Genetic characterization of high-risk human papillomaviruses in Ukraine and Latvia to inform national policy of cervical cancer prevention

Project work packages

1. Retrospective recruitment of cases of cervical cancer in Kyiv, Ukraine, and retro- and prospective recruitment of CC cases and high-grade cervical lesion (CL) cases in Riga, Latvia, and assembly of the study cohort.
2. Genotyping of HR HPVs to create comparative epidemiologic “portrait” of HPV associated CLs and CC in Latvia and Ukraine.
3. Whole genomic sequencing (WGS) of HR HPVs prevalent in Latvia and Ukraine to characterize them on molecular level and associate their conservation/variability with cervical pathology, identification of sequence signatures associated with parameters of CLs and CCs with the aim to exploit them as molecular markers for personalized prognosis of cervical disease course and outcome, and strategy of follow up and treatment.
4. Dissemination of project results and reaching project impact by informing international research community, Latvian and Ukrainian health authorities and stake holders on HPV status of women with cervical lesions and cancer, demonstrating acute need to implement HPV vaccination in Ukraine and advance and promote HPV vaccination among teenagers and adolescents as well as catch-up vaccination among adults in Latvia.
5. Harmonization of research activities of the leading Latvian and Ukrainian medical research institutions, training and career promotion for young researchers, and support of the research cooperation on national and international level.
6. Efficient project coordination and management to ensure attaining of project results by both teams.

Within this work program, the tasks of RSU team will be to continue monitoring the dynamic changes in the prevalence of HR HPV genotypes in CC cases (follow up of LZP project 2021/1-0484); determine HR HPV genotypes in CC cases collected by the Ukrainian partner; compare patterns of HR HPV spread; assemble and deposit into GenBank full genomes of HR HPV strains prevalent in Latvia and Ukraine; perform their comparative analysis; organize regular project team meetings, hybrid Workshops, virtual/hybrid conference on chronic viral infections and cancer, prepare abstracts for research conference and draft the manuscripts.

This will dissect the long-term effect(s) of HPV vaccination in Latvia as compared to non-vaccinated Ukrainian population, identifying imprints of immune escape. We will also define molecular signatures of disease severity of diagnostic/prognostic value. Project results will draw attention of the health care authorities of both countries to the necessity to support and promote HPV screening and vaccination, taking stand in anti-HPV/anti-cancer compaign. Project will strengthen research cooperation in the widening Europe.   

Ukrainian partner

R. E. Kavetsky Institute of experimental pathology, oncology and radiobiology (IEPOR) of National Academy of Sciences (NAS) of Ukraine

The IEPOR team includes two experience researchers – the project leader Elena Kashuba, Dr Hab, PhD, senior scientist Larysa Kovalevska, PhD, and two PhD students. The team works in the field of cell transformation, including virus-induced transformation. The team members worked with the Epstein-Barr virus (EBV)-induced cell transformation and on influence of human hepatitis virus C (HCV) on the development of liver tumors. The latest studies of the group targeted the role of Metastasis suppressor 1 (MTSS1), and its loss in the advanced tumor stages and metastatic tissues in nasopharyngeal carcinomas.  (The team also works on the development of nanoparticles for the directed transport of proteins and oligos.

Major publications of the researchers involved in the project on the subject of the project

1. Shcherbina V, Kovalevska L, Pedachenko E, Malysheva T, Kashuba E. Comparative Analysis of the Embryonal Brain Tumors Based on Their Molecular Features. Discov Med. 2023 Oct;35(178):733-749. doi: 10.24976/Discov.Med.202335178.69. PMID: 37811612.
2. Govorov I, Attarha S, Kovalevska L, Andersson E, Kashuba E, Mints M. STK4 protein expression pattern follows different trends in endometrioid and serous endometrial adenocarcinoma upon tumor progression. Sci Rep. 2022 Dec 22;12(1):22154. doi: 10.1038/s41598-022-26391-9. PMID: 36550267; PMCID: PMC9780310.
3. Govorov I, Attarha S, Kovalevska L, Andersson E, Kashuba E, Mints M Upregulation of PKN1 as a Prognosis Biomarker for Endometrial Cancer. Cancer Control. 2022 Jan-Dec;29:10732748221094797. doi: 10.1177/10732748221094797. PMID: 35533253; PMCID: PMC9092572.
4. Kovalevska L, Golenkov O, Kulahina Y, Callender T, Sizov F, Kashuba E. A Comparative Study on the Viability of Normal and Cancerous Cells upon Irradiation with a Steady Beam of THz Rays. Life (Basel). 2022 Mar 5;12(3):376. doi: 10.3390/life12030376. PMID: 35330127; PMCID: PMC8951499.
5. Zvejniece L, Kozireva S, Rudevica Z, Leonciks A, Ehlin-Henriksson B, Kashuba E, Kholodnyuk I. Expression of the Chemokine Receptor CCR1 in Burkitt Lymphoma Cell Lines Is Linked to the CD10-Negative Cell Phenotype and Co-Expression of the EBV Latent Genes EBNA2, LMP1, and LMP2. Int J Mol Sci. 2022 Mar 22;23(7):3434. doi: 10.3390/ijms23073434. PMID: 35408790; PMCID: PMC8998437.