| 1. |
- Abu Hamdeh, Sami, et al.
(författare)
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Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury
- 2018
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Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 28:4, s. 451-462
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Tidskriftsartikel (refereegranskat)abstract
- Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n = 12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n = 5), to post-mortem tissue of neurologically intact (NI) subjects (n = 4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n = 4). The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to NI and iNPH controls (P < 0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n = 4) had increased levels of Aβ oligomers/protofibrils (P < 0.05) and of both N-terminally intact and truncated Aβ42 (P < 0.05) compared to APOE ε3/4-negative TBI patients (n = 8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers. We conclude that soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI.
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| 2. |
- Afsun, Donya, et al.
(författare)
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Effects of a film-based parental intervention on vocabulary development in toddlers aged 18-21 months
- 2011
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Ingår i: Proceedings from Fonetik 2011. - Stockholm. ; , s. 105-108
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- SPRINT is a language intervention project aimed to study the outcome of a parental home training program on children’s language development and future reading and writing skills. This study, which derives data from the SPRINT project, intended to examine the possible effects of a parental-based film intervention. It was conducted on toddlers aged 18-21 months from the Stockholm area with at least one parent who has Swedish as a first language. Parents of 78 children participated in the study and filled in 3 SECDI-w&s questionnaires rating their children's productive vocabulary. Children were randomized to either the intervention or the control group. Results indicated that the interventiongroup demonstrated significantly higher scores over time, F (2,78) = 5,192, p < .007. In the light of previous research it is concluded that this intervention contributes to an increase in productive vocabulary. However, the scores of the intervention group did not exceed the average range for Swedish children in the same age span. Furthermore the possible impact of parental education and thepresence of siblings on productive vocabulary was discussed.
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| 3. |
- Andersson, Ida, et al.
(författare)
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Productive vocabulary size development in children aged 18-24 months - gender differences
- 2011
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Ingår i: Proceedings from Fonetik 2011. - Stockholm. ; , s. 109-112
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Several studies have shown slight differences in language skills between genders, favouring females. In order to investigate gender differences in speech production for Swedish children, the productive vocabulary size of 295 children, aged 18-24 months, was measured by the validated instrument SECDI-2. The size of the productive vocabulary was found to grow rapidly during this age. Significant gender differences were found at 21 and 24 months, but not at 18 months. The girls’ mean scores were higher.
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| 4. |
- Bark, Rusana, et al.
(författare)
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Sentinel node-assisted neck dissection in advanced oral squamous cell carcinoma - A new protocol for staging and treatment
- 2023
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Ingår i: Cancer Medicine. - : Wiley-Blackwell. - 2045-7634. ; 12:11, s. 12524-12534
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early-stage T1-T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN-technique in advanced OSCC (T3-T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC.Materials and Methods: In total, 85 patients with T1-T4 OSCC diagnosed 2019-2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT-CT to include all SNs.Results: Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early-stage disease. T3-T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1-T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3-T4 versus T1-T2 (p = 0.0398).Conclusion: SN-assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.
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| 5. |
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| 6. |
- de Flon, Caroline Haglund, et al.
(författare)
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High Levels of FGF11 Correlate with Poor Survival in Patients with Human Papillomavirus (HPV)-Positive Oropharyngeal Squamous Cell Carcinoma
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- To better identify patients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) and a poor prognosis after treatment, we compared the gene expression in tumours from patients with a poor or a favourable prognosis in a case-control setting. The results were thereafter validated in two separate cohorts on the RNA and protein levels. High RNA or protein expression of FGF11 was correlated with a poor patient survival in all three cohorts. Taken together, the data imply that FGF11 may play a major role in the prognosis of patients and that FGF11 could serve as a prognostic marker in HPV-positive oropharyngeal cancer.Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favourable prognosis. It has therefore been suggested that treatment should be individualized and separated by HPV status. However, additional prognostic markers are still needed before treatment can be individualized for this patient group. For this purpose, all patients diagnosed with HPV and p16-positive OPSCC in Stockholm 2000-2009, identified as having a partial/nonresponse to treatment and having viable tumour cells in their neck specimen with material available were categorized as cases. These were matched to controls (complete responders), and the differences in the gene expression were analysed. Two separate verification cohorts were identified including patients with HPV- and p16-positive OPSCC, and the data from the case-control study were verified by qPCR and immunohistochemistry (IHC) in the respective cohorts. A separation of gene expression in correlation with survival was observed in the case-control study, and FGF11 expression was identified as significantly differently expressed between the two groups. The prognostic role of FGF11 was validated in the two cohorts on the RNA and protein levels, respectively. Taken together, our findings suggest that FGF11 may indicate a poor prognosis in HPV-positive OPSCC and may serve as a prognostic biomarker.
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| 7. |
- Eeg-Olofsson, Orvar, et al.
(författare)
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Duchenne muscular dystrophy and idiopathic hyperCKemia in the same family
- 2008
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Ingår i: European journal of paediatric neurology. - : Elsevier BV. - 1090-3798 .- 1532-2130. ; 12:5, s. 404-7
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Tidskriftsartikel (refereegranskat)abstract
- Familial hyperCKemia is a rare condition, and a combination with Duchenne muscular dystrophy (DMD) is extremely rare. A boy showed muscle weakness from the age of 10 months and presented typical signs of DMD at the age of 18 months. The diagnosis was supported by markedly elevated serum creatine kinase (CK) value as well as by neurophysiological and muscle biopsy findings at the age of 23 months. The diagnosis was confirmed by identification of a stop codon in exon 43 (p.2095Arg>X) of the dystrophin gene. Interestingly, the father and his near relatives had increased serum CK values without any clinical symptoms or signs, nor a defect in caveolin-3 gene. We suggest that the occurrence of familial hyperCKemia may have triggered the early onset of symptoms in our patient.
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| 8. |
- Erickson, A, et al.
(författare)
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Spatially resolved clonal copy number alterations in benign and malignant tissue
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 608:7922, s. 360-
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Tidskriftsartikel (refereegranskat)abstract
- Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 9. |
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| 10. |
- Erickson, Andrew, et al.
(författare)
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The spatial landscape of clonal somatic mutations in benign and malignant tissue
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 11. |
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| 12. |
- Gallus, Roberto, et al.
(författare)
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Accuracy of p16 IHC in Classifying HPV-Driven OPSCC in Different Populations
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- High-risk human papillomavirus (HPV) infection is a defined etiopathogenetic factor in oropharyngeal carcinogenesis with a clear prognostic value. The P16 IHC (immunohistochemistry) is a widely accepted marker for HPV-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC); in the present paper, we discuss its reliability as a standalone marker in different populations. The literature suggests that rates of p16 IHC false positive results are inversely correlated with the prevalence of HPV-driven carcinogenesis in a population. We propose a formula that can calculate such a false positive rate while knowing the real prevalence of HPV-driven OPSCCs in a given population. As it has been demonstrated that p16 positive/HPV negative cases (i.e., false positives at p16 IHC) have the same prognosis as p16 negative OPSCC, we conclude that despite the valuable prognostic value of p16 IHC, relying only on a p16 IHC positive result to recommend treatment de-intensification could be risky. For this aim, confirmation with an HPV nucleic acid detection system, especially in areas with a low prevalence of HPV-related OPSCCs, should be pursued.Simple summaryp16 IHC is the HPV detection method suggested by the current version of the TNM (AJCC 8th edition) for oropharyngeal squamocellular carcinoma. However, its reliability has been extensively discussed, and its applicability in every context, especially the enrollment of patients in de-intensification protocols, is debatable. Here, we discuss its limits, especially in populations with a low prevalence of HPV-driven oropharyngeal squamocellular carcinoma, and suggest the possible actions to be taken to overcome such limitations.
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| 13. |
- Gärdlund, Linda, et al.
(författare)
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The use of polyelectrolyte complexes (PEC) as strength additives for different pulps used for production of fine paper
- 2007
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Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 22:2, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- In this work the application of polyelectrolyte complexes (PEC) to different pulps, to improve the strength of papers produced from them, is compared with conventional pulp beating. The pulps chosen for the investigation were a fully bleached chemical hardwood pulp (HBK), a fully bleached chemical softwood pulp (SBK), and a peroxide-bleached chemithermomechanical pulp (BCTMP). The polyelectrolytes used were a polyamideamine epichlorohydrine condensate (PAE), traditionally used as a wet-strength additive, and carboxymethylcellulose. Since the prepared complexes had an anionic charge, they could only be used after fibre pre-treatment with the cationic PAE. Results indicate that the addition of 2% PAE and 2% PEC can improve all the measured tensile strength properties of the sheets as much as is commonly achieved by mechanically beating the pulps. In fact, for the chemical pulps, PEC addition at the chosen level produced better results than did traditional beating, since the improved tensile index and tensile energy absorption could be achieved without any significant deterioration in the light scattering coefficient of the papers produced. However, with the BCTMP a significant decrease in light scattering could be detected, especially following the addition of PEC. Adding the chemicals (especially the PEC) increased the sheet density and this together with the increase in the tensile stiffness, following chemical addition, resulted in a constant bending stiffness of the sheets. However, based on the results it can be suggested that a combination of unbeaten HBK and BCTMP treated with PAE and PEC can be used to produce a strong paper with a high bending stiffness.
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| 14. |
- Johansson, Ann-Christine, et al.
(författare)
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Characterization of pyrolysis products produced from different Nordic biomass types in a cyclone pilot plant
- 2016
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Ingår i: Fuel processing technology. - : Elsevier. - 0378-3820 .- 1873-7188. ; 146, s. 9-19
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Tidskriftsartikel (refereegranskat)abstract
- Pyrolysis is a promising thermochemical technology for converting biomass to energy, chemicals and/or fuels. The objective of the present paper was to characterize fast pyrolysis products and to study pyrolysis oil fractionation. The products were obtained from different Nordic forest and agricultural feedstocks in a pilot scale cyclone pyrolysis plant at three different reactor temperatures. The results show that the main elements (C, H and O) and chemical compositions of the products produced from stem wood, willow, forest residue and reed canary grass are in general terms rather similar, while the products obtained from bark differ to some extent. The oil produced from bark had a higher H/Ceff ratio and heating value which can be correlated to a higher amount of pyrolytic lignin and extractives when compared with oils produced from the other feedstocks. Regardless of the original feedstock, the composition of the different pyrolysis oil fractions (condensed and aerosol) differs significantly from each other. However this opens up the possibility to use specifically selected fractions in targeted applications. An increased reactor temperature generally results in a higher amount of water and water insoluble material, primarily as small lignin derived oligomers, in the produced oil.
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| 15. |
- Jonsson, Eva Lindell, 1982-
(författare)
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Biomolecular markers in head and neck cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck cancer is a heterogeneous group of tumours, of which certain subgroups such as cancer of the mobile tongue frequently are associated with a relatively poor prognosis due to the high risk of regional failure and mortality rates that haven’t improved in a significant way over the last 3 decades, despite advancements in both diagnostics and treatment.Today we lack means to assess the biological aggressiveness of each individual tumour, which varies largely. Treatment comprises of surgery with additional radiotherapy and medical therapies in more advanced tumours.The focus in this thesis is on molecular biomarker expression in head and neck cancer and especially in association with radiotherapy. Increased knowledge paves the way to a more individualized cancer treatment aiming for better outcome and less overtreatment and sequelae.The aims of this thesis was:To map the effects of radiotherapy in both tumour and adjacent tissue for the possible markers hyaluronan, EGFR and mast cells.To investigate whether the expression of hyaluronan in the epithelium and connective tissue stroma and EGFR in the tumour correlates with the risk for developing cervical metastasis in N0 patients, and to find out whether the 3-year tumour-specific survival rates correlates with the expression of HA in the epithelium and EGFR in the tumour.To establish an animal model for radiation-induced mucositis and to use that model to examine the pattern of invading inflammatory cells.To investigate whether the expression of podoplanin in tongue cancer correlates with the risk for cervical metastasis and to determine whether the total amount of lymph vessels in the diagnostic biopsy has any impact on the clinical outcome.To investigate the differences in the metabolome of tongue cancer cell lines with different radiosensitivity.The most important findings of this thesis were:The expression of EGFR and hyaluronan hade the same pattern of expression in both tumour and adjacent tissues before radiotherapy. The expression of EGFR was increased in the epithelium of the adjacent tissue close to the tumour after radiotherapy.The intensity of the staining of hyaluronan was correlated to the 3-year survival rates in patients with tongue cancer.An experimental model for radiation-induced oral mucositis in rat was established and in this model a temporal pattern of macrophage invasion with two different subtypes of macrophages was found.There were no correlation between the expression of podoplanin in the tumour tissue and the cervical metastasis rate in patients with tongue cancer, but the younger patients were more likely to have a higher expression of podoplanin in their tumour than elder patients.Tongue cancer cell lines with different radiosensitivity respond to irradiation with different patterns of metabolic expressions.
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| 16. |
- Landin, David, et al.
(författare)
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Immune related proteins and tumor infiltratingCD8+ lymphocytes in hypopharyngeal cancer in relation to human papillomavirus (HPV) and clinical outcome
- 2020
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Ingår i: Head and Neck. - : John Wiley & Sons. - 1043-3074 .- 1097-0347. ; 42:11, s. 3206-3217
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypopharyngeal cancer (HPSCC) shows a poor clinical outcome, while HPSCC, caused by human papillomavirus (HPV), presents a better outcome. Here, HPCC, immune proteins, and tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were evaluated in relation to HPV and outcome.Methods: Fresh frozen tissue from four HPV-positive HPSCC, 39 HPV-negative HPSCC, and normal samples were analyzed for protein expression by the Proseek immuno-oncology immunoassay. CD8+ TIL numbers evaluated by immunohistochemistry on 144 formalin-fixed biopsies were analyzed in relation to clinical outcome.Results: Proteins differing between HPV-positive and negative HPSCC included CD8A, PD-L1, Fas ligand, and chemokines. High CD8+ TIL numbers were correlated to improve clinical outcome in HPV-negative HPSCC.Conclusions: High expression of immune proteins in HPV-positive HPSCC may explain the better clinical outcome. CD8+ TILs are of relevance for outcome of HPV-negative HPSCC, while tumors with high immune activity but poor patient survival suggest a role for immune therapy.
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| 17. |
- Landin, David, et al.
(författare)
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Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16
- 2022
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16(INK4a) undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.
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| 18. |
- Marklund, Linda, 2011-
(författare)
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Ett brott - två processer : Medling vid brott och unga lagöverträdare i straffprocessen
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A crime and the two processes meeting the young offender is the core of this work. The aim has been to analyze the areas that seem problematic when mediation (restorative justice) and criminal procedure for young people have to interact. The main questions have been: · Which restorative process is used and what is its purpose? · What is the legal status of restorative justice/mediation? · What are the roles of the parties and of the mediator? The method used in this work has been a traditional legal method in combination with participant observation. Additionally, a case study of mediation has been used to illustrate the mediation process. The restorative justice process that is used in Sweden is the victim offender mediation and it is organized as a semi independent service. According to the Mediation Act, the purpose of the process is: a) for the offender to gain further insight on the impact of the crime, and b) for victims to have the opportunity to process their experiences and resolve potential issues. Mediation has the ability to provide the parties to a conflict with closure and thus the possibility to move forward. As such, mediation serves as a complement as well as an alternative to the legal process. The results show that the Swedish mediation service needs more explicit support and education at all levels, and that there is a need for more well-defined rules and guidelines. The legal rules and guidelines must, however, not impede on the uniqueness of the mediation process; the voluntaries, the confidentiality, the equality, the reconciliation and the facilitation. If it does, the mediation process will end up as a pale copy of the law, and the mediators the new professionals who steal the conflict from those who really own it.
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| 19. |
- Marklund, Linda, 1975-
(författare)
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Skolmedling i teori och praktik
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to answer the questions; what and were does peer mediation fit into the theoretical and practical frameworks of mediation? How does peer mediation fit into the retributive legal system as it stands today? What problems can arise with the use of peer mediation, its organizations and with the use of adolescent peer mediators, in a legal perspective? When it comes to the question of where peer mediation has its theoretical framework the hypothesis in this thesis are that peer mediation, with respect to the practical framework, is a hybrid of the settlement driven mediation and the transformative mediation. The theoretical framework comes from the philosophy of restorative justice (RJ), primarily the victim-offender mediation in the sense that if peer mediation per se is not enough it has to bee a whole school approach for it to work. In RJ, the community is as important as the primarily parties, the offender and the offended. In school conflicts, the community is the whole school, and as such it has to bee the whole school that is involved in the conflict management program. The method used in this thesis is the traditional method of jurisprudence combined with two case studies. The first case study is the "Peer mediations Project" that in fact was the starting point for the research. The aim with this case study is too show how peer mediation can work in Sweden, both on an organizational and a practical level. In doing so it also highlights which legal questions that is relevant for this thesis. The second case study is the "Spice conflict". This case study aims to make researcher go deeper in the legal issues as well as to illuminate a school conflict and how it can progress. The fist chapter gives a background for peer mediation and the focus of this thesis, as well as the first contact with the two case studies. Chapter two gives a legal background for the thesis. Chapter three deals with conflict theory and chapter four with schools conflicts and the different programs there is to handle those conflicts. In chapter five the different mediations models are presented more in depth and discussed from at mediation perspective. Chapter six goes deeper into the second case study in an effort to resolve the legal issues that has arisen. In the last chapter there is a discussion which originates from the five Nordic principles of mediation, facilitative, peaceably, freely, confidently and restoratively, in conjunction whit mediation, conflict and legal theory.
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| 20. |
- Mehanna, Hisham, et al.
(författare)
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Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC) : a multicentre, multinational, individual patient data analysis
- 2023
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:3, s. 239-251
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Tidskriftsartikel (refereegranskat)abstract
- Background: p16(INK4a) (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications.Methods: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors.Findings: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74middot7%) of 7654 patients were male and 1940 (25middot3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10middot9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0middot744, p=0middot0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29middot7% vs 9middot0%, p<0middot0001). 5-year overall survival was 81middot1% (95% CI 79middot5-82middot7) for p16+/HPV+, 40middot4% (38middot6-42middot4) for p16-/HPV-, 53middot2% (46middot6-60middot8) for p16-/HPV+, and 54middot7% (49middot2-60middot9) for p16+/HPV-. 5-year disease-free survival was 84middot3% (95% CI 82middot9-85middot7) for p16+/HPV+, 60middot8% (58middot8-62middot9) for p16-/HPV-; 71middot1% (64middot7-78middot2) for p16-/HPV+, and 67middot9% (62middot5-73middot7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort.Interpretation: Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions.
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| 21. |
- Mints, Michael, et al.
(författare)
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Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.
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| 22. |
- Näsman, Anders, et al.
(författare)
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Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival
- 2013
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 2:4, s. 507-18
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Tidskriftsartikel (refereegranskat)abstract
- Patients with human papillomavirus DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPVDNA-) OSCC upon intensive oncological treatment. All HPVDNA+ OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16(INK4a), and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16(INK4a) and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPVDNA+ and 211/290 (73%) overexpressed p16(INK4a), which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16(INK4a) by univariate analysis. Upon stratification for HPV, HPVDNA+ OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPVDNA+ OSCC, p16(INK4a)+ overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPVDNA+ and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials. Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment.
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| 23. |
- Näsman, Anders, et al.
(författare)
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Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden : an epidemic of viral-induced carcinoma?
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:2, s. 362-6
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Tidskriftsartikel (refereegranskat)abstract
- In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53-81) 2000-2002; 77% (95% CI, 63-87) 2003-2005; and 93% (95% CI, 82-99) 2006-2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.
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| 24. |
- Piersiala, Krzysztof, et al.
(författare)
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Regulatory B cells producing IL-10 are increased in human tumor draining lymph nodes
- 2023
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 153:4, s. 854-866
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of different immune cell subsets, especially T cells, in anti-tumor immune response is well established. In contrast to T cells, the anti-tumor contribution of B cells has been scarcely investigated. B-cells are often overlooked, even though they are important players in a fully integrated immune response and constitute a substantial fraction of tumor draining lymph nodes (TDLNs) known also as Sentinel Nodes. In this project, samples including TDLNs, non-TDLNs (nTDLNs) and metastatic lymph nodes from 21 patients with oral squamous cell carcinoma were analyzed by flow cytometry. TDLNs were characterized by a significantly higher proportion of B cells compared with nTDLNs (P = .0127). TDLNs-associated B cells contained high percentages of naive B cells, in contrary to nTDLNs which contained significantly higher percentages of memory B cells. Patients having metastases in TDLNs showed a significantly higher presence of immunosuppressive B regulatory cells compared with metastasis-free patients (P = .0008). Elevated levels of regulatory B cells in TDLNs were associated with the advancement of the disease. B cells in TDLNs were characterized by significantly higher expression of an immunosuppressive cytokine-IL-10 compared with nTDLNs (P = .0077). Our data indicate that B cells in human TDLNs differ from B cells in nTDLNs and exhibit more naive and immunosuppressive phenotypes. We identified a high accumulation of regulatory B cells within TDLNs which may be a potential obstacle in achieving response to novel cancer immunotherapies (ICIs) in head and neck cancer.
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| 25. |
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| 26. |
- Sandström, Linda, et al.
(författare)
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Pyrolysis of Nordic biomass types in a cyclone pilot plant — Mass balances and yields
- 2016
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Ingår i: Fuel processing technology. - : Elsevier BV. - 0378-3820 .- 1873-7188. ; 152, s. 274-284
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Tidskriftsartikel (refereegranskat)abstract
- Fast pyrolysis of biomass results in a renewable product usually denoted pyrolysis oil or bio-oil, which has been suggested to be used as a direct substitute for fuel oil or as a feedstock for production of transportation fuels and/or chemicals. In the present work, fast pyrolysis of stem wood (originated from pine and spruce), willow, reed canary grass, brown forest residue and bark has been performed in a pilot scale cyclone reactor. The experiments were based on a biomass feeding rate of 20 kg/h at three different reactor temperatures. At the reference condition, pyrolysis of stem wood, willow, reed canary grass, and forest residue resulted in organic liquid yields in the range of 41 to 45% w/w, while pyrolysis of bark resulted in lower organic liquid yields. Two fractions of pyrolysis oil were obtained, denoted as the condensed and the aerosol fraction. Most of the water soluble molecules were collected in the condensed fraction, whereas the yield of water insoluble, heavy lignin molecules was higher in the aerosol fraction. Based on the results of the present work, willow, reed canary grass and forest residue are considered as promising raw materials for production of pyrolysis oil in a cyclone reactor.
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| 27. |
- Sivars, Lars, et al.
(författare)
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Human papillomavirus DNA detection in fine-needle aspirates as indicator of human papillomavirus-positive oropharyngeal squamous cell carcinoma : A prospective study
- 2017
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 39:3, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- Background. Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) has a better outcome than most head neck squamous cell carcinomas (HNSCCs) and an HPV-positive lymph node metastasis likely has an HPV-positive oropharyngeal SCC origin. Determining HPV-status in cervical lymph nodes by fine-needle aspiration cytology (FNAC) may be useful for diagnosis. Methods. FNACs from 66 patients with neck masses were prospectively examined for HPV DNA and HPV16 mRNA by a polymerase chain reaction (PCR)-based assay, and the data correlated to diagnosis and HPV-status obtained from histopathological specimens. Results. Aspirates from 17 of 66 patients, later diagnosed with HPV-positive oropharyngeal SCC, were HPV16 DNA-positive. HPV16 mRNA was detected in all cases with extractable RNA. All remaining FNACs, including 18 branchial cleft cysts, were HPV DNA-negative. HPV DNA status in the aspirates showed perfect concordance with corresponding biopsies. Conclusion. HPV16 DNA detection in fine-needle aspirations from neck masses is reliable and HPV16 DNA in a metastasis is a strong indicator of an HPV-positive oropharyngeal SCC.
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| 28. |
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| 29. |
- Stenfors, Cecilia U. D., et al.
(författare)
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Subjective Cognitive Complaints and the Role of Executive Cognitive Functioning in the Working Population : A Case-Control Study
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. UNSP e83351-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive functioning is important for managing work and life in general. However, subjective cognitive complaints (SCC), involving perceived difficulties with concentration, memory, decision making, and clear thinking are common in the general and working population and can be coupled with both lowered well-being and work ability. However, the relation between SCC and cognitive functioning across the adult age-span, and in the work force, is not clear as few population-based studies have been conducted on non-elderly adults. Thus, the present study aimed to test the relation between SCC and executive cognitive functioning in a population-based sample of employees. Methods: Participants were 233 employees with either high (cases) or low (controls) levels of SCC. Group differences in neuropsychological test performance on three common executive cognitive tests were analysed through a set of analyses of covariance tests, including relevant covariates. Results & Conclusions: In line with the a priori hypotheses, a high level of SCC was associated with significantly poorer executive cognitive performance on all three executive cognitive tests used, compared to controls with little SCC. Additionally, symptoms of depression, chronic stress and sleeping problems were found to play a role in the relations between SCC and executive cognitive functioning. No significant associations remained after adjusting for all these factors. The current findings contribute to an increased understanding of what characterizes SCC in the work force and may be used at different levels of prevention of- and intervention for SCC and related problems with executive cognitive functioning.
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| 30. |
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| 31. |
- Watanabe, Hiroyuki, et al.
(författare)
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Ipsilesional versus contralesional postural deficits induced by unilateral brain trauma : a side reversal by opioid mechanism
- 2020
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Ingår i: Brain Communications. - : Oxford University Press. - 2632-1297. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Unilateral traumatic brain injury and stroke result in asymmetric postural and motor deficits including contralateral hemiplegia and hemiparesis. In animals, a localized unilateral brain injury recapitulates the human upper motor neuron syndrome in formation of hindlimb postural asymmetry with contralesional limb flexion and the asymmetry of hindlimb nociceptive withdrawal reflexes. The current view is that these effects are developed due to aberrant activity of motor pathways that descend from the brain into the spinal cord. These pathways and their target spinal circuits may be regulated by local neurohormonal systems that may also mediate effects of brain injury. Here we evaluate if a unilateral traumatic brain injury induces hindlimb postural asymmetry, a model of postural deficits, and if this asymmetry is spinally encoded and mediated by the endogenous opioid system in rats. A unilateral right-sided controlled cortical impact, a model of clinical focal traumatic brain injury was centered over the sensorimotor cortex and was observed to induce hindlimb postural asymmetry with contralateral limb flexion. The asymmetry persisted after complete spinal cord transection, implicating local neurocircuitry in the development of the deficits. Administration of the general opioid antagonist naloxone and µ-antagonist β-funaltrexamine blocked formation of postural asymmetry. Surprisingly, κ-antagonists nor-binaltorphimine and LY2444296 did not affect the asymmetry magnitude but reversed the flexion side; instead of contralesional (left) hindlimb flexion the ipsilesional (right) limb was flexed. The postural effects of the right-side cortical injury were mimicked in animals with intact brain via intrathecal administration of the opioid κ-agonist U50,488 that induced hindlimb postural asymmetry with left limb flexion. The δ-antagonist naltrindole produced no effect on the contralesional (left) flexion but inhibited formation of the ipsilesional (right) limb flexion in brain-injured rats that were treated with κ-antagonist. The effects of the antagonists were evident before and after spinal cord transection. We concluded that the focal traumatic brain injury-induced postural asymmetry was encoded at the spinal level, and was blocked or its side was reversed by administration of opioid antagonists. The findings suggest that the balance in activity of the mirror symmetric spinal neural circuits regulating contraction of the left and right hindlimb muscles is controlled by receptors; and that this equilibrium is impaired after unilateral brain trauma through side-specific opioid mechanism.
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| 32. |
- Zupancic, Mark, et al.
(författare)
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Human papillomavirus (HPV) load is higher in HPVDNA/p16 positive than in HPVDNA positive/p16 negative oropharyngeal squamous cell carcinoma but does not differ significantly between various subsites or correlate to survival
- 2024
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Ingår i: Oral Oncology. - : Elsevier. - 1368-8375 .- 1879-0593. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivePatients with human papillomavirus DNA positive (HPVDNA+) and p16ink4a overexpressing (p16+) oropharyngeal squamous cell carcinoma (OPSCC), especially those with cancer in the tonsillar and base of tongue subsites as compared to other OPSCC subsites have a better outcome than those with only HPVDNA+ or only p16+ cancer. Likewise having a high viral load has been suggested to be a positive prognostic factor. We therefore hypothesized, that HPV viral load could vary depending on OPSCC subsite, as well as with regard to whether the cancer was HPVDNA+ and p16+, or only HPVDNA+, or only p16+ and that this affected outcome.Material and methodsTo address these issues HPV viral load was determined by HPV digital droplet (dd) PCR in tumor biopsies with previously known HPVDNA/p16 status from 270 OPSCC patients diagnosed 2000–2016 in Stockholm, Sweden. More specifically, of these patients 235 had HPVDNA+/p16+, 10 had HPVDNA+/p16-, 13 had HPVDNA-/p16+ and 12 had HPVDNA-/p16- cancer.ResultsWe found that HPVDNA+/p16+ OPSCC had a significantly higher viral load than HPVDNA+/p16- OPSCC. Moreover, there was a tendency for a higher viral load in the tonsillar and base of tongue OPSCC subsites compared to the other subsites and for a low viral load to correlate to a better clinical outcome but none of these tendencies reached statistical significance.ConclusionTo conclude, the mean viral load in HPVDNA+/p16+ OPSCC was higher than in HPVDNA+/p16- OPSCC, but there was no statistically significant difference in viral load depending on OPSCC subsite or on clinical outcome.
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