Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells

Head Neck. 2017 Apr;39(4):708-715. doi: 10.1002/hed.24673. Epub 2016 Dec 30.

Abstract

Background: 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.

Methods: Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks.

Results: 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.

Conclusion: 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.

Keywords: head and neck cancer; human papillomavirus; proton radiotherapy; radiosensitivity; relative biological effectiveness.

Publication types

  • Comparative Study

MeSH terms

  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / virology
  • Cell Survival / radiation effects
  • DNA Damage
  • DNA Repair / radiation effects
  • Female
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / radiotherapy*
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae / isolation & purification*
  • Proton Therapy / methods*
  • Radiation Tolerance
  • Radiotherapy / methods
  • Reference Values
  • Relative Biological Effectiveness*
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Cells, Cultured / radiation effects*