Introduction: Transoral surgery is effective in the treatment of select oropharyngeal squamous cell carcinomas (OPSCC). Due to its rising incidence, OPSCC related to the human papilloma virus (HPV) has been the focus of recent studies. Less attention has been paid to transoral resection of p16-negative OPSCC, which portends a poorer prognosis. We aim to report prognostic factors and oncologic outcomes unique to p16 negative OPSCC patients treated with primary transoral surgery.
Methods: A retrospective review was performed on patients with histologically confirmed p16-negative, previously untreated squamous cell carcinoma of the oropharynx. All patients were treated with transoral laser microsurgery or transoral robotic surgery from 1997 to 2016. Demographics, clinicopathological characteristics and oncologic outcomes were recorded. Performance status was based on the ECOG Scale of Performance Status. Comorbidities were based on the validated Adult Comorbidity Evaluation 27. Survival data was analyzed using the Kaplan-Meier (KM) and the Cox Proportional Hazard (PH) regression model.
Results: Fifty-six patients (46 male, 10 female) with a mean age of 62 years (SD: 11.8 years) were identified. Only 8 patients (14%) were never smokers. Thirty-three (62%) of the patients had an ECOG score of 0 and only 16 (30%) had moderate or severe comorbidities. Primary tumors were located in the tonsil (30), base of tongue (16), or soft palate (10). Patients primary tumors were staged as T1 (20), T2 (20), T3 (10) or T4 (4). The nodal basin was staged N1 (13), N2 (8), N2a (2), N2b (12), N2c (5), or N3 (1). 29 (52%) patients received adjuvant therapy. Median follow up was 29 months (range 0-127 months).
A total of 26 (46%) patients developed a recurrence at a median of 10 months (95%CI: 2.5-17.5 months). There were 15 local, 6 regional, and 9 distant recurrences. The 2 and 5-year KM estimates for disease-free survival (DFS) were 49% (95% CI: 35%-63%) and 36% (95% CI: 21%-50%), respectively. The 2 and 5-year KM estimates for overall survival (OS) were 76% (95% CI: 64%-88%) and 62%, (95% CI: 46%-78%), respectively.
Factors associated with OS in univariate analysis were advanced pathologic T stage (T3 or T4) (HR=6.0; 2.2 to 16.2) and soft tissue nodal metastasis (HR=4.0 (95% CI: 1.1 to 14.4). Multivariable analysis showed advanced pathologic T stage was the only significant variable with aHR=13.3 (95% CI: 2.9 to 61.4). Factors associated with DFS in univariate analysis were advanced pathologic T stage (HR=4.0; 95% CI: 1.88-8.53); soft tissue nodal metastasis (HR=2.6; 95% CI: 1.08-6.05) and angiolymphatic invasion (HR=4.0; 95% CI: 1.88-8.53). Only advanced pathologic T-stage remained significant in multivariable analysis (aHR=6.4; 95% CI: 1.40-29.22). There was no association between smoking status, comorbidity, ECOG score, pathological N-stage, margin status, extracapsular extension, or perineural invasion with OS or DFS.
Conclusion: In HPV-negative patients undergoing transoral surgery, advanced pathological T-stage is associated with reduced OS and DFS. Transoral surgery does not appear to have poorer oncologic outcomes in the treatment of HPV-negative patients and may be an option for a more minimally invasive approach compared to traditional open approaches or nonsurgical approaches.