Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OPSCC) is extremely radiosensitive. Radiotherapy plus high-dose cisplatin remains the standard of care but causes long-term toxicity. Treatment de-intensification approaches that reduce toxicity while maintaining survival are desirable for HPV-related OPSCC.
We conducted a single-arm, multicentre, phase 2 trial. Patients with newly diagnosed, biopsy-proven, American Joint Committee on Cancer (seventh edition) stage III or IV OPSCC positive for both p16 and HPV DNA were eligible. Patients with T4, N3, or T1N1 disease were excluded. Smoking history was not included in eligibility criteria. Patients received intensity-modulated radiation therapy (IMRT) of 70 Gy in 35 fractions or 70.4 Gy in 32 fractions without chemotherapy. The primary endpoint was complete response (CR) or complete metabolic response (CMR) 10 weeks after IMRT completion.
Between September 13, 2013 and November 15, 2016, 39 patients were enrolled according to a two-stage Simon design. Twenty-three (59%) patients had smoked for >10 pack-years. Thirty-six (92%) patients had tumors genotyped as HPV16. Thirty-seven (95%) patients received full-dose radiotherapy and 35 (90%) had CR or CMR. Median follow-up was 51 months (interquartile range 41-63). One (3%) patient had regional recurrence and three (8%) had distant metastasis. One patient died of disease. Two-year progression-free survival was 94% (95% confidence interval 81-99) and 2-year overall survival was 100%. Common grade 3 adverse events during IMRT included mucositis in ten (26%) patients and dysphagia in seven (18%) patients. None were dependent on a feeding tube at 1 month after IMRT completion. No grade 3 or 4 late adverse events were observed.
IMRT alone is associated with excellent response as well as reduced toxicity. IMRT alone could be a treatment option for carefully selected patients with locally advanced ‘true’ HPV-related OPSCC. Further studies are warranted.

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