Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Human papillomavirus (HPV) has been associated with multiple cancers in the anogenital and upper aerodigestive tracts. In the head and neck region, HPV-positive cancers are common in oropharynx, with rising incidence and a well-established association with more favorable patient outcomes. However, the relationship with prognosis of sinonasal squamous cell carcinoma (SNSCC) has been much less often studied and is presently unclear. To better elucidate this relationship, we performed a systematic review and meta-analysis of the biomedical literature to determine the aggregate effect across studies. In doing so, we observed significantly better overall survival associated with HPV-positive SNSCC. Therefore, we conclude that HPV testing may be useful for determining patient prognosis and potentially guiding treatment decisions. ABSTRACT: Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary survival curves for 5-year OS and estimating survival probability by HPV status at pre-specified time intervals from study-specific Kaplan-Meier curves generated 2-year DFS. Log HRs and log CIs were combined across studies to generate summary estimates and a corresponding 95% CIs for OS and DFS. We identified ten unique studies reporting on OS and four for DFS. We observed a significant association between HPV and OS (summary HR = 0.51, 95% CI: 0.38–0.70) with relatively low heterogeneity between studies. These results indicate that HPV is a significant predictor of more favorable survival for SNSCC, and thus may be a useful biomarker for prognostication and, potentially, treatment modulation.