.
In common with other E2F1 responsive genes such as p14(ARF) and B-myb,
the promoter of p73 is shown to be positively regulated in cell lines
and primary human keratinocytes by E7 proteins from oncogenic human
papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational
analysis revealed that transactivation of the p73 promoter by HPV 16E7
requires association with pRb. Expression of p73 in normal cervical
epithelium is confined to the basal and supra-basal layers. In contrast,
expression in neoplastic lesions is detected throughout the epithelium
and increases with grade of neoplasia, being maximal in squamous cell
cancers (SCC). Deregulation of expression of the N-terminal splice
variant p73Delta2 was observed in a significant proportion of cancers,
but not in normal epithelium. The frequent over-expression of p73Delta2,
which has recognized transdominant properties, in malignant and
pre-malignant lesions suggests a role in the oncogenic process in
cervical epithelium. Copyright 2002 The Cancer Research Campaign
27
UI - 11870518
AU - Kammer C; Tommasino M; Syrjanen S; Delius H; Hebling U; Warthorst U;
TI -
Pfister H; Zehbe I
Variants of the long control region and the E6 oncogene in European
human papillomavirus type 16 isolates: implications for cervical
disease.
SO - Br J Cancer 2002 Jan 21;86(2):269-73
AD - Institute of Virology, University of Cologne, Furst-Puckler-Strasse 56,
D-50935 Cologne, Germany.
High-risk human papillomavirus types, especially type 16, are risk
factors for cervical cancer. Preliminary studies suggest that HPV16
polymorphisms in the long control region or in the E6 gene may alter the
oncogenic potential of the virus. This could partially explain why some
lesions progress to cancer while others do not. A systematic study
combining the long control region and E6 has not been undertaken. This
prompted us to investigate the long control region and the E6 in
northern European women infected with human papillomavirus 16. We
identified the sequence variations of both regions and investigated the
long control region promoter activity among various isolates. In
addition, we correlated the distribution of long control region and E6
polymorphisms with disease status. We analyzed 45 samples from Swedish
and Finnish women. The long control region and the E6 gene were
sequenced after polymerase chain reaction long control region fragments
of six European isolates covering the majority of polymorphisms in this
region were ligated into the pALuc vector and used for luciferase
assays. In European HPV16 isolates, polymorphisms in the long control
region are more frequent than in the E6 gene. Nevertheless, the promoter
function was slightly increased in only one of the tested European long
control region variants. In addition, we found a specific European E6
variant, L83V, to be enriched in high-grade lesions and cancer rather
than a specific European long control region variant. The difference in
oncogenicity between European HPV16 genotypes is more probably due to an
altered property of the corresponding E6 proteins rather than to an
altered activity of the P97 promoter. Copyright 2002 The Cancer Research
Campaign
28
UI - 11870519
AU - Cheng Q; Lau WM; Chew SH; Ho TH; Tay SK; Hui KM
TI -
Identification of molecular markers for the early detection of human
squamous cell carcinoma of the uterine cervix.
SO - Br J Cancer 2002 Jan 21;86(2):274-81
AD - Laboratory of Gene Structure & Expression, Division of Cellular and
Molecular Research, National Cancer Centre, 11 Hospital Drive, 169610
Singapore.
To identify novel cellular genes that could potentially act as
predictive molecular markers for human cervical cancer, we employed
RT--PCR differential display, reverse Northern and Northern blot
analysis to compare the gene expression profiles between squamous cell
carcinoma biopsies and adjacent histo-pathological normal epithelium
tissues. Twenty-eight cDNA clones were isolated that were demonstrated
to be consistently over-expressed in squamous cell cervical cancer
biopsies of FIGO stages 1B to 3B. Most importantly, it was observed
that, in addition to their over-expression in cancer lesions, some of
these genes are upregulated in the presumably histo-pathological normal
adjacent tissues. Of particular interest is clone G30CC that has been
identified to be the gene that encodes S12 ribosomal protein. When
employed for RNA--RNA in situ hybridization experiments, expression of
G30CC could be detected in the immature basal epithelial cells of
histo-pathological normal tissues collected from cervical cancer
patients of early FIGO stages. In comparison, the expression of G30CC
was not detected in cervical tissues collected from patients admitted
for surgery of non-malignant conditions. These results allow the
distinct possibility of employing the ribosomal protein S12 gene as an
early molecular diagnostic identifier for the screening of human
cervical cancer and a potential target employed for cancer gene therapy
trials. Copyright 2002 The Cancer Research Campaign
29
UI - 11168078
AU - Gopalkrishna V; Aggarwal N; Malhotra VL; Koranne RV; Mohan VP; Mittal A;
TI -
Das BC
Chlamydia trachomatis and human papillomavirus infection in Indian women
with sexually transmitted diseases and cervical precancerous and
cancerous lesions.
SO - Clin Microbiol Infect 2000 Feb;6(2):88-93
AD - Division of Molecular Oncology, Institute of Cytology and Preventive
Oncology (Indian Council of Medical Research), New Delhi, India.
OBJECTIVES: Sexually transmitted diseases (STDs) and anogenital cance
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