The document discusses population-based cervical cancer screening in Turkey. It finds that cervical cancer is the 7th most common cancer in women in Turkey, with an estimated 1,443 new cases and 556 deaths annually. While Turkey has a national screening program, coverage is only around 20%. The document evaluates moving to HPV testing as the primary screening method, which could increase sensitivity and allow for longer screening intervals compared to traditional cytology-based screening. Overall, the document advocates for expanding and improving Turkey's cervical cancer screening program through increased uptake of HPV testing.

1. POPULATION BASED CERVICAL CANCER SCREENING
PROGRAMME IN TURKEY
Working Meeting on Comprehensive Cervical Cancer
Prevention and Control in UNFPA, EECARO and
ASRO Countries
M. Faruk Kose, MD
MoH Etlik Zubeyde Hanim Women’s Health
Teaching&Research Hospital, Ankara
Department of Gynecologic Oncology

2. Cancer Incidence and Mortality in Turkey
(All Women)
Incidence Mortality
9th
12th
IARC, Globocan 2008

3. Estimated Cancer Incidence
(15-44 Year-old Women)
Breast 3105
Thyroid 684
Ovary 486
Brain, CNS 437
Leukaemia 407
Colorectum 362
Cervix uteri
Non-Hodgkin lymphoma
345
340
7th
Stomach 323
Corpus uteri 221
0 500 1000 1500 2000 2500 3000 3500
IARC, Globocan 2008

4. Estimated Cervical Cancer
Incidence and Mortality in Turkey
Estimated number of cases: 1.443/3.7%
IARC, Globocan 2008 Estimated number of deaths: 556/2.3%

5. Globocan 2002 vs. 2008
2500
Cervix Ovary Corpus uteri
2000 1937
1804
1628
1500 1364 1443 1391
1247
1001
1000
726
556 581 519
500
0
Globocan Globocan Globocan Globocan Globocan Globocan
2002 2008 2002 2008 2002 2008
incidence mortality

6. Women Cancers in Turkey
MoH 1996 MoH 2002 MoH 2005
Number of Number of Number of
patients patients patients
Breast 3.755 Breast 5.271 Breast 12.414
Stomach 1.083 Skin 1.302 Skin 6.230
Ovary 823 Stomach 1.113 Thyroid 2.940
Skin 820 Endometrium 1.108 Lung 2.520
Colon 632 Ovary 1.074 Stomach 2.380
Lung 631 Colon 927 Colon 2.205
Cervix 623 Lung 855 Ovary 2.114
Brain 611 Hematologic 840 Hematologic 2.110
Hematologic 587 Brain 838 Endometrium 1.883
Rectum 540 Cervix 708 Cervix 1.855
Ministry of Health data

7. Cancer Incidence
(All women per 100.000, 2006)
Type of Cancer
Brain, Neural System
Uterine Cervix
Non-Hodgkin Lymphoma
Ovarium
Stomach
Trachea, Lung, and Bronch
Uterine Corpus
Thyroid
Colorectal
Breast
Incidence
Source: Department of Cancer Control

8. Cervical Cancer Incidence in Turkey
Incidence of the ICCs 2002-2008
5,00 4,76
4,8
4,50
4,4 4,4
4,5
4,00 3,96 4,3
Incidence (100.000)
3,50
3,00
2,50
2,00
2002 2003 2004 2005 2006 2007 2008
*Incidence rates of 2007&2008 are estimated

9. National Cancer Control Programme of Turkey
2009-2015: Headlines for Cervical Cancer
• Prevention
– Tobacco legislations and nicotine replacement therapies
– Measures for preventing sexual transmitted diseases
– HPV Vaccination
• Annual cost efficiency analysis
• Governmental reimbursement is in close future once a cost efficient
price can be reached
• Screening
– Free of charge through Cancer Early Detection, Screening and
Education Centers (KETEMs) upon invitations
– Population based + Opportunistic (Total 20% coverage rate)
• Treatment
– Free of charge to all citizens whatever the social security
coverage

10. Current Cervical Cancer
Screening Programme
• Screening Test: Pap smear
• Target Age Group: 30-65 years
• Screening Interval: 5 years
• Population based screening through KETEMs (free of
charge) + Opportunistic screening
• EU Quality guidelines are implemented with on site
monitorization and evaluation
• KETEMs have consultant Ob&Gyn specialist in addition
to other experts. If smear is abnormal, these
consultations, treatment after screenings and follow up
of patients are free fo charge without any strict referral
rules

11. Monitoring, Evaluation and Partners
• Monitoring and Evaluation Team exist
• On site evaluation
• Hard copy screening data are collected for 3 months
interval
• On site PAX system data collection system is under
construction with EU IPA project
• Partners
– Turkish Society of Gynecologic Oncology
– Turkish Society for Cervical Pathology and Colposcopy
– Turkish Federation Breast Disease
– Turkish Society of Radiology
– Patient advocacy groups, NGOs, UICC

12. Turkey’s Capacity for Cervical Cancer
Screening: Challenges and Lessons Learned
Pathologists: 1.140
Cytopathologists: None
Target Population (30-65): 14 million
Coverage Rate: 20%

13. Number of Pathologists in Turkey
Goverment
Hospitals
702
University Total
Hospitals
316 1.140
Private
122

14. Smear Number Per Day for
One Pathologist in Turkey
Estimated smear per day/pathologist
Mainly
Pap smear
evaluation
20-25 Pap
smears a day

15. How Many Smear Can be Analized
in One Year?
screened
Population has to be
1.140 Pathologists
220 Working days per year
220 x 25= 5.500 x
5.500 1.140=
6.270.000
?

16. Target Population
Only 35 Yrs
628.000
30-65 Yrs
14.419.711
35-65 Yrs
11.549.122
20-65 Yrs
21.715.000
20-70 Yrs
22.642.000

17. Sanliurfa Study: Study Objectives
• To see cervical cancer incidence in rural parts
• To evaluate the feasibility of VIA and VILI
screening
• To determine a national standard for Turkish
population based screening programme
19.05.2011 Türk Jinekolojik Onkoloji Derneği Toplantısı
İstanbul

18. Results of Sanliurfa Study
Abnormalities N (%)
ASC-US 144 (1.60)
ASC-H 6 (0.06)
AGC 5 (0.05)
LGSIL 7 (0.07)
HGSIL 2 (0.02)
Invasive Cancer 1 (0.01)
Total smear number: 9,079

19. Results of Umudum’s Study
Abnormalities %
ASC-US 4.00
LGSIL 0.40
HGSIL 0.19
Total smear number: 180,000
Umudum H, Int Cythopathology Congress, 2006

20. Turkish Cervical Cancer and
Cervical Cytology Research Group
Abnormal smears 1.76%
ASC-US 1.07%
ASC-H 0.07%
AGC 0.07%
LGSIL 0.3%
HGSIL 0.17%
Invasive Cancer 0.062%
Total smear number: 140,334/33 centers

21. Results of Hacettepe Study
HPV positivity 41 (4%)
ASCUS 9 (1.07%)
AGCUS 2 (0.2%)
LGSIL 2 (0.2%)
HGSIL 1 (0.1%)
Total case: 1.032

22. Potential Role of HPV Testing
in Cervical Screening
• Primary Screening
– Adjunct to Cytology
• Higher Sensitivity
• Longer Screening Interval
• Reduced Inadequate Rate
– Sole Primary Test
• Use of Cytology for Triage
– Self Sampling
• Improved Coverage

23. “Is HPV Testing at Least as Good..?”
WHO via IARC has stated
“There is sufficient evidence, based on surrogate
markers, that the efficacy of HPV testing, using a
validated system, as the primary screening modality
can be expected to be at least as good as that of
conventional cytology.”
WHO: World Health Organisation
IARC: International Agency for Research on Cancer

24. Cytology Sensitivity for CIN2+
(All ages)
CIN 2+
HART
Tuebingen
Hannover
Jena
French Public
French Private
Seattle
Canada
Combined
0% 10% 30% 50% 70% 90% 100%
Cytology Positivity

25. HPV Sensitivity for CIN2+
(All ages)
CIN 2+
HART
Tuebingen
Hannover
Jena
French Public
French Private
Seattle
Canada
Combined
0% 10% 30% 50% 70% 90% 100%
HPV Positivity

26. Summary of HPV vs Cytology
Sensitivity and Specificty
Sensitivity Specificity
Cytology 53% 97%
HPV testing 96% 92%

27. Hazard Ratios of Cervical Cancer Death Rates
Study Groups Rate/100.000 HR (95% CI)
Control 25.8 1.00
HPV 12.7 0.52 (0.33-0.83)
Cytology 21.5 0.89 (0.62-1.27)
VIA 20.9 0.86 (0.60-1.25)
Sankaranarayanan R, N Engl J Med, 2009

28. Efficacy of Laboratory Performance:
Cytology vs HPV Testing (CCCaST Study)
PAP HPV PAP HPV
100%
90%
80% PAP laboratory 1
70% PAP laboratory 2
60%
PAP laboratory 3
50%
40% HPV laboratory 1
30% HPV laboratory 2
20%
10%
0%
Sensitivity Specificity
Mayrand MH, Unpublished Data

29. Detection Ratio of CIN3+ After One
Negative Test
Groups Years CIN3+
Cytology 3 0.51% (0.23 – 0.77)
HPV 5 0.27% (0.12 – 0.45)
Ronco G, Lancet Oncol, 2010

30. Conclusion for Why HPV
• The risk of CIN2+ following a negative HPV test is
extremely low for at least 5-6 years
• HPV testing offers improved protection from CIN2+ and
invasive cancer after a negative test compared to the
protection afforded from a normal cytology
• HPV-based screening is more effective than cytology in
preventing invasive cervical cancer, by detecting
persistent high-grade lesions earlier and providing a
longer low-risk period. However, in younger women,
HPV screening leads to over-diagnosis of regressive
CIN2.

31. Performance of the HPV Testings for
CIN2+
Best testing
Cuzick J, J Med Virol, 2010

32. Performance of the HPV Testings for
CIN3+
Best testing
Cuzick J, J Med Virol, 2010

33. Conclusion for Performance of the
HPV Testings
• Five tests have sensitivity for CIN3+ ≥ 95%
– Hybrid Capture II (Qiagen), RealTime HR HPV (Abbott), APTIMA
(Gen-Probe), Amplicor (Roche), Linear Array (Roche)
• Of these five tests, Hybrid Capture II showed higher
sensitivity and lower specificity than the other four tests.
APTIMA and RealTime HR HPV were also more specific than
Cobas and BD HPV
• Differences in specificity may be partly due to different
analytic cutoffs leading also to differences in sensitivity
• PreTect HPV-Proofer is less sensitive much more specific
• Performance of p16INK4a was between PreTect HPV-
Proofer and the highly sensitive tests for both specificity
and sensitivity
Cuzick J, J Med Virol, 2010

34. HPV-Based Screening Program
“Proposed New Screening Algorithm - Population Aged 30-64”
HPV (-) HPV (+)
%92.4 %7.76
1.153.577 Wmn
Cytology
Normal
5-Year recall Normal or Borderline %6 ≥ Mild %1.6
HPV Testing & Cytology Colposcopy
at 6 -12 months
Cytology (-)
HPV (-) HPV (+) Cytology < mild Cytology ≥ mild
HPV (-) Cytology Borderline
HPV Testing & Cytology Colposcopy
Normal
at 6 -12 months
5-Year recall
%2.9 %2.5 %0.6
Wright TC Jr, EUROGIN, 2003 Paris; Cuzick J, Vaccine, 2008

35. HPV-Based Primary Screening Program
Completion of
1st screening round for
all women eligible at
baseline – by Nov 2015
Launch of new program
Nov 2011 Phase III (Full coverage
phase – 3-4mill capacity
by Nov 2014)
Phase IV
All KETEMs fully
Phase II (Extension Phase –
2+ mill capacity - Nov 2013) operational and
offering HPV screening
services
Phase I (Kick Off Phase - nationwide
1 mill capacity –2011)
2011 2012 2013 2014 2015
1 mill 3 mill 6 mill 9-10 mill 14 mill
Cumulative number women screened with HPV primary screening test

36. Way Forward/Future Plans

37. Way Forward/Future Plans

38. New Turkish Cervical Cancer Control Strategy
HPV
PRECANCER CANCER
15 Y 30 Y 35 Y 40 Y 45 Y 60 Y 65 Y
Current Cytology
Strategy
New HPV HPV DNA HPV DNA
Test 1 Test 2
Screening will continue for HPV (+)!
Strategy Vaccination

39. Thank You for Your Attention!

40. The Most Frequent Cancers In Women
Worldwide (In Thousands of New Cases Per Year)
Developed Developing
Breast 692 691
Colon/Rect 338 232
Cervix Uteri 77 453
Lung 242 272
Stomach 102 247
Corpus Utery 142 145
Liver 40 186
Ovary 100 125
Thyroid 74 89
N-H lymphoma 85 71
Oesophagus 18 138
Leukaemia 62 93
Pancreas 81 52
Brain, Nervous S. 40 71
Kidney 68 35
Melanoma of skin 82 15
Lip, Oral cavity 29 64
IARC, Globocan 2008

41. Incidence Rates of Cervical Cancer in
Europe
Age-standardized incidence rate per 100,000 and year
ICC cases/yr: 54,323 ICC deaths/yr: 25,102

42. The Most Frequent Women Cancers in
Europe
IARC, Globocan 2008

43. According to 2006 Estimates of the International
Agency for Research on Cancer
Breast Cancer
• 331,000 cases
• 90,000 deaths
Cervical Cancer
• 36,500 cases
• 15,000 deaths
Colorectal cancer
• 140,000 cases in women and 170,000 in men
• 68,000 deaths in women and 78,000 in men

44. Cancer Incidence and Mortality in Europe
(All Women)
Incidence Mortality
Breast 66.6 Breast 16.9
Colorectum 23.7 Lung 10.7
Lung 13.1 Colorectum 10.5
Corpus uteri 12.6 Ovary 5.4
Cervix uteri
Ovary
10.5
10.2
5th Stomach
Pancreas
5.4
5.0
Melanoma of skin 7.6 Cervix uteri 3.9
7 th
Thyroid 7.1 Brain, nervous system 3.1
Stomach 7.0 Leukaemia 3.0
Non-Hodgkin lymphoma 5.8 Corpus uteri 2.6
0 20 40 60 80 0 20 40 60 80
Annual age−standardized rates per 100,000 women (all ages)
IARC, Globocan 2008

45. Cancer Incidence and Mortality in Europe
(15-44 Year-old Women)
Incidence Mortality
Breast 29.9 Breast 4.7
nd
Cervix uteri
Thyroid 7.0
11.1
2nd Cervix uteri
Brain, nervous system
2.4
1.4
2
Melanoma of skin 6.7 Lung 1.3
Ovary 4.7 Colorectum 1.2
Colorectum 3.7 Ovary 1.2
Hodgkin lymphoma 3.0 Stomach 1.2
Brain, nervous system 2.7 Leukaemia 1.1
Non-Hodgkin lymphoma 2.3 Melanoma of skin 0.6
Lung 2.2 Non-Hodgkin lymphoma 0.5
0 20 40 60 80 0 20 40 60 80
Annual age−specific rates per 100,000 women (15-44 Yrs)
IARC, Globocan 2008

46. Incidence of Cancer in Turkey
300 256,4
271,7 275,4
246,5
Incidence (100.000)
236,3
250
200 168,69 158,1 166,8 169,9
154,15 142,9 149,7
150 127,92
113,03
100
50
0
2002 2003 2004 2005 2006 2007 2008
Kadın
Women
Erkek
Men

47. Primary Screening Pap vs HPV
Test % (%95 CI)
Pap 55.4 (33.6-77.2)
Sensitivity
HPV 94.6 (84.2-100)
Pap 96.8 (96.3-97.3)
Specificsity
HPV 94.1 (93.4-94.8)
Pap 7.1 (4.8-10.3)
PPV
HPV 6.4 (5.0-8.0)
Pap 99.8 (99.7-99.9)
NPV
HPV 100 (98.6-100)
*CCCaST: Canadian Cervical Cancer Screening Trial; Case # 10.171, 30-69 Y, CIN2+
Mayrand MH, N Engl J Med, 2007

48. Efficacy of HPV Testing for
the Detection of CIN
• The New Technologies for Cervical Cancer (NTCC)
Screening Study
• Case # 128.285
• FU 5-6 Yrs
• Randomization and second round after one year
– HPV testing group
– Cytology group
• Age intervals of analysis; 25-34 and 35-60 Yrs
HPV group Cytology group RD
Round one 206 101 2.03
Round two 16 32 0.51
Two rounds 221 133 1.66
Ronco G, Lancet Oncol, 2010

49. NTCC: the Detection of ICCs
HPV group Cytology group p
All ages
Round one 7 9 0.62
Round two 0 9 0.004
Total 7 18 0.028
35-60 Yrs
Round one 6 8 0.61
Round two 0 7 0.016
Total 6 15 0.052
25-34 Yrs
Round one 1 1 1.00
Round two 0 2 0.50
Total 1 3 0.37
Ronco G, Lancet Oncol, 2010

50. Sensitivity of the HPV Testings
Test (Producer) CIN2+ (%) CIN3+ (%)
Cytology; mild+ 88.5 92.3
Hybrid Capture II (Qiagen) 96.5 97.5
BD HPV (BD-ProExC) 94.8 95.8
Cobas (Roche) 95.5 96.1
PreTect HPV-Proofer (NorChip) 74.7 78.5
APTIMA (Gen-Probe) 95.0 97.1
RealTime HR HPV (Abbott) 93.0 95.0
p16INK4a (mtm Lab) 85.9 89.1
Cuzick J, J Med Virol, 2010