An Update on the Immunotherapy for Oropharyngeal Squamous Cell Carcinoma

Abstract

Oropharyngeal squamous cell carcinoma (OPSCC) is an uncommon malignancy worldwide. Remarkably, the rising incidence of OPSCC has been observed in many developed countries over the past few decades. On top of tobacco smoking and alcohol consumption, human papillomavirus (HPV) infection has become a major etiologic factor for OPSCC. The radiotherapy-based or surgery-based systemic therapies are recommended equally as first-line treatment, while chemotherapy-based strategy is applied to advanced diseases. Immunotherapy in head and neck squamous cell carcinoma (HNSCC) is currently under the spotlight, especially for patients with advanced diseases. Numerous researches on programmed death-1/programmed death-ligand 1 checkpoint inhibitors have proven beneficial to patients with metastatic HNSCC. In 2016, nivolumab and pembrolizumab were approved as the second-line treatment for advanced metastatic HNSCC by the USA Food and Drug Administration. Soon after, in 2019, the USA Food and Drug Administration approved pembrolizumab as the first-line treatment for patients with unresectable, recurrent, and metastatic HNSCC. It has been reported that HPV-positive HNSCC patients were associated with increased programmed death-ligand 1 expression; however, whether HPV status indicates different treatment outcomes among HNSCC patients treated with immunotherapy has contradicted. Notably, HPV-positive OPSCC exhibits a significantly better clinical response to primary treatment (i.e., radiotherapy, surgery, and chemotherapy) and a more desirable prognosis compared to the HPV-negative OPSCC. This review summarizes the current publications on immunotherapy in HNSCC/OPSCC patients and discusses the impact of HPV infection in immunotherapeutic efficacy, providing an update on the immune landscape and future perspectives in OPSCC.

Treatment options for oropharyngeal carcinoma — An umbrella review

“…Immunotherapy for OPSCC is currently in the spotlight, especially for patients with advanced diseases. Various studies on programmed death-1/programmed deathligand 1 checkpoint inhibitors have shown to be beneficial to patients with metastatic head and neck squamous cell carcinoma [3]. mAbs, such as nivolumab and pembrolizumab, were approved as the second-line treatment for advanced metastatic head and neck squamous cell carcinoma.…”

“…Advances in treatments have led to an improvement in survival outcomes over the past three decades, but, despite significant technical advances, oral cancer still has a significant mortality rate, with over 140,000 deaths recorded, representing nearly half of the incident cases (48%) [2]. Interestingly, HPV-positive OPSCC has shown to have a significantly better clinical response to primary treatment and a more desirable prognosis compared to the HPV-negative OPSCC [3].…”

“…Historically, OPSCC has been managed primarily with surgery and/or radiotherapy, both of which have evolved in the last decades. Chemotherapy-and immunotherapy-based strategies are usually used for patients with advanced diseases [3]. These days, old surgical approaches that involve large incisions and mandibulotomies are not preferred by most healthcare institutions because of their substantially high mortality and morbidity.…”

Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit

“…Among novel approaches, immunotherapy (IO) has become a standard of care for recurrent/metastatic head and neck cancers (HNCs), including OPSCC [ 2 , 3 ]. On these bases, ongoing trials are investigating the use of IO in this site, both in its early and advanced stages [ 4 ]. However, the estimated percentage of patients achieving a durable response to IO is still low [ 4 , 5 , 6 ], which suggests the need for additional predictive biomarkers than the already validated PDL-1 [ 7 ].…”

“…On these bases, ongoing trials are investigating the use of IO in this site, both in its early and advanced stages [ 4 ]. However, the estimated percentage of patients achieving a durable response to IO is still low [ 4 , 5 , 6 ], which suggests the need for additional predictive biomarkers than the already validated PDL-1 [ 7 ]. Of these, some blood count parameters (e.g., neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio) have been associated with response to IO in several solid neoplasms, including melanoma and non-small cell lung cancers [ 8 ].…”