Biomarkers of neoadjuvant immunotherapy for locally advanced head and neck cancer: A systematic review and meta-analysis

BACKGROUND: Despite the general advantages of neoadjuvant immunotherapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC), many patients do not achieve successful clinical outcomes. Hitherto, there has been a lack of biomarkers to predict the effect of neoadjuvant immunotherapy in LAHNSCC. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane databases until June 2024 for studies related to neoadjuvant immunotherapy for LAHNSCC. We calculated the pathological response rates after neoadjuvant immunotherapy for LAHNSCC according to biomarkers. Statistical analysis included correlation analysis with Spearman coefficient and the Mann-Whitney U test. RESULTS: This meta-analysis included 26 studies with a total of 980 patients enrolled. The results showed a correlation between pretreatment combined positive score (CPS) values and posttreatment pathological responses (Z = 0.289, P < .001). Patients with CPS above the cutoff of 5 had significantly higher posttreatment overall pathological response rates than those with CPS below the cutoff (relative risk [RR] = 1.852, P = .012). Similar results have been found in patients with CPS ≥ 10 (RR = 1.698, P = .015), patients with CPS ≥ 20 (RR = 1.488, P = .035), patients with CPS ≥ 30 (RR = 1.679, P = .028), patients with CPS ≥ 40 (RR = 1.783, P = .02), and patients with CPS ≥ 50 (RR = 1.819, P = .027). In addition, patients with human papillomavirus (HPV) positive status had significantly higher posttreatment pathological complete response rates than those with negative HPV status (RR = 2.15, P = .01). Moreover, there is a significant correlation between CD4+ tumor-infiltrating lymphocytes values and pathological responses (Z = 0.511, P = .01). CONCLUSIONS: Our findings suggest that CPS, HPV status, and CD4+ tumor-infiltrating lymphocytes values may be predictive biomarkers of the efficacy of neoadjuvant immunotherapy in patients with LAHNSCC. Further clinical studies are needed to validate our results.