Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils.

Lymphatic vessels form a critical component in the regulation of human health and disease. While their functional significance is increasingly being recognized, the comprehensive heterogeneity of lymphatics remains uncharacterized. Here, we report the profiling of 33,000 lymphatic endothelial cells (LECs) in human lymph nodes (LNs) by single-cell RNA sequencing. Unbiased clustering revealed six major types of human LECs. LECs lining the subcapsular sinus (SCS) of LNs abundantly expressed neutrophil chemoattractants, whereas LECs lining the medullary sinus (MS) expressed a C-type lectin CD209. Binding of a carbohydrate Lewis X (CD15) to CD209 mediated neutrophil binding to the MS. The neutrophil-selective homing by MS LECs may retain neutrophils in the LN medulla and allow lymph-borne pathogens to clear, preventing their spread through LNs in humans. Our study provides a comprehensive characterization of LEC heterogeneity and unveils a previously undefined role for medullary LECs in human immunity.

Psychosocial factors and patient and healthcare delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. PATIENTS AND METHODS: We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period. RESULTS: We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers. CONCLUSIONS: Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.

The effect of matrices on the gene expression profile of patient-derived head and neck carcinoma cells for in vitro therapy testing.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with a 5-year mortality rate of ~ 50%. New in vitro methods are needed for testing patients' cancer cell response to anti-cancer treatments. We aimed to investigate how the gene expression of fresh carcinoma tissue samples and freshly digested single cancer cells change after short-term cell culturing on plastic, Matrigel or Myogel. Additionally, we studied the effect of these changes on the cancer cells' response to anti-cancer treatments. MATERIALS/METHODS: Fresh tissue samples from HNSCC patients were obtained perioperatively and single cells were enzymatically isolated and cultured on either plastic, Matrigel or Myogel. We treated the cultured cells with cisplatin, cetuximab, and irradiation; and performed cell viability measurement. RNA was isolated from fresh tissue samples, freshly isolated single cells and cultured cells, and RNA sequencing transcriptome profiling and gene set enrichment analysis were performed. RESULTS: Cancer cells obtained from fresh tissue samples changed their gene expression regardless of the culturing conditions, which may be due to the enzymatic digestion of the tissue. Myogel was more effective than Matrigel at supporting the upregulation of pathways related to cancer cell proliferation and invasion. The impacts of anti-cancer treatments varied between culturing conditions. CONCLUSIONS: Our study showed the challenge of in vitro cancer drug testing using enzymatic cell digestion. The upregulation of many targeted pathways in the cultured cells may partially explain the common clinical failure of the targeted cancer drugs that pass the in vitro testing.

Clinical and prognostic significance of emergency MRI findings in neck infections.

OBJECTIVES: Due to its superior soft-tissue contrast and ability to delineate abscesses, MRI has high diagnostic accuracy in neck infections. Whether MRI findings can predict the clinical course in these patients is unknown. The purpose of this study was to determine the clinical and prognostic significance of various MRI findings in emergency patients with acute neck infections. MATERIALS AND METHODS: We retrospectively reviewed the 3-T MRI findings of 371 patients with acute neck infections from a 5-year period in a single tertiary emergency radiology department. We correlated various MRI findings, including retropharyngeal (RPE) and mediastinal edema (ME) and abscess diameter, to clinical findings and outcomes, such as the need for intensive care unit (ICU) treatment and length of hospital stay (LOS). RESULTS: A total of 201 out of 371 patients (54%) with neck infections showed evidence of RPE, and 81 out of 314 patients (26%) had ME. Both RPE (OR = 9.5, p < 0.001) and ME (OR = 5.3, p < 0.001) were more prevalent among the patients who required ICU treatment than among those who did not. In a multivariate analysis, C-reactive protein (CRP) levels, RPE, and maximal abscess diameter were independent predictors of the need for ICU treatment, and CRP, ME, and maximal abscess diameter were independent predictors of LOS. CONCLUSION: In patients with an acute neck infection that requires emergency imaging, RPE, ME, and abscess diameter, as shown by MRI, are significant predictors of a more severe illness. KEY POINTS: • Two hundred one out of 371 patients (54%) with neck infection showed evidence of retropharyngeal edema (RPE), and 81 out of 314 patients (26%) had mediastinal edema (ME). • Maximal abscess diameter, RPE, and C-reactive protein (CRP) were independent predictors of the need for intensive care unit (ICU) treatment, and maximal abscess diameter, ME, and CRP were independent predictors of length of hospital stay. • Prognostic significance of MRI findings was evident also while controlling for CRP values.

Magnetic resonance imaging findings in pediatric neck infections-a comparison with adult patients.

BACKGROUND: Differences in the functioning of the immune system and the anatomical proportions of the neck between children and adults lead to different manifestations of deep neck infections. Magnetic resonance imaging (MRI) may serve as an alternative to computed tomography (CT) as the primary imaging modality. OBJECTIVE: To study characteristic MRI findings and the diagnostic accuracy of MRI in pediatric deep neck infections. MATERIALS AND METHODS: We retrospectively studied a cohort of pediatric patients who underwent a neck 3-tesla MRI study over a five-year period. Inclusion criteria were: 1) emergency MRI findings indicating an infection, 2) infection as the final clinical diagnosis, 3) diagnostic image quality verified by the radiologist reading the study and 4) age under 18 years. Patient record data, including surgery reports, were compared with the MRI findings. RESULTS: Data of 45 children were included and analysed. Compared to adults, children had a higher incidence of retropharyngeal infection and lymphadenitis, and a lower incidence of peritonsillar/parapharyngeal infection. MRI showed evidence of an abscess in 34 children. Of these 34 patients, 24 underwent surgery, which confirmed an abscess in 21 but no abscess in three patients. In addition, three patients underwent surgery without MRI evidence of abscess, and an abscess was found in one of these cases. The measures of diagnostic accuracy among the children were sensitivity 0.96, specificity 0.77, positive predictive value 0.89, negative predictive value 0.91 and accuracy 0.89. Compared with adults, children had lower C-reactive protein, but a similar proportion of them had an abscess, and abscess size and rate of surgery were similar. CONCLUSION: Despite the differences in the infection foci, emergency MRI in children had equal diagnostic accuracy to that in adults.

Emergency neck MRI: feasibility and diagnostic accuracy in cases of neck infection.

BACKGROUND: Computed tomography (CT) has traditionally been the first-line imaging method in neck emergencies such as deep neck infections. Due to superior soft-tissue contrast, magnetic resonance imaging (MRI) may be an alternative to CT, also in emergency situations. PURPOSE: To characterize the use of routine MRI in neck emergencies, with an emphasis on clinical feasibility and diagnostic accuracy in cases of neck infection. MATERIAL AND METHODS: We conducted a retrospective cohort study of all primary neck MRI scans performed using a 3-T MRI device during a five-year follow-up period in a tertiary emergency radiology department. Imaging data were compared with final clinical diagnosis and surgical findings as reference standards. RESULTS: The search identified 461 primary neck MRI scans, of which 334 (72%) were performed on the basis of clinical suspicion of infection. Radiological evidence of infection was observed in 95% of these scans, and at least one abscess was detected in 229 cases (72% of confirmed infection). MRI had an overall technical success rate of 95% and had high positive predictive value for both infection (0.98) and detection of abscess (0.95). CONCLUSION: We found that emergency neck MRI can be successfully performed on most patients, and that MRI detects neck infection with a high accuracy. These results suggest that MRI may be an alternative to CT as the first or only imaging modality in neck emergencies.

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.

Deep neck space infections: an upward trend and changing characteristics.

PURPOSE: This study reviews our experience with deep neck space infections (DNIs) requiring surgical intervention, including cervical necrotizing fasciitis. The aim of the study was to identify predisposing and aggravating factors of the disease and recognize the possible factors that can lead to life-threatening complications and slow down the healing process. METHODS: We compare the results to previous data from 1985 to 2005 to find possible alterations and changing trends. The characteristics of four lethal cases are described. This retrospective analysis includes patient data from 2004 to 2015 in tertiary referral hospital and in total, 277 patients were found. RESULTS: Surgical drainage through a neck opening ± intraoral incision was made in 215 (77.6%) patients, an intraoral incision was only made in 62 patients (22.4%). ICU care was needed in 66 (23.8%) cases. Odontogenic etiology (44.8%) was the most common origin. The most common comorbidity was a psychiatric disorder and/or dementia and occurred in 55 (19.9%) patients. Patients with underlying illnesses were more likely to be admitted to the ICU (p = 0.020), required a longer ICU stay (p = 0.004) and repeated surgery (p = 0.009). Gas formation seemed to be predictive of a more severe course of infection. Early extraction of the odontogenic foci was related to a lower length of stay (LOS) (p = 0.039). CONCLUSION: The annual numbers have risen from 14 to 24 cases per year when compared to previous data. DNIs remain a cause of lethal complications; the mortality was 1.4% and overall complications occurred in 61 (22.0%) patients.

Expression of toll-like receptors in non-endemic nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. METHODS: In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. RESULTS: We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). CONCLUSIONS: TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.

Smartphone Otoscopy Performed by Parents.

Introduction:Implementation of pediatric telemedicine has been emphasized. We examined whether parents could perform smartphone otoscopy for the diagnosis of otitis media.Materials and Methods:We included children (6-35 months) attending day care with at least one episode of acute otitis media (AOM) within 90 days of the study entry. The timing for a teaching intervention was randomized. In the immediate teaching group, parents were taught smartphone otoscopy and cerumen was removed at the first visit. The delayed teaching group received the teaching intervention after 1 week's independent use. During the 60 study days, parents performed home examinations. The main outcome, the diagnostic quality of the tympanic membrane videos to determine healthy ear, otitis media with effusion (OME) and AOM diagnoses was measured with a structured video analysis independently by three physicians. Parents' experience was measured with a questionnaire.Results:AOM could be detected or excluded in 87% (609/699) of the videos during acute symptoms. After the teaching intervention, healthy ear, OME, or AOM could be diagnosed in 40% (521/1,293) of the videos. During the first week's intervention, one of the three diagnoses was attained in 33% (50/153) and in 12% (22/179) of the videos in the immediate and delayed teaching group, respectively (p < 0.001). The performance of the smartphone otoscopy examination was easy in 85% (35/41) of families.Discussion:After been taught, parents are able to perform smartphone otoscopy for the remote detection or exclusion of AOM.Conclusions:Future studies should assess the clinical usefulness of parent-performed smartphone otoscopy.

Outcome of nasopharyngeal carcinoma in Finland: A nationwide study.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in western countries and data on the outcome and histological presentation are scarce in nonendemic areas. We report here the outcome on all patients with NPC treated in Finland between 1990 and 2009. MATERIAL AND METHODS: The Finnish Cancer Registry database was used to identify the patients. Histopathological specimens and clinical records were reviewed to confirm the histological subtypes, prognostic factors, treatment techniques and outcome across different stage groups. RESULTS: Primary NPC was identified in 207 patients and 42 (20%) had keratinizing squamous cell carcinoma (SCC). The stage distribution was: I, 11%; II, 25%; III, 39%; IV, 25%. Of 191 patients treated with curative intent 85 (44%) received radiotherapy and 106 (56%) chemoradiotherapy. The five-year overall survival for all patients was 57% and for stages I-IV 87%, 69%, 55% and 31%, respectively. The five-year disease-specific and overall survival of all patients treated between 1990 and 1999 were 58% and 49%, and those between 2000 and 2009 66% and 63%, respectively. CONCLUSIONS: While survival rates are improving and comparable to other western countries they remain inferior to those of endemic countries. This may reflect the different biology of NPC in nonendemic areas, where keratinizing SCC is common.

Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland.

BACKGROUND: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period. METHODS: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent. RESULTS: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality. CONCLUSION: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients.

Potential role for inhibition of protein phosphatase 2A tumor suppressor in salivary gland malignancies.

The aetiology and pathogenesis of salivary gland malignancies remain unknown. To reveal novel molecular factors behind the development of salivary gland cancer, we performed gene expression analyses from Smgb-Tag mouse salivary gland samples. The overall purpose was to apply these results for clinical use to find new approaches for both possible therapeutic targets and more accurate diagnostic tools. Smgb-Tag mouse strain, in which salivary neoplasms arise through a dysplastic phase in submandibular glands, was investigated using genome-wide microarray expression analysis, ingenuity pathway analysis, RT-PCR, and immunohistochemistry. Thirty-eight human salivary gland adenoid cystic carcinoma samples were investigated using immunohistochemistry for validation purposes. Our genome-wide study showed that Ppp2r1b, a PP2A subunit encoding tumor suppressor gene, is underexpressed in submandibular gland tumors of Smgb-Tag mice. mTOR signaling pathway was significantly enriched and mTOR linked PP2A subunit gene B55 gamma was significantly underexpressed in the analyses. Furthermore, parallel immunohistochemical analysis of three PP2A inhibitors demonstrated that two PP2A inhibitors, CIP2A and SET, are highly expressed in both dysplastic and adenocarcinomatous tumors of the Smgb-Tag mice. In addition, all 38 investigated human salivary adenoid cystic carcinoma samples stained positively for CIP2A and most for SET. Finally, p-S6 staining showed activation of mTOR pathway in human adenoid cystic carcinoma samples. Our results suggest that PP2A inhibition either via PP2A subunit underexpression or PP2A inhibitor overexpression play an important role in the formation of salivary gland malignancy, potentially due to mTOR signaling activation.

Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models.

Malignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 - 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer. METHODS: Patient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations. RESULTS: The different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies. CONCLUSION: The results demonstrate the importance of understanding the differential biology and the molecular features associated with the different subtypes of sinonasal cancers. Patient-derived ex vivo tumor models can be a powerful tool for investigating these rare cancers and prioritizing targeted therapeutic strategies for future clinical development and personalized medicine.

MRI of acute neck infections: evidence summary and pictorial review.

Infection of the deep neck spaces is a life-threatening acute illness that requires prompt diagnosis and treatment. Magnetic resonance imaging (MRI) offers unsurpassed soft tissue discrimination and is therefore well suited for imaging neck infections. Recently, the feasibility, diagnostic accuracy, and clinical significance of this method have been documented in patients with acute neck infections. This review article summarizes the scientific evidence, provides a practical guide to image acquisition and interpretation, reviews the most common imaging findings, and discusses some difficult diagnoses and pitfalls in acute neck infections, to help both radiologists and clinicians in managing these critically ill patients.

MRI of odontogenic maxillofacial infections: diagnostic accuracy and reliability.

OBJECTIVES: To determine the diagnostic accuracy of emergency magnetic resonance imaging (MRI) in odontogenic maxillofacial infections, the clinical and surgical significance of MRI findings, and whether MRI can identify the tooth responsible for the infection. METHODS: A retrospective cohort study reviewed 106 emergency neck MRI scans of patients with neck infections of odontogenic origin. The diagnostic accuracy of MRI in identifying abscesses was studied relative to surgical findings. Correlations were analyzed between various MRI findings and clinical results and outcomes, such as the surgical approach (intraoral vs. extraoral). The ability of MRI findings to predict the causative tooth was assessed in a blinded multi-reader setting. RESULTS: Of the 106 patients with odontogenic infections, 77 (73%) had one or more abscesses. Imaging showed a sensitivity, specificity, and accuracy of 0.95, 0.84, and 0.92, respectively, for MRI diagnosis of an odontogenic abscess. Among the imaging findings, mediastinal edema was the strongest predictor of extraoral surgery. MRI showed bone marrow edema in the majority of patients, and multi-reader assessment showed good reliability. MRI was also able to predict the causative tooth accurately. CONCLUSIONS: Emergency neck MRI can accurately detect odontogenic abscesses and reliably point to the causative tooth. These results can increase the utility and reliance on emergency MRI in clinical decision-making.

Timing and frequency of oropharyngeal squamous cell carcinoma recurrences after treatment with curative intent.

BACKGROUND: The increasing number of patients under surveillance after treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC) places a great burden on healthcare providers. AIMS/OBJECTIVES: The aim of this study was to explore OPSCC recurrences in a long follow-up period: their site, frequency and timepoint after primary treatment, treatment and outcome. The secondary aim was to investigate if the recurrences are diagnosed on routine follow-up visits, and if the p16 status will have an effect on the pattern of recurrences. MATERIAL AND METHODS: We analyzed recurrences within a 10-year follow-up period after completed curatively intended treatment among OPSCC patients in Finland treated between 2000 and 2009. Patient-, tumor-, treatment- and follow-up -related parameters were investigated. RESULTS: Out of 495 patients with no residual tumor during the first six months, 71 (14%) were diagnosed with a recurrence, of which 47 were locoregional and 28 were treated with curative intent. Of the recurrences, 86% were diagnosed during the first 36 months after primary treatment. Only ten recurrences appeared after 36 months. The median OS after recurrence was 10.9 months. CONCLUSIONS AND SIGNIFICANCE: Routine follow-up longer than three years after treatment seems not to be effective in terms of detecting OPSCC recurrences.

Patient and health care delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Head and neck cancers (HNCs) are often diagnosed at an advanced stage. We investigated the lengths and factors associated with patient, primary health care (PHC), and specialist care (SC) delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. METHODS: A nationwide prospective questionnaire-based study (n = 203) with the 3-year long data collection period. RESULTS: The median patient, PHC and SC delays were 58, 13, and 43 days, respectively. Lower level of education, heavy alcohol use, hoarseness, difficulties breathing, and eventual palliative treatment associated with a longer patient delay. A lump on the neck or facial swelling associated with a shorter PHC delay. Conversely, if symptoms were treated as an infection, PHC delay was longer. The treatment modality and tumor site affected SC delay. CONCLUSIONS: Patient delay stands as the most notable factor contributing to delays before treatment. HNC symptom awareness thus remains especially important among HNC risk groups.

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.

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.