Interaction of HIV, herpesviruses and tumor microenvironment in the pathogenesis of colorectal cancer

In this analytical review, the authors present the epidemiology of HIV infection and malignant neoplasms, as well as the relationship between these diseases. At the end of 2023, the total number of people living with HIV was 39.9 million, with 77% of them receiving antiretroviral therapy (ART). With the introduction of ART, the mortality structure among HIV-positive individuals has changed: the incidence of AIDS-defining neoplasms (ADM) has decreased, but the proportion of non-AIDS-defining tumors (nADM) has increased. The main predictors of mortality from nADM are low CD4+ lymphocytes, old age, smoking, and coinfection with viral hepatitis. The epidemiology of colorectal cancer (CRC), which ranks third in incidence among oncological diseases, is considered. CRC most often develops from precancerous lesions such as adenomas and serrated lesions of the colon, and its risk increases with age, obesity, smoking, and low physical activity. Particular attention is paid to the relationship between HIV infection and the development of CRC, as well as the role of viruses such as Epstein-Barr virus and cytomegalovirus in carcinogenesis. HIV infection contributes to the development of chronic inflammatory processes in the colorectal localization, which may increase the risk of developing CRC. Possible mechanisms linking HIV with the development of CRC, including the impact of ART and immunosuppression, are discussed. Potential therapeutic approaches associated with the use of anti-HIV drugs for the treatment of cancer are also considered.

1. Laurence J. «AIDS at a Crossroads»: Highlights from the 2024 UNAIDS Report // AIDS Patient Care STDS. 2024. Vol. 38. Р. 493–494. https://doi.org/10.1089/apc.2024.0172.

2. May M.T., Gompels M., Delpech V., Porter K., Orkin C., Kegg S., Hay P., Johnson M., Palfreeman A., Gilson R., Chadwick D., Martin F., Hill T., Walsh J., Post F., Fisher M., Ainsworth J., Jose S., Leen C., Nelson M., Anderson J., Sabin C. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy // AIDS. 2014. Vol. 28. Р. 1193–1202. https://doi.org/10.1097/QAD.0000000000000243.

3. ВИЧ-инфекция у взрослых. Клинические рекомендации. 2024. [HIV infection in adults. Clinical guidelines. 2024 (In Russ.). https://cr.minzdrav.gov.ru/schema/79_2.

4. HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies // AIDS. 2008. Vol. 22. Р. 2143–2153. https://doi.org/10.1097/QAD.0b013e3283112b77.

5. Ehren K., Hertenstein C., Kümmerle T., Vehreschild J.J., Fischer J., Gillor D., Wyen C., Lehmann C., Cornely O.A., Jung N., Gravemann S., Platten M., Wasmuth J.C., Rockstroh J.K., Boesecke C., Schwarze-Zander C., Fätkenheuer G. Causes of death in HIV-infected patients from the Cologne–Bonn cohort // Infection. 2014. Vol. 42. Р. 135–140. https://doi.org/10.1007/s15010-013-0535-7.

6. Patel P., Hanson D.L., Sullivan P.S., Novak R.M., Moorman A.C., Tong T.C., Holmberg S.D., Brooks J.T. Incidence of Types of Cancer among HIV-Infected Persons Compared with the General Population in the United States, 1992–2003 // Ann. Intern. Med. 2008. Vol. 148. Р. 728–736. https://doi.org/10.7326/0003-4819-148-10-200805200-00005.

7. Leatherwood J.L. Gastric adenocarcinoma associated with human immunodeficiency virus (HIV) infection // J. Am. Osteopath. Assoc. 1991. Vol. 91, No. 7. Р. 695–697. PMID: 1938507.

8. Kan M., Wong P.H.P., Press N., Wiseman S.M. Colorectal and anal cancer in HIV/AIDS patients: A comprehensive review // Expert Rev. Anticancer. Ther. 2014. Vol. 14. Р. 395–405. https://doi.org/10.1586/14737140.2013.877843.

9. Bini E.J., Park J., Francois F. Use of Flexible Sigmoidoscopy to Screen for Colorectal Cancer in HIV-Infected Patients 50 Years of Age and Older // Arch. Intern. Med. 2006. Vol. 166. Р. 1626. https://doi.org/10.1001/archinte.166.15.1626.

10. Sigel C., Cavalcanti MS., Daniel T., Vakiani E., Shia J., Sigel K. Clinicopathologic Features of Colorectal Carcinoma in HIV-Positive Patients // Cancer Epidemiology, Biomarkers & Prevention. 2016. Vol. 25. Р. 1098–1104. https://doi.org/10.1158/1055-9965.EPI-15-1179.

11. WHO Regional Office for Europe, European Centre for Disease Prevention and Control. HIV/AIDS surveillance in Europe 2024–2023 data. Copenhagen: WHO Regional Office for Europe; 2024. URL: https://www.ecdc.europa.eu/sites/default/files/documents/HIV_Surveillance_Report_2024.pdf

12. Kaprin A.D., Voronin E.E., Rassokhin V.V., Rozenberg V.V., Nekrasova A.V., Falaleeva N.A., Ivanov S.A., Grivtsova L.Y. Malignant neoplasms associated with HIV infection. Problems and solutions (problem outline). Journal of Modern Oncology, 2021, Vol. 23, No. 3, pp. 502–507 (In Russ.). doi: 10.26442/18151434.2021.3.201041.

13. alaleeva N.A., Grivtsova L.Y., Gusev D.A. Malignant neoplasms in HIV patients in Russia: the story over a 20-year period. Journal of Modern Oncology, 2021, Vol. 23, No. 4, pp. 593–597 (In Russ.). doi: 10.26442/18151434.2021.4.201291.

14. Martel C., de, Georges D., Bray F., Ferlay J., Clifford G.M. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis // Lancet Glob. Health. 2020. Vol. 8. Р. 180–190. https://doi.org/10.1016/S2214-109X(19)30488-7.

15. Bray F., Laversanne M., Sung H., Ferlay J., Siegel R.L., Soerjomataram I., Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries // CA Cancer J. Clin. 2024. Vol. 74. Р. 229–263. https://doi.org/10.3322/caac.21834.

16. Kaprin A.D., Starinsky V.V., Shakhzadova A.O. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Moscow: P. A. Herzen Moscow Institute of Medical Sciences — branch of the Federal State Budgetary Institution «NMITS of Radiology» of the Ministry of Health of Russia, 2024. 276 p. (In Russ.). URL: https://oncology-association.ru/wp-content/uploads/2024/08/zis-2023-elektronnaya-versiya.pdf.

17. Arnold M., Abnet C.C., Neale R.E., Vignat J., Giovannucci E.L., McGlynn K.A., Bray F. Global Burden of 5 Major Types of Gastrointestinal Cancer // Gastroenterology. 2020. Vol. 159, No 1. Р. 335–349. doi: 10.1053/j.gastro.2020.02.068. PMID: 32247694; PMCID: PMC8630546.

18. Starostin R.A., Gataullin B.I., Valitov B.R., Gataullin I.G. Colorectal cancer: epidemiology and risk factors. Volga Oncological Bulletin, 2021, Vol. 12, No. 4 (48), pp. 52–59 (In Russ.). EDN CMPKOS. URL: https://oncovestnik.ru/archive/2021/2021-4/kolorektalnyj-rak-epidemiologiya-i-faktory-riska.

19. Pollock A.M., Quirke P. Adenoma screening and colorectal cancer // BMJ. 1991. Vol. 303. Р. 3–4. https://doi.org/10.1136/bmj.303.6793.3.

20. Ahmad R., Singh J.K., Wunnava A., Al-Obeed O., Abdulla M., Srivastava S.K. Emerging trends in colorectal cancer: Dysregulated signaling pathways (Review) // Int. J. Mol. Med. 2021. Vol. 47, No. 3. Р. 14. doi: 10.3892/ijmm.2021.4847. PMID: 33655327; PMCID: PMC7834960.

21. Correa P. Epidemiology of polyps and cancer // Major Probl. Pathol. 1978. Vol. 10. Р. 126–152. PMID: 359941.

22. Li F., Lai M. Colorectal cancer, one entity or three // J. Zhejiang Univ. Sci. B. 2009. Vol. 10. Р. 219–229. https://doi.org/10.1631/jzus.B0820273.

23. Markman J.L., Shiao S.L. Impact of the immune system and immunotherapy in colorectal cancer // J. Gastrointest. Oncol. 2015. Vol. 6, No. 2. Р. 208–223. doi: 10.3978/j.issn.2078-6891.2014.077. PMID: 25830040; PMCID: PMC4311093.

24. Nasi M., Pinti M., Mussini C., Cossarizza A. Persistent inflammation in HIV infection: established concepts, new perspectives // Immunol. Lett. 2014. Vol. 161, No. 2. Р. 184–188. doi: 10.1016/j.imlet.2014.01.008. PMID: 24487059.

25. Khryanin A.A., Pushkarev E.V., Bocharova V.K. HIV infection and the gut microbiome. HIV Infection and Immunosuppressive Disorders. 2023. Vol. 15, No. 4, pp. 25–35 (In Russ.). https://doi.org/10.22328/2077-9828-2023-15-4-25-35.

26. Yoder A.C., Guo K., Dillon S.M., Phang T., Lee E.J., Harper M.S., Helm K., Kappes J.C., Ochsenbauer C., McCarter M.D., Wilson C.C., Santiago M.L. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria // PLoS Pathog. 2017. Vol. 13, No. 2. Р. e1006226. doi: 10.1371/journal.ppat.1006226. PMID: 28241075; PMCID: PMC5344538.

27. Marchetti G., Bellistrì GM., Borghi E., Tincati C., Ferramosca S., La Francesca M., Morace G., Gori A., Monforte A.D. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy // AIDS. 2008. Vol. 22, No. 15. Р. 2035–2038. doi: 10.1097/QAD.0b013e3283112d29. PMID: 18784466.

28. Poles M.A., Boscardin W.J., Elliott J., Taing P., Fuerst M.M.P., McGowan I., Brown S., Anton P.A. Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals // J. Acquir. Immune Defic. Syndr. 2006. Vol. 43. Р. 65–68. https://doi.org/10.1097/01.qai.0000230524.71717.14.

29. Yukl S.A., Gianella S., Sinclair E., Epling L., Li Q., Duan L., Choi A.L.M., Girling V., Ho T., Li P., Fujimoto K., Lampiris H., Hare C.B., Pandori M., Haase A.T., Günthard H.F., Fischer M., Shergill A.K., McQuaid K., Havlir D.V., Wong J.K. Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy // J. Infect Dis. 2010. Vol. 202, No. 10. Р. 1553–1561. https://doi.org/10.1086/656722.

30. Yukl S.A., Shergill A.K., McQuaid K., Gianella S., Lampiris H., Hare C.B., Pandori M., Sinclair E., Günthard H.F., Fischer M., Wong J.K., Havlir D.V. Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy // AIDS. 2010. Vol. 24. Р. 2451–2460. https://doi.org/10.1097/QAD.0b013e32833ef7bb.

31. Peng X., Isnard S., Lin J., Fombuena B., Bessissow T., Chomont N., Routy J.P. Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis // J. Virus Erad. 2021. Vol. 7, No. 1. Р. 100033. doi: 10.1016/j.jve.2021.100033. PMID: 33664976; PMCID: PMC7906891.

32. Brenchley J.M., Douek D.C. The mucosal barrier and immune activation in HIV pathogenesis // Curr. Opin. HIV AIDS. 2008. Vol. 3. Р. 356– 361. https://doi.org/10.1097/COH.0b013e3282f9ae9c.

33. Alzahrani J., Hussain T., Simar D., Palchaudhuri R., Abdel-Mohsen M., Crowe S.M., Mbogo G.W., Palmer C.S. Inflammatory and immunometabolic consequences of gut dysfunction in HIV: Parallels with IBD and implications for reservoir persistence and non-AIDS comorbidities // EBioMedicine. 2019. Vol. 46. Р. 522–531. https://doi.org/10.1016/j.ebiom.2019.07.027.

34. Skamnelos A., Tatsioni A., Katsanos K.H., Tsianos V., Christodoulou D., Tsianos E.V. CD4 count remission hypothesis in patients with inflammatory bowel disease and human immunodeficiency virus infection: a systematic review of the literature // Ann. Gastroenterol. 2015. Vol. 28, No. 3. Р. 337–346. PMID: 26126511; PMCID: PMC4480170.

35. Di Stefano M., Favia A., Monno L., Lopalco P., Caputi O., Scardigno AC., Pastore G., Fiore JR., Angarano G. Intracellular and cell-free (infectious) HIV-1 in rectal mucosa // J. Med Virol. 2001. Vol. 65. Р. 637–643. https://doi.org/10.1002/jmv.2084.

36. Isnard S., Ramendra R., Dupuy F.P., Lin J., Fombuena B., Kokinov N., Kema I., Jenabian M-A., Lebouché B., Costiniuk C.T., Ancuta P., Bernard N.F., Silverman M.S., Lakatos P.L., Durand M., Tremblay C., Routy J.-P. Montreal Primary HIV Infection Study the CC of HSP and the CH and ACG. Plasma Levels of C-Type Lectin REG3 and Gut Damage in People With Human Immunodeficiency Virus // J. Infect Dis. 2020. Vol. 221. Р. 110–121. https://doi.org/10.1093/infdis/jiz423.

37. Zeitz M., Ullrich R., Schneider T., Kewenig S., Hohloch K., Riecken E.O. HIV/SIV enteropathy // Ann. N. Y. Acad. Sci. 1998. Vol. 859. Р. 139–148. https://doi.org/10.1111/j.1749–6632.1998.tb11118.x.

38. Crum-Cianflone N.F. HIV and the Gastrointestinal Tract // Infect. Dis. Clin. Pract. (Baltim Md). 2010. Vol. 18. Р. 283–285. https://doi.org/10.1097/IPC.0b013e3181f1038b.

39. Dillon S.M., Lee E.J., Kotter C.V., Austin G.L., Dong Z., Hecht D.K., Gianella S., Siewe B., Smith D.M., Landay A.L., Robertson C.E., Frank D.N., Wilson C.C. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia // Mucosal. Immunol. 2014. Vol. 7. Р. 983–994. https://doi.org/10.1038/mi.2013.116.

40. Gianella S., Massanella M., Wertheim J.O., Smith D.M. The Sordid Affair Between Human Herpesvirus and HIV // J. Infect. Dis. 2015. Vol. 212. Р. 845–852. https://doi.org/10.1093/infdis/jiv148.

41. Gianella S., Letendre S. Cytomegalovirus and HIV: A Dangerous Pas de Deux // J. Infect. Dis. 2016. Vol. 214. Р. 67–74. https://doi.org/10.1093/infdis/jiw217.

42. Maidji E., Somsouk M., Rivera J.M., Hunt P.W., Stoddart C.A. Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction // PLoS Pathog. 2017. Vol. 13. Р. e1006202. https://doi.org/10.1371/journal.ppat.1006202.

43. Gianella S., Chaillon A., Mutlu E.A., Engen P.A., Voigt R.M., Keshavarzian A., Losurdo J., Chakradeo P., Lada S.M., Nakazawa M., Landay A.L. Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals // AIDS. 2017. Vol. 31. Р. 2059–2067. https://doi.org/10.1097/QAD.0000000000001579.

44. Mirzaei H., Goudarzi H., Eslami G., Faghihloo E. Role of viruses in gastrointestinal cancer // J. Cell Physiol. 2018. Vol. 233. Р. 4000–4014. https://doi.org/10.1002/jcp.26194.

45. Marongiu L., Allgayer H. Viruses in colorectal cancer // Mol. Oncol. 2022. Vol. 16. Р. 1423–1450. https://doi.org/10.1002/1878-0261.13100.

46. Villiers E.-M., de, Gunst K., Chakraborty D., Ernst C., Bund T., Zur Hausen H. A specific class of infectious agents isolated from bovine serum and dairy products and peritumoral colon cancer tissue // Emerg. Microbes. Infect. 2019. Vol. 8. Р. 1205–1218. https://doi.org/10.1080/22221751.2019.1651620.

47. Chen H., Chen X.-Z., Waterboer T., Castro F.A., Brenner H. Viral infections and colorectal cancer: a systematic review of epidemiological studies // Int. J. Cancer. 2015. Vol. 137. Р. 12–24. https://doi.org/10.1002/ijc.29180.

48. Lieberman P.M. Virology. Epstein-Barr virus turns 50 // Science. 2014. Vol. 343. Р. 1323–1325. https://doi.org/10.1126/science.1252786.

49. Yuen S.T., Chung L.P., Leung S.Y., Luk I.S., Chan S.Y., Ho J. In situ detection of Epstein-Barr virus in gastric and colorectal adenocarcinomas // Am. J. Surg. Pathol. 1994. Vol. 18. Р. 1158–1163. https://doi.org/10.1097/00000478-199411000-00010.

50. Cho Y.J., Chang M.S., Park S.H., Kim H.S., Kim W.H. In situ hybridization of Epstein-Barr virus in tumor cells and tumor-infiltrating lymphocytes of the gastrointestinal tract // Hum. Pathol. 2001. Vol. 32. Р. 297–301. https://doi.org/10.1053/hupa.2001.22766.

51. Mehrabani-Khasraghi S., Ameli M., Khalily F. Demonstration of Herpes Simplex Virus, Cytomegalovirus, and Epstein-Barr Virus in Colorectal Cancer // Iran. Biomed. J. 2016. Vol. 20. Р. 302–306. https://doi.org/10.22045/ibj.2016.08.

52. Ahmed W., Philip P.S., Tariq S., Khan G. Epstein-Barr virus-encoded small RNAs (EBERs) are present in fractions related to exosomes released by EBV-transformed cells // PLoS One. 2014. Vol. 9. Р. e99163. https://doi.org/10.1371/journal.pone.0099163.

53. Dukers D.F., Meij P., Vervoort M.B., Vos W., Scheper R.J., Meijer C.J., Bloemena E., Middeldorp J.M. Direct immunosuppressive effects of EBV-encoded latent membrane protein 1 // J. Immunol. 2000. Vol. 165. Р. 663–670. https://doi.org/10.4049/jimmunol.165.2.663.

54. Zhao J., Liang Q., Cheung K.-F., Kang W., Lung R.W.M., Tong J.H.M., To K.F., Sung J.J.Y., Yu J. Genome-wide identification of Epstein-Barr virus-driven promoter methylation profiles of human genes in gastric cancer cells // Cancer. 2013. Vol. 119. Р. 304–312. https://doi.org/10.1002/cncr.27724.

55. Birdwell C.E., Prasai K., Dykes S., Jia Y., Munroe T.G.C., Bienkowska-Haba M., Scott R.S. Epstein-Barr virus stably confers an invasive phenotype to epithelial cells through reprogramming of the WNT pathway // Oncotarget. 2018. Vol. 9. Р. 10417–10435. https://doi.org/10.18632/oncotarget.23824.

56. Cadigan K.M., Waterman M.L. TCF/LEFs and Wnt signaling in the nucleus // Cold Spring Harb. Perspect. Biol. 2012. Vol. 4, No. 11. Р. a007906. doi: 10.1101/cshperspect.a007906. PMID: 23024173; PMCID: PMC3536346.

57. Horikawa T., Yang J., Kondo S., Yoshizaki T., Joab I., Furukawa M., Pagano J.S. Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma // Cancer Res. 2007. Vol. 67. Р. 1970–1978. https://doi.org/10.1158/0008-5472.CAN-06-3933.

58. Winberg G., Matskova L., Chen F., Plant P., Rotin D., Gish G., Ingham R., Ernberg I., Pawson T. Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases // Mol. Cell Biol. 2000. Vol. 20. Р. 8526–8535. https://doi.org/10.1128/MCB.20.22.8526-8535.2000.

59. Fernandes Q., Sher G., Prabhu K.S., Kuttikrishnan S., Merhi M., Dermime S., Junejo K., Bhat A.A., Uddin S. Beyond Viral Infections: The Multifaceted Roles of Human Papillomavirus and Epstein-Barr Virus in Shaping the Tumor Microenvironment // Discov. Med. 2024. Vol. 36. Р. 1–15. https://doi.org/10.24976/Discov.Med.202436180.1.

60. Revello M.G., Gerna G. Human cytomegalovirus tropism for endothelial/epithelial cells: scientific background and clinical implications // Rev. Med. Virol. 2010. Vol. 20. Р. 136–55. https://doi.org/10.1002/rmv.645.

61. Chiopris G., Veronese P., Cusenza F., Procaccianti M., Perrone S., Daccò V., Colombo C., Esposito S. Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment // Microorganisms. 2020. Vol. 8, No. 10. Р. 1516. doi: 10.3390/microorganisms8101516. PMID: 33019752; PMCID: PMC7599523.

62. Pannuti C.S., Vilas Boas L.S., Angelo M.J., Amato Neto V., Levi G.C., de Mendonca J.S., de Godoy C.V. Cytomegalovirus mononucleosis in children and adults: differences in clinical presentation // Scand. J. Infect. Dis. 1985. Vol. 17. Р. 153–156. https://doi.org/10.3109/inf.1985.17.issue-2.05.

63. Goodrum F. Human Cytomegalovirus Latency: Approaching the Gordian Knot // Ann. Rev. Virol. 2016. Vol. 3. Р. 333–357. https://doi.org/10.1146/annurev-virology-110615–042422.

64. Geder K.M., Lausch R., O’Neill F., Rapp F. Oncogenic transformation of human embryo lung cells by human cytomegalovirus // Science. 1976. Vol. 192. Р. 1134–1137. https://doi.org/10.1126/science.179143.

65. Doniger J., Muralidhar S., Rosenthal L.J. Human cytomegalovirus and human herpesvirus 6 genes that transform and transactivate // Clin. Microbiol. Rev. 1999. Vol. 12. Р. 367–382. https://doi.org/10.1128/CMR.12.3.367.

66. Cobbs C. Cytomegalovirus is a tumor-associated virus: armed and dangerous // Curr. Opin. Virol. 2019. Vol. 39. Р. 49–59. https://doi.org/10.1016/j.coviro.2019.08.003.

67. Lv Y.-L., Han F.-F., An Z.-L., Jia Y., Xuan L.-L., Gong L.-L., Zhang W., Ren L.-L., Yang S., Liu H., Liu L.-H. Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study // Intervirology. 2020. Vol. 63. Р. 10–16. https://doi.org/10.1159/000506683.

68. Bai B., Wang X., Chen E., Zhu H. Human cytomegalovirus infection and colorectal cancer risk: a meta-analysis // Oncotarget. 2016. Vol. 7. Р. 76735–76742. https://doi.org/10.18632/oncotarget.12523.

69. Akintola-Ogunremi O., Luo Q., He T.C., Wang H.L. Is cytomegalovirus associated with human colorectal tumorigenesis? // Am. J. Clin. Pathol. 2005. Vol. 123, No 2. Р. 244–249. PMID: 15842049.

70. Chen H.-P., Jiang J.-K., Chen C.-Y., Chou T.-Y., Chen Y.-C., Chang Y.-T., Lin S.-F., Chan C.-H., Yang C.-Y., Lin C.-H., Lin J.-K., Cho W.- L., Chan Y.-J. Human cytomegalovirus preferentially infects the neoplastic epithelium of colorectal cancer: a quantitative and histological analysis // J. Clin. Virol. 2012. Vol. 54. Р. 240–244. https://doi.org/10.1016/j.jcv.2012.04.007.

71. Teo W.H., Chen H.P., Huang J.C., Chan Y.J. Human cytomegalovirus infection enhances cell proliferation, migration and upregulation of EMT markers in colorectal cancer-derived stem cell-like cells // Int. J. Oncol. 2017. Vol. 51, No. 5. Р. 1415–1426. doi: 10.3892/ijo.2017.4135. Epub 2017 Sep 25. PMID: 29048611; PMCID: PMC5642395.

72. Jault F.M., Jault J.M., Ruchti F., Fortunato E.A., Clark C., Corbeil J., Richman D.D., Spector D.H. Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest // J. Virol. 1995. Vol. 69. Р. 6697–6704. https://doi.org/10.1128/JVI.69.11.6697-6704.1995.

73. Luo M.H., Rosenke K., Czornak K., Fortunato E.A. Human cytomegalovirus disrupts both ataxia telangiectasia mutated protein (ATM)- and ATM-Rad3-related kinase-mediated DNA damage responses during lytic infection // J. Virol. 2007. Vol. 81. Р. 1934–1950. https://doi.org/10.1128/JVI.01670-06.

74. Clement M., Humphreys I.R. Cytokine-Mediated Induction and Regulation of Tissue Damage During Cytomegalovirus Infection // Front Immunol. 2019. Vol. 10. Р. 78. https://doi.org/10.3389/fimmu.2019.00078.

75. Maussang D., Langemeijer E., Fitzsimons C.P., Stigter-van Walsum M., Dijkman R., Borg M.K., Slinger E., Schreiber A., Michel D., Tensen C.P., van Dongen G.A.M.S., Leurs R., Smit M.J. The human cytomegalovirus-encoded chemokine receptor US28 promotes angiogenesis and tumor formation via cyclooxygenase-2 // Cancer Res. 2009. Vol. 69. Р. 2861–2869. https://doi.org/10.1158/0008-5472.CAN-08-2487.

76. Sheng J., Sun H., Yu F.-B., Li B., Zhang Y., Zhu Y.-T. The Role of Cyclooxygenase-2 in Colorectal Cancer // Int. J. Med. Sci. 2020. Vol. 17. Р. 1095–1101. https://doi.org/10.7150/ijms.44439.

77. Yarchoan R., Uldrick T.S. HIV-Associated Cancers and Related Diseases // N. Engl. J. Med. 2018. Vol. 378. P. 1029–1041. https://doi.org/10.1056/NEJMra1615896.

78. Palefsky J.M. Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals: incidence and prevention in the antiretroviral therapy era // Curr. Opin. in HIV and AIDS. 2017. Vol. 12, No. 1. Р. 26–30. doi: 10.1097/COH.0000000000000336.

79. Kelly T.-A., Kim S., Jemmott L.S., Jemmott J.B. Predictors of Colorectal Cancer Screening Among African American Men Living with HIV // J. Community Health. 2021. Vol. 46. Р. 1099–1106. https://doi.org/10.1007/s10900-021-00997-y.

80. Darvishian M., Butt Z.A., Wong S., Yoshida E.M., Khinda J., Otterstatter M., Yu A., Binka M., Rossi C., McKee G., Pearce M., Alvarez M., Wong J., Cook D., Grennan T., Buxton J., Tyndall M., Woods R., Krajden M., Bhatti P., Janjua N.Z. Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada // Ther. Adv. Med. Oncol. 2021. Vol. 13. Р. 1758835921992987. https://doi.org/10.1177/1758835921992987.

81. Palella F.J., Baker R.K., Moorman A.C., Chmiel J.S., Wood K.C., Brooks J.T., Holmberg S.D. HIV Outpatient Study Investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study // J. Acquir. Immune Defic. Syndr. 2006. Vol. 43. Р. 27–34. https://doi.org/10.1097/01.qai.0000233310.90484.16.

82. Yu X., Li Z. The role of TARBP2 in the development and progression of cancers // Tumour. Biol. 2016. Vol. 37. Р. 57–60. https://doi.org/10.1007/s13277-015-4273-6.

83. Musinova Y.R., Sheval E.V., Dib C., Germini D., Vassetzky Y.S. Functional roles of HIV-1 Tat protein in the nucleus // Cell Mol Life Sci. 2016. Vol. 73. Р. 589–601. https://doi.org/10.1007/s00018-015-2077-x.

84. Huynh D., Vincan E., Mantamadiotis T., Purcell D., Chan C.-K., Ramsay R. Oncogenic properties of HIV-Tat in colorectal cancer cells // Curr. HIV Res. 2007. Vol. 5. Р. 403–409. https://doi.org/10.2174/157016207781023974.

85. Bumpers H.L., Huang M.-B., Powell M., Grizzle W.E., Lillard J.W., Okoli J., Bond V.C. Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer // Cancer Biol. Ther. 2005. Vol. 4. Р. 65–69. https://doi.org/10.4161/cbt.4.1.1377.

86. Chow W.A., Jiang C., Guan M. Anti-HIV drugs for cancer therapeutics: back to the future? // Lancet Oncol. 2009. Vol. 10. Р. 61–71. https://doi.org/10.1016/S1470-2045(08)70334-6.

87. Alburquerque-González B., Bernabé-García Á., Bernabé-García M., Ruiz-Sanz J., López-Calderón F.F., Gonnelli L., Banci L., Peña-García J., Luque I., Nicolás F.J., Cayuela-Fuentes M.L., Luchinat E., Pérez-Sánchez H., Montoro-García S., Conesa-Zamora P. The FDA-Approved Antiviral Raltegravir Inhibits Fascin1-Dependent Invasion of Colorectal Tumor Cells In Vitro and In Vivo // Cancers (Basel). 2021. Vol. 13, No. 4. Р. 861. https://doi.org/10.3390/cancers13040861.

88. Falcone A., Danesi R., Dargenio F., Pfanner E., Brunetti I., Del Tacca M., Nethersell A.B., Conte P.F. Intravenous azidothymidine with fluorouracil and leucovorin: a phase I-II study in previously untreated metastatic colorectal cancer patients // J. Clin. Oncol. 1996. Vol. 14. Р. 729– 736. https://doi.org/10.1200/JCO.1996.14.3.729.

89. Sherif D.A., Makled M.N., Suddek G.M. The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD-induced colorectal cancer in Wistar rats // Fundam. Clin. Pharmacol. 2021. Vol. 35. Р. 940–954. https://doi.org/10.1111/fcp.12679.