AUTHOR=Wichmann Gunnar , Lehmann Claudia , Herchenhahn Cindy , Kolb Marlen , Hofer Mathias , Wiegand Susanne , Dietz Andreas 

TITLE=Development of a Human Leukocyte Antigen Score to Predict Progression-Free Survival in Head and Neck Squamous Cell Carcinoma Patients

JOURNAL=Frontiers in Oncology

VOLUME=Volume 8 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00168

DOI=10.3389/fonc.2018.00168

ISSN=2234-943X

ABSTRACT=Background: In personalized medicine and treatment stratification of head and neck squamous cell carcinoma (HNSCC) the heterogeneous genetic background of patients is not considered. Human leukocyte antigen (HLA) alleles and HLA haplotypes (HLA-traits) are linked to development of HNSCC and affect progression-free survival (PFS) of HNSCC patients but most head and neck oncologists are not familiar with HLA-typing. Hence, we developed a HLA-score abstracting from complexity of HLA-typing results to facilitate potential use of HLA-associated hazard ratios (HR) for prognostic stratification. Methods: The HR for PFS of 8 HLA-traits shown to be independent predictors (Pi) of PFS in a test cohort (TC) of 90 HNSCC patients were used to build the HLA-score based on the natural logarithm (ln) of the Pi-associated HR. Crude ln-transformed HR of the 8 Pi, alleles B*13 [2], B*35 [1], B*51 [2], DQB1*06 [1], homozygous Cw [1], homozygous DRB4 [2], and haplotypes A*01/B*08 [-6] and B*08/C*07 [4], were summed up to yield the individual patient’s HLA-score. Receiver operating characteristic (ROC) and Kaplan-Meier curves were used to proof the suitability of the HLA-score as prognostic marker for PFS. An independent validation cohort (iVC) of 32 patients treated in the larynx organ preservation trial DeLOS-II was utilized for validation. Results: The individual HLA-scores (range -2 to 6) in TC classified HNSCC patients regarding PFS. ROC analysis (AUC = 0.750, CI 95% 0.665-0.836; P = 0.0000034) demonstrated an optimum cut-off for the HLA-score at 0.5 (97.9% sensitivity, 34.7% specificity), and 70/90 patients in TC with HLA-Score >0 had significant reduced PFS (P = 0.001). Applying the same classifier (HLA-score > 0) confirmed these findings in the iVC revealing reduced PFS of 25/32 patients (P = 0.040). Conclusions: HLA-traits constitute critical Pi. Considering the HLA-score may potentially facilitate the use of genetic information from HLA-typing for prognostic stratification e.g. within clinical trials.