CERVICAL CANCER SCREENING IN NIS COUNTRIES
The second of these EC-funded projects (Contract # ERB IC15-CT98-0321) was designed and initiated by the applicant as the coordinator while still in Kuopio, but at transition abroad in 1999, was transferred to Turku University (coordinated by prof. S.Syrjänen). This project belongs to the INCO-COPERNICUS Programme of EC, and is known as the NIS/CCE Cohort Study, continuing until the first quarter of 2002. This study is participated by 9 research groups from two EC countries (Finland and Italy) and those from three NIS/CCE countries (Russia, Belarus and Latvia), with the main focus being in the testing of different optional diagnostic tests (PAP smear, PCR and Hybrid Capture II) as screening tools of cervical cancer in these low-resource settings. Based on the excellent results of the organised massscreening programme in Finland, and on the know-how of the coordinator (having run this programme in East-Finland for 16 years), this multi-national project is testing the performance of three optional diagnostic tools in early detection of cervical cancer precursors. The long-term aim is to use this information as the basis for selecting the cost-effective strategies for cervical cancer prevention in these three NIS countries with high-incidence but limited resources for preventing this disease.

This combined cross-sectional and cohort study is based on meticulous examination and prospective follow-up of 3.187 women, representing patients in three categories of risk for cervical HPV infections and cancer. Due to the prospective nature of this study, the main publication activity had to be postponed until the termination of the follow-up. Thus, the full exploitation of the results was started just recently, and several important papers have been recently published.

1.Project Title:

ASSESSMENT OF GENITAL HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS AS A HEALTH PROBLEM IN RUSSIA, BELARUS AND LATVIA. MEASURES NECESSARY FOR THEIR EARLY DETECTION,
TREATMENT AND CONTROL OF CERVICAL CANCER
AND ITS PRECURSOR (CIN) LESIONS.
(Contract # ERB IC15-CT98-0321)

2.Partner Clinics:

1. Department of Pathology, University of Siena, Italy;
2. N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Moscow, Russia;
3. Russian Academy of Post-Graduate Medical Education, Moscow, Russia;
4. Novgorod Clinical Regional Hospital, Centralised Cytology Laboratory, Novgorod, Russia;
5. Novgorod Municipal Dermatovenereological Dispensary, Department of Gynaecology, Novgorod, Russia;
6. Novgorod Female Consultative Outpatient Hospital, Department of Gynaecology, Novgorod, Russia;
7. Research Institute of Oncology and Medical Radiology, Republican Centre of Clinical Cytology, Minsk, Belarus;
8. Minsk State Medical Institute, Department of Gynaecology and Obstetrics, Minsk, Belarus;
9. Latvian Cancer Centre, Department of Gynaecology, & Laboratory of Cytology, Riga, Latvia

3.Partners:

S. Syrjänen, Department of Oral Pathology, Institute of Dentistry, MediCity Research Laboratory, University of Turku, Lemminkäisenkatu 2, FIN-20520 Turku, Finland: stina.syrjanen@utu.fi (COORDINATOR)

I.P. Shabalova, N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Kashirskoye shosse, 24, RU-115478 Moscow, Russia; irenashab@mtu-net.ru

N. Petrovichev, N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Kashirskoye shosse, 24, RU-115478 Moscow, Russia; n_petrovichev@mtu-net.ru

V.P. Kozachenko, N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Kashirskoye shosse, 24, RU-115478 Moscow, Russia;

T. Zakharova. N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Kashirskoye shosse, 24, RU-115478 Moscow, Russia;

J. Pajanidi, Russian Academy of Post-Graduate Medical Education, 2 Botkinsky pas, build 17, 125101 Moscow, Russia;

J.I. Podistov, Russian Academy of Post-Graduate Medical Education, 2 Botkinsky pas, build 17, 125101 Moscow, Russia;

G. Chemeris, N.N. Blokhin Cancer Research Centre of Russian Academy of Medical Sciences (RAMS), Kashirskoye shosse, 24, RU-115478 Moscow, Russia;

L.G. Sozaeva, Russian Academy of Post-Graduate Medical Education, 2 Botkinsky pas, build 17, 125101 Moscow, Russia;

E.V. Lipova, Russian Academy of Post-Graduate Medical Education, 2 Botkinsky pas, build 17, 125101 Moscow, Russia;

I. Tsidaeva, Novgorod Clinical Regional Hospital, Centralised Cytology Laboratory, Galinina uliza 234, 30457 Novgorod, Russia;

O.G. Ivanchenko, Novgorod Clinical Regional Hospital, Centralised Cytology Laboratory, Galinina uliza 234, 30457 Novgorod, Russia; ood@mail.natm.ru

A.A. Pshepurko, Novgorod Clinical Regional Hospital, Centralised Cytology Laboratory, Galinina uliza 234, 30457 Novgorod, Russia;

S. Zakharenko, Novgorod Municipal Dermatovenereological Dispensary, Department of Gynaecology, Podgornyi pas 24, 30676 Novgorod, Russia;

R. Nerovjna, Novgorod Female Consultative Outpatient Hospital, Department of Gynaecology, Octobrskaya ulica 89, 30575 Novgorod, Russia;

L.B. Kljukina, Research Institute of Oncology and Medical Radiology, Republican Centre of Clinical Cytology, Tarasova ulica 340, 220050 Minsk, Belarus;

O.A. Erokhina, Research Institute of Oncology and Medical Radiology, Republican Centre of Clinical Cytology, Tarasova ulica 340, 220050 Minsk, Belarus;

M.F. Branovskaja, Minsk State Medical Institute, Department of Gynaecology and Obstetrics, Bolshovskaja pas 3, 220065 Minsk, Belarus;

M. Nikitina, Latvian Cancer Centre, Department of Gynaecology, & Laboratory of Cytology, Korytkova ul 35, 100200 Riga, Latvia; maritta@onkoc.mt.lv

V. Grunjberga, Latvian Cancer Centre, Department of Gynaecology, & Laboratory of Cytology, Korytkova ul 35, 100200 Riga, Latvia; valerija@onkoc.mt.lv

A. Grunberg, Latvian Cancer Centre, Department of Gynaecology, & Laboratory of Cytology, Korytkova ul 35, 100200 Riga, Latvia; alexandr@onkoc.mt.lv

A. Juschenko, Latvian Cancer Centre, Department of Gynaecology, & Laboratory of Cytology, Korytkova ul 35, 100200 Riga, Latvia; annajus@onkoc.mt.lv

P. Tosi, Department of Pathology, University of Siena, via delle Scotte, 6, I-53100 Siena, Italy, tosi@unisi.it

M. Cintorino, Department of Pathology, University of Siena, via delle Scotte, 6, I-53100 Siena, Italy, cintorino@unisi.it

R. Santopietro, Department of Pathology, University of Siena, via delle Scotte, 6, I-53100 Siena, Italy, r.santopietro@ao-siena.toscana.it

K.J. Syrjänen, Department of Oncology & Radiotherapy, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20521 Turku, Finland. kari.syrjanen@smwconsultants.fi (PROJECT DESIGNER)

4.Abstract:

ASSESSMENT OF GENITAL HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS AS A HEALTH PROBLEM IN RUSSIA, BELARUS AND LATVIA. Measures Necessary for Their Early Detection, Treatment and Control of Cervical Cancer and Its Precursor (CIN) Lesions.

Background:
To date, over 80 different human papillomavirus (HPV) types have been recognised and characterized, and a significant risk for the development of invasive cervical cancer has been ascribed to infections of the high-risk HPV types (IARC 1995). The natural history of cervical HPV infections seems to be identical with that of cervical precancer lesions (Syrjänen, 1997). An invasive cervical cancer invariably develops through these well defined precursor lesions (dysplasia, CIN), the early detection and eradication of which is a prerequisite for a successful prevention of cervical cancer. Although cervical cancer remains to be a major health problem worldwide (>500.000 new cases/year), it still is the only malignant human tumour which can be effectively prevented by medical intervention, as shown by the data e.g. from Finland, where an organized mass-screening programme has reduced the incidence of invasive cervical cancer to the lowest figures in the world, 2.7/105 (Syrjänen, 1997; Hakama, 1997). Because of the fact that organized mass-screening programmes are not realistic in most of the developing countries (including NIS/CCE), other measures should be searched for to alleviate the cancer burden in these areas, as recently recommended by the joint expert conference (WHO&EUROGIN)(Franco et al., 1996; 1997). Such alternative measures suggested include e.g. the screening of genital HPV infections by the available new molecular diagnostic tools (hybridization and PCR).
Objectives:
In the present proposal, an approach is made 1) to assess the magnitude of genital HPV infections, CIN and cervical cancer as a health problem in the participating NIS/CCE countries, 2) to disclose the risk groups for this disease within these countries, 3) to elucidate the optimal (and the minimum) requirements for an appropriate detection of these risk groups by taking into account the local (and limited) resources, and finally 4) by combining the research and development component of this project, to create an effective health care system in the participating NIS/CCE centers, capable of independently diagnosing and treating genital HPV and CIN, with the decreased disease burden due to cervical cancer as the main long-term objective. A potential European dimension will be provided by the future implementation of such a system in other European countries with cervical cancer as a major health problem.
Study Design:
This study is a classical population-based, crosss-sectional (prevalence) study combined with a prospective cohort study. Thus, during the first year of this project, consecutive series of women attending the participating centers in the NIS/CCE are screened for cervical HPV infections and CIN, and the positive women (=prevalence data, geographic variation) will then comprise the cohort to be prospectively followed-up in these centers up to the end of this 3-year project (=disease prognosis). To asssess the different levels of risk for HPV and CIN, the study is focused on two target populations of women in the NIS/CCE; 1) those attending the Gyn. Obst. clinics, and 2) those attending the STD clinics. The detection of the disease will be completed through two arms: 1) by PAP smears (ARM I), and 2) by PCR (ARM II). This enables the comparison of the efficacy, feasibility and cost-effectiveness of the new molecular diagnostic tools (PCR, ISH) with the traditional HPV/CIN detection methods (PAP smear, colposcopy, biopsy). PCR-negative women will consitute the Control Group for all HPV/CIN women, to be analysed for the epidemiological risk factors by questionnaires. Depending on the severity of the lesion on biopsy, the women are allocated to two mutually exclusive outcomes: 1) prospective follow-up, and 2) prompt treatment.
Partners and Coordination:
This proposal is a joint research project, contributed by three centers in two EC countries (Finland, Italy), and 5 centers from three NIS/CCE countries (Russia, Belarus, Latvia), with the Coordination in Kuopio, Finland and Scientific Coordination in Moscow, Russia.
Significance:
The main significance of the proposed cooperation will be in the fact the existing but clearly ineffective health care system in the NIS/CCE will be developed more efficient to cope with this major health problem. This can only be achieved by a joint research project with the expertise in the EC and utilizing their existing health care system as a reference.

For further details on study design, click here.