A matched comparison of human papillomavirus–induced squamous cancer of unknown primary with early oropharynx cancer

Objectives/Hypothesis Patients with human papillomavirus (HPV)–induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched‐pair analysis to compare outcomes between T0N1‐3M0 HPV+ CUP and T1‐2N1‐3M0 HPV+ oropharynx known primary (OPX). Study Design Retrospective cohort study at a single institution. Methods Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease‐free survival (DFS) and overall survival (OS) were calculated using Kaplan‐Meier analysis. Results Of 298 patients with T1‐2N1‐3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow‐up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3‐year DFS (89% vs. 85%, P = .44), and 3‐year OS (91% vs. 91%, P = .11), respectively. Conclusions Patients with T0N+M0 HPV‐induced CUP have similar survival outcomes to matched patients with T1‐2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early‐stage known primary OPX cancer. Level of Evidence 4. Laryngoscope, 128:1379–1385, 2018