Despite refinements to diagnostic and therapeutic approaches over the last two decades, the outcome of patients with head and neck squamous cell carcinoma (HNSCC) has not shown substantial improvements, especially regarding those with advanced-stage disease. Angiogenesis is believed to be a turning point in the development of solid tumors, being a premise for mass growth and potential distant dissemination. Cancer-induced angiogenesis is a result of increased expression of angiogenic factors, decreased expression of anti-angiogenic factors, or a combination of both. The assessment of angiogenesis has also emerged as a potentially useful biological prognostic and predictive factor in HNSCC. The aim of this review is to assess the level of current knowledge on the neo-angiogenesis markers involved in the biology, behavior, and prognosis of HNSCC. A search (between 1 January 2012 and 10 October 2022) was run in PubMed, Scopus, and Web of Science electronic databases. After full-text screening and application of inclusion/exclusion criteria, 84 articles are included. The current knowledge and debate on angiogenesis in HNSCC presented in the eligible articles are stratified as follows: (i) diagnostic markers; (ii) prognostic markers; (iii) predictive markers; and (iv) markers with a potential therapeutic role. Angiogenesis is a biological and pathological indicator of malignancies progression and has negative implications in prognosis of some solid tumors; several signals capable of tripping the “angiogenic switch” have also been identified in HNSCC. Although several studies suggested that antiangiogenic agents might be a valuable adjunct to conventional chemo-radiation of HNSCC, their long-term therapeutic value remains uncertain. Further investigations are required on combinations of antiangiogenic agents with conventional chemotherapeutic ones, immunotherapeutic and molecularly targeted agents in HNSCC. Additional data are necessary to pinpoint which patients could benefit most from these treatments.

Background/Objectives: Distant metastasis (DM), though uncommon at initial presentation, significantly worsens the prognosis of head and neck squamous cell carcinomas (HNSCCs). This review aimed to investigate the occurrence rates, patterns, and implications of HNSCC DM. Methods: A systematic search was performed in Scopus, PubMed and Web of Science. Results: Out of 7576 identified titles, 35 studies were included, encompassing 28,193 patients. The pooled rate of DM was 10.01%, with significant heterogeneity existing among the studies (I2: 94.13%). The most common metastatic sites were the lungs, bones, and brain (58%, 15%, 4%, respectively). Treatment modalities varied: overall, 20.4% of patients received radiotherapy alone, 7% underwent chemotherapy, and 4.5% received surgical metastasectomies. Combined treatments accounted for 18.3% of patients. However, 41.3% of patients received no treatment for DM. The median overall survival (OS) after DM diagnosis was 10.1 months. Studies highlighted a 36.3% two-year survival rate for patients with oligo-metastases, compared to the 7.4% rate for those with multiple metastases. At the time of DM diagnosis, half of the studied population presented with locoregional failure. Conclusions: Advanced imaging techniques and emerging systemic therapies offer hope for improved DM detection and treatment. However, continuous research is essential to develop therapeutic strategies that can enhance survival and improve the quality of life for patients with DM.

Background: Pott’s Puffy Tumor (PPT) in young-age patients is a rare clinical entity characterized by osteomyelitis of the frontal bone with a subperiosteal abscess collection. Previous reviews primarily consist of small, retrospective case series and anecdotal reports. This study aims to present the largest, most up-to-date systematic review of essential clinical findings, diagnostic modalities, microbiologic considerations, and treatment approaches for managing PPT in pediatric and adolescent populations. Methods: PubMed, Scopus, and Web of Science databases were systematically screened until 3 January 2024. The protocol of this investigation was registered on PROSPERO in January 2024, and the systematic review was performed according to the PRISMA statement. The study included 184 patients from 109 articles and an additional case from the authors’ institution. Results: PPT commonly stems from untreated rhinosinusitis, respectively, acute pansinusitis, frontal acute rhinosinusitis and chronic rhinosinusitis, and direct head trauma. Infections typically involve a polymicrobial anaerobe-predominant microbiome. Computed tomography and magnetic resonance imaging are routinely used for presurgical assessment and posttreatment surveillance. Intracranial complications were significantly associated with the type of surgical treatment (p value < 0.0001). Conclusions: PPT is a significant and relatively morbid disease often under-recognized and misdiagnosed due to its variable clinical presentation. Management includes both antimicrobial therapy and surgical intervention, emphasizing the importance of an interdisciplinary approach.

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer–containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumor ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumors selectively uptake PS (10 mg/kg, i.v.) with 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single PS nanoparticle–mediated PDT (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumors yielded significant apoptosis in 65.7% of tumor cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumor models. Complete tumor response was achieved in 65% of Cal-33 and 91% of MOC22 tumor mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumors, respectively. In buccal VX-2 rabbit tumors, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumors. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes. Significance: PS-PDT is a safe and repeatable treatment modality for OCSCC ablation. PS demonstrated tumor selective uptake and PS-PDT treatments achieved reproducible efficacy and effectiveness in multiple tumor models superior to other clinically tested photosensitizer drugs. Cosmetic and functional outcomes were excellent, and no clinically significant treatment-associated toxicities were detected. These results are enabling of window of opportunity trials for fluorescence-guided PS-PDT in patients with early-stage OCSCC scheduled for surgery.

Objective: The aim of this prospective clinical study is to evaluate the feasibility of the micro-laryngeal surgery (MLS) using a 3D operating exoscope (OE) in substitution to a conventional operating microscope (OM). Methods: A total of 41 consecutive patients were included (male: 26; median age: 55.0 years; IQR: 46.0-68.0). After each procedure, the surgeon and the scrub nurse were asked to fill out a tailored questionnaire on a 3-point Likert scale (1—not acceptable, 2—acceptable, 3—good) including 12 items. Results: The majority of the procedures were therapeutic (n = 31, 75.6%), while the remaining were diagnostic (n = 10, 24.4%). All surgeries were successfully completed without the support of the OM, and no complications or unwanted delays were detected. The majority of the individual items were judged “good” either by surgeons (n = 399, 81.1%) and scrub nurses (n = 287, 87.5%). The natural posture during the procedure, and the ease of use the joystick and focusing were the best-rated items by the surgeons. Conclusions: This study demonstrates the feasibility of MLS using the OE. Further comparative clinical studies are needed to clarify its real value in substitution to a conventional operating microscope and to better define advantages and disadvantages.