1. PROPHYLAXIS AND CERVICAL SCREENING IN BULGARIA- PAST, PROBLEMS AND FUTURE Dr. Petya Kostova, PhD Gynecology Clinic, National Oncology Hospital, Sofia; Bulgaria Assoc. Prof. Dr V. Zlatkov, PhD Gynecology Clinic, National Transport Hospital “King Boris III”, Sofia, Bulgaria

2. Significance of the problem (1) w Cervical cancer is one of the most common malignant diseases in the world with annual occurrence of 500 000 cases. It is placed 5th with its share of 7.3% of the total number of localizations in both sexes. w According to the WHO, 15% of all cancers in women belong to cervical cancer, about 20% of which are found in the developed countries and 80% in the developing countries.

3. Significance of the problem (2) Cancer Registry 2002 Bulgaria total of themwomen of them еndometrial, cancer cervical, ovarian patients number% % Cancer patients 216 881127 22758.732 24225.3 New cases 29 43514 05147.73 00121.4 Dead 15 7856 59541.889513.8

4. Structure of cancer incidence in female Bulgaria (2001)

5. Primary prophylaxis w It requires control and elimination of the etiopathogenesis of the disease. w There are no effective methods for sexual behavior regulation. w Over the past years, the effectiveness of preventive vaccines against HPV infections has been discussed: Cervarix® (GlaxoSmithKline) Gardasil® (Merck)

6. Secondary prophylaxis w Its aim is to detect and eliminate precancer states or early malignancies w It is performed on women with complaints and without clinical symptoms (screening). Types of screening population based & selective organized & opportunistic multi-phase & one-procedure

7. The principles of secondary prophylaxis w The disease, object of screening, should be a medico-social problem (with high incidence and mortality); w Its clinical course should be well known, with a preclinical phase corresponding to a biologically less aggressive period of development; w The screening test should be simple to use, safe, cheap, with high sensitivity, specificity and predictive value; w The treatment of the patients, diagnosed during the screening, to be effective and to reduce mortality.

8. Preventive effect of cervical screening

9. Possible results w When organized screening cover 70% of the target population, it is possible to achieve the following results:  30% of cancer cases to be actively detected  30% of the advanced cancer cases can be decreased >15% of mortality at screening localizations can be reduced

10. History of the screening in Bulgaria w Since 1956, prophylactic gynecological examinations have been conducted in Bulgaria.  K.Tsanev and D.Nikolova (1970) - introduced cytological screening as a routine test.

11. Cytological laboratry Past scheme in Bulgaria

12. General principles w The screening program involves all women over 30 years of age, both married and single, and is performed once every two years. w It is conducted by district gynecologists and nurses. Diagnostic cytological tests are performed in 14 laboratories based at the district oncological centers and the National Oncological Center. w According to the screening program, 1.5 mill. women are subject to examination.

13. Incidence of cervical cancer in Bulgaria (1970-2002) w An increase in the crude incidence was observed (12.7 to 26.9 % ооо ). w The same tendency was observed for the standardized incidence from 10.0 to 19.4 % ооо women.

14. Incidence according to age, residence and districts wIncidence (1970-1996) arise in all age groups (р<0.05), especially at 30-49 years. wIncidence (1981-1996) is higher at towns than in villages (р<0.05) w Standardized cervical cancer incidence (1991-1996 г.) varies according to districts from 6.1% ооо tо 23.1% ооо women.

15. Incidence of cervical cancer worldwide

16. Effect of screening on incidence (Scandinavian countries) M.Hakama, K.Louhivuori (1988)

17. Mortality of cervical cancer in Bulgaria (1970-2002) w An increase in the crude mortality was observed, reaching from 3.2 tо 9.8 % ооо. w The same was tendency for the standardized index-from 3.1 to 6.2 % ооо women.

18. Mortality of cervical cancer worldwide

19. Screening results Effect on mortality in Europe

20. Ratio between the patients with CIS and cervical cancer in Bulgaria (1975-2002) Ratio between the cancer in situ and invasive cancer for the studied period shows bigger frequency of invasive forms and the arisal of this ratio during the study period.

21. Ratio CIS / Ca (1) Most important is the comparison to EC countries. The ratio between CIS and invasive cancer is 3/1 in favour of in situ forms in EC. In Bulgaria, is the opposite. It is 5/1 due to the higher level of invasive cancer.

22. Ratio CIS / Ca (2) In the USA 55-60 mill. Pap tests are completed every year, the cost for them being $ 6 bln. Deaths - 3800 Cancer - 10300 USA

23. Stage distribution of cervical cancer in Bulgaria (1970-2002) For the whole studied period we cannot observe any improvement of level of early diagnostics with stable high level of advanced cases.

24. Screening coverage A bout 1.5 mill women were screened annually until 1989, after which there was a progressive drop and only 205 081 screening tests were reported in 1996. Legend: 1-Blagoevgrad; 2-Burgas; 3-Varna; 4-V. Тarnovо; 5-Vratsa; 6-Pleven; 7-Plovdiv; 8-Russe; 9-Sofia-city.; 10-Sofia-reg.;11-St. Zagora; 12-Shumen; 13-Haskovo; 14-Bulgaria

25. Share of women with biopsy The share of biopsies among the signalized women is low about 1/3, except 3 centers where it is more than 50%. This means that many women do not pass the step of precise diagnostics. Legend: 1-Blagoevgrad; 2-Burgas; 3-Varna; 4-V. Тarnovо; 5-Vratsa; 6-Pleven; 7-Plovdiv; 8-Russe; 9-Sofia-city.; 10-Sofia-reg.;11-St. Zagora; 12-Shumen; 13-Haskovo; 14-Bulgaria

26. Faults of past screening activity w Faults in organization w Faults in test w Faults in interpretation

27. Problems of organization They are connected with the following : w No team for management of the programme w No screening registry w Lack of call and recall system w No unified system for diagnostics of signalized women w No quality control on all screening levels.

28. Problems of test w Monitoring quality of cervical smears w Adequate preparation and storage of smears at laboratories w Timely cytological answer to clinicians w Registration of results in screening registry

29. Problems of interpretation w The need of unified cytological classification w The introduction of internal and external quality control at cytological laboratories w The continuous training and education of staff 4 3 2 1

30. What’s happened over the last 10 years?

31. w Over the past 10 years, different teams of the Ministry of Health have initiated the development of new cervical screening programme. w One of these teams, under the guidance of prof. Chernozemski and with our participation, created “The National Strategy for Prophylactic Oncological Screening in Bulgaria for the period 2001-2006” for the three main screening localizations - breast, uterine cervix and prostate. w It was accepted by a decree of the Council of Ministers № 880 / 22.12.2000, but it could not be realized in practice. Attempts at change

32. Recent situation Selective opportunistic screening Selective opportunistic screening Cash Payment (? Women) Cash Payment (? Women) Population screening Population screening Secondary prophylaxis ? Opportunistic screening Opportunistic screening Health Insurance system Health Insurance system 80 000 women Health Insurance system Health Insurance system Gynecologist GP / Gynecologist Gynecologist

33. Necessary changes w Restoration of the organized population cervical screening as a component of the health system. w Building a structure for management and screening registry. w Introduction of unified terminological system. w Establishment of quality control at cytological laboratories. w System for continuous education.

34. The basic components of the future cervical screening programme Qualification Management Education Efficiency & effectiveness Efficiency & effectiveness Quality control Quality control Cervical screening

35. Target and interval w Recommended target population is 1.8 mill. women (25-60 years) w The screening interval should be 3 years.

36. Potential prices of cervical screening w According to world standards the mean value of one conventional screening examination is 10 €. w In our country this price is lower, around 10 leva (5 €), because of lack of realistic assessment of human labor, overheads, and equipment value.

37. Prices of cervical cancer treatment according to stage for one year Cervical cancer Stages Number of cases in Bulgaria (2001) Prices according to EU data (Andrae Bengt - 2004) Per itemTotal St. III – IV34730 000 €10 410 000 € St. I – II6709 000 €6 030 000 € CIS275 300 €83 500 € Total1292-16 522 500 €

38. Which price is better ? w If the target population (25 - 60 years) is 1.8 mill, its full coverage will cost 9 mill €. w If screening interval is 3 years, it will cost 3 mill € yearly. w Treatment of cancer cases for one year – about 16 mill €.

39. Finally, we would like to recall the aphorism used by J. Bokhman ( 1989 ) : "... If a woman dies of uterine cancer, there is someone else beside the cancer itself, who is to be blamed for her death...".