HPV-positive HNSCC cell lines show strongly enhanced radiosensitivity after photon but not after carbon ion irradiation.

Background and Purpose: HPV positive (pos.) HNSCC cells are significantly more radiosensitive to photon irradiation as compared to HPV negative (neg.) cells. Functionally, this is considered to result from a reduced DSB repair capacity. It was now tested, whether such a difference is also observed when using carbon ion ( ¹² C) irradiation.
Material and Methods: Five HPV pos. and five HPV neg. HNSCC cell lines were irradiated with photons or ¹² C-ions using 2D or 3D cell culture conditions. Clonogenic survival was determined by colony formation assay and DSB repair by immunofluorescence using co-staining of γH2AX and 53BP1 foci.
Results: The pronounced difference in radiosensitivity known for these two entities when exposed to photons in 2D cell culture, was reduced when treated under 3D conditions. Irradiation with ¹² C-ions strongly enhanced cell killing, whereby increase was more pronounced for the HPV neg. when compared to the HPV pos. cell line (RBE = 2.81 vs. 2.14). As a consequence, after ¹² C-irradiation clonogenic survival was almost identical for the two entities as was demonstrated for all cell lines at a dose of 3 Gy. In line with this, the significant difference in DSB repair capacity between HPV pos. and neg. HNSCC cells, as seen after photon irradiation, was abrogated after ¹² C-irradiation.
Conclusion: While HPV pos. cells are significantly more radiosensitive to photons than HPV neg. cells, no significant difference was seen after ¹² C-irradiation. This needs to be considered when planning new clinical protocols for the treatment of HPV neg. and pos. tumors with ¹² C-ions.
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