ABSTRACT Objectives Post‐radiation nasopharyngeal biopsies in patients with nasopharyngeal carcinoma (NPC) are primarily performed to exclude recurrence, yet their utility in assessing radiotoxicity remains underexplored. This study characterizes two distinct histological patterns of necrosis: coagulative stromal necrosis (Type A) and microscopic osteoradionecrosis (ORN; Type B). We aim to analyze the association of these patterns with radiotherapy (RT)‐related complications. Methods Data from a cohort of 483 patients were reviewed. Study groups included Type A ( n = 30), Type B ( n = 12), and clinically diagnosed skull base osteoradionecrosis (cORN, n = 25). Controls were categorized by histological findings: ulcer ( n = 24), fibrosis ( n = 43), and viable lymphoid tissue ( n = 21). A comparison cohort of patients without posttreatment biopsy ( n = 63) was also included. Results Carotid blowout syndrome (CBS) occurred exclusively in the study groups: Type A (13.3%), Type B (8.3%), and cORN (12.0%). No CBS events were observed in the histological control groups or the comparison cohort. Notably, Type A biopsies were temporally clustered closely with CBS events, specifically occurring from 3 months before to 1 month after the episode. Conclusion Type A and Type B histological patterns are associated with an increased risk of carotid blowout, comparable to cORN. Type A may represent a “two‐hit” necrotic transition from a vulnerable fibrotic substrate. Beyond diagnosing recurrence, post‐RT biopsies may offer valuable insights into the status of deep tissues. Identifying these patterns can aid in risk stratification and potentially facilitate early intervention to mitigate severe complications. Level of Evidence 4.

Esophageal squamous cell carcinoma (ESCC) survivors remain at elevated risk of developing second primary oral cancer (SPOC), yet the role of intratumoral microbiomes in SPOC emergence is not fully understood. We performed 16 S rRNA V3-V4 sequencing on tumor brushings from 28 ESCC patients (20 SPOC-negative, 8 SPOC-positive) to profile microbial diversity, taxonomic composition, functional potential, and interaction networks. Alpha diversity metrics (Chao1, Shannon) did not differ significantly between groups (p > 0.05), whereas sparse partial least squares-discriminant analysis of beta diversity robustly separated SPOC-positive from SPOC-negative tumors (p < 0.001), identifying 32 discriminant amplicon sequence variants (ASVs) linked to 41 differential KEGG pathways. Intratumoral Spearman correlation networks (|r| > 0.3, p < 0.05) between the ten most abundant genera and these pathways revealed two distinct modules: a SPOC-associated network centered on Prevotella pallens and P. scopos, enriched in carbohydrate metabolism, PI3K-Akt signaling, and glycosaminoglycan degradation; and a non-SPOC network anchored by Alcaligenaceae, Cyanobiaceae, Rhodobacteraceae, and Prevotella oris, associated with macrolide biosynthesis and aminobenzoate degradation. These findings demonstrate that specific intratumoral microbial interaction networks distinguish ESCC patients who develop SPOC, and highlight network-based microbial signatures as promising biomarkers for SPOC risk stratification.

Accurate assessment of joint range of motion (ROM) and maximal mouth opening (MMO) is essential in the rehabilitation of patients with oral cancer. This study aimed to evaluate the concurrent validity and reliability of an artificial intelligence (AI)–assisted physiotherapy assessment system (AIMS) for measuring MMO, cervical, and shoulder ROM in patients with oral cancer, with a healthy control group for comparison. Twenty patients with oral cancer and 20 healthy individuals were included. ROM measurements obtained using AIMS were compared with clinician-based assessments using an electrogoniometer and a TheraBite ROM scale. Two human raters performed manual measurements. In the healthy group, all three raters assessed each movement, whereas in the patient group, AIMS and Rater 1 performed the assessments. Concurrent validity between the AIMS and clinician-based measurements was evaluated using intraclass correlation coefficients (ICC), standard error of measurement (SEM), minimal detectable change (MDC95), and Bland–Altman analysis. Within-session repeatability of the AIMS and human raters was evaluated using repeated measurements. The AIMS demonstrated variable concurrent validity across movement tasks. Concurrent validity was highest for shoulder abduction (ICC 0.68–0.80) followed by cervical lateral flexion (ICC 0.44–0.57), whereas lower agreement was observed for cervical rotation and MMO in the healthy group (ICC 0.03–0.35). In contrast, concurrent validity was generally higher in the patient group across all movement tasks (ICC 0.44–0.76). The AIMS demonstrated high within-session repeatability across repeated measurements. Bland–Altman analysis demonstrated relatively small mean bias across most movement tasks, although agreement varied according to movement and no consistent directional bias was observed. The AIMS demonstrated variable concurrent validity across movement tasks and high within-session repeatability, with the strongest performance observed for shoulder abduction and cervical lateral flexion. These findings support its potential as an objective tool for movement assessment in patients with oral cancer, while further refinement of cervical rotation and MMO is warranted.

Background The prognostic significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in early-stage oral squamous cell carcinoma (OSCC) remains uncertain. The role of postoperative radiotherapy (PORT) in this subgroup is debated. This study aimed to clarify the clinical impact of PNI/LVI and determine the effect of PORT across risk-stratified subsets of early-stage OSCC. Methods We retrospectively analyzed 6,121 patients with pT1-2N0M0 OSCC from the Taiwan Cancer Registry (2018-2022). Patients were categorized into Group A (PNI-/LVI-) and Group B (PNI+ and/or LVI+). Clinicopathological characteristics, survival outcomes, and the effect of PORT were assessed using multivariable analysis and propensity score matching (PSM). Results The PNI/LVI positivity occurred in 13.5% of patients and was independently associated with poorer differentiation, greater depth of invasion (> 5 mm), T2 classification, tongue subsite, lower BMI, and female sex. Group B patients exhibited significantly lower overall survival (HR 1.45, p = 0.001) and disease-free survival (HR 1.44, p < 0.001), with inferior locoregional control versus Group A. PORT significantly improved locoregional control in Group B (p = 0.005), but no overall or disease-free survival benefit was observed, likely due to effective salvage surgery. In contrast, in Group A, PORT offered no benefit and was associated with worse outcomes. Conclusions Perineural invasion and/or LVI represent key adverse prognosticators in early-stage OSCC. Postoperative radiotherapy selectively enhances locoregional control in intermediate-risk patients, but survival outcomes remain unaffected. A risk-adapted therapeutic approach is warranted, tailoring PORT to patients with adverse features and avoiding overtreatment in low-risk cases.

PURPOSETo quantify risk reduction in oral precancer and cancer with time since cessation of betel quid chewing, smoking, and alcohol drinking.PATIENTS AND METHODSWe conducted a multicenter case-control study in Taiwan of patients with invasive oral cancer (n = 768), visual/clinical oral precancer (n = 1,998), and hospital-based controls (n = 717, recalibrated/reweighted to represent the Taiwan general population). Weighted logistic regression was used to evaluate associations of duration, intensity, and time since cessation of betel quid chewing without tobacco, smoking, and alcohol drinking (modeled using splines and categorically) with oral precancer and cancer risk versus controls.RESULTSRisk of oral precancer increased with increased duration and intensity of chewing and smoking, and increased intensity of alcohol drinking. Risk of oral cancer increased with increased duration and intensity of chewing, increased duration of smoking, and increased intensity of alcohol drinking. For oral precancer, when compared with current users (defined as current users and individuals who quit for ≤2 years before study recruitment), odds ratios (ORs) for 10-year cessation of behaviors were as follows: chewing = 0.63 (bootstrap 95% CI, 0.43 to 0.83); smoking = 0.30 (95% CI, 0.18 to 0.41); and alcohol = 0.60 (95% CI, 0.34 to 0.86). Likewise, risk of oral cancer decreased with increasing time since cessation; ORs for 10-year cessation were as follows: chewing = 0.74 (95% CI, 0.44 to 1.05); smoking = 0.45 (95% CI, 0.22 to 0.67); and alcohol drinking = 0.55 (95% CI, 0.20 to 0.90). Adjusted population-attributable fractions show that cessation of chewing for ≥10 years would prevent an estimated 23.2% of oral precancers and 24.2% of oral cancers; cessation of smoking for ≥10 years would prevent 51.5% of oral precancers and 44.6% of cancers in Taiwan.CONCLUSIONOur findings support the potential for primary prevention of oral precancer and cancer through cessation of betel quid chewing (without tobacco), smoking, and alcohol drinking among current users.

Importance:Tests for total antibodies specific to the Epstein-Barr virus (EBV) BNLF2b gene-encoded putative protein (P85-Ab) have shown high sensitivity and specificity for detecting newly diagnosed nasopharyngeal carcinoma (NPC). However, independent validation of these findings is important before considering clinical application. Objective:To compare the performance of P85-Ab testing for NPC detection with a combined Epstein-Barr virus-specific IgA antibody score and a circulating EBV DNA algorithm. Design, Setting, and Participants:This was a multicenter case-control study conducted from July 2010 to December 2014 at 6 medical centers in northern and central Taiwan. Participants were patients with NPC and controls who all provided blood samples for EBV biomarker testing. Data were analyzed from January 2025 to January 2026. Exposures:Total antibodies specific to P85-Ab. For comparison, EBV viral capsid antigen/nuclear antigen 1 (VCA-IgA/EBNA1-IgA) antibody score and the circulating EBV DNA algorithm results were evaluated from the same archived blood specimens collected at enrollment. Results:The analysis included 892 patients with NPC (mean [SD] age, 48.6 [11.1] years; 191 females [21.4%] and 701 males [78.6%]) and 1804 individuals in the control group (mean [SD] age, 48.1 [12.2] years; 542 females [30.0%] and 1262 males [70.0%]). P85-Ab demonstrated a sensitivity of 92.5% (95% CI, 90.7%-94.3%) and specificity of 98.7% (95% CI, 98.2%-99.2%), higher than the EBV VCA-IgA/EBNA1-IgA score (sensitivity, 88.4%; specificity, 94.9%) and comparable to the circulating EBV DNA algorithm (sensitivity, 93.2%; specificity, 98.1%). Sensitivity for early-stage NPC was higher for P85-Ab (93%) than for the other 2 methods (87%). P85-Ab performance remained high across age, sex, region, ethnicity, family history, and smoking subgroups. At NPC incidence rates of 20 to 100 per 100 000 person-years, the numbers needed to screen were similar across the 3 approaches: 5656 and 1131 for EBV VCA-IgA/EBNA1-IgA; 5365 and 1073 for EBV DNA; and 5405 and 1081 for P85-Ab. Positive predictive value (PPV) was 0.4% for the EBV antibody score, 1.0% for the EBV DNA algorithm, and 1.4% for the P85-Ab test; at an incidence of 100 per 100 000, the PPVs increased to 1.7%, 4.7%, and 6.6%, respectively. Conclusions and Relevance:This multicenter case-control study found that P85-Ab testing had high sensitivity and specificity for early detection of NPC, with performance better than or comparable to existing EBV-based screening methods. These findings support the potential use of P85-Ab testing as a practical biomarker for population-based NPC screening.

BACKGROUND:The survival benefit of adjuvant radiotherapy/chemoradiotherapy (RT/CRT) in pT4aN0M0 gingival squamous cell carcinoma (GSCC) with adequate surgical margins remains unclear due to limited subsite-specific evidence. In this retrospective cohort study, we evaluated the associations of adjuvant RT/CRT with survival outcomes and identified prognostic factors in this clinically relevant subgroup. METHODS:We used the Taiwan Cancer Registry (2011-2021) to identify patients with first primary T4aN0M0 GSCC and clear resection margins (≥5 mm). Patients treated with surgery alone were compared with those receiving adjuvant RT/CRT. Cohorts were balanced via 1:1 propensity score matching (PSM) on age, sex, tumor depth, tumor differentiation, and comorbidity burden. Disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan-Meier estimates and Cox proportional hazards regression models. RESULTS:Among the 530 study patients, 75.3% (n = 399) received adjuvant RT/CRT. In the unmatched cohort, 5-year DSS and OS rates were similar for surgery alone vs. adjuvant RT/CRT (80% vs. 79%, p = 0.27; 67% vs. 72%, p = 0.99, respectively). After PSM (125 pairs), the 5-year DSS and OS rates were comparable, being 81% vs. 83% (p = 0.61) and 68% vs. 78% (p = 0.46), respectively. Multivariable analysis demonstrated that increasing age, moderate/poor differentiation, depth > 14 mm, and Charlson comorbidity index > 1 were independent prognosticators for DSS or OS, whereas adjuvant RT/CRT was not independently associated with better outcomes. CONCLUSION:For patients with T4aN0M0 GSCC and clear surgical margins, adjuvant RT/CRT did not confer a survival advantage over surgery alone, suggesting limited benefit of routine adjuvant therapy in this setting. Prospective studies are needed to validate this finding and to refine evidence-based risk stratification models.

6080 Background: Locoregional recurrence is the main cause of morbidity and mortality in HNSCC, yet therapeutic choices are limited by sequelae of previous treatment and the potential for significant loss of function. ASP-1929 PIT is a novel cancer-targeted technology, utilizing an anti-EGFR monoclonal antibody conjugated to the dye IR700, that is activated by 690 nm light to induce rapid selective tumor cell destruction and trigger immune response. Methods: This global phase 3 study was conducted at 40 study centers located in the US, Taiwan, Japan, India, and Ukraine. Patients with locoregionally recurrent HNSCC who had failed or progressed on or after at least 2 lines of therapy were randomized 2:1 to the PIT arm or SOC. The planned sample size was 275. In the PIT arm, each cycle consisted of ASP-1929 infusion (640 mg/m 2 ) on Day 1, followed 24 ± 4 hours later by illumination (50 J/cm 2 superficial and/or 100 J/cm interstitial). Retreatment occurred ≥4 weeks apart, based on tumor response, for up to 8 cycles. In the control arm, patients received the physician’s choice of standard of care (docetaxel, cetuximab, methotrexate, or paclitaxel) until disease progression, intolerable adverse effects, or discontinuation of study treatment. Safety and efficacy outcomes were evaluated, with a data cutoff of 30 April 2025. Results: Active patient enrollment was discontinued due to challenges in patient recruitment and changes in the SOC landscape. As of 17 December 2024, 135 patients had been enrolled, with 68 patients experiencing progression or death and 36 patients in the ongoing long-term survival follow-up phase of the study. Median age was 62.0 years; 80.7% were male. In PIT and SOC arms, 64.0% and 63.0% of patients had received ≥ 3 prior therapy lines. Despite similar progression-free survival (HR 0.91; 95% CI 0.24 - 3.45), median overall survival was 15.7 months in the PIT arm compared to 9.6 months in the SOC arm (HR 0.83; 95% CI 0.50 - 1.36). Objective response rate was 25.8% in the PIT arm and 15.2% in the SOC arm, and disease control rate was 68.5% and 43.5%, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58.3% of patients in the PIT arm and 36.4% of patients in SOC; however, fewer TEAEs led to dose modification, delay, or interruption in the PIT arm (15.5% vs 30.3%). Conclusions: Considering the limitations of the study data, these results support ASP-1929 PIT as a tolerable and clinically active treatment option for locoregional, recurrent HNSCC and its ongoing evaluation in the current randomized global Phase 3 ASP-1929-381 study. Clinical trial information: NCT03769506 .

PURPOSE:Locoregionally advanced oral cavity squamous cell carcinoma (LA-OCSCC) has marked physical, psychological, and functional burden. Patients remain at high risk of relapse, often experiencing psychosocial distress. This study examined lived experiences of LA-OCSCC patients in the Asia-Pacific region to identify opportunities to reduce anxiety and improve coping strategies. METHODS:115 participants were interviewed across Australia, Hong Kong, South Korea, Taiwan, and Vietnam, including LA-OCSCC patients who underwent surgery and adjuvant chemoradiotherapy, their caregivers, and multidisciplinary care teams (clinical radiation and medical oncologists, supportive care specialists, nurse/case managers, psychologists, dietitians, speech therapists, and dentists). The Psycho-Onco Emotional Anxiety (POEM) framework informed research materials and analysis. RESULTS:Physical and functional impairments from tri-modality treatment led to profound psychosocial distress, negative psychosexual well-being, and social withdrawal, diminishing quality of life. Patients also faced stigma associated with OCSCC and social constraints, including gender norms discouraging men from showing vulnerability or seeking support. Fear of recurrence driven by awareness of the aggressive and recurrent nature of OCSCC further exacerbates anxiety. Limited access to psychosocial care, coupled with a lack of recognition among patients and caregivers of its benefits, further restricted the implementation of patient-centered care. CONCLUSION:Defining the psychological and emotional burden of LA-OCSCC is a crucial step toward enabling HCPs to recognize distress early and apply targeted screening strategies that strengthen patient support, engagement, and adherence to care. IMPLICATIONS FOR CANCER SURVIVORS:Timely and integrated psychosocial and rehabilitative care is crucial to restoring function and reducing anxiety, addressing the long-term effects of treatment and ultimately improving cancer survivorship.

A high-risk margin is a recurrence risk factor in oral squamous cell carcinoma (OSCC), but its exact definition is debated. The effectiveness of the margin-to-depth-of-invasion ratio (MDR) in identifying high-risk margin remains to be determined. Patients who had a diagnosis of pT1-4N0 OSCC with negative margins (margin > 1 mm) recorded in the Taiwan Cancer Registry between January 2018 and December 2021 were reviewed. All patients were categorized into two groups: MDR < 0.5 and MDR ≥ 0.5. The study analyzed 7420 OSCC patients without a positive margin. Of these 7420 patients, 4669 (62.92

Supplementary Table S1 shows marker pathway allocation and corresponding citations

Supplementary Methods S1 expands upon data and statistical methods.

ObjectiveTo assess the feasibility of the Yale Swallow Protocol and refine it for parsimony.DesignCross-sectional study.SettingFour diverse units at a medical centre.ParticipantsHospitalised adults at high risk of dysphagia (i.e., those aged over 65 years, admitted for stroke, Parkinson's disease, or head and neck cancer treatment) using consecutive sampling.Main MeasuresA research nurse administered the protocol, recording adverse events, administration time, and failure rates, with an 85% failure rate threshold to assess the ceiling effect. The protocol consists of contraindications, cognitive screenings, oral motor examinations, and a 3-ounce water swallow challenge, but pass/fail decisions are based solely on contraindications and the water challenge. Parsimonious combinations of items were explored to refine and potentially shorten the protocol. The measurement precision of the refined and shortened protocols was evaluated using the Rasch model.ResultsOf the 502 patients enrolled (mean age 71; 59.8% male), no adverse events occurred, and the protocol took under 3 min. The failure rate was 41.8%, indicating no ceiling effect. Five well-fitting items were retained from cognitive screenings and oral motor examinations: location, year, tongue sticking out, lingual motion, and facial symmetry. Both refined protocol (contraindications, five well-fitting items and water challenge) and shortened protocol (contraindications and five well-fitting items) enhanced measurement precision beyond the original version.ConclusionThe Yale Swallow Protocol is a safe, quick, and ceiling-effect-free screening for identifying dysphagia, even among diverse high-risk hospitalised patients. Our study also refined the protocol, achieving better measurement precision than the original protocol.

AIM:Locoregionally advanced oral cavity squamous cell carcinoma (LA-OCSCC) imposes a high disease burden, significantly affecting patients' quality of life. We aimed to identify unmet needs and challenges faced by patients, caregivers, and healthcare professionals (HCPs) in diagnosis and managing LA-OCSCC. METHODS:In-depth interviews were conducted across Australia, Hong Kong, South Korea, Taiwan, and Vietnam with LA-OCSCC patients (n = 28), caregivers (n = 27), and HCPs (surgeons, clinical, radiation, and medical oncologists [n = 30]; nurses, case managers/coordinators, psychologists, speech therapists, dieticians, and dentists [n = 30]). Patients who received post-operative chemoradiotherapy for Stage III-IVB LA-OCSCC, their caregivers, and HCPs were eligible. The interview guide, design, and analysis were based on the Capability, Opportunity, Motivation, Behavior (COM-B) model. RESULTS:Major service gaps in timely diagnosis, treatment, patient-centered care, and therapeutic alliance were identified. Limited awareness of LA-OCSCC led to overlooked symptoms, delaying medical attention. General practitioners were perceived as less experienced in identifying LA-OCSCC symptoms accurately and promptly, with dentists being more informed. A shortage of nurses to support integrated multidisciplinary team discussions, patient education, and to relay patients' needs to specialists, compromised patient-centric care. Psychotherapeutic services were scarce, with supportive care professionals overextending to bridge the gap. CONCLUSION:This study examined LA-OCSCC care management in five Asia-Pacific countries/territories with varying healthcare systems and infrastructure. Given LA-OCSCC's aggressive nature and high burden from disease and treatment, patients and caregivers require support beyond medical interventions. A multi-stakeholder approach with clinical and community care is essential to ensure a comprehensive and sustainable approach to patient-centered care within the different health systems.

Sequential cancer therapy presents a critical challenge, as the impact of prior treatments on immunotherapy remains unclear. Here, we demonstrate that therapeutic stress from prolonged cetuximab exposure induces tumor-intrinsic resistance to immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC). In a multicenter analysis, extended cetuximab treatment correlates with poor ICB response and survival. Mechanistically, chronic therapeutic stress provokes an initial inflammatory response that transitions into immune resistance. A previously unknown post-translational modification, STAT1 lysine 637 acetylation, serves as the molecular switch driving this process. Triggered by treatment-induced tumor necrosis factor alpha (TNF-α), this acetylation impairs STAT1 dimerization and transcriptional activity, while treatment-induced interferon (IFN)-β promotes STAT1 phosphorylation at tyrosine 701 and subsequent degradation. These modifications disrupt tumor IFN-γ responsiveness. Importantly, STAT1 acetylation in pre-treatment tumor samples predicts ICB efficacy, underscoring its potential as a clinically relevant biomarker for guiding immunotherapy decisions.

BACKGROUND:The question as to whether prolonged diagnosis-to-surgery intervals (DSIs) may compromise survival outcomes in patients with oral cavity squamous cell carcinoma (OCSCC) remains unanswered. This nationwide study was designed to address this issue. METHODS:We analyzed data from 26,214 patients with first primary OCSCC identified in the Taiwanese Cancer Registry Database between 2011 and 2021. The optimal DSI cutoff was determined based on 5-year disease-specific survival (DSS) and overall survival (OS) rates using Cox regression analysis. Patients were categorized into three distinct DSI groups: ≤20 days (47 %), 21-31 days (31 %), and > 31 days (22 %). RESULTS:The 5-year DSS and OS rates for the ≤20/21-31/>31 days groups were 81 %/78 %/77 % and 73 %/70 %/68 %, respectively (both p < 0.0001). Patients in the ≤20 days group had a higher prevalence of pathological stages I-II. After adjustment for potential confounders in multivariable analysis, a DSI > 31 days (versus ≤ 20 days) retained independent associations with adverse outcomes at 5 years, with hazard ratios of 1.07 for both DSS and OS. Propensity score matching and multivariable analysis comparing DSI ≤ 20 days to DSI > 31 days stratified by pathological stage III-IV showed that higher DSS and OS rates were observed in patients with DSI ≤ 20 days than DSI > 31 days (68 %/66 %, p = 0.0586; 60 %/57 %, p = 0.0228, respectively), with hazard ratios of 1.09 for both DSS and OS. CONCLUSIONS:Our findings indicate that DSI is an independent predictor of 5-year DSS and OS in patients with OCSCC. A DSI exceeding 31 days, or even 21 days, may potentially decrease survival outcomes.