Advances in Oral and Maxillofacial Cancer Research: A Comprehensive Review

Abstract

Oral and maxillofacial cancers (OMC) remain a significant global public health concern due to their high incidence, mortality rates, and long-term morbidity. Key risk factors, including tobacco use, alcohol consumption, betel quid chewing, and human papillomavirus (HPV) infection, drive the heterogeneous etiology of these malignancies. Recent research efforts have elucidated the molecular pathogenesis of OMC, highlighting the crucial roles of genetic mutations, epigenetic alterations, and tumor–microenvironment interactions in disease initiation and progression. Advanced imaging modalities, such as PET/CT and PET/MRI, have improved diagnostic accuracy, while liquid biopsy approaches leveraging circulating tumor DNA (ctDNA) and salivary biomarkers offer promising avenues for early detection and post-treatment surveillance. Therapeutically, a multimodal paradigm combining surgery, radiotherapy, and chemotherapy has long been the standard of care. However, cutting-edge treatments—including targeted therapies against the epidermal growth factor receptor (EGFR) and the PI3K/AKT/mTOR pathway—are increasingly applied. Moreover, immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have provided durable responses in a subset of patients with advanced or recurrent disease, establishing immunotherapy as a vital component of the treatment armamentarium. Parallel innovations in surgical techniques, especially transoral robotic surgery (TORS), and reconstructive procedures using microvascular free flaps have substantially improved functional and aesthetic outcomes. Ongoing research aims to refine precision medicine strategies by integrating molecular diagnostics, genomic profiling, and predictive biomarkers to tailor individualized therapies. Future directions also emphasize combination regimens—such as immunotherapy paired with targeted or epigenetic drugs—designed to overcome therapeutic resistance. Alongside efforts to develop minimally invasive diagnostic tools, robust prevention measures focusing on lifestyle modifications and HPV vaccination are essential to mitigating the global burden of oral and maxillofacial cancers.