HPV Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • HPV Positive Oropharyngeal Squamous Cell Carcinoma (HPV⁺ OPSCC):
    • Radiation therpay (RT) + cetuximab vs RT + cisplatin (why substitution fails)
  • Clinical rule: 
    • In cisplatin-eligible HPV⁺ oropharynx cancer:
      • Do not replace cisplatin with cetuximab:
        • To “de-intensify”
    • Two large phase III trials showed:
      • Worse survival and control with cetuximab
    • RTOG-1016 (Lancet 2019; non-inferiority trial):
      • Design: 
        • RT + cetuximab vs RT + cisplatin 100 mg / m² × 2 in HPV⁺ OPSCC
        • Primary endpoint OS:
          • Non-Inferiority (NI) margin HR 1.45
      • Results (median f/u ~ 4.5 y):
        • 5-yr OS: 
          • 77.9% cetuximab vs 84.6% cisplatin:
            • HR 1.45 → non-inferior criterion failed:
              • Inferior with cetuximab
        • PFS: 
          • HR 1.72:
            • Worse with cetuximab
        • Locoregional failure: 
          • HR 2.05:
            • Higher with cetuximab
        • Acute / late grade ≥ 3 toxicity: 
          • Overall similar rates (different profiles):
            • So efficacy — not toxicity — drives the choice PubMed+1
    • De-ESCALaTE HPV (Lancet 2019; “low-risk” HPV⁺):
      • Design: 
        • RT + cetuximab vs RT + cisplatin
        • Primary end point:
          • Severe toxicity
      • Efficacy (≈ 2 y):
        • OS: 
          • 97.5% cisplatin vs 89.4% cetuximab:
            • HR ~ 5.0:
              • Significantly worse with cetuximab
        • Recurrence: 
          • 6.0% cisplatin vs 16.1% cetuximab:
            • HR ~ 3.4
        • Severe toxicity: 
    • Reinforcing data:
      • ARTSCAN III (mixed HNSCC, HPV- subset reported):
        • Concurrent cisplatin outperformed cetuximab with RT:
          • Mature results reiterate inferior outcomes with cetuximabPMC+1
      • Guidelines: 
        • NCCN and contemporary reviews state that RT + cisplatin remains standard for eligible HPV⁺ OPSCC:
          • Cetuximab – RT is reserved for:
            • True cisplatin ineligibility:
              • CrCl < 50 mL / min, grade ≥ 2 SNHL / neuropathy) JNCCN
  • How to use this at tumor board:
    • Eligible for cisplatin?
      • RT + cisplatin:
        • q3-weekly 100 mg / m² × 2 to 3, or weekly in appropriate settings:
          • To achieve ≥ 200 mg/m² cumulative if feasible (De-escalation ≠ drug substitution) PubMed
      • Cisplatin-ineligible? 
        • RT + cetuximab (or institutionally accepted alternatives) with explicit counseling that efficacy:
          • Is inferior to cisplatin in HPV⁺ disease:
            • Use only because platinum cannot be given JNCCN
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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