Elucidation of molecular mechanism of cervical cancer and its clinical application

• Project/Area Number: 26462540
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Fujita Health University
• Principal Investigator: Fujii Takuma 藤田保健衛生大学, 医学部, 教授 (10218969)
• Co-Investigator(Kenkyū-buntansha): 岩田 卓 慶應義塾大学, 医学部(信濃町), 講師 (30296652)
• Co-Investigator(Renkei-kenkyūsha): Takayanagi Atsushi 慶應義塾大学, 医学部, 講師 (80245464)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: human papillomavirus / vaccine / cervical cancer / 子宮頸癌 / ワクチン / ヒトパピローマウイルス / 子宮頸がん / パピローマウイルス / マイクロRNA / サイトカイン

Outline of Final Research Achievements

Monitoring the attribution of human papillomavirus (HPV) genotypes to cervical precancerous lesions is essential for evaluating the potential efficacy of HPV vaccines. Three procedures, Clinichip HPV test (Chip) and modified GP5+/6+ PCR coupled to fluorescent bead sorter detection (MGP) in exfoliated cervical cells (C-Chip and C-MGP, respectively) or formalin-fixed paraffin-embedded tissues (F-MGP), were compared to determine the appropriate genotyping procedures. In CIN 2/3 specimens, HPV16/18/31/33/45/52/58 hierarchical attribution was 88.4% (76/86) with C-Chip, 86.0% (74/86) with C-MGP, and 83.7% (72/86) with F-MGP (p = 0.49). Although F-MGP is theoretically a reliable method for determining HPV genotype attribution, it is acceptable to use C-Chip or C-MGP, coupled to the hierarchical attribution formula to correct the bias of multiple infections. These approaches using exfoliated cervical cells are practical for monitoring the efficacy of HPV vaccines.

Research Products

• [Journal Article] 当院における腹腔鏡下子宮体癌手術の術前診断の精度 (2017)
  • Author(s): 河合智之、鳥居 裕、大谷清香、市川亮子、植田高弘、藤井多久磨
  • Journal Title: 日本婦人科腫瘍学会雑誌 Volume: 35(1) Pages: 1-7
  • NAID: 40021099808
  • Peer Reviewed
• [Journal Article] Preoperative magnetic resonance imaging findings of myoma as risk factors for bleeding during laparoscopic myomectomy (2016)
  • Author(s): Ueda T, Murayama K, Nishizawa H, Fujii T, Toyama H
  • Journal Title: Fujita Med J Volume: 2(3) Pages: 59-61
  • NAID: 130005264394
  • Peer Reviewed
• [Journal Article] Ovarian clear cell adenocarcinoma revealed in a young patient during hormone therapy: a case report (2016)
  • Author(s): Kawai S, Ichikawa R, Ueda T, Urano M, Kuroda M, Fujii T
  • Journal Title: Fujita Med J Volume: 2(4) Pages: 77-79
  • NAID: 130005405026
  • Peer Reviewed
• [Journal Article] Comparison of methods using paraffin‐embedded tissues and exfoliated cervical cells to evaluate human papillomavirus genotype attribution (2016)
  • Author(s): Fujii T, Torii Y, Kukimoto I, Saito M, Iwata T, Takahashi H, Ichikawa R, Kawai S, Otani S, Aoki D
  • Journal Title: Cancer Sci Volume: 107(10) Issue: 10 Pages: 1520-1526
  • DOI: 10.1111/cas.13030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased levels of soluble corin in pre-eclampsia and fetal growth restriction (2016)
  • Author(s): Miyazaki J, Nishizawa H, Kambayashi A, Ito M, Noda Y, Terasawa S,Kato T,Miyamura H,Shiogama K,Sekiya T,Kurahashi H,Fujii T
  • Journal Title: Placenta Volume: 48 Pages: 20-25
  • Peer Reviewed
• [Journal Article] Changing state of gynecologic oncologist specialty in Japan. (2016)
  • Author(s): Fujii T
  • Journal Title: J Obstet Gynaecol Res Volume: 42 Issue: 5 Pages: 481-488
  • DOI: 10.1111/jog.12970
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 当院での子宮頸部円錐切除術術後出血に関する検討 (2016)
  • Author(s): 寺澤 すみれ、鳥居 裕、宮崎 純、大脇晶子、小川千紗、坂部慶子、野田佳照、大谷清香、伊藤真友子、市川亮子、宮村浩徳、西澤春紀、西尾永司、藤井多久磨
  • Journal Title: 東海産科婦人科学会雑誌 Volume: 53 Pages: 293-297
  • Peer Reviewed
• [Journal Article] Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center (2016)
  • Author(s): Kasuga Y, Nishio H, Miyakoshi K, Sato S, Sugiyama J, Matsumoto T, Tanaka K, Ochiai D, Minegishi K, Hamatani T, Iwata T, Morisada T, Nakamura M, Fujii T, Kuji N, Aoki D, Tanaka M
  • Journal Title: Int J Gynecol Cancer Volume: 26 Issue: 1 Pages: 163-168
  • DOI: 10.1097/igc.0000000000000571
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis? (2015)
  • Author(s): Koji Matsumoto, Hiroo Maeda, Akinori Oki, Naoyoshi Takatsuka, Toshiharu Yasugi, Reiko Furuta, Ranko Hirata, Akira Mitsuhashi, Kei Kawana, Takuma Fujii, Takashi Iwata, Yasuo Hirai, Masatoshi Yokoyama, Nobuo Yaegashi, Yoh Watanabe, Yutaka Nagai, Hiroyuki Yoshikawa
  • Journal Title: Cancer Science Volume: 106(10) Issue: 10 Pages: 1448-1454
  • DOI: 10.1111/cas.12760
  • Peer Reviewed / Open Access
• [Journal Article] 第2章 婦人科腫瘍分野 A.子宮頸癌 HPVスクリーニング検査 (2015)
  • Author(s): 藤井多久磨、市川亮子、鳥居 裕
  • Journal Title: 産科と婦人科 増刊号 Volume: 82 suppl Pages: 159-161
• [Journal Article] 第2章 婦人科腫瘍分野 A.子宮頸癌 HPV型判定検査 (2015)
  • Author(s): 藤井多久磨、市川亮子、鳥居 裕
  • Journal Title: 産科と婦人科 増刊号 Volume: 82 suppl Pages: 162-163
• [Journal Article] 特集 子宮頸癌治療の新たな選択肢 子宮頸癌のトランスレーショナルリサーチ (2015)
  • Author(s): 藤井多久磨、市川亮子、鳥居 裕、河合智之
  • Journal Title: 産婦人科の実際 Volume: 64 Pages: 2057-2062
• [Journal Article] Performance of p16INK4a/Ki-67 immunocytochemistry for identifying CIN2+ in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion specimens: a Japanese Gynecologic Oncology Group study. (2015)
  • Author(s): Fujii T, Saito M, Hasegawa T, Iwata T, Kuramoto H, Kubushiro K, Ohmura M, Ochiai K, Arai H, Sakamoto M, Motoyama T, Aoki D
  • Journal Title: International journal of clinical oncology Volume: 20 Issue: 1 Pages: 134-142
  • DOI: 10.1007/s10147-014-0688-0
  • Peer Reviewed / Open Access
• [Journal Article] Cytokine profile in cervical mucosa of Japanese patients with cervical intraepithelial neoplasia. (2015)
  • Author(s): Iwata T, Fujii T, Morii K, Saito M, Sugiyama J, Nishio H, Morisada T, Tanaka K, Yaguchi T, Kawakami Y, Aoki D
  • Journal Title: International journal of clinical oncology Volume: 20 Issue: 1 Pages: 126-133
  • DOI: 10.1007/s10147-014-0680-8
  • Peer Reviewed / Open Access
• [Journal Article] Age-related decrease of meiotic cohesins in human oocyte (2014)
  • Author(s): Tsutsumi M, Fujiwara R, Nishizawa H, Ito M, Kogo H, Inagaki H, Ohye T, Kato T, Fujii T, Kurahashi H
  • Journal Title: PLoS One Volume: 9, Issue: 5 Pages: 1-8
  • DOI: 10.1371/journal.pone.0096710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Surgical Anatomy imaging associated with cervical cancer treatment:A cadaveric study (2014)
  • Author(s): Nakamura M, Fujii T, Imanishi N, Jinzaki M, Yamada M, Kuribayashi S, Aoki D
  • Journal Title: Clin Anat Volume: 27 Issue: 3 Pages: 503-510
  • DOI: 10.1002/ca.22319
  • Peer Reviewed
• [Presentation] Symposium: Recent advances in gynecologic cancer surgery: Sparing Fertility / Retrospective analysis of fertility-sparing surgery for cervical cancer (2016)
  • Author(s): Fujii T, Nishio H, Sugiyama J, Iwata T, Tanaka K, Susumu N, Tsuda H, Minegishi K, Hamatani T, Yoshimura Y, Aoki D
  • Organizer: 40th World Congress of the International College of Surgeons
  • Place of Presentation: 京都国際会館、京都市
  • Year and Date: 2016-10-23
  • Int'l Joint Research
• [Presentation] Estimation of the Bethesda system with the cervical cytology and the following histology results from a single institution (2016)
  • Author(s): 大谷清香、鳥居 裕、市川亮子、伊藤真友子、河合智之、平澤 浩、黒田 誠、藤井多久磨
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2016-10-20
• [Presentation] Estimation of the Bethesda system with the cervical cytology and the following histology results from a single institution. (2016)
  • Author(s): Sayaka Otani , Yutaka Torii, Ryoko Ichikawa, Mayuko Ito, Tomoyuki Kawai, Hiroshi Hirasawa, Makoto Kuroda, Takuma Fujii
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-20
• [Presentation] ヒトパピローマウイルス感染予防ワクチンの効果を擦過細胞検体でモニタリングする際の注意点 (2016)
  • Author(s): 藤井多久磨、柊元巌、岩田卓、青木大輔
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2016-10-06
• [Presentation] Estimation of HPV genotype attribution using cervical exfoliated cells for m onitoring the efficacy of HPV vaccines (2016)
  • Author(s): Fujii Takuma, Kukimoto Iwao, Iwata Takashi, Aoki Daisuke
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-06
• [Presentation] Abnormal cervical cytology among Japanese young women (2016)
  • Author(s): Ichikawa R, Kawai S, Torii Y, Kuroda M, Fujii T
  • Organizer: The 19th international congress of Cytology
  • Place of Presentation: パシフィコ横浜,横浜市
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] Abnormal cervical cytology of Japanese young women (2016)
  • Author(s): Ryoko Ichikawa, Satoshi Kawai, Yutaka Torii1 , Makoto Kuroda2 , Fujii Takuma
  • Organizer: ICC2016
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] How do we estimate HPV genotype attribution using cervical exfoliated cells to monitor the efficacy of HPV vaccination? (2016)
  • Author(s): Torii Y, Fujii T, Iwata T, Aoki D
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム、東京都
  • Year and Date: 2016-04-21
• [Presentation] How do we treat and care the patient with multiple primaries followed with a recurrent anogenital cancer? ; A case report (2015)
  • Author(s): T.Fujii, A.Ohwaki, M.Saito, T.Iwata, I.Kukimoto, H.Sato, T.Okumoto, Y.Torii
  • Organizer: 30th International Papillomavirus Conference & Clinical Workshop (HPV 2015)
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] 特別講演 子宮頸がん予防に関する最近の話題－HPV検査とワクチンを中心に－ (2014)
  • Author(s): 藤井多久磨
  • Organizer: 第9回香川県STD研究会
  • Place of Presentation: ロイヤルパークホテル高松（香川県高松市）
  • Year and Date: 2014-11-21
  • Invited
• [Presentation] 特別講演 / 子宮頸部病変に対する手術 －過去・現在・そして未来への展望－ (2014)
  • Author(s): 藤井多久磨
  • Organizer: 栃木県産婦人科手術手技研究会第15回総会
  • Place of Presentation: ホテル東日本宇都宮（栃木県宇都宮市）
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] 専攻医教育プログラム4 / HPVワクチン (2014)
  • Author(s): 藤井多久磨
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2014-04-18 – 2014-04-20
  • Invited
• [Book] ヒトパピローマウイルス（HPV）ジェノタイプ判定．臨床検査データブック LAB DATA 2017-2018（監修：高久文麿，黒川 清，春日雅人，編集：北村 聖） (2017)
  • Author(s): 藤井多久磨
  • Total Pages: 2
  • Publisher: 医学書院
• [Book] 女性医療のすべて（編集：大田博明） (2016)
  • Author(s): 藤井多久磨
  • Total Pages: 2
  • Publisher: メディカルレビュー社
• [Book] 臨床検査データブック LAB DATA 2015-2016 (2015)
  • Author(s): 藤井多久磨
  • Total Pages: 1059
  • Publisher: 医学書院
• [Book] 婦人科診療ハンドブック (2014)
  • Author(s): 藤井多久磨
  • Total Pages: 470
  • Publisher: 中央医学社
• [Book] 婦人科癌診療Q&A －一つ上を行く診療の実践－ (2014)
  • Author(s): 藤井多久磨，仲村 勝
  • Total Pages: 339
  • Publisher: 中外医学社
• [Book] 女性医学ガイドブック更年期医療編 2014年度版 (2014)
  • Author(s): 鳥居 裕，藤井多久磨
  • Total Pages: 463
  • Publisher: 金原出版