SpatialView: an interactive web application for visualization of multiple samples in spatial transcriptomics experiments.

MOTIVATION: Spatial transcriptomics (ST) experiments provide spatially localized measurements of genome-wide gene expression allowing for an unprecedented opportunity to investigate cellular heterogeneity and organization within a tissue. Statistical and computational frameworks exist that implement robust methods for pre-processing and analyzing data in ST experiments. However, the lack of an interactive suite of tools for visualizing ST data and results currently limits the full potential of ST experiments. RESULTS: To fill the gap, we developed SpatialView, an open-source web browser-based interactive application for visualizing data and results from multiple 10× Genomics Visium ST experiments. We anticipate SpatialView will be useful to a broad array of clinical and basic science investigators utilizing ST to study disease. AVAILABILITY AND IMPLEMENTATION: SpatialView is available at https://github.com/kendziorski-lab/SpatialView (and https://doi.org/10.5281/zenodo.10223907); a demo application is available at https://www.biostat.wisc.edu/˜kendzior/spatialviewdemo/.

Luminescence Studies on Dy3+ Doped Calcium Aluminum Borosilicate (CABS) Glasses for White Light Emission and Applications in w-LEDs.

Dy3+ doped calcium aluminum borosilicate (CABS) glasses have been synthesized via quick melt quench technique. CABS: xDy3+ glasses (x = 0.1, 0.5, 1, 1.5 and 2 mol%) were subjected to various morphological and photoluminescence studies. X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy were conducted to study the structural and bonding nature of the undoped glass. The excitation spectra of Dy3+ doped CABS glasses under 574 nm emission show many sharp peaks amongst which the transition from 6H15/2 → 6P7/2 (351 nm) had the highest intensity. Under 351 nm excitation, glasses exhibit sharp peaks in the blue, yellow and red regions corresponding to the transitions 4F9/2 → 6H15/2, 6H13/2, 6H11/2 and 6H9/2 respectively. The dipole-dipole nature of the interaction between the Dy3+ ions is confirmed via Dexter theory and Inokuti-Hirayama (I-H) model. CIE coordinates estimated from the emission profiles of these glasses under 351 nm excitation fall in the white region. Considering that these glasses exhibit sharp visible emission under UV excitation, have stable yellow to blue (Y/B) ratios and fast decays with intense energy transfers, we propose to utilise these glasses for white light generation and other white light LED (w-LED) and solid-state lighting (SSL) applications.

Thermally stable Sm3+ -doped alkali zinc alumino borosilicate (AZABS) glass for warm white light generation and w-LED applications.

Samarium ion (Sm3+ )-doped alkali zinc alumino borosilicate (AZABS) glass was synthesized via quick melt quench technique. Various spectroscopic studies like optical absorption, photoluminescence (PL) emission, PL excitation, temperature-dependent PL and PL decay kinetics were performed on the as prepared glass system. Under 402 nm excitation, three sharp bands at wavelengths 563, 599 and 645 nm corresponding to transitions 4 G5/2 → 6 H5/2 , 6 H7/2 and 6 H9/2 , respectively, can be seen in the PL emission spectra. The 0.25 mol% Sm3+ glass has the highest intensity for these emissions. The lanthanide interaction in the glass matrix is dipole-dipole in nature as was proven from Dexter's analysis. The direct bandgap of 0.25 mol% Sm3+ -doped AZABS glass was calculated to be 2.88 eV. The lifetimes of the as prepared glass range from 1.93 ms for the lowest concentration of Sm3+ to 0.75 ms for the highest. From temperature dependent PL studies, the activation energy for 0.25 mol% Sm3+ -doped AZABS glass was found to be 0.19 eV which shows high thermal stability of this glass. We propose to utilize these Sm3+ -doped AZABS glasses for white-light emitting diodes (w-LEDs) and solid-state lighting (SSL) applications.

Structural, optical, and luminescence properties of Dy3+ -activated potassium calcium silicate phosphor for white light-emitting diodes.

A dysprosium (Dy3+ )-activated potassium calcium silicate (K4 CaSi3 O9 ) phosphor was prepared using a solid-state synthesis route. The phosphor had a cubic structure with the space group Pa 3 ¯ as confirmed using X-ray diffraction (XRD) measurements. Details of surface morphology and elemental composition of the as-synthesized undoped KCS phosphor was obtained using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) spectroscopy. The chemical structure as well as the vibrational modes present in the as-prepared KCS phosphor was analyzed using Fourier transform infrared (FT-IR) spectroscopy. Diffuse reflectance spectra (DRS) were used to determine the optical bandgap of the phosphors and were found to be in the optical range 3.52-3.71 eV. Photoluminescence (PL) spectra showed intense yellow emission corresponding to the 4 F9/2 →6 H13/2 transition under 350 nm excitation. Commission International de l'Eclairage colour chromaticity coordinates were evaluated using the PL spectral data lie within the white region. Dexter theory and the Inokuti-Hirayama (I-H) model were applied to study the nature of the energy transfer mechanism in the as-prepared phosphors. The relatively high activation energy of the phosphors was evaluated using temperature-dependent PL (TDPL) data and confirmed the high thermal stability of the titled phosphor. The abovementioned results indicated that the as-prepared KCS:Dy3+ phosphor was a promising candidate for n-UV-based white light-emitting diodes.

Clinical practice guidelines for management of head and neck squamous cell carcinoma of unknown primary: an AGREE II appraisal.

IMPORTANCE: Squamous cell carcinoma without a known primary is an uncommon form of head and neck cancer that requires multidisciplinary collaboration for effective management. OBJECTIVE: To evaluate the quality of clinical practice guidelines (CPG) using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. DESIGN: A systematic literature search was performed to identify CPGs pertaining to the diagnosis and treatment of head and neck squamous cell carcinoma of unknown primary (HNSCCUP). Data were abstracted from guidelines meeting inclusion criteria and appraised by four independent reviewers in the six domains of quality defined by the AGREE II. SETTING: Online database. PARTICIPANTS: None. EXPOSURE: None. MAIN OUTCOME(S) AND MEASURE(S): Quality domain scores and intraclass correlation coefficients (ICC) were calculated across domains to qualify inter-rater reliability. RESULTS: Seven guidelines met inclusion criteria. Two guidelines achieved a score of > 60% in five or more AGREE II quality domains to gain designation as 'high'-quality content. One "average-quality" guideline authored by the ENT UK Head and Neck Society Council achieved a score of > 60% in three quality domains. The remaining four CPGs demonstrated low-quality content, with deficits most pronounced in domains 3 and 5, suggesting a lack of rigorously developed and clinically applicable information. CONCLUSIONS AND RELEVANCE: As the diagnosis and treatment of head and neck cancer continues to evolve, identification of high-quality guidelines will become increasingly important. The authors recommend consulting HNSCCUP guidelines from the National Institute for Health and Care Excellence (NICE) or the American Society of Clinical Oncology (ASCO). TRIAL REGISTRATION: None.

Nodal Metastasis in Surgically Treated Oral Cavity Squamous Cell Carcinoma.

INTRODUCTION: Management of the neck in oral cavity squamous cell carcinoma (OCSCC) is essential to oncologic control and survival. The rates of lymph node metastasis (LNM) vary based on oral cavity tumor site and stage and influence treatment decisions. The aim of this paper was to describe clinical LNM for different tumor subsites and stages of surgically managed OCSCC. METHODS: We conducted a retrospective analysis of 25,846 surgically managed OCSCC patients from the National Cancer Database (NCDB) stratified by tumor subsite and clinical T-stage. For cN + patients, rates of pathologic LNM and absence of pathologic LNM were determined. For cN0 patients, outcomes included the rates of elective neck dissection (END) and occult LNM and predictors of occult LNM determined by a multivariable logistic regression model. RESULTS: A total of 25,846 patients (59.1% male, mean age 61.9 years) met inclusion criteria with primary tumor sites including oral tongue (50.8%), floor of mouth (21.2%), lower alveolus (7.6%), buccal mucosa (6.7%), retromolar area (4.9%), upper alveolus (3.6%), hard palate (2.7%), and mucosal lip (2.5%). Among all sites, clinical N+ rates increased with T-stage (8.9% T1, 28.0% T2, 51.6% T3, 52.5% T4); these trends were preserved across subsites. Among patients with cN + disease, the overall rate of concordant positive pathologic LNM was 80.1% and the rate of discordant negative pathologic LNM was 19.6%, which varied based on tumor site and stage. In the overall cohort of cN0 patients, 59.9% received END, and the percentage of patients receiving END increased with higher tumor stage. Occult LNM among those cN0 was found in 25.1% of END cases, with the highest rates in retromolar (28.8%) and oral tongue (27.5%) tumors. Multivariable regression demonstrated significantly increased rates of occult LNM for higher T stage (T2 OR: 2.1 [1.9-2.4]; T3 OR: 3.0 [2.5-3.7]; T4 OR: 2.7 [2.2-3.2]), positive margins (OR: 1.4 [1.2-1.7]), and positive lymphovascular invasion (OR: 5.1 [4.4-5.8]). CONCLUSIONS: Management of the neck in OCSCC should be tailored based on primary tumor factors and considered for early-stage tumors.

Quality appraisal of clinical practice guidelines for the use of radiofrequency ablation in the treatment of thyroid nodules and cancer.

INTRODUCTION: Radiofrequency ablation (RFA) has gained significant recent global interest in the treatment of benign thyroid nodules and thyroid cancer. It is a relatively new, minimally invasive, thermal ablation technique that is an alternative to surgery. Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the use of RFA in the treatment of benign thyroid nodules and thyroid cancers. These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised. OBJECTIVE: To identify and perform a quality appraisal of clinical practice guidelines for RFA in the treatment of benign thyroid nodules and thyroid cancer using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. METHODS: A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases from inception to November 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICCs) were calculated to determine level of agreement between reviewers. RESULTS: Seven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Two guidelines were classified "high" quality, one "average" quality, and the rest "low" quality. The "Clarity and Presentation" (65.68 ± 26.1) and "Editorial Independence" (61.32 ± 25.8) domains received the highest mean scores, while the "Applicability" (32.14 ± 22.8) and "Rigor of Development" (45.02 ± 29.8) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.722-0.944). CONCLUSION: Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of RFA guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies amongst guidelines in the indications and use of RFA.

Anatomy education in US Medical Schools: before, during, and beyond COVID-19.

BACKGROUND: Anatomy education in US medical schools has seen numerous changes since the call for medical education reform in 2010. The purpose of this study was to survey US medical schools to assess recent trends in anatomy education, the impact of the COVID-19 pandemic on anatomy teaching, and future directions of medical school anatomy curricula. METHODS: We sent a 29-item survey to anatomy course directors of 145 AAMC-associated allopathic medical schools inquiring about their schools' anatomy curricula. The survey contained objective discrete questions concerning the curricula changes preceding COVID-19 and those directly related to COVID-19. We also asked subjective and open-ended questions about the impact of COVID-19 and future directions of anatomy education. RESULTS: A total of 117/143 course directors (82%) completed the survey. Most schools (60%) reported a major change to their anatomy course within the past five years, including a decrease in total course time (20%), integration of anatomy into other courses (19%), and implementation of a "flipped classroom" (15%) teaching style. Due to COVID-19, there was a decrease in the fraction of course time dedicated to "hands-on" learning (p < 0.01) and teaching of clinical correlates (p = 0.02) and radiology (p < 0.01). Most course directors (79%) reported that COVID-19 had a negative impact on quality of learning due to decreased interactive or in-person (62%) learning and lack of dissection (44%). Incorporation of virtual-reality applications or 3D anatomy software (23%) and a decrease in cadaver dissection (13%) were the most common future anticipated changes. CONCLUSION: The constraints conferred by COVID-19 highlight the importance of maximizing interactive learning in the discipline of anatomy. In an era of social distancing and decreased emphasis on conventional anatomy dissection, adaptations of new technologies and teaching modalities may allow for traditional educational rigor to be sustained.

Enhanced Recovery After Surgery for Pediatric Cleft Repair: A Systematic Review and Meta-Analysis.

OBJECTIVE: Perform a systematic review assessing the efficacy of enhanced recovery after surgery (ERAS) protocols for cleft palate repair. Primary outcomes included hospital length of stay, readmission rates, and postoperative narcotic use. Secondary outcomes included complications, time to initial postoperative oral intake, and pain scores. DATA SOURCES: Cohort and randomized studies of ERAS protocols pertaining to cleft palate repair were identified by systematic review of Medline, Scopus, Embase, and grey literature. REVIEW METHODS: Data extracted included patient demographics, clinical care protocols, complication rates, postoperative narcotic use, time to initial postoperative oral intake, hospital length of stay, family satisfaction, and 30-day readmission. Meta-analysis was used to compare outcomes between patients enrolled in ERAS protocols versus those in conventional care pathways. RESULTS: Eight hundred sixty-five articles were screened, and 5 studies met full inclusion criteria. A total of 425 patients were included. Patients in ERAS protocols saw a mean reduction of - 23.96 hours in length of stay compared to controls (95% confidence interval [CI]: - 26.4, - 20.6). Patients in ERAS protocols also had decreased total morphine consumption (mean difference [MD]: - 3.88 mg; CI: - 4.31, - 3.45), and decreased time to first initial feed compared to controls (MD: - 3.88 hours; CI: - 4.3, - 3.5). There was no difference in readmission rates or complication rates between ERAS and control groups. CONCLUSIONS: ERAS protocols have seen limited use in pediatric patients. The present study sought to assess the impact of ERAS protocols following primary palatoplasty. Our results indicate decreased hospital length of stay, postoperative opioid consumption, and time to feeding, without increasing readmission rates or complication rates.

Appraisal of clinical practice guidelines for the evaluation and management of neck masses in children.

AIM: The purpose of this systematic review was to use the Appraisal of Guidelines for Research and Evaluation tool to assess the methodological quality of clinical practice guidelines (CPGs) for the workup and management of paediatric neck masses. METHODS: MEDLINE, Embase, Cochrane and grey literature were searched to identify CPG incorporating paediatric neck masses. Four authors with previous training of the Appraisal of Guidelines for Research and Evaluation tool evaluated the included studies. RESULTS: Nine studies met inclusion criteria. The highest scoring domains were 'Scope and Purpose' (74.0 ± 4.5) and 'Clarity of Presentation' (72.9 ± 6.3). The lowest scoring domains were 'Rigour and Development' (18.8 ± 7.5) and 'Applicability' (23.7 ± 6.1). One study was 'High' quality, three received scores of 'Average' and five were found to be 'Low' quality. CONCLUSION: The majority of paediatric neck mass CPGs were low to average quality. The domains in need of greatest improvement were 'Rigour and Development' and 'Applicability', suggesting significant concerns in current CPGs focused on paediatric neck masses.

Role of elective neck dissection and adjuvant radiation therapy in patients with polymorphous adenocarcinoma.

PURPOSE: To evaluate the role of elective neck dissection (END) and of adjuvant radiation (aRT) in polymorphous adenocarcinoma (PAC), previously known as polymorphous low-grade adenocarcinoma (PLGA). METHODS: Retrospective cohort study of patients in the National Cancer Database with a histology of PAC (coded as PLGA) at a head and neck site diagnosed between 2004 and 2015. Multivariable Cox proportional hazard modeling was used to assess overall survival in the overall population, and in sub-analyses of clinically N0 disease, positive resection margins, and late stage disease. RESULTS: A total of 922 patients [66.8% female; mean (SD) age, 60.9 (13.9) years] met inclusion criteria. 74.7% of patients received surgery alone, and 18.0% received surgery and aRT. Only 7.6% of patients with clinically N0 disease received an END, with 10.6% of these having at least one positive node. END did not have a survival benefit compared to no END [HR 1.28 (0.61-2.68)]. Compared to surgery alone, aRT did not have significantly increased survival in the overall population or in late stage [HR 0.68 (0.39-1.19) and HR 0.46 (0.18-1.22), respectively]. On sub-analysis of patients with positive resection margins, aRT had a significant survival benefit compared to surgery alone [HR 0.37 (0.14-0.99)]. CONCLUSION: PAC is a rare, slow-growing malignant tumor typically treated with surgical excision, with undefined indications for END or aRT. Our findings show END to not have a benefit to overall survival. In patients with positive resection margins, there was a survival benefit for aRT.

The Thermal Safety Profile of a New Bipolar Vessel Sealing Device for Thyroid Surgery.

INTRODUCTION: Bipolar electrocautery devices used to achieve intraoperative hemostasis carry risk of imparting thermal energy to adjacent tissue, leading to postoperative morbidity. The aim of this study was to compare a new vessel sealing device, the CoolSeal™ Reveal (Bolder Surgical, Louisville, Colorado), with an established industry standard device, the LigaSure™ Exact Dissector (Valleylab, Boulder, Colorado), to assess their safety and the extent to which they impart thermal damage to tissue during thyroid surgery. MATERIALS AND METHODS: Vascular bundles associated with the thyroid gland in anesthetized sheep were exposed and sealed with a single activation of each device and excised en bloc. Additionally, vascular structures of the sheep were also sealed 0, 1, or 2mm adjacent to the recurrent laryngeal nerve (RLN). Vascular and RLN samples were processed for histopathologic evaluation and assessed for extent of thermal injury, seal width, and coagulative changes. RESULTS: The mean thermal injury extent across all sample sizes and vessel types was significantly lower for the CoolSeal™ Reveal device (547.2 ± 27.9µm) compared to the LigaSure™ device (802.7± 48.6µm) (p<0.001). Seal widths were significantly smaller in samples sealed with the CoolSeal™ Reveal device (899.0 ± 14.9µm) than samples sealed with the LigaSure™ device (1645.3 ± 160.3µm) (p<0.001). CONCLUSION: The CoolSeal™ Reveal device demonstrates significantly lower thermal spread in vivo compared to the LigaSure™ Exact Dissector. These results indicate that the CoolSeal™ Reveal is an effective tool for sealing blood vessels and minimizing thermal damage to adjacent structures during delicate surgeries or in narrow surgical fields associated with the thyroid gland.

The PUF binding landscape in metazoan germ cells.

PUF (Pumilio/FBF) proteins are RNA-binding proteins and conserved stem cell regulators. The Caenorhabditis elegans PUF proteins FBF-1 and FBF-2 (collectively FBF) regulate mRNAs in germ cells. Without FBF, adult germlines lose all stem cells. A major gap in our understanding of PUF proteins, including FBF, is a global view of their binding sites in their native context (i.e., their "binding landscape"). To understand the interactions underlying FBF function, we used iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to determine binding landscapes of C. elegans FBF-1 and FBF-2 in the germline tissue of intact animals. Multiple iCLIP peak-calling methods were compared to maximize identification of both established FBF binding sites and positive control target mRNAs in our iCLIP data. We discovered that FBF-1 and FBF-2 bind to RNAs through canonical as well as alternate motifs. We also analyzed crosslinking-induced mutations to map binding sites precisely and to identify key nucleotides that may be critical for FBF-RNA interactions. FBF-1 and FBF-2 can bind sites in the 5'UTR, coding region, or 3'UTR, but have a strong bias for the 3' end of transcripts. FBF-1 and FBF-2 have strongly overlapping target profiles, including mRNAs and noncoding RNAs. From a statistically robust list of 1404 common FBF targets, 847 were previously unknown, 154 were related to cell cycle regulation, three were lincRNAs, and 335 were shared with the human PUF protein PUM2.

Survey Assessing Medical Student and Physician Knowledge and Attitudes Regarding the Opioid Crisis.

BACKGROUND: There is a national opioid misuse and overdose crisis. Consensus guidelines seek to inform practice and reduce risk; however, effect on clinician attitudes and knowledge remains unclear. METHODS: We surveyed 228 medical students and physicians in Wisconsin to assess their knowledge regarding at-risk patients, alternatives to opioids, and best treatment practices for opioid addiction. We also assessed attitudes about prescribing naloxone, relapse likelihood, and responsibility for the crisis. DISCUSSION: Enhancement of opioid-related education is both necessary to address knowledge gaps and desired by students and physicians.

NeuCode Labeling in Nematodes: Proteomic and Phosphoproteomic Impact of Ascaroside Treatment in Caenorhabditis elegans.

The nematode Caenorhabditis elegans is an important model organism for biomedical research. We previously described NeuCode stable isotope labeling by amino acids in cell culture (SILAC), a method for accurate proteome quantification with potential for multiplexing beyond the limits of traditional stable isotope labeling by amino acids in cell culture. Here we apply NeuCode SILAC to profile the proteomic and phosphoproteomic response of C. elegans to two potent members of the ascaroside family of nematode pheromones. By consuming labeled E. coli as part of their diet, C. elegans nematodes quickly and easily incorporate the NeuCode heavy lysine isotopologues by the young adult stage. Using this approach, we report, at high confidence, one of the largest proteomic and phosphoproteomic data sets to date in C. elegans: 6596 proteins at a false discovery rate ≤ 1% and 6620 phosphorylation isoforms with localization probability ≥75%. Our data reveal a post-translational signature of pheromone sensing that includes many conserved proteins implicated in longevity and response to stress.

Amorfrutins are potent antidiabetic dietary natural products.

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.

Accuracy of Salivary Circulating Tumor Human Papillomavirus DNA in Detecting Oropharyngeal Cancer: A Systematic Review and Meta-analysis.

Importance: Circulating tumor human papillomavirus DNA (ctHPV DNA) has shown potential as a biomarker capable of improving outcomes in patients with HPV-related oropharyngeal (OP) cancer. It can be isolated from plasma or saliva, with the latter offering reduced invasiveness and theoretic reduction of lead time. Objective: To perform a systematic review and meta-analysis on the accuracy of salivary ctHPV DNA for detecting HPV-associated OP cancer. Data Sources: Cochrane Library, Embase, PubMed, and Web of Science databases were searched from inception through October 2023. Study Selection: All patients who underwent salivary ctHPV DNA testing at presentation for possible or diagnosed HPV-related OP cancer were included. Non-English and review publications were excluded. Two authors independently voted on article inclusion with a third resolving conflicting votes. Data Extraction and Synthesis: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, multiple authors independently abstracted data and assessed bias of included articles. Bivariate random-effects meta-analysis was performed with I2 to assess for study heterogeneity. Main Outcomes and Measures: Sensitivities, specificities, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) with 95% CIs alongside area under the curve (AUC) of a summary receiver operating characteristic (SROC) curve were calculated. The initial analysis took place throughout December 2023. Results: Of 440 initially identified articles, 6 met inclusion criteria and demonstrated moderate heterogeneity (I2 = 36%) with low risk of bias and low applicability concerns. Overall, 263 total patients were included with a median (range) age of 58 (39-86) years, and 228 (87%) were male patients. Per updated prognostic staging criteria, localized tumors (ie, stages 1 or 2) comprised most cancers at 139 (77%), whereas advanced ones (ie, stages 3 or 4) comprised the remaining 41 (23%). Pooled sensitivity, specificity, PLR, NLR, and DOR values were 64% (95% CI, 36%-85%), 89% (95% CI, 46%-99%), 11.70 (95% CI, 0.37-77.00), 1.21 (95% CI, 0.08-7.00), and 139.00 (95% CI, 0.05-837.00), respectively. The AUC of the SROC curve was 0.80. Conclusions and Relevance: This study supports salivary ctHPV DNA as an acceptably specific test in detecting HPV-associated OP cancer that would benefit from testing in clinical trials prior to real-time implementation.

Primary Site Surgery in Distantly Metastatic Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors. RESULTS: Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone. CONCLUSIONS: Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2243-2251, 2024.