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

backgroundHuman 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.

methodsStudies 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.

resultsA 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.

conclusionOur 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.