Characteristic differences in radiation-induced DNA damage response in human papillomavirus-negative and human papillomavirus-positive head and neck cancers with accumulation of fractional radiation dose

Paul Reid; Alexander H Staudacher; Loredana G Marcu; Ian Olver; Leyla Moghaddasi; Michael P Brown; Eva Bezak

doi:10.1002/hed.26802

Characteristic differences in radiation-induced DNA damage response in human papillomavirus-negative and human papillomavirus-positive head and neck cancers with accumulation of fractional radiation dose

Head Neck. 2021 Oct;43(10):3086-3096. doi: 10.1002/hed.26802. Epub 2021 Jul 8.

Authors

Paul Reid¹, Alexander H Staudacher^{2

3}, Loredana G Marcu^{1

4}, Ian Olver⁵, Leyla Moghaddasi^{6

7}, Michael P Brown^{2

3

8}, Eva Bezak^{1

7}

Affiliations

¹ Cancer Research Institute, University of South Australia, Adelaide, South Australia, Australia.
² Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, South Australia, Australia.
³ School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
⁴ Faculty of Science, University of Oradea, Oradea, Romania.
⁵ School of Psychology, University of Adelaide, Adelaide, South Australia, Australia.
⁶ Genesis Care, Adelaide Radiotherapy Centre, Adelaide, South Australia, Australia.
⁷ Department of Physics, University of Adelaide, Adelaide, South Australia, Australia.
⁸ Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

PMID: 34235809
DOI: 10.1002/hed.26802

Abstract

Background: Superior treatment responses by patients with human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC), compared to patients with HNSCC from other causes, drive biomarker research to optimize treatment. Most HNSCC patients receive radiation therapy delivered as a fractionated course. Changing HPV status in HNSCC from a positive prognostic marker to a predictive one requires biomarkers that capture cellular radiation response to cumulative dose.

Methods: Nuclear enlargement, γH2AX expression and micronuclei count, were studied in six HNSCC cell lines after 4 Gy fractionated X-irradiation.

Results: All HNSCC cell lines displayed altered cellular responses, indicating increasing inability to repair radiation damage with subsequent radiation fractions. Increases in nuclear area were significantly greater among HPV positive cell lines (207% and 67% for the HPV positive and HPV negative groups, respectively).

Conclusions: A different character of DNA repair dysfunction in the HPV positive group suggests greater chromosomal translocation with accumulated radiation dose.

Keywords: HNSCC; HPV; fractionated radiation therapy; micronuclei; γH2AX.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alphapapillomavirus*
Cell Line, Tumor
DNA Damage
Head and Neck Neoplasms* / genetics
Head and Neck Neoplasms* / radiotherapy
Humans
Papillomaviridae / genetics
Papillomavirus Infections* / complications
Radiation Dosage