A systematic review and network meta-analysis of therapies for locally advanced head and neck squamous cell carcinoma with different HPV status

Infection with high-risk human papillomavirus (HPV) is considered a major cause of head and neck squamous cell carcinoma (HNSCC). However, the optimal treatment choice remains uncertain for both HPV-positive and HPV-negative locally advanced HNSCC (LA-HNSCC) in patients who are unable to tolerate surgery. To assess the effectiveness of various treatment strategies for HPV-positive and HPV-negative LA-HNSCC, this systematic review and network meta-analysis evaluated 4 databases and identified 31 relevant studies. The selected outcomes included overall survival, progression-free survival, locoregional control, distant metastasis, and disease-free survival. Hazard ratios with 95% confidence intervals were pooled for each outcome, and treatment modality rankings were calculated using the surface under the cumulative ranking curve. We found that induction chemotherapy combined with radiotherapy and chemoradiotherapy were optimal for HPV-positive patients, while concurrent chemoradiotherapy and concurrent chemoradiotherapy combined with targeted therapy were most effective for HPV-negative patients. These findings highlight the importance of individualised treatment protocols and lay the groundwork for future clinical trials to optimise outcomes in LA-HNSCC.