Supplementary Files
How to Cite
Downloads
Métricas Alternativas
Dimensions
Abstract
Cervical cancer is the main cause of mortality among women in populations with low and medium human development index. The infection with 14 genotypes of the high-risk human papillomavirus (HR-HPV) is the main cause of this cancer. Prophylactic vaccines prevent this infection if they are applied before the onset of sexual activity. Unvaccinated women should be screened with the HR-HPV test and receive the histopathological diagnosis and timely treatment. About 20% of women are HR-HPV positive, but very few have potentially malignant lesions. Women infected with HPV16 or 18 genotypes or women with European ancestry infected with Native American variants of HPV 16 have a higher risk of cancer. Also, those with a history of use of hormonal contraceptives and cigarette smoking. These factors seem to contribute to an increase in the expression of the HR-HPV oncoproteins E6 and E7, which leads to the deregulation of cell cycle control and finally to cancer. We present here the state of the art of the carcinogenic mechanisms of HPV-AR emphasizing the role of the E6 and E7 proteins, as well as the results of our study on the HPV16 or 18 genotyping, the positivity rate of the p16 and ki67 proteins, and the bioinformatic evaluation of the aberrant expression of miRNAs and their correlation with the degree of cervical lesions. These data contribute to validate the clinical potential of these biomarkers for the detection of potentially malignant lesions of the cervix.
References
Antinore, M. J., Birrer, M. J., Patel, D., Nader, L., McCance, D. J. (1996). The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors. EMBO J. 15 (8): 1950-1960. https://www.ncbi.nlm.nih.gov/pubmed/8617242
Arbyn, M., Ronco, G., Cuzick, J., Wentzensen, N., Castle, P. E. (2009). How to evaluate emerging technologies in cervical cancer screening? Int J Cancer. 125 (11): 2489-2496. Doi:10.1002/ijc.24774
Baena, A., Guevara, E., Almonte, M., Arias-Stella, J., Sasieni, P., Sánchez, G. I. (2017). Factors related to inter-observer reproducibility of conventional Pap smear cytology: A multilevel analysis of smear and laboratory characteristics. Cytopathology. 28 (3): 192-202. Doi: 10.1111/cyt.12410
Bergeron, C., Ikenberg, H., Sideri, M., Denton, K., Bogers, J., Schmidt, D., . . . Ridder, R. (2015). Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results. Cancer Cytopathol. 123 (6): 373-381. Doi: 10.1002/cncy.21542
Bergeron, C., Ronco, G., Reuschenbach, M., Wentzensen, N., Arbyn, M., Stoler, M., von Knebel Doeberitz, M. (2015).
The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: An update of
recent developments. Int J Cancer. 136 (12): 2741-2751. Doi: 10.1002/ijc.28900
Berumen, J., Ordóñez, R. M., Lazcano, E., Salmerón, J., Galván, S. C., Estrada, R. A., . . . Madrigal-de la Campa, A. (2001). Asian-American variants of human papillomavirus 16 and risk for cervical cancer: A case-control study.
J Natl Cancer Inst. 93 (17): 1325-1330. DOI: 10.1093/jnci/93.17.1325
Bosch, F. X., Lorincz, A., Munoz, N., Meijer, C. J., Shah, K. V. (2002). The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 55 (4): 244-265. DOI: 10.1136/jcp.55.4.244
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., Jemal, A. (2018). Global cancer statistics 2018:
GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. Doi: 10.3322/caac.21492
Burd, E. M. (2016). Human papillomavirus laboratory testing: The changing paradigm. Clin Microbiol Rev. 29 (2): 291-319. Doi: 10.1128/CMR.00013-15
Burk, R. D., Harari, A., Chen, Z. (2013). Human papillomavirus genome variants. Virology. 445 (1-2): 232-243. Doi:10.1016/j.virol.2013.07.018
Burk, R. D., Terai, M., Gravitt, P. E., Brinton, L. A., Kurman, R. J., Barnes, W. A., . . . Hildesheim, A. (2003). Distribution of human papillomavirus types 16 and 18 variants in squamous cell carcinomas and adenocarcinomas of the cervix. Cancer Res. 63 (21): 7215-7220. DOI: 14612516/Cancer Res.2003-09
Castle, P. E., Murokora, D., Perez, C., Alvarez, M., Quek, S. C., Campbell, C. (2017). Treatment of cervical intraepithelial lesions. Int J Gynaecol Obstet. 138 (Suppl 1): 20-25. Doi:10.1002/ijgo.12191
Castle, P. E., Stoler, M. H., Wright, T. C., Sharma, A., Wright, T. L., Behrens, C. M. (2011). Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: A subanalysis of the ATHENA study. Lancet Oncol. 12 (9): 880-890. Doi:10.1016/S1470-2045(11)70188-7
Clarke, M. A., Cheung, L. C., Castle, P. E., Schiffman, M., Tokugawa, D., Poitras, N., . . . Wentzensen, N. (2018). Five-year risk of cervical precancer following p16/ki-67dual-stain triage of HPV-positive women. JAMA Oncol. Doi:10.1001/jamaoncol.2018.4270 Colombian Ministry of Health (Ministerio de Salud y Protección Social). [Clinical Practice Guide (CPG) for the detection and management of precancerous cervical lesions]. In: Colombian Ministry of Health editor. Guia No GPC 2014-44. Bogota, Colombia.
Cornet, I., Gheit, T., Clifford, G. M., Combes, J. D., Dalstein, V., Franceschi, S., . . . Clavel, C. (2013). Human papillomavirus type 16 E6 variants in France and risk of viral persistence. Infect Agent Cancer. 8 (1): 4. Doi:10.1186/1750-9378-8-4
Cornet, I., Gheit, T., Franceschi, S., Vignat, J., Burk, R. D., Sylla, B. S., . . . Clifford, G. M. (2012). Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol. 86 (12): 6855- 6861. Doi:10.1128/jvi.00483-12
Cornet, I., Gheit, T., Iannacone, M. R., Vignat, J., Sylla, B. S., Del Mistro, A., . . . Clifford, G. M. (2013). HPV16 genetic variation and the development of cervical cancer worldwide. Br J Cancer. 108 (1): 240-244. Doi:10.1038/bjc.2012.508
de Boer, M. A., Peters, L. A., Aziz, M. F., Siregar, B., Cornain, S., Vrede, M. A., . . . Fleuren, G. J. (2004). Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands. Gynecol Oncol. 94 (2): 488-494. Doi:10.1016/j.ygyno.2004.05.037
de Sanjose, S., Quint, W. G., Alemany, L., Geraets, D. T., Klaustermeier, J. E., Lloveras, B., . . . Group, R. I. S. a. H. T. T. S. (2010). Human papillomavirus genotype attribution in invasive cervical cancer: A retrospective cross sectional worldwide study. Lancet Oncol. 11 (11):1048-1056. Doi:10.1016/S1470-2045(10)70230-8
de Villiers, E. M., Fauquet, C., Broker, T. R., Bernard, H. U., zur Hausen, H. (2004). Classification of papillomaviruses. Virology. 324 (1): 17-27. Doi:10.1016/j.virol.2004.03.033
Denny, L., de Sanjose, S., Mutebi, M., Anderson, B. O., Kim, J., Jeronimo, J., . . . Sankaranarayanan, R. (2017). Interventions to close the divide for women with breast and cervical cancer between low-income and middle-income countries and high-income countries. Lancet. 389 (10071): 861-870. Doi:10.1016/S0140-6736(16)31795-0
Doorbar, J. (2018). Host control of human papillomavirus infection and disease. Best Pract Res Clin Obstet Gynaecol. 47: 27-41. Doi: 10.1016/j.bpobgyn.2017.08.001
Doorbar, J., Egawa, N., Griffin, H., Kranjec, C., Murakami, I. (2015). Human papillomavirus molecular biology and disease association. Rev Med Virol, 25 Suppl 1, 2-23. Doi:10.1002/rmv.1822
Doorbar, J., Quint, W., Banks, L., Bravo, I. G., Stoler, M., Broker, T. R., Stanley, M. A. (2012). The biology and lifecycle of human papillomaviruses. Vaccine. 30 (Suppl 5): F55-70. Doi:10.1016/j.vaccine.2012.06.083
Dweep, H., & Gretz, N. (2015). miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 12 (8): 697. Doi: 10.1038/nmeth.3485
Eroschenko, V. P. (2008). Atlas of histology with functional correlation, female reproductive system. (Eleventh edition ed.). Philadelphia: Lippincott Williams & Wilkins. Finnen, R. L., Erickson, K. D., Chen, X. S., Garcea, R. L. (2003). Interactions between papillomavirus L1 and L2 capsid proteins. J Virol. 77 (8): 4818-4826. https://www.ncbi.nlm.nih.gov/pubmed/12663788.
Gaffikin, L., Lauterbach, M., Blumenthal, P. D. (2003). Performance of visual inspection with acetic acid for cervical cancer screening: A qualitative summary of evidence to date. Obstet Gynecol Surv. 58 (8): 543-550. Doi:10.1097/01.ogx.0000079632.98372.26
Glinge, C., Clauss, S., Boddum, K., Jabbari, R., Jabbari, J., Risgaard, B., Tfelt-Hansen, J. (2017). Stability of Circulating Blood-Based MicroRNAs - Pre-Analytic Methodological Considerations. PLoS One. 12 (2): e0167969. Doi:10.1371/journal.pone.0167969
Harden, M. E., & Munger, K. (2017). Human papillomavirus 16 E6 and E7 oncoprotein expression alters microRNA expression in extracellular vesicles. Virology. 508: 63-69. Doi: 10.1016/j.virol.2017.05.005
Herfs, M., Yamamoto, Y., Laury, A., Wang, X., Nucci, M. R., McLaughlin-Drubin, M. E., Crum, C. P. (2012). A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci USA. 109 (26): 10516-10521. Doi: 10.1073/pnas.1202684109
Hildesheim, A., Schiffman, M., Bromley, C., Wacholder, S., Herrero, R., Rodriguez, A., . . . Burk, R. D. (2001). Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst. 93 (4): 315-318.
Koliopoulos, G., Nyaga, V. N., Santesso, N., Bryant, A., Martin Hirsch, P. P., Mustafa, R. A., . . . Arbyn, M. (2017). Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev, 8, Cd008587. Doi: 10.1002/14651858.CD008587.pub2
Kori, M., & Yalcin Arga, K. (2018). Potential biomarkers and therapeutic targets in cervical cancer: Insights from the meta-analysis of transcriptomics data within network biomedicine perspective. PLoS One. 13 (7): e0200717. Doi: 10.1371/journal.pone.0200717
Li, M. Y., & Hu, X. X. (2015). Meta-analysis of microRNA expression profiling studies in human cervical cancer. Med Oncol. 32 (6): 510. Doi: 10.1007/s12032-015-0510-5.
Lopera, E. A., Baena, A., Flórez, V., Montiel, J., Duque, C., Ramírez, T., Sánchez, G. I. (2014). Unexpected inverse correlation between Native American ancestry and Asian American variants of HPV16 in admixed Colombian cervical cancer cases. Infect Genet Evol. 28: 339-348. Doi: 10.1016/j.meegid.2014.10.014
Luhn, P., Walker, J., Schiffman, M., Zuna, R. E., Dunn, S. T., Gold, M. A., Wentzensen, N. (2013). The role of co-factors in the progression from human papillomavirus infection to cervical cancer. Gynecol Oncol. 128 (2): 265-270. Doi: 10.1016/j.ygyno.2012.11.003
Mirabello, L., Yeager, M., Cullen, M., Boland, J. F., Chen, Z., Wentzensen, N., Schiffman, M. (2016). HPV16 Sublineage associations with histology-specific cancer risk using hpv whole-genome sequences in 3200 women. J Natl Cancer Inst. 108 (9): 108-116. Doi: 10.1093/jnci/djw100
Muñoz, N., Bosch, F. X., de Sanjosé, S., Herrero, R., Castellsagué, X., Shah, K. V., Group, I. A. f. R. o. C. M. C. C. S. (2003). Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 348 (6): 518-527. Doi: 10.1056/NEJMoa021641
Muñoz, N., Castellsagué, X., de González, A. B., Gissmann, L. (2006). Chapter 1: HPV in the etiology of human cancer. Vaccine. 24 (Suppl 3): S3/1-10. Doi: 10.1016/j.vaccine.2006.05.115
Münger, K., & Howley, P. M. (2002). Human papillomavirus immortalization and transformation functions. Virus Res.89 (2): 213-228.
Pim, D., & Banks, L. (2010). Interaction of viral oncoproteins with cellular target molecules: Infection with high- isk vs low-risk human papillomaviruses. Apmis. 118 (6-7): 471-493. Doi: 10.1111/j.1600-0463.2010.02618.x
Rodríguez, A. C., Schiffman, M., Herrero, R., Wacholder, S., Hildesheim, A., Castle, P. E., . . . Burk, R. (2008). Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. Journal of the National Cancer Institute. 100 (7): 513-517. Doi: 10.1093/jnci/djn044
Rodríguez, A. C., Schiffman, M., Herrero, R., Wacholder, S., Hildesheim, A., Castle, P. E., . . . Group, P. E. G. (2008). Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst. 100 (7): 513-517. Doi: 10.1093/jnci/djn044
Roman, A., & Munger, K. (2013). The papillomavirus E7 proteins. Virology. 445 (1-2): 138-168. Doi:10.1016/j.virol.2013.04.013
Sanchez, G. I., Kleter, B., Gheit, T., van Doorn, L. J., de Koning, M. N., de Sanjosé, S., . . . Quint, W. G. (2011). Clinical evaluation of polymerase chain reaction reverse hybridization assay for detection and identification of human papillomavirus type 16 variants. J Clin Virol. 51 (3): 165-169. Doi: 10.1016/j.jcv.2011.03.013
Saslow, D., Solomon, D., Lawson, H. W., Killackey, M., Kulasingam, S. L., Cain, J., . . . Pathology, A. S. f. C. (2012). American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 137 (4): 516-542. Doi: 10.1309/AJCPTGD94EVRSJCG
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., Howley, P. M. (1993). The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 75 (3): 495-505.
Schiffman, M., Herrero, R., Desalle, R., Hildesheim, A., Wacholder, S., Rodriguez, A. C., . . . Burk, R. D. (2005). The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 337 (1): 76-84. Doi: 10.1016/j.virol.2005.04.002
Stanczuk, G. A., Baxter, G. J., Currie, H., Forson, W., Lawrence, J. R., Cuschieri, K., . . . Arbyn, M. (2017). Defining optimal triage strategies for hrhpv screen-positive women-an evaluation of HPV 16/18 genotyping, cytology, and p16/Ki-67 cytoimmunochemistry. Cancer Epidemiol Biomarkers Prev. 26 (11): 1629-1635. Doi: 10.1158/1055-9965.epi-17-0534
Tornesello, M. L., Duraturo, M. L., Salatiello, I., Buonaguro, L., Losito, S., Botti, G., . . . Buonaguro, F. M. (2004). Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol. 74 (1): 117-126. Doi: 10.1002/jmv.20154
Turchinovich, A., Weiz, L., Langheinz, A., Burwinkel, B. (2011). Characterization of extracellular circulating microRNA. Nucleic Acids Res. 39 (16): 7223-7233. Doi: 10.1093/nar/gkr254
van der Heijden, E., Lopes, A. D., Bryant, A., Bekkers, R., Galaal, K. (2015). Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test. Cochrane Database Syst Rev. 1: Cd010757. DOI:10.1002/14651858.CD010757.pub2
Van Doorslaer, K. (2013). Evolution of the papillomaviridae. Virology. 445 (1-2): 11-20. Doi: 10.1016/j.virol.2013.05.012
Vande Pol, S. B., & Klingelhutz, A. J. (2013). Papillomavirus E6 oncoproteins. Virology. 445 (1-2): 115-137. Doi: 10.1016/j.virol.2013.04.026
Vargas-Robles, D., Magris, M., Morales, N., de Koning, M. N. C., Rodríguez, I., Nieves, T., . . . Domínguez-Bello, M. G. (2018). High rate of infection by only oncogenic human papillomavirus in Amerindians. mSphere. 3 (3). Doi: 10.1128/mSphere.00176-18
Walboomers, J. M., Jacobs, M. V., Manos, M. M., Bosch, F. X., Kummer, J. A., Shah, K. V., . . . Muñoz, N. (1999). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 189 (1): 12-19. Doi: 10.1002/(SICI)1096-9896(199909)189:1<12::AIDPATH431>3.0.CO;2-F
Wentzensen, N., Fetterman, B., Castle, P. E., Schiffman, M., Wood, S. N., Stiemerling, E., . . . Kinney, W. (2015). p16/Ki-67 Dual stain cytology for detection of cervical precancer in HPV-positive women. J Natl Cancer Inst. 107 (12): djv257. Doi: 10.1093/jnci/djv257
Yamada, T., Manos, M. M., Peto, J., Greer, C. E., Munoz, N., Bosch, F. X., Wheeler, C. M. (1997). Human papillomavirus type 16 sequence variation in cervical cancers: A worldwide perspective. J Virol. 71 (3): 2463-2472.
Yeo-Teh, N. S. L., Ito, Y., & Jha, S. (2018). High-Risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis. In Int J Mol Sci. 19.
Zsemlye, M. (2013). LSIL: Definition and management. Obstet Gynecol Clin North Am. 40 (2): 283-289. Doi: 10.1016/j.ogc.2013.03.008
Declaration of originality and transfer author's rights
The authors declare:
- The published data and reference materials have been duly identified with their respective credits and have been included in the bibliographic notes and citations that have been so identified and that should it be required, I have all releases and permissions from any copyrighted material.
- All material presented is free from any copyright and that I accept full legal responsibility for any legal claims relating to copyrighted intellectual property, fully exonerating from responsibility the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales.
- This work is unpublished and will not be sent to any other journal while waiting for the editorial decision of this journal. I declare that there is no conflict of interest in this manuscript.
- In case of publication of this article, all author´s rights are transferred to the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales, and so cannot be reproduced in any form without the express permission of it.
- By means of this document, if the article is accepted for publication by the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales, the Revista assumes the right to edit and publish the articles in national and international indices or data bases for academic and scientific use in paper, electronic, CD-ROM, internet form either of the complete text or any other known form known or to be known and non-commercial, respecting the rights of the authors.
Transfer of author rights
In case the article is approved for publication, the main author in representation of himself and his co-authors or the main author and his co-authors must cede the author rights of the corresponding article to the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales, except in the following cases:
The authors and co-authors will retain the right to revise, adapt, prepare derived works, oral presentations, and distribution to some colleagues of reprints of their own published work, if the corresponding credit is given to the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales. It is also permissible to publish the title of the work, summary, tables, and figures of the work in the corresponding web sites of the authors or their employers, also giving credit to the Revista.
If the work has been realized under contract, the author’s employer has the right to revise, adapt, prepare derivative works, reproduce, or distribute in hard copy the published work, in a secure manner and for the exclusive use of his employees.
If the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales were approached for permission by a third party for using, printing, or publishing specifically articles already published, the Revista must obtain the express permission of the author and co-authors of the work or of the employer except for use in classrooms, libraries, or reprinted in a collective work. The Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales reserves the possible use in its front cover of figures submitted with the manuscripts.
No other right, other than the author’s right, can be claimed by the Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales.