Simultaneous p53 and p16 Immunostaining for Molecular Subclassification of Head and Neck Squamous Cell Carcinomas.

PURPOSE: Our aim was to assess the ability of simultaneous immunohistochemical staining (IHC) for p16 and p53 to accurately subclassify head and neck squamous cell carcinomas (HNSCC) as HPV-associated (HPV-A) versus HPV-independent (HPV-I) and compare p53 IHC staining patterns to TP53 mutation status, p16 IHC positivity and HPV status. METHODS: We stained 31 HNSCCs for p53 and p16, and performed next-generation sequencing (FoundationOne©CDx) on all cases and HPV in-situ hybridization (ISH) when sufficient tissue was available (n = 23). p53 IHC staining patterns were assessed as wildtype (wt) or abnormal (abn) patterns i.e. overexpression, null or cytoplasmic staining. RESULTS: In a majority of cases (28/31) interpretation of p16 and p53 IHC was straightforward; 10 were considered HPV-A (p16+/p53wt) and 18 cases were HPV-I (p16-/p53abn). In the remaining three tumours the unusual immunophenotype was resolved by molecular testing, specifically (i) subclonal p16 staining and wild type p53 staining in a tumour positive for HPV and with no TP53 mutation (HPV-A), (ii) negative p16 and wild type p53 staining with a TP53 mutation and negative for HPV (HPV-I), and (iii) equivocally increased p16 staining with mutant pattern p53 expression, negative HPV ISH and with a TP53 mutation (HPV-I). CONCLUSION: Performing p16 and p53 IHC staining simultaneously allows classification of most HNSCC as HPV-A (p16 +, p53 wild type (especially basal sparing or null-like HPV associated staining patterns, which were completely specific for HPV-A SCC) or HPV-I (p16 -, p53 mutant pattern expression), with the potential for limiting additional molecular HPV or mutational testing to selected cases only.

Multiple DNA Viruses and HPV Integration in Inverted Papilloma and Associated Sinonasal Carcinoma.

OBJECTIVES: Sinonasal inverted papilloma (IP) has a locally destructive growth pattern, can relapse, and can undergo malignant transformation (IP-associated sinonasal squamous cell carcinoma (IP-SNSCC)). Human papillomaviruses (HPV)-6 and -16 are frequently detected in IPs. To clarify the possible roles of other DNA viruses in IPs, we explored viruses not studied in this context before. With the setting of pre- and post-malignant transformation samples, we investigated HPV genomes in depth to assess the integration of HPV into the human genome and the presence of minor intratypic variants. MATERIALS AND METHODS: We analyzed 35 IP samples representing 28 individuals, of which six had IP-SNSCC. For virus screening, we applied qPCR to detect 16 different DNA viruses in three virus families, comprising herpesviruses, parvoviruses, and polyomaviruses. In addition, targeted next generation sequencing (NGS) was used for detailed HPV analysis. RESULTS: We detected herpes-, parvo-, and polyomaviruses in 13/28 (46%) patients, with codetections of multiple viruses in six (21%) patients. NGS revealed HPV16 DNA in 2/6 IP-SNSCC and in their respective earlier benign IP samples, as well as in a plasma sample from one of these patients. HPV6 was detected in two IP samples without subsequent malignant transformation. We identified sequence reads containing junctions of HPV6 and HPV16 and host genome suggestive of viral integration. HPV6 and HPV16 minor intratypic variants were present across pre- and post-malignant transformation, with mostly nonsynonymous mutations. CONCLUSIONS: Multiple DNA viruses were present in IPs. HPV16 was detected only in IP-SNSCCs or in tumors that later underwent malignant transformation. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Inter-rater reliability and clinical relevance of subjective and objective interpretation of videofluoroscopy findings.

Background: Dysphagia is commonly evaluated using videofluoroscopy (VFS). As its ratings are usually subjective normal-abnormal ratings, objective measurements have been developed. We compared the inter-rater reliability of the usual VFS ratings to the objective measurement VFS ratings and evaluated their clinical relevance. Methods: Two blinded raters analyzed the subjective normal-abnormal ratings of 77 patients' VFS. Two other blinded raters analyzed the objective measurements of pharyngeal aerated area with bolus held in the oral cavity (PAhold), the pharyngeal area of residual bolus during swallowing (PAmax), the pharyngeal constriction ratio (PCR), the maximum pharyngoesophageal segment opening (PESmax), pharyngoesophageal segment opening duration (POD), airway closure duration (ACD), and total pharyngeal transit time (TPT). We evaluated the inter-rater agreement in the subjective ratings and the objective measurements. Clinical utility analysis compared the measurements with the VFS findings of pharyngeal phase abnormality, penetration/aspiration, and cricopharyngeal relaxation. Results: In the pharyngeal findings, the subjective analysis inter-rater agreement was mainly moderate to strong. The strongest agreements were on the pharyngeal residues and penetration/aspiration findings. The objective measurements had fair to good inter-rater agreement. Clinical utility analysis found statistically significant connections between TPT and pharyngeal phase abnormality, normal PCR and lack of penetration/aspiration, and normal PESmax and normal cricopharyngeal relaxation. Conclusions: The subjective analysis had moderate to strong inter-rater agreement in the pharyngeal VFS findings, especially concerning pharyngeal residues and penetration/aspiration detection, reflecting the efficacy and safety of swallowing. The objective measurements had fair to good inter-observer reproducibility and could thus improve the reliability of VFS diagnostics. Level of evidence: 4.

A prospective cohort study: The effects of preoperative E-health on the postoperative course of tonsillectomy patients.

PURPOSE: At our clinic, a significant portion of tonsillectomy (TE) preoperative assessments are conducted remotely. The aim of our study was to examine the variation in TE complications, contact rates, and reasons for patient contact between those evaluated preoperatively at the outpatient clinic (OPC), or remotely through virtual visits (VV), or via a digital care pathway (DCP). This investigation is critical for optimizing patient flow through the volume-intensive process of TE. METHODS: We conducted a prospective cohort study involving 422 patients who underwent TE at Helsinki University Hospital ENT clinic to investigate their 30-day postoperative course. We extracted information on postoperative contacts, complications, and demographic data. Postoperative contact rate was the primary outcome measure to evaluate whether telehealth patients suffered fewer postoperative issues. RESULTS: Patients from the OPC were least likely to seek medical assistance in the 30-day postoperative period. However, no significant difference was discovered compared to the remotely assessed DCP patients, and over entire TE episodes, the DCP patients had the fewest unplanned contacts compared to the VV and OPC cohorts. Furthermore, the care paths shared similar complication and contact method profiles with comparable post-tonsillectomy hemorrhage incidence. CONCLUSION: A preoperative DCP for TE appeared to carry similar postoperative contact and complication rates, as well as comparable contact method profiles compared to the OPC model. Given the high patient satisfaction and cost-consciousness associated with the DCP, our findings encourage a broader implementation of highly developed DCPs in preoperative assessment for TE.

The Water Swallow Test and EAT-10 as Screening Tools for Referral to Videofluoroscopy.

BACKGROUND: Videofluoroscopy (VFS) is the gold standard in evaluating dysphagia. Water swallow tests (WST) and the Eating Assessment Tool (EAT-10) are commonly used in dysphagia screening. We aimed to determine the feasibility of WST and EAT-10 as screening tools for referral to VFS. METHODS: Patients (n = 150, median age: 70.0 years, range: 19-92 years, 58.7% female) referred to VFS completed the WST and EAT-10 before the examination. In the WST, we evaluated both the qualitative parameters (coughing, possible change in voice) and quantitative parameters (average drinking bolus size, swallowing speed). Correlations of EAT-10 total scores and WST parameters to the VFS findings were analyzed both individually and combined. RESULTS: In the WST, the most specific (89.7%) predictor of normal VFS findings was the absence of coughing, and the most sensitive (79.1%) parameter to predict abnormal findings was a bolus size of ≤20 mL. Using a combination of coughing and a bolus size ≤20 mL (simplified WST), the sensitivity of predicting abnormal findings increased to 83.5%. The most sensitive (84.6%) predictor of penetration/aspiration was failing any parameter in the WST. Lack of coughing indicated an absence of penetration/aspiration with an 82.5% specificity. Swallowing speed or combining the EAT-10 results with the WST results did not enhance the sensitivity or specificity of the WST for predicting the VFS results. CONCLUSIONS: Coughing and average drinking bolus size are the most important parameters in WST when screening for referral to VFS, whereas the swallowing speed does not seem to be useful. The WST is superior to EAT-10 in predicting VFS findings. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1349-1355, 2024.

Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma: Association with Metabolic Tumor Burden Determined with FDG-PET/CT.

BACKGROUND: The detection of circulating tumor DNA (ctDNA) with next-generation sequencing (NGS) in venous blood is a promising tool for the genomic profiling of head and neck squamous cell carcinoma (HNSCC). The association between ctDNA findings and metabolic tumor burden detected with FDG-PET/CT imaging is of particular interest for developing prognostic and predictive algorithms in HNSCC. METHODS: Twenty-six prospectively enrolled HNSCC patients were eligible for further analysis. All patients underwent tumor tissue and venous liquid biopsy sampling and FDG-PET/CT before definitive oncologic treatment. An NGS-based commercial panel was used for a genomic analysis of the samples. RESULTS: Maximum variant allele frequency (VAF) in blood correlated positively with whole-body (WB) metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (r = 0.510, p = 0.008 and r = 0.584, p = 0.002, respectively). A positive liquid biopsy was associated with high WB-TLG using VAF ≥ 1.00% or ≥5.00% as a cut-off value (p = 0.006 or p = 0.003, respectively). Additionally, ctDNA detection was associated with WB-TLG when only concordant variants detected in both ctDNA and tissue samples were considered. CONCLUSIONS: A high metabolic tumor burden based on FDG imaging is associated with a positive liquid biopsy and high maximum VAF. Our findings suggest a complementary role of metabolic and genomic signatures in the pre-treatment evaluation of HNSCC.

Programmed death-ligand 1 and tumor-infiltrating lymphocytes (TILs) - low TIL density may predict poorer long-term prognosis in T1 laryngeal cancer.

We evaluated the prognostic role of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in T1 glottic laryngeal squamous cell carcinoma (LSCC). T1 glottic LSCC patients (n = 174) treated at five Finnish university hospitals between 2003 and 2013 were included. Tissue microarray (TMA) blocks were used for PD-L1 immunohistochemistry. TILs were scored from intratumoral and stromal regions in whole tissue sections. Of 174 patients, 92 (53%) had negative, 66 (38%) intermediate, and 16 (9%) high PD-L1 levels. Of 80 patients whose TILs were analyzed, 50 (63%) had low and 30 (38%) high stromal TIL density. Patients with a local recurrence or a new primary tumor of the larynx had lower TIL density than had other patients (p = 0.047). High PD-L1 expression with low stromal TIL density was associated with inferior 5-year disease-specific survival (85% vs. 100%, p = 0.02). In conclusion, in patients treated for T1 glottic LSCC, low stromal TIL density was associated with local recurrences and new primary tumors of the larynx. High PD-L1 expression with low stromal TIL density may be associated with worse survival in T1 glottic LSCC.

Virtual visits at the Helsinki Head and Neck Center during the COVID-19 pandemic: patient safety incidents and the experiences of patients and staff.

BACKGROUND: During the COVID-19 pandemic, health care had to find new ways to care for patients while reducing infection transmission. The role of telemedicine role has grown exponentially. METHODS: A questionnaire on experiences and satisfaction was sent to the staff of the Head and Neck Center of Helsinki University Hospital and to otorhinolaryngology patients treated remotely between March and June 2020. Additionally, patient safety incident reports were examined for incidents involving virtual visits. RESULTS: Staff (response rate 30.6%, (n = 116)) opinions seemed to be quite polarized. In general, staff felt virtual visits were useful for select groups of patients and certain situations, and beneficial in addition to face-to-face visits, not instead of them. Patients (response rate 11.7%, (n = 77)) gave positive feedback on virtual visits, with savings in time (average 89 min), distance travelled (average 31.4 km) and travel expenses (average 13.84€). CONCLUSIONS: While telemedicine was implemented during the COVID-19 pandemic to ensure patient treatment, its usefulness after the pandemic must be examined. Evaluation of treatment pathways is critical to ensure that quality of care is upheld while new treatment protocols are introduced. Telemedicine offers the opportunity to save environmental, temporal, and monetary resources. Nonetheless, the appropriate use of telemedicine is essential, and clinicians must be offered the option to examine and treat patients face-to-face.

Sinonasal inverted papilloma - malignant transformation and non-sinonasal malignancies.

OBJECTIVES: To assess malignant transformation rate, non-sinonasal malignancies, and factors contributing to recurrence in patients treated for sinonasal inverted papilloma (SNIP). STUDY DESIGN: Retrospective study. METHODS: We retrospectively reviewed medical records of all patients treated for SNIP (n = 296) between the years 1984-2014 at Helsinki University Hospital. Data from the Finnish Cancer Registry confirmed the number of those patients with sinonasal and non-sinonasal malignancies. RESULTS: Only 2 of 296 (0.7%) patients primarily diagnosed with benign SNIP developed sinonasal cancer in a mean follow-up of 5.8 years. The most common non-sinonasal cancer sites were similar to those reported for the whole Finnish population. None of the patients presented with an HPV-associated non-sinonasal malignancy. The recurrence rate among patients who underwent attachment-oriented surgery was significantly lower compared to those operated on with other approaches (40.2% vs. 56.6%, p = 0.006). Dysplasia in SNIP was associated with a higher recurrence rate (p < 0.001). CONCLUSIONS: Malignant transformation of SNIP was rare. Patients with SNIP were not prone to HPV-associated non-sinonasal malignancies. Endoscopic resection and attachment-oriented surgery have become predominant approaches in the treatment of SNIP; meanwhile, the total number of SNIP recurrences has decreased. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:506-511, 2023.

Otorhinolaryngology Virtual Visits During the COVID-19 Pandemic: A 2-Year Follow-Up Study.

Objective: To clarify how successful virtual visits were in different age groups and subspecialties of otorhinolaryngology during the COVID-19 pandemic, with a 2-year follow-up. Methods: We examined the progress of treatment and need for face-to-face follow-ups in a retrospective setting. Case records of all the visits marked as virtual between March and June 2020 in Helsinki University Hospital Department of Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) were reviewed. Results: Among 865 virtual visits, 71.2% (n = 616) clearly advanced treatment, 53.8% (n = 465) needed no face-to-face follow-up, and only 9.0% (n = 78) were followed by an unplanned visit within 6 months. Statistically significant differences were detected among different subspecialties and age groups. Virtual visits achieved clear progress of treatment most frequently in laryngology (119/149 visits, 79.9%) and in head and neck surgery (69/83 visits, 83.1%). Laryngology patients required the least face-to-face follow-ups (n = 38 scheduled, 25.5% of laryngology visits). Most visits with clear progress involved 18-29-year-olds (n = 100, 80.0%) and they also required least face-to-face follow-ups (n = 39, 31.2%). During the 6-month to 2-year follow-up, 82 patients (9.6%) contacted our clinic directly for outpatient treatment, 28 patients (3.3%) called or visited the emergency department, and 37 patients (4.3%) were referred to the ORL-HNS clinic again for the same issue. Conclusion: Virtual visits were beneficial for treatment of otorhinolaryngology patients, and unplanned visits afterward were rare. Differences in effectiveness among subspecialties suggest that the utility of telemedicine applications can be enhanced by examining more closely which patient and ailment characteristics favor virtual visits.

The continuous laryngoscopy exercise test in severe or in difficult-to-treat asthma in adults: a systematic review.

OBJECTIVE: A systematic review was performed to determine if the continuous laryngoscopy exercise test (CLE) has been used in the diagnostics of exercise dyspnea in adults with asthma, and whether inducible laryngeal obstruction (ILO) is found in those with asthma or with severe or difficult-to-treat asthma. DATA SOURCES: We used Scopus and PubMed databases. The articles published up to 13 August 2019 were considered. STUDY SELECTIONS: We excluded manuscripts that did not contain information about adult patients with asthma. We included six studies from 59 search results in Scopus and none from the 17 search results in PubMed. RESULTS: The articles included 455 study individuals. Of these, 229 (50.3%) had diagnosed asthma or were treated with asthma medication. Altogether 31/229 (13.5%) subjects with diagnosis of asthma or previous asthma treatment had exercise-induced laryngeal obstruction (EILO) as comorbidity. The CLE test was performed on 229 patients with asthma. The method was used only for differential diagnosis of exercise-induced dyspnea to confirm EILO. At least 10/455 (2.2%) out of the 455 subjects experienced adverse events. CONCLUSIONS: This systematic review revealed that only a small proportion of patients with asthma had undergone the CLE test to assess exercise-induced dyspnea. None of the selected manuscripts reported severity of asthma. Whether CLE provides a valuable diagnostic tool for patients with severe or difficult-to-treat asthma cannot be determined according to this review.

Survival and Larynx Preservation in Early Glottic Cancer: A Randomized Trial Comparing Laser Surgery and Radiation Therapy.

PURPOSE: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study. METHODS AND MATERIALS: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records. RESULTS: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575). CONCLUSIONS: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar.

Exome sequencing reveals candidate mutations implicated in sinonasal carcinoma and malignant transformation of sinonasal inverted papilloma.

We explored somatic mutations in dysplastic sinonasal inverted papilloma (SNIP), SNIP with concomitant sinonasal squamous cell carcinoma (SNSCC), and SNSCC without preceding SNIP. Ten SNIP and SNSCC samples were analyzed with exome sequencing and tested for human papillomavirus. The identified mutations were compared to the most frequently mutated genes in head and neck squamous cell carcinoma (HNSCC) in the COSMIC database. Exome sequencing data were also analyzed for mutations not previously linked to SNSCC. Seven of the most commonly mutated genes in HNSCC and SNSCC in COSMIC harbored mutations in our data. In addition, we identified mutations in 23 genes that are likely to contribute to SNIP and SNSCC oncogenesis.

HPV-Positive Status Is an Independent Factor Associated With Sinonasal Inverted Papilloma Recurrence.

OBJECTIVES: The present study aimed to evaluate human papillomavirus (HPV) occurrence in sinonasal inverted papilloma (SNIP), and to assess factors associated with HPV positivity and SNIP recurrence. STUDY DESIGN: Prospective study. METHODS: We prospectively collected clinical data and fresh tissue specimens from 90 consecutive patients treated for SNIP at Helsinki University Hospital, between 2015 and 2019. Fourteen patients with recurrent SNIP underwent repeated tumor sampling. All tissue specimens were analyzed for the presence of HPV. Factors associated with SNIP recurrence and HPV positivity were assessed. RESULTS: Among 107 SNIP specimens, 14 (13.1%) were positive for low-risk HPV and 6 (5.6%) were positive for high-risk HPV. HPV positivity was associated with an increased risk of recurrence (P = .004). Smoking was significantly associated with HPV positivity in SNIP (P = .01), but a history of HPV-related diseases or patient sexual habits did not correlate with HPV positivity. The recurrence rate was lower among patients with SNIP that underwent an attachment-oriented resection, compared to patients treated without attachment-oriented resections (78.6% vs 25.8%, P < .001). CONCLUSIONS: The risk of SNIP recurrence was highly associated with 1) HPV positivity and 2) surgery without an attachment-oriented resection. Oncogenic HPV was rare in SNIP. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1714-1718, 2022.

Finnish Version of the Eating Assessment Tool (F-EAT-10): A Valid and Reliable Patient-reported Outcome Measure for Dysphagia Evaluation.

Our aim was to validate a Finnish version of the Eating Assessment Tool (F-EAT-10) for clinical use and to test its reliability and validity in a multicenter nationwide study. Normative data were acquired from 180 non-dysphagic participants (median age 57.0 years, 62.2% female). Dysphagia patients (n = 117, median age 69.7 years, 53.0% female) referred to fiberoptic endoscopic evaluation of swallowing (FEES) completed F-EAT-10 before the examination and after 2 weeks. Patients underwent the 100-ml water swallow test (WST) and FEES was evaluated using the following three scales: the Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and the Dysphagia Outcome Severity Scale. An operative cohort of 19 patients (median age 75.8 years, 57.9% female) underwent an endoscopic operation on Zenker's diverticulum, tight cricopharyngeal muscle diagnosed in videofluorography, or both. Patients completed the F-EAT-10 preoperatively and 3 months postoperatively. The cut-off score for controls was < 3 (sensitivity 94.0%, specificity 96.1%) suggesting that ≥ 3 is abnormal. Re-questionnaires for test-retest reliability analysis were available from 92 FEES patients and 123 controls. The intraclass correlation coefficient was excellent for the total F-EAT-10 score (0.93, 95% confidence interval 0.91-0.95). Pearson correlation coefficients were strong (p < 0.001) for each of the questions and the total score. Internal consistency as assessed by Cronbach's alpha was excellent (0.95). Some correlations between findings in FEES and 100-ml WST with F-EAT-10 were observed. The change in subjective symptoms of operative patients paralleled the change in F-EAT-10. F-EAT-10 is a reliable, valid, and symptom-specific patient-reported outcome measure for assessing dysphagia among Finnish speakers.

T1 glottic laryngeal cancer: the role of routine follow-up visits in detecting local recurrence.

PURPOSE: We assessed the treatment outcome and the benefits of routine follow-up visits in T1 glottic laryngeal squamous cell carcinoma (LSCC). METHODS: Medical records of patients diagnosed with stage T1 glottic LSCC (N = 303) in five Finnish university hospitals between 2003 and 2015 were reviewed. Moreover, data from the Finnish Cancer Registry and the Population Register Center were collected. RESULTS: Of all 38 recurrences, 26 (68%) were detected during a routine follow-up visit, and over half (21 of 38, 55%) presented without new symptoms. Primary treatment method (surgery vs. radiotherapy) was not connected with 5-year disease-specific survival (DSS) or laryngeal preservation rate. CONCLUSION: The majority of recurrences were detected on a routine follow-up visit, and local recurrences often presented without new symptoms. Routine post-treatment follow-up of T1 glottic LSCC seems beneficial. TRIAL REGISTRATION: Trial registration number and date of registration HUS/356/2017 11.12.2017.

Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection.

Human bocavirus 1 (HBoV1), a nonenveloped single-stranded DNA parvovirus, causes mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children. HBoV1 often persists in nasopharyngeal secretions for months, hampering diagnosis. It has also been shown to persist in pediatric palatine and adenoid tonsils, which suggests that lymphoid organs are reservoirs for virus spread; however, the tissue site and host cells remain unknown. Our aim was to determine, in healthy nonviremic children with preexisting HBoV1 immunity, the adenotonsillar persistence site(s), host cell types, and virus activity. We discovered that HBoV1 DNA persists in lymphoid germinal centers (GCs), but not in the corresponding tonsillar epithelium, and that the cell types harboring the virus are mainly naive, activated, and memory B cells and monocytes. Both viral DNA strands and both sides of the genome were detected, as well as infrequent mRNA. Moreover, we showed, in B-cell and monocyte cultures and ex vivo tonsillar B cells, that the cellular uptake of HBoV1 occurs via the Fc receptor (FcγRII) through antibody-dependent enhancement (ADE). This resulted in viral mRNA transcription, known to occur exclusively from double-stranded DNA in the nucleus, however, with no detectable productive replication. Confocal imaging with fluorescent virus-like particles moreover disclosed endocytosis. To which extent the active HBoV1 GC persistence has a role in chronic inflammation or B-cell maturation disturbances, and whether the virus can be reactivated, will be interesting topics for forthcoming studies.IMPORTANCE Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown. Our study provides new insights into tonsillar HBoV1 persistence. We observed HBoV1 persistence exclusively in germinal centers where immune maturation occurs, and the main host cells were B cells and monocytes. In cultured cell lines and primary tonsillar B cells, we showed the virus uptake to be significantly enhanced by HBoV1-specific antibodies, mediated by the cellular IgG receptor, leading to viral mRNA synthesis, but without detectable productive replication. Possible implications of such active viral persistence could be tonsillar inflammation, disturbances in immune maturation, reactivation, or cell death with release of virus DNA, explaining the long-lasting HBoV1 airway shedding.

Overstay and Readmission in Ear, Nose, and Throat Day Surgery-Factors Affecting Postanesthesia Course.

AIMS: Many procedures in ear, nose, and throat (ENT) day surgery are carried out under local anesthesia in Finland, whereas many other countries use general anesthesia. We investigated overstay and readmission rates in local and general anesthesia at Helsinki University Hospital. MATERIAL AND METHODS: We conducted a retrospective study on ENT (n = 1011) day surgery patients within a 3-month period using the hospital's surgery database to collect data pertaining to anesthesia, overstays, readmissions, and contacts within 30 days of surgery. OBJECTIVES: We examined the effect of American Society of Anesthesiologists (ASA) class, age, sex, type of procedure, and anesthesia type on overstay, contact, and readmission rates. RESULTS: A multivariable logistic regression model included ASA class, age, sex, type of procedure, and anesthesia (local vs general). Sex, age, and type of procedure had an effect on the outcomes of overstay, readmission, or contact. With general anesthesia, 3.2% (n = 23) had an overstay or readmission compared to 1.4% (n = 4) after local anesthesia. This was mainly explained by the number of study outcomes in tonsillar surgery that was performed only in general anesthesia. CONCLUSIONS: Day surgery could be done safely using local anesthesia, as the number of study outcomes was no greater than in general anesthesia. Sex, type of procedure, and age affected the rate of study outcomes, but ASA class and anesthesia form did not. Our overstay, contact, and readmission rates are on the same level, or lower, than in international studies.

European white paper: oropharyngeal dysphagia in head and neck cancer.

PURPOSE: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. METHODS: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. RESULTS: Twenty-four sections on HNC-specific OD topics. CONCLUSION: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.