Detection of Human Papillomavirus DNA and E6/E7 mRNA from HPV Genotypes 16, 18, 31 and 33 in Histologically Confirmed Cases of Cervical Cancer and Precancerous Lesions in Burkina Faso
Introduction: Cervical cancer, caused by persistent high-risk human papillomavirus (HPV)
infection, remains a global public health problem. The cellular transformation
and maintenance of the malignant phenotype of these HPVs are attributed to the
viral oncoproteins E6 and E7. Objective: This study aims to detect the
presence of human papillomavirus DNA and E6/E7 oncoprotein mRNA of HPV
genotypes 16, 18, 31 and 33 in cases of cervical cancer and precancerous
lesions, histologically confirmed in Burkina Faso. Methods: This
descriptive cross-sectional study focused on cases of cervical cancer and
high-grade intraepithelial neoplasia (CIN) and was conducted from June to
December 2022. One hundred (100) samples of fixed and paraffin-embedded tissues
were collected from the pathological anatomy and cytology laboratories of
hospitals in the capital of Burkina Faso. High-risk human papillomavirus
(HR-HPV) DNA was detected using multiplex real-time PCR, while the presence of
E6 and E7 mRNA in cervical cancer and high-grade CIN samples was determined
using real-time Reverse Transcriptase-PCR (RT-PCR) with TaqMan probes. Results: The mean age of women diagnosed with cervical cancer and high-grade CIN was
50.81 ± 13.65 years, ranging from 22 to 82 years. Cervical cancer and
high-grade CIN were positive for at least one high-risk human papillomavirus
(HR-HPV) in 80% of cases. The most prevalent genotypes observed were HPV16, 18,
31, and 33, collectively accounting for 70.08% of cases. Of the 89 samples that
tested positive for HR-HPV genotypes 16, 18, 31, and 33, 88 (98.88%; 95% CI: [94.58 - 99.94]) were also
positive for the presence of mRNA encoding the E6 and E7 oncoproteins of HPV16,
18, 31, and 33. Conclusion: In the presence of HPV DNA, testing for E6
and E7 oncoprotein mRNA could serve as a promising biomarker and valuable tool
for improved assessment of the progression to cervical cancer.
References
[1]
Alain, S., Hantz, S. and Denis, F. (2010) Papillomavirus: Les virus et la physiopathologie de l’infection. Médecine Thérapeutique/Pédiatrie, 13, 5-19.
[2]
Dunne, E.F., Unger, E.R., Sternberg, M., McQuillan, G., Swan, D.C., Patel, S.S. and Markowitz, L.E. (2007) Prevalence of HPV Infection among Females in the United States. Journal of American Medical Association, 297, 813-819.
https://doi.org/10.1001/jama.297.8.813
[3]
Nubia, M. and Jacquard, A. (2008) Quelles données épidémiologiques sont nécessaires pour la mise en place de la vaccination contre le papillomavirus humain? La Presse Médicale, 37, 1377-1390. https://doi.org/10.1016/j.lpm.2008.04.008
[4]
Bruni, L., Diaz, M., Castellsague, X., Ferrer, E., Bosch, F.X. and de Sanjosé, S. (2010) Cervical Human Papillomavirus Prevalence in 5 Continents: Meta-Analysis of 1 Million Women with Normal Cytological Findings. The Journal of Infectious Diseases, 202, 1789-1799. https://doi.org/10.1086/657321
[5]
Faye, B, Gueye, S.A.A.M., Tine, J.A.D., Sarr, H. and Dièye, A. (2022) Molecular Genotyping of Human Papillomaviruses (HPV) in HIV+ and HIV− Women in Senegal. American Journal of Molecular Biology, 12, 54-66.
https://www.scirp.org/journal/ajmb
https://doi.org/10.4236/ajmb.2022.122006
[6]
Kabre, K.M., Ouermi, D., Zohoncon, T.M., Traore, F.P.W, Gnoumou, O.P.P., Ouedraogo, R.A., Yonli, A.T., Bado, P., Ouedraogo, P., Ouedraogo, T.C., Yelemkoure, T.E., Kuassi-Kpede, P.A., Obiri-Yeboah, D., Ouedraogo, C.M.R. and Simpore, J. (2022) Molecular Epidemiology of Human Papillomavirus in Pregnant Women in Burkina Faso. Biomolecular Concepts, 13, 334-340.
https://doi.org/10.1515/bmc-2022-0026
[7]
Munoz, N., Castellsagué, X., de González, A.B. and Gissmann, L. (2006) Chapter 1: HPV in the Etiology of Human Cancer. Vaccine, 24, S1-S10.
https://doi.org/10.1016/j.vaccine.2006.05.115
[8]
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. https://doi.org/10.3322/caac.21492
[9]
Chuang, L.T., Temin, S., Camacho, R., Duenas-Gonzalez, A., Feldman, S., Gultekin, M., et al. (2016) Management and Care of Women with Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline. Journal of Global Oncology, 2, 311-340.
https://doi.org/10.1200/JGO.2016.003954
[10]
Randall, T.C. and Ghebre, R. (2016) Challenges in Prevention and Care Delivery for Women with Cervical Cancer in Sub-Saharan Africa. Frontiers in Oncology, 6, Article 160. https://doi.org/10.3389/fonc.2016.00160
[11]
Gissmann, L., Boshart, M., Durst, M., Ikenberg, H., Wagner, D. and Zur, H. (1984) Presence of Human Papillomavirus in Genital Tumors. The Journal of Investigative Dermatology, 83, 17-19. https://doi.org/10.1038/jid.1984.16
[12]
Münger, K. and Howley, P.M. (2002) Human Papilloma Virus Immortalization and Transformation Functions. Virus Research, 89, 213-228.
https://doi.org/10.1016/S0168-1702(02)00190-9
[13]
Filippova, M., Parkhurst, L. and Duerksen-hughes, P.J. (2004) The Human Papillomavirus 16 E6 Protein Binds to Fas-Associated Death Domain and Protects Cells from Fas-Triggered Apoptosis. The Journal of Biological Chemistry, 279, 25729-25744.
https://doi.org/10.1074/jbc.M401172200
[14]
Frolov, M.V. and Dyson, N.J. (2004) Molecular Mechanisms of E2F-Dependent Activation and pRB-Mediated Repression. Journal of Cell Science, 117, 2173-2181.
https://doi.org/10.1242/jcs.01227
[15]
Rangarajan, A., Syal, R., Selvarajah, S., Chakrabarti, O., Sarin, A. and Krishna, S. (2001) Activated Notch1 Signaling Cooperates with Papillomavirus Oncogenes in Transformation and Generates Resistance to Apoptosis on Matrix Withdrawal through PKB/Akt. Virology, 286, 23-30. https://doi.org/10.1006/viro.2001.0867
[16]
Kusakabe, M., Taguchi, A., Sone, K., Mori, M. and Osuga, Y. (2023) Carcinogenesis and Management of Human Papillomavirus-Associated Cervical Cancer. International Journal of Clinical Oncology, 28, 965-974.
https://doi.org/10.1007/s10147-023-02337-7
[17]
Malla, R. and Kamal, M.A. (2021) E6 and E7 Oncoproteins: Potential Targets of Cervical Cancer. Current Medicinal Chemistry, 28, 8163-8181.
https://doi.org/10.2174/0929867327666201111145546
[18]
Wang, Y., Springer, S., Mulvey, C.L., Silliman, N., Schaefer, J., Sausen, M., et al. (2015) Detection of Somatic Mutations and HPV in the Saliva and Plasma of Patients with Head and Neck Squamous Cell Carcinomas. Science Translational Medicine, 7, 293ra104. https://doi.org/10.1126/scitranslmed.aaa8507
[19]
Zhang, J., Zhang, Y. and Zhang, Z. (2018) Prevalence of Human Papillomavirus and Its Prognostic Value in Vulvar Cancer: A Systematic Review and Meta-Analysis. PLOS ONE, 13, e0204162. https://doi.org/10.1371/journal.pone.0204162
[20]
Nikolic, N., Basica, B., Mandic, A., Surla, N., Gusman, V., Medic, D., Petrovic, T., Strbac, M. and Petrovic, V. (2023) E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women. Diagnostics, 13, Article 917. https://doi.org/10.3390/diagnostics13050917
[21]
Derbie, A., Mekonnen, D., Woldeamanuel, Y., Ostade, X.V. and Abebe, T. (2020) HPV E6/E7 mRNA Test for the Detection of High Grade Cervical Intraepithelial Neoplasia (CIN2+): A Systematic Review. Infectious Agents and Cancer, 15, Article No. 9. https://doi.org/10.1186/s13027-020-0278-x
[22]
Ouédraogo, C., Zohoncon, T.M., Traoré, E.M.A., Ouattara, S., Bado, P., Ouedraogo, C.T., Djigma, F.W., Ouermi, D., Obiri-Yeboah, D., Lompo, O., Akpona, S.A. and Simpore, J. (2016) Distribution of High-Risk Human Papillomavirus Genotypes in Precancerous Cervical Lesions in Ouagadougou, Burkina Faso. Open Journal of Obstetrics and Gynecology, 6, 196-204. http://www.scirp.org/journal/ojog
https://doi.org/10.4236/ojog.2016.64025
[23]
Zohoncon, T.M., Bado, P., Ouermi, D., Traoré, E.M.A., Ouattara, S., Djigma, F.W., Traore, I.M.A., Yonli, A.T., Obiri-Yeboah, D., Ouédraogo, C., Akpona, S.A., Lompo, O. and Simpore, J. (2016a) Molecular Characterization of High-Risk Human Papillomavirus Genotypes Involved in Invasive Cervical Cancer from Formalin-Fixed, Paraffin Tissues in Ouagadougou, Burkina Faso. International Journal of Current Research, 8, 39314-39318.
[24]
Zohoncon, T.M., Ouédraogo, T.C., Brun, L.V.C., Obiri-Yeboah, D., Djigma, W.F., Kabibou, S., Ouattara, S., Gomina, M., Yonli, A.T., Bazié, V.J.T.E., Ouédraogo, C., Lompo, O., Akpona, S.A. and Simpore, J. (2016) Molecular Epidemiology of High-Risk Human Papillomavirus in High-Grade Cervical Intraepithelial Neoplasia and in Cervical Cancer in Parakou, Republic of Benin. Pakistan Journal of Biological Sciences, 19, 49-56. https://doi.org/10.3923/pjbs.2016.49.56
[25]
Sanou-Lamien, A., Ki, R., Zohoncon-Kone, T.M., Ouedraogo, A.S., Konsegre, V., Ido, F., Savadogo, I., Traore-Millogo, F.D. and Lompo, O.M. (2018) Aspects socio-démographiques et histopathologiques des lésions précancéreuses de haut grade et cancéreuses du col utérin et caractérisation moléculaire des HPV oncogènes impliqués à Ouagadougou (Burkina Faso). Revue Africaine de Pathologie, 17, 48-55.
[26]
Valenca, J.E.C., Goncalves, A.K., da Silva, I.D.C.G., Junior, J.E., da Silva, T.T., Bruneska, D. and de Alencar Ximenes, R.A. (2016) High Risk HPV E6/E7 Oncoprotein Expression in Women with High Grade Squamous Intraepithelial Lesion. Revista Brasileira de Ginecologia e Obstetricia, 38, 154-159.
https://doi.org/10.1055/s-0036-1580713
[27]
Zohoncon, T.M., Djigma, W.F., Ouattara, A.K., Traore, I.M., Ouedraogo, R.A., Traore, E.M., Bado, P., Ouedraogo, T.C., Diarra, B., Ilboudo, M., Capo-Chichi, C.D., Obiri-Yeboah, D., Karou, S.D., Nayama, M., Horo, A., Kouakou, K.P., Gomina, M., Ouattara, S., Sanni, A., Simon, A., Ouedraogo, C. and Simpore J. (2020) Mapping of Fourteen High-Risk Human Papillomavirus Genotypes by Molecular Detection in Sexually Active Women in the West African Sub-Region. International Journal of Genetics and Molecular Biology, 12, 11-21.
[28]
Zohoncon, T.M., Ouedraogo, R.A., Djigma, F.W., Traore, L., Ouedraogo, T.C., Ilboudo, M., Ilboudo, R., Salambanga, C., Guigma, S.P., Tovo, S.F., Traore, M.A.E., Bado, P., Kande, A., Bisseye, C., Ouattara, A.K., Traore, I.M.A, Ouermi, D, Sagna, T., Yonli, A.T., Nadembega, W.M.C., Obiri-Yeboah, D., Gyebre, Y.M.C., Lompo, O.M., Ouedraogo, C.M.R. and Simpore, J. (2022) Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso. In: Budak, M. and Rajkumar, R., Eds., Molecular Mechanisms in Cancer (pp. 1-18). IntechOpen.
[29]
Clifford, G.M., Tully, S. and Franceschi, S. (2017) Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis from HPV Infection to Cervical Cancer. Clinical Infectious Diseases, 64, 1228-1235.
https://doi.org/10.1093/cid/cix135
[30]
OMS (2022) Le Burkina Faso introduit le vaccin contre le HPV (papillomavirus Humain) responsable du cancer du col de l’utérus.
https://www.afro.who.int/fr/countries/burkina-faso/news/le-burkina-faso-introduit-le-vaccin-contre-le-hpv-papillomavirus-humain-responsable-du-cancer-du-col
[31]
Argyri, E., Tsimplaki, E., Daskalopoulou, D., Stravopodis, D.J., Kouikoglou, O., Terzakis, E. and Panotopoulou, E. (2013) E6/E7 mRNA Expression of High-Risk HPV Types in 849 Greek Women. Anticancer Research, 33, 4007-4012.
[32]
Yu, T. and Wang, C. (2022) Clinical Significance of Detection of Human Papilloma Virus DNA and E6/E7 mRNA for Cervical Cancer Patients. Cellular and Molecular Biology (Noisy-le-Grand), 67, 155-159. https://doi.org/10.14715/cmb/2021.67.6.21
[33]
Cao, L., He, P., Yang, J., Long, X., Chen, Y., Yan, L. and Zhou, D. (2022) Predictive Value of HPV E6/E7 mRNA Detection on the Outcome of Cervical LSIL. Evidence-Based Complementary and Alternative Medicine, 2022, Article ID: 8747919.
https://doi.org/10.1155/2022/8747919
