Research Article

Correlation Between E6 and E7 Oncogene Mutation Human Papilloma Virus High Risk Type 16 with Retinoblastoma Protein Expression in Cervical Cancer

I Nyoman Bayu Mahendra
Udayana University, Indonesia
Erliana Fani
Udayana University, Indonesia
* Corresponding author
I Nyoman Gede Budiana
Udayana University, Indonesia
I Wayan Megadhana
Udayana University, Indonesia
Made Bagus Dwi Aryana
Udayana University, Indonesia
I Gde Sastra Winata
Udayana University, Indonesia
DOI icon 10.24018/ejmed.2022.4.6.1531

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Submitted 2022-10-02
Published 2022-12-08

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Introduction: The E6 and E7 oncoproteins of high-risk Human Papillomavirus (HPV) have crucial roles in cervical cancer pathogenesis by inhibiting p53 and retinoblastoma protein (pRb) which are tumor suppressor genes. Genetic sequence mutations of E6 and E7 oncogenes can affect E6/E7 protein functions that will change E7-pRB interaction. Furthermore, this condition will influence progression cervical cancer progression in several intratypic variants of high-risk HPV type 16.

Methods: A cross-sectional study was conducted from September 2020-September 2021, at the Obstetrics and Gynecology Outpatient Clinic, Prof Dr I. G. N. G. Ngoerah General Hospital. Consecutive sampling was taken by collecting cervical cancer tissue followed by isolation, amplification, and gene sequencing to assess E6 and E7 mutations. The expression of pRb was measured by immunohistochemical staining (IHC).

Results: From 100 cervical cancer subjects, 31 subjects were found HPV16 positive (19 wildtype and 12 mutants). The proportion of E6 and E7 mutants was 25.8% and 12.9% respectively. This study shows that T27C/F9F; A360G/E120E and G371A/R124K variants were found on E6 oncogene mutations, meanwhile, A86C/N29T; A86G/N29S; C229T/R77C and T285C/S95S variants were detected on E7 oncogene mutations. The types of E6 mutations were T27C (16.1%), A360G (6.4%) and G371A (1 subject; 3.2%). In addition, pRb expression was stronger in mutant group than wild-type group 60.5% vs. 53%. There was no correlation between retinoblastoma protein expression and mutations E6/E7 oncogene HPV Type 16 (PR 0.22; 95% CI 0.03-1.6; p value 0.10).

Conclusions: In cervical cancer, there is no significant difference between the expression of retinoblastoma protein in mutant vs wildtype E6 and E7 oncogene HPV16.

Keywords: Cervical cancer, HPV mutation, oncogene E6, oncogene E7, retinoblastoma protein

References

  1. Steben M, Duarte-Franco E. Human papillomavirus infection: epidemiology and pathophysiology. Gynecol Oncol. 2007; 107(2 Suppl 1): S2-5.
    DOI  |   Google Scholar
  2. Ganti K, Broniarczyk J, Manoubi W, Massimi P, Mittal S, Pim D, et al. The Human Papillomavirus E6 PDZ binding motif: from life cycle to malignancy. Viruses. 2015; 7(7): 3530-51.
    DOI  |   Google Scholar
  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 398-420.
    DOI  |   Google Scholar
  4. Aricandana PAE, Budiana ING. Characteristic of patients with cervival cancer in Sanglah General Hospital Denpasar. International Journal of Science and Research (IJSR). 2021; 10(7): 1021-1024.
     Google Scholar
  5. Egawa N, Egawa K, Griffin H, Doorbar J. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia. Viruses. 2015; 7(7): 3863-90.
    DOI  |   Google Scholar
  6. Wulandari D, Rachmadi L, Sudiro TM. Phylogenetic analysis and predicted functional effect of protein mutations of E6 and E7 HPV16 strains isolated in Indonesia. Medical Journal of Indonesia. 2015; 24(4): 197-205.
    DOI  |   Google Scholar
  7. Uchida C. The retinoblastoma protein: functions beyond the G1-S regulator. Curr Drug Targets. 2012; 13(13): 1622-1632.
    DOI  |   Google Scholar
  8. Engel BE, Cress WD, Santiago-Cardona PG. The retinoblastoma protein: a master tumor suppressor acts as a link between cell cycle and cell adhesion. Cell Health Cytoskelet. 2015; 7: 1-10.
    DOI  |   Google Scholar
  9. Zhe X, Xin H, Pan Z, Jin F, Zheng W, Li H, et al. Genetic variations in E6, E7 and the long control region of human papillomavirus type 16 among patients with cervical lesions in Xinjiang, China. Cancer Cell Int. 2019; 19: 65.
    DOI  |   Google Scholar
  10. Guilford JP. Fundamental statistics in psychology and education. New York: McGraw Hill. 1942: 145.
     Google Scholar
  11. Farahat FM, Faqih NT, Alharbi RS, Mudarris RI, Alshaikh SA, Al-Jifree HM. Epidemiological characteristics of cervical cancer in a tertiary care hospital, western Saudi Arabia: A retrospective record-based analysis from 2002-2018. Saudi Med J. 2021; 42(3): 338-341.
    DOI  |   Google Scholar
  12. Putri AR, Khaerunnisa S, Yuliati I. Cervical cancer risk factors association in patients at the gynecologic-oncology clinic of dr. soetomo hospital Surabaya. Indonesian Journal of Cancer. 2019; 13(4): 104-109.
    DOI  |   Google Scholar
  13. Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006; 6(7): 438-46.
    DOI  |   Google Scholar
  14. Green WD, Beck MA. Obesity Impairs the Adaptive Immune Response to Influenza Virus. Ann Am Thorac Soc. 2017; 14(Supplement_5): S406-S409.
    DOI  |   Google Scholar
  15. Milner JJ, Beck MA. The impact of obesity on the immune response to infection. Proc Nutr Soc. 2012; 71(2): 298-306.
    DOI  |   Google Scholar
  16. Bajos N, Wellings K, Laborde C, Moreau C, CSF Group. Sexuality and obesity, a gender perspective: results from French national random probability survey of sexual behaviours. BMJ. 2010; 340: c2573.
    DOI  |   Google Scholar
  17. Gunge VB, Juul KE, van den Brule AJC, Iftner T, Kjær SK. Sexual inactivity and occurrence of STIs in relation to weight status in women: Two large population-based studies. Women Health. 2018; 58(7): 790-805.
    DOI  |   Google Scholar
  18. Quek SC, Lim BK, Domingo E, Soon R, Park JS, Vu TN, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia across 5 countries in Asia. Int J Gynecol Cancer. 2013; 23(1): 148-56.
    DOI  |   Google Scholar
  19. de Boer MA, Peters LA, Aziz MF, Siregar B, Cornain S, Vrede MA, et al. Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands. Gynecol Oncol. 2004; 94(2): 488-94.
    DOI  |   Google Scholar
  20. Qmichou Z, Khyatti M, Berraho M, Ennaji MM, Benbacer L, Nejjari C, et al. Analysis of mutations in the E6 oncogene of human papillomavirus 16 in cervical cancer isolates from Moroccan women. BMC Infect Dis. 2013; 13: 378.
    DOI  |   Google Scholar
  21. Radhakrishna Pillai M, Sreevidya S, Pollock BH, Jayaprakash PG, Herman B. Human papillomavirus type 16 E6 and E7 gene variations in Indian cervical cancer. Gynecol Oncol. 2002; 87(3): 268-273.
    DOI  |   Google Scholar
  22. Boumba LM, Assoumou SZ, Hilali L, Mambou JV, Moukassa D, Ennaji MM. Genetic variability in E6 and E7 oncogenes of human papillomavirus Type 16 from Congolese cervical cancer isolates. Infect Agent Cancer. 2015; 10: 15.
    DOI  |   Google Scholar
  23. Salcedo M, Taja L, Utrera D, Chávez P, Hidalgo A, Pérez C, et al. Changes in retinoblastoma gene expression during cervical cancer progression. Int J Exp Pathol. 2002; 83(6): 275-86.
    DOI  |   Google Scholar
  24. Sen P, Ganguly P, Ganguly N. Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer. Oncol Lett. 2018; 15(1): 11-22.
    DOI  |   Google Scholar
  25. Zine El Abidine A, Tomaić V, Bel Haj Rhouma R, Massimi P, Guizani I, Boubaker S, et al. A naturally occurring variant of HPV-16 E7 exerts increased transforming activity through acquisition of an additional phospho-acceptor site. Virology. 2017; 500: 218-225.
    DOI  |   Google Scholar
  26. Wang H, Zhao Y, Chen M, Cui J. Identification of Novel Long Non-coding and Circular RNAs in Human Papillomavirus-Mediated Cervical Cancer. Front Microbiol. 2017; 8: 1720.
    DOI  |   Google Scholar


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