ABC3 and Quality Assurance - Dr Karin Denton Director of Cancer screening QA (SW)

ABC3 and Quality Assurance

           Dr Karin Denton
Director of Cancer screening QA (SW)

Aims of ABC3
• To update terminology
• To include management protocols for HPV
  triage and test of cure
• To update performance indicators

Adequacy
• Still awaiting HTA study
• No change

• HTA study will be published in May 13.
• Likely to be an updated version of the chapter
  on adequacy

Changes to terminology
Previous terminology   New Terminology                        Result code
Borderline change      Borderline change in Squamous cells     8
                       Borderline change in endocervical cells 9
Mild dyskaryosis       Low grade dyskaryosis                  3
Borderline change
(koilocytic)
Moderate dyskaryosis   High Grade dyskaryosis (moderate)      7
Severe dyskaryosis     High Grade dyskaryosis (severe)        4
Severe                 High grade dyskaryosis ?invasive       5
Dyskaryosis?invasive   squamous carcinoma
?Glandular Neoplasia   ?Glandular neoplasia of endocervical   6
                       type
                       ?Glandular neoplasia ( non cervical)   0

The revised BSCC terminology for abnormal
cervical cytology.
Denton KJ, Herbert A, Turnbull LS, Waddell C,
Desai MS, Rana DN, Dudding N, Smith JH;
British Society of Clinical Cytology.
Cytopathology. 2008 Jun;19(3):137-57

Negative ( result code 2)
• Samples may be reported as negative if
  classified “No further review” after scanning
  with the BD FocalPoint Slide profiler
• https://www.csp.nhs.uk/files/F000206_NHSCS
  P%20GPG4.pdf

Low Grade Dyskaryosis
               ( result code 3)
•Dyskaryotic cells with a nuclear:cytoplasmic diameter
ratio of

Low grade dyskaryosis

High Grade Dyskaryosis (Moderate)
•Dyskaryotic cells are present
with a nuclear:cytoplasmic
diameter ratio of >50%.

•Distinguishing precisely
between high-grade
dyskaryosis (moderate) and
high-grade dyskaryosis
(severe) is difficult and not
entirely reproducible.

• However, if the
nuclear:cytoplasmic diameter
ratio is felt to be

High Grade dyskaryosis ( Severe)
This should be used when
dyskaryotic cells are
present with a
nuclear:cytoplasmic
diameter ratio of no less
than 50%, and probably
>75%.

• Sections on difficulties in grading dyskaryosis
  and difficulties in the identification of
  dyskaryosis

High grade dyskaryosis/?invasive
       squamous cell carcinoma
             (result code 5)
• No significant changes from ABC2

? Glandular neoplasia of endocervical
                type
• No change from ABC2

?glandular neoplasia (non cervical)

Glandular neoplasia
non-cervical

?Glandular Neoplasia (non-cervical) -
                  difficulties
• IUCD Changes

• Significance of psammoma bodies in a slide
  lacking cytological abnormality

• Significance of endometrial cells

Borderline change in Squamous cells
• As currently (except koilocytes)
• No place for BC?high grade when HPV testing
  is used

Borderline change - Pitfalls
• Parakeratosis       • Increasingly
• Inflammation         important in the era of
• Metaplastic cells    HPV primary screening
• Atrophy

Keratinisation - Negative

Atrophy

Borderline change in endocervical
               cells
• Typically cell groups show either architectural
  or nuclear features suggesting CGIN.
• Borderline change in endocervical cells should
  be a rare diagnosis.
• Application of objective criteria and consensus
  reporting are recommended to maintain the
  specificity of the category and avoid
  unnecessary colposcopy.

BC in endocervical cells – difficulties
•   Cervicitis
•   Polyps
•   TEM
•   LUS

Management of borderline change
   and low grade dyskaryosis

Use of HPV testing outside Triage and
             TOC protocol
All cases to be discussed at CIN meeting first

Off label HPV testing?
•   Women undergoing long term colposcopy surveillance for low grade
    CIN or unresolved abnormal cytology, and have not been previously
    tested for HR-HPV. This could include women with cervical stenosis
    where colposcopy is non-contributory

•   Women who have undergone hysterectomy for CIN, or CIN was found in
    the hysterectomy specimen, and subsequently present with abnormal
    vault cytology but no evidence of high grade VAIN

•   Women who experience difficulty tolerating colposcopy and therefore
    the examination is unsatisfactory.

•   Women discussed at the colposcopy MDT because of persistent
    mismatch between high grade cytology and low grade histology when a
    decision has been made not to treat.

Standard Cytology Result, HPV
       Infection and Action Codes
Each time a woman is screened a standard set
of details is recorded on her cervical screening
record.

 -   the coded cytology result
-    the HPV infection code
-    the action code which indicates the
     recall

HPV Infection codes
•     0     no high risk HPV DNA detected
•     9     high risk HPV DNA detected
•     U     HPV test result unavailable or
            unreliable

• Under no circumstances may the 'U' infection code
  be used where an HPV test cannot be carried out
  due to equipment failure or any other problem
  unrelated to the quality of the sample.

Coding multiple diagnoses
In rare cases, a woman’s cytology test may reveal the co-existence of non-cervical
glandular neoplasia with cervical abnormalities. Treatment of the former falls outside
the scope of the NHS CSP, but the following protocol should be followed to ensure
appropriate management.

•Where a woman has non-cervical glandular neoplasia and any form of cervical
cytological abnormality, it is the latter that should be recorded and sent to NHAIS.
This will determine the woman’s management within the NHS CSP.

• However, arrangements must be made to inform the woman of her diagnosis of
noncervical glandular neoplasia. Such communications are particularly sensitive,
because the woman may previously have received a letter referring only to a
borderline or low-grade cytological abnormality.

• The woman must receive an urgent referral, probably to gynaecology. A member of
the consultant medical staff at the cervical cytology laboratory must ensure that the
referral is made and that failsafe procedures are in place, according to local
arrangements.

Performance indicators
‘the objective of cervical screening is to reduce
cervical cancer incidence and mortality by
screening with a high sensitivity for the
detection of CIN2 or worse, whilst maintaining
a high specificity’.

ABC2 performance monitoring
• Abnormality detection rate - 10-90th centiles
• Sensitivity (lab and individual)
  – Defined as proportion of abnormal cases identified at
    primary screening
  – 90% all grades
  – 95% high grade
• PPV
  – Defined as proportion of samples showing Moderate
    dyskaryosis or worse found to have CIN2 or worse
  – 10-90th centiles

Challenges of performance monitoring
      in a changing programme
•   LBC
•   HPV vaccine
•   HPV Triage and TOC
•   Lab configuration

ABC3 – mandatory performance
            monitoring
Criteria               Performance             Range
                       indicator
Inadequate sample      % all samples         5th - 95th percentile
reports
PPV for CIN2 or worse % of women referred    5th - 95th percentile
                      with high grade
                      cytology or worse
                      whose biopsy is
                      reported as CIN2 or
                      worse
Referral Value        Number of women        5th-95th percentile
                      referred to colposcopy
                      to detect one CIN2 or
                      worse lesion

TPV and RV
• TPV (Total predictive value)is the percentage
  of women referred who have a histological
  outcome of CIN2+
• RV ( referral value) is the inverse of TPV

80
60
40
20
 0       Referral Value from 2010/11 KC61 part C2

     1           2         3         4          5
                          RV

Measures which may be helpful

40
30
20
10
               PPV/APV
 0

     60   70             80             90     100
                        PPV%
               95% CI          Fitted values
               APV%

Mean CIN score
                                                     Examples
Outcome                                   Lab A          Lab B              Lab C
Cervical Cancer                           15             15                 15
CIN 3                                     50             50                 50
CIN2                                      30             50                 50
CIN1                                      10             35                 70
HPV only, no disease*                     5              15                 65
TOTAL                                     110            165                250
MCS                                       2.5            2.1                1.5
Lab A is operating at too high a specificity to detect all CIN 2 lesions and could be
considered as only having a high sensitivity for CIN 3. Lab B may be more closely
following the concept of a high detection for CIN 2 or worse whilst referring the
minimum number of women and Lab C by referring women who have a high
proportion of histological outcomes of CIN 1 and ‘HPV only’ operating at too low a
specificity.

SSS Results from different centres
    HPV positive rate by site and initial cytology 1

Site      Borderline                Mild                    Total

           n     HPV +ve        n          HPV +ve      n           HPV +ve
                     (%)                       (%)                      (%)

A       1263   866 (68.6)     404     370 (91.6)     1667    1236 (74.1)
B        643   224 (34.8)     523     384 (73.4)     1116     608 (52.1)
C       2557   1111 (43.4)   1507    1232 (81.8)     4064    2343 (57.7)
D        789   455 (57.7)     420     372 (88.6)     1209     827 (68.4)
E        663   406 (61.2)     557     500 (89.8)     1220     906 (74.3)
F        592   434 (73.3)     133     116 (87.2)     7255     550 (75.9)

Quality Assurance in the new
            NHS

8 Knowledge and
Intelligence Hubs
•   London
•   South West
•   South East
•   West Midlands
•   East Midlands
•   North West
•   Yorkshire and Humber
•   North East

Into the civil service...

Cervical screening QA
• No Change
  – Standards defined by national office
  – Regional QARC
  – Visits, reports, advice

Cervical Screening QA
• Will change
  – Some key posts not yet appointed
  – E-mail addresses
  – Incident management
  – Relationships with commissioners
     • AT’s
     • But also CCG’s, LA’s, and PHE
  – Routes for performance management
  – Direct accountability to national office