A high homologous recombination deficiency score is associated with poor survival and a non-inflamed tumor microenvironment in head and neck squamous cell carcinoma patients

Abstract

BackgroundHomologous recombination deficiency (HRD) is a predictive factor in ovarian cancer, breast cancer, and prostate cancer for Poly (ADP-ribose) polymerase inhibitors (PARPi) therapy. HRD is understudied in head and neck squamous cell carcinoma (HNSCC) and the impact of HRD on prognosis and the tumor immune microenvironment is unclear. MethodsWe studies eight head and neck cancer patients in our center and compared the HRD score for each HNSCC patient in The Cancer Genome Atlas (TCGA) cohort with corresponding clinical characteristic mRNA and mutation data. ResultsResults indicated that the clinical stage (P = 0.016), gender (P = 0.003), clinical T stage (P < 0.001), HPV 16 (P = 0.003), pathologic T stage (P = 0.002), and lymphovascular invasion (P = 0.004) were associated with a homologous recombination deficiency high score (HRD-H) by logistic analysis. Multivariate analysis showed that HRD-H was an independent factor predicting survival with the adjustment of age, gender, clinical T stage, clinical N stage, and clinical M stage (HR 95 %CI 1.517; 1.128–2.039, P = 0.006). The proportion of tumor mutation burden-high (TMB-H) and microsatellite instability-high (MSI-H) patients in HRD-H patients are relatively low (9.97% and 0.0% respectively). A non-inflamed tumor microenvironment was also found in HRD-H patients.In our center, we found that two HRD-L HNSCC patients presented with an inflamed tumor microenvironment and had a good response to PD-1 therapy. Interestingly, the higher HRD score was 31 and was a non-responder to ICI treatment. ConclusionsHRD-H is associated with poor outcome in HNSCC patients. Those patients may benefit from PARPi treatment rather than ICIs treatment for its non-inflamed tumor microenvironment.