Cervical cancer (CC) remains a current global issue, with >90% of cervical cancer cases being attributed to human papilloma virus (HPV). The highest burden of cervical cancer is reported in resource-depleted geographical areas with a high incidence of HPV infection. Recent developments in primary prevention include vaccinations against specific strains of HPV and the psychoeducation of the public. Yet, despite the availability of vaccinations, there is high incidence of both HPV and cervical cancer in developing countries, which is attributed to a multitude of barriers including inaccessibility to expensive vaccines. With regards to secondary prevention, progress is actively being made to develop more effective methods of screening and to specifically address the needs of low-income countries. In the past few years, more novel screening methods, such as self-assessment kits, immunohistochemistry and methylation marker analysis, have been developed. Barriers to screening in resource-depleted countries include limited financial resources and infrastructure to develop screening programmes, a lack of screening programmes that are accessible to populations, inadequate training of healthcare teams and stigma related to medical examinations performed as part of screening. Developing primary and secondary prevention programs, as well as addressing the barriers involved in countries with low socioeconomic levels, can drastically reduce morbidity and mortality rates associated with cervical cancer, thus reducing the burden associated with this gynaecological malignancy. Contents1. Introduction 2. Epidemiology and geographical inequalities in the burden of CC 3. Primary prevention and barriers faced by developing countries 4. Vaccinations 5. Psychoeducation 6. Secondary prevention and challenges faced by developing countries 7. Recent developments in screening methods 8. Barriers to screening in low resource countries and strategies for improvement 9. Conclusion

For the last few years Next Generation Sequencing technique and its applications has took the leading position in the arsenal of analytical methods that are used for studying the mechanisms of neoplastic progression. Among various experimental opportunities Next Generation Sequencing provides, RNA-sequencing (RNA-Seq) is of great importance as it makes possible unraveling the highest levels of genome expression regulation, which define the molecular phenotype of cells in composition of a tumor. Considerable amount of current studies carried out with the use of RNA-Seq method are designed as pan-cancer integrated research, in which special attention is payed to virus-associated tumors, including papillomavirus-dependent cervical cancer. This review paper summarizes the results of RNA-Seq studies published world-wide within 2017-2019 years and carried out using clinical samples from cervical cancer patients. New facts concerning such hot topics as genomic and transcriptomic instability, neoantigen load, cellular and molecular heterogeneity, tumor epigenetics, antitumor and antiviral immune response, chronic inflammation, immune exhaustion, phenotypic plasticity and tumor cell resistance, are considered. The whole spectrum of issues that are actively discussed in published literature is systematized according to three levels of organization: «molecular», «cellular» and «organismal». The findings reviewed in the paper convincingly illustrate that wide usage of RNA-Seq technology for profiling primary tumors does facilitate moving to a new level of our understanding of the mechanisms of carcinogenesis and emergence of new directions in cancer treatment, namely targeted and immune-therapy.

The review summarizes findings from the studies based on the application of technologies for transcriptome analysis to modern cellular model systems of human papillomavirus-associated cancer (HPV) (cervical cancer, head and neck tumors). A diversity of three-dimensional cancer models, such as spheroids, organoids (organotypic cultures), explants, mouse xenografts, are addressed. Particular attention is paid to the use of patient-derived biomaterial for establishing short-term cultures of primary tumor cells, as well as generating multicomponent (heterocellular) systems that comprise, together with the tumor component, other elements of its microenvironment. A number of unique biological properties of HPV-induced neoplasia are discussed, which make generating cell models a unique task.The novel findings in the field of molecular mechanisms of the onset and progression of HPV-associated cancer achieved by using RNA sequencing are presented for each variant of the model systems. These findings are considered in regard to applied aspects of their use, in terms of the opportunities for preclinical testing of new drugs, personalized diagnostics and selection of individual, most effective treatment regimens. The issues of drug resistance development, molecular-cellular heterogeneity, epigenetic reprogramming, and the role of the stromal microenvironment are reviewed. The paper accentuates the problems related to the limitations of the applicability of a particular model system. The areas with a significant lagging behind in omics research of virus-associated cancer in comparison with other types of oncological pathology and possible causes of this lag are noted. The future prospects for the development of model systems of HPV-associated tumors in the field of high-tech tissue engineering, in particular, the use of bioprinting and microfluidic biochips, are also outlined. The combination of these techniques with the methods of whole genome profiling will significantly increase the translational potential of the described model cell systems.