表 1. 因子対象者総数内訳対象者数内訳 % 因子対象者総数内訳対象者数内訳 % 年齢 歳 妊娠回数 0 回 58 8% 2024 歳 16 9% 1 回 0 19% 2529 歳 回 1 20% 04 歳 8 20% 回 歳 2 17% 4 回 9 6
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1 J Kanazawa Med Univ , 2016 HPV 要約 :( ) (HPV) ( ) 0 (CIN) 187 stepwiseregression ( ) CIN1 2 98% CIN % CIN grade HPV ( ) CIN grade キーワード : human papilloma virus (HPV) (CIN) 緒言 cervical intraepithelial neoplasia (CIN) human papilloma virus (HPV) (1) HPV HPV (2) HPV 9 () (2, 4) CIN1, 2 CIN grade CIN1, 2 研究方法 1. 対象 vaginal intraepithelial neoplasia (VAIN) 0 CIN 187 ( 1) 11 Loop Electrosurgical Excision Procedure (LEEP) 4
2 表 1. 因子対象者総数内訳対象者数内訳 % 因子対象者総数内訳対象者数内訳 % 年齢 歳 妊娠回数 0 回 58 8% 2024 歳 16 9% 1 回 0 19% 2529 歳 回 1 20% 04 歳 8 20% 回 歳 2 17% 4 回 9 6% 4044 歳 26 14% 5 回 6 4% 4549 歳 18 10% 6 回 2 50 歳 < 15 8% 7 回 1 CIN grade 179 I 67 7% 分娩回数 0 回 76 49% II 77 4% 1 回 24 15% III 5 20% 2 回 8 24% 結婚歴 168 未婚 59 5% 回 18 1 既婚 91 54% 初交からの期間 年 2 2 離婚 年 66 4% 初交年齢 歳 年 4 28% 14 歳 09 年 14 9% 15 歳 17 1 病変のサイズ (X/12) 18 1/ 歳 15 10% 2/ 歳 20 1% / 歳 40 26% 4/ % 19 歳 14 9% 5/12 2 1% 20 歳 27 17% 6/ % 21 歳 4 % 7/12 9 5% 22 歳 8/12 8 4% 2 歳 9/12 5 % 24 歳 2 10/12 25 歳 5 % 11/12 0 0% 喫煙 12/ % 能動喫煙 あり 46 29% HPV 型 なし あるいは 18 型 182 陽性 56 受動喫煙 あり 72 46% 陰性 % なし 84 54% Highrisk 型 182 陽性 % 能動 + 受動 あり 69 44% 陰性 6 5% なし 87 56% Probably highrisk 型 182 陽性 6 20% 陰性 % Lowrisk 型 182 陽性 12 7% 陰性 % 44
3 HPV 2. 方法 1) 治療方法 % 5 (5) 2ml 2) 副反応, 副作用調査 0 1 ) HPV 検査 ( ) DNA HPV HPV WHO (6) HPV16, 18 Highrisk (HR) 11 (1,, 5, 9, 45, 51, 52, 56, 58, 59, 68) Probably Highrisk 6 (5, 66, 67, 69, 7, 82) Lowrisk (LR) (6, 11, 40, 42, 4, 44, 54, 61, 70, 72, 81, 89) HPV Genosearch1 (MBL ) PCR Luminex PCRrSSO (6, 7) 1 HPV HPV6b, 11, 16, 18, 26, 1,, 5, 9, 42, 44, 45, 51, 52, 5, 54, 55, 56, 58, 59, 61, 62, 66, 68, 70, 71, 7, 82, 84, 90, CP6108 4) 治癒効果判定 CIN VAIN 2 negative for intraepithelial lesion or malignancy (NILM) 1 NILM HPV. 解析方法 ( ) ( ) CIN grade (1, 2, ) (12 ) ( ) HPV16, 18 HR 11 (1,, 5, 9, 45, 51, 52, 56, 58, 59, 68) Probably Highrisk 6 (5, 66, 67, 69, 7, 82) LR (6, 11, 40, 42, 4, 44, 54, 61, 70, 72, 81, 89) (6.1 ) ( 8.8 ) 2 Stepwiseregression (IBS SPSS Statistics ver21) CIN grade MannWhitney s Utest (IBS SPSS Statistics ver21) 4. 倫理的配慮, 107 結果 1. 子宮頸部および腟上皮内腫瘍患者の実態 CIN VAIN CIN 6.8% VAIN CIN VAIN1 79. VAIN2 16.7% HPV CIN1 CIN2 CIN 72.7% 84.8% 100% 2. 治療効果 VAIN CIN1 CIN2 CIN 69.2 ( 1) LEEP 11 (CIN1 1 CIN2 1 CIN 8 ) CIN1 1 LEEP LEEP LEEP CIN1 98. CIN2 98.4% CIN 69. ( 1) LEEP 1 CIN7 CIN CIN CIN CIN ( 2) VAIN VAIN CIN2 CIN CIN2 CIN CIN1 2 (P=0.0008)( 2) (P=0.00)( ) CIN grade HPV 45
4 HPV16 HPV18 HPV 12 図 1. CIN1 98. CIN2 98.4% CIN 69.. 治療の副反応とその後 ( ) 10% (17/170) 12.4% (21/170) 0 v4.0 JCOG (8) Grade 図 2. CIN CIN2 CIN CIN1 2 (P=0.0008) 図. CIN CIN2 CIN CIN1 2 (P=0.00) 4. フェノール療法に抵抗する因子の解析 ( ) ( ) CIN grade (1, 2, ) ( ) HPV16, 18 HR 11 (1,, 5, 9, 45, 51, 52, 56, 58, 59, 68) Probably Highrisk 6 (5, 66, 67, 69, 7, 82) LR (6, 11, 40, 42, 4, 44, 54, 61, 70, 72, 81, 89) 1 CIN grade (1, 2, ) MannWhitney s U test 2 Fisher s exact test CIN grade HPV16, 18 5 (6.1 ) HPV16, 18 CIN grade 6 CIN1 CIN2 CIN 46
5 HPV ( 2) ( 8.8 ) HPV 16, 18 CIN grade 5 CIN1 CIN2 CIN ( 2) HPV16, 18 ( 1) HPV16, 18 HR HPV CIN grade ( 2) 考察 2 (a) 治療期間について有意な因子に関する考察 CIN1 CIN2 CIN CIN grade HPV 表 2. 治療期間に影響する因子 治療回数に影響する因子 解析 単変量解析 多変量解析 単変量解析 多変量解析 因子 オッズ比 95%CI オッズ比 95%CI 年齢 結婚歴 初交からの年数 妊娠回数 分娩回数 能動喫煙 受動喫煙 受動喫煙含む喫煙 HPV16,18 type 陽性 Highrisk HPV 陽性 Probably Highrisk HPV 陽性 Lowrisk HPV 陽性 CIN grade CIN vs. CIN CIN2 vs. CIN 病変の範囲が広い 初交年齢が若い CIN1 CIN2 CIN CIN1 CIN2 CIN 47
6 表 1. ( ) 表 2.HPV16, 18 ( ) 単変量解析 単変量解析 因子年齢結婚歴初交からの期間 Highrisk HPV 陽性 Probably Highrisk HPV 陽性 Lowrisk HPV 陽性妊娠回数分娩回数 HPV16,18 型陽性 CIN grade 病変の範囲が広い初交年齢が早い 因子年齢結婚歴初交年齢が早い初交からの期間 Probably Highrisk HPV 陽性 Lowrisk HPV 陽性妊娠回数分娩回数受動喫煙含む喫煙病変の範囲が広い Highrisk HPV 陽性 CIN grade HPV16, 18 HR HPV CIN grade (b) 治療回数について有意な因子に関する考察 CIN1 CIN2 CIN CIN grade HPV (c) 妊娠回数が治療期間に影響するが, 治療回数には影響しない結果に関する考察 CIN grade LEEP CIN LEEP (ablation) ablation CIN (9, 10) CIN 2.98 (11) 0. (12) LEEP 916% 24% (1, 14, 15) LEEP 10 (16) LEEP 1.70 (17) LEEP (18, 19) CIN 48
7 HPV 利益相反の開示 文 1. : now ( ). MB Derma 2012; 19: : HPV. 2009; 61: Moscicki AB, Shiboski S, Hills NK et al: Regression of lowgrade squamous intraepithelial lesions in young women. Lancet 2004; 64: Sasagawa T, Takagi H, Makinoda S: Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer. J Infect Chemother 2012; 18: Lin TM, Lee SS, Lai CS et al: Phenol burn. Burns 2006; 2: Sasagawa T, Maehama T, Ideta K et al: Populationbased study for human papillomavirus (HPV) infection in young women in Japan: A multicenter study by the Japanese human papillomavirus disease education research survey group (JHERS). J Med Virol 2016; 88: Ozaki S, Kato K, Abe Y et al: Analytical performance of newly developed multiplex human papillomavirus genotyping assay using Luminex xmap TM technology (Mebgen TM HPV Kit). J Virol Methods 2014; 204: 780. 献 8. v4.0 JCOG doctor/tool/ctcaev4j_ pdf #search= 9. Ueda M, Ueki K, Kanemura M et al: Diagnostic and therapeutic laser conization for cervical intraepithelial neoplasia. Gynecol Oncol 2006; 101: Yamaguchi H, Ueda M, Kanemura M et al: Clinical efficacy of conservative laser therapy for earlystage cervical cancer. Int J Gynecol Cancer 2007; 17: Melnikow J, McGahan C, Sawaya GF et al: Cervical intraepithelial neoplasia outcomes after treatment: longterm followup from the British Columbia Cohort Study. J Natl Cancer Inst 2009; 101: Chew GK, Jandial L, Paraskevaidis E et al: Pattern of CIN recurrence following laser ablation treatment: longterm followup. Int J Gynecol Cancer 1999; 9: Andersen ES, Pedersen B, Nielsen K: Laser conization: the results of treatment of cervical intraepithelial neoplasia. Gynecol Oncol 1994; 54: Vedel P, Jakobsen H, KrygerBaggesen N et al: Fiveyear follow up of patients with cervical intraepithelial neoplasia in the cone margins after conization. Eur J Obstet Gynecol Reprod Biol 199; 50: GhaemMaghami S, Sagi S, Majeed G et al: Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a metaanalysis. Lancet Oncol 2007; 8: Kocken M, Helmerhorst TJ, Berkhof J et al: Risk of recurrent highgrade cervical intraepithelial neoplasia after successful treatment: a longterm multicohort study. Lancet Oncol 2011; 12: Kyrgiou M, Koliopoulos G, MartinHirsch P et al: Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and metaanalysis. Lancet 2006; 67: Arbyn M, Kyrgiou M, Simoens C et al: Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: metaanalysis. BMJ 2008; 7: a Jakobsson M, Gissier M, Paavonen J et al: Loop electrosurgical excision procedure and the risk for preterm birth. Obstet Gynecol 2009; 114:
8 Evaluation of Efficacy of Drug Therapy for HPV InfectionRelated Diseases of Cervix and Vagina, and Analysis of Factors Influencing the Therapeutic Effect Satoko Fujita Department of Reproductive and Perinatal Medicine, Kanazawa Medical University Graduate School of Medical Science, Uchinada, Ishikawa , Japan Objective: The goals of the study were to examine the safety and efficacy of local phenol therapy as a new treatment for human papilloma virus (HPV) infectionrelated diseases of the cervix and vagina, and to clarify factors associated with resistance to healing of lesions. Methods: The subjects were 187 patients with cervical intraepithelial tumor (CIN), including 0 patients with vaginal intraepithelial tumor (VAIN), who gave written consent to undergo phenol treatment. HPV typing was performed using the conventional method and by cytology using cervical scraped cells before and during treatment. HPV was typed using Genosearch1 (MBL, Nagoya, Japan). Cytology was performed every 2 months during the treatment period. Reexamination was performed when cytology normalized, and the case was judged to be cured if cytology remained normal 4 weeks later. Associations of lifestyle factors and test results with time to cure and frequency of treatment were examined by multiple logistic analysis using the stepwiseregression method. Results: The cure rate of phenol therapy for CIN1 and CIN2 was 98%, and 69. for CIN. Adverse reactions of phenol therapy included lower abdominal pain and an uncomfortable feeling during and after treatment in 10% of patients. Almost all subjects complained of mild vertigo and lightheadedness. These adverse reactions were transient and mostly disappeared before the patients left the hospital. Blood was collected from 0 subjects before treatment and one month after treatment, and the absence of abnormalities in liver and renal function was confirmed. There was no cervical shortening or narrowing in any patients, and 7 became pregnant naturally and gave birth after completion of treatment. In multivariate analysis, prolongation of the duration of phenol therapy was associated with high CIN grade, high frequency of pregnancy, wide range of lesions, and first sexual intercourse at a young age; and an increased frequency of treatment was associated with high CIN grade, wide range of lesions, and first sexual intercourse at a young age. Infection with a highrisk HPV type or smoking (including passive smoking) were related to lesion size and sexual intercourse at a young age. Discussion: A high CIN grade, extent of lesions, and first sexual intercourse at a young age were associated with resistance to cure. These findings suggest that it may be necessary to select surgery or drug therapy based on the lesion size and to provide education regarding sexual intercourse at a young age and smoking as risk factors for HPVrelated diseases. Key Words: human papilloma virus (HPV) infection, ablation, phenol, cervical intraepithelial tumor (CIN) 50
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