Liquid-based Cytology (LBC) method for Gynecologic cytologyLenny Sari RS Kanker Dharmais

Metode Liquid-based pada Gynecologic cytology yaitu Metode yang dilakukan dengan memasukkan sikat endoserviks/ brush kedalam cairan pengawet yang kemudian dilakukan prosesing melalui tahap dispersi sel, pengumpulan sel dan transfer sel pada gelas objek dan menghasilkan lapisan yang monolayer dengan diameter 20mm.

The Cervical SmearImpact of Pap Smear Screening

Number of Deaths Per Year

A 50 year old test with a remarkable history of success most common cancer screening test Reduced death rate significantly2000

1940

Conventional Pap SmearSources of False Negative Results (FNR)1, 2, 3

Screening error1/3 of FNRs Screening errorsabnormal cells are present on the slide but missed by a cytologist Interpretive errorscells not classified correctly

Sampling/preparation errors2/3 of FNRs Cells not collected on the sampling device Cells collected are not transferred to the slide Poorly preserved cells1 Gay JD, et al.: False-Negative Results in Cervical Cytologic Studies, Acta Cytologica 1985, Vol. 29(6):1043-6 2 Joseph MG, et al.: Cyto-Histological Correlates in a Colposcopic Clinic: A 1-Year Prospective Study, Diagnostic Cytolopathology 1991, Vol. 7(5):477-81 3 Linder J, et al., ThinPrep Papanicolau Testing to Reduce False-Negative Cervical Cytology, Arch Pathol Lab Med 1998, Vol. 122(2):139:44

Discover a More Accurate TestPhysicians OfficeStill a Simple ProcessStep 1 Step 2 Step 3

Obtain

Rinse

Seal

In the LaboratoryA Significant ImprovementStep 1 Step 2 Step 3

Load

Process

Screen

Sampling Is a ConcernPercentage of Obtained Sample Transferred onto the SlideEPITHELIAL CELLS (000s)Cells transferred to slide1400 1200 1000 800 600 400 200 0

Cells rinsed from collection device after smear prepared

92%of cells left on collection device

93%of cells left on collection device

82%of cells left on collection device

More than 80% of the cell sample may be discarded with the collection device after the conventional Pap smear1.

Swab/Spatula

Endocervical Brush/Spatula

Broom-like Device

1

Hutchinson ML, et al., Homogeneous sampling accounts for the increased diagnostic accuracy using the ThinPrep Processor, Am J Clin Patholo 1994; 215-219

The ProblemThe ProblemThe Conventional Cervical SmearA cervical sample containing precancerous cells (red) Non-randomized portion of cells

Over 80% of cells discarded Sample may not reflect patients actual condition

Smear spray-fixed and sent to lab Missing cells, obscuring elements

The SolutionThe SolutionLiquid base method Pap TestA cervical sample containing precancerous cells (red) Virtually 100% of cells collected into Liquid base vial

Cells immediately preserved and sent to lab Increased opportunity to detect early signs of abnormality Filtration process disperses, randomizes cells

More representative and clear thin layer of cells

More Homogeneous SampleThe Conventional Smear Liquid base method Pap Test

Majority of cells not captured Non-representative transfer of cells

Virtually all of the sample is collected Randomized, representative transfer of cells

1

Hutchinson ML, et al., Homogeneous sampling accounts for the increased diagnostic accuracy using the ThinPrep Processor, Am J Clin Patholo 1994; 101:215-219

Pivotal TrialDesign

6,747 patients 6 sites 3 Screening Centers and 3 Hospitals Screening population: Low rates of cervical abnormality (10%) Used to show ThinPrep would detect disease effectively when tested with a high number of patients with abnormalities

Split-sample, blinded, matched pairLee et al., Comparison of Conventional Papanicolaou Smears and a Fluid-Based, Thin-Layer System for Cervical Cancer Screening, Obstetrics and Gynecology, 1997, Vol. 90(2):278-84

Pivotal TrialDiagnostic Results Screening Population 65% Increase200500

High Risk Population 6% IncreaseThe ThinPrep Pap Test400

191

The ThinPrep Pap Test Conventional Smear

446 422

Conventional Smear

300

100

116200

100

0

0

OVERALL RESULTS

OVERALL RESULTS

Lee et al., Comparison of Conventional Papanicolaou Smears and a Fluid-Based, Thin-Layer System for Cervical Cancer Screening, Obstetrics and Gynecology, 1997, Vol. 90(2):278-84

Pivotal TrialSpecimen Adequacy Results

Improves specimen quality significantly over conventional Pap smear by reducing Air drying artifact Mucus Blood Inflammation

28%

54% Reduction

3%

Conventional Smear

The ThinPrep Pap Test

Lee et al., Comparison of Conventional Papanicolaou Smears and a Fluid-Based, Thin-Layer System for Cervical Cancer Screening, Obstetrics and Gynecology, 1997, Vol. 90(2):278-84

Roberts , et al.Laverty and Associates, Sydney, Australia

35,560 split-sample patients 94% reduction of unsatisfactory cases 12% increased detection of significant abnormality 16% increased detection of biopsy-proven HGEA No loss in specificity

HGEA* Cases Detected+ 16%273 236

Conventional Smear

The ThinPrep Pap Test

Medical Journal of Australia, 1997, Vol. 167(3):466-69 * HGEA=High Grade Epithelial Abnormalities

Yeoh, et al.Diagnostic Pathology Laboratory, Hong Kong 16,541 ThinPrep Pap Tests results vs. 7,258 conventional smears Improved sensitivity with a higher positive predictive value of 94.2% Higher yield of samples containing endocervical cells Biopsy confirmation

Increased HSIL Detection+ 28%

Another advantage was the ability to perform HPV DNA assays on equivocal cases.

Conventional Smear

The ThinPrep Pap Test

Yeoh GPS et al, Evaluation of the ThinPrep Papanicolaou test in clinical practice, HKMJ 1999; 5:233-9

Weintraub, et al.Laboratoire Weintraub, Geneva, Switzerland

39,864 ThinPrep results vs. 130,381 conventional smears Improved sensitivity with an odds ratio of 1.86 for HSIL and 3.41 for LSIL Decrease in the ASCUS:SIL ratio Biopsy confirmation

Increased HSIL Detection

+ 186%

There was an excellent agreement between the cytologic diagnosis of HSIL and the results of the subsequent histological evaluation.

Conventional Smear

The ThinPrep Pap Test

Weintraub, J. Efficacy of a liquid-based thin layer method for cervical cancer screening in a population with a low incidence of cervical cancer, Diagn Cytopathol 2000 Jan;22(1):52-59

Diaz-Rosario, et al.Quest Diagnostics, Inc. Cambridge, MA, USA

56,339 ThinPrep test results vs. 74,756 conventional slides Decreased ASCUS/SIL ratio by 39.11% Increased detection of HSIL by 102.54% Increased detection of LSIL by 71.65%ThinPrep produced increased detection of premalignant precursors while improving the specimen adequacy.

Increased HSIL Detection

+ 102.54%

Conventional Smear

The ThinPrep Pap Test

Diaz-Rosario LA et al. Performance of a Fluid-Based, Thin-Layer Papanicolaou Smear Method in Clinical Setting of an Independent Laboratory and an Outpatient Screening Population in New England, Arch Patholo Lab Med 1999, Vol. 123(9):817-21

Clinical Performance SummaryBenefits Over The Conventional Pap Smear The ThinPrep Pap Test has improved specimen quality1 The ThinPrep Pap Test has higher sensitivity and positive predictive value2 The ThinPrep Pap Test has a higher yield of samples containing endocervical cells2 The ThinPrep Pap Test produced increased detection of pre-malignant precursors3

1 Lee KR et al. Comparison of Conventional Papanicolaou Smears and a Fluid-Based, Thin-Layer System for Cervical Cancer Screening, Obstetrics and Gynecology, 1997 Vol. 90(2):278-84 2 Yeoh GPS et al. Evaluation of the ThinPrep Papanicolaou test in clinical practice, HKMJ 1999; 5:233-9 3 Diaz-Rosario LA et al. Performance of a Fluid-Based, Thin-Layer Papanicolaou Smear Method in Clinical Setting of an Independent Laboratory and an Outpatient Screening Population in New England, Arch Patholo Lab Med 1999, Vol. 123(9):817-21

SummaryLiquid-based method A replacement for the conventional Pap smear Significantly more effective for the detection of LSIL and more severe lesions Specimen quality is significantly improved

Additional Testing Residual Specimen Remains in the Vial Ability to perform Human Papilloma Virus (HPV) testing from the vial, which may be useful to triage women in low-risk or high-risk groups 1,2 Currently evaluating adjunct testing for additional STDs e.g., chlamydia,3 gonorrhea, trichomonas and herpes.

SummaryLiquid-based method Is a more accurate test for the early detection of cervical cancer precursors Results in a significant improvement in specimen quality with a decreased number of unsatisfied cases Creates the opportunity for additional testing from the patients sample Is the foundation for automation and a total system approach The best possible results from the best possible sample

Automatic Capping System Automatic Cell Transfer System Automatic Filter Supply system Membrane Filtration Method (20mm Speculum Vision) Convenient (Operating Control by Touch Screen LCD Panel) Economical Quickness

Cell prep the full automatic Liquid Based Cytology solutions

Tahapan Process

More Accurate and CleanCurrent Cancer Screening Methods Methods macroscopic examination Pap Smear Liquid-Based Cytology

Equipment specificity & screening ability

MRI, CT above 3cm 96% below 1cm 24.8%

PET

Smear

CellPrep High