The surgical procedure of head and neck reconstruction following tumor ablation presents challenges due to its intricate anatomical space, complex operation, and elevated risk. The emphasis on both functionality and aesthetics has spurred advancements in the precision of surgical methods. Advancements in digital surgical technologies, such as virtual surgical planning, computer-aided design and manufacturing, navigation, robotic surgery, artificial intelligence, and the utilization of patient-specific implants, have the potential to enhance the precision and effectiveness of reconstructive procedures. In this study, the implementation and advancements of digital techniques in reconstructive surgery for head and neck oncology are reviewed.

Background: Pain is the most frequent complication in patients with oral squamous cell carcinoma (OSCC) and is associated with poor prognosis. Calcitonin gene–related peptide (CGRP), abundantly expressed in sensory neurons, has been implicated in multiple pain disorders; however, its role in cancer-associated pain remains unclear. We investigated the relationship between CGRP and OSCC-associated pain and evaluated the analgesic potential of Rimegepant, a CGRP-receptor antagonist approved for migraine. Methods: Plasma CGRP was measured in OSCC patients and correlated with preoperative pain scores and clinical outcomes over a 30-month follow-up. Immunohistochemistry quantified CGRP within tumor-infiltrating nerve fibers. In a unilateral orthotopic tongue OSCC mouse model, we compared the analgesic effects of Rimegepant with carprofen and tramadol. RNA-sequencing of ipsilateral trigeminal ganglia from treated mice was performed to explore potential mechanisms. Results: Plasma CGRP levels were positively correlated with patient-reported pain severity and were associated with reduced overall survival. Increased CGRP expression in tumor-infiltrating nerves was linked to greater pain intensity and lymph node metastasis. In an OSCC mouse model, both systemic and local administration of Rimegepant significantly attenuated facial mechanical hypersensitivity. Transcriptomic analysis of trigeminal ganglia, together with RT–qPCR validation, revealed suppression of innate immune and neuroinflammatory pathways following Rimegepant treatment. Conclusions: Our findings link sensory-nerve-derived CGRP to OSCC-associated pain and support further evaluation of CGRP receptor antagonism as a potential analgesic strategy in cancer.

This protocol details the surgical procedure for genetically manipulating cervical lymph node (LN)-innervating nociceptive neurons in mice. We describe steps for exposing cervical LNs, microinjecting retrograde adeno-associated viruses (AAVs), and verifying viral transduction in the trigeminal ganglia. This approach enables specific labeling, chemogenetic inhibition, or gene knockout in LN-innervating neurons to study neuroimmune crosstalk. For complete details on the use and execution of this protocol, please refer to Zhang et al.¹.

Tumor budding (TB), defined as single tumor cells or small clusters (≤4 cells) at the invasive front, is a strong adverse prognostic feature in oral squamous cell carcinoma (OSCC). However, the stromal regulators and molecular mechanisms that drive TB remain unclear. Here, we developed a tumor‐budding organoid (TBO) model that faithfully recapitulates the OSCC tumor‐stroma interface and budding dynamics. By integrating this model with single‐cell RNA sequencing (scRNA‐seq), in situ RNA sequencing (isRNA‐seq), and functional perturbations, we identify platelet‐derived growth factor receptor alpha ⁺ /integrin α2 ⁺ (PDGFRα ⁺ /integrin α2 ⁺ ) cancer‐associated fibroblasts (CAFs) as the key stromal subset promoting OSCC budding. OSCC cells recruit PDGFRα ⁺ CAFs through PDGFA/PDGFRα signaling. These CAFs engage OSCC cells through two complementary crosstalk pathways: (1) heterotypic E‐cadherin/integrin α2β1 adhesion that transmits biomechanical cues to activate YAP signaling and induce epithelial‐mesenchymal transition (EMT)‐like programs; and (2) tunneling nanotube (TNT)‐mediated mitochondrial transfer that enhances oxidative phosphorylation (OXPHOS) and bioenergetic supply in budding cells. Targeted inhibition of TNT‐mediated mitochondrial transfer markedly suppresses TB in TBO and xenograft models. Together, our results reveal a mechano‐metabolic symbiosis between PDGFRα ⁺ /integrin α2 ⁺ CAFs and OSCC cells that drives TB and provides actionable targets to block this aggressive metastatic precursor.