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Sökning: WFRF:(Munck Wikland Eva)

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1.
  • Koskinen, Walter J., et al. (författare)
  • Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study
  • 2007
  • Ingår i: Journal of Cancer Research and Clinical Oncology. - Springer. - 1432-1335. ; 133:9, s. 673-678
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumor-cell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence. Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux disease (GERD) were evaluated Methods Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the study. HPV DNA was determined with MY09/11 and GP5+/6+ nested PCR and SPF10 PCR hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire concerning risk factors was filled in. Results Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis. Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated with survival, although it correlated with heavy drinking. Conclusion In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and promoted early carcinogenesis.
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2.
  • Millrud, Camilla Rydberg, et al. (författare)
  • Nod-like receptors in head and neck squamous cell carcinoma
  • 2013
  • Ingår i: Acta Oto-Laryngologica. - Taylor & Francis. - 1651-2251. ; 133:12, s. 1333-1344
  • Tidskriftsartikel (refereegranskat)abstract
    • Conclusion: The capability of Nod1 to recognize bacteria along with its altered expression and ability to cause an immunological response in head and neck cancer suggest a novel pathway for bacteria to interfere with ongoing cancer inflammation. Objective: Nucleotide oligomerization domain (Nod)-like receptors (NLRs) comprise a recently discovered family of pattern-recognition receptors. In addition to their protective function against infections, accumulating evidence suggests a role for these receptors in various diseases, including cancer. The present study was designed to explore the presence of NLRs in head and neck squamous cell carcinoma, and to determine if these cells have the ability to respond immunologically to ligand stimulation. Methods: The pharyngeal squamous cell carcinoma cell lines Detroit-562 and FaDu were used as a model for head and neck cancer, and compared to healthy primary human nasal epithelial cells. Analyses were performed using immuno-histochemistry, real-time RT-PCR, Luminex Multiplex Immunoassay, ELISA, and flow cytometry. Results: The expression profile of NLRs in head and neck cancer cells differed from that seen in healthy epithelial cells. Further, Nod1 stimulation induced an immunological response in tumor cells that differed from the response in normal epithelial cells, especially regarding the expression of beta-defensin 2, granulocyte monocyte colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), intercellular adhesion molecule-1 (ICAM-1), and cell survival.
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3.
  • Bersani, Cinzia, et al. (författare)
  • A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer
  • 2017
  • Ingår i: Oral Oncology. - Elsevier. - 1368-8375 .- 1879-0593. ; 68, s. 53-59
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective: Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. Material and methods: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8(+) TILs, HPV16 mRNA and HLA class I expression were included. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set, the performance of which was evaluated in the validation set. Results: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168 and 90 patients in the respective sets. No treatment improved prognosis compared to radiotherapy alone. CD8(+) TIL counts and young age were the strongest predictors of survival, followed by T-stage &lt;3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. A model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set. Furthermore, the model identified 35% of our cohort that was over-treated and could safely have received de-escalated therapy. Conclusion: CD8(+) TIL counts, age, T-stage and E2 expression could predict progression-free survival, identifying patients eligible for randomized trials with milder treatment, potentially reducing side effects without worsening prognosis.</p>
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4.
  • Bersani, Cinzia, et al. (författare)
  • Targeted sequencing of tonsillar and base of tongue cancer and human papillomavirus positive unknown primary of the head and neck reveals prognostic effects of mutated FGFR3
  • 2017
  • Ingår i: OncoTarget. - 1949-2553 .- 1949-2553. ; 8:21, s. 35339-35350
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV- cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+TSCC/BOTSSCC and HPV+ HNCUP and HPV- TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes.</p><p>PATIENTS AND METHODS: DNA from 348 TSCC/BOTSCC and 20 HNCUP from patients diagnosed 2000-2011, was sequenced by the Ion Proton sequencing platform using the Ion AmpliSeq Cancer Hotspot Panel v2 to identify frequently mutated regions in 50 cancer related genes. Ion Torrent Variant Caller software was used to call variants.</p><p>RESULTS: 279 HPV+ TSCC/BOTSCC, 46 HPV- TSCC/BOTSCC and 19 HPV+ HNCUP samples qualified for further analysis. Mutations/tumor were fewer in HPV+ TSCC/BOTSCC and HNCUP, compared to HPV- tumors (0.92 vs. 1.32 vs. 1.68). Differences in mutation frequency of TP53 and PIK3CA were found between HPV+ TSCC/BOTSCC and HNCUP and HPV- TSCC/BOTSCC. In HPV+TSCC/BOTSCC presence of FGFR3 mutations correlated to worse prognosis. Other correlations to survival within the groups were not disclosed.</p><p>CONCLUSIONS: In HPV+ TSCC/BOTSCC mutation of PIK3CA was most frequently observed, while TP53 mutations dominated in HPV- TSCC/BOTSCC. In HPV+ TSCC/BOTSCC and HNCUP, mutations/tumor were similar in frequency and fewer compared to that in HPV- TSCC/BOTSCC. Notably, FGFR3 mutations in HPV+ TSCC/BOTSCC indicated worse prognosis.</p>
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5.
  • Dahlgren, Liselotte, et al. (författare)
  • Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients.
  • 2004
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 112:6, s. 1015-9
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The frequency of human papilloma virus (HPV) and its influence on clinical outcome was analyzed retrospectively in pre-treatment paraffin embedded biopsies from 110 patients with tongue cancer. The presence of HPV DNA was examined in 85 mobile tongue tumors and 25 base of tongue tumors by a polymerase chain reaction (PCR) with 2 general primer pairs, GP5+/6+ and CPI/IIG. When HPV-DNA was found, HPV-type specific primers and direct sequencing were used for HPV sub-type verification. Twelve of 110 (10.9%) samples were HPV-positive; 9 for HPV-16, 1 for HPV-33, 1 for HPV-35 and 1 could not be analyzed because of shortage of DNA. HPV was significantly more common in base of tongue tumors (10/25, 40.0%) compared to tumors of the mobile tongue (2/85, 2.3%). The influence of HPV on clinical outcome in mobile tongue cancer could not be studied, due to that HPV was present in too few cases. Of the 19 patients with base of tongue cancer that were included in the survival analysis, however, 7 patients with HPV-positive base of tongue cancer had a significantly favorable 5-year survival rate compared to the 12 HPV-negative patients. In conclusion, HPV is significantly more common in base of tongue cancer than in mobile tongue cancer, and has a positive impact on disease-specific survival in patients with base of tongue cancer.</p>
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6.
  • Dahlstrand, Hanna, et al. (författare)
  • Presence of human papillomavirus in tonsillar cancer is a favourable prognostic factor for clinical outcome.
  • 2004
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 24:3b, s. 1829-35
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The purpose of this article is to review the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. Current data in scientific reports and data from the Karolinska Hospital and Karolinska Institute, Sweden, demonstrate that approximately half of all tonsillar cancer is HPV-positive. Moreover, patients with HPV-positive cancer have a lower risk of relapse and longer survival compared to patients with HPV-negative tonsillar cancer. The favourable outcome for patients harbouring HPV-positive tonsillar cancer cannot be attributed to increased radiosensitivity, since there is no significant difference in sensitivity to radiotherapy between HPV-positive and -negative tonsillar cancer. However, HPV-positive cancer exhibits less genetic instability i.e. shows a lower degree of aneuploidy and a tendency to have fewer chromosomal aberrations, when compared to HPV-negative tonsillar cancer.</p>
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7.
  • Danielsson, Daniel, et al. (författare)
  • Influence of genetic background and oxidative stress response on risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer
  • 2016
  • Ingår i: Head and Neck. - 1043-3074 .- 1097-0347. ; 38:3, s. 387-393
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Osteoradionecrosis (ORN) of the mandible is a severe complication of head and neck radiotherapy (RT) treatment, where the impact of individual radiosensitivity has been a suggested explanation. Methods: A cohort of patients with stage II/III ORN was compared to matched controls. Blood was collected and irradiated in vitro to study the capacity to handle radiation-induced oxidative stress. Patients were also genotyped for 8 single-nucleotide polymorphisms (SNPs) in genes involved in the oxidative stress response. Results: A difference in 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) levels was found between the patient cohorts (p = 0.01). The SNP rs1695 in glutathione s-transferase p1 (GSTP1) was also found to be more frequent in the patients with ORN (p = .02). Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the 2 biomarkers to be significant factors which influense risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer. Conclusion: The current study indicates that oxidative stress response contributes to individual radiosensitivity and healthy tissue damage caused by RT and may be predicted by biomarker analysis.</p>
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8.
  • Danielsson, Daniel, et al. (författare)
  • Reduced oxidative stress response as a risk factor for normal tissue damage after radiotherapy: a study on mandibular osteoradionecrosis
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • <p>Background</p><p>The use of radiotherapy (RT) to treat cancer involves exposure of normal tissues. Factors that promote the development of normal tissue damage are poorly understood. An increased individual sensitivity to ionizing radiation is a likely candidate, but general phenotypes for late adverse effects of RT are difficult to define. We have found osteoradionecrosis (ORN) in the mandible as a well-defined model phenotype for an in-depth study of clinical and biological risk factors for developing late adverse effects to RT.</p><p>Methods</p><p>A cohort of patients with stage 2/3 ORN following RT for head and neck cancer (HCN) was studied and compared to a closely matched control group. Blood samples from the patients were collected and irradiated <em>in vitro</em> and the capacity to handle radiation-induced oxidative stress was investigated by measuring the level of 8-oxo-dG in serum 60 min post exposure. The patients were also genotyped for eight SNPs in genes involved in the oxidative stress response and previously studied in the context of individual radiosensitivity. Results from these endpoints were analyzed in conjunction with clinical data using multivariate analysis and an ORN risk model was constructed.</p><p> </p><p>Findings</p><p>A significant difference in 8-oxo-dG levels was found between the patient cohorts, indicating a heterogeneous response to oxidative stress induced by the <em>in vitro</em> γ-radiation. The SNP rs1695 in GSTP1 was found to be significantly more frequent in the ORN+ compared to ORN- group. Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the two biomarkers to be the most significant.</p><p> </p><p>Interpretation: The current study indicates that patient-related factors are a major source of individual variation in normal tissue response to RT. Two of the studied genetic biomarkers are strong factors in the described risk model of ORN.</p>
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9.
  • Ekberg, Tomas, 1966- (författare)
  • Diagnosis and Radioimmunotherapy of Head and Neck Squamous Cell Carcinomas
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The diagnosis and treatment of patients with advanced tumors in the head and neck is an interesting challenge where there is a need for new approaches in diagnostics and adjuvant treatment. Differences in antigen expression between tumors and normal tissues provide a means for application of antibody-based targeting techniques. By targeting a structure that is abundant on tumor cells and limited on normal cells, radioactivity can be delivered.</p><p>The use of positron emission tomography (PET) in patients with head and neck tumors is evaluated in this thesis. PET using the tracer fluorodeoxyglucose (FDG) is found to play an important diagnostic role and often has a direct clinical impact on planned surgery or other treatment. Possible targeting structures are also investigated in this thesis, and it is concluded that the EGFR and CD44v6 stand out as possible antigens for targeting approaches of squamous cell carcinomas in the head and neck (HNSCC). A radioimmunoassay for quantification of EGFR and CD44v6 is validated and concluded to be a valuable complement to immunohistochemistry for the analysis of tumors and for the planning of radioimmunotherapy. Finally, promising results of radioimmunotherapy in tumor bearing mice with the monoclonal antibody U36 labeled with the alpha emitter astatine-211 are presented.</p><p>These results demonstrate how differences between tumors and normal tissues can be used to improve diagnostic outcomes and indicate that radioimmunotherapy can be a future adjuvant therapy or treatment of residual disease in HNSCC.</p>
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10.
  • Hammarstedt, Lalle, et al. (författare)
  • Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer.
  • 2006
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 119:11, s. 2620-2623
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p &lt; 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.</p>
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