вход по аккаунту



код для вставкиСкачать
The Promise and Risk of a New Technology
The Lehigh Valley Hospital’s Experience with Liquid-Based Cervical Cytology
William B. Dupree, M.D.1
Harry Z. Suprun, M.D., F.I.A.C.1
David G. Beckwith, Ph.D.1
John J. Shane, M.D.1
Vincent Lucente, M.D.2
Department of Pathology, Health Network Laboratories, Allentown, Pennsylvania.
Department of Obstetrics and Gynecology, Lehigh Valley Hospital, Allentown, Pennsylvania.
The authors wish to thank: Eugene Alexandrin,
M.D., Kelly Frankenfield, B.S., C.T., A.S.C.P., Stephen Klasko, M.D., M.B.A., Kimberly Kemp, B.S.,
M.T., A.S.C.P., Gazi Abdulhay, M.D., Cynthia
Sagullo, M.D., and Elizabeth Dellers, M. D., for
their part in the Health Network Laboratories Experience with liquid-based cervical cytology.
Address for reprints: William B. Dupree, M.D.,
Health Network Laboratories, 2024 Lehigh Street,
Allentown, PA 18103.
Received September 2, 1997; revisions received
December 15, 1997, and January 12, 1998; accepted January 22, 1998.
© 1998 American Cancer Society
‘‘If you can look into the seeds of time and say which
grain will grow and which will not, speak then to me. . .’’
Macbeth, Act 1, Scene 3
nearly silent revolution in women’s health care began in May
1996 when the Federal Drug Administration (FDA) approved the
Thin Prep 2000t System for cervical carcinoma screening. The promise of this new technology is to provide a method by which cytopathologists can easily look into the ‘‘seeds’’ (cells) of time to predict
which cervical lesions will grow (neoplasia) and which will not. This
promise is coupled with a potential reduction in 1) atypical squamous
cells of undetermined significance (ASCUS) and atypical glandular
cells of undetermined significance (AGUS) diagnoses; 2) needless
patient anxiety brought about by spurious ASCUS/AGUS; and 3)
escalation of healthcare costs fueled by needless repeat Papanicolaou
(Pap) tests, colposcopy, and cervical cone biopsies. This potential for
improved quality of care and overall healthcare cost reduction has
spawned a degree of optimism not experienced in cytology since the
days of Papanicolaou.
Mass population screening has proven to be effective in reducing
2– 6
the mortality from cervical carcinomas. Data from Fidler et al. imply
that approximately 75,000 women have to be screened annually to
detect a single case of cervical carcinoma. Approximately 50 million
Pap smears are performed annually in the U.S. Of these, approxi8
mately 8% are abnormal. These abnormal Pap smears result in an
annual cost approaching $6 billion to diagnose and treat. Many
factors contribute to this inefficiency of scale (Table 1). However, one
of the questions we have to face as a society is whether our system
under managed care models will continue to pay for the relatively
small percentage of malignancies that currently are detected by an
inefficient screening and management program. The stage is ready for
a new technology that will improve the efficiency of screening for
cervical disease and provide for adjuvant testing that could help us to
better separate those ‘‘which will grow’’ from those ‘‘which will not.’’
The allure of liquid-based cervical cytology is potent (Table 2). Trends
in preliminary data reported from Lehigh Valley Hospital, which was
among the first wave of laboratories in the nation to adopt Thin Prep
technology, suggest that the promise may be a reality of practice.
Although other liquid-based cytology methodologies are evolving
(Autocyte Prept, Elon College, NC) the focus of this discussion is
limited to our experience with the Thin Prept method developed by
Cytyc Corporation (Boxboro, MA).
Liquid-Based Cervical Cytology/Dupree et al.
Factors Contributing to the Inefficiency of Scale of Cervical Vaginal
Cytology Screening9 –15
Inherent inefficiency due to the screening nature of the test
Technical shortcomings of the test
A Sampling
Variable intervals for repeat Pap
A Normal setting
B Abnormal setting
The borderline Pap dilemma13,19–36,50,54
A lack of consensus as to management of borderline cervical lesions
Malpractice climate in U.S.
ASCUS: atypical squamous cells of undetermined significance; AGUS: atypical glandular cells of
undetermined significance; Pap: Papanicolaou smear.
The New Technology
With Thin Prept methods the clinician obtains the
gynecologic specimen from the patient in the usual
manner either by the FDA-approved cervical broom,
plastic spatula, or cytobrush. The clinician then rinses
the collection device in a vial containing an alcoholbased preservative solution (Preserv-cyt [Cytyc Corp.])
for transport to the cytology laboratory. The vial and
matching slide are placed into the Thin Prep processor
along with a disposable filter cylinder. The Thin Prep
processor automatically prepares the slide in three
steps: dispersion, filtration, and transfer of the cells to
the slide.
Because cellular material on Thin Prept slides has
been collected in a solution and then filtered, its microscopic presentation results in a somewhat different
appearance than on conventional Pap smears. Of distinct advantage for cytotechnologists is the decreased
need to switch between low and high power objectives
for screening information. As a result of immediate
wet fixation, the nuclear hyperchromatic staining appearance, typically associated with squamous lesions
on conventional Pap smears, is reduced. On Thin Prep
slides, cell nuclei often take on a more delicate vesicular appearance and cytoplasmic differentiation becomes an increasingly important indicator of cell origin. Some cytologic characteristics of the liquid-based
method are slightly different from those of the conventional Pap smears; however, the similarities greatly
outweigh the differences.
Health Network Laboratories’ Experience with Thin Prep
Health Network Laboratories (HNL), the clinical laboratory service of Lehigh Valley Hospital, first employed
the Thin Prept method in January 1997. When Thin
Prept results from the initial period of January
through September 1997 were compared with the
same 1996 9-month interval of conventional Pap
smears taken from the same patient pool, certain positive trends were noted. Although more time is required to accrue numbers that will support rigorous
statistical analysis, preliminary trends tend to support
the promise of Thin Prep technology (Table 3).
Results of conventional cervical smears prepared
by the standard Pap technique after alcohol fixation
reported from January through September 1996 were
compared with the liquid-based cervical cytology
preparations (Thin Prept) results that were reported
from January through September 1997 (Table 3). The
general patient sample space for both periods of time
was identical, comprised of cervical cytology specimens taken from the same private, group, and clinic
practices. The six cytotechnologists and three cytopathologists handling the cases were the same for
both time periods. The interobserver variability between the cytotechnologists was approximately 2%.
Data regarding interobservor variability between the
three cytopathologists were not available.
Although the plastic spatula and cytobrush now
have been approved by the FDA for use with the Thin
Prept system, during the initial phase of HNL experience, clinicians were limited to the ‘‘broom’’ sampling
device, the only appliance earlier approved by the FDA
for Thin Prept. This fact, coupled with the learning
curve inherent in any new technology, may have contributed to the 284 additional cases deemed ‘‘unsatisfactory due to lack of endocervical elements,’’ garnered by the liquid-based method. The costs incurred
by repeating many of these Pap tests was assumed by
HNL as part of the developmental expense of instituting a new test.
The 1997 liquid-based Pap test results reflected
159 fewer cases of AGUS and 218 fewer cases of ASCUS
than the equivalent 1996 conventional Pap smear interval. This trend in part may be due to a more effective presentation of cells. Although the reduction in
needless patient anxiety is indisputable, it is more
difficult to calculate the magnitude of the healthcare
cost savings. It is the general consensus among gynecologists that ASCUS/AGUS findings warrant increased patient monitoring. However, experts are divided as to which algorithm represents optimal
management. A balance must be reached between
overtreatment of cytologic changes (which in the majority of cases would regress) and underdiagnosis of a
minority of women at risk for a high grade lesion.
In addition, ASCUS management guidelines may not
necessarily be applied uniformly from locale to locale
or even by members of the same clinical practice
CANCER (CANCER CYTOPATHOLOGY) August 25, 1998 / Volume 84 / Number 4
The ‘‘Promise’’ of Liquid-Based Cervical Cytology Specimens (Thin Prept, CYTYC Corporation)
The ‘‘promise’’
The problem
(Thin Prep)
(Conventional Pap smear)
I Enhanced recovery of cells38,39,40
Eighty percent of cervical cells lost with
discarded cervical collection device37
Up to 40% comprised by artifact41
II Reduction obscurring artifacts
A Preservative solution lyses RBCs
B Obscuring clumps of mucus
C Aggregates of ‘‘polys’’
D Cellular overlap reduction
E Air-dried artifact eliminated
III Advantage for cytotechnologist
A Improved cell presentation
IV Ancillary tests
Liquid-based specimen container
serves as ready source of cells for
ancillary studies such as HPV
V Cost
Cost benefit studies and outcome
studies will justify use of liquidbased cervical cytology screening
The ‘‘hope’’
Significant reduction in false-negative rate38–40 (increased sensitivity)
Reduction in diagnosis
ASCUS/AGUS due to specimen compromise
A Fewer repeat Pap tests
B Fewer colposcopies
C Fewer biopsies (Increased sensitivity)42,54
Up to 40% compromised by artifact41
Reduction in screening-related stress15
Greater productivity45
Elimination of added cost and inconvenience of a repeat specimen
The majority of ancillary studies require
repeat specimen
The conventional Pap test is undervalued
Minimal added cost will be justified by cost benefit and outcome
Pap: Papanicolaou smear; RBCs: red blood cells; ASCUS: atypical squamous cells of undetermined significance; AGUS: atypical glandular cells of undetermined significance; HPV: human papillomavirus.
Preliminary HNL Liquid-Based Cytology Results Compared with Conventional Cervical Smear Results–1996
Total preparations
Turnaround time
Conventional cervical smears
(January–September 1996)
Liquid-based cytology preparations
(January–September 1997)
22,323 cases
12 days
19,351 cases
6 days
2972 fewer liquid-based cases
284-case increase in liquid-based method
218-case decrease in liquid-based method
159-case decrease in liquid-based method
52-case increase in liquid-based method
7-case increase in liquid-based method
Turnaround time decrease of 6 days for
liquid-based method
ASCUS: atypical squamous cells of undetermined significance; AGUS: atypical glandular cells of undetermined significance; LSIL: low grade squamous intraepithelial lesion; HSIL: high grade squamous intraepithelial
group. In areas in which sensitivity of detection of
squamous intraepithelial lesions (SIL) is of paramount
importance, colposcopy and biopsy make sense. However, in areas in which a more cost-effective approach
is preferred, cytologic follow-up may be utilized. In a
similar fashion, management options for AGUS include: 1) repeat cytologies at more frequent intervals;
2) colposcopy with biopsy as indicated and endocervical curettage/cytobrush specimens; or 3) cone biopsy. Regardless of differences in philosophies and
attendant management strategies, the potential reduction of spurious ASCUS and AGUS cases will spell
significant savings in needless patient anxiety and
healthcare costs. Preliminary numbers indicate that
the liquid-based Pap tests potentially identified 52
additional cases of low grade SIL (LSIL) and 7 additional cases of high grade SIL (HSIL). This potential
enrichment of significant diagnoses may in part be
due to a reduction in ASCUS/AGUS cases due to a
compromise in the conventional smear or actually
may reflect a greater sensitivity linked to superior
sampling by the clinician and Thin Prept method. An
added positive feature of Thin Prept technology was a
unanimous vote of increased job satisfaction among
Liquid-Based Cervical Cytology/Dupree et al.
HNL cytotechnologists. This finding was coupled with
a 20% increase in productivity and a reduction of
turnaround time from 12 to 6 days.
The Risk of New Technology
Many uncertainties face cytology laboratories that will
be processing Pap smears in the late 1990s. In an age
of managed care and at best marginal reimbursement,
some cytology laboratories have found it difficult to
even recoup the cost of performing the test. Medical
malpractice suits against pathologists and cytotechnologists who allegedly miss abnormal cells may now
charge homicide. Will there be tort reforms? Will the
promise of liquid-based cytology and automated
screening be realized? Will the new technology be
cost-effective? Will society and payers of healthcare
put their money where the value is? Faced with these
uncertainties, many prominent cytology laboratories
are wondering whether the risk/benefit ratio warrants
the continuation of even conventional Pap services
and are reluctant to explore new technologies because
of increased cost and potential medicolegal risks.
The clinical and scientific allure of liquid-based
technology is potent. Early experience at HNL suggests that the scientific and clinical promise of Thin
Prept are real. However, the early acquisition of any
new technology forces the sponsoring institution to
assess risk centering around operational issues such
as test performance, test quality, cost, reimbursement,
customer acceptance, customer satisfaction, improved clinical outcomes, and obsolescence. The opposite perspective from risk is organizational advantage, which for a new technology includes market
recognition, competitive edge, better patient outcomes, new sources of profit, and more satisfied employees. A risk/benefit analysis was conducted as part
of Lehigh Valley Hospital’s decision to adopt Thin
Prept methods as an alternative to conventional
methods of Pap smear processing.
In keeping with Lehigh Valley Hospital’s commitment to offering the most up-to-date and cost-effective technologies to improve community health
outcomes, assessment of liquid-based Pap smear
technology became a high priority. To evaluate the
potential risk of failed performance and suboptimal
quality one must ignore marketing propaganda coupled with testimonials and rely heavily on the critical
review of pilot studies employing the new technology
in question. A careful review of preliminary studies in
conjunction with FDA analysis quickly demonstrated
the clinical and scientific validity of the method. Meetings with gynecologists and gynecologic oncologists
revealed a similar level of confidence enjoined with
conservative optimism. A program to acquaint gyne-
cologists, residents, and office support teams with the
technical aspects of the new liquid-based process was
instituted and met with guarded enthusiasm. This initial introductory program is critical to create a relatively problem free transition from conventional to
liquid-based Pap smears and promote customer acceptance. In addition, to ensure patient satisfaction a
short educational program was crafted explaining the
advantages of Thin Prep, which warrant the relatively
small increase in cost. Programs were devised to inform patients that depending on the policies of their
health care payer, some of this additional cost might
represent an out-of-pocket expense. With the final
decision to implement liquid-based Pap smears, a cytotechnologist-cytopathologist team attended training
sessions at Cytyc Corporation headquarters and after
certification became instructors to certify the remaining cytotechnologists and pathologists at HNL. Split
sample testing including conventional Pap smears
and liquid-based preparations was instituted to validate the in-house procedure. Our recommendation is
that all users of the liquid-based method allow time
and resources for adequate training with split sample
trials to mitigate risks occurring during familiarization
of technologists and pathologists with a new method.
The risk associated with adding increased costs to
an already underreimbursed test was of concern. Today laboratories are scrutinizing their costs closely
and realizing that previously established reimbursement rates do not even come close to covering the true
cost of conventional Pap smears.50 An April 1996 article in the Dark Report, a business intelligence service
for clinical laboratory executives, reported that even
large commercial laboratories are subjecting their laboratory services to rigorous cost analyses and finding
that the Pap smear is a major money loser. Whether
laboratories will be able to move prices upward to
recover full costs, the author speculated, could vary
regionally according to competition.51,52 With these
problems keenly in mind, it was our contention that,
when legally possible, the consumer would be willing
to shoulder the minimal added financial burden once
educated as to the advantages of the test. Although
work remains to be done, in general women are beginning to understand better the importance of
screening tests for cervical carcinoma. Women want a
test that is reliable, accurate, and predictive and that
ideally leads to as few questionable results and repeat
testing as possible. HNL market research indicated
that women in the Lehigh Valley would be willing to
pay for this test even if the payment is above and
beyond that covered by their insurance. Our first belief, now supported by the preliminary trends reported
here, was that the promise of the new technology to
CANCER (CANCER CYTOPATHOLOGY) August 25, 1998 / Volume 84 / Number 4
reduce both patient anxiety and the overall outlay of
community expenses in detecting and managing cervical disease would be realized. We chose to assume
the risk related to reimbursement. To date several
insurers have agreed to reimburse all or in some instances at least a part of the minimally increased
charge. As predicted, women whose insurance plans
will not cover the expense are choosing to pay out-ofpocket. Our customer acceptance data indicate
women appreciate the option to have their Pap smears
prepared using liquid-based technology and in some
instances insist on the method.
Another risk in adopting any new technologic advance is the risk of obsolescence. Monolayer technology finds its origin in the quest for the perfect automated screening device. It is our opinion that liquidbased technology will play a key role in more efficient
and accurate automated screening in the future. In
addition, this new technology lends itself more effectively to the triage of LSIL as well as ASCUS/AGUS on
the basis of human papillomavirus viral typing. We
believe that liquid-based Pap technology will prepare
our laboratory for the day when these additional technologies become a central part of the diagnosis and
management of cervical disease. The liquid-based Pap
technology is one of several technologies we have
chosen to invest in as part of an automation initiative.
It is viewed as an investment that will in the future
‘‘pay off’’ by enhancing methods for Pap screening
that should improve clinical outcomes and productivity, and reduce overall cost of care.
As an additional immediate advantage, our implementation of the liquid-based method has greatly improved our cytotechnologist job satisfaction rating,
increased our market share, and provided HNL with
the opportunity to support our Women’s Health Program.
calating costs and the plethora of new medical alternatives, the federal government, insurers, physicians,
hospital administrators, and nurses have initiated critical reviews with a single goal: to determine which of
our medical technologies truly are effective. One approach to such a review is embodied in the rapidly
growing field of outcomes research.53 It is hoped that
with more liquid-based Pap tests and their outcome
studies, our ability to evaluate whether liquid-based
systems will truly allow us to better ‘‘look into the
seeds’’ (cells) ‘‘of time’’ and predict ‘‘which will grow
and which will not.’’
Comparison of conventional Pap smears and fluidbased thin layer systems are beginning to show a
statistically significant increase in the sensitivity of
liquid-based systems over conventional Pap tests.55
Preliminary experience of HNL suggests that the
promise of liquid-based cervical cytology preparations
not only improves the sensitivity of the cytology test
but also greatly enhances the overall quality of the
cervicovaginal cytology service. Although the promise
of liquid-based cervicovaginal cytology appears to be
real, cautious optimism is indicated. The past 20 years
have been remarkable for the rapid proliferation of
new medical procedures and technologies. At the
same time the cost of these new technologies also has
increased extraordinarily. Spurred by these rapidly es-
Wilbur DC, Cibas ES, Merritt S, James LP, Berger BM, Bonfiglio TA. Thin Prep Processor: clinical trials demonstrate on
increased detection rate of abnormal cervical cytology specimen. Am J Clin Pathol 1994;101:209 –14.
Wingo PA, Tong T, Bolden S. Cancer statistics, 1995. CA
Cancer J Clin 1995;45:8 –30.
Richart RM, Meijer C, Greenberg MD, Schiffman MH, Cox
JT. Using HPV tests to manage patients with abnormal Pap
smears. Contemp Obstet Gynecol 1995;40:65– 88.
Benedet JL, Anderson GH, Matisic JP. A comprehensive program for cervical cancer detection and management. Am J
Obstet Gynecol 1992;166:1254 –9.
Sparen P, Gustafsson L, Friberg LG, Poten J, Bergstrom R,
Adam HO. Improved control of invasive cervical cancer in
Sweden over six decades, by earlier clinical detection and
better treatment. J Clin Oncol 1995;13:715–25.
Walton RJ. Cervical cancer screening programs: II. Screening for carcinoma of the cervix. Can Med Assoc J 1976;114:
Fidler HK, Boyes DA, Worth AJ. Cervical cancer detection in
British Columbia. J Obstet Gynecol Br Commonw 1968;75:
392– 404.
Sheets EE. Clinical management of abnormal pap smears.
In: Cibas E, Lee K, editors. recent advances in diagnostic
cytology. Boston: Harvard Medical School, 1996:126 –9.
Coppleson LW, Brown B. Estimation of screening error rate
from the observed detection rates in repeated cervical cytology. Am J Obstet Gynecol 1974;119:953– 8.
Dehner LP. Cervicovaginal cytology, false negative results
and standards of practice. Am J Clin Pathol 1993;99:45–7.
Figge DC, Bennington JL, Schweid AI. Cervical cancer after
initial negative and atypical vaginal cytology. Am J Obstet
Gynecol 1970;108:422– 8.
Frost JK. Diagnostic accuracy of ‘‘cervical smears.’’ Obstet
Gynecol Surv 1969;24:893–908.
Richart RM, Vaillant HW. Influence of cell collection techniques upon cytological diagnosis. Cancer 1965;18:1474 – 8.
Vooijs GP, Elias A, van der Graaf Y, Poelen-van de Berg M.
The influence of sample takers on the cellular composition
of cervical smears. Acta Cytol 1986;30:251–7.
Demay RM. To err is human—to sue, American. Diagn
Cytopathol 1996;15(3):iii–vi.
Chen F, Trapido EJ, Davis K. Differences in stage at presentation of breast and gynecologic cancers among whites,
blacks and Hispanics. Cancer 1994;73:2838 – 42.
Carlson JW, Twiggs LB. Clinical applications of molecular
biopsy screening for human papilloma virus. Obstet Gynecol
1992;35(1):13– 6.
Liquid-Based Cervical Cytology/Dupree et al.
18. Ashfag R, Liang Y, Saborian MH. Evaluation of PAPNETt
system for rescreening of negative cervical smears. Diagn
Cytopathol 1995;13:31– 6.
19. Birdsong GG. Automated rescreening of Papanicolaou
smears: what are the implications? Diagn Cytopathol 1995;
13:283– 6.
20. Kurman RJ, Solomon D. The Bethesda system for reporting
cervical/vaginal cytologic diagnoses. New York: SpringerVerlag, 1994:30 – 43.
21. Robb JA. The ‘‘ASCUS’’ swamp. Diagn Cytopathol 1994;11:
319 –20.
22. Lee KR, Manna EA, St. John T. Atypical endocervical glandular cells: accuracy of cytologic diagnosis. Diagn Cytopathol 1995;13:202– 8.
23. Wilbur DC, Bonfiglio TA. Editorial comments: atypical squamous cells in cervical smears—resolving a controversy. Diagn Cytopathol 1993;9:423–9.
24. Sidawy MK, Tabbara SO. Reactive change and atypical squamous cells of undetermined significance in Papanicolaou
smears: a cytohistologic correlation. Diagn Cytopathol 1993;
25. Genest D, Dean B, Galvane KE, Lee K, LaGuette J, Sheets E,
et al. Subclassification of atypical Pap smears and the likelihood of squamous intra epithelial lesion (SIL) on subsequent biopsy [abstract]. Mod Pathol 1996;9:34A.
26. Frable WJ. Litigation cells: definition and observation on a
cell type in cervical vaginal smears not addressed by the
Bethesda System. Diagn Cytopathol 1994;11:213–5.
27. Voytek TM, Kannan V, Kline TS. Atypical parakeratosis. ‘‘A
marker of dysplasia?’’ Diagn Cytopathol 1996;15:288 –91.
28. Davey DD, Naryshkin S, Nielsen ML, Kline TS. Atypical
squamous cells of undetermined significance: interlaboratory comparison and quality assurance monitors. Diagn Cytopathol 1994;11(4):390 – 6.
29. Sherman ME, Schiffman MH, Lorincz AT, Manos MM, Scott
DR, et al. Toward objective quality assurance in cytopathology. Am J Clin Pathol 1994;102:182–7.
30. Interlaboratory Comparison Program In Cervicovaginal Cytology. 1993 PAP supplemental questionnaire on laboratory
practice: ASCUS. St. Louis, MO: College of American Pathologists, 1994.
31. Raffle AE, Alden B, MacKenzie EF. Detection rates for abnormal smears: what are we screening for? Lancet 1995;345:
1469 –73.
32. Herbst AL. The Bethesda system for cervical/vaginal cytologic diagnoses: a note of caution. Obstet Gynecol 1990;76:
449 –50.
33. Raab SS, Isacson C, Layfield LJ, Lenel JC, Flagel DB, Thomas
PA. Atypical glandular cells of undetermined significance:
cytologic criteria to separate clinically significant from benign lesions. Am J Clin Pathol 1995;104:574 – 82.
34. Selvaggi SM. Cytologic features of squamous cell carcinoma
in situ involving endocervical glands in endocervical brush
specimens. Acta Cytol 1994;38:687–92.
35. Wilbur DC, Mulford DM, Sickel JZ, Atkinson KM. The problem of endocervical atypia: new cytologic presentation of
normal endocervical cells and squamous neoplasia. Acta
Cytol 1994;38:808 –12.
36. Babkowski RC, Wilbur DC, Rutkowski MA, Facik MS, Bonfiglio TA. The effects of endocervical canal topography, tubal
metaplasia, and high canal sampling on the cytologic presentation of non-neoplastic endocervical cells. Am J Clin
Pathol 1996;105:403–10.
37. Hutchinson ML, Isenstein LM, Goodman A, et al. Homogenous sampling accounts for increased diagnostic accuracy
using the Thin Prep processor. Am J Clin Pathol 1994;101:
38. Joseph MG, Cragg F, Wright VC, Kontozoglou TE, Downing
P, Marks FR. Cyto histological correlates in a colposcopic
clinic: a 1-year perspective study. Diagn Cytopathol 1991;
7(5):477– 81.
39. Hutchinson ML, Cassin CM, Ball HG III. The efficacy of an
automated preparation device for cervical cytology. Am J
Clin Pathol 1991;96:300 –5.
40. Hutchinson ML, Agarual P, Denault T, Berger B, Cibas ES. A
new look at cervical cytology: Thin Prep multicenter trial
results. Acta Cytol 1992;36:499 –504.
41. Davey DD, Nielsen ML, Rosenstock W, Kline TS. Terminology and specimen adequacy in cervicovaginal cytology: the
College of American Pathologists Interlaboratory Comparison Program experience. Arch Pathol Lab Med 1992;116:
42. Noumoff JS. Atypia in cervical cytology as a risk factor for
intraepithelial neoplasia. Am J Obstet Gynecol 1987;156:628 –
43. Lindheim SR, Smith-Nguyen G. Aggressive evaluations for
atypical squamous cells in Papanicolaou smears. J Reprod
Med 1990;35:971–3.
44. Data on file, Cytyc Corporation
45. Rules and regulations. Federal Register 1992;57:7137– 86.
46. Koss LG. Cervical (Pap) smear: new directions. Cancer 1993;
71(Suppl):1406 –12.
47. Sherman M, Solomon D, Kurman RJ, Stults M. Bethesda,
MD: ALTS Study NCI Work in Progress.
48. Douglas KL. Thin Prep morphology reference manual.
CYTYC Corp, 1994: 2– 4.
49. Kurman RJ, Henson DE, Herbst A, Noller KL, Schiffman MH.
Interim guidelines for management of abnormal cervical
cytology. JAMA 1994;271:1866 –9.
50. Goff BA, Atanasoff P, Brown E, Muntz HG, Bell DA, Rice LW.
Endocervical glandular atypia in Papanicolaou smears. Obstet Gynecol 1992;79:101– 4.
51. Pelehach L. Appraising the Pap smear. Arch Pathol Lab Med
1997;28:440 –9.
52. Michel R. Losses from Pap smear testing may trigger higher
test prices. Dark Rep 1996 April 8:1–15.
53. Chelmow D. Outcomes research applied to obstetrics— gynecology. Contemp Obstet Gynecol 1996;41:131– 43.
54. Solomon D. Diagnostic cytology toward the 21st century. In:
International Expert Conference, Proceedings of Task Force
on ASCUS and AGUS Criteria, Position Paper, 1997.
55. Lee KR, Ashfaq R, Birdsong GC, et al. Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer
system for cervical cancer screening. Obstet Gynecol 1997;
90(2):278 – 84.
Без категории
Размер файла
83 Кб
Пожаловаться на содержимое документа