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

Li Wang; Xiaochun Wang; Yuting Li; Shichao Han; Jinming Zhu; Xiaofang Wang; David P. Molkentine; Pierre Blanchard; Yining Yang; Ruiping Zhang; Narayan Sahoo; Michael Gillin; Xiaorong Ronald Zhu; Xiaodong Zhang; Jeffrey N. Myers; Steven J. Frank

doi:10.1002/hed.24673

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

Li Wang, Xiaochun Wang, Yuting Li, Shichao Han, Jinming Zhu, Xiaofang Wang, David P. Molkentine, Pierre Blanchard, Yining Yang, Ruiping Zhang, Narayan Sahoo, Michael Gillin, Xiaorong Ronald Zhu, Xiaodong Zhang, Jeffrey N. Myers, Steven J. Frank

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English (US)
Pages (from-to)	708-715
Number of pages	8
Journal	Head and Neck
Volume	39
Issue number	4
DOIs	https://doi.org/10.1002/hed.24673
State	Published - Apr 1 2017

Keywords

head and neck cancer
human papillomavirus
proton radiotherapy
radiosensitivity
relative biological effectiveness

ASJC Scopus subject areas

Otorhinolaryngology

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10.1002/hed.24673

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Wang, L., Wang, X., Li, Y., Han, S., Zhu, J., Wang, X., Molkentine, D. P., Blanchard, P., Yang, Y., Zhang, R., Sahoo, N., Gillin, M., Zhu, X. R., Zhang, X., Myers, J. N., & Frank, S. J. (2017). Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells. Head and Neck, 39(4), 708-715. https://doi.org/10.1002/hed.24673

Wang, L , Wang, X , Li, Y, Han, S, Zhu, J, Wang, X, Molkentine, DP, Blanchard, P, Yang, Y, Zhang, R, Sahoo, N, Gillin, M, Zhu, XR , Zhang, X , Myers, JN & Frank, SJ 2017, 'Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells', Head and Neck, vol. 39, no. 4, pp. 708-715. https://doi.org/10.1002/hed.24673

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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.",

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author = "Li Wang and Xiaochun Wang and Yuting Li and Shichao Han and Jinming Zhu and Xiaofang Wang and Molkentine, {David P.} and Pierre Blanchard and Yining Yang and Ruiping Zhang and Narayan Sahoo and Michael Gillin and Zhu, {Xiaorong Ronald} and Xiaodong Zhang and Myers, {Jeffrey N.} and Frank, {Steven J.}",

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AU - Wang, Xiaofang

AU - Molkentine, David P.

AU - Blanchard, Pierre

AU - Yang, Yining

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AU - Sahoo, Narayan

AU - Gillin, Michael

AU - Zhu, Xiaorong Ronald

AU - Zhang, Xiaodong

AU - Myers, Jeffrey N.

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N2 - 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.

AB - 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.

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

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