BACKGROUND:The incidence of oral squamous cell carcinoma (OSCC) is rising in patients under the age of 50, without smoking or alcohol abuse. Viruses are not a causative factor of OSCC in younger patients. The oral microbiome has not been evaluated in this unique patient cohort for a potential bacterial etiology. METHODS:We report the bacterial diversity and composition of the largest cohort of OSCC patients with whole genome sequencing (n = 72) and compare it with oral mucosa from healthy controls (n = 10) using the Strengthening the Organization and Reporting of Microbiome Studies guidelines. RESULTS:The microbial diversity between tumor, normal mucosa from cancer patients and healthy control mucosa is significantly different, with specific species (Streptococcus mitis, Haemophilus haemolyticus, and Cutibacterium acnes) reduced in normal mucosa of cancer patients as compared with healthy controls (adjusted P < .05). The microbial diversity is significantly higher in younger patients as compared with older patients (P < .001), with a reduced abundance of anaerobes in older patients (Aggregatibacter segnis, Gemella morbillorum, Peptostreptococcus stomatis, Filifactor alocis, and Porphyromonas endodontalis; adjusted P < .05). CONCLUSION(S):The OSCC tissue of younger patients is significantly more polymicrobial, and their OSCC microbiomes harbor more anaerobic bacteria as compared with older patients. This compositional difference builds the hypothesis that the oral microbiome of younger OSCC patients may have a more hypoxic, immunosuppressive tumor microenvironment with its associated implications for treatment resistance and a potential link to baseline poor dentition.

PURPOSE:Efficient resource allocation in surgery requires thorough economic evaluation that reflects the true costs of a procedure, with micro-costing being a primary method. Existing economic studies on microvascular jaw reconstruction of the jaw often exclude or estimate key cost-drivers. The aim of this study was to estimate the direct financial costs and cost-drivers associated with surgical reconstruction of the jaw from the perspective of the healthcare provider. METHODS:A retrospective micro-costing study from the perspective of the healthcare provider was performed on 100 patients who underwent mandibular or maxillary free flap reconstruction. Direct financial costs of activities (in USD) from admission to discharge were examined, and classified into operative and perioperative admission periods. RESULTS:The mean cost for the entire admission was $36,415.95 ± 14,246.56 comprising 57.7% from the operative period and 42.3% from the perioperative admission period. Ward staffing and consumables (35.7%), prostheses (25.0%), and operating room staffing (21.0%) were the largest cost contributors. In adjusted analyses, higher costs were associated with vasculopathy (+$9142.02, p = 0.044), ASA IV ($19,495.93, p = 0.023), tracheostomy (+$10,445.81, p = 0.012), return to the operating room (+$19,920.22, p = 0.005), and return to the intensive care unit (+$25,316.26, p = 0.014). CONCLUSION:Jaw reconstruction is associated with considerable direct financial costs to the healthcare provider with complications requiring return to the operating room and/or return to the intensive care unit the critical key cost-drivers. These insights will support future health technology assessments focused on jaw reconstruction to assist decision-makers in implementing or reimbursing these procedures.

OBJECTIVE:We aimed to describe the prevalence of preoperative micronutrient abnormalities, protein-energy malnutrition (PEM), and their association with postoperative complications in patients undergoing head and neck free flap reconstruction (HNFFR). METHODS:A single institution, retrospective cohort study of adults requiring HNFFR was performed. Patient data and pre-operative serological parameters were extracted from the electronic medical record. Nutritional status was assessed by the Patient Generated-Subjective Global Assessment (PG-SGA) tool. RESULTS:About 261 patients met inclusion criteria with the predominant undergoing surgery involving the oral cavity (n = 203; 77.8%). The combined prevalence of moderate and severe malnutrition was 27.2%. Hypovitaminosis C was present in 64 patients (36.8%) and was associated with an increased likelihood of a complication on both univariate (OR 1.9 [1.01-3.51; 95% CI]) and multivariate (OR 2.2 [1.12-4.29; 95% CI]) analysis. On further subgroup univariate analysis, increased age, hypertension, macrocytosis, PG-SGA score and moderate malnutrition were associated with postoperative medical complications. An increased length of stay was also associated with complications on univariate and multivariate analysis. CONCLUSION:Hypovitaminosis C was associated with an increased risk of postoperative complications. Early screening and intervention for micronutrient depletion and PEM prior to surgery may reduce these risks for patients undergoing HNFFR. LEVEL OF EVIDENCE: 3:

BACKGROUND:Free tissue transfer is standard of care in the reconstruction of large defects in the head and neck. Many patients who undergo free flap reconstruction have had prior head and neck radiotherapy (HNRT). The aim of this study is to compare the surgical outcomes of HNRT versus HNRT naïve patients undergoing free flap reconstruction in a large Australian cohort. METHODS:Data from patients who underwent free flap reconstruction of head and neck defects between January 2017 and December 2020 were extracted from a prospectively collated database at Chris O'Brien Lifehouse (Sydney, Australia). Participants were divided into two groups based on whether or not they had HNRT prior to their free flap procedures. Subgroup analysis was performed comparing patients with mucosal vs. those with cutaneous disease reconstruction. RESULTS:From a total of 525 patients who had undergone free flap reconstruction, 117 (22.3%) had prior HNRT. Prior HNRT was associated with higher rates of flap complications (14.5% vs. 7.8%, p = 0.045), recipient site complications (31.6% vs. 21.1%, p = 0.025), and higher Clavien Dindo Classification (p = 0.040). In the mucosal disease subgroup, prior HNRT was associated with higher rates of flap complications (17.2% vs. 7.8%, p < 0.001). In the cutaneous disease subgroup, there was no difference in complication rates between HNRT naïve and those who had prior HNRT. CONCLUSION:Prior HNRT increases the risk of both flap and recipient-site complications. However, this mainly occurs in patients undergoing reconstruction of mucosal disease.

BACKGROUND:The incidence of head and neck cancer (HNC) is rising globally, with patients undergoing extensive surgical resection for advanced disease frequently requiring prophylactic tracheostomy to secure the airway in the early postoperative period. Specialised HNC nurses undertake extended scope tracheostomy procedures, including tube changes and decannulations, yet practice varies widely between institutions and no standardised training framework exists. AIMS AND OBJECTIVES:To benchmark the roles and responsibilities of specialised HNC nurses in tracheostomy management across Australia, and to explore the facilitators, barriers and enablers of nurse-led extended practice. DESIGN:National mixed-methods study. METHODS:An online REDCap questionnaire was distributed to nurses with inpatient HNC tracheostomy experience within the past 5 years (n = 22). A subset participated in semi-structured interviews (n = 11), analysed using inductive thematic analysis. RESULTS:Most participants were senior metropolitan-based nurses with over 12 years of HNC experience. Nine (41%) performed tracheostomy tube changes and 14 (64%) conducted decannulations. Thematic analysis identified six themes: the central role of the multidisciplinary team; education and patient support; training and skill acquisition; extended scope of practice; challenges to nurse-led management; and benefits of nurse-led management. Skill acquisition was facilitated by mentoring and high-volume exposure; barriers included collegial resistance, equipment access and workload pressures. CONCLUSIONS:Specialised HNC nurses report undertaking extended scope tracheostomy procedures across a range of Australian centres, with mentoring, high-volume clinical exposure and multidisciplinary collaboration described as key enablers. Standardised competency frameworks may help to reduce inter-institutional variation; however, the safety, efficiency and patient-level outcomes of these models were not directly evaluated in this study and warrant formal investigation in future research. RELEVANCE TO CLINICAL PRACTICE:This study provides the first national descriptive data on the role of nurses in tracheostomy management for patients with HNC in Australia and offers a foundation for the development of standardised training pathways. The potential impact of such pathways on efficiency, length of stay and nursing workforce capacity warrants formal evaluation in future studies.

AIM:Head and neck cancer (HNC) survivors experience complex survivorship needs compared to other cancer types. This is exacerbated for people living in regional and remote (rural) areas of Australia, who experience poorer outcomes, higher physical and psychological needs, and poorer quality of life compared to their metropolitan counterparts. Little is known about the general survivorship experiences of rural HNC survivors in New South Wales (NSW), Australia. This study aims to explore the general survivorship experiences of people living with HNC in rural areas of NSW, Australia. METHODS:HNC survivors living in rural NSW were recruited, and semi-structured interviews were conducted to explore their general survivorship experiences. The interviews were recorded, transcribed, and analyzed using a qualitative thematic analysis approach until saturation of themes was reached. RESULTS:Semi-structured interviews were conducted with 17 participants, with a mean age of 65 years. The most common diagnoses were oral cavity (41%) and oropharyngeal cancers (29%). Six key themes emerged around general survivorship experiences among participants: 1) financial impacts, 2) physical effects, 3) psychosocial effects, 4) clinical management, 5) information and support needs, and 6) access. CONCLUSIONS:Rural cancer survivors face unique survivorship concerns, exacerbated by living further from specialist care. The unmet needs of people living in rural areas include financial reimbursement, psychosocial services and support, and access to survivorship care closer to home. Understanding cancer survivors' experiences throughout the care journey can identify unmet needs. By recognizing these needs, they can be more readily addressed by government policy and other interventions.

ABSTRACTBackgroundThe post‐treatment survivorship period marks the transition away from acute care and poses distinct challenges for individuals with head and neck cancer (HNC). This can be especially challenging for people in regional areas who travel long distances to access care and experience unique challenges in accessing health services.AimTo investigate unmet needs and healthcare utilisation of survivors of HNC in regional areas.MethodsInvitations were sent to 619 survivors of HNC living in rural New South Wales, Australia, who were 1–15 years post‐treatment. Participants self‐reported unmet survivorship needs and the strength of these needs using the Cancer Survivors' Unmet Needs Measure. Health care utilisation over the preceding 12 months was collected using an investigator‐designed questionnaire.ResultsOne hundred and seventeen responses were received (19% response rate). Participants were predominantly male (65%), had oropharynx cancer (52%), with mean age of 70.2 years. Some 54% of participants reported at least one unmet need, and 40% rated these unmet needs as 'strong'. Top unmet needs included concern about recurrence (24%), access to local services (15%), and financial support (15%). 94% of participants reported seeing their GP, while 62% visited a dental clinic; only 10% sought professional psychosocial support despite prevalent unmet needs.ConclusionRural survivors of HNC in Australia have substantial unmet psychosocial needs yet demonstrate low utilisation of professional psychosocial support. This may reflect the limited availability or accessibility of services for this population, which could be addressed with shared models of care utilising both GP‐led and telehealth services.

Background: Accidental parathyroidectomy in thyroid surgery refers to inadvertent resection of parathyroid tissue during thyroidectomy and is associated with temporary hypoparathyroidism and permanent hypoparathyroidism. This cohort study set out to identify the incidence and risk factors for accidental parathyroidectomy and hypoparathyroidism in patients undergoing total thyroidectomy with the aim of developing a risk stratification to aid clinical practice by predicting which patients are at risk of post-operative hypoparathyroidism. Methods: A retrospective analysis of patients from three Australian tertiary referral hospitals from 2010 to 2020 who underwent total thyroidectomy was performed using the Sydney Head and Neck Cancer Institute database. Chi-square and Fisher's exact tests were used to determine the significance of associations between variables. Logistic regression was used to determine predictors for the risk stratification tables and were constructed using the predicted probabilities of significant variables. Results: A total of 295 patients were included in this study. Accidental parathyroidectomy was reported in 78/295 (26%) of cases and was associated with temporary hypoparathyroidism [P<0.001; odds ratio (OR) =3.1; 95% confidence interval (CI): 1.81-5.31] and permanent hypoparathyroidism (P=0.04; OR =17.75; 95% CI: 2.1-149.94). Significant risk factors identified for accidental parathyroidectomy were malignancy (P=0.015; OR =1.91; 95% CI: 1.13-3.26) and central lymph node dissection (P<0.001; OR =4.94; 95% CI: 2.44-10.2). Temporary hypoparathyroidism was also associated with malignancy (P=0.044; OR =1.63; 95% CI: 1.01-2.65), central lymph node dissection (P<0.001; OR =4.74; 95% CI: 2.32-10.2) and auto-transplantation of parathyroid glands (P<0.001; OR =3.03; 95% CI: 1.85-5.00). Permanent hypoparathyroidism was associated with malignancy (P=0.006; OR =16.82; 95% CI: 0.95-297.19). Risk stratification tables were generated providing predicted probability for hypoparathyroidism and accidental parathyroidectomy providing probability values for each event occurring for a given set of pre-operative parameters. Maximal risk for temporary hypoparathyroidism of 74.1% occurred with thyroidectomy for malignant disease, neck dissection and parathyroid auto-transplantation and maximal risk for accidental parathyroidectomy was 59.5% and occurred with a thyroidectomy was performed for malignant disease and required a neck dissection. Whenever a central neck dissection was performed, the risk of temporary hypoparathyroidism was greater than 50% and auto-transplantation of parathyroid resulted in risks greater than 40%. Conclusions: Accidental parathyroidectomy occurs commonly and is associated with malignancy and central neck dissection. Hypoparathyroidism is strongly associated with malignancy, central lymph node dissection, and auto-transplantation. The reported risk stratification tables can assist in the post-operative management of patients by identifying patients most at risk of requiring post-operative calcium and vitamin D supplementation.

Precision medicine is a likely future for all cancer treatment but may have its greatest impact on less common, high-mortality, and molecularly heterogeneous cancers. TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare, aggressive cancer with poor survival due to the lack of effective therapies and relevant models to facilitate research. In this study, we establish the first matched patient-derived xenograft and cell line model for TFCP2-rearranged intraosseous RMS, coupled with comprehensive multiomic and functional analyses, to discover and preclinically validate novel actionable molecular targets for this malignancy. Sequencing analyses of matched patient tumor and xenograft material revealed alterations in gene networks associated with the oncogenic, potentially targetable PI3K/AKT pathway. Preclinical assessments revealed that targeting the pathway with a small-molecule PI3K/mTOR inhibitor dactolisib presents a promising treatment approach for this rare cancer, decreasing cancer cell viability in vitro and significantly reducing tumor growth in vivo. Parallel identification of the codeletion of adjacent genes cyclin-dependent kinase inhibitor 2A and methylthioadenosine phosphorylase in these tumors led us to further explore protein arginine methyltransferase 5 inhibition as a potential therapeutic approach. Strikingly, combined inhibition of protein arginine methyltransferase 5 and PI3K/mTOR signaling synergistically enhanced antitumor response and significantly improved survival in vivo. This study highlights the importance of new patient-derived models for the elucidation of the biology of rare cancers and identification of new therapeutic entry points, with clear implications for the future treatment of TFCP2-rearranged intraosseous RMS.

BACKGROUND:Monitoring delivery of cancer care is critical to improve outcomes in increasingly resource-constrained settings. The aim of this study was to develop a priority set of multidisciplinary quality indicators (QIs) for benchmarking and monitoring the quality of care for head and neck cancer (HNC) in Australia. METHODS:Following a systematic literature review, a modified Delphi consensus process was undertaken with Australian health professionals and people with lived experience of HNC. Consensus was sought over three rounds. In Rounds 2 and 3, participants rated the importance of QIs on a scale of 1 (not at all important) to 7 (highly important). QIs reached consensus if they had a mean importance score ≥ 6 (out of 7) and ≥ 75% of participants rated them 6 or 7. RESULTS:The systematic review identified 317 unique QIs, and 81 were chosen for presentation in Rounds 2 of the Delphi. In Round 2, 66 health professionals and 12 people with lived experience of HNC reached consensus on 48 QIs, with three reworded and one new QI added. Fifty-two QIs were presented in Round 3; 42 health professionals and 10 people with lived experience participated, reaching consensus on 24 QIs. Most of the QIs fell under the treatment domain, with commencement of curative treatment and documentation of surgical margins attaining the highest consensus. CONCLUSION:We developed a priority set of 24 clinically relevant QIs for HNC, which will be tested in a clinical quality registry to benchmark optimal management of HNC and outcomes.

BACKGROUND:Regional metastasis occurs in 5% of cutaneous squamous cell carcinoma (cSCC). The aim of this study is to assess the impact of margin status of regional metastases on survival. METHODS:A retrospective review of 401 patients with nodal metastases from cSCC. Margin status of nodal metastases was classified as clear (>1 mm), close (<1 mm), or involved. Cox regression and Kaplan-Meier methods were used to assess associations with overall and disease-specific survival (OS and DSS). RESULTS:Of the 401 patients with nodal metastases (median age 75, 85.3% male), 43.6% had involved margins, 27.4% had close margins, and 28.9% had clear margins. Involved margins were significantly associated with reduced OS and DSS on univariable analysis. Multivariable analysis confirmed that involved margins independently predicted worse DSS (HR 1.92, 95% CI 1.15-3.19, p = 0.01). Other independent prognostic factors included size of deposit (HR 1.02, 95% CI 1.01-1.04, p < 0.001), number of deposits (HR 1.05, 95% CI 1.02-1.08, p < 0.001), and the presence of perineural invasion (HR 1.84, 95% CI 1.14-2.98, p = 0.01). CONCLUSIONS:Clear surgical margins during the removal of regional metastases of cSCC improves survival outcomes. This study highlights the importance of careful preoperative evaluation to achieve a complete (R0) surgical resection. LEVEL OF EVIDENCE:3 Laryngoscope, 135:2379-2384, 2025.

BACKGROUND:Submandibular gland pathology is common but rarely reported. This study was performed to evaluate demographic, pathological, and survival outcomes associated with submandibular gland extirpation. METHODS:Retrospective analysis of patients treated in a single quaternary-care institution between 1989 and 2022 was performed. RESULTS:Four hundred and sixty patients underwent submandibular gland extirpation with a female preponderance (n = 271, 59%) and a mean age of 51 years. Older age was associated with increased risk of malignancy (P < 0.001). Submandibular calculus was the most common pathology, with gland extirpation for this indication decreasing over time (P = 0.005). Pleomorphic adenoma was the most common benign tumour (n = 96, 52.7% of total tumours), and adenoid cystic carcinoma was the most common malignant tumour (n = 25, 13.7% of total tumours). CONCLUSIONS:Submandibular calculus remains the most common indication for submandibular gland extirpation, although the rate is decreasing over time. Pleomorphic adenoma continues to be the most common tumour of the submandibular gland, whilst adenoid cystic carcinoma is the most common malignant tumour. The incidence of benign versus malignant tumours has remained constant over the period of this study.

6048 Background: Survival in recurrent/metastatic HNmSCC remain poor. PD-1 inhibitors have become standard of care, demonstrating improved overall survival and toxicity when compared to chemotherapy and targeted therapy. Biomarkers such as PD-Ligand(L)1 combined proportion score (CPS) remain rudimentary, with CPS >20 showing a response rate of only 23% to pembrolizumab (KEYNOTE-048). We used high-dimensional imaging mass cytometry (IMC) to explore predictive biomarkers in HNmSCC pts receiving PD-1 inhibitor-based therapy. Methods: We retrospectively analysed 27 formalin-fixed paraffin embedded tissue samples from 24 pts prior to receiving PD-1 inhibitor-based therapy between May 2016 – April 2021. Clinicopathological characteristics including PD-L1, p16 status, prior treatment and survival data were collected. Pts were classified into responders (RES, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 complete response (CR) or partial response (PR), stable disease (SD) >6 months (mths)) and non-responders (non-RES, RECIST SD <6 mths or disease progression (PD)). An antibody panel (n = 40) was created to interrogate specific components of interest within the TME and was analysed by IMC using the HyperionTM Imaging System. Results: Of the 24 patients, 16/24 were male and median age 57.6 year. 8 pts were RES (RECIST CR, n = 1; PR, n = 3; SD > 6 mths, n = 4) and 14 pts were non-RES (RECIST SD < 6 mths, n = 1; PD, n = 11; clinical PD, n = 4). Four patients underwent rapid clinical disease progression prior to progress imaging and were categorised as non-RES. At time of data cut off on January 2024, and 23/24 pts had progressed on treatment. The cellular landscape within the TME was similar, irrespective of the location of the primary and p16 status. However, distinct immune profiles were observed between RES vs non-RES: RES showed higher infiltrates of CD4+ T cells, B cells, PD-1+ CD8+ T cells (P < 0.05) and both central memory and effector memory T cell subsets (p < 0.01). In contrast, non-RES showed high frequencies of CD44+ NK cells. Key cell interactions within the TME identified proliferating malignant squamous cells closely interacting with CD8+ T cells, CD4+ Tregs and endothelial cell in RES but not interacting in non-RES. Further spatial regional analysis identified a distinct tissue architecture with hallmarks of Tertiary Lymphoid-like Structures (TLS), present in higher proportions in RES. RES pts with TLS proportions >20% (n = 3) had a progression free survival of 80.3 mths, 26.8 mths and NE (unrelated death at 15.6 mths). Conclusions: The findings of this study identify mechanisms of PD-1 inhibitor response and resistance in HNmSCC pts, providing a unique opportunity to guide combination strategies and improve outcome.

BackgroundThe Jaw-in-a-Day (JIAD) procedure aims to achieve immediate functional occlusion via a single-stage approach to maxillofacial reconstruction. While JIAD has gained popularity since its inception by Levine and colleagues, efficacy and outcome data remain limited. In this report, we discuss our experience with the JIAD technique at an Australian tertiary referral centre.MethodsA retrospective review of all JIAD procedures performed from April 2022 to December 2023 was conducted. Clinicopathologic data reviewed included demographic information, primary diagnosis, anatomical site of disease, and history of pre-operative radiotherapy. Outcome measures of interest included operative time, number of implants placed, post-operative complications and implant survival.ResultsNineteen patients were identified for the study. Two maxillary and 17 mandibular JIAD procedures were performed. The most common indications were squamous cell carcinoma (n = 8) and ameloblastoma (n = 5). Surgical complications included recipient site wound infection (n = 3), flap dehiscence (n = 2), haematoma formation (n = 1), and neck abscess associated with partial flap failure (n = 1). No total flap failures were identified. Of the 55 total implants placed, one implant failure occurred 2-months post-operatively. No loss of irradiated implants (n = 21) was observed. The median time to adjuvant radiotherapy was 57 days (range, 32-61). Eighteen of 19 patients (95%) achieved immediate dental rehabilitation, and 15/19 patients (79%) retained a functional prosthesis by the end of the follow-up period.ConclusionsOur series supports the feasibility of single-stage reconstruction for both benign and malignant indications. Further research is required to understand the long-term functional, aesthetic, and health-related quality-of-life outcomes with the JIAD technique. In this case series, we discuss our early experience with the Jaw in a Day (JIAD) technique at an Australian tertiary referral centre. Our research demonstrates that the JIAD procedure predictably achieves immediate dental restoration in patients undergoing major maxillofacial reconstruction, and supports the feasibility of its use for both benign and malignant indications.image

BACKGROUND:Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes. METHODS:Patients were recruited from an institutional database. Semi-structured interviews were conducted according to the Model of Pathways to Treatment. Thematic analysis was based on the four main intervals in the framework using a data-driven analytical method. RESULTS:Seventeen participants were interviewed. Facilitators included patients' past experiences, symptom progression, trust in healthcare professionals (HCPs), and capacity to leverage relationships. Barriers included difficult diagnoses, limited access to cancer services, lack of care coordination, and lack of awareness of PNS among primary health care providers. CONCLUSION:These findings emphasise the complexity early diagnosis and treatment of PNS. Interventions like clinical practice guidelines, education for HCPs, and telehealth could facilitate timely detection and management.