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PubMed2026

Genomic insights into an optrA-carrying plasmid associated with linezolid resistance in clinical Enterococcus faecalis isolates, Argentina.

The spread of the transferable optrA gene poses an increasing threat to the clinical efficacy of oxazolidinones. Here, we characterized a novel optrA-carrying plasmid, pEfa-optrA-Arg, from a linezolid-resistant Enterococcus faecalis clinical isolate from Argentina. The 68,653-bp conjugative plasmid harbored optrA together with multiple antimicrobial resistance genes and showed high similarity to a plasmid previously identified in a bovine isolate from Switzerland. pEfa-optrA-Arg, or a closely related variant, was also detected in E. faecalis isolates from several Argentinian hospitals, highlighting the role of horizontal gene transfer in the spread of antimicrobial resistance across human and animal reservoirs within the One Health continuum.

Enterococcus faecalis↗
PubMed2026

Artificial intelligence-supported double reading in European population breast cancer screening: A systematic review and meta-analysis of prospective programs.

BACKGROUND: Most European population mammography screening programs rely on double reading with arbitration, a model that delivers mortality benefit but is increasingly challenged by radiologist workload, variable specificity, and interval cancers. Artificial intelligence (AI) is being evaluated to support or optimize these established European screening pathways. PURPOSE: To synthesize prospective or program-embedded evaluations of AI conducted within European-style population screening programs and to estimate exploratory program-level absolute risk differences (RDs) per 1000 examinations for cancer detection rate (CDR) and recall. MATERIALS AND METHODS: We performed a prespecified, focused evidence synthesis of three large studies embedded within routine population screening programs operating under European-relevant workflows: MASAI (randomized AI-supported risk triage within a national program), ScreenTrustCAD (prospective paired-reader evaluation with AI as an independent reader in a double-reading framework), and PRAIM (nationwide decision-referral implementation). Outcomes were harmonized as AI-control RDs per 1000 examinations. Random-effects pooling used Hartung-Knapp-Sidik-Jonkman models. For the paired-reader design, sensitivity analyses applied a Kish effective sample-size approach across plausible within-examination correlations (ρ = 0.3-0.8). Positive predictive value (PPV) and workflow/time outcomes were summarized descriptively. RESULTS: Across 597,419 examinations, the pooled CDR RD was +0.9 per 1000 (95% CI -0.0 to +1.8; I2 ≈ 12%), consistent with a modest directional increase with borderline statistical uncertainty. The pooled recall RD was -0.6 per 1000 (95% CI -3.1 to +2.1; I2 ≈ 41-43%), indicating no consistent recall increase across screening programs. Where reported, PPV was higher with AI-supported screening. Efficiency signals included 44.3% fewer total readings in MASAI and shorter reading times for AI-normal examinations in PRAIM; in PRAIM, a program-level safety-net mechanism recovered 204 cancers that would otherwise have been missed. CONCLUSION: In European population screening programs characterized by double reading and arbitration, prospective program-embedded evidence suggests that AI integration may yield a small absolute increase in cancer detection (≈1/1000) without a consistent increase in recall, alongside improved PPV and efficiency signals. These findings suggestAI primarily as a complementary reader within European screening workflows, with implementation requiring explicit quality assurance and monitoring of interval cancers and stage distribution.

Humans↗
PubMed2026

ReMeDy: A Flexible Statistical Framework for Region-Based Detection of DNA Methylation Dysregulation.

Region-based epigenome-wide association studies have demonstrated improved statistical power and biological interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily through changes in mean methylation levels associated with a phenotype of interest. Substantial evidence indicates that phenotype-associated methylation alterations may also manifest through changes in methylation variability or through joint shifts in mean and variability. Despite this, no existing statistical framework jointly models mean-variance methylation changes in a region-based manner. We propose ReMeDy, a flexible statistical framework that uses a hierarchical likelihood approach within a generalized linear model setting to identify differentially methylated regions, variably methylated regions, and regions exhibiting joint differential and variable methylation at a genome-wide scale. Unlike existing models, ReMeDy operates directly on biologically defined co-methylated regions, allowing it to naturally capture spatial correlation inherent in DNA methylation array data, while avoiding reliance on heuristic, user-defined tuning parameters such as smoothing spans and kernel bandwidths that can substantially influence results and introduce subjectivity. Through extensive simulation studies and comprehensive benchmarking against popular models, we demonstrate that ReMeDy maintains false discovery and Type-I error rates at nominal levels while achieving consistently higher statistical power across a wide range of realistic scenarios. Application to population-level DNA methylation data further shows that ReMeDy identifies biologically meaningful regions and pathways implicated in complex human diseases that are not captured by conventional mean-based analyses alone. ReMeDy is implemented as an open-source R package and is freely available at https://github.com/SChatLab/ReMeDy.

DNA Methylation↗
PubMed2025

Understanding Dynamics: A Systematic Review of the Attitudes, Knowledge, and Competencies of European Frontline Professionals Toward Domestic Abuse.

There remains a paucity of European research on attitudes and responses to domestic abuse from frontline workers and professionals who regularly encounter domestic abuse or engage with domestic abuse legislation. This systematic review synthesized qualitative, quantitative, and mixed-method peer-reviewed studies that explored professionals' knowledge, attitudes, and competencies related to domestic abuse. The professionals included medical staff (doctors, nurses, midwives), social care professionals, police officers, and criminal justice practitioners. The review was conducted on current European studies published between 2014 and 2025 and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases consulted included APA PsycInfo, Scopus, Web of Science, PubMed, Sociological Abstracts, International Bibliography of the Social Sciences, Social Services Abstracts, and Google Scholar. Full-text review was performed on 273 articles, of which 36 were deemed appropriate for inclusion. The review included 8 multi-country studies spanning the United Kingdom (England, Scotland, and Wales), and 28 single-country studies conducted in England, Sweden, Turkey, Portugal, the Republic of Ireland, Wales, Bosnia, Spain, Italy, Slovenia, and Hungary. A narrative and thematic synthesis categorized professional attitudes toward domestic abuse into four emergent themes: attitudes toward engagement and responsibility, attitudes toward victims, knowledge and understanding of domestic abuse, and attitudes as predictors of professional practice. This review addresses a dearth of research and provides recommendations for promoting proactive practice among professionals most likely to receive disclosures of abuse.

Humans↗
PubMed2026

Effects of Family-Based Intervention for Childhood Obesity on Parental and Offspring Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Childhood obesity is a global public health issue with strong familial and intergenerational transmission. However, existing syntheses often overlook the active role of parents and fail to assess outcomes beyond the child. This systematic review and meta-analysis specifically investigate the effects of family-based interventions, which position parents as active co-agents of change, on health outcomes for both children with obesity and their parents. METHODS: A systematic review and meta-analysis were conducted. Six databases were searched for randomized controlled trials (RCTs) targeting children with obesity and at least one family member. Primary outcomes were children's BMI z-score and parental BMI; secondary outcomes included other adiposity measures and dietary behaviors. Outcomes for both children and parents were synthesized. Subgroup analyses were conducted based on intervention characteristics. Risk of bias was assessed using RoB 2, and evidence certainty was evaluated using GRADE. RESULTS: Twenty RCTs with 1740 participants were included in the meta-analysis. The interventions demonstrated a significant reduction in children's BMI z-score. Additional benefits were observed for long-term BMI z-score and percentage of total body fat. The most effective interventions commonly integrate health education, behavioral strategies, and motivational support. Subgroup analyses indicated that interventions positioning parents as active co-participants, rather than mere supporters, yielded larger effects. However, no significant effects were found on parental BMI. CONCLUSION: This study demonstrates that family-based interventions can confer significant benefits for children with obesity. Their success hinges on strategically framing parents as active co-agents and integrating motivational strategies.

Humans↗
PubMed2026

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P&#x2009;<&#x2009;0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P&#x2009;<&#x2009;0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P&#x2009;=&#x2009;0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans↗
PubMed2026

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans↗
PubMed2026

Access to maternity services for women asylum seekers and refugees: A transnational document analysis of international, European regional, and United Kingdom governance.

Women asylum seekers and refugees face persistent barriers to maternity care (antenatal, intrapartum and postnatal care) across high-income countries, yet the upstream governance shaping access remains under-examined. Although legally distinct, both groups share protection-seeking experiences and are addressed jointly in governance documents. This study examined and synthesised how international (macro), European regional (meso), and United Kingdom (UK, micro) governance documents frame and operationalise maternity service access. Sixty-four documents were analysed using the READ framework. Inductive analysis of macro and meso documents identified six access dimensions: universal coverage; cultural and linguistic adaptation; rights-based approaches; multi-agency collaboration; data, monitoring and accountability; and quality of care. These dimensions structured assessment of UK governance, with jurisdictions rated strong, moderate or weak. Alignment was fragmented: Wales, Scotland and Northern Ireland exempted asylum seekers from charging, whereas England retained charging provisions. Multi-agency collaboration was consistently articulated, yet none of the 35 UK government documents focused on maternity access for this population, and none required outcome monitoring disaggregated by asylum or refugee status. UK governance appears coordinated in form but fragmented in substance. UK-wide minimum standards and routine recording of these data, with safeguards against immigration-related use, could strengthen coherence and accountability and improve visibility of inequities.

Refugees↗
PubMed2026

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4&#x2009;days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15&#x2009;kcal kg FFM-1 day-1) and maintaining energy availability at 45&#x2009;kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and &#x3b2;-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, &#x3b2;-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40%&#x2009;&#xb1;&#x2009;14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male↗
PubMed2026

Genital surgery in children with differences of sex development (DSD): Strengths and concerns across diverging regulations in four European countries.

Differences of Sex Development (DSD) is a collective term for a heterogeneous group of rare congenital conditions characterized by atypical genetic, gonadal, or genital sexual development. The treatment of children with DSD, particularly the indications for and timing of surgical interventions, has been the subject of debate for decades. In recent years, social developments emphasizing children's rights to self-determination and bodily integrity, along with increasing societal acceptance of atypical sex characteristics, have encouraged a more cautious approach toward early genital surgery in children with DSD. In 2019, the European Parliament adopted a resolution urging Member States to enact legislation prohibiting elective genital surgical interventions on intersex infants and children. Since then, several countries have indeed implemented restrictive measures, including legal bans on early surgical procedures. In this paper, we share the experiences and insights gained in recent years as pediatric urologists working in four neighboring countries in multidisciplinary university centers specializing in DSD care and research. We focus on current approaches to the care of children with DSD, the evolution of relevant national policies over time, and the nature and impact of recently introduced restrictive regulations on early surgical interventions. By presenting perspectives from pediatric urologists across these four countries, we aim to contribute to ongoing discussions on the alignment and refinement of surgical treatment practices for children with DSD.

Humans↗
PubMed2026

Efficacy and Safety of Mechanical Insufflation-Exsufflation in Invasively Ventilated Critically Ill Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is increasingly used in invasively ventilated adults in the intensive care unit (ICU), yet its therapeutic efficacy and safety remain uncertain due to inconsistent evidence. AIM: To synthesize evidence on the clinical efficacy and safety of MI-E in this population and to examine methodological and clinical heterogeneity underlying reported outcomes. STUDY DESIGN: A systematic review and meta-analysis of randomized studies (including RCTs and randomized crossover trials), conducted following PRISMA guidelines, with risk of bias assessed using the Cochrane risk-of-bias tool. RESULTS: Five randomized controlled trials involving 310 patients were included. Meta-analysis showed that mechanical insufflation-exsufflation (MI-E) significantly increased sputum clearance (SMD&#x2009;=&#x2009;0.63, 95% CI, 0.32-0.93; p&#x2009;<&#x2009;0.00011; I2&#x2009;=&#x2009;38%) without affecting oxygenation (MD&#x2009;=&#x2009;0.28, 95% CI, -0.53 to 1.09; p&#x2009;=&#x2009;0.50; I2&#x2009;=&#x2009;9%). Data on respiratory mechanics, ventilation duration and ICU stay could not be pooled. No serious adverse events were reported. CONCLUSIONS: MI-E significantly improves sputum clearance in invasively ventilated critically ill adults, with no severe adverse events reported in the included studies. Its effects on other outcomes remain inconclusive due to limited data and heterogeneity. Standardized protocols and larger trials are needed. RELEVANCE TO CLINICAL PRACTICE: Clinicians may consider MI-E as an adjunct for respiratory secretion management. Application should be guided by structured patient assessment and individualized parameter adjustment. Future research should standardize interventions and target well-defined patient subgroups to inform clear practice guidelines. TRIAL REGISTRATION: The review protocol was registered in the International Prospective Register of Systematic Reviews, with registration number CRD42023403299.

Humans↗
PubMed2026

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20&#x2009;weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR]&#x2009;=&#x2009;0.922, p&#x2009;=&#x2009;0.024) and treatment interruption (OR&#x2009;=&#x2009;0.550, p&#x2009;=&#x2009;0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR&#x2009;=&#x2009;0.972, p&#x2009;=&#x2009;0.049) and treatment interruption (OR&#x2009;=&#x2009;0.257, p&#x2009;<&#x2009;0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20&#x2009;weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans↗
PubMed2026

Nasopharyngeal Carriage Rate, Risk Factors, and Co-Resistance Patterns of Methicillin-Resistant Staphylococcus aureus in Ethiopia: Systematic Review and Meta-Analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) nasopharyngeal carriage is a major global health concern linked to severe infections and transmission. However, comprehensive evidence on the burden of MRSA carriage, antimicrobial resistance, and associated risk factors in Ethiopia remains limited. This study aimed to estimate pooled prevalence, resistance pattern, and determinants of nasopharyngeal MRSA carriage. PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, and gray literature were searched for cross-sectional studies published between January 2015 and December 2025. Two groups of reviewers screened studies based on predefined criteria. The risk of bias was assessed using the Joanna Briggs Institute tool. Pooled prevalence and resistance proportions were estimated using a random-effects model, and pooled odds ratios (ORs) were calculated using the Mantel-Haenszel method. Heterogeneity and publication bias were assessed, and a sensitivity analysis was conducted. A total of 1040 records were identified, and 20 studies (6869 participants) were included. The pooled carriage prevalence was 7.3% (95% CI, 5.0-10.8), with substantial heterogeneity (I2&#x2009;=&#x2009;95.5%). Resistance was highest to tetracycline (55.75%) and lowest to clindamycin (12.66%). Increased odds of carriage were associated with prior hospitalization (OR, 3.49) and antibiotic use (OR, 2.35). Inconsistent variable coding across included studies limited the inclusion of other potential risk factors. Evidence of publication bias was detected, suggesting that the pooled prevalence should be interpreted with appropriate caution. The findings indicate a considerable burden of MRSA and highlight the need for strengthened antimicrobial stewardship, improved surveillance, and targeted prevention efforts in higher-risk populations. This review was registered in PROSPERO (CRD420251047192).

Ethiopia↗
PubMed2026

Insights from expert panels on the EU clinical evaluation consultation procedure.

BACKGROUND: The Clinical Evaluation Consultation Procedure (CECP) under the EU Medical Device Regulation aims to strengthen and harmonize the assessment of high-risk medical devices. This review summarizes early insights from expert panels to support improved clinical evaluation practices. RESEARCH DESIGN AND METHODS: This review analyses 34 expert panel opinions derived from 281 CECP submissions between April 2021 and December 2025. Statements from opinions were systematically extracted, de-duplicated, and grouped into thematic categories, with independent review and validation. The analysis focuses on common challenges found during the consultation procedure of the expert panels on the content of the clinical assessment in relation to clinical evidence, benefit-risk assessment, intended purpose alignment, and post-market clinical follow-up planning. RESULTS: Expert panel findings highlight recurrent issues in the sufficiency, consistency, and transparency of clinical evidence, underscoring the need for improved standardization and clearer guidance. CONCLUSIONS: Strengthening documentation quality and alignment across stakeholders will enhance the robustness, efficiency, and predictability of conformity assessments for high-risk medical devices.

Humans↗
PubMed2026

Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.

Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced-choice substance guesses, certainty ratings, decision factors, and subjective substance effects, the analyses characterize blinding integrity and its relation to the substance experience. Results indicate that overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern, with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological substance effects. Prior substance experiences did not influence accuracy of forced-choice substance guesses. These findings provide empirical guidance for the design and reporting of blinding procedures in psychedelic trials and underscore the value of systematic, multi-level assessment of blinding integrity.

Humans↗
PubMed2026

Novel Germline ELP1 Splice-Acceptor Variant in NF1-Negative Optic Pathway Glioma: Expanding the Clinical Spectrum Associated With ELP1 Variation.

We report a 7-year-old boy with NF1-negative optic pathway glioma harboring a novel germline ELP1 splice-acceptor variant (NM_003640.5:c.2205-2A>G) identified by whole-exome sequencing. The variant was likely pathogenic (ACMG/AMP: PVS1, PM2) and inherited from an asymptomatic father, consistent with incomplete penetrance, expanding the limited evidence linking germline ELP1 variation to gliomas.

Humans↗
PubMed2026

Diagnostic utility of high-risk HPV polymerase chain reaction-based testing in head and neck FNA specimens with indeterminate cytomorphology.

BACKGROUND: Fine-needle aspiration (FNA) is critical in the initial diagnosis of many high-risk human papillomavirus (HR-HPV)-associated, metastatic oropharyngeal squamous cell carcinomas. Updated guidelines recommend HR-HPV-specific polymerase chain reaction (PCR) analysis over p16 immunohistochemistry on FNA specimens because p16 performs poorly on cytology material. PCR-based assays on liquid cytology material have demonstrated excellent analytic performance; however, the diagnostic utility of a positive HR-HPV PCR result in specimens with indeterminate cytomorphology remains uncharacterized. METHODS: The authors retrospectively identified 279 head and neck FNA specimens that had paired HR-HPV PCR testing on residual liquid cytology material over a 5-year period. The positive predictive value for histopathologically confirmed squamous cell carcinoma on surgical follow-up was calculated within each cytologic interpretive category. RESULTS: The HR-HPV PCR results were positive in 50.2% of specimens, negative in 40.9%, and indeterminate in 9.0%. The HR-HPV positivity rate ranged from 0% in specimens categorized as negative for malignancy to 57.3% in cytologically positive specimens, with 19.0%, 41.2%, and 50.0% positivity in the atypical, suspicious, and nondiagnostic categories, respectively. Among cytologically indeterminate specimens with positive HR-HPV PCR results (n&#xa0;=&#xa0;14), the positive predictive value was 100% (95% confidence interval, 78.5%-100.0%). Blinded slide review additionally identified 15 cytologically positive specimens in which the definitive malignant interpretation depended substantially on HR-HPV positivity; all 15 were confirmed as squamous cell carcinoma. CONCLUSIONS: A positive HR-HPV PCR result on liquid cytology material carries a positive predictive value of 100% for malignancy in cytologically indeterminate head&#xa0;and neck FNA specimens. These findings support integrating HR-HPV PCR analysis into routine cytologic interpretation with the potential to upgrade some indeterminate specimens to malignant when HR-HPV is detected, expediting definitive treatment and sparing patients additional, invasive sampling.

Humans↗