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MAJOR RESEARCH PROJECTS

During his carreer as an academic researcher initiated in the early 1970's at University of Helsinki, the company President has shown exceptional scientific productivity in several different research projects covering highly diverse fields of biomedical research. The main projects carried out since the early 1970's by Prof. Syrjänen can be divided in two categories; 1) Domestic, and 2) International.

1.DOMESTIC RESEARCH PROJECTS
Production of the scientific communications started at the Department of Pathology, University of Helsinki, with the completion of the M.D. Thesis, published in 1975. After military service (1975-1976), the research continued in Jorvi Hospital, Espoo, followed by the Päijät-Häme Central Hospital (Lahti), and Kuopio University and Kuopio University Hospital. As a result of the research activity during the >40-year time span in Finland and abroad, a total of 900 original publications (monographs, reviews, book chapters), and 527 congress abstracts (and other scientific communications) have been produced (1975-2018.)

1.1.Tumor-host relationships and experimental immunology research
During 1972-1978, the main interest of the research was focused on lymph nodes and their reactions to human and experimental cancer. This work (also including experimental animal research) continued (although with gradually declining intensity) until the early 1980’s, and culminated in the writing of a monograph: The Lymph Nodes. Reactions to Experiment and Human Tumors, published in 1982, including a comprehensive review of the work done by that time. These studies are closely linked with the experimental immunology studies in the early 1980's in Kuopio, assessing some of the basic mechanisms of T-cell re-circulation and T-B cell interactions, using the chicken bursa model. This led to first evidence on the role of chicken bursa as a peripheral lymphatic organ with definite T-cell compartment as well.

1.2.Papillomavirus research
The applicant became interested in genital Human papillomavirus (HPV) lesions already in February 1977 (while in Jorvi Hospital), following the primary reports on their newly recognized association with cervical cancer precursors few weeks earlier. The frequent association of HPV lesions with all grades of cervical precancer lesions became evident immediately. These early observations formed the starting point to the applicant.s interest in papillomaviruses, which has continued 25 years by now, and being focused on HPV lesions not only in the genital tract, but also on those found in upper aeordigestive tract.

These early papers from the late 1970’s and early 1980’s (with important pioneering reports) together with the two subsequent Papillomavirus Textbooks (1987 and 2000) and large number of communications from the Kuopio Cohort Study (1981-1998), have created the basis of the applicant.s worldwide recognition as one of the pioneers in HPV research. This is evidenced by the progressively growing number of invited reviews, editorials and book chapters, as well as invited presentations in international congresses, approaching 200 in total.

Since 1981, prof. Syrjänen established an internationally recognized Papillomavirus research group in Kuopio. The major achievement by which this group is best known worldwide, is the set-up and continuation of a unique long-term prospective follow-up (cohort) study for HPV-infected women for 18 years (1981-1998). Kuopio PAPILLOMAVIRUS PROJECT was the first prospective cohort study in the world, when started in October 1981 and continued to be the only one of its kind until the early 1990.s. Apart from the published almost 400 papers, the major achievements of the PAPILLOMAVIRUS PROJECT include 20 Doctoral Thesis, and organization of the most important annual Papillomavirus conference (the 1985 International Papilloma Virus Workshop) in Kuopio. Since its onset, the project received support e.g. from NIH/NCI (USA)(1985-1987), and its results have been presented as invited lectures in congresses throughout the world.

The data accumulated from papillomavirus research by the mid 1980’s were summarized in the 16 chapters (contributed by prominent international experts) of the first ever published HPV textbook entitled: Papillomaviruses and Human Disease, edited by K. Syrjänen, L. Gissmann & L.G. Koss (Springer Verlag, 1987). As a tribute to our project, discontinued in Kuopio 1999, the second textbook: Papillomavirus Infections in Human Pathology (615 pages, 21 Chapters) was authored together with Prof. Stina Syrjänen (Wiley & Sons, 2000), being the most comprehensive source of information available on HPV-associated human pathology today. Since 1993, a part of Kuopio Papillomavirus Group moved to Turku University, where the work was continued with Prof. Stina Syrjänen as the head. Collaboration between the Kuopio and Turku groups was intense and beneficial to the Project, while capable of utilizing the facilities of two Universities. Results of this collaboration are found in the list of papers (items from #400 onwards).

1.3.Breast cancer studies
Although best recognized by his contributions in papillomavirus research, Prof. Syrjänen has maintained his old interest in another major focus of the present-day cancer research, i.e., breast cancer, particularly its biological prognostic factors. This interest was revived in the early 1990's, when Kuopio Cancer Research Centre (KCRC) was established in 1988 and Prof. Syrjänen was elected as the first Chairman of the Board and Scientific Director. In 1991, KCRC designed and started another major prospective cohort study focused on breast cancer patients, known as KUOPIO BREAST CANCER STUDY. In few years, over 500 women with breast cancer, 1.000 women with benign breast tumour, and additional 700 age-matched healthy (population) controls, were enrolled in this major project, headed by the applicant until 1996. By the late 1990's a substantial number (60-70 items) of original reports (and two doctoral thesis) have been published from this project, many of which in prestigious international cancer and pathology journals (see Published Papers).

 

2.INTERNATIONAL RESEARCH PROJECTS
Apart from being the designer and coordinator of the above two major domestic research projects, Prof. Syrjänen has gained widely recognized experience as an initiator, designer and coordinator of a number of multi-national research projects funded e.g. by the different programmes of the European Commission (EC). This uninterrupted funding from the EC since 1994, currently extends until 2005.

2.1.HPV and oesophageal cancer
The first of these multi-national projects (Contract # TS3* CT94-0295) was part of the STD3 Programme, covering the period 1994-1997. In this project, the researchers working in three EC-countries (Germany, Finland, Italy) got access to a unique material of over 2.000 tissue biopsies collected from 700 patients with oesophageal cancer in the high-incidence area of Henan Province, North China. Oesophageal cancer is another human malignancy, suggested to be associated with HPV by the applicant in his pioneering studies in 1982, and subsequently studied for this evidence by several other groups (see the special chapter of the HPV Textbook). This Oesophageal Cancer Project was officially terminated in 1997, but the outflow of scientific reports continued until recently. The milestone report of this project was the single largest series (>700 cases) of oesophageal carcinomas ever analysed for HPV, providing conclusive evidence on the association of this tumour virus in oesophageal squamous cell cancer, at least in the high-risk areas of this disease.

2.2.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.

The study design, partners and the progress of the NIS/CCE Cohort Study are presented in more detail on separate sites, found by clicking here for the NIS/CCE Cohort Study websites.

2.3.Cervical cancer screening strategies in Latin America
The third and still ongoing EC-project (Contract # ICA4-CT-2001-10013) is funded by the INCO-DEV Programme and covers the period 2001-2005. This extensive project is participated by 8 research groups from three EC countries (Finland, Italy, Slovenia) and from two Latin American countries (Brazil and Argentina). The official title of the project is: IMPROVING HEALTH SYSTEMS TOWARDS EQUALITY-BASED CONTROL OF CERVICAL CANCER IN LATIN AMERICA. Comparing PAP Smear Cytology, Aided Visual Inspection, Cervicography and Human Papillomavirus (HPV) Testing as Optional Screening Tools in Brazil and Argentina (the LAMS Study).

The objective is to elaborate the research data needed to design a cost-effective strategy for cervical cancer screening in Brazil and Argentina, by using a combined cross-sectional (n=12.000) and cohort (n=1.000) study of women examined in four different clinics for the prevalence, pathogenesis and natural history of CIN and HPV infections. The performance characteristics (sensitivity, specificity, negative- and positive predictive value, as well as ROC=receiver operating characteristics) of the traditional diagnostic tools (PAP smear cytology, colposcopy) are compared with those of the HPV detection methods (Hybrid Capture II and PCR) and those of the suggested screening tools for low-resource-settings (aided visual inspection, cervicography and self-sampling for HPV) in detecting significant cervical pathology (high-grade CIN lesions and cervical cancer). The long-term objective of this project is to acquire the necessary data for the basis of designing a sustainable and cost-effective strategy for an organised cervical cancer prevention programme in Brazil and Argentina.

This 3-year project is scheduled to proceed a) by establishing the magnitude of cervical cancer and its precursors as a health problem (i.e., prevalence) in target populations at different risk, b) to testing of the performance (sensitivity, specificity, PPV, NPV, ROC) of these optional diagnostic tools, and c) ending up with the synthesis of these data with a feasibility analysis and guidelines, how to improve the health systems by creating a cost-effective strategy for an equality-based cervical cancer control in these two LAM countries.

The study design, partners and the progress of the LAMS Study are presented in more detail on separate sites, found by clicking here for the LAMS Study websites.

2.4.HPV infections in HIV-infected women
Another ongoing project, funded by the Italian Ministry of Health, was started in Italy in 2002. This multi-centre research project (coordinated at the National Health Institute, ISS, Rome by Dr. M. Branca), known as PathogenISS Project, was designed by the Prof. Syrjänen, being the scientific coordinator of the project. Based on several well defined hypothesis, the major focus is on 1) in assessment of the differences in the prevalence of genital HPV infections, CIN and cervical cancer in immunocompromised and immunocompetent women; 2) in disclosing the risk factors responsible for the different predisposition to HPV infections and CIN in HIV+ and HIV- women; 3) in elucidating, by prospective follow-up, a) the differences in the biological behaviour of HPV infections and their induced CIN lesions, and b) to assess the biological mechanisms behind these differences; 4) to evaluate the risk for imminent development of invasive cancer by close monitoring of the lesions progressing to CIN III; and 5) in analyzing the prognostic factors in HIV-negative and HIV-positive women progressed to invasive cancer, in a retrospective series.

The strength of PathogenISS project is in its design, where several research centres in different parts of Italy are contributing the patients (HIV+ and HIV-, infected by HPV) into the prospective cohort, which is combined with the meticulous molecular biological analysis of similar samples collected from a retrospective series of women with all grades of CIN and also cervical cancer. The general long-term objective of this joint research project is to increase our understanding of the basic mechanisms regulating the biological behaviour of cervical HPV infections and their associated cancer precursors in both HIV-negative and HIV-positive women. These published data will have important implications in designing new strategies of early detection, accurate diagnosis and effective treatment of these patients, to be implemented as part of an organized cervical cancer prevention policy in this country.

 

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