LBC – Sink or Swim?

Thames Valley Cytology Society

Bedford

24th June 2004

NICE Guidance

October 2003:

NICE recommends that LBC is used as

the primary means of processing samples

in the cervical screening programme in

England and Wales

NICE Guidance

There is currently insufficient evidence to

recommend one LBC product over

another.

The NHSCSP and SCW may wish to

consider evaluating further different

products as the method is introduced.

Conventional Smears

False Negative Rate of up to 55% Sampling and interpretative errors

Borderline Rates of up to 6.4%70% are truly negative

30% represent more severe abnormality

Inadequate Rates of 9.7%

Sources Of False NegativesSampling issues (70%)

– cells not collected on the sampling device– cells collected, but not transferred to the slide

Interpretative issues (30%)

– abnormal cells present on slide but either not seen or misinterpreted

The ProblemThe ProblemThe Problem

The Conventional Cervical SmearThe Conventional Cervical Smear

A cervical sample containing precancerous

cells (red)

A cervical sample containing precancerous

cells (red)

Non-randomized portion of cells

Non-randomized portion of cells

Over 80% of cells discardedOver 80% of

cells discarded

Smear spray-fixed and sent to lab

Smear spray-fixed and sent to lab

Missing cells, obscuring elements

Missing cells, obscuring elements

Sample may not reflect patient’s actual condition

Sample may not reflect patient’s actual condition

The Solution

The SolutionThe SolutionThe ThinPrep® Pap Test™The ThinPrep® Pap Test™

A cervical sample containing precancerous

cells (red)

A cervical sample containing precancerous

cells (red)

Virtually 100% of cells collected into

ThinPrep vial

Virtually 100% of cells collected into

ThinPrep vial

Cells immediatelypreserved and

sent to lab

Cells immediatelypreserved and

sent to lab

Filtration process disperses, randomizes cells

Filtration process disperses, randomizes cells

More representative and clear thin layer

of cells

More representative and clear thin layer

of cells

Increasedopportunity to

detect early signsof abnormality

Increasedopportunity to

detect early signsof abnormality

Evidence BaseClinical Validation ThinPrep® Improvement

Patients LSIL+ HSIL+ S.Q.Split-Sample Lee et al. 6,747 65% 36% 54%

Corkill et al. 1,583 110% 54% N/ARoberts et al. 81,754 26% 15% 91%

Direct-to-Vial Scottish Pilot 30,228 92% 84% 76%Diaz-Rosario 56,339 72% 103% ???Papillo et al. 8,574 52% 55% 52%Weintraub et al. 18,247 184% 94% 93%Bolick 10,694 181% 173% 70%Johnson et al. 902 71% 125% 41%Guidos/Selvaggi 9,583 267% 233% 97%Quddus 14,216 24% 35% 28%Hornish 30,431 N/A 83% N/A

>60 peer reviewed international publications from 4 Continents

Does LBC increase sensitivity?

Educational biasLab / Smear takers

Study design biasSplit sample / Direct-to-Vial

Population biasSelf-selecting / Non-screening

End point biasDyskaryosis as ‘surrogate’ / lack of histological confirmation

Does LBC decrease inadequate rates?

SurePath 5000 cells

Thinprep 40000 cells

Conventional 50000 cells?

Weighted Average (total 30,228)

Conventional % ThinPrep %

Unsatisfactory 7.63 1.84

Borderline 3.98 3.67Mild 1.10 2.12 92%↑

Moderate 0.45 0.97Severe 0.65 1.06 84% ↑

Scottish Pilot Results

• No major storage problems • Reduced workload for smear takers• 349/350 smear takers preferred ThinPrep®

• Increased productivity in laboratories• Sharp reduction in the unsatisfactory rate • Less anxiety and discomfort for women• More appropriate referrals to colposcopy• Allows scope for further developments in the screening programme

Scottish Pilot Conclusions

Vial storage Modular storage units available

(File-a-Vial)

150 vial capacity

Example:

• 30,000 samples pa • 4 week cycle• 2,500 vials • 17 units

ThinPrep® T2000 Processor

SurePath

Why I like the SurePath Liquid-Based

PAP Test

David R Bolick

RPS Sandy, Utah

SurePath

SurePath and ThinPrep

Similarities:

Diagnostic rates

Detection rates of HPV from vial

Histology/Cytology correlation rates

SurePath

SurePath and ThinPrep

Differences:

Inadequate rates

False negative fraction

Detection of abnormalities in clusters

SurePath

SurePath and ThinPrep

Inadequate rates:

SurePath 0.18% 26/14419

ThinPrep 0.37% 123/33198

SurePath

SurePath and ThinPrep

False negative fraction:

LSIL % HSIL %

SurePath 6.8 0.0

ThinPrep 14.0 16.0

SurePath screened TWICE ; ThinPrep screened ONCE

SurePath

SurePath and ThinPrep

Abnormalities in clusters:

AGUS Endom Adenoca

SurePath 0.13 0.24 0.05

ThinPrep 0.09 0.13 0.02

LBCLBC is on the way.

5 year conversion timescale is too long

Major retraining exercise for labs

Benefits in terms of productivity and scope for future developments

Good for smear takers and women

Issues around sensitivity / specificity / inadequate rates will be answered in long run

Expensive solution