Objective: To evaluate the impact of postoperative radiotherapy (PORT) on oncological outcomes in node-negative early-stage oral squamous cell carcinoma (OSCC) with perineural invasion (PNI). Methods: A systematic review and meta-analysis was conducted using the PubMed, EMBASE, and Scopus databases for the period from 2000 to 2024. Studies comparing PORT versus observation in pN0 early-stage OSCC with PNI were included. Oncological outcomes assessed included overall survival (OS), disease-free survival (DFS), and local control (LC). A random-effects model was used to calculate log odds ratios, and heterogeneity was assessed using tau², chi², and I² statistics. Results: Seven retrospective studies comprising 522 patients (281 PORT, 241 no-PORT) were included. The 3-year overall survival (OS) was 86.3% in the PORT group compared to 71.1% in the no-PORT group (logOR = −1.03, p = 0.0012), while the 5-year OS was 88.1% versus 77.3% (logOR = −0.97, p = 0.0061). Disease-free survival (DFS) also favored PORT, with 3-year DFS at 86.3% versus 58.1% (logOR = −1.19, p < 0.001) and 5-year DFS at 86.3% versus 55% (logOR = −0.78, p = 0.003). Local control (LC) was higher in the PORT group, with 3-year LC rates of 89% compared to 72.2% in the no-PORT group (logOR = −1.13, p = 0.025). Conclusions: PORT significantly improves OS, DFS, and LC in node-negative early-stage OSCC with PNI as the sole adverse feature.

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC—including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates—were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or “orthogonal” testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice.

Background/Objectives: Total glossectomy (TG) is among the most radical operations in head and neck oncology. While it can achieve local control in advanced oral tongue squamous cell carcinoma, survival and functional outcomes are inconsistently reported, and pooled estimates remain limited. This study aimed to systematically evaluate survival, functional recovery, and prognostic factors following primary TG. Methods: We conducted a proportional meta-analysis of studies reporting outcomes after primary TG for oral tongue squamous cell carcinoma. Studies combining TG with laryngectomy, salvage settings, or second primary tumors were excluded. Two reviewers independently screened, extracted data, and assessed quality with the Newcastle–Ottawa Scale. Pooled 1-, 3-, and 5-year overall survival (OS) with 95% confidence intervals (CIs) was calculated using a random-effects model. Heterogeneity was quantified (Q, τ², I²), and robustness was assessed with sensitivity analyses. Disease-free survival (DFS) and functional outcomes (swallowing, airway, speech) were narratively summarized due to inconsistent reporting. Results: Ten studies (1992–2022) comprising 261 patients met the criteria. Pooled OS was 81% (95% CI, 71–90) at 1 year, 55% (95% CI, 41–68) at 3 years, and 47% (95% CI, 27–67) at 5 years, with rising heterogeneity (I² up to 89%). The post-2000 series showed improved 5-year OS (63%). Adverse prognostic factors included advanced T stage, nodal disease (N+), and positive margins. Functional recovery varied: 15–30% remained gastrostomy-dependent and 20–25% aspirated, while reconstruction and structured rehabilitation improved outcomes. Conclusions: Survival after TG declines beyond the first year, with under half surviving at 5 years, though modern outcomes appear better. Significant functional morbidity underscores the need for multidisciplinary care. Future biomarker-driven studies should refine patient selection and prognostic assessment.