Outcomes for recurrent or metastatic head and neck cancer by HPV status: a systematic review and meta-analysis

Human papillomavirus (HPV)-positive (HPV+) recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) exhibits distinct clinical behavior compared with HPV-negative (HPV-) R/M HNSCC. However, most studies reference historical efficacy benchmarks from cohorts combining HPV+ and HPV- R/M HNSCC for comparison with the efficacy of novel therapeutics. This analysis aims to assess differential outcomes specific to HPV+ and HPV- R/M HNSCC to reflect HPV-associated prognostic considerations.

Studies from March 2006 to June 2024 were searched. All therapeutic trials in R/M HNSCC that reported outcomes by HPV status were included. Meta-analyses were conducted to evaluate overall survival (OS) as the primary outcome of interest, objective response rate, and progression-free survival as secondary outcomes. Weighted averages were used to estimate the outcome measures for each group.

A total of 10 studies representing 3509 patients met the inclusion criteria. For the first-line setting, the weighted average OS estimates were 20.7 months (95% CI, 19.4-21.9) and 12.2 months (95% CI, 11.9-12.4) for HPV+ and HPV- HNSCC, respectively. For the second or later line treatment setting, the weighted average OS estimates were 11.1 months (95% CI, 10.2-12.1) and 8.3 months (95% CI, 7.9-8.6) for HPV+ and HPV- subgroups, respectively.

Our analysis demonstrated a clinically meaningful difference between in the HPV+ and HPV- R/M HNSCC populations. These findings support the establishment of HPV-specific outcome benchmarks, which are essential for prognostic awareness, optimizing therapeutic development, and accurately interpreting clinical trial data.