Treatment Approach for HPV-Positive Squamous Cell Carcinoma of the Oropharynx
The treatment strategy for HPV-positive oropharyngeal squamous cell carcinoma should be the same as for HPV-negative oropharyngeal cancer, despite the better prognosis of HPV-positive disease. 1
Standard Treatment Options
Early Stage Disease (T1-2, N0-1)
- Standard options include either radiotherapy (RT) or transoral surgery (TORS) followed by adjuvant therapy if indicated 1
- Early disease should be treated with single-modality treatment when possible 1
- Treatment selection should be based on patient and treatment-related factors, as conservative surgery and RT may provide similar locoregional control 1
Locally Advanced Disease (T3-4, N0 or T1-4, N1-3)
- Standard options are either:
- Surgery plus adjuvant (chemo)radiotherapy, or
- Primary concurrent chemoradiotherapy 1
- Concomitant chemoradiotherapy increases locoregional control and overall survival compared with RT alone 1
- The standard chemotherapy regimen is cisplatin at 100 mg/m² on days 1,22, and 43 of concurrent RT (70 Gy) 1
- For patients unfit for cisplatin, alternatives include carboplatin with 5-FU, cetuximab with RT, or hyperfractionated/accelerated RT without chemotherapy 1, 2
Surgical Approach
- Transoral robotic surgery (TORS) is an option for selected patients with HPV-positive oropharyngeal cancer 1
- Selective neck dissection or sentinel node biopsy is recommended for surgically treated tumors (bilateral for near-midline tumors) 1
- Neck dissection is not recommended after chemoradiotherapy in cases of negative FDG-PET and normal-sized lymph nodes at 12 weeks post-treatment 1
Adjuvant Therapy After Surgery
Postoperative RT is recommended for patients with: 1
- pT3-4 tumors
- Resection margins with macroscopic (R2) or microscopic (R1) residual disease
- Perineural infiltration
- Lymphatic infiltration
- More than one invaded lymph node
- Presence of extracapsular infiltration
Postoperative chemoradiotherapy is recommended for patients with: 1
- R1 resection (positive margins)
- Extracapsular extension/rupture
Postoperative RT or chemoradiotherapy should start within 6-7 weeks of surgery 1
Radiation Therapy Considerations
- All patients should be treated by intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) 1
- For definitive chemoradiotherapy, the standard dose is 70 Gy 1, 3
- For postoperative RT without positive margins or extranodal extension, 56-60 Gy is recommended 3
Treatment of Recurrent/Metastatic Disease
For recurrent/metastatic disease expressing PD-L1 (CPS ≥1): 1
- Pembrolizumab in combination with platinum/5-FU
- Pembrolizumab monotherapy (when rapid tumor shrinkage is not needed)
For recurrent/metastatic disease not expressing PD-L1: 1
- Platinum/5-FU/cetuximab remains the standard therapy
- TPEx (docetaxel, platinum, cetuximab) is also a treatment option
Nivolumab is approved for recurrent/metastatic patients who progress within 6 months of platinum therapy 1
Important Considerations
- HPV status should be determined using p16 immunohistochemistry, which serves as a surrogate marker and prognostic factor for oropharyngeal cancer 1
- Despite better prognosis in HPV-positive disease, treatment de-escalation remains investigational and is not currently recommended outside clinical trials 1
- Recent studies have shown excellent outcomes with standard treatment approaches, underscoring the need for caution with de-intensification strategies 4
- Patients with HPV-positive oropharyngeal cancer with adverse pathological features benefit from adjuvant radiotherapy, with improved survival compared to those who do not receive adjuvant RT 5
Follow-up
- Close follow-up is essential to detect early locoregional recurrence or new primaries and to monitor treatment toxicities 1
- Clinical follow-up with head and neck examination by flexible endoscopy should be performed every 2-3 months during the first year 1
- PET-CT is recommended approximately 3 months after definitive chemoradiation to assess response 3