Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL-6, IL-8 and other cytokines were modulated by autophagy. Notably, when HNSCC cells were co-cultured with normal fibroblasts they upregulated autophagy through IL-6, IL-8 and bFGF. In a mouse xenograft model of HNSCC, pharmacological inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression.

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth and ( < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR. HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. .

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In this preliminary study, TORS supraglottic laryngectomy was a safe procedure with good functional outcomes.

Objective To determine swallowing, speech and quality of life (QOL) outcomes following transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). Design Prospective cohort study. Setting Tertiary care academic comprehensive cancer center. Patients 81 patients with previously untreated OPSCC. Intervention Primary surgical resection via TORS and neck dissection as indicated. Main Outcome Measures Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) pre-operatively and at 3 weeks as well as 3, 6 and 12 months post-operatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-Tube). Clinicopathological and follow-up data were also collected. Results Mean follow-up time was 22.7 months. HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, 67% respectively. There were overall declines in speech, eating, aesthetic, social and overall QOL domains in the early post-operative periods. However, at 1 year post-TORS scores for aesthetic, social and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (p<0.05), while age > 55 years correlated with lower speech and aesthetic scores (p<0.05). HPV status did not correlate with any QOL domain. G-Tube rates at 6 and 12 months were 24% and 9%, respectively. The extent of TORS (> 1 oropharyngeal site resected) and age > 55 years predicted the need for a G-Tube at any point after TORS (p<0.05). Conclusions Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and advanced age tend to decrease QOL.

Mandibular reconstruction presents unique functional and aesthetic challenges to the reconstructive surgeon. This review will cover current techniques for mandibular reconstruction, including the various plating strategies for rigid fixation, the choice of osseous donor site, and the concurrent reconstruction of associated soft tissue defects. Recent developments and future horizons in mandibular reconstruction including the use of virtual surgical planning and tissue engineering will also be addressed.

Background Delays in postoperative radiotherapy (PORT) for head and neck cancer (HNC) increase the risk for recurrence and mortality. The multifactorial nature of delays calls for an in‐depth understanding of potential contributors from the patient's and provider's perspectives. We sought to identify causes of delays in adjuvant radiotherapy initiation for HNC. Methods We performed a mixed‐methods study including patients with HNC care team members. Forty in‐depth interviews were performed (26 patients; 14 care team members). Timing and demographic data were collected from medical records. Results Median time from surgery to radiotherapy initiation was 45 days; 15 participants began after 42 days. Process delays and failure to communicate the urgency and significance of PORT initiation contributes to delays. Patients with a strong social support system experience less delays. Conclusions Achieving reductions in PORT initiation requires efficient care coordination, improved communication between interdisciplinary teams, and strengthening social support systems for patients with HNC.

IMPORTANCE Ficlatuzumab can be used to treat head and neck squamous cell carcinoma (HNSCC) by inhibiting c-Met receptor-mediated cell proliferation, migration, and invasion. OBJECTIVE To understand the effect of ficlatuzumab on HNSCC proliferation, migration, and invasion. DESIGN, SETTING, AND PARTICIPANTS The effects of ficlatuzumab on HNSCC proliferation, invasion, and migration were tested. Mitigation of c-Met and downstream signaling was assessed by immunoblotting. The tumor microenvironment has emerged as an important factor in HNSCC tumor progression. The most abundant stromal cells in HNSCC tumor microenvironment are tumor-associated fibroblasts (TAFs). We previously reported that TAFs facilitate HNSCC growth and metastasis. Furthermore, activation of the c-Met tyrosine kinase receptor by TAF-secreted hepatocyte growth factor (HGF) facilitates tumor invasion. Ficlatuzumab is a humanized monoclonal antibody that sequesters HGF, preventing it from binding to and activating c-Met. We hypothesized that targeting the c-Met pathway with ficlatuzumab will mitigate TAF-mediated HNSCC proliferation, migration, and invasion. Representative HNSCC cell lines HN5, UM-SCC-1, and OSC-19 were used in these studies. EXPOSURES FOR OBSERVATIONAL STUDIES The HNSCC cell lines were treated with ficlatuzumab, 0 to 100 µg/mL, for 24 to 72 hours. MAIN OUTCOMES AND MEASURES Ficlatuzumab inhibited HNSCC progression through c-Met and mitogen-activated protein kinase (MAPK) signaling pathway. RESULTS Ficlatuzumab significantly reduced TAF-facilitated HNSCC cell proliferation (HN5, P< .001; UM-SCC-1, P< .001), migration (HN5, P = .002; UM-SCC-1, P = .01; and OSC-19, P = .04), and invasion (HN5, P = .047; UM-SCC-1, P = .03; and OSC-19, P = .04) through a 3-dimensional peptide-based hydrogel (PGmatrix). In addition, ficlatuzumab also inhibited the phosphorylation of c-Met at Tyr1234/1235 and p44/42 MAPK in HNSCC cells exposed to recombinant HGF. CONCLUSIONS AND RELEVANCE We demonstrate that neutralizing TAF-derived HGF with ficlatuzumab effectively mitigates c-Met signaling and decreases HNSCC proliferation, migration, and invasion. Thus, ficlatuzumab effectively mitigates stromal influences on HNSCC progression.