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Fecha Publicación: 2007-12-21
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Molano, M., Moreno Acosta, P., & Bravo, M. M. (2007). Types and variants of human papillomavirus in patients with cervical cancer submitted to radiotherapy. Biosalud, 6, 45–57. Recuperado a partir de https://revistasojs.ucaldas.edu.co/index.php/biosalud/article/view/5844
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INTRODUCCIÓN: los virus del papiloma humano de alto riesgo y la presencia de algunas variantes han sido asociados con el incremento del riesgo de cáncer cervical. Sin embargo, existen muy pocos estudios en los que se haya analizado su presencia en pacientes antes y después de ser remitidos a radioterapia. OBJETIVOS: analizar la presencia del virus del papiloma humano y de variantes de E7/VPH16 en 60 mujeres con cáncer cervical antes y después del tratamiento con radioterapia. MATERIALES Y MÉTODOS: la detección y tipificación del VPH antes y después de radioterapia se basó en un GP5+/GP6+ PCR –Inmunoensayo enzimático. Variantes de E7/VPH16 se detectaron mediante PCR -Polimorfismo conformacional de cadena sencilla y confirmadas por secuencia directa. RESULTADOS: antes de radioterapia, 50 de 60 pacientes (83.3%) fueron positivas para VPH, siendo el VPH16 (53,3%) el más prevalente. Después de radioterapia, de 55 pacientes que asistieron, 19 (34,6%) fueron VPH positivas. Esta disminución en la detección del VPH fue estadísticamente significativa (p<0,0005). El análisis de E7/VPH16 mostró que 20 muestras (62,5%) amplificaron para este gen antes de radioterapia, 18 (90%) de estas muestras tuvieron un patrón de corrido por SSCP idéntico al patrón prototipo y dos muestras mostraron un patrón de corrido diferente. La secuencia de estas dos muestras mostró mutaciones silenciosas en las posiciones nt 732 (T-to-C), 789 (T-to-C) y 795 (T-to-G). Después de radioterapia, a ninguna muestra se le detectó mutaciones, seis pacientes mostraron infección persistente por VPH16 y tuvieron por SSCP un patrón de corrido similar al prototipo. Las muestras que inicialmente mostraron un patrón de corrido diferente fueron negativas para E7/VPH16 después de radioterapia. CONCLUSIONES: se detectaron pocas variantes en E7/VPH16 antes de la radioterapia y parece que este tratamiento no causa mutaciones en el gen.
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Arias H, Moreno AP, Corredor JC, Molano M, Orozco D, Van den Brule AJC. Detección del virus del papiloma humano por métodos no radioactivos. Neoplasia 1997; 14:45-50.
Bachtiary B, Obermair A, Dreier B, Birner P, Breitenecker G, Knocke TH, et al. Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer. Int J Cancer 2002; 102:237-43.
Brisson J, Bairati I, Morin C, Fortier M, Bouchard C, Christen A, et al. Determinants of persistent detection of human papillomavirus DNA in the uterine cervix. J Infect Dis 1996; 73:794-9.
Buonaguro FM, Tornesello ML, Salatiello I, Okong P, Buonaguro L, Giraldo E, et al. The Uganda study on HPV variants and genital cancers. J Clin Virol 2000; 19:31-41.
Chan SY, Ho L, Ong CK, Chow V, Drescher B, Durst M, et al. Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind. J Virology 1992; 66:2057-66.
Cheng G, Icenogle J, Kinbauer R, Hubbert N, Han Ch, Lowy D, et al. Divergent human papillomavirus type 16 variants are serologically cross-reactive. J Infec Dis 1995; 172:1584-7.
De Roda Husman AM, Walboomers JMM, Van der Brule AJC, Mejer CJLM, Snijders PJF. The use general primers GP5 and GP6 elongated at their 3’ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995; 76:1057-62.
DeWeese TL, Walsh JC, Dillehay LE, Kessis T, Hedrick L, Cho KR, et al. Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation. Int J Radiat Oncol Biol Phys 1997; 37:145-54.
Einhorn N, Trope C, Ridderheim M, Boman K, Sorbe B, Cavallin-Stahl E. A systematic overview of radiation therapy effects in cervical cancer (cervix uteri). Acta Oncol 2003; 42:546-56.
Ellis JRM, Keating PJ, Baird J, Hounsell EF, Renouf DV, Rowe M, et al. The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer. Nat Med 1995; 1:464-70.
Eschle D, Durst M, Ter Meulen J, Luande J, Eberhardt HC, Pawlita M, et al. Geographical dependence of sequence variation in the E7 gen of human papillomavirus type 16. J Gen Virol 1992; 73:1829-32.
Etherington IJ, Ellis JR, Luesley DM, Moffitt DD, Young LS. Histologic and immunologic association of an HPV16 variant in LSIL smears. Gynecol Oncol 1999; 72:56-9.
Fujimura M, Ostrow RS, Okagaki T. Implication of Human Papillomavirus in Postirradiation Dysplasia. Cancer 1991; 68:2181-5.
Ginnoudis A, Herrington CS. Human papillomavirus variants and squamous neoplasia of the cervix. J Pathol 2001; 193:295-302.
Hall EJ. Time, dose, and fractionation in radiotherapy. In: Hall D, ed. Radiobiology for the Radiologist. 3rd ed. Philadelphia: J. B. Lippincott; 1988. p. 239-59.
Hampson L, El Hady ES, Moore JV, Kitchener H, Hampson IN. The HPV16 E6 and E7 proteins and the radiation resistance of cervical carcinoma. FASEB J 2001; 15:1445-7.
Hayashi K, Yandell DW. How sensitive is PCR-SSCP? Hum Mutat 1993; 2:338-46.
Herzog TJ. New approaches for the management of cervical cancer. Gynecol Oncol 2003; 90:S22-S27.
Hildesheim A, Schiffman MH, Bromley C, Wacholder S, Herrero R, Rodriguez A, et al. Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst 2001; 93:315-8.
Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998; 338:423-8.
Icenogle JP, Sathya P, Miller D, Tucker RA, Rawls WC. Nucleotide and amino acid sequence variation in the L1 and E7 open reading frames of human papillomavirus type 6 and type 16. Virology 1991; 184:101-7.
Jacobs MV, Husman AM, Van den Brule AJC, Snijders PJF, Meijer CJ, Walboomers JMM. Groupspecific differentiation between high and low human papillomavirus genotypes by general primer mediated PCR and two cocktails of oligonucleotide probes. J Clin Microbiology 1995; 33:901-5.
Jacobs MV, Snijders PJF, Van den Brule AJC, Helmerhorst JM, Meijer CJ, Walboomers JMM. A general primer GP5+/6+ mediated PCR enzime-immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol 1997; 35:791-5.
Jones DL, Munger K. Interactions of the human papillomavirus E7 protein with cell cycle regulators. Semin Cancer Biol 1996; 7:327-37.
Kirnbauer R, Taub J, Greenstone H, Roden R, Durst M, Gissmann L, et al. Efficient self-assembly of human papillomavirus type 16 L1 and L1–L2 into virus-like particles. J Virology 1993; 67:6929-36.
Liaw KL, Hildesheim A, Burk RD, Gravitt P, Wacholder S, Manos MM, et al. A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types. J Infect Dis 2001; 183:8-15.
Liu SS, Cheung AN, Ngan HY. Differential gene expression in cervical cancer cell lines before and after ionizing radiation. Int J Oncol 2003; 22:1091-9.
Londesborough P, Ho L, Terry G, Cuzick J, Wheeler C, Singer A. Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities. Int J Cancer 1996; 69:364-8.
Longatto LA, Filho A, Maeda MY, Oyafuso MS, Alves VA, Kanamura CT, et al. Cytomorphologic evidence of human papillomavirus infection in smears from the irradiated uterine cervix. Acta Cytol 1997; 41:1079-84.
McMurray HR, Nguyen D, Westbrook TF, McCance DJ. Biology of human papillomaviruses. Int J Exp Pathol 2001; 82:15-33.
Milde-Langosch K, Riethdorf S, Loning T. Association of human papillomavirus infection with carcinoma of the cervix uteri and its precursor lesions: theoretical and practical implications. Virchows Arch 2000; 437:227-33.
Molano M, Van den Brule AJC, Plummer M, Weiderpass E, Posso H, Arslan A, et al. Determinants of clearance of human papillomavirus infections in Colombian women with normal cytology: a population-based, 5-year follow-up study. Am J Epidemiol 2003; 158:486-94.
Muñoz N, Bosch FX. HPV and cervical neoplasia: review of case/control and cohort studies. In: Muñoz N, Bosch FX, Shah KV. eds. Epidemiology of Cervical Cancer and Human Papillomavirus. IARC Scientific Publ. No. 119, Lyon (France): IARC; 1992. p. 251-61.
Muñoz N, Bosch FX, De San José S, Viladiu P, Tormo J, Moreo P, et al. El virus del papiloma humano en la etiología del cáncer cervicouterino. Bol Oficina Sanit Panam 1993; 115:301-9.
Nagai Y, Toma T, Moromizato H, Maehama T, Asato T, Kariya K, et al. Persistence of human papillomavirus infection as a predictor for recurrence in carcinoma of the cervix after radiotherapy. Am J Obstet Gynecol 2004; 191:1907-13.
Philips AC, Vousden KH. Human papillomavirus and cancer: the viral transforming genes. Cancer Surv 1999; 33:55-74.
Radhakrishna PM, Sreevidya S, Pollock BH, Jayaprakash PG, Herman B. Human papillomavirus type 16 E6 and E7 gene variations in Indian cervical cancer. Gynecol Oncol 2002; 87:268-73.
Santin AD, Hermonat PL, Ravaggi A, Chiriva-Internati M, Pecorelli S, Parham PG. Radiationenhanced expression of E6/E7 transforming oncogenes of human papillomavirus-16 in human cervical carcinoma. Cancer 1998; 83:2346-52.
Smits HL, Traanberg KF, Krul MR, Prussia PR, Capone B, Bruyn A, et al. Identification of a unique group of human papillomavirus type 16 sequence variants among clinical isolates from Barbados. J Gen Virol 1994; 75:2457-62.
Song YS, Kee SH, Kim JW, Park NH, Kang SB, Chang WH, et al. Major sequence variants in E7 gene of human papillomavirus type 16 from cervical cancerous and noncancerous lesions of Korean women. Gynecol Oncol 1997; 66:275-81.
Stoppler MC, Ching K, Stoppler H, Clancy K, Schlegel R, Icenogle J. Natural variants of the human papillomavirus type 16 E6 protein differ in their abilities to alter keratinocyte differentiation and to induce p53 degradation. J Virol 1996; 70:6987-93.
Van den Brule AJC, Meijer CÉL, Bakels V, Kenemans P, Walboomers JMM. PCR based detection of genital HPV genotypes. J Clin Microbiol 1990; 28:2739-43.
Van Duin M, Snijders PJF, Vossen MTM, Klaassen E, Voorhorst F, Verheijen RHM, et al. Analysis of human papillomavirus 16 E6 variants in relation to p53 codon 72 polymorphism genotypes in cervical carcinogenesis. J Gen Virol 2000; 81:317-25.
Villa LL, Sichero L, Rahal P, Caballero O, Ferenczy A, Rohan T, et al. Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J Gen Virol 2000; 81:2959-68.
Walboomers JM, Jacobs MV, Manos MM, Bosh FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189:12-9.
Woodman CBJ, Collins S, Winter H, Bailey A, Ellis J, Prior P, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet 2001; 357:1831-6.
Xi Long Fu, Demers W, Koutsky LA, Kiviat NB, Holmes KK, Galloway DA. Analysis of human papillomavirus type 16 variants indicates establishment of persistent infection. J Infect Dis 1995; 172:747-55.
Xu X, Pang T, Guo Z, Mazurenko N, Kisselijov F, Ponten J, et al. HPV16 E6 gene variations in invasive cervical carcinoma and cancer in situ from Russian patients. Br J Cancer 2001; 84:791-5.
Zehbe I, Wilander E, Delius H, Tommasino M. Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res 1998; 58:829-33.
Bachtiary B, Obermair A, Dreier B, Birner P, Breitenecker G, Knocke TH, et al. Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer. Int J Cancer 2002; 102:237-43.
Brisson J, Bairati I, Morin C, Fortier M, Bouchard C, Christen A, et al. Determinants of persistent detection of human papillomavirus DNA in the uterine cervix. J Infect Dis 1996; 73:794-9.
Buonaguro FM, Tornesello ML, Salatiello I, Okong P, Buonaguro L, Giraldo E, et al. The Uganda study on HPV variants and genital cancers. J Clin Virol 2000; 19:31-41.
Chan SY, Ho L, Ong CK, Chow V, Drescher B, Durst M, et al. Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind. J Virology 1992; 66:2057-66.
Cheng G, Icenogle J, Kinbauer R, Hubbert N, Han Ch, Lowy D, et al. Divergent human papillomavirus type 16 variants are serologically cross-reactive. J Infec Dis 1995; 172:1584-7.
De Roda Husman AM, Walboomers JMM, Van der Brule AJC, Mejer CJLM, Snijders PJF. The use general primers GP5 and GP6 elongated at their 3’ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995; 76:1057-62.
DeWeese TL, Walsh JC, Dillehay LE, Kessis T, Hedrick L, Cho KR, et al. Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation. Int J Radiat Oncol Biol Phys 1997; 37:145-54.
Einhorn N, Trope C, Ridderheim M, Boman K, Sorbe B, Cavallin-Stahl E. A systematic overview of radiation therapy effects in cervical cancer (cervix uteri). Acta Oncol 2003; 42:546-56.
Ellis JRM, Keating PJ, Baird J, Hounsell EF, Renouf DV, Rowe M, et al. The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer. Nat Med 1995; 1:464-70.
Eschle D, Durst M, Ter Meulen J, Luande J, Eberhardt HC, Pawlita M, et al. Geographical dependence of sequence variation in the E7 gen of human papillomavirus type 16. J Gen Virol 1992; 73:1829-32.
Etherington IJ, Ellis JR, Luesley DM, Moffitt DD, Young LS. Histologic and immunologic association of an HPV16 variant in LSIL smears. Gynecol Oncol 1999; 72:56-9.
Fujimura M, Ostrow RS, Okagaki T. Implication of Human Papillomavirus in Postirradiation Dysplasia. Cancer 1991; 68:2181-5.
Ginnoudis A, Herrington CS. Human papillomavirus variants and squamous neoplasia of the cervix. J Pathol 2001; 193:295-302.
Hall EJ. Time, dose, and fractionation in radiotherapy. In: Hall D, ed. Radiobiology for the Radiologist. 3rd ed. Philadelphia: J. B. Lippincott; 1988. p. 239-59.
Hampson L, El Hady ES, Moore JV, Kitchener H, Hampson IN. The HPV16 E6 and E7 proteins and the radiation resistance of cervical carcinoma. FASEB J 2001; 15:1445-7.
Hayashi K, Yandell DW. How sensitive is PCR-SSCP? Hum Mutat 1993; 2:338-46.
Herzog TJ. New approaches for the management of cervical cancer. Gynecol Oncol 2003; 90:S22-S27.
Hildesheim A, Schiffman MH, Bromley C, Wacholder S, Herrero R, Rodriguez A, et al. Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst 2001; 93:315-8.
Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998; 338:423-8.
Icenogle JP, Sathya P, Miller D, Tucker RA, Rawls WC. Nucleotide and amino acid sequence variation in the L1 and E7 open reading frames of human papillomavirus type 6 and type 16. Virology 1991; 184:101-7.
Jacobs MV, Husman AM, Van den Brule AJC, Snijders PJF, Meijer CJ, Walboomers JMM. Groupspecific differentiation between high and low human papillomavirus genotypes by general primer mediated PCR and two cocktails of oligonucleotide probes. J Clin Microbiology 1995; 33:901-5.
Jacobs MV, Snijders PJF, Van den Brule AJC, Helmerhorst JM, Meijer CJ, Walboomers JMM. A general primer GP5+/6+ mediated PCR enzime-immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. J Clin Microbiol 1997; 35:791-5.
Jones DL, Munger K. Interactions of the human papillomavirus E7 protein with cell cycle regulators. Semin Cancer Biol 1996; 7:327-37.
Kirnbauer R, Taub J, Greenstone H, Roden R, Durst M, Gissmann L, et al. Efficient self-assembly of human papillomavirus type 16 L1 and L1–L2 into virus-like particles. J Virology 1993; 67:6929-36.
Liaw KL, Hildesheim A, Burk RD, Gravitt P, Wacholder S, Manos MM, et al. A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types. J Infect Dis 2001; 183:8-15.
Liu SS, Cheung AN, Ngan HY. Differential gene expression in cervical cancer cell lines before and after ionizing radiation. Int J Oncol 2003; 22:1091-9.
Londesborough P, Ho L, Terry G, Cuzick J, Wheeler C, Singer A. Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities. Int J Cancer 1996; 69:364-8.
Longatto LA, Filho A, Maeda MY, Oyafuso MS, Alves VA, Kanamura CT, et al. Cytomorphologic evidence of human papillomavirus infection in smears from the irradiated uterine cervix. Acta Cytol 1997; 41:1079-84.
McMurray HR, Nguyen D, Westbrook TF, McCance DJ. Biology of human papillomaviruses. Int J Exp Pathol 2001; 82:15-33.
Milde-Langosch K, Riethdorf S, Loning T. Association of human papillomavirus infection with carcinoma of the cervix uteri and its precursor lesions: theoretical and practical implications. Virchows Arch 2000; 437:227-33.
Molano M, Van den Brule AJC, Plummer M, Weiderpass E, Posso H, Arslan A, et al. Determinants of clearance of human papillomavirus infections in Colombian women with normal cytology: a population-based, 5-year follow-up study. Am J Epidemiol 2003; 158:486-94.
Muñoz N, Bosch FX. HPV and cervical neoplasia: review of case/control and cohort studies. In: Muñoz N, Bosch FX, Shah KV. eds. Epidemiology of Cervical Cancer and Human Papillomavirus. IARC Scientific Publ. No. 119, Lyon (France): IARC; 1992. p. 251-61.
Muñoz N, Bosch FX, De San José S, Viladiu P, Tormo J, Moreo P, et al. El virus del papiloma humano en la etiología del cáncer cervicouterino. Bol Oficina Sanit Panam 1993; 115:301-9.
Nagai Y, Toma T, Moromizato H, Maehama T, Asato T, Kariya K, et al. Persistence of human papillomavirus infection as a predictor for recurrence in carcinoma of the cervix after radiotherapy. Am J Obstet Gynecol 2004; 191:1907-13.
Philips AC, Vousden KH. Human papillomavirus and cancer: the viral transforming genes. Cancer Surv 1999; 33:55-74.
Radhakrishna PM, Sreevidya S, Pollock BH, Jayaprakash PG, Herman B. Human papillomavirus type 16 E6 and E7 gene variations in Indian cervical cancer. Gynecol Oncol 2002; 87:268-73.
Santin AD, Hermonat PL, Ravaggi A, Chiriva-Internati M, Pecorelli S, Parham PG. Radiationenhanced expression of E6/E7 transforming oncogenes of human papillomavirus-16 in human cervical carcinoma. Cancer 1998; 83:2346-52.
Smits HL, Traanberg KF, Krul MR, Prussia PR, Capone B, Bruyn A, et al. Identification of a unique group of human papillomavirus type 16 sequence variants among clinical isolates from Barbados. J Gen Virol 1994; 75:2457-62.
Song YS, Kee SH, Kim JW, Park NH, Kang SB, Chang WH, et al. Major sequence variants in E7 gene of human papillomavirus type 16 from cervical cancerous and noncancerous lesions of Korean women. Gynecol Oncol 1997; 66:275-81.
Stoppler MC, Ching K, Stoppler H, Clancy K, Schlegel R, Icenogle J. Natural variants of the human papillomavirus type 16 E6 protein differ in their abilities to alter keratinocyte differentiation and to induce p53 degradation. J Virol 1996; 70:6987-93.
Van den Brule AJC, Meijer CÉL, Bakels V, Kenemans P, Walboomers JMM. PCR based detection of genital HPV genotypes. J Clin Microbiol 1990; 28:2739-43.
Van Duin M, Snijders PJF, Vossen MTM, Klaassen E, Voorhorst F, Verheijen RHM, et al. Analysis of human papillomavirus 16 E6 variants in relation to p53 codon 72 polymorphism genotypes in cervical carcinogenesis. J Gen Virol 2000; 81:317-25.
Villa LL, Sichero L, Rahal P, Caballero O, Ferenczy A, Rohan T, et al. Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J Gen Virol 2000; 81:2959-68.
Walboomers JM, Jacobs MV, Manos MM, Bosh FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189:12-9.
Woodman CBJ, Collins S, Winter H, Bailey A, Ellis J, Prior P, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet 2001; 357:1831-6.
Xi Long Fu, Demers W, Koutsky LA, Kiviat NB, Holmes KK, Galloway DA. Analysis of human papillomavirus type 16 variants indicates establishment of persistent infection. J Infect Dis 1995; 172:747-55.
Xu X, Pang T, Guo Z, Mazurenko N, Kisselijov F, Ponten J, et al. HPV16 E6 gene variations in invasive cervical carcinoma and cancer in situ from Russian patients. Br J Cancer 2001; 84:791-5.
Zehbe I, Wilander E, Delius H, Tommasino M. Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res 1998; 58:829-33.
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