Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status

Data indicate a better prognosis for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV and p16 detection are established markers for HPV-related HNSCC. Both are accepted as survival-independent predictors. Previous studies investigating the survival in HNSCC patients depending on HPV+/- and p16(+/-) status consistently found discordant results with p16(-)/HPV+ and p16(+)/HPV-. However, no meta-analysis regarding the survival according to combined HPV/p16 status has been performed yet. The objective of this study was to discriminate the impact of combined HPV+/- and p16(+/-) status on survival. Data sources were identification and review of publications assessing survival of the distinct subgroups with both p16 and HPV investigated in HNSCC until February, 2015. A meta-analysis was performed to classify survival and clinical outcomes. 18 out of 397 articles (4424 patients) were eligible for the meta-analysis. The percent proportion of the subgroups was 25 % for HPV+/p16(+), 61.2 % for HPV-/p16(-), 7.1 % for HPV-/p16(+) and 6.8 % for HPV+/P16(-). The meta-analysis showed a significantly improved 5-year overall survival (OS), 5-year disease-free survival and their corresponding hazard ratio for HPV+/p16(+) HNSCC in comparison to HPV-/p16(-), HPV+/p16(-) and HPV-/p16(+). The 5-year OS of the HPV-/p16(+) subgroup was intermediate while HPV+/p16(-) and HPV-/p16(-) HNSCC had the shortest survival. With current therapeutic strategies, survival of patients with HNSCC is better if associated with HPV+/p16(+) or HPV-/p16(+). Clinical trials are needed to confirm the distinct survival pattern and to investigate possible differences in survival for HPV+/p16(-) and HPV-/p16(+) HNSCC. To further differentiate p16(+) HNSCC, HPV testing may be advisable.