From the Guidelines

Treatments for Oropharyngeal Cancers are primarily based on the stage and HPV status of the disease.

Surgery: Primary surgery, including neck dissection, is an option for early-stage (T1-2, N0-1) oropharyngeal cancers 1.
Definitive Radiotherapy: Definitive radiotherapy is also an option for early-stage oropharyngeal cancers, and may be combined with concurrent systemic therapy for patients with T1-T2 N1 disease who are at high risk for locoregional recurrence 1.
Chemoradiation: Concurrent systemic therapy, such as cisplatin, with radiotherapy is a recommended treatment approach for locally advanced resectable disease (T3-4a, N0-1; or any T, N2-3) 1.
Adjuvant Therapy: Adjuvant chemotherapy/radiotherapy is recommended for patients with adverse pathologic features, such as extracapsular nodal spread and/or positive mucosal margin 1.
Immunotherapy: Immunotherapy agents, such as nivolumab and pembrolizumab, are options for patients with recurrent or metastatic H&N cancer who have progressed on or after platinum-based chemotherapy 1.

HPV-positive: Patients with HPV-positive oropharyngeal cancer tend to have a better prognosis and may be eligible for deintensification treatment protocols, which are currently being investigated in clinical trials 1.
HPV-negative: Patients with HPV-negative oropharyngeal cancer may require more intensive treatment approaches, such as concurrent systemic therapy with radiotherapy 1.

Patient Preferences: Treatment decisions should take into account patient preferences and the potential risks and benefits of each treatment approach 1.
Quality of Life: Late toxicity and quality of life are concerns for patients with locally advanced HPV-positive oropharyngeal cancer, and treatment decisions should aim to minimize these risks 1.

From the Research

The standard care for advanced oropharyngeal cancer has been chemoradiotherapy, although surgical approaches followed by adjuvant treatment have been proposed 2.
Different strategies should be considered for the specific patient's treatment: surgery, chemotherapy, and radiation therapy or combinations of them 2.
Transoral approaches, including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS), have revolutionized the surgical approach to squamous cell carcinoma (SCC) of the oropharynx 3.
Both early and advanced-stage oropharyngeal tumors can be managed successfully with surgery, with or without adjuvant therapy 3.

Robotic surgery or open approaches with reconstructive flaps can be considered in advanced stages, resulting in the de-intensification of subsequent systemic therapy and fewer related side effects 2.
Transoral resection (as opposed to classic open approaches) + neck dissection + adjuvant radio- (chemo-) therapy has been observed for oropharyngeal carcinoma over the last 20 years 4.
TORS (TOS) was associated with fewer tumor-positive resection margins (R1), a lower number of recurrences, fewer intraoperative tracheostomies, a shorter inpatient stay, and a shorter duration of postoperative nasal tube feeding compared to open surgery 4.

Early SCCs of the oropharynx (T1-2) may be managed effectively with either surgery or primary irradiation 5.
Advanced SCCs of the oropharynx (T3-4, nodally aggressive, or both) require multimodal approaches consisting of either surgery along with adjuvant irradiation or concurrent chemoradiation along with salvage surgery (as necessary) 5.
Intensity-modulated radiation therapy has the potential to reduce toxicities and morbidity while offering equivalent local control rates 6.

The treatment choice is influenced by tumor variability and prognostic factors, but it also depends on cancer extension, extranodal extension, nervous invasion, human papilloma virus (HPV) presence 2.
HPV-related OPSCC is strongly associated with a favorable overall survival (OS) and disease-free survival rate (DSS); by contrast, HPV-negative OPSCC often flags a worse prognosis 2.
The American Joint Committee on Cancer (AJCC) differentiates OPSCC treatment and prognosis based on HPV status 2.