Hologic thinprep 2000 Operator's Manual

ThinPrep

®

2000 Processor

LABORATORY SOLUTIONS

Operator’s Manual

Operator’s Manual

MAN-02585-001 Rev. 005

ThinPrep® 2000 System
Operator’s Manual

HOLOGIC, INC.HOLOGIC (UK) LIMITED
250 CAMPUS DRIVE UNIT 2, LINK 10 NAPIER WAY
MARLBOROUGH, MA 01752 USA CRAWLEY, WEST SUSSEX RH10 9RA
T

EL: 1-800-442-9892 UNITED KINGDOM

1-508-263-2900 TEL: [phone]

F

AX: 1-508-229-2795 FAX: [phone]

W

EB: WWW.HOLOGIC.COM

MAN-02585-001

Caution: Federal law restricts this device to sale by or on the order of a physician, or any other
practitioner licensed by the law of the State in which the practitioner practices to use or order the use
of the device and are trained and experienced in the use of the ThinPrep 2000 System.

Preparation of microscope slides using the ThinPrep 2000 System should be performed only by
personnel who have been trained by Hologic or by organizations or individuals designated by
Hologic.

Evaluation of microscope slides produced with the ThinPrep 2000 System should be performed only
by cytotechnologists and pathologists who have been trained to evaluate ThinPrep-prepared slides
by Hologic or by organizations or individuals designated by Hologic.

© Hologic, Inc., 2014. All rights reserved. No part of this publication may be reproduced,
transmitted, transcribed, stored in a retrieval system, or translated into any language or computer
language, in any form, or by any means, electronic, mechanical, magnetic, optical, chemical, manual,
or otherwise, without the prior written permission of Hologic, 250 Campus Drive, Marlborough,
Massachusetts, 01752, United States of America.

Although this guide has been prepared with every precaution to ensure accuracy, Hologic assumes
no liability for any errors or omissions, nor for any damages resulting from the application or use of
this information.

This product may be covered by one or more U.S. patents identified at
http://hologic.com/patentinformation

Hologic, CytoLyt, PreservCyt and ThinPrep are registered trademarks of Hologic, Inc. or its
subsidiaries in the United States and/or other countries. All other trademarks are the property of
their respective companies.

Caution: Changes or modifications to this unit not expressly approved by the party responsible
for compliance could void the user’s authority to operate the equipment.

Document number: AW-08263-001 Rev. 004

Instructions for Use

ThinPrep 2000

ThinPrep 2000

Instructions for Use

Instructions For Use

MAN-02624-001 Rev. 003 page 1 of 15

INTENDED USE

The ThinPrep
smear preparation for use in screening for the presence of atypical cells, cervical cancer, or its
precursor lesions (Low-grade Squamous Intraepithelial Lesions, High-grade Squamous
Intraepithelial Lesions), as well as all other cytologic categories as defined by The Bethesda

System for Reporting Cervical/Vaginal Cytologic Diagnoses

®

2000 System is intended as a replacement for the conventional method of Pap

1

.

SUMMARY AND EXPLANATION OF THE SYSTEM

The ThinPrep process begins with the patient’s gynecologic sample being collected by the
clinician using a cervical sampling device which, rather than being smeared on a microscope
slide, is immersed and rinsed in a vial filled with 20 ml of PreservCyt
The ThinPrep sample vial is then capped, labeled, and sent to a laboratory equipped with a
ThinPrep 2000 Processor.

At the laboratory, the PreservCyt sample vial is placed into a ThinPrep 2000 Processor and a
gentle dispersion step breaks up blood, mucus, non-diagnostic debris, and thoroughly mixes the
cell sample. The cells are then collected on a ThinPrep Pap Test Filter specifically designed to
collect diagnostic cells. The ThinPrep 2000 Processor constantly monitors the rate of flow
through the ThinPrep Pap Test Filter during the collection process in order to prevent the
cellular presentation from being too scant or too dense. A thin layer of cells is then transferred
to a glass slide in a 20 mm-diameter circle, and the slide is automatically deposited into a
fixative

solution.

The ThinPrep Sample Preparation Process

®

Solution (PreservCyt).

(1) Dispersion (2) Cell Collection (3) Cell Transfer

The ThinPrep Pap Test Filter rotates within the
sample vial, creating currents in the fluid that
are strong enough to separate debris and
disperse mucus, but gentle enough to have no
adverse effect on cell appearance.

A gentle vacuum is created within the ThinPrep
Pap Test Filter, which collects cells on the
exterior surface of the membrane. Cell
collection is controlled by the ThinPrep 2000
Processor’s software that monitors the rate of
flow through the ThinPrep Pap Test Filter.

After the cells are collected on the membrane,
the ThinPrep Pap Test Filter is inverted and
gently pressed against the ThinPrep Microscope
Slide. Natural attraction and slight positive air
pressure cause the cells to adhere to the
ThinPrep Microscope Slide resulting in an even
distribution of cells in a defined circular area.

MAN-02624-001 Rev. 003 page 2 of 15

As with conventional Pap smears, slides prepared with the ThinPrep

®

2000 System are examined
in the context of the patient’s clinical history and information provided by other diagnostic
procedures such as colposcopy, biopsy, and human papillomavirus (HPV) testing, to determine
patient management.

The PreservCyt
and transport medium for gynecologic specimens tested with the Cervista
Cervista

®

®

Solution component of the ThinPrep 2000 System is an alternative collection

®

HPV HR Test, the

HPV 16/18 Test, the Roche cobas® HPV Test and the Digene Hybrid Capture
System HPV DNA. Refer to the respective manufacturer’s package inserts for instructions for
using PreservCyt Solution for collection, transport, storage, and preparation of specimens for use
in those systems.

The PreservCyt Solution component of the ThinPrep 2000 System is an alternative collection
and transport medium for gynecologic specimens tested with the Hologic APTIMA COMBO 2
CT/NG Assays, the Hologic APTIMA

x

CT Q

Amplified DNA Assay. Refer to the respective manufacturer’s package inserts for

®

Trichomonas vaginalis Assay, and the BD ProbeTec™

®

instructions for using PreservCyt Solution for collection, transport, storage, and preparation of
specimens for use in those systems.

The PreservCyt Solution component of the ThinPrep 2000 System is also an alternative
collection and transport medium for gynecologic specimens tested with the Roche Diagnostics
COBAS AMPLICOR

TM

CT/NG assay. Refer to Hologic’s labeling (Document #MAN-02063-

001) for instructions for using PreservCyt Solution for collection, transport, storage, and
preparation of specimens and to the Roche Diagnostics COBAS AMPLICOR CT/NG package
insert for instructions for use of that system.

LIMITATIONS

 Gyne cologic sa mples col lected fo r preparat ion using the T hinPrep 2 000 System should be

collected using a broom-type or endocervical brush/plastic spatula combination collection
devices.

 Preparation of microscope slides using the ThinPrep 2000 System should be performed only

by personnel who have been trained by Hologic or by organizations or individuals
designated by Hologic.

 Evaluation of microscope slides produced with the ThinPrep 2000 System should be

performed only by cytotechnologists and pathologists who have been trained to evaluate
ThinPrep prepared slides by Hologic or by organizations or individuals designated by
Hologic.

 Supplies used in the ThinPrep 2000 System are those designed and supplied by Hologic

specifically for the ThinPrep 2000 System. These include PreservCyt Solution vials,
ThinPrep Pap Test Filters, and ThinPrep Microscope Slides. These supplies are required for
proper performance of the system and cannot be substituted. Product performance will be
compromised if other supplies are used. After use, supplies should be disposed of in
accordance with local, state, and federal regulations.

 A ThinPrep Pap Test Filter must be used only once and cannot be reused.
 The performance of HPV DNA and CT/NG testing on reprocessed sample vials has not been

evaluated.

MAN-02624-001 Rev. 003 page 3 of 15

WARNINGS

 For In Vitro Diagnostic Use
 PreservCyt Solution contains methanol, which is poisonous and may be fatal or cause

blindness if swallowed. Methanol vapor may be harmful. PreservCyt is flammable; keep
away from fire, heat, sparks, and flame. Other solutions must not be substituted for
PreservCyt Solution. PreservCyt Solution should be stored and disposed of in accordance
with local, state, and federal regulations.

 Do not process a cerebral spinal fluid (CSF) specimen or other sample type that is suspected

of possessing prion infectivity (PrPsc) derived from a person with a TSE, such as
Creutzfeldt-Jakob disease, on a ThinPrep processor. A TSE-contaminated processor cannot
be effectively decontaminated and therefore must be properly disposed of in order to avoid
potential harm to users of the processor or service personnel.

PRECAUTIONS

 Specific processing steps must be followed before and during use of the ThinPrep 2000 processor

if planning to perform Chlamydia trachomatis and Neisseria gonorrhoeae testing, using the Roche
Diagnostics COBAS AMPLICOR CT/NG test, on the residual specimen after a slide has been
prepared using a ThinPrep 2000 processor. Follow the procedures found in Chapter 5B of the
ThinPrep 2000 Operator’s Manual.

 This equipment generates, uses and can radiate radio frequency energy, and if not installed and

used in accordance with the Operator’s Manual, may cause interference to radio communications.
Operation of this equipment in a residential area is likely to cause harmful interference, in which
case the user will be required to correct the interference at his/her own expense.

 PreservCyt Solution with cytologic sample intended for ThinPrep Pap testing must be stored

between 15

 PreservCyt Solution with cytologic sample intended for CT/NG testing using the Roche

Diagnostics COBAS AMPLICOR CT/NG test must be stored between 4
and tested within 6 weeks of collection.

 PreservCyt Solution was challenged with a variety of microbial and viral organisms. The

following table presents the starting concentrations of viable organisms, and the number of viable
organisms found after 15 minutes in the PreservCyt Solution. The log reduction of viable
organisms is also presented. As with all laboratory procedures, universal precautions should be
followed.

oC

(59oF) and 30oC (86oF) and tested within 6 weeks of collection.

o

C (39oF) and 25oC (77oF)

MAN-02624-001 Rev. 003 page 4 of 15

Organism Initial Concentration

Candida albicans 5.5 x 105 CFU/mL >4.7

Aspergillus niger* 4.8 x 105 CFU/mL 2.7

Escherichia coli 2.8 x 105 CFU/mL >4.4

Staphylococcus aureus 2.3 x 105 CFU/mL >4.4

Pseudomonas aeruginosa 2.5 x 105 CFU/mL

Mycobacterium tuberculosis** 9.4 x 105 CFU/mL 4.9

Rabbitpox virus 6.0 x 106 PFU/mL 5.5***

HIV-1 1.0 x 10

* After 1 hour >4.7 log reduction

** After 1 hour >5.7 log reduction
*** Data is for 5 minutes

Log Reduction after

15 min.

>4.4

7.5

TCID50/mL 7.0***

PERFORMANCE CHARACTERISTICS: REPORT OF CLINICAL
STUDIES

A prospective multi-center clinical study was conducted to evaluate the performance of the ThinPrep
2000 System in direct comparison to the conventional Pap smear. The objective of the ThinPrep
clinical study was to demonstrate that gynecologic specimens prepared using the ThinPrep 2000
System were at least as effective as conventional Pap smears for the detection of atypical cells and
cervical cancer or its precursor lesions in a variety of patient populations. In addition, an assessment of
specimen adequacy was performed.

The initial clinical study protocol was a blinded, split sample, matched pair study, for which a
conventional Pap smear was prepared first, and the remainder of the sample (the portion that normally
would have been discarded) was immersed and rinsed into a vial of PreservCyt Solution. At the
laboratory, the PreservCyt sample vial was placed into a ThinPrep 2000 Processor and a slide was then
prepared from the patient’s sample. ThinPrep and conventional Pap smear slides were examined and
diagnosed independently. Reporting forms containing patient history as well as a checklist of all
possible categories of The Bethesda System were used to record the results of the screening. A single
independent pathologist reviewed all discrepant and positive slides from all sites in a blinded fashion to
provide a further objective review of the results.

LABORATORY AND PATIENT CHARACTERISTICS

Cytology laboratories at three screening centers (designated as S1, S2, and S3) and three hospital
centers (designated as H1, H2, and H3) participated in the clinical study. The screening centers in the
study serve patient populations (screening populations) with rates of abnormality (Low-grade
Squamous Intraepithelial Lesion [LSIL] and more severe lesions) similar to the United States average
of less than 5%.
(hospital populations) characterized by high rates (>10%) of cervical abnormality. Data on race

2

The hospital centers in the study serve a high risk referral patient population

MAN-02624-001 Rev. 003 page 5 of 15

demographics was obtained for 70% of the patients that participated in the study. The study population
consisted of the following race groups: Caucasian (41.2%), Asian (2.3%), Hispanic (9.7%), African
American (15.2%), Native American (1.0%) and other groups (0.6%).

Table 1 describes the laboratories and the patient populations.

Table 1: Site Characteristics

Site Type of

Population

S1 Screening 300,000 1,386 18.0 - 84.0 10.6% 8.8% 2.3%
S2 Screening 100,000 1,668 18.0 - 60.6 0.3% 10.7% 2.9%
S3 Screening 96,000 1,093 18.0 - 48.8 0.0% 7.1% 3.8%

H1 Hospital 35,000 1,046 18.1 - 89.1 8.1% 40.4% 9.9%
H2 Hospital 40,000 1,049 18.1 - 84.4 2.1% 18.2% 12.9%
H3 Hospital 37,000 981 18.2 - 78.8 11.1% 3 8.2% 24.2%

Laboratory Characteristics Clinical Study Demographics

Patient

Laboratory

Volume -

Smears per

Year

Cases Patient

CLINICAL STUDY RESULTS

The diagnostic categories of The Bethesda System were used as the basis of the comparison between
conventional and ThinPrep
statistical analyses for all clinical sites are presented in Tables 2 through 11. Cases with incorrect
paperwork, patient’s age less than 18 years, cytologically unsatisfactory slides, or patients with a
hysterectomy were excluded from this analysis. Few cases of cervical cancer (0.02%
represented in the clinical study, as is typical in the United States patient population.

®

findings from the clinical study. The diagnostic classification data and

Age Range

Post-Meno-

pausal

Previous

Abnormal Pap

Smear

Convent.

Prevalence

LSIL+

3

) were

Table 2: Diagnostic Classification Table, All Categories

ThinPrep NEG
ASCUS

AGUS 13 2 3 0 1 0 1 20
LSIL 114 84 0 227 44 0 0 469
HSIL 11 15 0 35 104 2 0 167
SQ CA 0 0 0 0 0 1 0 1
GL CA 0 0 0 0 0 0 0 0
TOTAL 5680 521 8 367 167 3 1 6747

Abbreviations for Diagnoses: NEG = Normal or negative, ASCUS = Atypical Squamous Cells of
Undetermined Significance, AGUS = Atypical Glandular Cells of Undetermined Significance, LSIL = Low­grade Squamous Intraepithelial Lesion, HSIL = High-grade Squamous Intraepithelial Lesion, SQ CA =
Squamous Cell Carcinoma, GL CA = Glandular Cell Adenocarcinoma

Conventional

NEG ASCUS AGUS LSIL HSIL SQ CA GL CA TOTAL

5224 295 3 60 11 0 0 5593

318

125 2 45 7 0 0 497

MAN-02624-001 Rev. 003 page 6 of 15

Table 3: Three Category Diagnostic Classification Table

Conventional

NEG ASCUS/AGUS+ LSIL+ TOTAL

ThinPrep NEG

ASCUS/

AGUS+

LSIL+ 125 99 413 637

TOTAL 5680 529 538 6747

5224 298 71 5593

331 132 54 1154

Table 4: Two Category Diagnostic Classification Table, LSIL and More Severe Diagnoses

Conventional

NEG/ASCUS/

AGUS+

ThinPrep NEG/ASCUS/

AGUS+

LSIL+ 224 413 637

TOTAL 6209 538 6747

5985 125 6110

LSIL+ TOTAL

Table 5: Two Category Diagnostic Classification Table, ASCUS/AGUS and More Severe Diagnoses

NEG ASCUS/AGUS+ TOTAL

ThinPrep NEG

ASCUS/

AGUS+

TOTAL 5680 1067 6747

5224 369 5593

456 698 1154

MAN-02624-001 Rev. 003 page 7 of 15

The diagnostic data analysis from the sites is summarized in Table 6 and 7. When the p-value is significant (p <

0.05), the method favored is indicated in the tables.

Table 6: Results by Site, LSIL and More Severe Lesions

Site

S1

Cases ThinPrep

LSIL+

1,336 46 31 48% 0.027 ThinPrep

Convent.

LSIL+

Increased

Detection*

p-Value Method

Favored

S2
S3

H1
H2

H3

*Increased detection = ThinPrep® LSIL+ - Conventional LSIL+ x 100%

Conventional LSIL+

1,563 78 45 73% <0.001 ThipPrep
1,058 67 40 68% <0.001 ThinPrep

971 125 96 30% <0.001 ThinPrep
1,010 111 130 (15%) 0.135 Neither

809 210 196 7% 0.374 Neither

For LSIL and more severe lesions, the diagnostic comparison statistically
favored the ThinPrep

®

method at four sites and was statistically equivalent at

two sites.

Table 7: Results by Site, ASCUS/AGUS and More Severe Lesions

Site

S1 1,336 117 93 26% 0.067 Neither
S2 1,563 124 80 55% <0.001 ThinPrep
S3 1,058 123 81 52% <0.001 ThinPrep

Cases ThinPrep

ASCUS+

Convent.
ASCUS+

Increased

Detection*

p-Value Method

Favored

H1 971 204 173 18% 0.007 ThinPrep
H2 1,010 259 282 (8%) 0.360 Neither
H3 809 327 359 (9%) 0.102 Neither

*Increased detection = ThinPrep ASCUS+ - Conventional ASCUS+ x 100%

Conventional ASCUS+

For ASCUS/AGUS and more severe lesions, the diagnostic comparison statistically favored the
ThinPrep method at three sites and was statistically equivalent at three sites.

One pathologist served as an independent reviewer for the six clinical sites, receiving both slides from
cases where the two methods were either abnormal or discrepant. Since a true reference cannot be
determined in such studies and therefore true sensitivity cannot be calculated, the use of an expert
cytologic review provides an alternative to histologic confirmation by biopsy or human papillomavirus
(HPV) testing as a means for determining the reference diagnosis.

The reference diagnosis was the more severe diagnosis from either of the ThinPrep or conventional
Pap slides as determined by the independent pathologist. The number of slides diagnosed as abnormal
at each site, compared to the reference diagnosis of the independent pathologist, provides the
proportion of LSIL or more severe lesions (Table 8) and the proportion of ASCUS/AGUS or more
severe lesions (Table 9). The statistical analysis allows a comparison of the two methods and a
determination of which method is favored when using the independent pathologist for expert cytologic
review as the adjudicator of the final diagnosis.

MAN-02624-001 Rev. 003 page 8 of 15

Table 8: Independent Pathologist Results by Site, LSIL and More Severe Lesions

Site

S1 50 33 25 0.170 Neither

S2 65 48 33 0.042 ThinPrep

S3 77 54 33 <0.001 ThinPrep

H1 116 102 81 <0.001 ThinPrep

H2 115 86 90 0.876 Neither

H3 126 120 112 0.170 Neither

For LSIL and more severe lesions, the diagnostic comparison statistically favored the ThinPrep method at three sites and
was statistically equivalent at three sites.

Table 9: Independent Pathologist Results by Site, ASCUS/AGUS and More Severe Lesions

Site

S1 92 72 68 0.900 Neither
S2 101 85 59 0.005 ThinPrep
S3 109 95 65 <0.001 ThinPrep

H1 170 155 143 0.237 Neither
H2 171 143 154 0.330 Neither
H3 204 190 191 1.000 Neither

For ASCUS/AGUS and more severe lesions, the diagnostic comparison statistically favored the ThinPrep method at two sites
and was statistically equivalent at four sites.

Cases

Positive

by Independent

Pathologist

Cases

Positive

by

Independent

Pathologist

ThinPrep

Positive

ThinPrep

Positive

®

Conventional

Positive

Conventional

Positive

p-Value Method Favored

p-Value Method Favored

MAN-02624-001 Rev. 003 page 9 of 15

Table 10 below shows the summary for all sites of the descriptive diagnosis for all Bethesda System categories.

Table 10: Summary of Descriptive Diagnosis

Descriptive Diagnosis

Number of Patients: 6747

Benign Cellular Changes:
Infection:

Trichomonas Vaginalis
Candida spp.
Coccobacilli
Actinomyces spp.
Herpes
Other

Reactive Cellular Changes
Associated with:

Inflammation
Atrophic Vaginitis
Radiation
Other

Epithelial Cell Abnormalities:

Squamous Cell:
ASCUS
favor reactive
favor neoplastic
undetermined
LSIL
HSIL
Carcinoma
Glandular Cell:
Benign Endometrial cells in
Postmenopausal Women
Atypical Glandular Cells (AGUS)
favor reactive
favor neoplastic
undetermined
Endocervical Adenocarcinoma

Note: Some patients had more than one diagnostic subcategory.

ThinPrep

N % N %

1592

136
406
690

2
3

155

353

32

2

25

1159

501
128
161
213
469
167

1

7

21

9
0

12

0

23.6

2.0

6.0

10.2

0.0

0.0

2.3

5.2

0.5

0.0

0.4

17.2

7.4

1.9

2.4

3.2

7.0

2.5

0.0

0.1

0.3

0.1

0.0

0.2

0.0

Conventional

1591

185
259
608

3
8

285

385

48

1

37

1077

521
131
140
250
367
167

3

10

9
4
3
2
1

23.6

2.7

3.8

9.0

0.0

0.1

4.2

5.7

0.7

0.0

0.5

16.0

7.7

1.9

2.1

3.7

5.4

2.5

0.0

0.1

0.1

0.1

0.0

0.0

0.0

Table 11 shows the rates of detection for infection, reactive changes, and the total benign cellular
changes for both the ThinPrep

®

and conventional methods at all sites.

Table 11: Benign Cellular Changes Results

N % N %
Benign
Cellular
Changes Reactive

Total*

* Total includes some patients that may have had both an infection and reactive cellular change.

Infection

Changes

ThinPrep

1392 20.6 1348 20.0

412 6.1 471 7.0

1592 23.6 1591 23.6

Conventional

MAN-02624-001 Rev. 003 page 10 of 15

Tables 12, 13, and 14 show the specimen adequacy results for the ThinPrep method and conventional
smear method for all of the study sites. Of the 7,360 total patients enrolled, 7,223 are included in this
analysis. Cases with patient’s age less than 18 years or patients with a hysterectomy were excluded
from this analysis.

Two additional clinical studies were conducted to evaluate specimen adequacy results when samples
were deposited directly into the PreservCyt

®

vial, without first making a conventional Pap smear. This
specimen collection technique is the intended use for the ThinPrep 2000 System. Tables 15 and 16
present the split sample and direct to vial results.

Table 12: Summary of Specimen Adequacy Results

Specimen Adequacy

Number of Patients: 7223

Satisfactory 5656 78.3 5101 70.6
Satisfactory for Evaluation but
Limited by:

Air-Drying Artifact
Thick Smear
Endocervical Component Absent
Scant Squamous Epithelial
Component
Obscuring Blood
Obscuring Inflammation
No Clinical History
Cytolysis
Other

Unsatisfactory for Evaluation:

Air-Drying Artifact
Thick Smear
Endocervical Component Absent
Scant Squamous Epithelial
Component
Obscuring Blood
Obscuring Inflammation
No Clinical History
Cytolysis
Other

Note: Some patients had more than one subcategory.

ThinPrep Conventional

N % N %

1431

1
9

1140

150

55

141

12
19
10

136

0
0

25

106

23

5
0
0

31

Table 13: Specimen Adequacy Results

Conventional

ThinPrep SAT
SBLB

UNSAT

SAT SBLB UNSAT TOTAL

4316 1302 38 5656

722

63 41

665 44 1431

19.8

0.0

0.1

15.8

2.1

0.8

2.0

0.2

0.3

0.1

1.9

0.0

0.0

0.3

1.5

0.3

0.1

0.0

0.0

0.4

32 136

2008

136

65

681

47

339

1008

6

119

26

114

13

7

11

47
58
41

0
4
9

27.8

1.9

0.9

9.4

0.7

4.7

14.0

0.1

1.6

0.4

1.6

0.2

0.1

0.2

0.7

0.8

0.6

0.0

0.1

0.1

TOTAL

SAT=Satisfactory, SBLB=Satisfactory But Limited By, UNSAT=Unsatisfactory

5101 2008 114

7223

MAN-02624-001 Rev. 003 page 11 of 15

Table 14: Specimen Adequacy Results by Site

Site Cases Thin

Prep
SAT

Cases

S1

1,386 1092 1178 265 204 29 4

Con­vent.
SAT

Cases

Thin
Prep

SBLB

Cases

Con­vent.

SBLB

Cases

Thin
Prep

UNSAT

Cases

Con­vent.

UNSAT

Cases

S2

S3
H1
H2
H3

All Sites

1,668 1530 1477 130 178 8 13
1,093 896 650 183 432 14 11
1,046 760 660 266 375 20 11
1,049 709 712 323 330 17 7

981 669 424 264 489 48 68

7,223 5656 5101 1431 2008 136 114

The Satisfactory But Limited By (SBLB) category can be broken down into many subcategories,
one of which is the absence of Endocervical Component. Table 15 shows the Satisfactory But
Limited By category “No ECC’s” for ThinPrep

®

and conventional slides.

Table 15: Specimen Adequacy Results by Site, SBLB Rates for no Endocervical Component.

SBLB Due to No ECC’s

Site Cases ThinPrep

SBLB-

no ECC’s

S1
S2

S3

1,386 237 17.1% 162 11.7%
1,668 104 6.2% 73 4.4%

1,093 145 13.3% 84 7.7%

ThinPrep

SBLB-

no ECC’s (%)

Conventional

SBLB-

no ECC’s

Conventional

SBLB-

no ECC’s (%)

H1
H2
H3

All Sites

1,046 229 21.9% 115 11.0%
1,049 305 29.1% 150 14.3%

981 120 12.2% 97 9.9%

7,223 1140 15.8% 681 9.4%

For the results of the clinical study involving a split-sample protocol, there was a 6.4 percent difference
between conventional and ThinPrep methods in detecting endocervical component. This is similar to
previous studies using a split sample methodology.

DIRECT-TO-VIAL ENDOCERVICAL COMPONENT (ECC) STUDIES

For the intended use of the ThinPrep
into a PreservCyt

®

vial, rather than splitting the cellular sampl e. It was expected that this woul d result in

®

2000 System, the cervical sampling device will be rinsed directly

an increase in the pick-up of endocervical cells and metaplastic cells. To verify this hypothesis, two
studies were performed using the direct-to-vial method and are summarized in Table 16. Overall, no
difference was found between ThinPrep and conventional methods in these two studies.

MAN-02624-001 Rev. 003 page 12 of 15

Table 16: Summary of Direct-to-vial Endocervical Component (ECC) Studies

Study Number of

Direct-to-Vial
Feasibility
Direct-to-Vial
Clinical Study

1. Direct-to-Vial Feasibility study compared to overall clinical investigation conventional Pap
smear SBLB-No Endocervical Component rate.

2. Direct-to-Vial Clinical study compared to site S2 clinical investigation conventional Pap smear
SBLB-No Endocervical Component rate.

DIRECT-TO-VIAL HSIL+ STUDY

Following initial FDA approval of the ThinPrep System, Hologic conducted a multi-site direct-to-vial
clinical study to evaluate the ThinPrep 2000 System versus conventional Pap smear for the detection of
High Grade Squamous Intraepithelial and more severe lesions (HSIL+). Two types of patient groups
were enrolled in the trial from ten (10) leading academic hospitals in major metropolitan areas
throughout the United States. From each site, one group consisted of patients representative of a
routine Pap test screening population and the other group made up of patients representative of a
referral population enrolled at the time of colposcopic examination. The ThinPrep specimens were
collected prospectively and compared against a historical control cohort. The historical cohort
consisted of data collected from the same clinics and clinicians (if available) used to collect the
ThinPrep specimens. These data were collected sequentially from patients seen immediately prior to
the initiation of the study.

The results from this study showed a detection rate of 511 / 20,917 for the conventional Pap smear
versus 399 / 10,226 for the ThinPrep slides. For these clinical sites and these study populations, this
indicates a 59.7% increase in detection of HSIL+ lesions for the ThinPrep specimens. These results
are summarized in Table 17.

Table 17: Summary of Direct-to-Vial HSIL+ Study

Site

S1
S2
S3
S4
S5
S6
S7
S8
S9

S10

Total CP

(n)

2,439 51 2.1 1,218 26 2.1
2,075 44 2.1 1,001 57 5.7
2,034 7 0.3 1,016 16 1.6
2,043 14 0.7 1,000 19 1.9
2,040 166 8.1 1,004 98 9.8
2,011 37 1.8 1,004 39 3.9
2,221 58 2.6 1,000 45 4.5
2,039 61 3.0 983 44 4.5
2,000 4 0.2 1,000 5 0.5
2,015 69 3.4 1,000 50 5.0

Evaluable

Patients

SBLB due to No

Endocervical

Component

Comparable
Conventional Pap
Smear Percentage

299 9.36% 9.43%1

484 4.96% 4.38%2

HSIL+

Percent

(%)

Total TP

(n)

HSIL+

Percent

(%)

Percent

Change (%)

+2.1
+168.5
+357.6
+177.3

+20.0

+111.1

+72.3
+49.6

+150.0

+46.0

Total

20,917 511 2.4 10,226 399 3.9

59.7( p<0.001)

Percent Change (%) = ((TP HSIL+/TP Total)/(CP HSIL+/CP Total)-1) *100

MAN-02624-001 Rev. 003 page 13 of 15

GLANDULAR DISEASE DETECTION – PUBLISHED STUDIES

The detection of endocervical glandular lesions is an essential function of the Pap test. However,
abnormal glandular cells in the Pap sample may also originate from the endometrium or from
extrauterine sites. The Pap test is not intended to be a screening test for such lesions.

When suspected glandular abnormalities are identified, their accurate classification as true glandular
versus squamous lesions is important for proper evaluation and subsequent treatment (e.g. choice of
excisional biopsy method versus conservative follow-up). Multiple peer-reviewed publications
report on the improved ability of the ThinPrep 2000 System to detect glandular disease versus the
conventional Pap smear. Although these studies do not consistently address sensitivity of different Pap
testing methods in detecting specific types of glandular disease, the reported results are consistent with
more frequent biopsy confirmation of abnormal glandular findings by the ThinPrep Pap Test compared
to conventional cytology.

Thus, the finding of a glandular abnormality on a ThinPrep Pap Test slide merits increased attention
for definitive evaluation of potential endocervical or endometrial pathology.

CONCLUSIONS

The ThinPrep
populations and may be used as a replacement for the conventional Pap smear method for the detection
of atypical cells, cervical cancer, or its precursor lesions, as well as all other cytologic categories as
defined by The Bethesda System.

The ThinPrep 2000 System is significantly more effective than the conventional Pap smear for the
detection of Low-grade Squamous Intraepithelial (LSIL) and more severe lesions in a variety of patient
populations.

Specimen quality with the ThinPrep 2000 System is significantly improved over that of conventional
Pap smear preparation in a variety of patient populations.

®

2000 System is as effective as the conventional Pap smear in a variety of patient

4-9

MATERIALS REQUIRED

MATERIALS PROVIDED

The ThinPrep 2000 System consists of the following components:

 ThinPrep Processor Instrument (Model TP 2000)  2 filter Caps
 PreservCyt
 ThinPrep Pap Test Filter for Gynecologic Applications  Power cord
 Program Memory Card for Gynecologic Applications  ThinPrep Microscope slides
 Waste bottle assembly - includes bottle, bottle cap,

tubing set, fittings, waste filter

Additional items supplied:

 ThinPrep 2000 Operator’s Manual
 10 fixative vials

MATERIALS REQUIRED BUT NOT PROVIDED

 Slide staining system and reagents  20 ml PreservCyt
 Standard laboratory fixative  ThinPrep
 Coverslips and mounting media  Cervical collection device

®

Solution vial  2 spare filter seal O-rings

®

Solution vial

®

Pap Test Filter for Gynecologic Applications

MAN-02624-001 Rev. 003 page 14 of 15

STORAGE

 Store PreservCyt Solution between 15°C (59°F) and 30°C (86°F). Do not use beyond the expiration

date printed on the container.

 Store PreservCyt Solution with cytologic sample intended for ThinPrep Pap testing between 15°C

(59°F) and 30°C (86°F) for up to 6 weeks.

 Store PreservCyt Solution with cytologic sample intended for CT/NG testing using the Roche

Diagnostics COBAS AMPLICOR CT/NG test between 4°C (39°F) and 25°C (77°F) for up to 6
weeks.

BIBLIOGRAPHY

1. Solomon D., Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, Raab S,

Sherman M, Wilbur D, Wright T, Young N, for the Forum Group Members and the
2001 Bethesda Workshop. The 2001 Bethesda System Terminology for Reporting
Results of Cervical Cancer. JAMA. 2002;287:2114-2119.

2. Jones HW. Impact of The Bethesda System, Cancer 77 pp. 1914-1918, 1995.

3. American Cancer Society. Cancer Facts and Figures, 1995.

4. Ashfaq R, Gibbons D, Vela C, Saboorian MH, Iliya F. ThinPrep Pap Test. Accuracy for

glandular disease. Acta Cytol 1999; 43: 81-5

5.

Bai H, Sung CJ, Steinhoff MM: ThinPrep Pap Test promotes detection of glandular lesions
of the endocervix. Diagn Cytopathol 2000;23:19-22

6. Carpenter AB, Davey DD: ThinPrep Pap Test: Performance and biopsy follow-up un a university

hospital. Cancer Cytopathology 1999; 87: 105-12

7. Guidos BJ, Selvaggi SM. Detection of endometrial adenocarcinoma with the ThinPrep Pap test.

Diagn Cytopathol 2000; 23: 260-5

8. Schorge JO, Hossein Saboorian M, Hynan L, Ashfaq R. ThinPrep detection of cervical and

endometrial adenocarcinoma: A retrospective cohort study. Cancer Cytopathology 2002; 96: 338­43

9. Wang N, Emancipator SN, Rose P, Rodriguez M, Abdul-Karim FW. Histologic follow-up of

atypical endocervical cells. Liquid-based, thin-layer preparation vs. conventional Pap smear. Acta
Cytol 2002; 46: 453-7

TECHNICAL SERVICE AND PRODUCT INFORMATION

For technical service and assistance related to use of the ThinPrep 2000 System, contact Hologic:
Telephone: [phone]
Fax: [phone]

For international or toll-free blocked calls, please contact 1-508-263-2900.
Email: [e-mail]

Hologic, PreservCyt, ThinPrep, and associated logos are registered trademarks of Hologic, Inc. and/or its subsidiaries in the
United States and other countries. All other trademarks, registered trademarks, and product names are the property of their
respective owners.

Hologic, Inc.
250 Campus Drive
Marlborough, MA 01752
1-800-442-9892
www.hologic.com

Hologic UK
Unit 2, Link 10 Napier Way
Crawley, West Sussex RH10 9RA
United Kingdom
[phone]

©2014 Hologic, Inc. All rights reserved.

AW-07100-001 Rev. 003

MAN-02624-001 Rev. 003 page 15 of 15

ThinPrep 2000 System

for Gynecologic Use

for Gynecologic Use

ThinPrep 2000 System

ThinPrep® 2000 System
For Gynecologic Use

Section 1 (white tabs) describes the use of the
ThinPrep

®

2000 system for gynecologic applications. In addition, it

contains all information regarding the installation, operation, and

®

maintenance of the ThinPrep

2000 processor.

ThinPrep 2000 Processor Operator’s Manual

i

This page intentionally left blank.

ii

ThinPrep 2000 Processor Operator’s Manual

Table of Contents

Chapter One

INTRODUCTION

TABLE OF CONTENTS

SECTION A:

SECTION B:

SECTION C

SECTION D:

SECTION E:

SECTION F:

Chapter Two

THINPREP 2000 INSTALLATION

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

Overview and Function
of the ThinPrep

Principles of Operation 1.7

: ThinPrep 2000 System Technical Specifications 1.12

Internal Quality Control 1.16

ThinPrep 2000 Hazards 1.16

Disposal 1.19

General 2.1

Action Upon Delivery 2.1

Preparation Prior to Installation 2.2

Internal Packaging Removal 2.2

Connecting the Waste Bottle 2.6

Inserting the Program Memory Card 2.7

®

2000 System 1.1

SECTION G:

SECTION H:

SECTION I

SECTION J:

SECTION K:

Chapter Three

PRESERVCYT SOLUTION

SECTION A:

SECTION B:

Connecting the Power Cord 2.8

Turning On Your ThinPrep 2000 Processor 2.9

: Run a Blank Sample 2.11

Storage and Handling - Post Installation 2.12

Turning Off the ThinPrep 2000 Processor 2.12

Introduction 3.1

PreservCyt® Solution 3.2

ThinPrep 2000 Processor Operator’s Manual

iii

TABLE OF CONTENTS

Chapter Four

GYNECOLOGIC SAMPLE PREPARATION

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

Introduction 4.1

Collection Preparation 4.2

Specimen Collection 4.3

Special Precautions 4.5

Specimen Processing 4.6

Sample Preparation Troubleshooting 4.7

Chapter Five A

OPERATING INSTRUCTIONS

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

:Introduction 5A.1

Optional Instructions for Ancillary Testing 5A.2

Material Requirements 5A.4

Pre-operation Checklist 5A.5

Overview of
Loading the ThinPrep

SECTION F:

Loading the PreservCyt Sample Vial 5A.7

®

2000 Processor 5A.6

SECTION G:

SECTION H:

SECTION I:

SECTION J:

SECTION K:

SECTION L:

SECTION M:

SECTION N:

iv

ThinPrep 2000 Processor Operator’s Manual

Loading the ThinPrep Pap Test Filter 5A.8

Loading the ThinPrep Microscope Slide 5A.11

Loading the Fixative Vial 5A.14

Closing the Door 5A.15

Selecting and Initiating a Sequence 5A.16

Unloading the ThinPrep 2000 Processor 5A.18

Interrupting the Slide Preparation Process 5A.20

Status, Maintenance, and Test Screens 5A.21

TABLE OF CONTENTS

Chapter Five B

OPERATING INSTRUCTIONS

FOR PROCESSING COBAS AMPLICOR™ CT/NG SAMPLES

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

SECTION G:

SECTION H

SECTION I

: Loading the ThinPrep Microscope Slide 5B.11

SECTION J:

SECTION K

SECTION L

SECTION M:

SECTION N:

SECTION O

Introduction 5B.1

Material Requirements 5B.2

Pre-operation Checklist 5B.4

Overview of

®

Loading the ThinPrep

2000 Processor 5B.5

Preparing the Filter Caps 5B.6

Loading the Fixative Vial 5B.7

Loading the ThinPrep Pap Test Filter 5B.8

: Loading the PreservCyt Sample Vial 5B.10

Closing the Door 5B.14

: Selecting and Initiating a Sequence 5B.15

: Unloading the PreservCyt Sample Vial 5B.18

Unloading the ThinPrep Microscope Slide 5B.11

Unloading the Filter Assembly 5B.20

: Interrupting the Slide Preparation Process 5B.21

SECTION P:

Status, Maintenance, and Test Screens 5B.22

Chapter Six

INSTRUMENT TROUBLESHOOTING

SECTION A:

SECTION B:

SECTION C:

SECTION D:

Introduction 6.1

How to use this Section 6.2

Contents 6.3

Error History 6.37

ThinPrep 2000 Processor Operator’s Manual

v

TABLE OF CONTENTS

Chapter Seven

MAINTENANCE

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

SECTION G:

SECTION H:

SECTION I:

SECTION J:

SECTION K

SECTION L:

SECTION M:

Introduction 7.1

Emptying Waste Bottle 7.2

Filter Cap Cleaning 7.4

Filter Cap O-ring Lubrication 7.5

Filter Seal O-ring Replacement 7.6

Door Cleaning 7.7

Cap Seal Cleaning 7.8

General Cleaning 7.9

Waste Tubing Replacement 7.10

Waste Filter Replacement 7.14

: Emptying and Cleaning the Catch Tray 7.16

Moving The ThinPrep® 2000 Processor 7.17

Maintenance Schedule 7.18

Chapter Eight

FIXATION, STAINING, AND COVERSLIPPING

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

Introduction 8.1

Fixation 8.2

Staining 8.3

Coverslipping 8.6

References 8.6

Chapter Nine

THINPREP PAP TEST TRAINING PROGRAM 9.1

INDEX

vi

ThinPrep 2000 Processor Operator’s Manual

1. Introduction

1. Introduction

INTRODUCTION

1

SECTION

A

Chapter One

Introduction

This chapter describes an overview and the principles of operation of the ThinPrep® 2000 system for
gynecologic sample processing.

Note:

Specific processing steps using the ThinPrep 2000 system must be followed for specimens

undergoing subsequent testing for
Roche Diagnostics COBAS AMPLICOR™ CT/NG test. (See Chapter 5B, “Operating
Instructions for Processing COBAS AMPLICOR™ CT/NG Samples”.)

Chlamydia trachomatis

and

Neisseria gonorrhoeae

using the

OVERVIEW AND FUNCTION OF THE THINPREP® 2000 SYSTEM

The ThinPrep 2000 system is used in the processing of fluid-based gynecologic specimens for use
with the ThinPrep

microscope slides in preparation for staining, coverslipping and screening. The processor produces
thin, uniform preparations of cells on ThinPrep microscope slides.

Indication for Use

Intended Use

The ThinPrep 2000 system is intended as a replacement for the conventional method of Pap smear
preparation for use in screening for the presence of atypical cells, cervical cancer, or its precursor
lesions (Low Grade Squamous Intraepithelial Lesions, High Grade Squamous Intraepithelial
Lesions), as well as all other cytologic categories as defined by The Bethesda System for Reporting

Cervical/Vaginal Cytologic Diagnoses

®

Pap test. The samples are collected, processed, transferred and fixed onto

1

.

1. Kurman RJ, Solomon D. The Bethesda System for Reporting Cervical/Vaginal Cytologic Dis­eases, Springer-Verlag, New York 1994.

ThinPrep 2000 Processor Operator’s Manual

1.1

1

INTRODUCTION

ThinPrep

®

2000

CYTYC

corporation

Figure 1-1 The ThinPrep 2000 Processor and Waste Bottle

Summary and Explanation of the System

The ThinPrep process begins with the patient’s gynecologic sample being collected by the clinician
using a cervical sampling device which, rather than being smeared on a microscope slide, is

®

immersed and rinsed in a vial filled with PreservCyt

Solution. The ThinPrep sample vial is then

capped, labeled, and sent to a laboratory equipped with a ThinPrep 2000 processor.

At the laboratory, the PreservCyt sample vial is placed into a ThinPrep 2000 processor and a gentle
dispersion step breaks up blood, mucus, non-diagnostic debris, and thoroughly mixes the cell
sample. The cells are then collected on a ThinPrep Pap test filter specifically designed to collect
diagnostic cells. The ThinPrep 2000 processor constantly monitors the rate of flow through the
ThinPrep Pap test filter during the collection process in order to prevent the cellular presentation
from being too scant or too dense. A thin layer of cells is then transferred to a glass slide in a 20-mm­diameter circle. The slide is then automatically deposited into a fixative solution.

1.2

ThinPrep 2000 Processor Operator’s Manual

1

The ThinPrep Sample Preparation Process

1. Dispersion 2. Cell Collection 3. Cell Transfer

(1) Dispersion

The ThinPrep Pap test filter
rotates within the sample
vial, creating currents in the
fluid that are strong enough
to separate debris and
disperse mucus, but gentle
enough to have no adverse
effect on cell appearance.

(2) Cell Collection

A gentle vacuum is created
within the ThinPrep Pap test
filter, which collects cells on
the exterior surface of the
membrane. Cell collection is
controlled by the ThinPrep
2000 processor’s software that
monitors the rate of flow
through the ThinPrep Pap test
filter.

(3) Cell Transfer

After the cells are collected on
the membrane, the ThinPrep
Pap test filter is inverted and
gently pressed against the
ThinPrep microscope slide.
Natural attraction and slight
positive air pressure cause the
cells to adhere to the ThinPrep
microscope slide resulting in
an even distribution of cells in
a defined circular area.

INTRODUCTION

As with conventional Pap smears, slides prepared with the ThinPrep 2000 system are examined in
the context of the patient’s clinical history and information provided by other diagnostic procedures
such as colposcopy, biopsy, and human papillomavirus (HPV) testing, to determine patient
management.

Limitations

•

Gynecologic samples collected for preparation using the ThinPrep 2000 system should be
collected using a broom-type cervical collection device or endocervical brush/plastic
spatula combination collection device.

ThinPrep 2000 Processor Operator’s Manual

1.3