title: Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Coordes
authors.affiliation: Institute of Medical Biometrics and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lenz
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Minoo
authors.initials: M
authors.lastname: Lenarz
authors.affiliation: Clinic for Gynecology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. andreas.albers@charite.de.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Albers
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000821:virology; D018572:Disease-Free Survival; D005260:Female; D019942:Genes, p16; D006258:Head and Neck Neoplasms / Q000150:complications / Q000235:genetics / Q000401:mortality* / Q000821:virology; D006801:Humans; D008297:Male; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D011379:Prognosis; D017594:Publication Bias; D012306:Risk
keywords: Head and neck cancer; Human papillomavirus; Meta-analysis; Survival; p16