Biological predictors of radiosensitivity in head and neck squamous cell carcinoma.
OBJECTIVE
The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation.


METHODS
The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed.


RESULTS
Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis.


CONCLUSIONS
P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation.


CONCLUSIONS
The findings may improve patient-specific therapy according to individual tumor characteristics.
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Mathias
M
Fiedler
Institute of Pathology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Florian
F
Weber
Department of Radiotherapy, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Matthias G
MG
Hautmann
Department of Otorhinolaryngology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Frank
F
Haubner
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Torsten E
TE
Reichert
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Christoph
C
Klingelhöffer
Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Stephan
S
Schreml
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Johannes K
JK
Meier
Institute of Pathology, University Hospital of Erlangen, Krankenhausstraße 8/10, 91054, Erlangen, Germany.
Arndt
A
Hartmann
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. tobias.ettl@ukr.de.
Tobias
T
Ettl
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011836:Radiation Tolerance / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor
Head and neck cancer; PD-1; PD-L1; Survivin; c-Met; p16