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.

Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands

“…In another study inactivation of the p16 promotor by methylation has been shown (43). These findings suggested the multiple roles of p16 in carcinogenesis of malignancies in addition to HPV-related pathogenesis, explaining the discrepancy of HPV-DNA and p16 expression (16,23). Further laboratory and clinical studies should be designed with the aim to elucidate the underlying biological cause of the distinct HPV/p16 pattern.…”

“…Univariate and multivariate analysis for factors with potential influence on overall survival in 67 patients with adenoid cystic carcinoma. (pN 2-3 vs. pN 0-1 seen from our previous studies (35,36) and others (23,37) (23). Therefore, a p16 IHC followed by HPV detection is suggested for subgroup classification referring to prognosis and therapy strategies.…”

“…Therefore, p16 is considered a specific marker equivalent to DNA-sequencing for high-risk HPV (HR-HPV) and is widely used in routine histopathological screening (20). Clinically important is that the presence of high-risk HPV and p16 expression in HNSCC is correlated with a better survival as compared to tumors with no evidence of HPV infection (21)(22)(23). Both HPV-DNA and the expression of p16 were investigated in the present study cohort of SACC.…”

Efficacy and toxicity of docetaxel combination chemotherapy for advanced squamous cell cancer of the head and neck

“…Following the introduction of the TAX 323 and 324 studies, induction chemotherapy drew significant scientific and clinical interest, leading to further investigations (3,5,6). The use of docetaxel in the treatment regimen was evaluated in those studies.…”

“…Over 350,000 deaths from head and neck cancer were estimated to have occurred in 2008 worldwide (2). The frequency, incidence rates and locations of SCCHN vary widely among countries and continents (2)(3)(4).…”