Abstract
Photon-based radiotherapy (XRT) is one of the most frequently used treatment modalities for HPV-negative and HPV-positive locally advanced head and neck squamous cell carcinoma (HNSCC). However, locoregional recurrences and normal RT-associated toxicity remain major problems for these patients. Proton therapy (PT), with its dosimetric advantages, can present a solution to the normal toxicity problem. However, issues concerning physical delivery and the lack of insights into the underlying biology of PT hamper the full exploitation of PT. Here, we assessed the radiobiological processes involved in PT in HPV-negative and HPV-positive HNSCC cells. We show that PT and XRT activate the DNA damage-repair and stress response in both HPV-negative and HPV-positive cells to a similar extent. The activation of these major radiobiological mechanisms resulted in equal levels of clonogenic survival and mitotic cell death. Altogether, PT resulted in similar biological effectiveness when compared to XRT. These results emphasize the importance of dosimetric parameters when exploiting the potential of increased clinical effectiveness and reduced normal tissue toxicity in PT treatment.