A systematic review and meta-analysis of prognostic indicators in patients with head and neck malignancy treated with immune checkpoint inhibitors.

INTRODUCTION: Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance.

METHODS: A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS).

RESULTS: The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult.

CONCLUSION: In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.