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

Abstract

Background and purposeHPV 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 (12C) irradiation. Material and methodsFive HPV pos. and five HPV neg. HNSCC cell lines were irradiated with photons or 12C-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. ResultsThe 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 12C-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 12C-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 12C-irradiation. ConclusionWhile HPV pos. cells are significantly more radiosensitive to photons than HPV neg. cells, no significant difference was seen after 12C-irradiation. This needs to be considered when planning new clinical protocols for the treatment of HPV neg. and pos. tumors with 12C-ions.