Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered Human Leukocyte Antigen frequencies

Background Effective immune surveillance critically depend on proteins encoded by genes of the major histocompatibility complex, human leukocyte antigen (HLA) alleles. As we recently could demonstrate a link between altered HLA allele and haplotype frequencies in head and neck squamous cell carcinoma (HNSCC) related to classical risk factors alcohol and tobacco, we were interested if the findings and the predictive value of our HLA score could be replicated in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC independent from localization of the primary tumor.

Methods Leukocyte DNA of n=94 HPV-driven HNSCC patients underwent HLA typing using BmT OneLambda SSO kits. Frequencies of HLA alleles, antigens and haplotypes were compared with published frequencies using chi-square tests. Differences in outcome linked to particular antigens and haplotypes was analyzed using Kaplan-Meier plots and Cox proportional hazard regression.

Results Besides remarkable deviation from published antigen and haplotype frequencies and an enrichment of rare antigens and haplotypes, we found altered antigen and haplotype frequencies also linked to deviating progression- (PFS) as well as tumor-specific (TSS) and overall survival (OS). HLA antigens and haplotypes represent independent outcome predictors in HPV-driven OPSCC.

Conclusions Despite standardized diagnostic procedures and treatment, HLA antigens and haplotypes define subgroups within HPV-driven HNSCC patients with deviating outcome.

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Artikel online veröffentlicht:
12. Mai 2023