Neoadjuvant immunotherapy in advanced oral cancer: Emerging treatment paradigms

Locally advanced borderline resectable oral cancer poses significant treatment challenges due to its infiltrative nature and high relapse rates, leading to poor prognosis. Neoadjuvant immunotherapy may offer a novel therapeutic approach, potentially altering the standard of care for advanced oral cancer. Two patients with locally advanced tongue cancer, initially deemed inoperable, were treated with neoadjuvant immunotherapy. The first patient received 4 cycles of taxane, cisplatin, and pembrolizumab, while the second received 12 cycles of nivolumab and methotrexate. Both patients exhibited excellent clinical responses at the primary site and in regional lymph nodes. Following treatment, one patient underwent primary closure, and the other had a nasolabial flap with marginal mandibulectomy. Intraoperative frozen sections indicated tumor-free margins in both cases. These two cases underscore the potential of neoadjuvant immunotherapy in managing borderline resectable oral squamous cell carcinoma (OSCC), initially deemed inoperable. The favorable outcomes highlight the need for more research and clinical trials to further assess the efficacy of this approach in head and neck cancers. In this review, we explore the scientific rationale, current clinical evidence, and key debated topics, including the evaluation of pathological and radiological responses. •Challenge of Borderline Resectable Oral Cancer: Locally advanced, borderline resectable oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to its infiltrative nature, high relapse rates, and poor prognosis.•Neoadjuvant Immunotherapy: Neoadjuvant immunotherapy, particularly with immune checkpoint inhibitors (ICIs) like pembrolizumab and nivolumab, shows potential in shrinking tumors, making inoperable cases resectable.•Case Report Success: Two cases of previously inoperable tongue cancer treated with neoadjuvant immunotherapy showed excellent clinical responses, enabling successful surgical resections with tumor-free margins.•Scientific Rationale: Immune checkpoint blockade reactivates the host's immune response, potentially offering more durable treatment effects in head and neck squamous cell carcinoma (HNSCC) compared to conventional chemotherapy.•FutureImplications: The promising results in these cases highlight the need for further research and clinical trials to validate neoadjuvant immunotherapy as an effective strategy for managing advanced HNSCC, possibly altering the s