title: Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells.
abstract: Human papillomavirus (HPV)-positive oropharyngeal carcinomas response better to X-ray therapy (XRT) than HPV-negative disease. Whether HPV status influences the sensitivity of head and neck cancer cells to proton therapy or the relative biological effectiveness (RBE) of protons versus XRT is unknown.
  
  
  
  Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks.
  
  
  
  HPV-positive cells were more sensitive to protons and the unrepaired double-strand breaks were more numerous in HPV-positive cells than in HPV-negative cells (p < .001). Protons killed more cells than did XRT at all fraction sizes (all RBEs > 1.06). Cell line type and radiation fraction size influenced the RBE.
  
  
  
  HPV-positive cells were more sensitive to protons than HPV-negative cells maybe through the effects of HPV on DNA damage and repair. The RBE for protons depends more on cell type and fraction size than on HPV status. © 2016 Wiley Periodicals, Inc. Head Neck 39: 708-715, 2017.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Shichao
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David P
authors.initials: DP
authors.lastname: Molkentine
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yining
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Narayan
authors.initials: N
authors.lastname: Sahoo
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael
authors.initials: M
authors.lastname: Gillin
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiaorong Ronald
authors.initials: XR
authors.lastname: Zhu
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frank
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D006801:Humans; D008297:Male; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D061766:Proton Therapy / Q000379:methods*; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000379:methods; D012016:Reference Values; D012062:Relative Biological Effectiveness; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
keywords: head and neck cancer; human papillomavirus; proton radiotherapy; radiosensitivity; relative biological effectiveness