Maria Abreu, Vanessa Branco, Filipa Ferreira, Ana Martins
Immune checkpoint inhibitors have improved outcomes in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), although durable complete responses (CRs) remain uncommon. The optimal duration of immunotherapy is not yet established. We report the case of a 69-year-old female smoker diagnosed in November 2015 with human papillomavirus (HPV)16-positive squamous cell carcinoma of the oropharynx (base of tongue), staged cT2N2bM0. Following induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, and concurrent chemoradiotherapy with cisplatin, persistent disease was confirmed by biopsy. In December 2016, she underwent extensive surgery that included partial pharyngectomy with tracheostomy + hemiglossectomy + bilateral neck dissection + microvascular free flap reconstruction with positive margins (ypT4aN2R1). Following surgery with positive margins, complementary systemic therapy was administered (paclitaxel, followed by cetuximab combined with methotrexate). In 2019, the patient presented with locoregional cutaneous recurrence, which required hemostatic palliative radiotherapy. Nivolumab was initiated in December 2019, and a CR was achieved about two months later, by February 2020. Treatment was discontinued in February 2021 due to immune-related toxicity (bullous pemphigoid, Common Terminology Criteria for Adverse Events v5.0, grade 3). Remarkably, the patient has maintained a CR for more than four years after discontinuation of immunotherapy, as confirmed by imaging in 2025. This case highlights the potential for durable CRs after immunotherapy discontinuation in heavily pretreated HPV-positive HNSCC, raising important questions regarding optimal treatment duration, patient selection, and the role of immune-related adverse events as a potential marker of response.