Relapse Rates with Surgery Alone in HPV-Related Intermediate- and High-Risk-Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review

Abstract

Indications for adjuvant therapy including radiation therapy (RT) and chemotherapy after surgery for oropharyngeal squamous cell cancer (OPSCC) were defined prior to the predominance of human papilloma virus-related (HPV+) disease. Risk factors for relapse were likewise determined prior to the development of minimally invasive surgeries (MIS) such as transoral robotic surgery and transoral laser microsurgery. This study aimed to evaluate whether historic risk categories and indications for adjuvant therapy in the pre-HPV and pre-MIS era were associated with clinically significant relapse rates in HPV+ OPSCC patients undergoing MIS. A multi-institutional retrospective review of intermediate and high risk HPV+ OPSCC patients not receiving adjuvant therapy after MIS was performed. Perineural invasion (PNI), lymphovascular invasion (LVI), T3-T4, or >=N2 disease were considered to be intermediate risk factors and extracapsular extension (ECE) or positive margins were considered to be high risk features based on established risk categories. Histopathologic review evaluated LVSI, PNI, and/or ECE for patients whose initial pathology reports did not comment specifically on the presence or absence of these parameters, when available. Univariate Cox Proportional Hazards models were used to assess clinical and pathologic risk factors for all relapses. Median follow-up was 42.9 months. Among all 53 patients, the three year cumulative incidence of relapse was 26.0%. The three year cumulative incidence was 11.8% in the 37 intermediate risk patients and 52.4% in the 16 high risk patients. LVI was missing for 17 patients and PNI for 18 patients. On univariate analysis, only high risk status was significantly associated with an increased risk of relapse, HR=3.9 (p=0.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. With a median post-salvage follow-up of 20.6 months for these 10 patients, none of the patients had experienced a second relapse at time of last follow up. Risk category was associated with clinically significant relapse rates after MIS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer. ECE had the highest association with relapse. Most intermediate risk category patients had 1 intermediate risk factor. Missing LVI and PNI data are limitations of this analysis. Like HPV- patients, HPV+ patients with traditional intermediate and high risk features should be offered adjuvant therapy. However, given the potential for salvage therapy and relatively low risk for relapse in intermediate risk patients, de-escalation of adjuvant treatment remains an open consideration best answered by a prospective, randomized trial.