Croatian Society for Colposcopy and Cervical Pathology

Phone: 00385-1-3787-361

Fax: 00385-1-3768-272

E-mail: frane.grubisic@zg.tel.hr

See new information of the Croatian Society about "Abnormal Cytologyc and Pathohystological Finding of the Uterine Cervix".

About the Society

The Croatian Society for Colposcopy and Cervical Pathology is a professional and scientific body of the Croatian Medical Association, which brings together physicians and other highly qualified experts from the area of gynaecology and obstetrics, gynaecopathology, gynaecocytology, and work in the Republic of Croatia.

The Assembly of the Croatian Society of Colposcopy and Cervical Pathology, in session on 07.04. 1999, in Zagreb, passed the constitutional act of the Society. The work of the Society is in line with the objectives and tasks of the Croatian Medical Association.

The headquarters of the society is in Zagreb, the Clinic for Gynaecological Disorders and Obstetrics, Clinical Hospital of the Sisters of Mercy, Zagreb, Vinogradska cesta 29. Tel: 00385 1 3787361; fax: 00385 1 3768272

The President of the Croatian Society for Colposcopy and Cervical Pathology is:

Doc. dr sc. Goran Grubiić

In Buenos Aires, Argentina, on 9 Nov 1999. on 10 World Congress of Colposcopy and Cervical Pathology, Croatian Society was received as the member of IFCPC.

Our society consists from 120 members. They have shown great interest to development of colposcopy attending

The First croatian course of colposcopy held on 20 June 1998 in Zagreb (200 participants and reputable guest prof. Mario Peroni from Ascoli Piceno)

The reasons for constitution of Society were:

A) Increasing number of young women (young nulliparae and those for childbearing) with abnormal Pap smears who need colposcopy.

B) Current status in Croatia is following: Taking in the mind that about 2 000 000 women need almost once in 3 years Papa smear screening, this is the great task for about 450 gynecologists in Croatia who must yearly take about 670 000 Pap smears

C) Among 2.000.000 women in 3 years we can expect about 2,5% abnormal Pap smears, i.e. 17 000 colposcopies in 3 years

D) Emerges the necessity for educated colposcopists, and that is the main task of our young society

E) All that points out the need for clinical units for cervical dysplasia and lower genital tract.

F) The great possibilities of new telecomunication approach will enable modern communication with reputable experts for consulting and in the same moment

achieving the best results.

The basic tasks of the Society are:

1. Ongoing work to improve the professional and scientific qualifications of its members.
2. The organisation of professional and scientific meetings, congresses, seminars, lectures and further qualification courses.
3. Collaboration with scientific, teaching and health organisations for the purpose of as effective work as possible in the professional and scientific fields.
4. The presentation of colposcopy, within the context of secondary measures for the prevention of neoplastic changes of the cervix and the lower genital tract, in professional and scientific bodies of the Croatian Medical Association.
5. The development of ongoing collaboration with other societies and sections in the CMA in areas of joint interest.
6. Collaboration with colposcopy and cervical pathology associations in other countries.
7. Representation of the national interests in international associations.
8. Establishing criteria for professional qualifications of physicians and standards in health care, and where necessary the provision of opinions about the professional and scientific qualifications of physicians in the area of the Society’s activity.
9. Raising the health culture of the population by the use, among other things, of the media.
10. Cultivation and development of the principles of medical ethics among its members, and the development of connections among its members.
11. Supervision of the professional work of its members and other specialists interested in colposcopy and cervical pathology, and taking measures for the protection of patients or for the protection of its own members.

On 25 Nov 2000 we organise scientific symposium dealing with 75 anniversary of colposcopy with following programme:

-From Hinselmann´s colposcope to the digitalised immaging

-Histopathology and immuncytochemistry in HPV induced lesions of the uterine cervix.

-Diagnostic problems of the praeclinical carcinoma of the uterine cervix and so called "occult carcinoma of the uterine cervix".

-Cytological classification of the uterine cervix.

-Colposcopical classification Rome 1990.

-Development of ectropion.

-STD in Croatia - current status.

-Modern approach in the diagnosis of HPV induced lesions of the lower female genital tract and the role of colposcopy.

-Is it possible complete recovery if HPV induced lesions?.

-Cervical atypias in pregnancy and role of the colposcopy.

-Principles of the conservative approach to cervical atypias in nulliparous women.

-The role of the colposcopy in the rape victims.

-Adolescent rape victims and colposcopy.

-The diagnosis and therapy of the male partner.

-The role of the peniscopy.

-Microcolpocervicoscopy.

-Modern approach in the treatment of the preinvasive lesions of the uterine cervix.

-Ambulatorial treatment.

-Clinical treatment.

-The control of the quality in the colposcopy.

-The acceptance of the diagnostic-therapeutical algorhytm.

In 2001, in cooperation with Medical faculty of Zagreb and Croatian medical chamber we start with permanent education of colposcopy and cervicovaginal pathology among gynecologist and nurses because the cervical cancer is still the first cause of gynecological illness in women in Croatia.

The course will take part at hospital where I work, will last 2-3 days, and will be organised according to interests of clinical practice.

It enclose main lectures:

Cytology, histopathology and colposcopy from benign ectropion to microinvasive carcinoma, lectures which will be fulfilled with colposcopic "training" in cooperation with experienced colposcopist after informed consent with every woman who will underwent colposcopic examination and further explanation.

Of course, according to our constitutional act we plan to organise subdivisions in Split, Osijek and Rijeka, which have Medical faculties and colleagues really interested for development of colposcopy.

In our everyday practice we apply International colposcopical terminology accepted in Rome, at 7 th World congress on May 17 th 1990., and modified Bethesda cytological classification which performed our reputable cytologists, pathologists and gynecologists (1992).

Some works which were presented at international symposiums:

- Epidemiologycal data related to the establishment of colposcopy in Croatia.

Grubii G, Lepui D.

According to the Croatian register for 1990, breast cancer dominates (more than 20%). Adding all recently discovered CIS and IC, the frequency of cervical cancer increases up to 15% and takes the second place, after the breast cancer.

The non-invasive cervical cancer is discovered two times more than the invasive ; it is 62,5% of all recently discovered cases of non-invasive cancer and 37,5% of invasive cancer.

Attention!!!

An increase of all recently discovered cases of non-invasive cervical cancer is higher within last 15 years than the decrease of invasive cancer.

Consequently, the incidence of cervical cancer is increased in total:

- 1150 new patient was discovered in 1990 compared to 800 patient in 1969

- This presents an increase for almost 50%, although the number of female population has not grown during this period.

- The frequency of cervical cancer is diminished less than expected (only for 30% during 21 years,1969-1990. period).

- The proportion in favour of CIS is not the result of improved education of female population, but of the increased incidence of cervical cancer generally, as well as CIS.

Female population up to 40 years

- Every ninth recently discovered cancer is invasive

- In the population of women who are 40 years old and older invasive cervical cancer is three times more frequent than non invasive

- It seems there is no positive results in this group relating the prevention of cervical cancer

-The relation between the invasive and non-invasive is the same as it was 20 years ago

What should we do?

- To educate and inform the female population, who are over 40 years, about early diagnosis of cervical cancer, because they are responsible for relatively poor results in the decrease of the incidence of cervical cancer

- On the other hand, younger women are responsible for the increase in the incidence of the non-invasive cancer

The comparison to the world statistics

- The most acceptable is the comparison between Croatia and Finland (European countries, the number of inhabitants is almost equal, Finland has one of the oldest and most precise registers for cancer)

- The frequency of cervical cancer and CIS in Croatia and Finland is 1:1

- Finland reached this level in the period 1970-1974

- Croatia reached that proportion 15 years later and that indicates our real delay in comparison to the well-developed European countries

- In Croatia that proportion was 1:1,9 and in Finland 1:1,4 in 1990

- Such report from Finland is the result of thourough and energetic reduction of cervical cancer appearance, started back in 1986

- It is probably a result of the change of the approach and relation between sexes

- The warnings and pieces of advice of the modern medicine related to the age of the first sexual contact should be respected

- There is also well developed diagnostc procedure and treatment of sexually transmitted diseases

- The incidence is still high in Croatia and very similar is noticed in Finland 15-20 years ago

- All above mentioned should encourage us to make an over efforts in order to reduce the incidence of invasive cervical cancer in Croatia

Importance of health education

- Large number of girls knows about cervical cancer (95%) in Croatia and Finland

- Every second girl in Croatia knows about PAPA test, but in Finland 90% of girls knows about PAPA test

- In the high school population, every forth girl knows about PAPA test and in Finland more than 90% girls of same age

Strategy of prevention and early diagnosis

- To discover and to treat sexually transmited diseases (HPV,HSV II) and chronic iritations (bacterial cervicitis and colpitis)

- Primary prevention should include "pure sexual life" and younger generation should be informed abour the risk of sexually transmitted diseases,which are not only oncogenic, but could influence on the reproduction

- Every third sexually active woman, who is over 15 years, should undergo the cytological examination (PAPA test) once yearly

- It is 670 000 cytological examination per year in Croatia

- Colposcopy should be performed if a woman has an abnormal cytological finding (unless it is being performed as a part of the routine examination)

- Therefore, if an abnormal cytological smear is found in 2,5% women (Dražančić et all.), it emerges the necessity to perform about 17 000 colposcopic examinations in the period of three years

- This data present an indication to educate more gynecologists in colposcopy through well organized courses

Grce M, Husnjak K, Magdi L, Ilija M, Zla ki M, Lepui D, Luka J, Hodek B, Grizelj V, Kurjak A, Kusi Z, Paveli K.

Detection and typing of human papilloma viruses by polimerase chain reaction in cervical scrapes in Croatian women with abnormal cytology, European Journal of Epidemiology, 1997; 13: 645-651

In 163 patients (43%) out of 379, aged 17-64, cervical intraepithelial neoplasia was associated with human papilloma virus (HPV)

HPV 16 in 33 patients (20,2%)

HPV 31 in 29 patients (17,8%)

HPV 6/11 in 42 patients (25,8%)

HPV 6/11 strongly associated with CIN I (33,8% or 55 patients)

HPV 31 strongly associated with CIN II (22,9% or 37 patients)

HPV 16 strongly associated with CIN III (50,0% or 81 patients)

The presence of different types of HPV significantly increased (Pearson chi square test value being X2 - 8,11 p 0,043 ) from 35,5% to 61,1% along with the severity of cervical intraepithelial neoplasia.The youngest women (<20 years) exhibited the highest rate of HPV infection and thereby exposed to the oncogenic virus early in their life.

According to data from previous work by the same author (Grce M, Magdić L, Kocijan I, Pavelić K. Increase of human papilloma virus infection among men and women in Croatia, Anticancer Res. 1996;16:1039-1042) the number of female patients bearing HPV-CIN increases from 4,6% (6 out of 129 in 1990 to 38,2% (26 out of 68 in 1993.)

According to our completed experience, it is necessary to establish cervical dysplasia clinical unit in order to manage, study and follow these risk groups.

The lecture was presented at Imagerie en gynecologie 1998 held in Paris.

Sexually Transmitted Diseases In Croatia

Goran Grubii

Monitoring is done via mandatory notification of infectious diseases.

According to the current Regulations about the manner of notification, the following are specially notified:

- gonorrhoea

- syphilis

- AIDS

- hepatitis B

- chlamydia and other STDs are notified together.

There is an absolute respect for physician confidentiality and patient confidentiality during processing in the hygienic-epidemiological department.

Syphillis and gonorrhea Since the mid-80s there has been a clear, very gradual downward trend

We owe this to:

a) the good organisation of the epidemiological service and clinical treatment services;

b) the existence of effective therapy,

c) the effect of a broad action of medical education measures ever since the early 80s, for the sake of preventing and suppressing AIDS,

d) a positive change in the behaviour of the population, because the same precautionary measures apply not only to AIDS but also to all other STDs,

AIDS shows a relatively favourable trend with from 2 — 16 (mainly 8 — 16) infected annually in the last 12 years. In Europe, Croatia occupies the 25^th position for AIDS sufferers per one million inhabitants (a total of 125 infected in 1998, or 27 per 1 000 000 of the population, while some other countries in Europe have 800 per 1 000 000). At the moment AIDS in Croatia will not follow Western European models, there being no explosive growth. In Croatia, AIDS has been smouldering in the last 12 years, ever since it entered the population. (PEF, Borčić B.)

Hepatitis B, more of a parenteral and blood-borne disease, and partially sexually transmissible, has shown for decades in Croatia a practically stationary low endemic trend with an average of 200 — 250 people infected per year. According to the most recent results available from the Transfusion Centre, this is annually below 1% prevalence of HbsAg positive persons.

Chlamydiasis urogenitalis also shows a stationary trend.

- The number of reported patients ranges between 200 and 300 per year.

- On the other hand, from laboratories that undertake microbiological diagnoses, we can learn that the number of positive findings is significantly higher.

- According to clinical experience, this is frequently a matter of asymptomatic infections.

- These also require treatment and care because it is not known when later in life they might cause sickness, chronic infection and later consequences of chronic infection.

- Chlamydiasis urogenitalis in women is a marker of sexual behaviour.

A permanent irritant, if untreated it is responsible for sterility, ectopic pregnancies, and acts as a cofactor in cervical cancer.

Sicknesses related to HSV II, HPV, mycoplasmata and other STDs are very likely more numerous than is shown in the tables, but there are certain unknowns in the proportion of clinical manifestations to number of infected persons (with positive microbiological or genotype findings).

The presence of HPV in the population corresponds to the generally accepted pyramid (Walton et al.), with about 1.5% of the sexually active female population being included at the apex, which means about 30,000 women in the case of Croatia (Audy 1992 in Klinika)

This entails the obligation to provide sexual education from the first years of secondary school.

Also, it entails the responsibility for what might perhaps be called a pure sexual life.

Manifest HPV infection requires treatment in the dysplasia unit in gynaecological clinics and departments, for the sake of the prevention of neoplastic changes in the cervix, vagina and vulva.

Close co-operation with an STD specialist is necessary for the treatment of the male partner.

In this, we are just at the beginning in Croatia.

This lecture was presented at Ascoli Piceno in April 2000.

Lletz Versus Cone:Our Experience

Grubii G, Hodek B, Klari P, Lepui D, Pirki A, Vukosavi Cimi B, FureR

Univ. hosp. Sestre milosrdnice, Ob/Gyn Clinic. Zagreb, Vinogradska 29, Croatia

Objective: Relation between age and operative treatment protocol (cytology, colposcopy, punch biopsy, LLETZ and cold knife conisation)
Setting: Colposcopy unit in Ob/Gyn Clinic Univ hosp.Sestre milosrdnice, Vinogradska 29,Zagreb,Croatia
Patients and methods: Retrospective examination from 1. Dec 1994. to 31 Jan 1997. in 105 women with LLETZ and 97 with cold knife conisation.
Results: In LLETZ group prevailed younger women (20-29 yr.) whereas in coned those between 30-40 yr. The severe dysplasia in LLETZ specimen prevailed in 31 (29,5%). In age group 24-29 yr. there were 15 with severe dysplasia (14,3%). The same diagnosis in cold knife conisation was present in 46 (58,2%),and specially increases in age group 30-40 (37 of 79 or 46,8%). In younger women of conisation group there were 9 severe dysplasias or 11,4%.

The poster was presented at First European congress of colposcopy and cervical pathology held on September 1998 at Dublin, Ireland

"Abnormal Cytologyc and Pathohystological Finding of the Uuterine Cervix".

N. Ljubojevic, S. Babic, S. Audy-Jurkovic, A. Ovanin-Rakic, G. Grubišic,

D.Ljubojevic-Grgec

Diagnostic and therapeutic guideline in cytological diagnosis of cervical atypia ( ASCUS, CIN I-CIN III)

1.a. When PAP test indicates the ASCUS (Atypical Squamous Cell of Undetermined Significance) with or without HPV infection, and if inflammation of other etiology (Trichomonas vaginalis, Chlamidia trachomatis, Candida albicans et al.) is present, it is necessary to provide the antiinflammatory treatment. Cytological control has to be done in 4 months time, and in case of normal cytological finding the examination will be repeated in 6 months. If the finding of ASCUS+HPV is persistent after 4 months, it is necessary to do the HPV DNA typing and colposcopy. Cytological examination should be done in 6 moths in
case of satisfactory colposcopic finding and HPV of low oncogene risk, and in 4 months in case of HPV of high oncogene risk. It is necessary to conduct the histological verification of the lesion in case of satisfactory colposcopic finding and abnormal finding. In case of unsatisfactory colposcopic finding and if lesion is partially visible, it is important to do the target biopsy or endocervical excohleation. Further procedure depends on the histological findings.

2.a. When PAP test indicates CIN I with or without HPV infection it is recommended to provide the antiinflammatory treatment before the HPV DNA typing. In case of HPV of low oncogene risk or negative finding, cytological examination should be performed in 4 months. If PAP test shows normal cytological finding it should be repeated in 6 months, but if CIN+HPV still persists colposcopic examination is performed. With satisfactory colposcopic finding and normal finding, cytological control should be performed in 4 months (HPV of low oncogene risk) or 6 months (HPV of high oncogene risk). If there is an abnormal colposcopic finding, histological verification of visible lesions is necessary (target biopsy of exocervix or/and vagina and endocervical curettage- ecc.).

3.a. If PAP test indicates CIN II with or without HPV infection, it is ecessary to perform the HPV DNA typing and colposcopy and to provide the treatment of previous inflammations of other etiology. With atisfactory colposcopy and negative finding, it is recommended to do the cytological control in 3 months (HPV of high oncogene risk) or 4 months ( HPV of low oncogene risk). In case of abnormal colposcopic finding and unsatisfactory colposcopy, the procedure is the same as in the case of CIN I.

4.a. When PAP test indicates CIN III with or without HPV infection, it is important to perform the colposcopy, with previous treatment of inflammation. With satisfactory colposcopy and negative finding the cytological and colposcopic control will be performed in 2 months. In case of abnormal colposcopic finding, it is necessary to perform the target egsocervical biopsy and ecc. With unsatisfactory colposcopy the procedure is the same as in the case of CIN I or CIN II.

N. Ljubojevic, S. Babic, S. Audy-Jurkovic, G. Grubišic, D. Ljubojevic-Grgec

Diagnostic and therapeutic guideline in cytological diagnosis of cervical glandular atypia (AGCUS, GIL I, GIL II and AIS)

a.) When PAP test indicates the presence of AGCUS (atypical glandular cells of undetermined significance) with or without HPV infection, it is possible to deal with reactive changes, glandular intraepithelial lesion of first and second grade (GIL I and GIL II), GIL III or AIS (adenocarcinoma in situ). In case of suspicious reactive changes, it is highly ecommended to perform the cytological control in 4 months or in case of normal finding in 6 months. If the finding on the cytological control indicates possible presence of AGCUS or GIL I and GIL II, it is necessary to perform the colposcopy (with use of endocervical speculum), followed by the histological analysis of bioptic material and endocervical curretage sample. If the first PAP tesr shows GIL I and GIL II, colposcopy and histological verification is necessary, and possibly another cytological control in 4 months. In case of suspicious AIS or verified AIS, the procedure is the same-colposcopy followed by histological verification. If colposcopy reveals that lesion is visible, it is necessary to do the target biopsy, endocervical curretage and in female population over 35 years the curretage is performed. When PAP test indicates the AGCUS of endometrial origin, curretage or hysteroscopy with endometrial biopsy is performed.

b.) When histological diagnosis (with previous cytological diagnosis of AGCUS and AIS) shows normal finding or GIL I, cytological control (using Cytobrush) is to be done in 2 months. If AGCUS, GIL I, GIL II and AIS persist on cytological control, it is the indication for knife conisation as the diagnostic and therapuetic procedure. In case of patohistological verification og GIL II and AIS, knife conisation is performed; conus should be cilindric, so that all glandular crypts are affected.

2.b.) Patohistological diagnosis of the sample of the target biopsy or endocervical curretage may show coilocytosis or normal finding. In case of such finding and and concomittant HPV infection (HPV of low oncogene risk), cytological and colposcopic control, until the regresiion or progression of such a finding, is performed every 6 months, and with HPV of high oncogene risk every 4 months. When patohistological diagnosis shows CIN I with koilocytosis, cytological and colposcopic control is the same, depending on HPV type. If CIN I with koilocytosis and with HPV of low oncogene risk persists more than 2 years, and CIN I with koilocytosis and with HPV of high oncogene risk for more than a year, one of exempted surgical procedure is recommended. It may be LLETZ ( excision of transformation zone with low-voltage diathermic oop)
or one of locally destructive methods, e.g. kriotherapy or CO2 laser vaporization. When PHD shows CIN II or higher grade of dysplasia, we usually follow the guideline for those diagnoses, no matter if previous PHD shows CIN I.

3.b.) When PHD (with previous cytological diagnosis of CIN II+/- HPV) shows normal finding, CIN I with koilocytosis or koilocytosis only, therapeutic guide- line for CIN I is followed. If PHD confirms the histological diagnosis of CIN II with HPV of low oncogene risk, cytological and colposcopic control is repeated 3 months after the patohistological examination. In case of normal finding or CIN II+/- HPV, therapeutic guideline for CIN I is followed. If CIN II+/- HPV still persists cytological and colposcopic control every four months, up to one year, is recommended. But, if lesion persists or even progresses, depending on the age, parity and colposcopic finding, one of exempted surgical rocedures is recommended (as in the case of persisting CIN I). If cytological and colposcopic finding indicates its worsening or CIN III+/-HPV, therapeutic guideline for CIN II should be followed. When PHD confirms the cytological diagnosis of CIN II with HPV type of high oncogene risk, the cytological and colposcopic control should be done in 2 months. In case of normal finding or regression of CIN I+/-HPV, therapeutic guideline for CIN I is followed. If CIN II persists , cytological and colposcopic control should be performed every three months. If lesion persists or progresses, depending on age, parity and col- poscopic finding, one of several methods of exempted surgical procedures is recommended. If controle examination shows the progression, therapeutic guideline for CIN III is followed. The same guideline is used when PHD indicates CIN III.

4.b.) When PHD (with previous cytological diagnosis of CIN III+/-HPV) shows normal finding, koilocytosis, CIN I and CIN II with koilocytosis, cytological control is performed two months after PHD. If PAP test indicates the regression (CIN II or lower grade of dysplasia), therapeutic guideline for CIN II is followed. But, if CIN III persists and repeated colposcopy shows visible lesion, diagnostic and therapeutic procedure is recommended. One of several methods can be chosen (cold knife conisation, LLETZ, CO2 laser cone biopsy) in order to get the final patohistological diagnosis. When patohistological exami- nation confirms the cytological diagnosis of CIN III, the cytological nad colposcopic control should be performed in two months. In case of regression of CIN I+/- HPV or normal finding (when lesion is partially or completely removed by biopsy) HPV DNA typing is recommended; therapeutic guideline for CIN I is followed.If cytological and colposcopic control indicates that lesion still persists (CIN II and CIN III+/-HPV), it is necessary to perform one of excision methods as the surgical procedure, depending on age, parity and colposcopic finding. When PHD of target biopsy or endocervical curretage sample shows microinvasive cancer (FIGO stage IA 1- the depth of invasion up to 3 mm and free lymphocapillar spaces), diagnostic and therapeutic procedure – cold knife conization- is performed.

"Cytology Guideline"

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