HPV HPV HPV 50% 1 HPV 96%, 93% HPV 90% HPV16/18 8 HPV HPV HPV16/18 HPV16/18 1,9,10 HPV16/18 70% HPV16/18 HPV HPV 11 HPV HPV HPV HPV16/18 HPV
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1 62 1 pp HPV HPV 10 HPV HPV HPV HPV population impact HPV HPV HPV DNA HPV 100 genomic type HPV HPV HPV HPV HPV 1 sexually transmission HPV 1 HPV 2 HPV HPV (high-risk HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 66, 68 HPV TEL: FAX: kkawana-tky@umin.ac.jp HPV low-risk HPV HPV6, 11, 42, 43, 44 HPV HPV 2-6 HPV-DNA 70 80% HPV 9 HPV HPV HPV DNA % % % % DNA % 18 40% 22 80% HPV HPV HPV-DNA HPV HPV intraepithelial lesion: IN HPV 1 7,8
2 HPV HPV HPV 50% 1 HPV 96%, 93% HPV 90% HPV16/18 8 HPV HPV HPV16/18 HPV16/18 1,9,10 HPV16/18 70% HPV16/18 HPV HPV 11 HPV HPV HPV HPV16/18 HPV16 /18 HPV HPV HPV16/18 HPV 8 HPV WHO 1999 HPV HPV 100% 45% HPV16 15% HPV18 HPV52, 58, 31, 33 HPV16 18 HPV HPV , % HPV16 18 HPV HPV16 18 HPV very high-risk HPV HPV HPV16 18
3 pp 罹患率 対人口 10 万人 以上 診断年齢 ( 歳 ) HPV16/18 HPV HPV16/ HPV16 18 HPV % HPV HPV16, 18 HPV16 18 HPV HPV ,6 75% juvenileonset recurrent respiratory papillomatosis: JORRP HPV6/11 JORRP 2 12 JORRP HPV HPV6/ JORRP ,13 HPV HPV6/11 JORRP
4 HPV 2 HPV 4 HPV GSK MSD 16/18 型 16/18/6/11 型 AS HPV16,18 (CIN2,3) HPV16,18 (CIN1-3, AIS) (VIN1-3) (VaIN1-3) HPV6/11 0, 1, 6 3 0, 2, 6 HPV Glaxo Smith Kline GSK Merck MSD 1 HPV L1 virus-like particle: L1-VLP HPV HPV L1-VLP HPV16, 18 L1-VLP 2 HPV 16, 18, 6, 11 L1-VLP 4 HPV HPV 2 HPV 2 HPV16/ HPV HPV 1 4 HPV 14 HPV 3 0, 1, 6 0, 2, 6 1 HPV HPV HPV % HPV 10 non-responder /18 6/11/16/18 CIN2+ 100% 15,16 2 DNA per-protocol efficacy: PPE HPV PPE Intention-totreat ITT 50% 2 CIN2+ HPV16,18 HPV HPV HPV16/18 30 HPV16/18
5 pp HPV16/ 価 HPV ワクチン 4 価 HPV ワクチン () () HPV3 ( ) 92.9% (1 vs 53) HPV3 ( ) 100% (0 vs 45) ( ) 52.8% (82 vs 174) ( ) 53.0% (79 vs 168) (Paavonen J, Lancet, 2009) (Munoz N., JNCI, 2010) HPV16/18 HPV 7 8 HPV16/18 HPV HPV HPV HPV16, % 17 40% HPV L1-VLP HPV HPV CIN2+ 15 HPV16/18 CIN2+ HPV31+16 CIN2+ HPV16 CIN2+ Lancet HPV HPV16/18 HPV16/18 HPV CIN2+ HPV16/18 16 HPV CIN % % 18 40% HPV16/18 HPV CIN2+ HPV HPV52, 58 CIN2+ HPV16/18 HPV 4 5 HPV16, 18 HPV VPD 4 HPV 4 HPV ,19,20 14 HPV-DNA 6/11/16/ 18 perprotocol efficacy: PPE PPE HPV6/11/16/18 CIN2/3, AIS, VIN2/3, VaIN2/3 100% HPV HPV HPV6/11 HPV16/18 intention-to-treat: ITT 50% 70 80% 3 ITT 2007 HPV
6 HPV HPV6/11/16/ PPE CIN2/3, AIS VIN2/3 VaIN2/3 ITT CIN2/3, AIS VIN2/3 VaIN2/3 n cases n cases 7,864 7,900 7,900 4,689 8,823 8,956 8,956 8, ,865 7,902 7,902 4,735 8,860 8,969 8,969 8, ,100 67,100 55,100 91,99 40,60 40,89 38,98 73,85 CIN2/3: AIS: VIN2/3: VaIN2/3: % % 21, / HPV HPV HPV ITT HPV 16, 18 HPV DNA 16, 18 10% 30% % DNA PPE HPV16/18 CIN % HPV DNA HPV16/ ITT HPV16, 18 CIN % ITT HPV16, 18 CIN HPV16, 18 PPE HPV 21 HPV16 18 DNA CIN2+ 3 HPV HPV HPV HPV CIN2+ DNA 3 100% DNA CIN2+
7 pp HPV 22 16, 18 HPV HPV 4 HPV HPV 71 4 HPV 4 HPV FDA HPV HPV HPV HPV HPV 4 HPV ~ 1 6 ~ 3 HPV 1 zur Hausen, H. Papillomavirus and cancer: from basic studies to clinical application. Nat Rev Cancer, 2: , Insinga RP, Dasbach EJ, Elbasha EH, Epidemiologic natural history and clinical management of human papillomavirus (HPV) Disease: a critical and systemat- ic review of the literature in the development of an HPV dynamic transmission model, BMC Infect Dis, 9: , Gissmann L, Wolnik L, Ikenberg H, et al., Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci USA, 80: , ,,IASR,29: , , : , The current status of development of prophylactic vaccines against human papillomavirus infection. Report of a technical meeting. Geneva, February, Gillison ML, Chaturvedi AK, Lowy DR, HPV prophylactic vaccine and the potential prevention of noncervical cancers in both men and women, Cancer, 113: , Bosch FX, et al.: Human papillomavirus and cervical cancer - burden and assessment of causality. J Natl Cancer Inst Monogr, 31: 3-13, Vinokurova S, Wentzensen N, Kraus I, Klaes R, Driesch C, Melsheimer P, Kisseljov F, D_rst M, Schneider A, von Knebel Doeberitz M. Type-dependent integration frequency of human papillomavirus genomes in cervical lesions. Cancer Res, 68: , Kawana K, et al., Expression of CD1d and ligandinduced cytokine production are tissue-specific in mucosal epithelia of the human lower reproductive tract. Infect Immun, 76: , Kimberlin DW: Current status of antiviral therapy for juvenile-onset recurrent respiratory papillomatosis. Antiviral Res 63: , Reeves WC. et al. Arch Otolaryngol Head Neck Surg. 129: , CDC, FDA licensure of quadrivalent HPV vaccine (HPV4, Gardasil) for use in males and guidance from the ACIP, MMWR, 59(20), Paavonen J, Naud P, Salmer n J,et al ; HPV PATRICIA Study Group, Greenacre M.: Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): Final analysis of a double-blind, randomised study in young women. Lancet, 374: , Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsagu X, Skinner SR, Apter D, Naud P, Salmer n J, Chow SN, Kitchener H, Teixeira JC, Hedrick J, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, De Carvalho NS, Germar MJ, Peters K, Mindel A, De Sutter P, Bosch FX, David MP, Descamps D, Struyf F, Dubin G. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol.13:89-99,
8 pp Miura S, Matsumoto K, Oki A, Satoh T, Tsunoda H, Yasugi T, Taketani Y, Yoshikawa H. Do we need a different strategy for HPV screening and vaccination in East Asia? Int J Cancer. 119: , De Carvalho N, Teixeira J, Roteli-Martins CM, et al., Sustained efficacy and immunogenicity of the HPV- 16/18 AS04-adjuvanted vaccine up to 7.3 years in young adult women, Vaccine 28: , Kjaer SK, et al., A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (types 6/11/16/18) vaccine against high-grade cervical and external genital lesions, Cancer Prev Res, 2: , Mu_oz N, et al.: Impact of Human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst 102: , Donovan B, et al., Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data, Lancet Infect Dis, E-pub, Fairley CK, et al., Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women. Sex Transm Infect, 85: , Brotherton J, Fridman M, May CL, et al., Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet, 377: , Konno R, Dobbelaere KO, Godeaux OO, Tamura S, Yoshikawa H., Immunogenicity, reactogenicity, and safety of human papillomavirus 16/18 AS04-adjuvanted vaccine in Japanese women: interim analysis of a phase II, double-blind, randomized controlled trial at month 7. Int J Gyne Cancer, 19: , Inoue M et al. The evaluation of human papillomavirus DNA testing in primary screening for cervical lesions in a large Japanese population.: Int J Gynecol Cancer. 16, , Garland SM, Ault KA, Gall SA, et al on behalf of the Quadrivalent Human Papillomavirus Vaccine Phase III Investigators, Pregnancy and Infant Outcomes in the Clinical Trials of a Human Papillomavirus Type 6/11/16/18 Vaccine. Obstet Gynecol, 114: , Human papillomavirus prophylactic vaccine Kei KAWANA Assistant Professor Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo Hongo, Bunkyo-ku, Tokyo kkawana-tky@umin.ac.jp Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is years old and became 20 years younger than that at The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.
59 2 pp.243-2482009 1. 20 30 35-39 2 HPV HPV16 HPV18 HPV16/18 2 Cervarix HPV16/18 HPV6/11 4 Gardasil CIN2/3 AIS 100% 10 HPV 110 26 HPV human papillomavirus, HPV 15 16, 18, 31, 33, 35, 39, 45, 51, 52, 56,
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