Purpose/Objective: When treated by radiotherapy, patients with squamous cell carcinomas of the head and neck (HNSCC) positive for HPV and p16 possess a clearly favorable prognosis as compared to those with HPV-negative HNSCC when the therapeutic regimens applied include radiotherapy. It was the aim of this work to study whether this phenomenon may be caused by an enhanced cellular radiosensitivity. Materials and Methods: The radiation response of five HPV and p16 positive cell lines was

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... to the response of five HPV and p16 negative HNSCC strains. Cells were characterized with regard to cellular radiosensitivity, G1-and G2-arrest, apoptosis and residual DNA double strand breaks (DSB). Methods comprised the colony formation assay, the detection of PARP cleavage, the fluorescencebased detection of caspase activity, propidium iodide staining, the colcemid-based G1-efflux assay and the immunofluorescence staining of gH2AX and 53BP1 foci. Results: On average, the cellular radiosensitivity of the five HNSCC cell lines positive for HPV and p16 was clearly enhanced when compared to the sensitivity of the HPV negative cells (SF3= 0.2827 vs. 0.4455). This increase does not result from an increase in apoptosis or the execution of a permanent G1-arrest, but is rather associated with both, elevated levels of residual DSBs and extensive G2-arrest. Conclusions: Increased cellular radiosensitivity due to compromised DNA repair capacity is likely to contribute to the improved outcome of patients with HPV/p16 positive tumors when treated by radiotherapy.