What is the recommended treatment for a patient with oropharyngeal T4N2 squamous cell carcinoma that is PD-L1 (Programmed Death-Ligand 1) positive and p16 positive?

Treatment for Oropharyngeal T4N2 Squamous Cell Carcinoma with PD-L1 and p16 Positivity

Concomitant chemoradiotherapy (CRT) with cisplatin is the standard treatment for T4N2 oropharyngeal squamous cell carcinoma that is PD-L1 and p16 positive. 1

Primary Treatment Approach

The treatment strategy for this patient should follow the established guidelines for locally advanced oropharyngeal cancer, regardless of HPV/p16 status:

1. First-line treatment: Concomitant chemoradiotherapy (CRT)

   • Standard chemotherapy: Cisplatin 100 mg/m² on days 1,22, and 43 of radiotherapy 1
   • Radiotherapy: Total dose of 70 Gy using IMRT or VMAT technique 1

2. For patients unfit for cisplatin, alternative options include:

   • Carboplatin combined with 5-FU plus radiotherapy
   • Cetuximab plus radiotherapy
   • Hyperfractionated or accelerated radiotherapy without chemotherapy 1

Important Considerations

HPV/p16 Status

Despite the p16 positivity (suggesting HPV association) and its known better prognosis, the EHNS-ESMO-ESTRO guidelines explicitly state: "The treatment strategy for HPV-positive SCCHN should be the same as HPV-negative SCCHN" 1. This recommendation carries a high level of evidence [I, A].

PD-L1 Status

While PD-L1 positivity is important for recurrent/metastatic disease treatment decisions, it does not alter the primary treatment approach for locally advanced disease. PD-L1 testing is primarily used to guide treatment in the recurrent/metastatic setting 1.

Post-Treatment Evaluation

• FDG-PET/CT is recommended 3 months after completion of CRT to assess response 1
• Neck dissection is not recommended if FDG-PET is negative and lymph nodes are of normal size at 12 weeks post-CRT 1

Follow-up Protocol

• Clinical follow-up with flexible endoscopy every 2-3 months during the first 2 years
• Every 6 months for years 3-5
• Annually thereafter 1
• Baseline post-treatment imaging at 3 months 1

Treatment Outcomes and Prognosis

Patients with p16-positive oropharyngeal cancer generally have better outcomes than those with p16-negative disease. Studies show:

• Higher rates of response to treatment
• Better locoregional control
• Improved disease-specific and overall survival 2

Common Pitfalls to Avoid

1. Do not de-escalate treatment based solely on p16 status

   • Despite better prognosis in p16-positive disease, treatment de-escalation remains investigational 1

2. Do not delay treatment initiation

   • Treatment delays negatively impact locoregional control 1

3. Do not omit multidisciplinary team discussion

   • Treatment strategy must be discussed in a multidisciplinary team including all supportive specialties 1

4. Do not underestimate the importance of nutritional support

   • Evaluate nutritional status before treatment and provide enteral nutrition if significant malnutrition is present 1

5. Do not neglect proper follow-up

   • Regular follow-up is essential to detect recurrence or new primaries and monitor treatment toxicities 1