Cervical Cancer Screening Across Europe by mikeholy

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									Cervical Cancer Screening Across
             Europe
              Peter Sasieni
    Professor of Biostatistics & cancer
              Epidemiology
Cervical screening – the basics
            To maximise
            To maximise
            To maximise
            To maximise             To minimise
                                    To minimise
                                    To minimise
                                    To minimise
            benefit
            benefit
            benefit
            benefit                 harm
                                    harm
                                    harm
                                    harm
            Invite, remind
             Invite, remind
            Invite, remind          Informed choice
                                     Informed choice
                                    Informed choice
            Invite, remind          Informed choice
Coverage
Coverage
Coverage
Coverage    Convenient, pleasant
             Convenient, pleasant
            Convenient, pleasant
            Convenient, pleasant
                                    Prevent over-
                                     Prevent over-
                                    Prevent over-
                                    Prevent over-
                                    screening
                                     screening
                                    screening
                                    screening
             Identify disease,
            Identify disease,
            Identify disease,        Don’t mislabel healthy
                                    Don’t mislabel healthy
                                    Don’t mislabel healthy
Test
Test        Identify disease,       Don’t mislabel healthy
Test
Test         accurate, repeatable Quality control
            accurate, repeatable
            accurate, repeatable
            accurate, repeatable     Quality control
                                    Quality control
                                    Quality control
             Failsafe
            Failsafe                 Avoid anxiety
                                    Avoid anxiety
            Failsafe                Avoid anxiety
Triage
Triage
Triage
             Identify those needing Avoid over-treatment
            Identify those needing Avoid over-treatment
            Identify those needing Avoid over-treatment
             treatment
            treatment
            treatment
             Failsafe
            Failsafe                 Minimal side-effects
                                    Minimal side-effects
Treatment
Treatment    Effective treatment
            Effective treatment
            Before new cancers      As infrequently as
Recall      develop                 possible
Trends in cervical cancer: 1950-1999
     Coverage of target age group (25-64):
                1989 to 2008
                                 1989 to 1994 - Percentage of target population less than 5.5 years since last test

 Coverage increased             1995 to 2008 - Percentage of target population less than 5 years since last test

                           100
  rapidly after 1989
    Over 80%: 1992-2005   80


    Below 80% 2006-08     60


 87.1% in the last 10     40
  years
                           20



                             0
        Cervical Cancer Incidence in England 1975-2002
                    Age Standardised(European)
              Incidence trends
18



                                  Programme Start
16
14
12
10
 8




     1975    1980      1985       1990       1995   2000
                               Year
  Success of Cytology
                                                     Age-specific mortality rates by birth cohort
  Screening in the UK                                     England and Wales 1950-2008




                                                20
• Both analysis of trends




                             Mortality Rate per 100 000 women
                                                        15
  and case-control                                                                                       1910-14

  studies suggest that
                                                                                                         1920-24
  screening is preventing



                                              10
   – About 80% of cervical
                                                                                                   1930-34
      cancer
   – Over 90% of cervical                                                                    1940-44

      cancer mortality             5                                                   1950-54
                                                                                 1960-64

   in screened women                                                       1970-74
                                                0




                                                                0   20    40           60          80
                                                                         Age (yr)
         Cytology Sensitivity - CIN2+

                                           CIN 2+
      HART
   Tuebingen
    Hannover
     Jena
 French Public
 French Private
    Seattle
    Canada


   Combined
                  0%          10%   30% 50% 70%           90%   100%
                                    Cytology Positivity
Cuzick et al, Int J Ca 2006
                     FIGO Stage
Women with recorded FIGO Stage by Age

FIGO                            Age Group
Stage       20-34      35-49      50-64       65+         Total
 1A       859(58%)   840(41%)   214(21%)     74(7%)    1987(35%)

  1B      494(33%)   773(38%)   384(37%)    264(24%)   1915(34%)

  2        82(5%)    235(12%)   231(22%)    338(30%)   886(16%)

  3+       59(4%)    182(9%)    210(20%)    436(39%)   887(16%)

 Total   1494(100%) 2030(100%) 1039(100%) 1112(100%) 5675(100%)
    The English Programme
• Target population 14 million women
  – Aged 25-64
• Liquid based cytology
  – 3 yearly 25-49
  – 5-yearly 50-64
• £157million/year in England
    The importance of audit
• Ensure that the screening programme is
  working
• Identify good practice
• Influence
  – Clinical practice
  – Laboratory procedures
  – Failsafe management
  – Programme policy
Questions to be addressed (1)
• How effective is screening?
  – In screened women?
  – In the population?
• How frequently are women actually
  screened?
• What happens to women after an early
  repeat?
• What happens to women referred to
  colposcopy?
Questions to be addressed (2)
• What are the advantages of more
  frequent screening?
• From what age should women first be
  screened?
• Is there reason to continue screening
  beyond age 50?
• How often do women get cervical
  cancer after being treated for CIN3?
Percent with a negative smear in last 5.5
                 years
                   100%

                   90%

                   80%

                   70%
      Percentage




                   60%

                   50%

                   40%

                   30%

                   20%

                   10%

                    0%
                              20-29             30-39            40-49             50-59            60-69

                          Controls                           Age (years)

                          1B+ Cancer Cases

                     Unpublished Data from the UK Audit of Screening Histories 2009 (including 425 cases aged 20-29).
Maximal interval between smears

• Look back up to 10 years (to 1988 or
  age 20)
• What was the longest period during that
  time without a smear?
                                      Protection by age, all cancer
                  Age 30-44                                  Age 45-59                            Age 60-74
1.2
      1
.8
.6
.4
.2
      0




                                           7.5-10




                                                                                 7.5-10




                                                                                                                      7.5-10
          < 3.5




                                                     < 3.5




                                                                                          < 3.5
                  3.5-5.5



                            5.5-7.5




                                                             3.5-5.5



                                                                       5.5-7.5




                                                                                                  3.5-5.5



                                                                                                            5.5-7.5
                                      Maximum interval with no smear (years)
                                                    Relative risk                    95% CI
                     Protection for stage 1B+ sqamous cancer
                                    By age group
                  Age 30-44                                 Age 45-59                            Age 60-74
1.2
      1
.8
.6
.4
.2
      0




                                           7.5-10




                                                                                7.5-10




                                                                                                                     7.5-10
          < 3.5




                                                    < 3.5




                                                                                         < 3.5
                  3.5-5.5



                            5.5-7.5




                                                            3.5-5.5



                                                                      5.5-7.5




                                                                                                 3.5-5.5



                                                                                                           5.5-7.5
                                      Maximum interval with no smear (years)
                      Upper age of screening
                • Analysis of cases and controls aged 65-79
                • Strong protection within 7 years of a smear
                • Moderate protection 8-14 years after smear
                       1
Relative risk




                      .5
                       0




                           0      5             10                15   20
                                      Years since last screen
                                           RR            95% CI
 Areas of Development since 2000
• Policy
    –   Age-intervals
    –   Management of mild dyskaryosis
    –   Definition of mild dyskaryosis
    –   Post colposcopy management
•   Cytology
    – Liquid- based collection media
    – Computer-assisted reading
•   HPV
    – Triage of borderline or mild cytology
    – Post-treatment surveillance
    – Primary screening
EUROPE
              Key References
• Cervical cancer screening policies and
  coverage in Europe
  – Anttila et al
  – European Journal of Cancer 45 (2009) 2649-2658
• Process performance of cervical screening
  programmes in Europe
  – Ronco et al
  – European Journal of Cancer 45 (2009) 2659-2670
       Organised or Opportunistic
Organised                        Opportunistic
• Database of the entire         • Over screens wealthy
  population
                                 • Under screens poor
• Invitations for first screen
  and recalls                    • Lack of quality control
• Free screening & treatment     • Lack of failsafe
                                 • Even when effective, not
                                   efficient
         Policies in EU 2005-08
                    No. Countries
No programme        2
Ad hoc              13
Population based    12
Cervical Cancer Screening in Europe

                                  Nationwide
                                  Organised

                                  Organised
                                  (Roll-Out)

                                  Nationwide
                                  Opportunistic

                                  Localised
                                  Opportunistic




                                                  23
Cervical Cancer Screening Across EC

              6%                    Nationwide Organised

                              34%
                                    Nationwide Organised -
                                    Rolling Out

                                    Nationwide
     49%                            Opportunistic

                             11%    Private Provision
                                    Localised
                                    Opportunistic


           % of Population

                                                             24
       Lifetime number of tests
No. tests    No. countries   Frequency
45+          6               Annual
21           1               2-yearly
14-15        6               3-yearly
12-13        8               3-5 yearly
6-9          4               5 yearly
None         2
            Age-range
Lower age        Upper age
• 15-30          • 59 – no limit
• Mode 25        • Mode 64
       Huge variation within EU
Minimal screening          Excessive screening
• Bulgaria                 • Luxembourg
• Romania                  • Germany
• Poland
• Portugal


 Finland: more tests outside the programme than
 in the programme!
              Cytology results
• ≥ ASCUS
  – 1.2% (Germany), 2.4% (Poland)
  – 10.3% (Slovenia), 6.6% (England)


• ≥ HSIL
  – ≤0.3% (France, Poland, Germany, Italy)
  – 1.7% (Denmark)
   Management of ASCUS & LSIL
• Immediate referral – colposcopy
• Repeat cytology
• HPV triage
A PROPOSAL FOR BLACK SEA STATES
 Screen four times over a lifetime
• Ages 38, 35, 45 and 57
                Primary Test
• HPV
  – Extremely high negative predictive value
  – Suitable for extended screening interval
  – Easily automated
  – Not dependent on human judgement
  – Robust to poor sample collection
         Secondary Test (Triage)
• Cytology (ideally reflex)
  – HSIL         → colonoscopy + mandatory biopsy
  – ASCUS/LSIL   → 12 month repeat
  – Negative     → 24 month repeat
             Repeat HPV test
• HPV Positive → reflex cytology
  – ASCUS+ → colposcopy
  – Negative → 12 month repeat


• HPV negative → routine

• Second repeat
  – HPV positive → colposcopy
               Post colposcopy
• After 1st colposcopy
  – 12 month HPV test (if positive repeat colposcopy,
    negative discharge)
• At 2nd colposcopy
  – Mandatory biopsy;
     • if <CIN2 3-yearly HPV testing
• Post treatment
  – 3 yearly HPV testing
       Programme infrastructure
• Population registry for call & recall
• Samples sent to central, quality controlled
  laboratories
   – HPV testing to include “test of sample adequacy”
   – Results sent promptly to both woman and her GP
      • 96% within 4 weeks, 100% within 8 weeks
• Colposcopy appointments to be “chased” by
  phone or text
• Repeat cytology appointments to be monitored
  centrally
• Reminders for defaulters to be sent to GP
                        Quality
• Good information with invitation
• Training school for sample takers
   – Technique
   – Counselling
• Female sample takers
• Clean, pleasant, secure clinics
• Colposcopy training
   – Don’t rely on interprative skills
   – Concentrate on safe and effective treatment
• Gather statistics
   – Process measures
   – Quality measures
   – Outcomes
THANK YOU

								
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