Study on the mechanisms of acquiring cancer stem cell-like characteristics related with HPV-16 E6 gene in oral squamous cell carcinomas

• Project/Area Number: 15K11290
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Sugiyama Masaru 広島大学, 医系科学研究科(歯), 教授 (70187681)
• Co-Investigator(Kenkyū-buntansha): 重石 英生 広島大学, 医歯薬保健学研究科(歯), 講師 (90397943)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: HPV / リスクファクター / 口腔癌 / HPV16 / 癌幹細胞 / 口腔 / 中咽頭

Outline of Final Research Achievements

Oral rinse and gargle samples obtained from 94 healthy individuals were tested for HPV16 DNA by PCR. The percentage of HPV16-positive cases was higher in the gargle (28.7%) as compared to the oral rinse (16.0%) samples. In the oral rinse samples, males showed a significantly higher rate of HPV16 than females.To identify the risk factors for oral HPV infection, we performed systematic review and meta-analysis of studies reporting the prevalence of oral HPV infection in healthy individuals. Sexual behavior and smoking were importantly related to oral HPV infection in healthy individuals.

Academic Significance and Societal Importance of the Research Achievements

咽頭含嗽サンプルが口腔含嗽サンプルよりもHPV16 DNA陽性率が高い理由として，中咽頭の組織学的特徴の関与が考えられた．また，口腔内の衛生環境とHPV感染には密接な関連があり，口腔衛生状態を良好に保つことは，口腔のHPV感染を予防するために重要であると考えられる. HPV関連口腔癌の予防を科学的根拠に基づいて行うために，HPV DNA陽性口腔癌におけるHPVの役割を明確にする必要があり，口腔HPV感染の基礎および臨床的研究の推進が望まれる．

Research Products

• [Journal Article] High HPV16 E6 viral load in the oral cavity is associated with an increased number of bacteria: A preliminary study. (2018)
  • Author(s): Shigeishi H, Sugiyama M, Ohta K, Yokoyama S, Sakuma M, Murozumi H, Kato H, Takechi M.
  • Journal Title: Biomed Rep. Volume: 8 Pages: 59-64
  • Peer Reviewed / Open Access
• [Journal Article] Human Papillomavirus (HPV) 感染と口腔癌の関係について―最近の研究から―（総説） (2017)
  • Author(s): 重石英生，杉山 勝
  • Journal Title: 口腔衛生学会雑誌 Volume: 67 Pages: 149-159
  • Peer Reviewed / Open Access
• [Journal Article] Human Papillomavirus (HPV) 感染と口腔癌の関係について －最近の研究からー (2017)
  • Author(s): 重石英生、杉山 勝
  • Journal Title: 口腔衛生学会雑誌 Volume: 印刷中
  • NAID: 130005936927
  • Peer Reviewed
• [Journal Article] Risk factors for oral human papillomavirus in healthy individuals: A systematic review and meta-analysis. (2016)
  • Author(s): Shigeishi H, Sugiyama M
  • Journal Title: J Clini Med Res Volume: 8 Pages: 721-729
  • Peer Reviewed
• [Journal Article] Higher prevalence and gene amplification of HPV16 in oropharynx as compared to oral cavity. (2016)
  • Author(s): Shigeishi H, Sugiyama M, Ohta K, Rahman MZ, Takechi M.
  • Journal Title: J Appl Oral Sci Volume: 24 Pages: 397-403
  • Peer Reviewed
• [Journal Article] CD44(high) /ALDH1(high) head and neck squamous cell carcinoma cells exhibit mesenchymal characteristics and GSK3β-dependent cancer stem cell properties. (2016)
  • Author(s): Seino S, Shigeishi H, Hashikata M, Higashikawa K, Tobiume K, Uetsuki R, Ishida Y, Sasaki K, Naruse T, Rahman MZ, Ono S, Simasue H, Ohta K, Sugiyama M, Takechi M.
  • Journal Title: J Oral Pathol Med Volume: 45 Issue: 3 Pages: 180-188
  • DOI: 10.1111/jop.12348
  • Peer Reviewed / Open Access
• [Journal Article] Professional oral health care reduces the duration of hospital stay in patients undergoing orthognathic surgery. (2016)
  • Author(s): Shigeishi H, Rahman MZ, Ohta K, Ono S, Sugiyama M, Takechi M.
  • Journal Title: Biomed Rep. Volume: 4 Pages: 55-58
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological analysis of salivary gland carcinomas and literature review. (2015)
  • Author(s): Shigeishi H, Ohta K, Okui G, Seino S, Hashikata M, Yamamoto K, Ishida Y, Sasaki K, Naruse T, Rahman MZ, Uetsuki R, Nimiya A, Ono S, Shimasue H, Higashikawa K, Sugiyama M, Takechi M.
  • Journal Title: Mol Clin Oncol. Volume: 3 Pages: 202-206
  • Peer Reviewed / Open Access
• [Presentation] 口腔のHPV感染とその危険因子の検索． (2017)
  • Author(s): 重石 英生，杉山 勝
  • Organizer: 第66回日本口腔衛生学会・総会, 2017 年6月1日，山形.
• [Presentation] 口腔のHPV感染の危険因子およびHPV陽性口腔癌の臨床病理学的特徴－最近の研究から－． (2017)
  • Author(s): 重石 英生，杉山 勝. 太田 耕司，東川 晃一郎，武知 正晃.
  • Organizer: 第62 回日本口腔外科学会総会・学術大会, 2017 年10月21日，京都.
• [Presentation] 口腔のHPV感染の危険因子およびHPV陽性口腔癌の臨床病理学的特徴について． (2017)
  • Author(s): 重石 英生，杉山 勝.
  • Organizer: 第26 回日本口腔感染症学会総会・学術大会, 2017 年11月12日，豊橋市.
• [Presentation] 口腔と中咽頭におけるHPV16感染のリスクファクターの検索 (2016)
  • Author(s): 重石英生、杉山 勝、太田耕司、西 裕美、武知正晃
  • Organizer: 第26回日本産業衛生学会全国協議会
  • Place of Presentation: 京都市
• [Presentation] Association of clinicopathological factors with HPV16 infection in oral cavity and oropharynx. (2016)
  • Author(s): Shigeishi H, Sugiyama M, Ohta K, Nishi H, Takechi M
  • Organizer: 第27回日本臨床口腔病理学会
  • Place of Presentation: 広島市
• [Presentation] 口腔内HPV感染と臨床病理学的指標との関係 (2015)
  • Author(s): 重石 英生，杉山 勝，清野 紗矢香、箸方 美帆、太田 耕司，武知 正晃
  • Organizer: 第8回 日本口腔検査学会総会・学術大会
  • Place of Presentation: 神奈川歯科大学大講堂（横須賀）
  • Year and Date: 2015-10-03