Preview

South Russian Journal of Cancer

Advanced search

Status and molecular genetic parameters of papillomavirus infection: individual characteristics and associative links with clinical and morphological factors of cervical cancer

https://doi.org/10.37748/2686-9039-2024-5-2-6

EDN: qmhkdo

Abstract

Purpose of the study. Study of the characteristics of human papillomavirus (HPV) infection, comparison of HPV status, molecular and genetic parameters of HPV high risk (HR) with the clinical and morphological characteristics of cervical cancer.

Materials and methods. The study included 240 patients with morphologically verified cervical cancer stages I–III, in whom the presence of HPV DNA of 14 genotypes was examined before treatment; upon detection, viral load (VL), the presence and degree of DNA integration into the genome of the host cell were examined.

Results. A number of statistically significant associative relationships have been identified between the molecular and genetic parameters of HPV infection and clinical and morphological indicators of the tumor process, in particular the relationship of HPV-negative CC with age and stage of the disease; HPV infection with several genotypes and HPV genotype – with the histological type of tumor; VL – with age, stage and histological type of tumor. Significant associative connections have been established between the molecular genetic parameters of the virus itself: genotype and level of VL, genotype and integration of HPV DNA into the host genome, as well as a negative linear correlation between VL and the degree of integration.

Conclusion. The obtained data on the relationship between the molecular and genetic parameters of HPV infection and traditional prognostic factors can become the basis for further research on the development of prognostic models for the purpose of personalizing multimodal treatment programs.

About the Authors

L. S. Mkrtchian
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Liana S. Mkrtchian – Dr. Sci. (Med.), leading researcher, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-5027-5331, SPIN: 3352-0814, AuthorID: 147713, ResearcherID: JBJ-0493-2023, Scopus Author ID: 6601999343


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



V. I. Kiseleva
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Valentina I. Kiseleva – Cand. Sci. (Biol.), leading researcher, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0003-3565-1981, SPIN: 2865-4070, AuthorID: 81608, ResearcherID: T-1073-2017, Scopus Author ID: 7004413804


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



L. I. Krikunova
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Lyudmila I. Krikunova – Dr. Sci. (Med.), professor, chief researcher, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0003-1842-156X, SPIN: 2845-6710, AuthorID: 93505, ResearcherID: JCT-3165-2023, Scopus Author ID: 6506081959


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



B. V. Boyko
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Boris V. Boyko – PhD Student, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0009-0009-6821-5335, ResearcherID: JDC-4676-2023


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



V. R. Gusarova
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Victoria R. Gusarova – PhD student, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-7819-2730, ResearcherID: HMD-3406-2023


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



G. P. Bezyaeva
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Galina P. Bezyaeva – research associate, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-4942-6892, SPIN: 8900-4710, AuthorID: 87889, ResearcherID: JFJ-8132-2023, Scopus Author ID: 6506415163


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



L. V. Panarina
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Larisa V. Panarina – research associate, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0009-0001-9237-2869, SPIN: 9602-8908, AuthorID: 113918, ResearcherID: JFJ-8238-2023, Scopus Author ID: 6506225026


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



S. A. Ivanov
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; Peoples Friendship University of Russia
Russian Federation

Sergei A. Ivanov – Dr. Sci. (Med.), professor, corresponding member of the Russian Academy of Sciences (RAS), director of A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation; professor of the Department of Oncology and Radiology named after V. P. Kharchenko at the Medical Institute, Peoples Friendship University of Russia, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0001-7689-6032, SPIN: 4264-5167, AuthorID: 710405, ResearcherID: N-8221-2017, Scopus Author ID: 16070399200


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



A. D. Kaprin
P. A. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; National Medical Research Radiological Centre; Peoples Friendship University of Russia
Russian Federation

Andrey D. Kaprin – Dr. Sci. (Med.), professor, Academician of the Russian Academy of Sciences, Academician of the Russian Academy of Education, director of P. A. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Moscow, Russian Federation; general director of National Medical Research Radiological Centre, Obninsk, Russian Federation; head of the Department of Oncology and Radiology named after V. P. Kharchenko at the Medical Institute, Peoples Friendship University of Russia, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0001-8784-8415, SPIN: 1759-8101, AuthorID: 96775, ResearcherID: K-1445-2014, Scopus Author ID: 6602709853


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



I. A. Zamulaeva
A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Irina A. Zamulaeva – Dr. Sci. (Biol.), professor, head of the Department of Radiational Biochemistry, A. F. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-6136-8445, SPIN: 9542-6211, AuthorID: 87777, ResearcherID: R-4906-2016, Scopus Author ID: 6603693422


Competing Interests:

Ivanov S. A., Kaprin A. D. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest



References

1. Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019 Jan 12;393(10167):169–182. https://doi.org/10.1016/S0140-6736(18)32470-X

2. Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020 Feb;8(2):e191–e203. https://doi.org/10.1016/S2214-109X(19)30482-6

3. Злокачественные новообразования в России в 2021 году (заболеваемость и смертность). Под ред. А. Д. Каприна, В. В. Старинского, А. О. Шахзадовой. М.: МНИОИ им. П. А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России. 2021, 252 с.

4. Choi S, Ismail A, Pappas-Gogos G, Boussios S. HPV and Cervical Cancer: A Review of Epidemiology and Screening Uptake in the UK. Pathogens. 2023 Feb 11;12(2):298. https://doi.org/10.3390/pathogens12020298

5. Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, et al. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020 Oct 1;383(14):1340–1348. https://doi.org/10.1056/NEJMoa1917338

6. Li M, Du X, Lu M, Zhang W, Sun Z, Li L, et al. Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing, China. J Med Virol. 2019 Mar;91(3):473–481. https://doi.org/10.1002/jmv.25331

7. Zhou HL, Zhang W, Zhang CJ, Wang SM, Duan YC, Wang JX, et al. Prevalence and distribution of human papillomavirus genotypes in Chinese women between 1991 and 2016: A systematic review. J Infect. 2018 Jun;76(6):522–528. https://doi.org/10.1016/j.jinf.2018.02.008

8. Zhang J, Cheng K, Wang Z. Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis. Arch Gynecol Obstet. 2020 Dec;302(6):1329–1337. https://doi.org/10.1007/s00404-020-05787-w

9. De Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov;11(11):1048–1056. https://doi.org/10.1016/S1470-2045(10)70230-8

10. Höhn AK, Brambs CE, Hiller GGR, May D, Schmoeckel E, Horn LC. 2020 WHO Classification of Female Genital Tumors. Geburtshilfe Frauenheilkd. 2021 Oct;81(10):1145–1153. https://doi.org/10.1055/a-1545-4279

11. Park KJ, Selinger CI, Alvarado-Cabrero I, Duggan MA, Kiyokawa T, Mills AM, et al. Dataset for the Reporting of Carcinoma of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR). Int J Gynecol Pathol. 2022 Nov 1;41(Suppl 1):S64–S89. https://doi.org/10.1097/PGP.0000000000000909

12. Xu X, Feng T, Li D, Lou H, Lan H. Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China. BMC Infect Dis. 2022 Dec 15;22(1):941. https://doi.org/10.1186/s12879-022-07888-0

13. Im SS, Wilczynski SP, Burger RA, Monk BJ. Early stage cervical cancers containing human papillomavirus type 18 DNA have more nodal metastasis and deeper stromal invasion. Clin Cancer Res. 2003 Sep 15;9(11):4145–4150.

14. Ma X, Yang M. The correlation between high-risk HPV infection and precancerous lesions and cervical cancer. Am J Transl Res. 2021;13(9):10830–10836.

15. Zuo J, Huang Y, An J, Yang X, Li N, Huang M, et al. Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a long-term follow-up. Chin J Cancer Res. 2019 Apr;31(2):389–399. https://doi.org/10.21147/j.issn.1000-9604.2019.02.13

16. Мкртчян Л. С. Химиолучевое лечение местнораспространенного рака шейки матки и факторы прогноза: дис. ... д-ра мед. наук. Обнинск, 2020, 335 с. EDN: BJWUMO

17. Каприн А.Д., Киселева В.И., Мкртчян Л.С, Замулаева И. А., Шипулина О. Ю., Крикунова Л. И. Способ прогнозирования клинического исхода местно-распространенных форм рака шейки матки. Патент РФ № 2674675. Заявление: 07.02.2018 г.; Опубликовано: 12.12.2018 г.

18. Чуруксаева О. Н. Повышение эффективности лечения больных местнораспространенным раком шейки матки: дис. … д-ра мед. наук. Томск, 2013, 280 с.

19. Tjalma WA, Fiander A, Reich O, Powell N, Nowakowski AM, Kirschner B, et al. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe. Int J Cancer. 2013 Feb 15;132(4):854–867. https://doi.org/10.1002/ijc.27713

20. Шипулина О. Ю. Эпидемиологические особенности и меры профилактики онкогинекологической патологии папилломавирусной этиологии: автореф. дис … канд. мед. наук. М., 2013, 24 с.

21. Pilch H, Günzel S, Schäffer U, Tanner B, Brockerhoff P, Maeurer M, et al. The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic parameters and prognostic significance: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University. Int J Gynecol Cancer. 2001;11(1):39–48. https://doi.org/10.1046/j.1525-1438.2001.011001039.x

22. Okonogi N, Kobayashi D, Suga T, Imai T, Wakatsuki M, Ohno T, et al. Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer. Oncol Lett. 2018 Jan;15(1):459–466. https://doi.org/10.3892/ol.2017.7327

23. Tong SY, Lee YS, Park JS, Namkoong SE. Human papillomavirus genotype as a prognostic factor in carcinoma of the uterine cervix. Int J Gynecol Cancer. 2007;17(6):1307–1313. https://doi.org/10.1111/j.1525-1438.2007.00933.x

24. Na J, Li Y, Wang J, Wang X, Lu J, Han S. The correlation between multiple HPV infections and the occurrence, development, and prognosis of cervical cancer. Front Microbiol. 2023;14:1220522. https://doi.org/10.3389/fmicb.2023.1220522

25. Zhang L, Bi Q, Deng H, Xu J, Chen J, Zhang M, et al. Human papillomavirus infections among women with cervical lesions and cervical cancer in Eastern China: genotype-specific prevalence and attribution. BMC Infect Dis. 2017 Jan 31;17(1):107. https://doi.org/10.1186/s12879-017-2223-1

26. Ibragimova MK, Tsyganov MM, Karabut IV, Churuksaeva ON, Shpileva ON, Bychkov VA, et al. Integrative and episomal forms of genotype 16 of human papillomavirus in patients with cervical intraepithelial neoplasia and cervical cancer. Vopr Virusol. 2016 Dec 28;61(6):270–274. https://doi.org/10.18821/0507-4088-2016-61-6-270-274

27. Kim JY, Park S, Nam BH, Roh JW, Lee CH, Kim YH, et al. Low initial human papilloma viral load implicates worse prognosis in patients with uterine cervical cancer treated with radiotherapy. J Clin Oncol. 2009 Oct 20;27(30):5088–5093. https://doi.org/10.1200/JCO.2009.22.4659

28. Shukla S, Mahata S, Shishodia G, Pande S, Verma G, Hedau S, et al. Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer. Indian J Med Res. 2014 Apr;139(4):531–543.

29. Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W, Jiang B, et al. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2014 Feb;24(2):185–199. https://doi.org/10.1101/gr.164806.113

30. Huang SS, Hao DZ, Zhang Y, Liu HM, Shan WS. Progress in studies of the mechanisms and clinical diagnosis of cervical carcinoma associated with genomic integration of high-risk human papillomavirus DNA. Yi Chuan. 2017 Sep 20;39(9):775–783. https://doi.org/10.16288/j.yczz.17-151

31. Li H, Yang Y, Zhang R, Cai Y, Yang X, Wang Z, et al. Preferential sites for the integration and disruption of human papillomavirus 16 in cervical lesions. J Clin Virol. 2013 Apr;56(4):342–347. https://doi.org/10.1016/j.jcv.2012.12.014

32. Kiseleva VI, Mkrtchyan LS, Ivanov SA, Lyubina LV, Bezyaeva GP, Panarina LV, et al. The Presence of Human Papillomavirus DNA Integration is Associated with Poor Clinical Results in Patients with Third-Stage Cervical Cancer. Bull Exp Biol Med. 2019 Nov;168(1):87–91. https://doi.org/10.1007/s10517-019-04654-2

33. Nambaru L, Meenakumari B, Swaminathan R, Rajkumar T. Prognostic significance of HPV physical status and integration sites in cervical cancer. Asian Pac J Cancer Prev. 2009;10(3):355–360.

34. De Boer MA, Jordanova ES, Kenter GG, Peters AA, Corver WE, Trimbos JB, et al. High human papillomavirus oncogene mRNA expression and not viral DNA load is associated with poor prognosis in cervical cancer patients. Clin Cancer Res. 2007 Jan 1;13(1):132–138. https://doi.org/10.1158/1078-0432.CCR-06-1568

35. Киселева В. И., Крикунова Л. И., Любина Л. В., Мкртчян Л. С., Безяева Г. П., Панарина Л. В. и др. Количественная нагрузка вируса папилломы человека 16 типа и прогнозирование эффективности лечения рака шейки матки. Радиация и риск (бюллетень национального радиационно-эпидемиологического регистра). 2011;20(2):58–63. EDN: NYGSPX


Review

For citations:


Mkrtchian L.S., Kiseleva V.I., Krikunova L.I., Boyko B.V., Gusarova V.R., Bezyaeva G.P., Panarina L.V., Ivanov S.A., Kaprin A.D., Zamulaeva I.A. Status and molecular genetic parameters of papillomavirus infection: individual characteristics and associative links with clinical and morphological factors of cervical cancer. South Russian Journal of Cancer. 2024;5(2):53-65. https://doi.org/10.37748/2686-9039-2024-5-2-6. EDN: qmhkdo

Views: 380


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2686-9039 (Online)