PROPHYLAXIS AND CERVICAL SCREENINGIN BULGARIA- PAST, PROBLEMS AND FUTURE

Dr. Petya Kostova, PhDGynecology Clinic,

National Oncology Hospital, Sofia; Bulgaria

Assoc. Prof. Dr V. Zlatkov, PhDGynecology Clinic,

National Transport Hospital “King Boris III”, Sofia, Bulgaria

Significance of the problem (1)

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.

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.

Significance of the problem (2)

Cancer Registry

2002

Bulgariatotal

of them women

of them

еndometrial,

cancer

cervical,

ovarian

patients

number % number %Cancer patients

216 881 127 227 58.7 32 242 25.3

New cases 29 435 14 051 47.7 3 001 21.4

Dead 15 785 6 595 41.8 895 13.8

24.6 24.3

3.94.7

5.15.47.1

9.7

7.5

7.7

0

5

10

15

20

25

30

Sites

%

Structure of cancer incidence in female Bulgaria (2001)

Primary prophylaxis

It requires control and elimination of the etiopathogenesis of the disease.

There are no effective methods for sexual behavior regulation.

Over the past years, the effectiveness of preventive vaccines against HPV infections has been discussed:

Cervarix® (GlaxoSmithKline) Gardasil® (Merck)

Secondary prophylaxis

Its aim is to detect and eliminate precancer states or early malignancies

It is performed on women with complaints and without clinical symptoms (screening).

Types of screening

• population based & selective

• organized & opportunistic

• multi-phase & one-procedure

The principles of secondary prophylaxis

The disease, object of screening, should be a medico-social problem (with high incidence and mortality);

Its clinical course should be well known, with a preclinical phase corresponding to a biologically less aggressive period of development;

The screening test should be simple to use, safe, cheap, with high sensitivity, specificity and predictive value;

The treatment of the patients, diagnosed during the screening, to be effective and to reduce mortality.

Preventive effect of cervical screening

Frequency of screening

Reduction of cumulative risk

Number of tests

1 year 93.3 % 30

2 years 92.5 % 15

3 years 91.4 % 10

5 years 83.9 % 6

10 years 64.2 % 3

Possible results

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

History of the screening in Bulgaria

Since 1956, prophylactic gynecological examinations have been conducted in Bulgaria .

K.Tsanev and D.Nikolova (1970) - introduced cytological screening as a routine test.

CERVICAL

SCREENING

NOC-Sofia Regional DOZ

Women

under 30 years

Women

over 30 years

District

Ob/Gyn

Examination

PAP smear

(+) test(-) test

Colposcopy

Precancer CancerNormal finding

Cytological

laboratry

Past scheme

in Bulgaria

General principles

The screening program involves all women over 30 years of age, both married and single, and is performed once every two years.

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.

According to the screening program, 1.5 mill. women are subject to examination.

Incidence of cervical cancer in Bulgaria (1970-2002)

0

5

10

15

20

25

30

Year

105

Crude

Standardized

An increase in the crude incidence was observed (An increase in the crude incidence was observed (12.7 12.7 to to 26.26.99 % %оооооо).).The same tendency was observed for the standardized incidence from The same tendency was observed for the standardized incidence from 10.0 to 19.4 10.0 to 19.4 %%оооооо women. women.

Incidence according to age, residence and districts

Incidence (1970-1996) arise in all age groups (р<0.05), especially at 30-49 years.

Incidence (1981-1996) is higher at towns than in villages (р<0.05)

Standardized cervical cancer incidence (1991-1996 г.) varies according to districts from 6.1%ооо tо 23.1%ооо women.

Incidence of cervical cancer worldwide

Incidence

Levels Countries/regions Registries (x 10 5)

Low from 3 to 9 x 10 5 Scandinavian,USA,Canada, England, Israel

Finland (3.62), USA (4.05)

Medium from 10 to 20 x 10 5 Parts of EC, Central Europe, Japan, Australia and some in Asia

Australia (12.5) Japan (16.0) Slovenia (18.5)

High from 21 to 30 x 10 5 South-East Europe, Russia Bulgaria- (26.9)

Poland (23.8) Russia (28.6)

Very high Over 30 x 10 5 South America, Africa Zimbabwe (67.21) Brazil (64.78)

Effect of screening on incidence (Scandinavian countries)

M.Hakama, K.Louhivuori (1988)

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

1945 1950 1955 1960 1965 1970 1975 1980 1985

Years

per

105

Denmark

Norway

Iceland

Sweden

Finland

Mortality of cervical cancer in Bulgaria (1970-2002)

0

2

4

6

8

10

12

Year

105

Crude

Standardized

An increase in the crude mortality was observed, reaching from An increase in the crude mortality was observed, reaching from 3.2 3.2 ttо о 99..88 % %оооооо..The same was tendency for the standardized index-from 3.1 to 6.2 The same was tendency for the standardized index-from 3.1 to 6.2 %%оооооо women. women.

Mortality of cervical cancer worldwideCOUNTRIES Stand. mortality

(%ооо) Israel 1.42

Japan 1.98

USA 2.70

Finland 3.00

Germany 3.51

Bulgaria 6.2

Poland 8.23

Romania 10.01

Venezuela 10.51

Chile 14.87

2

3

4

5

6

7

8

9

1970 1975 1980 1985 1990 1995 2000 2005

Bulgaria

United Kingdom

EUROPE

EU average

Nordic average

Screening results Effect on mortality in Europe

19

75

19

77

19

79

19

81

19

83

19

85

19

87

19

89

19

91

19

93

19

95

19

97

19

99

20

01

0

5

10

15

20

25

30

Years

105

CaCIS

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.

Ratio CIS / Ca (1)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

ЕС Bulgaria

CISCa

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.

Ratio CIS / Ca (2)

In the USA 55-60 mill. Pap tests are completed every year,

the cost for them being $ 6 bln.

Per year

AGC-180 000

HSIL 300 000

LSIL–2 mill. women

ASCUS – 3 mill. women

Deaths - 3800

Cancer - 10300USA

Stage distribution of cervical cancer in Bulgaria (1970-2002)

0

100

200

300

400

500

600

700

800

Year

Number

stages I+II

stages III+IV

without stage

For the whole studied period we cannot observe any improvement of level of early diagnostics with stable high level of advanced cases.

Screening coverage About 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.

0

20

40

60

80

100

120

%

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Oncological dispensaries

mean for the period

1980

1995

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

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.

0100200

300400500600700

800900

1000

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Oncological dispensaries

Number

signalized

with biopsy

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

Faults of past screening activity

Faults in organization Faults in test Faults in interpretation

Problems of organization

They are connected with the following :

No team for management of the programme

No screening registry Lack of call and recall system No unified system for diagnostics of

signalized women No quality control on all screening levels.

Problems of test

Monitoring quality of cervical smears Adequate preparation and storage of smears at

laboratories Timely cytological answer to clinicians Registration of results in screening registry

Problems of interpretation

The need of unified

cytological classification

The introduction of internal

and external quality control

at cytological laboratories

The continuous training and

education of staff

4

3

2

1

What’s happened over the last 10 years?

Over the past 10 years, different teams of the Ministry of Health have initiated the development of new cervical screening programme.

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.

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

Recent situation

Selectiveopportunistic

screening

Selectiveopportunistic

screening

CashPayment

(? Women)

CashPayment

(? Women)

Population

screening

Population

screening

Secondary

prophylaxis

?

Opportunistic

screening

Opportunistic

screening

HealthInsurance

system

HealthInsurance

system

80 000 women

HealthInsurance

system

HealthInsurance

system

Gynecologist GP / GynecologistGynecologist

Necessary changes

Restoration of the organized population cervical screening as a component of the health system.

Building a structure for management and screening registry.

Introduction of unified terminological system.

Establishment of quality control at cytological laboratories.

System for continuous education.

The basic components of the future cervical screening programme

QualificationQualification

ManagementManagement

EducationEducation

Efficiency &effectiveness

Efficiency &effectiveness

Qualitycontrol

Qualitycontrol

Cervicalscreening

Target and interval

Recommended target population is 1.8 mill. women (25-60 years)

The screening interval should be 3 years.

Potential prices of cervical screening

According to world standards the mean value of one conventional screening examination is 10 €.

In our country this price is lower, around 10 leva (5 €), because of lack of realistic assessment of human labor, overheads, and equipment value.

Prices of cervical cancer treatment according to stage for one year

Cervical cancerStages

Number of cases in Bulgaria (2001)

Prices according to EU data(Andrae Bengt - 2004)

Per item Total

St. III – IV 347 30 000 € 10 410 000 €

St. I – II 670 9 000 € 6 030 000 €

CIS 275 300 € 83 500 €

Total 1292 - 16 522 500 €

Which price is better ?

If the target population (25 - 60 years) is 1.8 mill, its full coverage will cost 9 mill €.

If screening interval is 3 years, it will cost 3 mill € yearly.

Treatment of cancer cases

for one year –

about 16 mill €.

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...".