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.