| 1. |
- Astradsson, Thorsteinn
(författare)
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Systemic inflammation and prognostic markers in patients with head and neck cancer
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with head and neck cancer (HNC) often present with weight loss and malnutrition caused by systemic inflammation and dysphagia. This thesis explores the effects of systemic and local inflammation in the context of head and neck cancer treatment. The main aim of Paper I was to investigate whether trismus after radiotherapy affects the 5-year overall survival rate in a cohort of 244 patients with HNC. The maximum interincisal opening (MIO) of the patients was measured before treatment, 2, 6, and 12 months after the termination of radiotherapy, and trismus was defined as MIO ≤ 35 mm. All patients received instructions on jaw-opening exercises. The highest prevalence of trismus at 12 months was seen in patients with oral cancer (44%) and oropharyngeal cancer (37%) and it can be concluded that these patients should primarily be offered jaw-opening exercises. Patients with trismus at 12 months after termination of treatment had a tendency towards a worse overall 5-year survival rate than patients without trismus (p=0.64).Paper II explored the expression levels of cytokines and growth factors in serum before and up to one year after treatment. The cohort consisted of 30 patients with HNC and blood was drawn on four occasions and analyzed for 10 cytokines and 4 growth factors. Patients who received chemoradiotherapy had higher expression levels of IL-1β, IL-6, and IL-10 than other treatment groups at 7 weeks after the start of treatment. Patients with recurrence within 12 months after termination of treatment had higher expression levels of IL-1β, IL-6, IL-8, and IL-10 than the remaining patients at 7 weeks.In Paper III the expression levels of 83 immuno-oncologically significant proteins were determined at the same four time points as in Paper II in a cohort of 180 patients with HNC using a proteomics technique. Fifteen proteins had either decreased or increased expression levels at 7 weeks compared to pre-treatment expression levels. Treatment with radiotherapy with concomitant cisplatin was shown to be connected to significantly decreased expression of 13 proteins at 7 weeks after the start of treatment compared to radiotherapy which demonstrates an immunomodulatory effect of cisplatin also apparent in Paper II.The aim of Paper IV was to investigate how pre-treatment body mass index and fat free mass index correlate with early death in a cohort of 404 patients with head and neck squamous cell carcinoma (HNSCC). Body mass composition was measured at diagnosis using bioelectrical impedance analysis. Patients who died within 6 months of the start of treatment had significantly lower FFMI at diagnosis compared with patients who survived beyond 6 months (17.6 kg/m2 and 19.5 kg/m2, respectively, p=0.035). It can be recommended that assessment of fat free mass index should be included in the management of patients with HNSCC prior to treatment.
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| 2. |
- Gebre-Medhin, Maria, et al.
(författare)
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ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
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| 3. |
- Grün, Nathalie, et al.
(författare)
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Human papillomavirus prevalence in mouthwashes of patients undergoing tonsillectomy shows dominance of HPV69, without the corresponding finding in the tonsils.
- 2017
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:8, s. 588-593
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of human papillomavirus (HPV) in tonsillar squamous cell carcinomas (TSCC) is of interest, since a considerable proportion of TSCC in Sweden and other Western countries is HPV positive. Nevertheless, the natural history of HPV in normal tonsils, and the progression from localized infection to pre-malignant lesion to cancer are poorly understood. The aim of this study was to investigate whether HPV types found in mouthwash samples correlated to those in tonsillar tissue from the same individuals undergoing tonsillectomy.METHODS: Mouthwash samples from 232 patients, aged 3-56 years, undergoing tonsillectomy, the majority with chronic tonsillitis, were collected at the time of surgery and analysed for the presence of 27 HPV types by a bead based multiplex assay.RESULTS: An HPV prevalence of 10.3% (24/232) was observed in mouthwash samples, with HPV 69 being the dominant type (10/24). Ten patients were positive for high risk HPV (HPV 16, 33, 35, 45, 56, 59). None of the tonsils resected from patients with HPV-positive mouthwash samples were positive for HPV.CONCLUSIONS: Despite an oral HPV prevalence of 10.3% in mouthwash samples from tonsillectomized patients, with dominance of HPV 69, none of the corresponding tonsillar samples exhibited the presence of HPV.
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| 4. |
- Hammarstedt-Nordenvall, Lalle, et al.
(författare)
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Distribution of sentinel nodes from parotid tumors - A feasibility study
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:9, s. 19667-19672
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its ' clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors.Materials and Methods: Prosepective observational study in 30 patients with benign or low-grade T1-T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound-guided peritumoral injection with a technetium-99 (Tc-99 m) laballed tracer followed by a SPECT-CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed.Results: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors.Conclusions: The use of SN-technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity.
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| 5. |
- Högmo, Anders, et al.
(författare)
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Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
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| 6. |
- 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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| 7. |
- Marsk, Elin, et al.
(författare)
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Validation of a Swedish version of the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE) scale
- 2013
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 133:6, s. 662-669
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Swedish versions of the Facial Disability Index (FDI) and Facial Clinimetric Evaluation (FaCE) scale are psychometrically valid. Both questionnaires can be used for clinical studies on peripheral facial palsy patients, and provide important information on quality of life. Objectives: To translate and validate Swedish versions of the FDI and FaCE scale in patients with peripheral facial palsy. Methods: Translation of the original questionnaires followed international guidelines. Internal consistency and test-retest stability were assessed in adult patients with stable peripheral facial palsy. Facial function was examined with the Sunnybrook and House-Brackmann scales. Subjects answered the questionnaires twice with a 2-week interval. Validity was assessed by comparing FDI and FaCE scale scores to SF-36 and Sunnybrook/House-Brackmann scores. Results: Ninety-three patients were included, 53% women and 47% men, mean age 56.9 years and mean duration of palsy 51.9 months. The questionnaires showed good/excellent psychometric properties with Cronbach's alpha scores between 0.76 and 0.92. In the test-retest analysis, intra-class correlation coefficients were very good for both questionnaires with scores of 0.83-0.97. Both questionnaires showed good sensitivity to discriminate between patients with varying degrees of facial dysfunction. Moderate to strong correlation was found between the social domains in the questionnaires when compared with the equivalent domains in SF-36.
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| 8. |
- Schindele, Alexandra, 1967-
(författare)
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Mapping viruses in non-malignant tonsils, nasal polyps, sinonasal inverted papilloma and laryngeal cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The upper respiratory tract is exposed to viruses, which can lead to infection and cancer development. We chose to study common and/or chronic diseases along with common and cancer related viruses in the upper airway. High-risk human papillomavirus (HPV) causes cancer in tonsils and base of tongue, and Epstein-Barr virus (EBV) in the nasopharynx. p16 is used as a site-specific tumor marker for HPV. Human cytomegalovirus (HCMV) and human adenovirus (HAdV) are proposed to be oncomodulatory. It is unclear what significance these viruses have in benign tonsillar disease, chronic rhinosinusitis with nasal polyps (CRSwNP), sinonasal inverted papillomas (SIP) and laryngeal squamous cell carcinoma (LSCC). If virus is identified, it could make possible the use of current vaccines in prevention and treatment, as well as protection of healthcare providers.Material and Methods: We analyzed 40 benign tonsils, 45 paired nasal polyp and healthy nasal mucosa samples, 53 SIP and 78 LSCC samples. We used PCR/microarrays (PapilloCheck®) for HPV detection and genotyping, immunohistochemistry (IHC) for p16 expression and real-time PCR for EBV, HCMV and HAdV detection. Additionally, Epstein-Barr encoding region (EBER) in situ hybridization (ISH) was used for EBV localization and count.Results: HPV and p16 were not co-expressed, and p16 levels were low in benign tonsils, nasal polyps, and paired controls. Also, 9% of LSCC samples were high-risk HPV 16 positive and over-expressed p16.EBV-positive cells were detected in 65% of the tonsils, nasal polyps (36%) versus controls (12%), 30% of SIP cases and 33% of LSCC samples.Conclusions: EBV is commonly identified in benign tonsils, nasal polyps, SIP and LSCC, when using sensitive and robust detection methods. At the same time, viral infection with HPV, HCMV or HAdV appears to be uncommon in these conditions. p16 does not emerge as a reliable marker for HPV infection in LSCC.
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| 9. |
- Wennerberg, Johan, et al.
(författare)
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Results from a prospective, randomised study on (accelerated) preoperative versus (conventional) postoperative radiotherapy in treatment of patients with resectable squamous cell carcinoma of the oral cavity : The ARTSCAN 2 study
- 2022
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 166, s. 26-32
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeAn earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed.Materials and methodsPatients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed.Results250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF.Toxicity was more pronounced in preoperative AF.ConclusionThis study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.
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| 10. |
- Wu, Shengru, et al.
(författare)
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Tonsillar microbiota : A cross-sectional study of patients with chronic tonsillitis or tonsillar hypertrophy
- 2021
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Ingår i: mSystems. - 2379-5077. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Chronic tonsillitis (CT) and tonsillar hypertrophy (TH) are common tonsillar diseases that are related to infection and inflammation. Little is known about tonsillar microbiota and its role in CT and TH. This study aims to identify palatine tonsillar microbiota both on the surface and in the core tissues of CT and TH patients. In total, 22 palatine tonsils were removed and collected from CT and TH patients who underwent surgery. The surface and core microbiota in the tonsils of CT and TH patients were compared using 16S rRNA gene sequencing of V3-V4 regions. Differential tonsillar microbiotas were found in the CT versus TH patients and surface versus core tissues. Further, a higher relative abundance of bacterial genera, including Haemophilus, Streptococcus, Neisseria, Capnocytophaga, Kingella, Moraxella, and Lachnospiraceae [G-2] in patients with TH and Dialister, Parvimonas, Bacteroidales [G-2], Aggregatibacter, and Atopobium in patients with CT, was observed. Of these, the differential genera of Dialister, Parvimonas, and Neisseria served as key factors in the tonsillar microbiota network. Notably, four representable tonsillar microbial types were identified, with one, consisting of a higher abundance of Haemophilus and Neisseria, exclusively detected in the TH patients. This study analyzed the different tonsillar microbiota from the surface and core tissues of CT and TH patients. Several bacteria and various microbial types related to CT and TH were identified, along with potential bacterial networks and related immune pathways.IMPORTANCE: The human microbiota has been shown to be functionally connected to infectious and inflammation-related diseases. So far, only limited studies had been performed on tonsillar microbiota, although tonsils play an essential role in the human immune defense system and encountered numerous microorganisms. Our work presented different tonsillar microbiota from surface and core tissues of chronic tonsillitis (CT) and tonsillar hypertrophy (TH) patients. Notably, one tonsillar microbiota type, which contains a higher abundance of Haemophilus and Neisseria, was only detected in the TH patients. Furthermore, certain bacteria, such as Haemophilus, Neisseria, Dialister, and Parvimonas, may serve as microbial biomarkers to discriminate CT patients from TH patients. These data provide important microbiota data in the tonsillar research area and are highly useful for researchers both in the oral microbiome field and clinical field.
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