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The University of Oxford is launching the UNIQ+ Graduate Summer School this year and the Nuffield Department of Surgical Sciences (NDS) is delighted to be taking part.
Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.
Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.
Neurophysiological effects of high-frequency spinal cord stimulation on cortico-sensory areas in large ovine animal model.
Spinal Cord Stimulation (SCS) has been a cornerstone in managing chronic pain since the late 1960s. However, traditional SCS is often associated with variable efficacy and side effects, driving the development of advanced techniques like high-frequency SCS (hSCS). Previous studies have demonstrated that the power of high-frequency cerebral oscillations increases as a function of stimulus intensity and plays a critical role in local neural processing of peripheral sensory stimuli. Extending from the current body of literature, we hypothesized that hSCS could selectively influence stimulus-triggered neural oscillations involved in sensory processing and perception. Using electrocorticography (ECoG) in sheep (n = 4), we investigated the effects of 8.2 KHz hSCS on low-frequency (4-30 Hz) and high-frequency (70-150 Hz) oscillations in ovine somatosensory and association cortices. Neural signals were recorded before, and after hSCS application to assess frequency-specific modulation of cortical activity. Our findings reveal that hSCS induces broad suppression of high-frequency oscillations across both cortical regions. In contrast, low-frequency oscillations were selectively suppressed or enhanced in both cortices. Furthermore, a linear mixed model analysis revealed that low-frequency oscillations better predict high-frequency modulation in the association than the somatosensory cortex, highlighting a reciprocal low-/high-frequency relationship between cortices. These distinct effects on cortical oscillations suggest potential supraspinal mechanisms through which hSCS may exert its analgesic effects. Our findings provide new insights for optimizing neuromodulation strategies in pain management, emphasizing the role of frequency-specific modulation in sensory and cognitive pain processing. PERSPECTIVE: This study demonstrates that high-frequency spinal cord stimulation modulates cortical oscillations in a frequency- and region-specific manner, suggesting a supraspinal mechanism of pain. These findings advance our understanding of how neuromodulation influences sensory components of pain, with implications for optimizing stimulation protocols in chronic pain management.
Self-interactive learning: Fusion and evolution of multi-scale histomorphology features for molecular traits prediction in computational pathology.
Predicting disease-related molecular traits from histomorphology brings great opportunities for precision medicine. Despite the rich information present in histopathological images, extracting fine-grained molecular features from standard whole slide images (WSI) is non-trivial. The task is further complicated by the lack of annotations for subtyping and contextual histomorphological features that might span multiple scales. This work proposes a novel multiple-instance learning (MIL) framework capable of WSI-based cancer morpho-molecular subtyping by fusion of different-scale features. Our method, debuting as Inter-MIL, follows a weakly-supervised scheme. It enables the training of the patch-level encoder for WSI in a task-aware optimisation procedure, a step normally not modelled in most existing MIL-based WSI analysis frameworks. We demonstrate that optimising the patch-level encoder is crucial to achieving high-quality fine-grained and tissue-level subtyping results and offers a significant improvement over task-agnostic encoders. Our approach deploys a pseudo-label propagation strategy to update the patch encoder iteratively, allowing discriminative subtype features to be learned. This mechanism also empowers extracting fine-grained attention within image tiles (the small patches), a task largely ignored in most existing weakly supervised-based frameworks. With Inter-MIL, we carried out four challenging cancer molecular subtyping tasks in the context of ovarian, colorectal, lung, and breast cancer. Extensive evaluation results show that Inter-MIL is a robust framework for cancer morpho-molecular subtyping with superior performance compared to several recently proposed methods, in small dataset scenarios where the number of available training slides is less than 100. The iterative optimisation mechanism of Inter-MIL significantly improves the quality of the image features learned by the patch embedded and generally directs the attention map to areas that better align with experts' interpretation, leading to the identification of more reliable histopathology biomarkers. Moreover, an external validation cohort is used to verify the robustness of Inter-MIL on molecular trait prediction.
Local anaesthetic transperineal biopsy versus transrectal prostate biopsy in prostate cancer detection (TRANSLATE): a multicentre, randomised, controlled trial.
BACKGROUND: Prostate cancer diagnosis requires biopsy, traditionally performed under local anaesthetic with ultrasound guidance via a transrectal approach (TRUS). Local anaesthetic ultrasound-guided transperineal biopsy (LATP) is gaining popularity in this setting; however, there is uncertainty regarding prostate sampling, infection rates, tolerability, side-effects, and cost-effectiveness. TRANSLATE was a randomised clinical trial that aimed to compare detection of Gleason Grade Group (GGG) 2 or higher prostate cancer, side-effects, tolerability, and patient-reported outcomes, after LATP versus TRUS biopsy. METHODS: In this randomised clinical trial which was done at ten hospitals in the UK, patients aged 18 years or older were eligible if investigated for suspected prostate cancer based on elevated age-specific prostate-specific antigen or abnormal digital rectal examination, and if biopsy-naive having received pre-biopsy MRI on a 1·5 or higher Tesla scanner. Individuals were excluded if they had any previous prostate biopsy, extensive local disease easily detectable by any biopsy (prostate-specific antigen >50 ng/mL or entire gland replaced by tumour on MRI), symptoms of concurrent or recent urinary tract infection, history of immunocompromise, need for enhanced antibiotic prophylaxis, absent rectum, or inability to position in lithotomy. Participants were randomly assigned in a 1:1 ratio to receive LATP or TRUS biopsy, using web-based software with a randomisation sequence using a minimisation algorithm to ensure balanced allocation across biopsy groups for minimisation factors (recruitment site, and location of the MRI lesion). The primary outcome was detection of GGG 2 or higher prostate cancer, analysed in the modified intention-to-treat population (all randomly assigned to treatment who had a biopsy result available). Key secondary endpoints assessing post-biopsy adverse events were infection, bleeding, urinary and sexual function, tolerability, and patient-reported outcomes. This trial is registered with ClinicalTrials.gov (NCT05179694) and at ISRCTN (ISRCTN98159689), and is complete. FINDINGS: Between Dec 3, 2021, and Sept 26, 2023, 2078 (76%) of 2727 assessed individuals were eligible, and 1126 (41%) of 2727 agreed to participate. 1044 (93%) of the 1126 participants were White British. Participants were allocated to TRUS (n=564) or LATP (n=562) biopsy, and were followed up at time of biopsy, and at 7 days, 35 days, and 4 months post-biopsy. We found GGG 2 or higher prostate cancer in 329 (60%) of 547 participants with biopsy results randomly assigned to LATP compared with 294 (54%) of 540 participants with biopsy results randomly assigned to TRUS biopsy (odds ratio [OR] 1·32 [95% CI 1·03-1·70]; p=0·031). Infection requiring admission to hospital within 35 days post-biopsy occurred in 2 (<1%) of 562 participants in the LATP group compared with 9 (2%) of 564 in the TRUS group. No statistically significant difference was observed in the reporting of overall biopsy-related complications (LATP 454 [81%] of 562 vs TRUS 436 [77%] of 564, OR 1·23 [95% CI 0·93 to 1·65]), urinary retention requiring catheterisation (LATP 35 [6%] of 562 vs TRUS 27 [5%] of 564), urinary symptoms (median International Prostate Symptom Score: LATP 8 [IQR 4-14] vs TRUS 8 [4-13], OR 0·36 [95% CI -0·38 to 1·10]), nor sexual function (median International Index of Erectile Function score: LATP 5 [2-25] vs TRUS 8 [3-24], OR -0·60 [-1·79 to 0·58]) at 4 months after biopsy. Trial participants more commonly reported LATP biopsy to be immediately painful and embarrassing compared with TRUS (LATP 216 [38%] of 562 vs TRUS 153 [27%] of 564; OR 1·84 [95% CI 1·40 to 2·43]). Serious adverse events occurred in 14 (2%) of 562 participants in the LATP group and 25 (4%) of 564 in the TRUS group. INTERPRETATION: Among biopsy-naive individuals being investigated for possible prostate cancer, biopsy with LATP led to greater detection of GGG 2 or higher disease compared with TRUS. These findings will help to inform patients, clinicians, clinical guidelines, and policy makers regarding the important trade-offs between LATP and TRUS prostate biopsy. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment.
Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease.
BACKGROUND: It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with (i) stable PCa (sPCa) postprimary or salvage RT, (ii) progressing PCa (pPCa) post-RT, and (iii) de novo metastatic PCa (mPCa). METHODS: A cohort of 19 patients with diagnostic prostate biopsies (n = 6 sPCa, n = 5 pPCa, n = 8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3'RNA sequencing (3'RNAseq) (n = 19), nanoString analysis (n = 12), and Illumina 850k methylation (n = 8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes and methylated genomic regions (MGRs). RESULTS: Eighteen of 19 samples provided useable 3'RNAseq data. Principal component analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ~600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p
Emerging strategies in the transplantation of HCV-infected pancreases to uninfected recipients: A narrative review.
The scarcity of suitable candidates for solid organ transplantation (SOT) represents a major barrier to the reduction of waiting lists. The introduction of direct-acting antiviral (DAA) therapeutics eliminates many of the risks associated with the transplantation of Hepatitis C Virus (HCV)-infected donor organs (D+) to uninfected recipients (R-) and may facilitate access to a substantial organ pool, previously considered unacceptably high risk. The extent of clinical investigation into the safety and feasibility of HCV D+/R- SOT varies between allograft types. Here, we review the current state of pancreatic HCV D+/R-transplant research. Studies are limited to small cohorts who received pancreas allografts from HCV-viraemic donors alongside a regimen of DAA therapy. As of 2025, seven studies investigated a total of 22 patients, using prophylactic or reactive treatment regimens. Outcomes have been positive, with universal viral eradication, favourable allograft function, and minimal HCV-related complications. A favourable adverse event profile is reported, mirroring studies in other transplanted organs. With the aim to increase clinical use of pancreatic HCV D+/R- SOT, further investigation in the field is necessary to validate these preliminary data. Larger studies are essential to evaluate long-term sequelae and optimise treatment protocols to subsequently establish a standard of care.
Commercialization of medical artificial intelligence technologies: challenges and opportunities.
Artificial intelligence (AI) is already having a significant impact on healthcare. For example, AI-guided imaging can improve the diagnosis/treatment of vascular diseases, which affect over 200 million people globally. Recently, Chiu and colleagues (2024) developed an AI algorithm that supports nurses with no ultrasound training in diagnosing abdominal aortic aneurysms (AAA) with similar accuracy as ultrasound-trained physicians. This technology can therefore improve AAA screening; however, achieving clinical impact with new AI technologies requires careful consideration of commercialization strategies, including funding, compliance with safety and regulatory frameworks, health technology assessment, regulatory approval, reimbursement, and clinical guideline integration.
Innovations and strategies for effective implementation of post pregnancy contraception services: Learnings from the FIGO PPIUD initiative.
The global unmet need for contraception continues to be unacceptably high at 218 million. The vast majority of these are women living in low and middle income countries, with a particularly high unmet need in the postpartum period. The FIGO PPIUD initiative demonstrated that it is feasible to embed counselling on contraception and insertion of PPIUD in maternity services. Implementation of these services was greatly enhanced by ensuring that counselling was culturally sensitive and appropriately given through specifically trained individuals, that task sharing was maximized in order to increase access, and that a high fundal placement was achieved resulting in low expulsion rates. Financing for contraception in LMICs is currently precarious and vulnerable to international politics. PPIUD is highly cost-effective. Expansion of contraception services including PPIUD has the potential to impact positively on climate change and a country's development profile if expanded on a large scale.
Impact and outcomes of the Emerging Leaders Programme: a mixed-methods evaluation of a leadership development programme for healthcare professionals.
BACKGROUND: The significance of effective medical leadership in enhancing healthcare outcomes has been widely acknowledged. This study evaluates the Emerging Leaders Programme, a multidisciplinary leadership development initiative for healthcare professionals at a UK Hospital Trust. METHODS: The evaluation spanned three cohorts (2017-2019) and a total of 54 participants, employing mixed methods to assess participant reactions, learning, behaviour changes and organisational impact. Quantitative pre-/post-measures included the Primary Colours Questionnaire (PCQ), Medical Leadership Competency Framework Questionnaire (MLCFQ) and Brief Resilience Scale (BRS), while qualitative data were gathered via free-text comments and long-term follow-up interviews. RESULTS: The programme had high satisfaction ratings, with particularly positive feedback relating to the multidisciplinary cohort and experiential learning via Quality Improvement projects. Findings indicated improvements in participants' leadership skills, knowledge, confidence and job satisfaction. Organisational outcomes included increased organisational interest in quality improvement and individual career progression. CONCLUSION: The results highlight the value of a structured leadership programme in developing healthcare leaders and driving organisational improvements, with long-term effects. Recommendations for future programmes include multidisciplinary involvement, experiential learning, inspiring speakers and embedded mixed-methods evaluation.
Patients' priorities in kidney stone disease.
INTRODUCTION: Engaging with patients and the public is essential to design and deliver impactful research. Enhancing the relevance of research and tailoring treatments to align with patients' preferences can facilitate improved clinical care. METHODS: We aimed to identify the research, support and treatment priorities of individuals with kidney stone disease (KSD) using a 25-question survey in inpatient and outpatient urology departments. RESULTS: Forty-four individuals with KSD responded to our survey; 28 (64%) had experienced multiple KSD episodes and 11 reported 5 or more episodes. Median self-rated quality-of-life (QoL) impact (0 = negligible; 10 = severe) was 7.00 out of 10.00 (interquartile range [IQR]: 5.00-9.00), equivalent in individuals with single and recurrent stone episodes. Pain (n = 34), haematuria (n = 28) and anxiety (n = 22) were the primary factors contributing to QoL impact. Participants prioritised research into preventing recurrence, alleviating pain and slowing stone growth. More than one-third desired more information about KSD. Most (n = 36) felt 'likely' or 'very likely' to take medication to reduce their risk of KSD and 25 would commit to life-long therapy. Daily dosing was acceptable to 13 participants if risk of KSD recurrence was reduced by 50%, rising to 34 respondents if risk of recurrence was reduced by 75%. Most respondents (n = 44) expressed willingness to have genetic testing to facilitate personalised medicine research. CONCLUSIONS: Our findings emphasise symptoms contributing to reduced physical and psychological wellbeing in patients with KSD. We highlight the need for research into developing therapies to prevent stone recurrence, alleviate pain and slow stone growth, and for educational materials. Responses indicate an appetite for personalised medicine and oral medications in KSD.
Global burden of vision impairment due to age-related macular degeneration, 1990–2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021
Background: Age-related macular degeneration (AMD) is a growing public health concern worldwide, as one of the leading causes of vision impairment. We aimed to estimate global, national, and region-specific prevalence and disability-adjusted life-years (DALYs) along with tobacco as a modifiable risk factor to aid public policy addressing AMD. Methods: Data on AMD were extracted from the Global Burden of Disease, Injuries, and Risk Factor Study 2021 database in 204 countries and territories, 1990–2021. Vision impairment was defined and categorised by severity as follows: moderate to severe vision loss (visual acuity from <6/18 to 3/60) and blindness (visual acuity <3/60 or a visual field <10 degrees around central fixation). The burden of vision impairment attributable to AMD was subsequently estimated. These estimates were further stratified by geographical region, age, year, sex, Healthcare Access and Quality (HAQ) Index, and Socio-demographic Index (SDI) levels. Additionally, the effect of tobacco use, a modifiable risk factor, on the burden of AMD was analysed, and projections of AMD burden were estimated through to 2050. These projections also included scenario modelling to assess the potential effects of tobacco elimination. Findings: Globally, the number of individuals with vision impairment due to AMD more than doubled, rising from 3·64 million (95% uncertainty inverval [UI] 3·04–4·35) in 1990 to 8·06 million (6·71–9·82) in 2021. Similarly, DALYs increased by 91% over the same period, from 0·30 million (95% UI 0·21–0·42) to 0·58 million (0·40–0·80). By contrast, age-standardised prevalence and DALY rates declined, with prevalence rates decreasing by 5·53% (99·50 per 100 000 of the population [95% UI 83·16–118·04] in 1990 to 94·00 [78·32–114·42] in 2021) and DALY rates dropping by 19·09% (8·38 [5·70–11·53] to 6·78 [4·70–9·32]). These rates showed a consistent decrease in higher SDI quintiles, reflecting the negative correlation between HAQ Index and AMD burden. A general downward trend was observed from 1990 to 2021, with the largest age-standardised reduction occurring in the low-middle SDI quintile. The global contribution of tobacco to age-standardised DALYs decreased by 20%, declining from 12·45% (95% UI 7·73–17·37) in 1990 to 9·96% (6·12–14·06) in 2021. By 2050, the number of individuals affected by AMD is projected to increase from 3·40 million males (95% UI 2·81–4·17) in 2021 to 9·02 million (5·72–14·20) and from 4·66 million females (3·88–5·65) to 12·32 million (8·88–17·08). Eliminating tobacco use could reduce these numbers to 8·17 million males (5·59–11·92) and 11·15 million females (8·58–14·48) in 2050. Interpretation: While the total prevalence and DALYs due to AMD have steadily increased from 1990 to 2021, age-standardised prevalence and DALY rates have declined, probably reflecting the effect of population ageing and growth. The consistent decrease in age-standardised rates with higher SDI levels highlights the crucial role of health-care resources and public policies in mitigating AMD-related vision impairment. The downward trend observed from 1990 to 2021 might also be partially attributed to the reduced effect of tobacco as a modifiable risk factor, with declines in tobacco use seen globally and across all SDI quintiles. The burden of vision impairment due to AMD is projected to increase to about 21·34 million in 2050. However, effective tobacco regulation has the potential to substantially reduce AMD-related vision impairment, particularly in lower SDI quintiles where health-care resources are limited. Funding: Gates Foundation.
Missed opportunities for health promotion and disease prevention: lifestyle interventions in primary care for individuals with hypertension, hyperlipidemia, obesity and type 2 diabetes
Non-communicable diseases (NCDs) like hypertension, type 2 diabetes, hyperlipidemia, and obesity, are a leading cause of mortality and have shown rising prevalence trends over the last few decades. Lifestyle interventions, particularly diet and physical activity, are an effective approach to addressing the underlying risk factors of these preventable NCDs, but their integration into the primary care practice remains underutilized. This review synthesizes evidence from systematic reviews and meta-analyses published between 2019 and 2024 to provide evidence-based recommendations for the integration of lifestyle interventions into primary care pathways. The included articles were noted for their risk of bias because of poor study design. While consideration must be given to the quality of evidence for these interventions because of the risk of bias, there is good evidence to support the use of several types of interventions including: diet modification (e.g. food replacement, calorie restriction, intermittent/periodic fasting); diet education and counselling; individual and group-based exercise interventions; interventions that aim to promote general physical activity in daily life; as well as combined dietary and physical activity interventions delivered individually, in groups, at a community level as well as through smartphone-supported applications. It is important for the health and care community to explore and implement alternative means of generating evidence, integrating lifestyle interventions into care pathways and increasing investment in the lifecycle of these interventions, which can promote health and prevent disease.
Development of a patient-centred tool for use in total hip arthroplasty.
BACKGROUND: The aim of this project was to develop a tool using the experience of previous patients to inform patient-centred clinical decision-making in the context of total hip arthroplasty (THA). We sought out the patients' views on what is important for them, leveraging registry data, and providing outcome information that is perceived as relevant, understandable, adapted to a specific patient's profile, and readily available. METHODS: We created the information tool "Patients like me" in four steps. (1) The knowledge basis was the systematically collected detailed exposure and outcome information from the Geneva Arthroplasty Registry established 1996. (2) From the registry we randomly selected 275 patients about to undergo or having already undergone THA and asked them via interviews and a survey which benefits and harms associated with the operation and daily life with the prosthesis they perceived as most important. (3) The identified relevant data (39 predictor candidates, 15 outcomes) were evaluated using Conditional Inference Trees analysis to construct a classification algorithm for each of the 15 outcomes at three different time points/periods. Internal validity of the results was tested using bootstrapping. (4) The tool was designed by and pre-tested with patients over several iterations. RESULTS: Data from 6836 primary elective THAs operated between 1996 and 2019 were included. The trajectories for the 15 outcomes from the domains pain relief, activity improvement, complication (infection, dislocation, peri-prosthetic fracture) and what to expect in the future (revision surgery, need for contralateral hip replacement) over up to 20 years after surgery were presented for all patients and for specific patient profiles. The tool was adapted to various purposes including individual use, group sessions, patient-clinician interaction and surgeon information to complement the preoperative planning. The pre-test patients' feedback to the tool was unanimously positive. They considered it interesting, clear, complete, and complementary to other information received. CONCLUSION: The tool based on a survey of patients' perceived concerns and interests and the corresponding long-term data from a large institutional registry makes past patients' experience accessible, understandable, and visible for today's patients and their clinicians. It is a comprehensive illustration of trajectories of relevant outcomes from previous "Patients like me". This principle and methodology can be applied in other medical fields.
Tremor Asymmetry and the Development of Bilateral Phase-Specific Deep Brain Stimulation for Postural Tremor.
BACKGROUND: Tremor phase-locked deep brain stimulation (DBS) has been shown to modulate symptom severity in postural tremor, including essential and dystonic tremor, with less energy than existing systems. Previous studies focused on unilateral stimulation; it remains unknown how tremor asymmetry interacts with stimulation in the context of bilateral phase-locked DBS. METHODS: Archival limb acceleration from nine essential tremor patients was analyzed for asymmetries in tremor amplitude, frequency, and instability, and their relationship with continuous high-frequency DBS (cDBS). Bilateral phase-locked DBS was tested in one essential tremor and one dystonic tremor patient. RESULTS: Postural tremor is asymmetric, with larger tremor power linked to smaller amplitude and frequency stability in one hand. These asymmetries were significantly reduced during cDBS, with greater effects on larger amplitude tremors. Bilateral phasic DBS effects were also asymmetric. CONCLUSIONS: This study enhances understanding of tremor asymmetry and its relationship with DBS, offering insights for patient-specific tremor treatments. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Clinical Factors Influencing the Compliance With National Head and Neck Cancer Targets in the United Kingdom: Results From a National Cohort Study
Introduction: In the United Kingdom, it is the standard of care that treatment decisions in all new cases of head and neck cancer (HNC) are discussed at a multidisciplinary team meeting (MDT). The aim of this project was to gain a national perspective on the scope of current HNC treatment, compliance with national cancer pathway targets, and their influence on survival outcomes. Methods: A multicentre, retrospective, national observational study of primary HNC patients was discussed at a specialist MDT between September and November 2021. Results: Data on 1488 patients were included from 50 UK departments. The most common subsite was oropharynx (35.4%, 522), of which 61.7% (263) were HPV positive. Median time of referral to diagnosis, MDT decision to treatment, and referral to first definitive treatment in primary HNCs managed curatively were 37 (interquartile range [IQR] 22–57), 42 (IQR 29–65), and 74 (IQR 54–101) days, respectively. Compliance with the 28-day, 31-day, and 62-day targets were met in 32.8% (488), 33.3% (495), and 34.6% (515), respectively. On multivariate analysis, patients with urgent cancer referrals, T1–T2 stage disease, and not undergoing a general anaesthetic biopsy were associated with greater compliance with national pathway targets. Conclusion: This study highlights the majority of UK HNC patients are not meeting national pathway targets and delays are seen at all points in the HNC journey. Improving adherence with national best practice standards will contribute to reducing time to treatment for HNC.