Can the submandibular gland be preserved during neck dissection in patients with oral squamous cell carcinoma？A systematic review and meta-analysis.

De-escalation strategies in the treatment of oral squamous cell carcinoma: A cross-sectional study in oral and maxillofacial surgery in Germany, Austria, and Switzerland.

Efficacy of PD-1 inhibitor plus induction chemotherapy for nasopharyngeal carcinoma with high-grade extranodal extension: a multicenter retrospective analysis.

Recurrences and Survival in Oropharyngeal Squamous Cell Carcinoma According to p16 Status and Extranodal Extension.

IJV invasion is a rare but significant occurrence in PTC. Although the current staging system categorizes T stages based on organ invasion, the classification for IJV invasion remains unclear. We evaluated the prognostic impact of internal jugular vein (IJV) involvement by extrathyroidal extension (ETE) and extranodal extension (ENE) in papillary thyroid carcinoma (PTC) and investigated the appropriate T-stage classification for ETE to the IJV. This retrospective study included PTC patients who underwent surgery between 2005 and 2011 at our hospital. We analyzed patients with IJV resection due to ETE or ENE, dividing them into ETE and ENE groups. We also compared the ETE group's prognoses with those of patients with stage III or IV PTC to evaluate the T4a vs. T4b classification. Among 5482 PTC cases, 17 were in the ETE group and 47 in the ENE group. We compared the ETE group's prognoses with those of the patients with stage III or IV PTC to evaluate the T4a vs. T4b classification. Compared to the ENE patients, the ETE patients had significantly lower 10-year overall survival (40.6% vs. 81.9%; HR 2.77, 95% CI: 0.99-7.67) and disease-specific survival (44.3% vs. 92.6%; HR 6.81, 95% CI: 1.68-27.51). Survival for ETE to the IJV was significantly worse than for stage III PTC but comparable to stage IV. ETE to the IJV showed a poor prognosis, comparable to stage IV, whereas ENE to the IJV had a favorable prognosis even though we did not exclude the presence of high-risk factors. ETE to the IJV represents an aggressive disease course in PTC, warranting careful consideration in staging and treatment planning.

Malignant salivary gland tumors represent a highly diverse group of neoplasms, their heterogeneity likely arising due to variable origin in different tissue components. Emerging evidence suggests that SOX-2 and EZH-2 play critical roles in salivary gland carcinogenesis, being related to tumor cell stemness potential, along with accelerated tumor progression and unfavorable clinical outcomes. The aim of this study was to assess the association between SOX-2 and EZH-2 expression, survival parameters, and tumors' pathological characteristics in a group of patients with primary epithelial malignant salivary gland tumors (MSGTs) and to evaluate their value as diagnostic and prognostic markers. Our study group comprised 104 patients with primary epithelial MSGTs diagnosed in "Sf. Spiridon" County Hospital, Iasi, over a period of fifteen years. Pathological parameters and survival evaluation, along with SOX-2 and EZH-2 immunohistochemistry assessment and scoring, were conducted, and the associations between different parameters were analyzed. High SOX-2 immunoexpression was significantly associated with lymphatic invasion (LY) (p = 0.003), pT stage (p = 0.010), histological tumor type (p = 0.003), and tumor grading (p = 0.037), while high EZH-2 immunoexpression was significantly associated with perineural invasion (PnI) (p < 0.001), vascular invasion (p = 0.038), LY (p = 0.001), tumor grading (p = 0.002), and pathological extranodal extension (pENE) (p = 0.018). The tumors with high SOX-2 and EZH-2 expressions were associated with a reduced overall survival (OS) (p = 0.013 and p = 0.011). Cox regression analysis revealed that pT (HR = 1.826, p = 0.019), LY (HR = 0.318, p = 0.007), and tumor grade (HR = 0.505, p = 0.021) added to high SOX-2 and EZH-2 immunoexpression independently predicted a poor survival outcome (HR = 2.373, p = 0.016 and HR = 2.746, p = 0.015). Our findings suggest that SOX-2 and EZH-2 may serve as biomarkers of aggressive behavior and a poor prognosis in primary epithelial MSGTs, providing potential opportunities for precision-targeted therapies.

Artificial intelligence (AI) is rapidly reshaping head and neck surgical oncology by augmenting decision-making across the full perioperative continuum. This state-of-the-art review aims to provide head and neck surgical oncologists with a conceptual framework for understanding and critically appraising AI tools entering clinical practice, summarizing how machine learning, deep learning, and generative AI are being integrated into contemporary surgical workflows. Preoperative applications include detection of occult nodal metastasis and extranodal extension. Intraoperative innovations include augmented reality-assisted navigation, real-time margin assessment, and improving visual clarity and tissue handling for robotic platforms. Postoperatively, AI can predict complications like free flap failure and oncologic outcomes. Large language models are being operationalized for clinician-facing applications such as documentation and inbox support, as well as patient-facing education. Despite promising results, broad clinical deployment remains limited by concerns about privacy, validation, reliability, safety, and ethics. Widespread adoption will require prospective clinical trials, robust governance, and human-centered workflows that ensure AI remains a safe, assistive copilot.

The Head and Neck Cancer International Group (HNCIG) recently proposed standardized classifications for imaging-detected extranodal extension (iENE) and pathological ENE (pENE). We evaluated the prognostic value of iENE in pENE-positive head and neck squamous cell carcinoma (HNSCC) treated with postoperative chemoradiotherapy (CRT). Patients with pENE-positive HNSCC who underwent postoperative CRT were retrospectively analyzed. iENE and pENE were re-classified using HNCIG criteria. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Ninety-two patients were included. iENE grades 2-3 were associated with significantly worse outcomes than grades 0-1 (3-year RFS: 68.5% vs. 31.5%, log-rank p = 0.0002; 3-year OS: 85.0% vs. 63.2%, log-rank p = 0.02). In multivariable analysis, iENE was the only independent prognostic factor for RFS and OS. Preoperative iENE is a prognostic factor in pENE-positive HNSCC after postoperative CRT, with grades 2-3 identifying a very high-risk population.

Circulating tumor DNA (ctDNA) is a biomarker of disease status in patients with human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPSCC). To assess clinicopathologic variables associated with circulating tumor human papillomavirus DNA (ctHPVDNA) before and after surgery. The retrospective review and cohort study was conducted at a tertiary academic medical center and included patients with HPV-mediated OPSCC who were treated with upfront surgery between September 2021 and April 2025. Data were analyzed between September 2025 and December 2025. Clinicopathologic variables, including demographic characteristics, pathologic T and N stage, American Joint Committee on Cancer Staging Manual, 8th edition stage, tumor size, margin status, pathologic extranodal extension (pENE), and lymphovascular and perineural invasion. Multivariable negative binomial regression was used to identify clinicopathologic factors associated with preoperative ctHPVDNA, which was measured using tumor tissue-modified viral HPV DNA. Factors associated with detectable postoperative ctHPVDNA were evaluated using logistic regression. A total of 104 patients (mean [SD] age, 59 [10] years; 20 female individuals [19%] and 84 male individuals [81%]; 3 Black individuals [3%] and 101 White individuals [97%]) with HPV-associated OPSCC who were treated with upfront surgery had preoperative ctHPVDNA measurements, and 74 patients had preoperative and postoperative assessments. The mean (SD) preoperative ctHPVDNA level was 2786 (9714) copies/mL. On multivariable negative binomial regression, higher estimated glomerular filtration rate (eGFR; rate ratio [RR], 1.05; 95% CI, 1.01-1.09) and higher pathologic N stage (RR, 12.30; 95% CI, 2.65-57.5) were independently associated with higher preoperative ctHPVDNA levels, whereas perineural invasion (PNI; RR, 0.23; 95% CI, 0.07-0.83) and pathologic extranodal extension (pENE; RR, 0.11; 95% CI, 0.04-0.28) were associated with lower levels. Detectable postoperative ctHPVDNA was observed in 15 of 74 patients (20.2%) and was associated with more than 4 positive lymph nodes (odds ratio [OR], 4.86; 95% CI, 1.39-19.49) higher preoperative ctHPVDNA levels (OR, 1.17; 95% CI, 1.04-1.36), PNI (OR, 2.95; 95% CI, 0.51- 15.51), and pENE (OR, 3.38; 95% CI, 0.84-13.29). Recurrence occurred for 3 of 15 patients (20.0%) with detectable postoperative ctHPVDNA compared with 8 of 59 patients (13.6%) with undetectable ctHPVDNA. Among patients with undetectable postoperative ctHPVDNA, 4 locoregional recurrences occurred in individuals who declined guideline-concordant adjuvant therapy. The results of this cohort study illuminate the biological and clinical factors associated with ctHPVDNA shedding and clearance, potentially offering guidance for integrating ctHPVDNA into biomarker-driven clinical trials.

Low-dose fractionated radiotherapy combined with induction chemotherapy in high-risk nasopharyngeal carcinoma: An open-label, randomized phase 2 trial.

Introduction: Oral Squamous Cell Carcinoma (OSCC) is the most common malignancy of the head and neck region, with a global mortality of approximately 177,000 deaths reported in 2018. Despite advances in diagnostic techniques and therapeutic modalities, the five-year survival rate remains around 50%. Cervical Lymph Node (LN) metastasis is a critical prognostic factor, even in early-stage OSCC. Although OSCC generally follows a predictable pattern of LN spread, a phenomenon known as skip metastasis—wherein tumour cells bypass adjacent lymph nodes and involve non sequential nodes—has been observed, particularly in carcinomas of the tongue. This atypical metastatic behaviour complicates treatment strategies and underscores the need for further investigation. The 8th edition of the Tumour Node Metastasis (TNM) staging system emphasises parameters such as extranodal extension and Depth of Invasion (DOI), which may correlate with metastatic patterns. Need of the study: This study aims to investigate the association between DOI and skip metastasis in OSCC to enhance the understanding of lymphatic spread patterns. By clarifying this relationship, the study seeks to support more accurate risk stratification, refine surgical management—particularly neck dissection strategies—and ultimately contribute to improved prognostication and personalised treatment planning for patients with OSCC. Materials and Methods: This is a cross-sectional study over a period of 12 months, from July 2025 to June 2026 will be conducted in the Department of Oral Pathology and Microbiology, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research (DMIHER), a tertiary care hospital in Sawangi Meghe, Wardha, Maharashtra, India. A total of 80 Haematoxylin and Eosin (H&amp;E)-stained OSCC slides will be analysed for lymph node involvement, both qualitatively and quantitatively, under low and high magnification (400×). The depth of invasion will be measured from the deepest point of tumour infiltration into the connective tissue using a Leica DMLB2 research microscope. Blinded evaluations will be performed independently by two histopathologists, including the primary investigator and a co-researcher.

Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma with a marked propensity for early regional lymph node metastasis. Although MCC most often arises on sun-exposed head and neck skin in older adults, tumors of the lower extremity are uncommon and may be mistaken for benign hemorrhagic lesions. A 54-year-old woman developed a rapidly enlarging, hemorrhagic mass in the left suprapatellar thigh. Magnetic resonance imaging demonstrated an extracompartmental subcutaneous soft-tissue mass without quadriceps muscle invasion. Wide local excision including the quadriceps fascia was performed. Histopathologic examination showed a dermal/subcutaneous small blue round cell neoplasm with brisk mitotic activity. Immunohistochemistry demonstrated diffuse cytoplasmic synaptophysin positivity, paranuclear dot-like CK20 reactivity, chromogranin A positivity, and negative MCPyV staining; TTF-1, S100, melan-A, HMB-45, and hematolymphoid markers were negative. Staging positron emission tomography/computed tomography identified ipsilateral inguinal nodal involvement. Therapeutic inguinal lymph node dissection revealed metastatic MCC in one of four lymph nodes without extranodal extension. The final stage was pT3 pN1b cM0 (AJCC 8th edition), corresponding to stage IIIB disease. Adjuvant radiotherapy (57 Gy in 20 fractions) was delivered to the primary bed and ipsilateral inguinal basin. The patient remains disease-free at 5-year follow-up. Lower-extremity MCC can mimic hemorrhagic or post-traumatic lesions, contributing to diagnostic delay. Persistent or rapidly enlarging "hematoma-like" lesions warrant early biopsy, and timely pathologic nodal staging is essential. Multimodal management can achieve durable control even in node-positive disease.

Evaluation of submandibular gland involvement in oral squamous cell carcinoma patients.

Detection of extranodal extension (ENE) can guide treatment planning for patients with oropharyngeal squamous cell carcinoma (OPSCC). This systematic review identifies molecular biomarkers predictive of ENE in both Human Papillomavirus (HPV)-positive and HPV-negative OPSCC. A systematic review was conducted for relevant articles published between 1996 and July 2025. Studies were included if they included exclusively patients with OPSCC and evaluated the presence of ENE based on molecular biomarkers. Ten studies met inclusion criteria. Tumor tissue modified viral (TTMV)-HPV DNA was not associated with ENE. Biomarkers associated with ENE included NOTCH-1 and WNT mutations and expression of podoplanin, Her3, and myoferlin. These biomarkers have also been linked with epithelial-mesenchymal transition (EMT) in cancer cells. Multiple genomic and molecular biomarkers have been identified in association with ENE in OPSCC, suggesting that ENE is characterized by an EMT phenotype.

The WHO classification includes squamous cell carcinoma (SCC) and neuroendocrine carcinoma as two histotypes of HPV-associated oropharyngeal carcinoma (HPV + OPC). Among SCC, the recognized subtypes include non-keratinizing, keratinizing, papillary, adenosquamous, ciliated adenosquamous, lymphoepithelial, spindle cell, and basaloid subtypes. This retrospective study included 379 consecutive cases of HPV+ OPC resected between 2017 and 2024. The morphologies included SCC (83.4%), adenosquamous carcinoma (n=11, 2.9%, including 6 with cilia), combined neuroendocrine carcinoma and SCC (n=3, 0.8%), adenocarcinoma (n=1, 0.3%), and undifferentiated carcinoma (n=1, 0.3%). Among SCC subtypes, the most common was non-keratinizing (n=316), followed by papillary (n=22), lymphoepithelial (n=9), basaloid (matrix-producing, n=9), keratinizing (n=6), and spindle cell (sarcomatoid, n=1). Tumors could display various histologic features, such as papillary architecture (29.2%), lymphoepithelial regions (10.3%), and basaloid (matrix-producing) areas (7.1%). On univariate survival analysis, adverse histologic features included any percentage of glandular differentiation, a basaloid component, extranodal extension (ENE), and low stromal tumor infiltrating lymphocytes (sTIL). Basaloid areas and extranodal extension were independent adverse prognostic factors identified on multivariate survival analysis. Herein, we report two histotypes of HPV+ OPC not yet recognized by the WHO classification, being adenocarcinoma and undifferentiated carcinoma. Additionally, multiple adverse histologic features were identified, including basaloid components and ENE as independent prognostic factors. Therefore, recognizing and reporting such features in the pathology report of HPV+ OPC, even when present in minor proportions, is important for risk stratification and clinical management. Not applicable.

Mastectomy rates are increasing in young patients despite few data supporting improved outcomes. We investigated the association between surgical approach and survival in young patients with breast cancer. Retrospective review identified women ≤40 years old with operable, non-metastatic invasive breast cancer treated between 2010-2019. Cox proportional hazard analyses, stratified by hormone receptor and human epidermal growth factor receptor 2 (HER2) status, identified factors associated with increased risk of recurrence and death. Of 588 patients, 65% underwent mastectomy and 35% breast conserving surgery (BCS). Median follow-up was 5.9 years. Overall recurrence and mortality rates were 15% and 12%, respectively. On multivariable analysis, black race [hazard ratio (HR), 2.14 (1.26-3.61), p = 0.005], lymphovascular space invasion (LVSI) [HR, 1.98 (1.17-3.36), p = 0.01], and extranodal extension [HR, 2.12 (1.09-4.12), p = 0.03] were associated with increased risk of death. Stage III disease [HR, 2.06 (1.05-4.03), p = 0.04] and LVSI [HR, 2.18 (1.43-3.32), p<0.001] were associated with increased risk of recurrence. Increasing age decreased the risk of death [HR, 0.94 (0.88-0.99), p = 0.02] and recurrence [HR, 0.95 (0.90-0.99), p = 0.02]. Mastectomy versus BCS did not impact recurrence [HR, 1.18 (0.73-1.92), p = 0.51] or overall survival (OS) [HR, 0.86 (0.46-1.58), p = 0.62] in the entire cohort. BCS was associated with increased risk of recurrence in the hormone receptor-/HER2+ subtype [HR, 9.06 (1.03-80.00), p = 0.047] but did not affect survival. OS does not differ by surgery type in young patients with breast cancer. Future research should focus on racial disparities in breast cancer care.

Abstract Context The optimal radioactive iodine (RAI) activity for intermediate-risk papillary thyroid cancer (PTC) remains uncertain, and evidence to guide individualized treatment is limited. Objective To compare recurrence between moderate- and high-activity RAI and to identify clinicopathologic factors associated with persistent or recurrent disease. Design Retrospective cohort study. Setting Tertiary academic thyroid cancer clinic Patients Adults with intermediate-risk PTC treated between 2010 and 2022. Intervention Moderate- (30 to 90 mCi) vs high-activity RAI (&amp;gt;90 mCi) as initial postoperative therapy. Main Outcome Measure(s) Primary outcome: time to recurrence. Secondary outcome: composite of persistent or recurrent disease at last follow-up. Results Among 181 patients, 94 received moderate-activity RAI and 87 received high-activity RAI. Over a median follow-up of 52 months, 18 recurrences occurred (crude: 3/94 vs 15/87). High-activity RAI was not associated with improved recurrence-free survival (inverse probability of treatment weighting [IPTW]-weighted hazard ratio 2.73; 95% confidence interval [CI] 0.74 to 10.01). Persistent or recurrent disease occurred in 61 patients (34%) with no association in IPTW models (hazard ratio 0.97; 95% CI 0.53 to 1.76). Extranodal extension, microscopic extrathyroidal extension, larger lymph node deposit size, and older age were associated with persistent or recurrent disease. Conclusions High-activity RAI was not associated with improved recurrence versus moderate-activity in intermediate-risk PTC. This study is among the first to evaluate moderate-activity RAI as a distinct comparator. Findings support moderate-activity RAI as a reasonable risk-adapted approach. Prospective studies are needed to validate these results.

The right innominate interarteriovenous lymph nodes (RIAVLN) represent a distinct nodal group situated between the right innominate artery and vein. This area lies outside the conventional level VI-VII boundaries in thyroid carcinoma surgery and is seldom addressed in standard guidelines. Metastasis in this region is difficult to detect and surgically challenging due to its proximity to major vascular structures. This study aimed to analyze the clinical characteristics and surgical management of RIAVLN metastasis in patients with thyroid carcinoma. We retrospectively reviewed 103 patients with thyroid carcinoma who underwent RIAVLN dissection between July 2017 and January 2024. All patients had preoperative contrast-enhanced CT scans suggesting nodal metastasis in this region. Demographic data, tumor subtype, surgical approach, and pathological findings were analyzed. The surgical technique emphasized cervical exposure of the carotid sheath, mobilization of the common carotid artery, and careful dissection of the interarteriovenous space, with partial sternotomy reserved for cases with severe adhesion or bleeding risk. The mean patient age was 39.9 ± 12.3 years (range, 18-68), with 42 males and 61 females. The cohort included 24 primary papillary, 63 recurrent papillary, 2 primary medullary, and 13 recurrent medullary thyroid carcinoma cases. Overall, 93 patients (90.3%) were successfully treated via a transcervical approach, while 10 (9.7%) required partial sternotomy. The mean number of RIAVLN dissected was 3.1 ± 2.9, and metastasis was confirmed in 77 patients (74.8%). The mean number of metastatic nodes among positive cases was 1.5 ± 2.4, with extranodal extension observed in 12 patients (11.7%). No major vascular injury or operative mortality occurred. RIAVLN metastasis is relatively common in recurrent thyroid carcinoma and represents an anatomically unique nodal group not covered by traditional classifications. In most cases, complete clearance can be safely achieved through a transcervical approach. Partial sternotomy should be reserved for patients with dense adhesions or high bleeding risk. Recognition of this region as a potential site of recurrence and mastery of its surgical anatomy are crucial for achieving optimal oncologic outcomes in thyroid cancer surgery.

&lt;b&gt;Introduction:&lt;/b&gt; The ninth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor-node-metastasis (TNM) system for patients with non-metastatic nasopharyngeal carcinoma (NPC) was based on data from endemic regions, and it required validation for application to non-endemic regions. &lt;br&gt;&lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of this study was to compare the performance of the 8&lt;sup&gt;th&lt;/sup&gt; and the 9&lt;sup&gt;th&lt;/sup&gt; editions of the AJCC/UICC TNM system for patients with non-metastatic NPC from non-endemic regions. &lt;br&gt;&lt;br&gt;&lt;b&gt;Materials and methods:&lt;/b&gt; Using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2021, we re-classified NPC patients using 8&lt;sup&gt;th&lt;/sup&gt; and the 9&lt;sup&gt;th&lt;/sup&gt; edition staging based on surrogate markers of advanced radiological extranodal extension (nodes described as "fixed") and compared the prediction performance of both staging editions for overall survival (OS) and cancer specific survival (CSS). &lt;br&gt;&lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Our analysis included 4981 patients with a median follow-up of 99.0 months. Comparing the 9&lt;sup&gt;th&lt;/sup&gt; version of AJCC/UICC (TNM-9) with TNM-8, only 29 (1.8%) patients with N1 and 47 (3.3%) patients with N2 were upstaged to N3 in TNM-9. In comparisons based on OS, TNM-9 did not outperform TNM-8 with regard to hazard consistency (2.2326 &lt;i&gt;vs&lt;/i&gt; 1.9160), hazard discrimination (1.4092 &lt;i&gt;vs&lt;/i&gt; 1.0947), sample size balance (0.3476 &lt;i&gt;vs&lt;/i&gt; 0.3398), and percent variance explained (0.2704 &lt;i&gt;vs&lt;/i&gt; 0.2704). The area under the receiver operating characteristic curve (AUC) values of TNM-9 and TNM-8 were 0.5299 and 0.5330 for OS (P = 0.549), respectively. The AUC values of TNM-9 and TNM-8 were 0.5332 and 0.5357 for CSS (P = 0.345), respectively. &lt;br&gt;&lt;br&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Restaging according to TNM-9 criteria involved only minor changes in the distribution of nodal (N) categories. Neither the TNM-9 nor the TNM-8 staging system demonstrated adequate overall discrimination between each stage group classification in terms of OS and CSS for patients with non-metastatic NPC from a non-endemic region.

Redefining high-risk extranodal extension in head and neck cancer: beyond the minor-major dichotomy.