title: Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines.
abstract: Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation.While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Busch
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.|Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Becker
authors.affiliation: Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kriegs
authors.affiliation: Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Gatzemeier
authors.affiliation: Institute of Toxicology, University Medical Center Düsseldorf, Düsseldorf, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Krüger
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Möckelmann
authors.affiliation: Institute of Toxicology, University Medical Center Düsseldorf, Düsseldorf, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritz
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.affiliation: Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Rothkamm
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.|Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Rieckmann
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D027383:Papillomaviridae / Q000254:growth & development* / Q000502:physiology; D011836:Radiation Tolerance / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: HNSCC; HPV; cisplatin