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Introduction. Head and neck squamous cell carcinoma is the 6th most common malignant tumor. It is characterized by immune response evasion and drug resistance. To stimulate antitumor immune response, antibodies against such cell cycle checkpoints as programmed cell death 1 (pD-1) and programmed death-ligand 1 (pD-L1) are used. However, effectiveness of monotherapy with these checkpoint inhibitors turned out to be low, and combinations with other antitumor drugs have high risk of adverse events.Aim. To determine the most practical ways to influence epigenetic factors in treatment of head and neck squamous cell carcinoma.Materials and methods. Scientific literature published between 2011 and 2022 and indexed in the eLIBRARY, Scopus, woS, NCBI databases (398 articles, of which 76 were used) was analyzed.Results. prospects of development of epigenetic stimulation of expression of retroelements located in tumor genomes through inhibition of DNA methyltransferases, deacetylases and histone methyltransferases were considered. when retroelements are activated, their transcripts form double-stranded RNA stimulating T killers and interferon response (virus mimicry). for DNA methyltransferase inhibitors, restoration of tumor suppressor genes which are hypermethylated in squamous cell carcinoma is also observed. However, retroelement activation is a driver mechanism of carcinogenesis, and their nonspecific expression can lead to tumor progression and formation of secondary tumors. Therefore, in the virus mimicry method it is practical to use as targets microRNA complementary to retroelements which recruit epigenetic factors to their loci (RNA-directed DNA methylation), as well as antisense oligonucleotides against oncogenic microRNA associated with retroelements. These approaches allow to inhibit retroelements participating in carcinogenesis. Nonspecific method of retrotransposon activity suppression is being developed in antitumor therapy, but data show successful application of only reverse transcriptase inhibitors preventing insertions and progression of genomic instability. we have performed analysis of scientific literature on transposable elements-derived microRNA associated with head and neck squamous cell carcinoma. As a result, 31 microRNAs were identified, derived from: LINE: miR-1249, -151a, -211, -2355, -28, -31, -3144, -374a, -374b, -421, -450b, -511, -576, -577, -582, -708, -769, -887, -95; HERv: miR-1269a, -1911, -3200, -495; non-autonomous SINE: miR-335, -342, -378a, -3934, -487b; DNA transposons: miR-224, -584, -652. These microRNAs can serve as the basis for epigenetic therapy of head and neck squamous cell carcinoma.
Introduction. Head and neck squamous cell carcinoma is the 6th most common malignant tumor. It is characterized by immune response evasion and drug resistance. To stimulate antitumor immune response, antibodies against such cell cycle checkpoints as programmed cell death 1 (pD-1) and programmed death-ligand 1 (pD-L1) are used. However, effectiveness of monotherapy with these checkpoint inhibitors turned out to be low, and combinations with other antitumor drugs have high risk of adverse events.Aim. To determine the most practical ways to influence epigenetic factors in treatment of head and neck squamous cell carcinoma.Materials and methods. Scientific literature published between 2011 and 2022 and indexed in the eLIBRARY, Scopus, woS, NCBI databases (398 articles, of which 76 were used) was analyzed.Results. prospects of development of epigenetic stimulation of expression of retroelements located in tumor genomes through inhibition of DNA methyltransferases, deacetylases and histone methyltransferases were considered. when retroelements are activated, their transcripts form double-stranded RNA stimulating T killers and interferon response (virus mimicry). for DNA methyltransferase inhibitors, restoration of tumor suppressor genes which are hypermethylated in squamous cell carcinoma is also observed. However, retroelement activation is a driver mechanism of carcinogenesis, and their nonspecific expression can lead to tumor progression and formation of secondary tumors. Therefore, in the virus mimicry method it is practical to use as targets microRNA complementary to retroelements which recruit epigenetic factors to their loci (RNA-directed DNA methylation), as well as antisense oligonucleotides against oncogenic microRNA associated with retroelements. These approaches allow to inhibit retroelements participating in carcinogenesis. Nonspecific method of retrotransposon activity suppression is being developed in antitumor therapy, but data show successful application of only reverse transcriptase inhibitors preventing insertions and progression of genomic instability. we have performed analysis of scientific literature on transposable elements-derived microRNA associated with head and neck squamous cell carcinoma. As a result, 31 microRNAs were identified, derived from: LINE: miR-1249, -151a, -211, -2355, -28, -31, -3144, -374a, -374b, -421, -450b, -511, -576, -577, -582, -708, -769, -887, -95; HERv: miR-1269a, -1911, -3200, -495; non-autonomous SINE: miR-335, -342, -378a, -3934, -487b; DNA transposons: miR-224, -584, -652. These microRNAs can serve as the basis for epigenetic therapy of head and neck squamous cell carcinoma.
Introduction. High-risk human papilloma virus (Hpv), especially genotype 16, causes oropharyngeal squamous cell carcinoma (OSCC). It is detected in about 70 % of tumors developing from lymphoid tissue of the tonsils or the base of the tongue. Due to the increased number of Hpv-positive OSCC, Hpv status is considered a marker of OSCC clinical outcome. Easy testing, low cost, reliability, and high sensitivity of immunohistochemical analysis for p16INk4a allowed to widely use this method for Hpv status determination.Aim. To determine the association between programmed death-ligand 1 (pD-L1) and p53 expression and presence of indirect Hpv marker – p16INk4a – in patients with OSCC.Materials and methods. The study included 76 patients with OSCC т1–4N0–3m0 who received treatment at the Republican Specialized Scientific and practical medical Center of Oncology and Radiology (n = 37) and its Tashkent branch (n = 39) between 2015 and 2020. for all selected patients, retrospective immunohistochemical analysis for the presence of p16INk4a, pD-L1 and р53 in tumor samples fixed with formalin in paraffin blocks was performed. In our work, immunohistochemical examination for p16INk4a was the only relevant tool for Hpv status determination. To reinforce its prognostic significance, we used additional molecular markers pD-L1 and p53 which play an important role in carcinogenic transformation and OSCC progression.Results. The results of immunohistochemical analysis showed that p16INk4a overexpression was accompanied by positive pD-L1 reaction in 46 % (6/13) of cases; there were no cases of positive expression of mutant type p53. wild type p53 was identified in only 1 (3 %) case in combination with p16INk4a overexpression.Conclusion. The developed panel consisting of 3 molecular markers (p16INk4a, pD-L1 and р53) may open new horizons in accurate prognosis, risk stratification and understanding of OSCC molecular signature. This, in turn, will help clinicians in selection of individual therapy strategies for treatment de-escalation and outcome optimization.
Introduction. Th e growing incidence of oropharyngeal cancer is driven by an increase in frequency of HPV-associated oropharyngeal cancer. Th e morbidity pattern of oropharyngeal cancer is area-specific.Aim. To analyze the oropharyngeal cancer diagnosis and treatment in the Republic of Bashkortostan for 2020.Materials and methods. Th e authors carried out a 2020 retrospective analysis of the diagnosis and treatment results of patients with oropharyngeal cancer. 79 patients were identified with this diagnosis. 84.8% (67/79) among them were males and 15.2% females (12/79). Th e mean age of the patients was 59.1 years. Th e site of primary tumor was on the oropharynx lateral wall in 37.8% cases (30/79), in the tongue root area — 24.1% (19/79), in the tonsils area — 17.7% (14/79), on the soft palate — 16.5% (13/79), on the oropharynx posterior wall — 3.8% (3/79).Results. Examination of tumor morphological types revealed squamous cell carcinoma (SCC) with various degrees of differentiation in 92.4% cases (73/79), adenocarcinoma of minor salivary gland — in 6.3% (5/79) and sarcoma in 1.2% (1/79). 57.5% of 73 patients with SCC (42/73) underwent protein (p16) immunohistochemistry, while 42.5% of the patients (31/73) did not. According to a surrogate marker for HPV, the following results were obtained for 42 patients: p16-positive in 23.8% cases (10/42), p16-negative in 76.2% (32/42). Stage distribution according to TNM-7: stage I — 11.4% (9/79), stage II — 17.7% (14/79), stage III — 36.7% (29/79), stage IV — 46.8% (37/79). Stage distribution according to TNM-8 (patients who underwent p16 immunohistochemistry): stage I — 11.9% (5/42), stage II — 23.8% (10/42), stage III — 19% (8/42), stage IV — 45.2% (19/42). In 2020, 72% of patients (57/79) received definitive treatment, 10.1% (8/79) — palliative care, 15.2% (12/79) — supportive care, and 2.5% (2/79) refused medical treatment.Discussion. Th e various types of radiation therapy were used as the main defi nitive treatment for patients with oropharyngeal cancer in 69.2% cases (45/65). Only 18.5% of patients (12/65) underwent surgery, 58.3% of which (7/12) received post-surgery radiation therapy.Conclusion. 57.5% of patients (42/73) were detected with HPV status, 23.8% (10/42) revealed surrogate markers for HPV association. 69.2% of patients (45/65) received radiation therapy as the definitive treatment. 18.5% of patients (12/65) underwent surgery, 58.3% of which (7/12) received postsurgery radiation therapy.
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