Search Results (103)

Total laryngectomy (TL) is still the standard treatment for advanced laryngeal and hypopharyngeal cancer, with pharyngeal reconstruction being a challenging determinant of outcomes. We searched PubMed/MEDLINE, Scopus, and Web of Science from inception to July 2026 for studies reporting pharyngeal reconstruction techniques or fistula outcomes after TL. This narrative review synthesizes current evidence on reconstruction following TL across three domains: prevention, reconstruction, and management of pharyngocutaneous fistula (PCF). Defect classification into minimal, partial, and circumferential categories guides reconstructive decision-making, each supported by a distinct evidence stream. Risk stratification identifies prior radiotherapy, poor nutritional status, sarcopenia, and salvage setting as the strongest PCF predictors. For minimal defects, stapler-assisted closure reduces PCF risk in primary TL, and double-layer manual closure outperforms single-layer repair. Partial defects in the salvage setting benefit from vascularized tissue augmentation, with pedicled onlay flaps associated with lower fistula rates than primary closure or free flap patching. For circumferential defects, network meta-analytic data suggest that the free jejunal flap ranks highest for fistula prevention. Comparative cohort data indicate that anterolateral thigh flaps may offer better long-term speech outcomes. The optimal choice depends on the outcome prioritized. Salivary bypass tubes represent the most consistently supported adjunct for fistula and stenosis prevention. PCF management follows a stage-based approach: conservative care for early fistulas, negative pressure wound therapy as a bridge in subacute cases, and vascularized flap reconstruction for chronic or refractory fistulas. Full article

Background/Objectives: Supraglottic and hypopharyngeal carcinomas are aggressive malignancies that are often diagnosed at advanced stages. Timely recognition of these malignancies is influenced by many factors, such as endoscope quality and experience. This study evaluated the potential of artificial intelligence (AI) to support real-time detection and classification of such lesions during flexible endoscopy in the outpatient clinic. Methods: A previously developed deep learning (DL) algorithm was extended from a glottic lesion model to the unified localization and classification of glottic, supraglottic, and hypopharyngeal lesions during flexible endoscopy. Lesion frames were extracted from endoscopy videos obtained at two head and neck oncology centers and one secondary referral center between 2012 and 2024. These frames were annotated and labeled based on histopathological or clinically confirmed reference diagnoses. The primary outcome was the unified model’s performance in detection of lesions per frame. After training (70% of data), the positive predictive value (precision) and sensitivity (recall) of this model were calculated on an independent test set (30% of data), stratified by subsite and tumor (T-) classification. Secondly, the model’s binary classification performance (benign or malignant) was evaluated. Results: From 490 supraglottic and hypopharyngeal endoscopy videos, 40,059 frames with a benign or malignant lesion were extracted and added to the 56,036 glottic lesion frames in the database, comprising 1336 lesion videos and 123 healthy control videos (total n = 1459). On the test set, the model achieved a detection precision of 92.1% (95% CI: 90.9–93.2) and a recall of 73.3% (95% CI: 69.8–76.6). Detection performance increased with higher T-stage. Among correctly detected lesion instances in a malignancy-dominated test set (65.3% of lesion instances), sensitivity for malignancy detection was 94.3% (95% CI: 91.8–96.5). Combined end-to-end performance for correct malignant lesion detection and classification was estimated at 69.1% (object-level recall 73.3% × classification sensitivity 94.3%). Evaluation of 33 lesion-free videos demonstrated a mean frame-level specificity of 46.6% and a median of 19 false positive detections per video. Conclusions: This is the first study to report a DL model for real-time endoscopic detection and classification of benign and malignant laryngeal and pharyngeal lesions. The developed model showed promising lesion detection and cancer classification performance in the evaluated test set. T1 tumor detection remains an important limitation, particularly because early-stage detection is a primary aim of AI-assisted endoscopy. Further model testing is required in real-world lesion prevalence settings, where external validation and clinical usability should be investigated. Full article

The potential impact of propofol on head and neck cancer (HNC) progression and clinical outcomes, in relation to both direct effects on tumor biology and indirect effects mediated by perioperative immune and inflammatory responses, remains controversial. Most mechanistic evidence currently available for HNC originates from studies of oral squamous cell carcinoma. Accordingly, mechanistic findings are interpreted primarily as OSCC-derived evidence and should not be generalized to all HNC subsites without further validation. To address this, we critically examined propofol’s potential role as a perioperative anesthetic modulator of tumor biology and host responses. Preclinical studies have demonstrated that propofol suppresses proliferation, induces apoptosis, inhibits angiogenesis, and enhances 5-fluorouracil chemosensitivity. Conversely, other studies report enhanced epithelial–mesenchymal transition, migration, and invasion through SNAI1 upregulation, highlighting the context-dependent nature of propofol-mediated effects. The generalizability of these molecular observations to other HNC subsites, including laryngeal, hypopharyngeal, and oropharyngeal cancers, remains unclear. Clinically, propofol-based total intravenous anesthesia has been associated with reduced postoperative pulmonary complications and improved perioperative recovery. However, currently available HNC-specific studies have not demonstrated a consistent improvement in overall or recurrence-free survival. These discrepancies likely reflect tumor heterogeneity, variations in experimental design, perioperative confounding factors, and differences in host immune and inflammatory responses. This narrative review was based on literature identified through PubMed, Scopus, and Google Scholar, and integrates current mechanistic, immunological, and clinical evidence regarding propofol exposure during cancer surgery. Current evidence supports the perioperative benefits of propofol-based anesthesia; however, its long-term oncologic significance in HNC remains inconclusive and warrants further prospective, mechanism-driven, and biomarker-guided investigations. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) remains a global public health challenge with significant morbidity and mortality. Emerging epidemiological data indicate a rising global incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Serology for early HPV antigens has been highlighted as a relevant biomarker for HPV-associated OPSCC. This study aimed to determine the seroprevalence of HPV16 E6 antibodies in HNSCC patients in the state of Espírito Santo, Brazil. Methods: This is a prospective longitudinal cohort study in which 287 patients with HNSCC were enrolled, recruited from two oncology centers in Espírito Santo between 2011 and 2018, along with 68 cancer-free individuals. Serum samples were analyzed using the HPV16 E6 GST Capture ELISA assay. Statistical analysis was performed using SPSS. Binary logistic regression was employed to identify independent predictors of seropositivity. Results: The overall seroprevalence of HPV16 E6 antibodies was 7.3%. Seropositivity was observed in tumors of the oral cavity (6.2%) and oropharynx (13.3%). Patients with OPSCC demonstrated a significantly higher likelihood of seropositivity compared to those with tumors of the oral cavity, larynx, and hypopharynx (OR = 2.96, 95% CI: 1.21–7.28, p = 0.018). The highest frequency of HPV16 E6-positive cases occurred in tumors of the palatine tonsils (OR = 6.00; 95% CI: 1.58–22.89; p < 0.009). No seropositive cases were observed in hypopharyngeal or laryngeal tumors. Among patients with OPSCC and oral cavity squamous cell carcinoma (OCSCC), HPV16 E6 serostatus did not significantly correlate with sociodemographic, behavioral, or clinical tumor characteristics. Conclusions: Our findings reinforce the predilection of HPV-associated carcinogenesis for the oropharynx, more specifically in the palatine tonsils. In addition, this study highlights HPV16 E6 serology as a potential biomarker for HPV-driven OPSCC and underscores Brazil’s epidemiological heterogeneity, warranting standardized clinical validation. Full article

Objectives: This study investigates the association of pretreatment underweight, sarcopenia, and cancer cachexia with survival outcome in hypopharyngeal cancer (HPC) radiotherapy. Methods: This retrospective observational study analyzed 167 patients with newly diagnosed HPC treated with definitive radiotherapy. The definitions of underweight, sarcopenia, and cancer cachexia are based on the international consensus of the European Palliative Care Research Collaborative. Underweight and sarcopenia were analyzed in all 167 patients, while cachexia analyses were restricted to the 117 patients for whom pretreatment weight-loss data were available. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test, and subsequently analyzed using multivariate Cox proportional hazards models. Results: The median follow-up period was 28 months. Cachexia analyses were restricted to the 117 patients for whom pretreatment weight-loss data were available; of these, 45 (38%) met criteria for cancer cachexia. Patients with underweight (n = 76, 46%) or cancer cachexia had significantly lower locoregional control, disease-free survival, and overall survival compared to those not underweight and without cachexia, respectively, whereas there was no difference in any outcome between patients with sarcopenia (n = 54, 32%) and those without. Given the definitional overlap among underweight, sarcopenia, and cachexia, these three variables were entered into the multivariate analysis separately—which included age, sex, performance status, double cancer, T-classification, N-classification, chemotherapy administration, treatment era, and radiation dose—confirming that underweight and cancer cachexia remained independently associated with worse LRC, DFS, and OS. In the fully adjusted multivariate Cox proportional hazards models, the hazard ratios for mortality risk were 1.9 (95% confidence interval [CI], 1.1–3.4; p = 0.030) and 2.0 (95% CI, 1.1–3.8; p = 0.032) for patients with underweight or cancer cachexia, respectively. Conclusions: Pretreatment underweight and cancer cachexia negatively impact survival outcomes, including locoregional control, in HPC radiotherapy. Prospective studies with standardized nutritional assessment protocols, pre-specified intervention arms, and sufficient sample sizes are essential to validate these findings and to establish the clinical benefit of pre-treatment nutritional optimization in this patient population. Full article

Background/Objectives: Lamiaceae species are valuable sources of bioactive natural products, often associated with anti-infective properties. This study investigated chemical composition and bioactivities of dry hydroethanolic extracts and essential oils from Micromeria nervosa (Desf.) Benth. aerial parts from two localities. Methods: Extracts and essential oils were analyzed using LC-DAD-QTOF-MS/MS and GC-FID/MS, respectively. Antimicrobial activity was assessed against 14 strains (microdilution method), and antiviral activity against three viruses by determining cytopathic effects, viral titers (end-point dilution assay) and viral loads (qPCR/RT-qPCR). Cytotoxicity was evaluated on three cancer cell lines (MTT assay) and antioxidant potential using three colorimetric tests. Composition–activity correlation was statistically analyzed; in silico molecular docking/dynamics simulations were performed. Results: Thirty-five compounds were annotated in extracts, including 30 reported for the first time in this species, with rosmarinic acid as the main component. Essential oils contained 31 constituents, dominated by carvacrol. Newly detected phenolics included lithospermic acid and several salvianolic and clinopodic acids. Extracts and oils exhibited notable antibacterial activity, especially against five Gram-positive strains (MIC = 0.313–2.5 mg/mL), and oils showed marked anticandidal effects (MIC = 0.313–0.625 mg/mL) and enhanced cytotoxicity against colon, gastric and hypopharyngeal cancer cells (selectivity indices ≥ 1.66). Extracts displayed potent antiviral activity against human herpesvirus 1 (HHV-1) and adenovirus Ad5, reducing cytopathic effects and viral titers, with qPCR revealing decreased HHV-1 load. In silico analysis suggested HHV-1 glycoprotein D binding. Extracts also showed strong antioxidant potential. Conclusions: These findings demonstrate that M. nervosa is a rich source of compounds with antimicrobial/antiviral, cytotoxic and antioxidant activities, warranting further research. Full article

Bile acids are widely distributed in the human gastrointestinal tract. A literature review indicates that bile acids may have a role in initiating cancers in every organ of the digestive system. The estimated number of new digestive system cancers world-wide in 2022 was about 5 million. In the particular case of colon cancer, secondary bile acids produced in response to a high fat diet disrupt colonic epithelial cell mitochondrial membranes. This disruption leads to the release of oxidative free radicals that damage DNA, potentially leading to carcinogenic mutations. High levels of colonic bile acids may also alter the gut microbiome, with some bacteria causing inflammation and increased reactive oxygen species leading to DNA damage. Also, bile acids taken up by receptors on the surface of gastrointestinal tract cells can activate NF-kB. In turn, NF-kB may activate a super-enhancer at an oncogene. Bile acid reflux also plays a significant role in esophageal adenocarcinoma, stomach cancer and small intestine carcinogenesis. In addition, cancers of the pancreas, liver, and biliary tract can be caused by the constriction of the common bile duct leading to reflux of bile acids back into these organs. Gastroesophageal reflux involving bile acids may also contribute to hypopharyngeal squamous cell carcinogenesis. Thus, bile acids are a likely major contributory cause of cancer throughout the digestive tract. Full article

Introduction: Extranodal extension (ENE) is a well-established adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC), associated with reduced survival and the need for intensified therapy. Nutritional status—commonly assessed using the Prognostic Nutritional Index (PNI) and Body Mass Index (BMI)—also influences outcomes in HNSCC. However, whether or not ENE correlates with nutritional status has not been previously investigated. Methods: We conducted a retrospective cohort study of 109 treatment-naïve HNSCC patients with pathologically confirmed nodal metastases who underwent primary tumor resection and neck dissection between 2014 and 2025 at a national tertiary center. ENE status was determined histologically. Nutritional status was evaluated using BMI, PNI, serum albumin, and percentage of weight loss at diagnosis. Statistical analyses included t-tests, Chi-square tests, ANOVA, Cox regression, Kaplan–Meier survival analysis, and Full Factorial General Linear Models. Results: ENE was present in 54.1% of patients and significantly reduced overall survival (Kaplan–Meier p = 0.006; Cox regression RR = 1.927, p = 0.008). No significant differences in BMI, PNI, weight loss, or serum albumin were observed between ENE-positive and ENE-negative groups. ENE prevalence varied significantly by tumor origin (p = 0.018), being highest in hypopharyngeal cancers (75.8%) and lowest in oral cavity tumors (25.0%). ENE status was independent of tobacco use, alcohol abuse, and all nutritional markers across TNM 8/9 subgroups. Conclusions: ENE is a strong prognostic marker in HNSCC, appearing to be independent of nutritional status. The demonstrated heterogeneity of ENE prevalence among tumor subsites supports the need for individualized management approaches. Full article

Background: Extranodal extension (ENE) is a critical prognostic factor in head and neck squamous cell carcinoma (HNSCC) and was incorporated into the AJCC eighth-edition staging system. However, the concordance between clinical (cENE) and pathological (pENE) ENE remains poorly understood in real-world practice. Methods: We conducted a retrospective analysis using Taiwan Cancer Registry (TCR) long-form data from 2018 to 2022, focusing on four major HNSCC sites (oral cavity, oropharynx, hypopharynx, and larynx). The diagnostic gap was defined as the difference between pENE and cENE positivity rates. Results: Among 29,830 patients, a persistent diagnostic gap was observed across all sites: laryngeal (20.8%), hypopharyngeal (20.4%), oropharyngeal (11.5%), and oral cavity (9.9%). For oral cavity cancer, the gap did not narrow over the 5-year period (p = 0.9788). Furthermore, in oral cavity cancer, medical centers demonstrated a larger gap than non-medical centers (10.5% vs. 8.4%), a phenomenon we term the “Quality-Gap Paradox”. Conclusions: A significant diagnostic gap persists in HNSCC, highlighting the limitations of current imaging. The Quality-Gap Paradox, observed in oral cavity cancer, suggests this is driven by a complex interplay of factors including superior pathological detection in high-volume centers. Our findings underscore the need for advanced, personalized risk-stratification tools to bridge this gap and improve patient management. Full article

Background: Laryngeal and hypopharyngeal cancers (LHCs) exhibit heterogeneous outcomes after definitive radiotherapy (RT). Large language models (LLMs) may enhance prognostic stratification by integrating complex clinical and imaging data. This study validated two pre-trained LLMs—GPT-4o-2024-08-06 and Gemma-2-27b-it—for outcome prediction in LHC. Methods: Ninety-two patients with non-metastatic LHC treated with definitive (chemo)radiotherapy at Linkou Chang Gung Memorial Hospital (2006–2013) were retrospectively analyzed. First-order and 3D radiomic features were extracted from intra- and peritumoral regions on pre- and mid-RT CT scans. LLMs were prompted with clinical variables, radiotherapy notes, and radiomic features to classify patients as high- or low-risk for death, recurrence, and distant metastasis. Model performance was assessed using sensitivity, specificity, AUC, Kaplan–Meier survival analysis, and McNemar tests. Results: Integration of radiomic features significantly improved prognostic discrimination over clinical/RT plan data alone for both LLMs. For death prediction, pre-RT radiomics were the most predictive: GPT-4o achieved a peak AUC of 0.730 using intratumoral features, while Gemma-2-27b reached 0.736 using peritumoral features. For recurrence prediction, mid-RT peritumoral features yielded optimal performance (AUC = 0.703 for GPT-4o; AUC = 0.709 for Gemma-2-27b). Kaplan–Meier analyses confirmed statistically significant separation of risk groups: pre-RT intra- and peritumoral features for overall survival (for both GPT-4o and Gemma-2-27b, p < 0.05), and mid-RT peritumoral features for recurrence-free survival (p = 0.028 for GPT-4o; p = 0.017 for Gemma-2-27b). McNemar tests revealed no significant performance difference between the two LLMs when augmented with radiomics (all p > 0.05), indicating that the open-source model achieved comparable accuracy to its proprietary counterpart. Both models generated clinically coherent, patient-specific rationales explaining risk assignments, enhancing interpretability and clinical trust. Conclusions: This external validation demonstrates that pre-trained LLMs can serve as accurate, interpretable, and multimodal prognostic engines for LHC. Pre-RT radiomic features are critical for predicting mortality and metastasis, while mid-RT peritumoral features uniquely inform recurrence risk. The comparable performance of the open-source Gemma-2-27b-it model suggests a scalable, cost-effective, and privacy-preserving pathway for the integration of LLM-based tools into precision radiation oncology workflows to enhance risk stratification and therapeutic personalization. Full article

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I² = 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted. Full article

Background/Objectives: The implementation of adaptive radiation therapy (ART) is increasingly becoming widely available in the clinical practice of radiotherapy (RT). For patients with pharyngeal cancer receiving RT, this study aimed to develop a deep learning (DL) model by merging baseline and ART simulation computed tomography (CT) images to predict treatment outcomes. Methods: Clinical and imaging data from 162 patients of newly diagnosed oropharyngeal or hypopharyngeal cancer were analyzed. All completed definitive treatment and their baseline and ART non-contrast simulation CTs were utilized for training. After augmentation of the CT images, a deep contrastive learning model was employed to predict the occurrence of local recurrence (LR), neck lymph node relapse (NR), and distant metastases (DM). Receiver operating characteristic curve analysis was conducted to evaluate the model’s performance. Results: Over a median follow-up period of 34 months, 53 (32.7%), 36 (22.2%), and 23 (14.0%) patients developed LR, NR, and DM, respectively. Following the integration of prediction results from baseline and ART simulation CTs, the area under the curve for predicting the occurrence of LR, NR, and DM reached 0.773, 0.747, and 0.793. At the same time, the accuracy for the three endpoints was 72.4%, 74.7%, and 75.7%, respectively. Conclusions: For patients with pharyngeal cancer ready to receive RT-based treatment, our proposed models can predict the development of LR, NR, or DM through baseline and ART simulation CTs. External validation needs to be conducted to confirm the model’s performance. Full article

Hypopharyngeal carcinoma (HPC) represents the most prognostically unfavorable subtype among head and neck malignancies. Platinum-based neoadjuvant chemotherapy serves as a critical therapeutic approach for improving outcomes in hypopharyngeal carcinoma; however, its efficacy remains suboptimal due to the high incidence of chemoresistance. Current research on chemoresistance has primarily focused on head and neck squamous cell carcinoma (HNSCC), yet significant heterogeneity exists between hypopharyngeal carcinoma and other head and neck tumors, limiting the direct applicability of broader HNSCC research findings to hypopharyngeal carcinoma. This review systematically summarizes recent advances in understanding the mechanisms underlying chemoresistance in hypopharyngeal carcinoma, with emphasis on the comprehensive elucidation of key mechanisms, including apoptosis evasion, enhanced DNA damage repair, augmented autophagy, and increased drug efflux. Moreover, three noteworthy special scenarios involving cancer stem cells (CSCs), epithelial–mesenchymal transition (EMT), and cancer-associated fibroblasts (CAFs) are discussed. These entities not only intrinsically participate in multiple chemoresistance mechanisms but also interact synergistically, thereby further exacerbating chemoresistance in hypopharyngeal carcinoma. Full article

Background/Objectives: Total laryngectomy (TL) remains a key treatment option for advanced laryngeal cancer. Primary tracheoesophageal puncture (TEP) with voice prosthesis (VP) enables early speech restoration and is increasingly adopted, even in patients with conditions traditionally considered contraindications, such as prior/adjuvant radiotherapy, extended resections, and immediate reconstructive procedures. This study evaluates complication rates and long-term outcomes associated with primary TEP in these settings. Methods: A retrospective cohort of 101 patients undergoing TL for laryngeal or hypopharyngeal squamous cell carcinoma at the University Hospital of Sassari (August 2017–December 2024) was analyzed. Demographic, clinical, surgical, and oncological data were collected, with a particular focus on postoperative early complications and late sequelae and oncological outcomes. Results: Primary TEP was performed in 78 patients (77.2%). Overall, pharyngocutaneous fistula occurred in 6/101 patients (5.9%), postoperative bleeding in 5/101 (5.0%), and dysphagia in 11/101 (10.9%), with only 2/11 (2.0%) requiring intervention. Mean follow-up was 44.6 ± 3.2 months (median 41, range 4–93). No significant association was found between primary TEP and complication rates, including in patients undergoing enlarged TL with pectoralis major reconstruction. Conclusions: Primary TEP appears safe and effective, even in cases requiring extended resections and reconstructive procedures. It should be considered to enhance functional recovery and postoperative quality of life for all motivated patients undergoing total laryngectomy without patient-related contraindications. Our findings may constitute a step towards personalized medicine in laryngeal oncology as they support priortizing patient-specific factors, such as pneumological and neurological clinical conditions and level of cooperation, over purely surgical considerations. Full article

Background: Hospital-based data can complement registry estimates for cranio-maxillofacial (CMF) oncology, particularly in under-reported regions. We aimed to describe the institutional case-mix of CMF tumor diagnoses, standardized to ICD-10 sites, and to quantify trends using visit-normalized indicators. Methods: We conducted a retrospective, observational, single-center, hospital-based study of diagnosis-level encounters (2012–2016). Diagnoses were recoded to ICD-10 and restricted to CMF sites (lip, oral cavity, major salivary glands, oropharynx/hypopharynx, nasal cavity/middle ear, paranasal sinuses, eye/adnexa). The primary indicator uses a strict CMF set (malignant CMF codes plus D00.0 and D14.1); odontogenic cysts and non-neoplastic jaw lesions (K09–K10) were excluded, while benign CMF neoplasms are reported descriptively for site distributions. Results: We identified 2729 malignant CMF diagnoses over 2012–2016, peaking in 2014 (n = 751) and lowest in 2016 (n = 367). The combined malignant rate (per 1000 total visits) was 30.6, 43.9, 52.6, 34.4, and 26.7 for 2012→2016. The proportion of malignancies within the strict CMF set was 99.2%, 97.3%, 97.9%, 96.8%, and 95.1%, respectively (overall 97.4%). The most frequent malignant sites cumulatively were the palate (n = 416), parotid gland (n = 376), floor of mouth (n = 344), gingiva (n = 282), and mouth, unspecified (n = 179). Conclusions: After ICD-10 recoding and restriction to CMF sites, malignant tumors predominated within the institutional, diagnosis-level case-mix, with a 2014 peak followed by a decline. These indicators are case-mix monitors and not population incidences; interpretation should consider coding practices and service-mix changes across years. Full article