Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood
. Here we show that human papillomavirus (HPV)-specific B cell ...responses are detectable in samples from patients with HPV-positive head and neck cancers, with active production of HPV-specific IgG antibodies in situ. HPV-specific antibody secreting cells (ASCs) were present in the tumour microenvironment, with minimal bystander recruitment of influenza-specific cells, suggesting a localized and antigen-specific ASC response. HPV-specific ASC responses correlated with titres of plasma IgG and were directed against the HPV proteins E2, E6 and E7, with the most dominant response against E2. Using intratumoral B cells and plasma cells, we generated several HPV-specific human monoclonal antibodies, which exhibited a high degree of somatic hypermutation, consistent with chronic antigen exposure. Single-cell RNA sequencing analyses detected activated B cells, germinal centre B cells and ASCs within the tumour microenvironment. Compared with the tumour parenchyma, B cells and ASCs were preferentially localized in the tumour stroma, with well-formed clusters of activated B cells indicating ongoing germinal centre reactions. Overall, we show that antigen-specific activated and germinal centre B cells as well as plasma cells can be found in the tumour microenvironment. Our findings provide a better understanding of humoral immune responses in human cancer and suggest that tumour-infiltrating B cells could be harnessed for the development of therapeutic agents.
T cells are important in tumour immunity but a better understanding is needed of the differentiation of antigen-specific T cells in human cancer
. Here we studied CD8 T cells in patients with human ...papillomavirus (HPV)-positive head and neck cancer and identified several epitopes derived from HPV E2, E5 and E6 proteins that allowed us to analyse virus-specific CD8 T cells using major histocompatibility complex (MHC) class I tetramers. HPV-specific CD8 T cells expressed PD-1 and were detectable in the tumour at levels that ranged from 0.1% to 10% of tumour-infiltrating CD8 T lymphocytes (TILs) for a given epitope. Single-cell RNA-sequencing analyses of tetramer-sorted HPV-specific PD-1
CD8 TILs revealed three transcriptionally distinct subsets. One subset expressed TCF7 and other genes associated with PD-1
stem-like CD8 T cells that are critical for maintaining T cell responses in conditions of antigen persistence. The second subset expressed more effector molecules, representing a transitory cell population, and the third subset was characterized by a terminally differentiated gene signature. T cell receptor clonotypes were shared between the three subsets and pseudotime analysis suggested a hypothetical differentiation trajectory from stem-like to transitory to terminally differentiated cells. More notably, HPV-specific PD-1
TCF-1
stem-like TILs proliferated and differentiated into more effector-like cells after in vitro stimulation with the cognate HPV peptide, whereas the more terminally differentiated cells did not proliferate. The presence of functional HPV-specific PD-1
TCF-1
CD45RO
stem-like CD8 T cells with proliferative capacity shows that the cellular machinery to respond to PD-1 blockade exists in HPV-positive head and neck cancer, supporting the further investigation of PD-1 targeted therapies in this malignancy. Furthermore, HPV therapeutic vaccination efforts have focused on E6 and E7 proteins; our results suggest that E2 and E5 should also be considered for inclusion as vaccine antigens to elicit tumour-reactive CD8 T cell responses of maximal breadth.
A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of ...view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90%±8%, sensitivity of 89%±9%, and specificity of 91%±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94%±6%, sensitivity of 94%±6%, and specificity of 95%±6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery.
Recently published and ongoing trials are helping to define the role of transoral robotic surgery for oropharyngeal cancer. Evidence to date supports the use of surgery as a valuable tool in the ...multidisciplinary deescalation of low-risk human papillomavirus-related oropharyngeal squamous cell carcinoma.
Retrospective study.
To analyze the results and effectiveness of percutaneous screws (PS) with midline microscopic transforaminal decompression (MTFD) technique in reducing adult stiff lytic ...high-grade spondylolisthesis (HGSL) and compare it with the conventional technique.
Pedicle screw cannulation and segmental kyphosis negotiation are surgical challenges in HGSL. Open reduction is the preferred approach. PS have the advantage of optimized trajectory and minimized soft tissue exposure. The role of minimally invasive surgery in HGSL remains unknown. We propose a hybrid technique combining PS with MTFD for lytic HGSL.
This study included 25 patients with adult lytic HGSL (Meyerding grade III and IV) operated using a hybrid technique from 2012 to 2015. Data were compared with retrospective data on conventional open reduction (n=23) operated from 2000 to 2015. The minimum follow-up was 5 years. Clinical outcomes were assessed using the Visual Analog Scale (VAS) score and modified Oswestry Disability Index (m-ODI). The spinopelvic and perioperative parameters were recorded. The inter-body fusion and adjacent segment degeneration (ASD) were assessed on radiographs at the final follow-up.
The average age in the MTFD and open groups was 45.84±12.70 years (nine males and 16 females) and 49.26±13.33 years (eight males and 15 females), respectively. Further, 22 and three patients in the MTFD group and 19 and four in the open group had grade III and IV listhesis, respectively. The MTFD group demonstrated less operative time, blood loss, and hospital stays than the open group. Significant improvements were observed in VAS and m-ODI in subsequent follow-ups in both groups. The MTFD group fared better at 3 months but outcomes were comparable at the final follow-up. Both techniques were equally effective in restoring spinopelvic parameters. The incidence of ASD is comparable.
The technique was proven effective in reducing HGSL. The long-term clinical and radiological outcomes were favorable and comparable with the conventional approach.
Tributyltin (TBT), an organotin endocrine-disrupting substance, is recognized as one of the important toxic environmental pollutants. The present study was carried out to investigate the toxic ...effects of TBT on behavior and the ovary of adult zebrafish with a focus on oxidative stress markers and oocyte maturation. Adult zebrafish were exposed to three different concentrations (125, 250, and 500 ng/L of water) of TBT for 28 days. TBT exposure produced a concentration-dependent negative effect on the body weight and behavior (anxiety-like symptoms) of adult zebrafish. Alterations in the activity of superoxide dismutase (SOD) and catalase (CAT), the total antioxidant capacity of ovarian tissue by the highest exposure level of TBT resulted in lipid peroxidation as indicated by increased malondialdehyde (MDA) level. The numbers of early-vitellogenic oocytes were significantly increased in zebrafish exposed to TBT as low as 125 ng/L. However, the numbers and size of fully-grown (mature) oocytes were significantly reduced in the highest exposure group only. Correlation between the MDA level and pre-vitellogenic oocytes in the 500 ng/L group indicated that lipid peroxidation prevented the maturation of pre-vitellogenic oocytes. TBT exposure produced significant histological changes in the ovary as evidenced by disturbed maturation of oocytes. In conclusion, TBT adversely affected the maturation of oocytes in zebrafish ovary through oxidative stress-mediated mechanisms.
•Tributyltin (TBT) exposure negatively affected the body weight and behavior of adult zebrafish.•TBT exposure caused oxidative stress on the ovary.•TBT-exposed fish showed histological changes in the ovary.•TBT prevented the maturation of pre-vitellogenic oocytes and reduced the number and size of fully-grown oocytes.
This study intends to investigate the feasibility of using hyperspectral imaging (HSI) to detect and delineate cancers in fresh, surgical specimens of patients with head and neck cancers.
A clinical ...study was conducted in order to collect and image fresh, surgical specimens from patients (
= 36) with head and neck cancers undergoing surgical resection. A set of machine-learning tools were developed to quantify hyperspectral images of the resected tissue in order to detect and delineate cancerous regions which were validated by histopathologic diagnosis. More than two million reflectance spectral signatures were obtained by HSI and analyzed using machine-learning methods. The detection results of HSI were compared with autofluorescence imaging and fluorescence imaging of two vital-dyes of the same specimens.
Quantitative HSI differentiated cancerous tissue from normal tissue in
surgical specimens with a sensitivity and specificity of 91% and 91%, respectively, and which was more accurate than autofluorescence imaging (
< 0.05) or fluorescence imaging of 2-NBDG (
< 0.05) and proflavine (
< 0.05). The proposed quantification tools also generated cancer probability maps with the tumor border demarcated and which could provide real-time guidance for surgeons regarding optimal tumor resection.
This study highlights the feasibility of using quantitative HSI as a diagnostic tool to delineate the cancer boundaries in surgical specimens, and which could be translated into the clinic application with the hope of improving clinical outcomes in the future.
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Background
The prognostic relevance of human papillomavirus (HPV) status in patients with nonoropharyngeal (OPX) squamous cell cancer (SCC) of the head and neck is controversial. In the current ...study, the authors evaluated the impact of high‐risk HPV status on overall survival (OS) in patients with non‐OPX SCC using a large database approach.
Methods
The National Cancer Data Base was queried to identify patients diagnosed from 2004 through 2014 with SCC of the OPX, hypopharynx (HPX), larynx, and oral cavity (OC) with known HPV status. Survival was estimated using Kaplan‐Meier methods; distributions were compared using log‐rank tests. Propensity score–matching and inverse probability of treatment weighing (IPTW) methods were used; cohorts were matched based on age, sex, Charlson‐Deyo score, clinical American Joint Committee on Cancer (AJCC) group stage, treatments received, and anatomic subsite. Propensity analyses were stratified by group stage of disease.
Results
A total of 24,740 patients diagnosed from 2010 through 2013 were analyzed: 1085 patients with HPX, 4804 with laryngeal, 4,018 with OC, and 14,833 with OPX SCC. The percentages of HPV‐positive cases by disease site were 17.7% for HPX, 11% for larynx, 10.6% for OC, and 62.9% for OPX. HPV status was found to be prognostic in multiple unadjusted and propensity‐adjusted non‐OPX populations. HPV positivity was associated with superior OS in patients with HPX SCC with a hazard ratio (HR) of 0.61 (P < .001 by IPTW), in patients with AJCC stage III to IVB laryngeal SCC (HR, 0.79; P = .019 by IPTW), and in patients with AJCC stage III to IVB OC SCC (HR, 0.78; P = .03 by IPTW).
Conclusions
Positive high‐risk HPV status appears to be associated with longer OS in multiple populations of patients with non‐OPX head and neck disease (HPX, locally advanced larynx, and OC). If prospectively validated, these findings have implications for risk stratification.
In the current study, the authors evaluate the prognostic relevance of high‐risk human papillomavirus status in patients with nonoropharyngeal head and neck squamous cell carcinomas using a large database approach given conflicting prior reports. Human papillomavirus positivity appears to be associated with superior overall survival in 9907 patients with hypopharyngeal and American Joint Committee on Cancer stage III to stage IVB squamous cell carcinomas of the oral cavity and larynx using propensity‐matched and propensity‐weighed methods.
Objectives/Hypothesis:
Preferred treatment of oral/plunging ranulas remains controversial. We present our experience with ranulas at the University of North Carolina (UNC) and review the literature.
...Methods:
Retrospective review. From 1990 to 2007, 16 oral ranulas and 10 plunging ranulas were treated at UNC. Combining the UNC series with the literature identified 864 cases for review. An online survey was conducted to identify current treatment patterns.
Results:
In the UNC series, procedures for oral ranulas varied from ranula excision (50%), combined ranula and sublingual gland excision (44%), excision of the ranula along with the sublingual gland and submandibular gland (6%). A cervical approach was used in nine plunging ranula cases. One case was treated transorally with sublingual gland removal and evacuation of the ranula. Otherwise, the plunging ranula was removed along with the sublingual gland (20%), submandibular gland (50%), or both (20%). One hundred fifty‐one complications were identified from the literature. Recurrence was considered a complication and was most prevalent (63%). Nonrecurrent complications included tongue hypesthesia (26%), bleeding/hematoma (7%), postoperative infection (3%), and Wharton's duct injury (1%). Sublingual gland excision yielded the fewest complications (3%). Procedures and associated complication rates were: transoral excision of sublingual gland (3%); transoral excision of sublingual gland and ranula (12%); marsupialization (24%); transcervical excision of sublingual gland, submandibular gland, and ranula (33%); OK‐432 (49%); and aspiration (82%).
Conclusions:
Based on our review, definitive treatment yielding lowest recurrence and complication rates for all ranulas is transoral excision of the ipsilateral sublingual gland with ranula evacuation. Laryngoscope, 2009
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