HPV感染病変の段階的管理におけるHPVジェノタイプの意義と 免疫の関与について
子宮頸癌や子宮頸部異形成(CIN)はHPV感染が原因となる。HPV予防ワクチンの普及とともに子宮頸癌が減少することが期待されているが、根絶までには時間を要する。子宮頸癌排除のための段階的戦略として、HPV予防ワクチン接種による1次予防、検診による早期発見やCIN管理による2次予防、子宮頸癌発症後の治療介入における3次予防に分けられる。本稿では、特に2次予防段階におけるHPVジェノタイプに基づいたCIN管理方法について概説するとともに、HPVに対するヒト免疫応答についても概説する。...
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| Published in | Reproductive Immunology and Biology Vol. 35; pp. 9 - 15 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本生殖免疫学会
2020
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 1881-607X 1881-7211 |
| DOI | 10.3192/jsirib.35.9 |
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| Abstract | 子宮頸癌や子宮頸部異形成(CIN)はHPV感染が原因となる。HPV予防ワクチンの普及とともに子宮頸癌が減少することが期待されているが、根絶までには時間を要する。子宮頸癌排除のための段階的戦略として、HPV予防ワクチン接種による1次予防、検診による早期発見やCIN管理による2次予防、子宮頸癌発症後の治療介入における3次予防に分けられる。本稿では、特に2次予防段階におけるHPVジェノタイプに基づいたCIN管理方法について概説するとともに、HPVに対するヒト免疫応答についても概説する。 |
|---|---|
| AbstractList | 子宮頸癌や子宮頸部異形成(CIN)はHPV感染が原因となる。HPV予防ワクチンの普及とともに子宮頸癌が減少することが期待されているが、根絶までには時間を要する。子宮頸癌排除のための段階的戦略として、HPV予防ワクチン接種による1次予防、検診による早期発見やCIN管理による2次予防、子宮頸癌発症後の治療介入における3次予防に分けられる。本稿では、特に2次予防段階におけるHPVジェノタイプに基づいたCIN管理方法について概説するとともに、HPVに対するヒト免疫応答についても概説する。 |
| Author | 川名, 敬 田口, 歩 |
| Author_xml | – sequence: 1 fullname: 田口, 歩 organization: 東京大学 産婦人科教室 〒113-8655 東京都文京区本郷7-3-1 – sequence: 1 fullname: 川名, 敬 organization: 日本大学 産婦人科教室 〒173-8610 東京都板橋区大谷口上町30番1号 |
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| References | 1) Van Doorslaer K, Tan Q, Xirasagar S, Bandaru S, Gopalan V, Mohamoud Y, Huyen Y, McBride AA. The Papillomavirus Episteme: a central resource for papillomavirus sequence data and analysis. Nucleic Acids Res. 2013;41(Database issue):D571-8. doi: .10.1093/nar/gks984 3) Matsumoto K, Oki A, Furuta R, Maeda H, Yasugi T, Takatsuka N, Mitsuhashi A, Fujii T, Hirai Y, Iwasaka T, Yaegashi N, Watanabe Y, Nagai Y, Kitagawa T, Yoshikawa H; Japan HPV And Cervical Cancer Study Group. Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study. Int J Cancer. 2011;128:2898-910. doi: .10.1002/ijc.25630 14) Jiang B, Xue M. Correlation of E6 and E7 levels in high-risk HPV16 type cervical lesions with CCL20 and Langerhans cells. Genet Mol Res. 2015;14:10473-81. doi: .10.4238/2015.September.8.8 23) Chen XJ, Han LF, Wu XG, Wei WF, Wu LF, Yi HY, Yan RM, Bai XY, Zhong M, Yu YH, Liang L, Wang W. Clinical Significance of CD163+ and CD68+ Tumor-associated Macrophages in High-risk HPV-related Cervical Cancer. J Cancer. 2017;8:3868-3875. doi: .10.7150/jca.21444 4) Taguchi A, Hara K, Tomio J, Kawana K, Tanaka T, Baba S, Kawata A, Eguchi S, Tsuruga T, Mori M, Adachi K, Nagamatsu T, Oda K, Yasugi T, Osuga Y, Fujii T. Multistate Markov Model to Predict the Prognosis of High-Risk Human Papillomavirus-Related Cervical Lesions. Cancers (Basel). 2020;12:270. doi: .10.3390/cancers12020270 12) Guess JC, McCance DJ. Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3alpha production. J Virol. 2005;79:14852-62. doi: .10.1128/JVI.79.23.14852-14862.2005 15) Miura S, Kawana K, Schust DJ, Fujii T, Yokoyama T, Iwasawa Y, Nagamatsu T, Adachi K, Tomio A, Tomio K, Kojima S, Yasugi T, Kozuma S, Taketani Y. CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein: a possible mechanism for immune evasion by HPV. J Virol. 2010;84:11614-23. doi: .10.1128/JVI.01053-10 11) Iijima N, Goodwin EC, Dimaio D, Iwasaki A. High-risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans cells. Virology. 2013;444:257-62. doi: .10.1016/j.virol.2013.06.020 20) Molling JW, de Gruijl TD, Glim J, Moreno M, Rozendaal L, Meijer CJ, van den Eertwegh AJ, Scheper RJ, von Blomberg ME, Bontkes HJ. CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia. Int J Cancer. 2007;121:1749-55. doi: .10.1002/ijc.22894 21) Kojima S, Kawana K, Tomio K, Yamashita A, Taguchi A, Miura S, Adachi K, Nagamatsu T, Nagasaka K, Matsumoto Y, Arimoto T, Oda K, Wada-Hiraike O, Yano T, Taketani Y, Fujii T, Schust DJ, Kozuma S. The prevalence of cervical regulatory T cells in HPV-related cervical intraepithelial neoplasia (CIN) correlates inversely with spontaneous regression of CIN. Am J Reprod Immunol. 2013;69:134-41. doi: .10.1111/aji.12030 9) Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998;12:2061-72. doi: .10.1101/gad.12.13.2061 13) Jimenez-Flores R, Mendez-Cruz R, Ojeda-Ortiz J, Muñoz-Molina R, Balderas-Carrillo O, de la Luz Diaz-Soberanes M, Lebecque S, Saeland S, Daneri-Navarro A, Garcia-Carranca A, Ullrich SE, Flores-Romo L. High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract. Immunology. 2006;117:220-8. doi: .10.1111/j.1365-2567.2005.02282.x 2) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 100B:1-441, 2012. Available from: http://monographs.iarc.fr/ENG/Monographs/vol100B/index.php 18) Ikeda Y, Uemura Y, Asai-Sato M, Nakao T, Nakajima T, Iwata T, Akiyama A, Satoh T, Yahata H, Kato K, Maeda D, Aoki D, Kawana K. Safety and efficacy of mucosal immunotherapy using human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine for the treatment of high-grade squamous intraepithelial lesion (HSIL): the study protocol of a randomized placebo-controlled clinical trial (MILACLE study). Jpn J Clin Oncol. 2019;49:877-880. doi: .10.1093/jjco/hyz095 6) Richards KH, Wasson CW, Watherston O, Doble R, Eric Blair G, Wittmann M, Macdonald A. The human papillomavirus (HPV) E7 protein antagonises an Imiquimod-induced inflammatory pathway in primary human keratinocytes. Sci Rep. 2015;5:12922. doi: .10.1038/srep12922 16) Kawana K, Adachi K, Kojima S, Taguchi A, Tomio K, Yamashita A, Nishida H, Nagasaka K, Arimoto T, Yokoyama T, Wada-Hiraike O, Oda K, Sewaki T, Osuga Y, Fujii T. Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients. Vaccine. 2014;32:6233-9. doi: .10.1016/j.vaccine.2014.09.020 5) Hasan UA, Zannetti C, Parroche P, Goutagny N, Malfroy M, Roblot G, Carreira C, Hussain I, Müller M, Taylor-Papadimitriou J, Picard D, Sylla BS, Trinchieri G, Medzhitov R, Tommasino M. The human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter. J Exp Med. 2013;210:1369-87. doi: .10.1084/jem.20122394 22) Kawachi A, Yoshida H, Kitano S, Ino Y, Kato T, Hiraoka N. Tumor-associated CD204(+) M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. Cancer Sci. 2018;109:863-870. doi: .10.1111/cas.13476 8) Cortese MS, Ashrafi GH, Campo MS. All 4 di-leucine motifs in the first hydrophobic domain of the E5 oncoprotein of human papillomavirus type 16 are essential for surface MHC class I downregulation activity and E5 endomembrane localization. Int J Cancer. 2010;126:1675-82. doi: .10.1002/ijc.25004 10) Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem. 2000;275:6764-9. doi: .10.1074/jbc.275.10.6764 17) Komatsu A, Igimi S, Kawana K. Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells. Vaccine. 2018;36:3423-3426. doi: .10.1016/j.vaccine.2018.05.009 7) Campo MS, Graham SV, Cortese MS, Ashrafi GH, Araibi EH, Dornan ES, Miners K, Nunes C, Man S. HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology. 2010;407:137-42. doi: .10.1016/j.virol.2010.07.044 19) Liu G, Sharma M, Tan N, Barnabas RV. HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer. AIDS. 2018;32:795-808. doi: .10.1097/QAD.0000000000001765 |
| References_xml | – reference: 6) Richards KH, Wasson CW, Watherston O, Doble R, Eric Blair G, Wittmann M, Macdonald A. The human papillomavirus (HPV) E7 protein antagonises an Imiquimod-induced inflammatory pathway in primary human keratinocytes. Sci Rep. 2015;5:12922. doi: .10.1038/srep12922 – reference: 2) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. Volume 100 B. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 100B:1-441, 2012. Available from: http://monographs.iarc.fr/ENG/Monographs/vol100B/index.php – reference: 13) Jimenez-Flores R, Mendez-Cruz R, Ojeda-Ortiz J, Muñoz-Molina R, Balderas-Carrillo O, de la Luz Diaz-Soberanes M, Lebecque S, Saeland S, Daneri-Navarro A, Garcia-Carranca A, Ullrich SE, Flores-Romo L. High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract. Immunology. 2006;117:220-8. doi: .10.1111/j.1365-2567.2005.02282.x – reference: 20) Molling JW, de Gruijl TD, Glim J, Moreno M, Rozendaal L, Meijer CJ, van den Eertwegh AJ, Scheper RJ, von Blomberg ME, Bontkes HJ. CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia. Int J Cancer. 2007;121:1749-55. doi: .10.1002/ijc.22894 – reference: 8) Cortese MS, Ashrafi GH, Campo MS. All 4 di-leucine motifs in the first hydrophobic domain of the E5 oncoprotein of human papillomavirus type 16 are essential for surface MHC class I downregulation activity and E5 endomembrane localization. Int J Cancer. 2010;126:1675-82. doi: .10.1002/ijc.25004 – reference: 4) Taguchi A, Hara K, Tomio J, Kawana K, Tanaka T, Baba S, Kawata A, Eguchi S, Tsuruga T, Mori M, Adachi K, Nagamatsu T, Oda K, Yasugi T, Osuga Y, Fujii T. Multistate Markov Model to Predict the Prognosis of High-Risk Human Papillomavirus-Related Cervical Lesions. Cancers (Basel). 2020;12:270. doi: .10.3390/cancers12020270 – reference: 7) Campo MS, Graham SV, Cortese MS, Ashrafi GH, Araibi EH, Dornan ES, Miners K, Nunes C, Man S. HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology. 2010;407:137-42. doi: .10.1016/j.virol.2010.07.044 – reference: 12) Guess JC, McCance DJ. Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3alpha production. J Virol. 2005;79:14852-62. doi: .10.1128/JVI.79.23.14852-14862.2005 – reference: 3) Matsumoto K, Oki A, Furuta R, Maeda H, Yasugi T, Takatsuka N, Mitsuhashi A, Fujii T, Hirai Y, Iwasaka T, Yaegashi N, Watanabe Y, Nagai Y, Kitagawa T, Yoshikawa H; Japan HPV And Cervical Cancer Study Group. Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study. Int J Cancer. 2011;128:2898-910. doi: .10.1002/ijc.25630 – reference: 9) Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998;12:2061-72. doi: .10.1101/gad.12.13.2061 – reference: 15) Miura S, Kawana K, Schust DJ, Fujii T, Yokoyama T, Iwasawa Y, Nagamatsu T, Adachi K, Tomio A, Tomio K, Kojima S, Yasugi T, Kozuma S, Taketani Y. CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein: a possible mechanism for immune evasion by HPV. J Virol. 2010;84:11614-23. doi: .10.1128/JVI.01053-10 – reference: 23) Chen XJ, Han LF, Wu XG, Wei WF, Wu LF, Yi HY, Yan RM, Bai XY, Zhong M, Yu YH, Liang L, Wang W. Clinical Significance of CD163+ and CD68+ Tumor-associated Macrophages in High-risk HPV-related Cervical Cancer. J Cancer. 2017;8:3868-3875. doi: .10.7150/jca.21444 – reference: 18) Ikeda Y, Uemura Y, Asai-Sato M, Nakao T, Nakajima T, Iwata T, Akiyama A, Satoh T, Yahata H, Kato K, Maeda D, Aoki D, Kawana K. Safety and efficacy of mucosal immunotherapy using human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine for the treatment of high-grade squamous intraepithelial lesion (HSIL): the study protocol of a randomized placebo-controlled clinical trial (MILACLE study). Jpn J Clin Oncol. 2019;49:877-880. doi: .10.1093/jjco/hyz095 – reference: 14) Jiang B, Xue M. Correlation of E6 and E7 levels in high-risk HPV16 type cervical lesions with CCL20 and Langerhans cells. Genet Mol Res. 2015;14:10473-81. doi: .10.4238/2015.September.8.8 – reference: 16) Kawana K, Adachi K, Kojima S, Taguchi A, Tomio K, Yamashita A, Nishida H, Nagasaka K, Arimoto T, Yokoyama T, Wada-Hiraike O, Oda K, Sewaki T, Osuga Y, Fujii T. Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients. Vaccine. 2014;32:6233-9. doi: .10.1016/j.vaccine.2014.09.020 – reference: 11) Iijima N, Goodwin EC, Dimaio D, Iwasaki A. High-risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans cells. Virology. 2013;444:257-62. doi: .10.1016/j.virol.2013.06.020 – reference: 22) Kawachi A, Yoshida H, Kitano S, Ino Y, Kato T, Hiraoka N. Tumor-associated CD204(+) M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. Cancer Sci. 2018;109:863-870. doi: .10.1111/cas.13476 – reference: 17) Komatsu A, Igimi S, Kawana K. Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells. Vaccine. 2018;36:3423-3426. doi: .10.1016/j.vaccine.2018.05.009 – reference: 1) Van Doorslaer K, Tan Q, Xirasagar S, Bandaru S, Gopalan V, Mohamoud Y, Huyen Y, McBride AA. The Papillomavirus Episteme: a central resource for papillomavirus sequence data and analysis. Nucleic Acids Res. 2013;41(Database issue):D571-8. doi: .10.1093/nar/gks984 – reference: 5) Hasan UA, Zannetti C, Parroche P, Goutagny N, Malfroy M, Roblot G, Carreira C, Hussain I, Müller M, Taylor-Papadimitriou J, Picard D, Sylla BS, Trinchieri G, Medzhitov R, Tommasino M. The human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter. J Exp Med. 2013;210:1369-87. doi: .10.1084/jem.20122394 – reference: 21) Kojima S, Kawana K, Tomio K, Yamashita A, Taguchi A, Miura S, Adachi K, Nagamatsu T, Nagasaka K, Matsumoto Y, Arimoto T, Oda K, Wada-Hiraike O, Yano T, Taketani Y, Fujii T, Schust DJ, Kozuma S. The prevalence of cervical regulatory T cells in HPV-related cervical intraepithelial neoplasia (CIN) correlates inversely with spontaneous regression of CIN. Am J Reprod Immunol. 2013;69:134-41. doi: .10.1111/aji.12030 – reference: 10) Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem. 2000;275:6764-9. doi: .10.1074/jbc.275.10.6764 – reference: 19) Liu G, Sharma M, Tan N, Barnabas RV. HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer. AIDS. 2018;32:795-808. doi: .10.1097/QAD.0000000000001765 |
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| Title | HPV感染病変の段階的管理におけるHPVジェノタイプの意義と 免疫の関与について |
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