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Background   Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including  γ H2AX, RAD51, and PARP1. Moreover, the role of [ 18 F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated.Methods   HPV-positive and HPV-negative cell lines were used to evaluate the  γ H2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated  in vitro , and survival was investigated via colony-formation assay. [ 18 F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and  γ H2AX foci were quantified using patient-derived oropharyngeal tumor specimens.Results   Differences in DNA repair were detected, showing higher RAD51 and  γ H2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [ 18 F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status.Conclusion   The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [ 18 F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients.

[18F]PARPi Imaging Is Not Affected by HPV Status In Vitro