Elective neck irradiation does not improve regional control or survival in pT3-T4N0 oral cavity SCC after high-yield neck dissection: A retrospective multicenter analysis.

Achieving adequate resection margins (i.e., ≥5 mm of healthy tissue surrounding the tumor) in oral cavity squamous cell carcinoma (OCSCC) is difficult. This review discusses recent developments to guide surgical resection. It highlights the transition from the subjective conventional approaches to emerging, objective photonics-based methods. Specimen-driven intraoperative assessment of resection margins (IOARM) has significantly improved surgical outcomes. However, IOARM is subjective; moreover, it lacks widespread adoption due to reliance on a dedicated team of specialists. Raman spectroscopy is an objective, fast, nondestructive, and label-free technique that is suitable for IOARM. The latest Raman-based prototype demonstrates high precision. Integrating Raman-guided IOARM into the surgical-pathological workflow offers a practical, scalable approach to real-time, objective margin assessment, thereby improving patient outcomes.

Tobacco use, alcohol consumption, and infection with human papilloma virus (HPV) are well-established risk factors for head and neck squamous cell carcinomas (HNSCC). However, the incidence of oral cancer, particularly in the mobile tongue, has been rising in non-smoker/non-drinker and HPV-negative patients, suggesting the emergence of a new clinical entity. To understand in molecular terms this subtype of oral cavity squamous cell carcinomas (OCSCC) with no-identified risk factor (NIRF), we analyzed the available public head and neck cancer multi-omics data. We identified mutational signatures that stratified 253 OCSCC and 94 laryngeal cancer cases, used as tobacco-only-related controls, according to their clinico-pathological characteristics. We show that tobacco, depending on the anatomical site, triggers distinct mutational processes and further demonstrate that the single-base-substitution (SBS) signature SBS16 in OCSCC is associated with tobacco smoking, reflecting the combined effects of smoking and drinking. Importantly, we identified a tongue cancer-enriched NIRF OCSCC subgroup exhibiting significantly increased endogenous clock-like mutagenesis, while another NIRF subgroup manifested with elevated apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC)-associated mutagenesis. Both NIRF OCSCC subgroups harbored specific cancer driver mutations and distinct methylation patterns, which differed from those observed in OCSCC linked to traditional HNSCC risk factors, reflecting unique molecular programs underlying disease development. Specifically, NIRF-OSCC exhibited pronounced immune evasion strategies and antimicrobial transcriptomic responses. Our study presents the first molecular and genomic characterization of the emerging NIRF OCSCC subtype likely driven by increased endogenous mutagenesis and responses to microbial insults. These findings warrant future detailed investigations into etiology and have implications for clinical management and cancer prevention.

Metastasis significantly decreases survival in oral cavity squamous cell carcinoma (OSCC). Even patients initially staged as cN0 may develop cervical or distant metastases during follow-up. Risk factors contributing to metastasis in this group are not fully understood. A retrospective cohort study was conducted on patients with primary cN0 OSCC treated between 2016 and 2020. Of the 195 N0 OSCC patients included, 19 (9.7%) developed metastasis. Heavy alcohol use (HR 4.05, 95% CI:1.38-11.92, p=0.011) and depth of invasion (DOI) (HR 1.10, 95% CI:1.01-1.20, p=0.021) were significantly associated with the development of metastasis. Age, gender, site, neck procedure, radiotherapy, and T-class were not statistically significant predictors in this analysis. Metastases occurred in nearly 10% of c/pN0 patients. Alcohol use and DOI were independent predictors, highlighting the need for individualized follow-up strategies and further research into alcohol-related OSCC.

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. 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. 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. 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. 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.

Currently, the first-line treatment for the most common form of head and neck squamous cell carcinoma (HNSCC), oral cavity squamous cell carcinoma (OSCC), is surgical resection, followed by risk-adapted treatments, such as chemoradiotherapy.However, with the current standard of care and even the emergence of new treatments, such as checkpoint blockade, the overall survival for advanced, recurrent disease remains high, and the prevalence of head and neck cancer is projected to continue to increase in the coming years. Thus, deeper investigation into current standard-of-care modalities, in addition to novel therapeutics, is necessary to translate potential and promising treatment options to patients with HNSCC. Preclinical models are utilized to evaluate the safety and efficacy of potential treatment interventions. Unfortunately, current preclinicalmodels fail to fully embody the surgical procedure many patients receive, as they primarily involve non-surgical treatment modalities, like radiation, chemotherapy, or immunotherapy. Furthermore, existing surgical models are limited by additional reagents needed to support the establishment of tumors in orthotopic sites and the requirement of microsurgery for tumor removal. This warrants the generation of improved and simplified preclinical models to investigate therapeutics and gain insight into locoregional tumor recurrence and treatment resistance. This article describes a novel syngeneic clinically relevant orthotopic murine subtotal resection model that recapitulates the standard of care in OSCC. This model simplifies existing models and results in measurable recurrence following surgical resection of buccal mucosal tumors. Use of this model may lead to valuable insights into tumor recurrence and treatment resistance in patients with OSCC. The establishment of this preclinical model paves the way for further work to investigate how OSCC responds to post-resection adjuvant therapies, capturing the tumor state at the clinically relevant window at which patients generally begin such subsequent treatments.

Changing patterns in tongue, oral cavity, laryngeal and hypopharyngeal squamous cell carcinomas in New Zealand: Incidence, trends and survival from 2006 to 2022.

Treatment of early-stage oral cavity squamous cell carcinoma at low-volume facilities impacts surgical margins and survival: an analysis of 22,258 patients from the NCDB.

Background/Objectives: Identifying the causes of sentinel lymph node biopsy (SLNB) failure in early-stage oral cavity squamous cell carcinoma (OCSCC) is essential for refining surgical protocols and optimizing patient selection. This study aimed to evaluate the diagnostic performance, predictors of false-negative (FN) results, and long-term oncological outcomes of SLNB in patients with early-stage OCSCC. Methods: A retrospective, single-centre cohort study was conducted on 220 patients with cT1-cT2 N0 M0 OCSCC who were surgically treated between 2017 and 2024. Preoperative lymphatic mapping was performed using 99mTc-nanocolloid and SPECT/CT. All sentinel lymph nodes (SLNs) underwent an ultrastaging protocol involving serial sectioning and immunohistochemistry. Diagnostic accuracy, survival outcomes, and clinicopathological predictors of FNs were analysed. Results: The SLN identification rate was 99.1%. Metastatic involvement was detected in 49 patients (22.3%), preventing 77.7% of the cohort from undergoing unnecessary neck dissection. Bilateral lymphatic drainage was observed in 55.9% of floor of the mouth tumours. During a median follow-up of 36 months, the diagnostic performance showed a sensitivity of 81.7%, a negative predictive value of 93.6%, and an overall accuracy of 95.0%. Analysis of the 11 FN cases showed that both depth of invasion (DOI) (6.0 mm vs. 3.0 mm; p = 0.010) and maximal tumour dimension (25 mm vs. 15 mm; p = 0.0008) were significant predictors of diagnostic failure. The five-year overall survival rate was significantly superior in patients with negative SLNs compared to the SLN-positive group (82% vs. 61%; p < 0.001). Conclusions: SLNB is an accurate and reliable staging tool for early-stage OCSCC, providing personalised lymphatic mapping that harmonizes oncological efficacy with the avoidance of overtreatment. However, an increased DOI and a larger tumour size significantly raise the risk of FN events, indicating the need for close postoperative surveillance in these high-risk subgroups.

Squamous cell carcinoma (SCC) of the oral cavity mostly presents with advanced disease. Though standard of care is surgery followed by radiation, there is a long wait time in many Indian centres during which some patients progress. We devised a simple, relatively non-toxic oral metronomic chemotherapy (OMCT) regimen aimed at preventing disease progression during the waiting period. Patients with stage III and IV oral cavity SCC were prospectively included in the trial as per inclusion criteria. They received at least 1 cycle of OMCT unless progression of disease before completion. A maximum of 2 cycles were given, and patients with either stable disease or partial response were operated any time after completion of 1 cycle of OMCT. Progressive disease was managed either with surgery, concurrent chemoradiation or IV NACT f/b surgery or concurrent chemoradiation. Details of sociodemographic, diagnosis, treatment and follow up were collected. 81 patients received at least 1 cycle and were evaluable. The most common oral cavity subsite involved was the buccal mucosa (46%) with stage III (49%) and IVA (51%) equally distributed. 13 (16%) patients had developed grade I toxicities to OMCT. Among 81, 10 (12%) had partial response, and 57 (71%) had stable disease. 14 patients (17%) had disease progression. Oral metronomic chemotherapy in the form of Methotrexate, Capecitabine and Cyclophosphamide is an effective, safe and feasible option to bridge the waiting list period for surgery in locally advanced operable oral cavity squamous cell carcinoma. The online version contains supplementary material available at 10.1007/s13193-026-02596-6.

Retroauricular robotic neck dissection is a remote-access approach designed for cervical nodal clearance while concealing the incision. We describe our operative technique and early feasibility in carefully selected patients with early oral cavity squamous cell carcinoma (OCSCC). The surgical workflow-including incision design, flap elevation, robotic docking, level-wise dissection, and reconstructive considerations-is detailed with emphasis on technical pearls and pitfalls. A concise descriptive dataset is presented. Retroauricular robotic neck dissection is technically feasible in selected patients when meticulous technique and appropriate case selection are applied. Outcomes should be interpreted as feasibility signals rather than comparative evidence.

Prospective evaluation of locoregional control in oral cavity squamous cell carcinoma with lower or mid infratemporal fossa involvement treated with surgery and adjuvant concurrent chemoradiotherapy

CT-defined posterior extension predicts pathological nodal metastasis in lower oral cavity squamous cell carcinoma.

Programmed cell death ligand-1 (PD-L1) is involved in T-cell regulation by acting as an immune checkpoint inhibitor, and its expression is being widely studied in various malignancies. The following study was designed to examine the role of PD-L1 and its association with HPV in oral squamous cell carcinomas in the Indian population. Immunohistochemistry for PD-L1 and p16 was done on the resection specimens. Combined positive score (CPS) was evaluated for PD-L1; a CPS ≥ 1and < 20 was considered low-positive, and a CPS ≥ 20 was considered strong positive. Diffuse and strong nuclear and cytoplasmic expression of p16 in ≥ 70% tumor cells was considered positive (block) expression. A total of 188 cases were included in the study. PD-L1 expression was seen in a total of 86.1% (162 cases); of these, 67.02% (126 cases) showed strong expression of PD-L1 with a CPS ≥ 20. A significant correlation was observed between PD-L1 expression and tumor stage, with higher PD-L1 expression in advanced stages T2-4 compared to T1 (p-value = 0.014). No significant correlation of PD-L1 with p16 positivity, lymph node metastases, or tumor grade was observed. High PD-L1 expression was observed in more than 80% of cases, regardless of HPV status, suggesting that targeted immunotherapy with PD-L1 inhibitors can be an effective treatment in the Indian subpopulation, especially in those with advanced-stage tumors.

SummaryBackgroundNon-surgical management of oral cavity squamous cell carcinoma (OSCC) has poorer outcomes compared to surgery. In borderline resectable tumors, historical neoadjuvant chemotherapy achieves surgical conversion in only about 40%. Combining low-dose immunotherapy and oral metronomic therapy (OMT) with chemotherapy may enhance resection rate and survival.MethodsBetween April 2023 and April 2024, patients deemed ‘borderline resectable’ OSCC based on predefined criteria by a multidisciplinary tumor board were prospectively offered this Phase II single-arm interventional trial setting. Patients received two 21-day cycles of carboplatin, nab-paclitaxel, low-dose nivolumab, and six weeks of erlotinib, methotrexate, celecoxib, with additional cycle(s) if needed. Primary endpoint was R0 resection rate. Secondary endpoints were objective response rate, pathologic response, safety, event-free survival (EFS), and overall survival (OS). Immune biomarkers and Volumetric assessment were exploratory endpoints. The trial was prospectively registered in the Clinical Trial Registry of India (CTRI/2023/04/051617).FindingsOf 34 patients, all except one completed planned neoadjuvant therapy. After 2 cycles, 22 (66·6%) had partial response and 11 had stable disease; none progressed. Twenty six underwent surgery; 25 achieved R0 resection (25/33–75·7% conversion). Four of seven remaining patients received additional cycle(s); three subsequently achieved R0 resection. Overall conversion rate was 90·3% (28/31) excluding 2 patients who refused further treatment. Major pathological response occurred in 12 patients (41·4%), including four with pathological complete response. Grade ≥3 toxicities occurred in 5 of 34 patients (14·7%), with no treatment-related deaths. One patient had grade 4 diarrhea with grade 4 acute kidney injury.InterpretationThe NeoLOCUS regimen offers an affordable, outpatient chemo-immunotherapy approach that improves surgical conversion and pathological response in borderline resectable OSCC.FundingFluid Research Grant- 10.13039/501100005918Christian Medical College, Vellore, India.

The radial forearm free flap (RFFF) has been a mainstay in head and neck reconstruction due to its reliability and pliability, but it carries notable donor-site morbidity. The super-thin anterolateral thigh free flap (ST-ALTFF) has recently emerged as a versatile alternative. A retrospective chart review was performed including patients who underwent free flap reconstruction with either ST-ALTFF or RFFF following oral cavity squamous cell carcinoma resection. Demographic and peri-operative variables were collected, and statistical analysis was performed using the t-test, Mann-Whitney U test, and Fisher exact probability test. Twenty-one patients underwent ST-ALTFF and twenty-two underwent RFFF reconstruction. Patients receiving RFFF were more likely to be female (n = 16, p < 0.001) and have higher mean BMI (p = 0.048). Operative time was shorter with ST-ALTFF versus RFFF (509 vs. 594 min, p < 0.011). Other patient variables, complications, gastrostomy tube placement, and post-operative pain were similar. ST-ALTFF represents a viable reconstructive option with promising peri-operative outcomes compared to RFFF.

Frozen section (FS) is commonly used for intraoperative margin assessment in oral cavity squamous cell carcinoma (OCSCC). Its value in recurrent or previously treated cases, however, remains uncertain. We retrospectively analyzed prospectively collected data from 510 patients with histologically confirmed OCSCC treated between April 2018 and August 2022. Patients were divided into Group A (recurrent/second primaries/previously treated, n = 247) and Group B (treatment-naïve, n = 263). A 1-cm gross margin was targeted for all resections. FS and permanent sections were reviewed by three institutional pathologists. Margins were defined as positive (tumor/ moderate to severe dysplasia at the cut edge or < 1 mm), close (1-5 mm), and free (> 5 mm). Primary outcomes included initial FS margin status, number of additional resections (recuts), and final histopathology margin status. On initial FS, a significantly higher proportion of patients in Group A had close or positive margins (34.41%, 85/247) compared to Group B (1.52%, 4/263), with the difference being highly statistically significant (p < 0.0001). After intraoperative revision, 72 of the 85 patients (84.70%) in Group A achieved negative margins on a second margin revision, and an additional 9 patients (10.58%) required a third margin revision to achieve negative margins. Overall, only 4 of the 510 patients (0.78%) in the entire cohort had close or positive margins on final histopathology, and all four were from Group A. On final HPE, 3 patients had close margins and 1 had a persistent positive margin. Gross examination with an adequate margin may be sufficient for treatment-naïve OCSCC. However, for previously treated cases, FS significantly aids in achieving intraoperative margin clearance and reduces final positive margins. The study's primary aim was not to assess oncologic outcomes, but rather to emphasize the necessity of FS in complex cases who had undergone multiple prior treatments where gross inspection is unreliable.

Abdominal Wall Tumor Seeding of Oral Cavity Squamous Cell Carcinoma.

Outcomes of patients with oral cavity squamous cell carcinomas with perineural invasion treated with adjuvant intensity modulated radiation therapy (IMRT)

Prognostic implication of the expression of minichromosome maintenance protein 5 (MCM 5) in oral cavity squamous cell carcinomas-a study on cases from a tertiary care centre