Browsing by Subject "head and neck cancer"

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  • Keskin, Mutlu; Lähteenmäki, Hanna; Rathnayake, Nilminie; Räisänen, Ismo T.; Tervahartiala, Taina; Pärnänen, Pirjo; Senisik, Ahmet Murat; Karacetin, Didem; Balkanay, Ayben Yentek; Heikkilä, Pia; Hagström, Jaana; Rautava, Jaana; Haglund, Caj; Gursoy, Ulvi Kahraman; Silbereisen, Angelika; Bostanci, Nagihan; Sorsa, Timo (2021)
    Background: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy. Research design and methods: Eleven patients, aged 28-74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe (R)/ORALyzer (R)) for aMMP-8 and ELISA for IL-6. Results: HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachment-loss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1-3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels. Conclusions: Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.
  • Hyytiäinen, Aini; Wahbi, Wafa; Väyrynen, Otto; Saarilahti, Kauko; Karihtala, Peeter; Salo, Tuula; Al-Samadi, Ahmed (2021)
    Background Head and neck squamous cell carcinoma (HNSCC) carries poor survival outcomes despite recent progress in cancer treatment in general. Angiogenesis is crucial for tumour survival and progression. Therefore, several agents targeting the pathways that mediate angiogenesis have been developed. We conducted a systematic review to summarise the current clinical trial data examining angiogenesis inhibitors in HNSCC. Methods We carried out a literature search on three angiogenesis inhibitor categories-bevacizumab, tyrosine kinase inhibitors and endostatin-from Ovid MEDLINE, Cochrane Library, Scopus and ClinicalTrials.gov database. Results Here, we analysed 38 clinical trials, total of 1670 patients, investigating 12 angiogenesis inhibitors. All trials were in phase I or II, except one study in phase III on bevacizumab. Angiogenesis inhibitors were used as mono- and combination therapies together with radio-, chemo-, targeted- or immunotherapy. Among 12 angiogenesis inhibitors, bevacizumab was the most studied drug, included in 13 trials. Although bevacizumab appeared effective in various combinations, it associated with high toxicity levels. Endostatin and lenvatinib were well-tolerated and their anticancer effects appeared promising. Conclusions Most studies did not show benefit of angiogenesis inhibitors in HNSCC treatment. Additionally, angiogenesis inhibitors were associated with considerable toxicity. However, some results appear encouraging, suggesting that further investigations of angiogenesis inhibitors, particularly in combination therapies, for HNSCC patients are warranted. Systematic Review Registration PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020157144.
  • Filippou, Artemis; Pehkonen, Henna; Karhemo, Piia-Riitta; Väänänen, Juho; Nieminen, Anni I.; Klefström, Juha; Grenman, Reidar; Mäkitie, Antti; Joensuu, Heikki; Monni, Outi (2021)
    Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that derive from the mucosal epithelium of the upper aerodigestive tract and present high mortality rate. Lack of efficient targeted-therapies and biomarkers towards patients' stratification are caveats in the disease treatment. Anoctamin 1 (ANO1) gene is amplified in 30% of HNSCC cases. Evidence suggests involvement of ANO1 in proliferation, migration, and evasion of apoptosis; however, the exact mechanisms remain elusive. Aim of this study was to unravel the ANO1-dependent transcriptional programs and expand the existing knowledge of ANO1 contribution to oncogenesis and drug response in HNSCC. We cultured two HNSCC cell lines established from primary tumors harboring amplification and high expression of ANO1 in three-dimensional collagen. Differential expression analysis of ANO1-depleted HNSCC cells demonstrated downregulation of MCL1 and simultaneous upregulation of p27Kip1 expression. Suppressing ANO1 expression led to redistribution of p27Kip1 from the cytoplasm to the nucleus and associated with a cell cycle arrested phenotype. ANO1 silencing or pharmacological inhibition resulted in reduction of cell viability and ANO1 protein levels, as well as suppression of pro-survival BCL2 family proteins. Collectively, these data provide insights of ANO1 involvement in HNSCC carcinogenesis and support the rationale that ANO1 is an actionable drug target.
  • Almada-Correia, Inês; Neves, Pedro Miguel; Mäkitie, Antti; Ravasco, Paula (2019)
    Introduction: Head and neck cancer (HNC) patients show a high risk of malnutrition due to the lifestyle habits adopted prior to the diagnosis as well as to the compromising impact of both the anatomical location of the tumor and the treatment modalities on food intake. Weight change, measurement of skinfold thickness, biochemical parameters, bioelectrical impedance analysis (BIA), computed tomography (CT), magnetic resonance (MRI), or dual-energy x-ray absorptiometry (DXA) are available techniques to evaluate nutritional status and/or body composition in the clinical practice. Evaluating body composition alterations in HNC patients is essential to be able to offer the best therapeutical interventions. In this paper, we review the existing literature regarding body composition evaluation in HNC patients to determine, which is the most suitable method for this population, regarding availability in the day-to-day practice, patient burden, cost, sensibility, and specificity.Methodology: A literature search for relevant papers indexed in MEDLINE, Cochrane Library and Scielo was conducted, with no publication date restriction and for all published articles until the 31 January, 2019. All the papers written in English, with interventions in humans, exclusively considering HNC patients were selected.Results: A total of 41 studies with different methodologies were included in this review. In 15 studies BIA was the used assessment method and three of them also evaluated skinfold thickness and one was a bioelectric impedance vector analysis (BIVA). Body composition assessment was made with DXA in eight studies, one of which also included muscle biopsies. In two studies the chosen method was both BIA and DXA. CT/ positron emission tomography-CT was applied in 11 studies and one also included MRI. In two studies body composition was assessed with skinfold measurements alone and one study only used BIVA.Conclusions: Despite the different existing body composition assessment tools, it seems that skeletal muscle mass (SMM) measurement at the level of cervical spine C3 vertebra may be a reliable method for SMM assessment as it strongly correlates with cross-sectional area measures at the level of L3 and it allows a cost-effective body composition assessment without the need for additional radiation exposure.
  • Szukalska, Marta; Szyfter, Krzysztof; Florek, Ewa; Rodrigo, Juan P.; Rinaldo, Alessandra; Mäkitie, Antti A.; Strojan, Primoz; Takes, Robert P.; Suarez, Carlos; Saba, Nabil F.; Braakhuis, Boudewijn J. M.; Ferlito, Alfio (2020)
    Simple Summary The risk of developing cancer is always higher for tobacco smokers than for non-smokers. Electronic cigarettes (e-cigarettes) have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products, due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to traditional tobacco cigarettes. In conclusion, the studies discussed in the review strongly suggest that more long-term studies are needed to better address the safety of e-cigarettes. E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC). The objective of the review was to compare the molecular and health effects of e-cigarette use in relation to the effects of traditional cigarette smoking in the upper respiratory tract, and to assess the safety and effect of e-cigarettes on HNC risk. A review for English language articles published until 31 August 2020 was made, using a PubMed (including MEDLINE), CINAHL Plus, Embase, Cochrane Library and Web of Science data. The authors reviewed articles on both toxic and carcinogenic compounds contained in e-cigarettes and their molecular and health effects on the upper respiratory tract in comparison to tobacco cigarettes. The risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of e-cigarettes compared with tobacco smokers. However, more long-term studies are needed to better address the safety of e-cigarettes.
  • Mäkitie, Antti A.; Almangush, Alhadi; Youssef, Omar; Metsälä, Markus; Silen, Suvi; Nixon, Iain J.; Haigentz, Missak; Rodrigo, Juan P.; Saba, Nabil F.; Vander Poorten, Vincent; Ferlito, Alfio (2020)
    Head and neck cancer (HNC) comprises a heterogeneous group of upper aerodigestive tract malignant neoplasms, the most frequent of which is squamous cell carcinoma. HNC forms the eighth most common cancer type and the incidence is increasing. However, survival has improved only moderately during the past decades. Currently, early diagnosis remains the mainstay for improving treatment outcomes in this patient population. Unfortunately, screening methods to allow early detection of HNC are not yet established. Therefore, many cases are still diagnosed at advanced stage, compromising outcomes. Exhaled breath analysis (EBA) is a diagnostic tool that has been recently introduced for many cancers. Breath analysis is non-invasive, cost-effective, time-saving, and can potentially be applied for cancer screening. Here, we provide a summary of the accumulated evidence on the feasibility of EBA in the diagnosis of HNC.
  • Mroueh, Rayan; Tanskanen, Tomas; Haapaniemi, Aaro; Salo, Tuula; Malila, Nea; Mäkitie, Antti; Pitkäniemi, Janne (2020)
    Background Reported patterns of familial aggregation of head and neck cancer (HNC) vary greatly, with many studies hampered by the limited number of subjects. Methods Altogether 923 early-onset ( Results Of all early-onset HNC families, only 21 (2.3%) had familial HNC cancers at any age and less than five familial early onset HNC cancers among first-degree relatives. The cumulative risk of HNC for siblings by age 60 (0.52%) was at population level (0.33%). No increased familial risk of early-onset HNC could be discerned in family members (SIR 2.68, 95% CI 0.32-9.68 for first-degree relatives). Conclusions Our study indicates that the cumulative and relative familial risk of early-onset HNC is modest in the Finnish population and, at most, only a minor proportion of early-onset HNCs are due solely to inherited genetic mutations.
  • Björkman, Kajsa; Pietarinen, Petra; Mäkitie, Antti; Markkanen-Leppänen, Mari (Helsingfors universitet, 2017)
    Background: Fiberoptic endoscopic evaluation of swallowing (FEES) is an established non-invasive and radiation-safe evaluation method of the pharyngeal swallowing function. The focus is in the diagnosis of dysphagia, consideration of its treatment and in finding compensation techniques for impaired swallowing. We aimed at investigating the feasibility and outcome of FEES at our institution. Patients and Methods: The study group comprised all the 117 patients who had a FEES performed during the years 2011 and 2012 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Results: Patients who were considered otherwise healthy prior to FEES presented significantly more often with globus symptoms compared with patients with a neurological disorder (p=0.009) or those diagnosed with a head and neck (HN) malignancy (p=0.011). Patients with a neurological disorder had significantly more aspiration (p=0.014), suffered more from swallowing initiation difficulties (p=0.031) and more often had a pneumonia (p<0.005) compared to the patients who had been considered healthy. Aspiration and pneumonia correlated with the underlying disease (r=0.382 p<0.005), as well as with the degree of dysphagia. Conclusions: FEES served well as a second-stage diagnostic tool for dysphagia in a multidisciplinary environment. Patients with no obvious underlying cause for dysphagia presented more often with globus, compared to patients with a diagnosed malignant tumour in the head and neck region, or with a neurological diagnosis. Aspiration, pneumonia and the degree of dysphagia correlated with the underlying cause of dysphagia.
  • Tuomainen, Katja; Al-Samadi, Ahmed; Potdar, Swapnil; Turunen, Laura; Turunen, Minna; Karhemo, Piia-Riitta; Bergman, Paula; Risteli, Maija; Åström, Pirjo; Tiikkaja, Riia; Grenman, Reidar; Wennerberg, Krister; Monni, Outi; Salo, Tuula (2020)
    In vitro cancer drug testing carries a low predictive value. We developed the human leiomyoma-derived matrix "Myogel" to better mimic the human tumor microenvironment (TME). We hypothesized that Myogel could provide an appropriate microenvironment for cancer cells, thereby allowing more in vivo-relevant drug testing. We screened 19 anticancer compounds, targeting the epidermal growth factor receptor (EGFR), MEK, and PI3K/mTOR on 12 head and neck squamous cell carcinoma (HNSCC) cell lines cultured on plastic, mouse sarcoma-derived Matrigel (MSDM), and Myogel. We applied a high-throughput drug screening assay under five different culturing conditions: cells in two-dimensional (2D) plastic wells and on top or embedded in Matrigel or Myogel. We then compared the efficacy of the anticancer compounds to the response rates of 19 HNSCC monotherapy clinical trials. Cancer cells on top of Myogel responded less to EGFR and MEK inhibitors compared to cells cultured on plastic or Matrigel. However, we found a similar response to the PI3K/mTOR inhibitors under all culturing conditions. Cells grown on Myogel more closely resembled the response rates reported in EGFR-inhibitor monotherapy clinical trials. Our findings suggest that a human tumor matrix improves the predictability of in vitro anticancer drug testing compared to current 2D and MSDM methods.
  • Koskinen, Tuomas (Helsingfors universitet, 2017)
    BACKGROUND: Complication rates following neck dissection (ND) have been assessed in many studies, but only few of those have incorporated a well-established grading system for severity. Our aim was to assess the incidence and the severity of ND complications using the Clavien-Dindo Classification of Surgical Complications (CSC) and to review possible risk factors. PATIENTS AND METHODS: Documents of the patients (n=194) who underwent ND at the Helsinki University Hospital in 2014 were retrospectively reviewed. Seventy-six patients were identified for further review as they were operated on by the same otorhinolaryngology surgery team without coinciding microvascular transfer. CSC was used to evaluate the severity of complications related to ND for the first 30 postoperative days. Statistical analyses were performed to assess possible risk factors. RESULTS: One quarter (27.6%) of the patients recovered from ND without any deviation from normal postoperative course (CSC Grade 0). More than half (57.9%) of the patients received CSC Grade I and II interventions postoperatively. Postoperative surgical intervention in the operation room (CSC Grade IIIb) was required for 14.5% of the patients. There were no life threatening complications or deaths. No statistically significant patient-related risk factors were identified. Dissection of fewer neck levels was associated with fewer complications. DISCUSSION: Complication rates were higher in this study than in other studies focusing on ND, partly due to careful registration and classification of all complications. However, infection rates were lower than in other studies and there were no life threatening complications, suggesting a good competence level of surgical management.
  • Sikiö, Jenna (Helsingin yliopisto, 2017)
    Background: Some oral health factors have been associated with a higher risk for head and neck cancers (HNCs) and most clearly the existing evidence refers to an association between periodontitis and HNC. Aims: To examine oral health in a subset of HNC patients, namely patients with oropharyngeal cancer (OPC) or oral cavity cancer (OCC), and to compare these two tumor sites in this regard. Subjects and Methods: A retrospective study consisting of a series of OPC and OCC patients diagnosed between 2005-2008 at the Helsinki University Hospital, Helsinki, Finland. Study subjects were randomly selected from hospital registries. Oral health at diagnosis was assessed by reviewing the corresponding panoramic radiographs. We used modified Total Dental Index (Mattila et al. 1989) to assess oral health as a whole. Results: In univariate analysis the difference in modified Total Dental Index (mean 3,49 ±0,20 for OPC vs. 2,85 ±0,22 for OCC) was statistically significant, but after adjusting for age, gender, smoking, and heavy alcohol consumption statistical significance was lost. When individual dental variables were considered, the only statistically significant difference in univariate analysis was found concerning residual roots (mean 0,60 ±0,21 for OPC vs. 0,19 ±0,15 for OCC). Conclusions: The present findings demonstrate a fairly poor oral health status among oral and oropharyngeal cancer patients. The observed prevalence of caries and periodontitis seems to be even more common than among the Finnish general population. Whether or not there are differences in oral health risk factors between OPC and OCC patients cannot be reliably established in this study. Further studies with larger sample sizes are needed to confirm our findings either way.
  • Dawka, Sagarika (Helsingin yliopisto, 2021)
    Head and neck squamous cell carcinoma (HNSCC) is a diverse group of cancers defined by their localization in the head and neck region. These cancers are recognized for the heterogeneity between tumors from separate patients (inter-patient heterogeneity) as well as between cell types within individual tumors (intra-tumoral heterogeneity). Heterogeneity poses a major clinical challenge by making accurate diagnosis and selection of treatment options difficult. This study aims to improve precision of prognosis, quantify heterogeneity in HNSCC, and address its functional implications using two approaches: (1) profiling a set of HNSCC patient tumors using multiplexed immunohistochemistry and single-cell computational methods to identify a set of phenotypic descriptors correlating with differences in survival; and (2) using patient-derived cancer cell lines to investigate which cellular features correlate with relevant functional properties such as plasticity, invasiveness, clonogenicity and tumorsphere-forming abilities of cells. Epithelial-mesenchymal transition (EMT) as well as excistence of stem cell like states have been implicated in cancer aggressiveness and poor outcomes. We thus focused on identification of putative EMT, partial EMT (pEMT) and stem cell-like states. Based on a combination of morphometric analyses and stem cell- and EMT marker profiling, our computational method assigned patients into groups with different survival probabilities, and these patients’ tumors were found to differ in their expression of the stem cell transcription factor Sox2, the EMT transcription factor Slug, and in their morphometric parameters. Functional studies of patient-derived cell lines found that significant differences exist in protein expression, morphological features and cell behaviours between cell lines in vitro, and that inhibiting EMT promotes clonogenicity and can increase Sox2 expression. Thus, this study highlights important heterogeneous patient phenotypes and cellular behaviours in HNSCC, and implicates the need for a multimodal approach to diagnosis and therapy of this cancer.
  • Matović, Jelena (Helsingin yliopisto, 2019)
    Boron Neutron Capture Therapy is a binary cancer treatment based on the nuclear capture and fission reaction which occur when 10B is irradiated with low energy thermal neutrons. BNCT has throughout the years shown noticeable clinical results with the boron delivery agents that are currently available for testing. However, these delivery agents display deficiencies on multiple frontiers. My goal was to synthesize three different carbohydrate delivery agents for BNCT. Carbohydrate delivery agents have great potential for multiple reasons. They have low toxicity, high aqueous solubility and a high amount of boron atoms can be attached to a single molecule. These three synthesized molecules, 6-O-o-carboranylmethyl-D-glucopyranose, (O)-carboranylmethyl -D-glucopyranoside, (O)-carboranylmethyl -D-glucopyranoside, consist out of a glucose moiety and a carborane cage at both anomeric positions 1 as well as position 6. The synthetic pathways developed were 5-6 steps long and the overall yields varied between 13-15%. The synthesized molecules are currently undergoing biological evaluation.