What is the Role of Trans‐Oral Robotic Surgery (TORS) in HPV Negative Oropharyngeal Cancer?

BACKGROUND Transoral robotic surgery (TORS) has become increasingly accepted as a treatment modality in Human papillomavirus (HPV) positive T1/T2 oropharyngeal squamous cell carcinoma (OPSCC). Various studies have shown better oncologic and survival outcomes in HPV positive OPSCC patients, compared to HPV negative OPSCC. National Comprehensive Cancer Network (NCCN) guidelines recommend surgical excision or radiotherapy in T1/T2 OPSCC for both HPV positive as well as HPV negative tumors. Results have been comparable when HPV positive OPSCC patients have been treated with TORS versus radiotherapy in early stage disease. However, the role of TORS in HPV negative OPSCC has not been well elucidated. Existing literature focuses on the surgical outcomes of HPV positive OPSCC especially with TORS; however, the results of surgical and oncologic outcomes in HPV negative OPSCC patients have been largely limited to subset analysis of large OPSCC cohorts. There are no largescale prospective trials, which have studied TORS in HPV negative OPSCC. In fact, a Phase II randomized controlled trial (RTOG 1221, NCT01953952) was formulated to compare the survival outcomes in patients with T1/T2, N1-N2b HPV negative OPSCC, but unfortunately this trial was closed due to poor accrual rate and a relative decline in HPV-negative OPSCC. This review summarizes the available literature and investigates the role of TORS in HPV negative OPSCC. LITERATURE REVIEW Baliga et al. recently published the outcomes of a large cohort of 17,150 T1/T2 OPSCC patients, 2680 of which underwent TORS from a National cancer database (NCDB) query. The authors reported that the differences in overall survival (OS) between HPV positive and HPV negative groups were not statistically significant. (HPV positive: Hazard ratio HR 0.75, P = .20 and HPV negative HR 0.84, P = .43). The authors commented that the role of TORS in HPV negative OPSCC has not been well documented as there is a dearth of prospective studies looking at this cohort of patients. Another study by Mahmoud et al. queried the NCDB for outcomes of TORS in OPSCC. One hundred eight patients were HPV negative. On a subset analysis using the proportional hazards model, 103 HPV negative patients who underwent TORS were compared with 103 case-matched HPV negative patients with radiotherapy. The 3-year survival was 84% {(95% confidence interval CI 76%–91%) versus 66% (95% CI 57%–77%) P = . 01} for TORS versus radiotherapy, respectively. These results suggest that surgery for HPV negative OPSCC is feasible with reasonable oncologic outcomes. The authors commented that until prospective studies are designed to investigate the outcomes of surgery in HPV negative OPSCC, large datasets like the NCDB should be explored to answer this question. These studies correlated well with the promising results of a multi-institutional retrospective study by de Almeida in 2015. A subset analysis of 61 HPV negative OPSCC patients who underwent TORS was performed. The authors did not report any statistically significant differences in survival between the HPV positive and HPV negative groups. The 2-year locoregional control rate was 95% and 92% (P = .52) among HPV positive and HPV negative patients, respectively. Further, the 2 years OS was 96.7% and 93.7% (P = .23) among HPV positive and HPV negative patients, respectively. The authors, however, felt that their finding of OPSCC patients having comparable survival following TORS, irrespective of the HPV status needed further validation as the number of HPV negative patients was low in their study. From the Department of Otolaryngology/Head Neck Surgery (A.A., B.A.C., C.-A.O.N.), LSU Health, Shreveport, Louisiana, U.S.A. ; Surgical Service (A.A., C.-A.O.N.), Otolaryngology Section, Overton Brooks VA Medical Center, Shreveport, Louisiana, U.S.A. Editor’s Note: This Manuscript was accepted for publication on October 26, 2020. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Cherie-Ann O. Nathan, MD, FACS; Professor and Chairman Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Director of Head and Neck Surgical Oncology, Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, LA 71130-3932. E-mail: cnatha@lsuhsc.edu