Abstract
Human papillomavirus (HPV) status is a favorable prognostic marker for patients with oropharyngeal squamous cell carcinoma (OPSCC) and non-metastatic head and neck non-OPSCC. We evaluated the impact of HPV status on overall survival (OS) for patients with Stage IVC non-OPSCC. Patients diagnosed with Stage IVC non-OPSCC and known HPV status between 2010-2013 were identified in the National Cancer Database. Univariate and multivariate analyses were performed to determine factors associated with OS. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in OS analyses. Multiple imputation method was used for sensitivity analysis. We identified 708 patients with Stage IVC non-OPSCC with 30% being HPV-positive. Unadjusted median survival was 10.3 months for HPV-negative patients and 21.4 months for HPV-positive patients (p<0.0001). Age ≥ 65 and tumor diameter were associated with worse OS (p<0.05) while treatment versus no treatment and HPV-positive status were associated with improved OS on multivariate analysis (p<0.001). Adjusted median survival for patients with HPV-negative and HPV-positive disease was 11.1 months and 23.8 months, respectively (p<0.001). On unadjusted subgroup analysis, patients with HPV-positive oral cavity disease exhibited improved outcomes (p<0.0001) while HPV-positive hypopharynx (p<0.06) and larynx (p<0.12) patients exhibited a trend for improved OS compared to HPV-negative patients. The survival advantage associated with HPV positivity was maintained on sensitivity analysis (p<0.01). These data demonstrate a clinically meaningful association between HPV status and OS in patients with non-OSPCC presenting with Stage IVC disease. In the absence of randomized data, these findings support active consideration of HPV status in clinical decision making, clinical trial design, and patient counseling regarding prognosis.
Highlights
Human papillomavirus (HPV) is a powerful independent marker for patients with oropharyngeal squamous cell carcinoma (OPSCC)
Age ≥ 65 and tumor diameter were associated with worse overall survival (OS) (p
Several individual series have reported similar results . 11-13 In a single institution series evaluating oral cavity squamous cell carcinoma, p16 was overexpressed in 44% of patients examined and shown to be a favorable prognostic factor correlating with improved overall survival and relapse-free survival [11]
Summary
Human papillomavirus (HPV) is a powerful independent marker for patients with oropharyngeal squamous cell carcinoma (OPSCC). Patients with HPV-positive OPSCC exhibit a reduction in the risk of death by approximately half of that compared to patients with HPVnegative tumors [1,2,3,4] Despite these improved outcomes, 10-30% of patients will experience disease progression within 3 years following completion of their definitive therapy [5,6,7]. 11-13 In a single institution series evaluating oral cavity squamous cell carcinoma, p16 was overexpressed in 44% of patients examined and shown to be a favorable prognostic factor correlating with improved overall survival and relapse-free survival [11]. A more recent series supported the favorable prognostic implications of p16 over-expression in SCC from an unknown primary compared with those that were p16-negative [13]
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