De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer

Abstract

Current adjuvant treatment guidelines for oropharyngeal squamous cell carcinoma treated with primary surgery are based on studies that predate the human papillomavirus (HPV) era. HPV-associated oropharynx carcinoma (HPV-OPC) has a much more favorable prognosis compared to HPV-unassociated cancer and is increasingly considered to be a distinct disease entity due to its unique etiology, presentation, and behavior. Currently, there is significant interest in adjuvant treatment de-intensification of HPV-OPC patients in order to reduce treatment-related toxicity while maintaining excellent clinical outcomes. Here, we review the evidence and rationale underlying the ongoing prospective trials of adjuvant treatment de-intensification for HPV-OPC patients.

Tumor‐infiltrating lymphocyte quantification stratifies early‐stage human papillomavirus oropharynx cancer prognosis

“…10,37 The success of these studies is dependent on accurate patient selection, yet there is no consensus on the clinicopathologic criteria that constitute intermediate-risk disease. [38][39][40] Our data show that TIL density was associated with recurrence in both clinical and pathologic AJCC8 earlystage patients in analyses adjusted for factors associated with recurrence in early-stage disease, ENE and PNI. These results suggest that with clinical or pathological staging criteria, TIL density is an independent prognostic factor for recurrence in both early-stage (stage I or II) and stage I disease.…”

“…Combinations of these clinicopathologic factors are currently in place to stratify risk in deintensification studies . The success of these studies is dependent on accurate patient selection, yet there is no consensus on the clinicopathologic criteria that constitute intermediate‐risk disease …”

Long‐term analysis of transorally resected p16 + Oropharynx cancer: Outcomes and prognostic factors

“…52 The current study is limited in its scope to assess treatment deintensification, but we anticipate that transoral surgery with riskstratified adjuvant therapy will play a relevant role in the future to reduce chemoradiation-related toxicities, including dysphagia 53 in HPV-related OPSCC. 54 For functional outcomes at a follow-up of ≥ 60 months, we observed a tracheostomy rate of 1% due to indications of recurrence and laryngeal chondroradionecrosis. The swallowing function, as assessed by the FOSS, was normal/ nutritive in 83% of the patients.…”

“…During our study period, institutional deintensification strategies evolved toward eliminating radiation to the primary site in margin‐negative resected T1 to T2 tumors, and to the contralateral neck for well‐lateralized tumors, as well as reducing the ipsilateral radiation dose to 60 Gy . The current study is limited in its scope to assess treatment deintensification, but we anticipate that transoral surgery with risk‐stratified adjuvant therapy will play a relevant role in the future to reduce chemoradiation‐related toxicities, including dysphagia in HPV‐related OPSCC …”

Primary vs nodal site PET/CT response as a prognostic marker in oropharyngeal squamous cell carcinoma treated with intensity‐modulated radiation therapy

“…This heterogeneity has been most famously correlated with human papilloma virus (HPV) status and smoking history, which are now being used to inform patient treatment and new research directions. [8][9][10] Although the data demonstrating prognostic value of PET/CT are not as established as that for HPV or smoking status, PET/CT results have shown potential to predict patient outcomes. Studies have analyzed pretreatment metabolic activity, midtreatment metabolic activity, and posttreatment metabolic activity, establishing all of them to be useful indicators of prognosis.…”