Nodal response after 46 Gy of intensity‐modulated radiotherapy is associated with human papillomavirus–related oropharyngeal carcinoma

Objectives/Hypothesis This study aimed to analyze the effect of human papillomavirus (HPV)‐associated T1‐2 node‐positive oropharyngeal squamous cell carcinoma (OPSCC) on nodal response, recurrent disease, and survival in patients treated according to the Rotterdam protocol. Study Design Retrospective cohort study. Methods In total, 77 patients with T1‐2 OPSCC with nodal disease, treated between 2000 and 2012, were included in this study. Patients were treated according to the Rotterdam protocol: 46 Gy of IMRT followed by a local boost using cyberknife or brachytherapy (22 Gy) and neck dissection. The presence of HPV was determined by p16INK4A immunostaining. Outcomes were overall survival, disease‐free survival, and the extent of nodal response. Nodal stage was determined following the 7th and 8th American Joint Cancer Committee/Union for International Cancer Control classification. Results Overall, 68.4% of patients had p16‐positive disease, and 35.4% of all patients achieved complete nodal response (pN0) after 46 Gy of intensity‐modulated radiotherapy (IMRT). Based on the 7th TNM classification, nodal response (partial or complete) was significantly associated with HPV status (P = .002). Patients with p16‐positive OPSCC had an odds ratio (OR) of 4.6 to achieve complete nodal response. However, smoking interacted with this effect. Applying the 8th TNM classification, complete or partial response was associated with HPV status but was not significant (OR: 1.7, P = .138). Complete nodal response led to 100% overall survival in p16‐positive OPSCC patients. Conclusions HPV‐related OPSCCs are associated with complete nodal response after 46 Gy of IMRT. Patients with full regional control (pN0) after IMRT and subsequent neck dissection show a significantly better overall survival, but smoking negatively interacts with this effect. Level of Evidence 4. Laryngoscope, 128:2333–2340, 2018