Palavras-chave
Virus del Papiloma Humano
diagnóstico molecular
transformación maligna
infección crónica
diagnóstico molecular
transformación maligna
infección crónica
Como Citar
Rincón, D., Morales, L., & Rincón Orozco, B. (2017). Modernas metodologías diagnosticas para la detección del Virus del Papiloma Humano y prevención del cáncer de cuello uterino. Salud UIS, 49(3), 478–488. https://doi.org/10.18273/revsal.v49n3-2017006
Resumo
Los Virus del Papiloma Humano (VPH) presentes en mucosa clasificados como de “alto riesgo” son agentes etiológicos de patologías oncológicas como cáncer de cuello uterino, ano, pene, vulva y cáncer orofaríngeo. Actualmente el principal método de tamizaje utilizado en Colombia para detección de cáncer de cuello uterino es la citología cervical, presentando una moderada cobertura en la población femenina y una sensibilidad cercana al 50%. El objetivo de este trabajo es describir las técnicas modernas utilizadas para la detección del VPH y prevención de los cánceres producidos por estos virus. Se llevó a cabo una revisión de literatura de las ultimas metodologías diagnosticas en la infección viral por VPH y marcadores de malignidad en muestras cervicales. La citología cervical es un recurso altamente específico y de bajo costo, pero poco sensible para la detección y prevención de cáncer de cuello uterino, que puede ser complementado con las tecnologías modernas revisadas con el objetivo de obtener un diagnóstico temprano del VPH como agente etiológico de estas enfermedades malignas.
Palabras clave: Virus del Papilloma Humano, diagnóstico molecular, transformación maligna, infección crónica.Referências
1. Ghittoni R, Accardi R, Chiocca S, Tommasino M. Role of human papillomaviruses in carcinogenesis. Ecancermedicalscience. 2015; 9(526): 1-9. DOI: 10.3332/ecancer.2015.526.
2. Moerman-herzog A, Nakagawa M. Early defensive mechanisms against human papillomavirus infection. Clin Vaccine Immunol. 2015; 22(8): 850-857. DOI: 10.1128/CVI.00223-15.
3. Egawa N, Egawa K, Griffin H, Doorbar J. human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses. 2015; 7(7): 3863-3890. DOI: 10.3390/v7072802.
4. Letian T, Tianyu Z. Cellular receptor binding and entry of human papillomavirus. Virol J. 2010; 7: 2. DOI: 10.1186/1743-422X-7-2.
5. Schiller JT, Lowy DR. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nat Rev Microbiol. 2012; 10(10): 681-692. DOI: 10.1038/nrmicro2872.
6. Sana DE, Mayrink de Miranda P, Pitol BC, Moran MS, Silva NN, Guerreiro da Silva ID, et al. Morphometric evaluation and nonclassical criteria for the diagnosis of HPV infection and cytological atypia in cervical samples. Diagn Cytopathol. 2013;41(9). 785-792. DOI: 10.1002/dc.22955.
7. Horvath C a J, Boulet G a V, Renoux VM, Delvenne PO, Bogers J-PJ. Mechanisms of cell entry by human papillomaviruses: an overview. Virol J. 2010; 7:11. DOI: 10.1186/1743-422X-7-11.
8. Roden R, Wu T-C. How will HPV vaccines affect cervical cancer?. Nat Rev Cancer. 2006; 6(10): 753-763. DOI: 10.1038/nrc1973 9. Piñeros M, Gamboa O, Hernández-Suárez G, Pardo C, Bray F. Patterns and trends in cancer mortality in Colombia 1984-2008. Cancer Epidemiol. 2013; 37(3): 233-239. DOI: 10.1016/j.canep.2013.02.003.
10. Cendales R, Pardo C, Uribe C, Lopez G, Yepez MC, Bravo LE. Data quality at population-based cancer registries in Colombia. Biomedica. 2012; 32(4): 536-544. DOI: 10.1590/S0120-41572012000400009.
11. Morales LA, Rincón DF, Rincón-Orozco B. Avances en el desarrollo de nuevas vacunas profilácticas y terapéuticas contra el Virus del Papiloma Humano. Rev Univ Ind Santander Salud. 2016; 48(3): 385-391. DOI: http://dx.doi.org/10.18273/revsal.v48n3-2016012.
12. INSTITUTO NACIONAL DE SALUD. Protocolo de vigilancia en salud publica cancer de mama y cuello uterino. República de Colombia, Ministerio de Salud. V02- 05-01 2016
13. Murillo R, Wiesner C, Cendales R. Comprehensive evaluation of cervical cancer screening programs : the case of Colombia. Salud Publica Mex. 2011; 53(6): 469-478.
14. Murillo R, Cendales R, Wiesner C, Piñeros M, Tovar S. Efectividad de la citología cérvico-uterina para la detección temprana de cáncer de cuello uterino en el marco del sistema de salud de Colombia. Biomédica. 2009; 29(3): 344–351. DOI: http://dx.doi.org/10.7705/biomedica.v29i3.7.
15. Lucumí D, Gómez L. Accesibilidad a los servicios de salud en la práctica de citología reciente de cuello uterino en una zona urbana de Colombia. Rev Esp Salud Pública. 2004; 78: 367-377.
16. Agorastos T, Chatzistamatiou K, Katsamagkas T, Koliopoulos G, Daponte A, Constantinidis T, et al. Primary Screening for cervical cancer based on high-risk human papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology. PLoS One. 2015; 10(3): e0119755. DOI: 10.1371/journal.pone.0119755.
17. Comparetto C, Borruto F. Cervical cancer screening: a never-ending developing program. World J Clin cases. 2015; 3(7): 614-624. DOI: 10.12998/wjcc.v3.i7.614.
18. Quinley K, Gormley R, Ratcliffe S, Shih T, Szep Z, Steiner A, et al. Use of mobile telemedicine for cervical cancer screening. J Telemed Telecare. 2011; 17(4): 203-209. DOI: 10.1258/jtt.2011.101008.
19. Ricard-Gauthier D, Wisniak A, Catarino R, van Rossum AF, Meyer-Hamme U, Negulescu R, et al. Use of smartphones as adjuvant tools for cervical cancer screening in low-resource settings. J Low Genit Tract Dis. 2015; 19(4): 295-300.
20. Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM. Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int. 2013; 2013: 519619. DOI: http://dx.doi.org/10.1155/2013/519619.
21. Sahasrabuddhe V, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011; 6(9): 1-25. DOI: 10.2217/fmb.11.87.
22. Van Raemdonck GAA, Tjalma WAA, Coen EP, Depuydt CE, Van Ostade XWM. Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid. PLoS One. 2014; 9(9): e106488. DOI: https://doi.org/10.1371/journal.pone.0106488.
23. Banno K, Iida M, Yanokura M, Kisu I, Iwata T, Tominaga E, et al. MicroRNA in Cervical Cancer: OncomiRs and tumor suppressor miRs in diagnosis and treatment. Sci World J. Hindawi Publishing Corporation; 2014;2014:8. DOI: http://dx.doi.org/10.1155/2014/178075
24. Goodman A. HPV testing as a screen for cervical cancer. Bmj. 2015; 350: h2372–h2372. DOI: https://doi.org/10.1136/bmj.h2372.
25. Chan PKS, Picconi MA, Cheung TH, Giovannelli L, Park JS. Laboratory and clinical aspects of human papillomavirus testing. Crit Rev Clin Lab Sci. 2012; 49(4): 117-136. DOI: 10.3109/10408363.2012.707174.
26. Alameda F, Garrote L, Mojal S, Sousa C, Muset M, LLoveras B, et al. Cervista HPV HR test for cervical cancer screening a comparative study in the catalonian population. Arch Pathol Lab Med. 2015; 139(2): 241-244. DOI: 10.5858/arpa.2014-0012-OA84921465153&partnerID=40&md5=6389a98104d21da764bd932fed1edd5d.
27. Youens KE, Hosler G a., Washington PJ, Jenevein EP, Murphy KM. Clinical Experience with the Cervista HPV HR Assay. J Mol Diagnostics. Elsevier Inc.; 2011; 13(2): 160-166. DOI: 10.1016/j.jmoldx.2010.11.016.
28. HOLOGIC. Aptima HPV 16 18/45 Genotype Assay. AW-12821 Rev. 001. 2007-2015.
29. Paes EF, de Assis AM, Teixeira CSC, Aoki FH, Teixeira JC. Development of a multiplex PCR Test with automated genotyping targeting e7 for detection of six high-risk human papillomaviruses. PLoS One. 2015; 10(6): e0130226. DOI: https://doi.org/10.1371/journal.pone.0130226.
30. Wang H-Y, Park S, Kim S, Lee D, Kim G, Kim Y, et al. Use of hTERT and HPV E6/E7 mRNA RT-qPCR TaqMan Assays in combination for diagnosing high-grade cervical lesions and malignant tumors. Am J Clin Pathol. 2015; 143(3): 344-351. DOI: 10.1309/AJCPF2XGZ2XIQYQX.
31. Origoni M, Cristoforoni P, Carminati G, Stefani C, Costa S, Sandri MT, et al. E6/E7 mRNA testing for human papilloma virus-induced high-grade cervical intraepithelial disease (CIN2/CIN3): a promising perspective. Ecancermedicalscience. 2015; 9: 533. DOI: 10.3332/ecancer.2015.533.
32. Poljak M, Kocjan Bostjan J, Ostrbenk A, Seme K. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update. J Clin Virol. 2016;76 (Suppl 1): S3-S13. DOI: 10.1016/j.jcv.2015.10.023.
33. Schweizer J, Lu PS, Mahoney CW, Berard-BErgery M, Ho M, Ramasamy V, et al. Feasibility Study of a Human Papillomavirus E6 Oncoprotein Test for Diagnosis of Cervical Precancer and cancer. 2010; 48(12): 4646-4648. DOI: 10.1128/JCM.01315-10.
34. Kunnev D, Freeland A, Qin M, Leach RW, Wang J, Shenoy RM, Pruitt SC. Effect of minichromosome maintenance protein 2 deficiency on the locations of DNA replication origins. Genome Res. 2015; 25(4): 558-569. DOI: 10.1101/gr.176099.114.
35. Kumar A, Ehrenshaft M, Tokar E, Mason R, Sinha B. Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells. Biochimica et Biophysica Acta (BBA) - General Subjects.2016; 1860(7): 1519-1527. DOI: http://dx.doi.org/10.1016/j.bbagen.2016.04.009.
36. Aksenova V, Turoverova L, Khotin M, et al. Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB. Oncotarget. 2013; 4(2): 362-372.
37. Wang H, Park S, Lee D, Kim S, Kim G, Hwa K, et al. Prevalence of type-specific oncogenic human papillomavirus infection assessed by HPV E6 / E7 mRNA among women with high-grade cervical lesions. Int J Infect Dis. 2015; 37: 135-142. DOI: 10.1016/j.ijid.2015.06.018.
38. U.S. Food and Drug Administration. Devices@FDA.
39. Persson M, Wendel S, Ljungblad L, Johansson B, Weiderpass E, Andersson S. High-risk human papillomavirus E6/E7 mRNA and L1 DNA as markers of residual/recurrent cervical intraepithelial neoplasia. Oncol Rep. 2012; 28(1): 346-352. DOI: 10.3892/or.2012.1755.
40. INSTITUTO NACIONAL DE SALUD. Norma técnica para la detección temprana del cáncer de cuello uterino y guía de atención de lesiones preneoplásicas de cuello uterino. República de Colombia, Ministerio de Salud. Imprenta Nacional de Colombia. 2000; 44-48
2. Moerman-herzog A, Nakagawa M. Early defensive mechanisms against human papillomavirus infection. Clin Vaccine Immunol. 2015; 22(8): 850-857. DOI: 10.1128/CVI.00223-15.
3. Egawa N, Egawa K, Griffin H, Doorbar J. human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses. 2015; 7(7): 3863-3890. DOI: 10.3390/v7072802.
4. Letian T, Tianyu Z. Cellular receptor binding and entry of human papillomavirus. Virol J. 2010; 7: 2. DOI: 10.1186/1743-422X-7-2.
5. Schiller JT, Lowy DR. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nat Rev Microbiol. 2012; 10(10): 681-692. DOI: 10.1038/nrmicro2872.
6. Sana DE, Mayrink de Miranda P, Pitol BC, Moran MS, Silva NN, Guerreiro da Silva ID, et al. Morphometric evaluation and nonclassical criteria for the diagnosis of HPV infection and cytological atypia in cervical samples. Diagn Cytopathol. 2013;41(9). 785-792. DOI: 10.1002/dc.22955.
7. Horvath C a J, Boulet G a V, Renoux VM, Delvenne PO, Bogers J-PJ. Mechanisms of cell entry by human papillomaviruses: an overview. Virol J. 2010; 7:11. DOI: 10.1186/1743-422X-7-11.
8. Roden R, Wu T-C. How will HPV vaccines affect cervical cancer?. Nat Rev Cancer. 2006; 6(10): 753-763. DOI: 10.1038/nrc1973 9. Piñeros M, Gamboa O, Hernández-Suárez G, Pardo C, Bray F. Patterns and trends in cancer mortality in Colombia 1984-2008. Cancer Epidemiol. 2013; 37(3): 233-239. DOI: 10.1016/j.canep.2013.02.003.
10. Cendales R, Pardo C, Uribe C, Lopez G, Yepez MC, Bravo LE. Data quality at population-based cancer registries in Colombia. Biomedica. 2012; 32(4): 536-544. DOI: 10.1590/S0120-41572012000400009.
11. Morales LA, Rincón DF, Rincón-Orozco B. Avances en el desarrollo de nuevas vacunas profilácticas y terapéuticas contra el Virus del Papiloma Humano. Rev Univ Ind Santander Salud. 2016; 48(3): 385-391. DOI: http://dx.doi.org/10.18273/revsal.v48n3-2016012.
12. INSTITUTO NACIONAL DE SALUD. Protocolo de vigilancia en salud publica cancer de mama y cuello uterino. República de Colombia, Ministerio de Salud. V02- 05-01 2016
13. Murillo R, Wiesner C, Cendales R. Comprehensive evaluation of cervical cancer screening programs : the case of Colombia. Salud Publica Mex. 2011; 53(6): 469-478.
14. Murillo R, Cendales R, Wiesner C, Piñeros M, Tovar S. Efectividad de la citología cérvico-uterina para la detección temprana de cáncer de cuello uterino en el marco del sistema de salud de Colombia. Biomédica. 2009; 29(3): 344–351. DOI: http://dx.doi.org/10.7705/biomedica.v29i3.7.
15. Lucumí D, Gómez L. Accesibilidad a los servicios de salud en la práctica de citología reciente de cuello uterino en una zona urbana de Colombia. Rev Esp Salud Pública. 2004; 78: 367-377.
16. Agorastos T, Chatzistamatiou K, Katsamagkas T, Koliopoulos G, Daponte A, Constantinidis T, et al. Primary Screening for cervical cancer based on high-risk human papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology. PLoS One. 2015; 10(3): e0119755. DOI: 10.1371/journal.pone.0119755.
17. Comparetto C, Borruto F. Cervical cancer screening: a never-ending developing program. World J Clin cases. 2015; 3(7): 614-624. DOI: 10.12998/wjcc.v3.i7.614.
18. Quinley K, Gormley R, Ratcliffe S, Shih T, Szep Z, Steiner A, et al. Use of mobile telemedicine for cervical cancer screening. J Telemed Telecare. 2011; 17(4): 203-209. DOI: 10.1258/jtt.2011.101008.
19. Ricard-Gauthier D, Wisniak A, Catarino R, van Rossum AF, Meyer-Hamme U, Negulescu R, et al. Use of smartphones as adjuvant tools for cervical cancer screening in low-resource settings. J Low Genit Tract Dis. 2015; 19(4): 295-300.
20. Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM. Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int. 2013; 2013: 519619. DOI: http://dx.doi.org/10.1155/2013/519619.
21. Sahasrabuddhe V, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011; 6(9): 1-25. DOI: 10.2217/fmb.11.87.
22. Van Raemdonck GAA, Tjalma WAA, Coen EP, Depuydt CE, Van Ostade XWM. Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid. PLoS One. 2014; 9(9): e106488. DOI: https://doi.org/10.1371/journal.pone.0106488.
23. Banno K, Iida M, Yanokura M, Kisu I, Iwata T, Tominaga E, et al. MicroRNA in Cervical Cancer: OncomiRs and tumor suppressor miRs in diagnosis and treatment. Sci World J. Hindawi Publishing Corporation; 2014;2014:8. DOI: http://dx.doi.org/10.1155/2014/178075
24. Goodman A. HPV testing as a screen for cervical cancer. Bmj. 2015; 350: h2372–h2372. DOI: https://doi.org/10.1136/bmj.h2372.
25. Chan PKS, Picconi MA, Cheung TH, Giovannelli L, Park JS. Laboratory and clinical aspects of human papillomavirus testing. Crit Rev Clin Lab Sci. 2012; 49(4): 117-136. DOI: 10.3109/10408363.2012.707174.
26. Alameda F, Garrote L, Mojal S, Sousa C, Muset M, LLoveras B, et al. Cervista HPV HR test for cervical cancer screening a comparative study in the catalonian population. Arch Pathol Lab Med. 2015; 139(2): 241-244. DOI: 10.5858/arpa.2014-0012-OA84921465153&partnerID=40&md5=6389a98104d21da764bd932fed1edd5d.
27. Youens KE, Hosler G a., Washington PJ, Jenevein EP, Murphy KM. Clinical Experience with the Cervista HPV HR Assay. J Mol Diagnostics. Elsevier Inc.; 2011; 13(2): 160-166. DOI: 10.1016/j.jmoldx.2010.11.016.
28. HOLOGIC. Aptima HPV 16 18/45 Genotype Assay. AW-12821 Rev. 001. 2007-2015.
29. Paes EF, de Assis AM, Teixeira CSC, Aoki FH, Teixeira JC. Development of a multiplex PCR Test with automated genotyping targeting e7 for detection of six high-risk human papillomaviruses. PLoS One. 2015; 10(6): e0130226. DOI: https://doi.org/10.1371/journal.pone.0130226.
30. Wang H-Y, Park S, Kim S, Lee D, Kim G, Kim Y, et al. Use of hTERT and HPV E6/E7 mRNA RT-qPCR TaqMan Assays in combination for diagnosing high-grade cervical lesions and malignant tumors. Am J Clin Pathol. 2015; 143(3): 344-351. DOI: 10.1309/AJCPF2XGZ2XIQYQX.
31. Origoni M, Cristoforoni P, Carminati G, Stefani C, Costa S, Sandri MT, et al. E6/E7 mRNA testing for human papilloma virus-induced high-grade cervical intraepithelial disease (CIN2/CIN3): a promising perspective. Ecancermedicalscience. 2015; 9: 533. DOI: 10.3332/ecancer.2015.533.
32. Poljak M, Kocjan Bostjan J, Ostrbenk A, Seme K. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update. J Clin Virol. 2016;76 (Suppl 1): S3-S13. DOI: 10.1016/j.jcv.2015.10.023.
33. Schweizer J, Lu PS, Mahoney CW, Berard-BErgery M, Ho M, Ramasamy V, et al. Feasibility Study of a Human Papillomavirus E6 Oncoprotein Test for Diagnosis of Cervical Precancer and cancer. 2010; 48(12): 4646-4648. DOI: 10.1128/JCM.01315-10.
34. Kunnev D, Freeland A, Qin M, Leach RW, Wang J, Shenoy RM, Pruitt SC. Effect of minichromosome maintenance protein 2 deficiency on the locations of DNA replication origins. Genome Res. 2015; 25(4): 558-569. DOI: 10.1101/gr.176099.114.
35. Kumar A, Ehrenshaft M, Tokar E, Mason R, Sinha B. Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells. Biochimica et Biophysica Acta (BBA) - General Subjects.2016; 1860(7): 1519-1527. DOI: http://dx.doi.org/10.1016/j.bbagen.2016.04.009.
36. Aksenova V, Turoverova L, Khotin M, et al. Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB. Oncotarget. 2013; 4(2): 362-372.
37. Wang H, Park S, Lee D, Kim S, Kim G, Hwa K, et al. Prevalence of type-specific oncogenic human papillomavirus infection assessed by HPV E6 / E7 mRNA among women with high-grade cervical lesions. Int J Infect Dis. 2015; 37: 135-142. DOI: 10.1016/j.ijid.2015.06.018.
38. U.S. Food and Drug Administration. Devices@FDA.
39. Persson M, Wendel S, Ljungblad L, Johansson B, Weiderpass E, Andersson S. High-risk human papillomavirus E6/E7 mRNA and L1 DNA as markers of residual/recurrent cervical intraepithelial neoplasia. Oncol Rep. 2012; 28(1): 346-352. DOI: 10.3892/or.2012.1755.
40. INSTITUTO NACIONAL DE SALUD. Norma técnica para la detección temprana del cáncer de cuello uterino y guía de atención de lesiones preneoplásicas de cuello uterino. República de Colombia, Ministerio de Salud. Imprenta Nacional de Colombia. 2000; 44-48
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