Browsing by Subject "Head and neck cancer"

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  • Koivunoro, Hanna; Kankaanranta, Leena; Seppälä, Tiina; Haapaniemi, Aaro; Mäkitie, Antti; Joensuu, Heikki (2019)
    Background and purpose: Head and neck squamous cell carcinoma (HNSCC) that recurs locally is a therapeutic challenge. We investigated the efficacy of boron neutron capture therapy (BNCT) in the treatment of such patients and the factors associated with treatment response and survival. Methods and materials: Seventy-nine patients with inoperable, locally recurred HNSCC were treated with L-boronophenylalanine-mediated BNCT in Espoo, Finland, between February, 2003 and January, 2012. Prior treatments consisted of surgery and conventionally fractionated radiotherapy to a median cumulative dose of 66 Gy (interquartile range [IQR], 59-70 Gy) administered with or without concomitant chemotherapy. Tumor response was assessed using the RECISTv. 1.0 criteria. Results: Forty patients received BNCT once (on 1 day), and 39 twice. The median time between the 2 treatments was 6 weeks. Forty-seven (68%; 95% confidence interval [CI], 57-79%) of the 69 evaluable patients responded; 25 (36%) had a complete response, 22 (32%) a partial response, 17 (25%) a stable disease lasting for a median of 4.2 months, and 5 (7%) progressed. The patients treated with BNCT twice responded more often than those treated once. The median follow-up time after BNCT was 7.8 years. The 2-year locoregional progression-free survival rate was 38% and the overall survival rate 21%. A high minimum tumor dose and a small volume were independently associated with long survival in a multi-variable analysis. Conclusions: Most patients responded to BNCT. A high minimum tumor dose from BNCT was predictive for response and survival. (C) 2019 The Authors. Published by Elsevier B.V.
  • Almangush, Alhadi; Alabi, Rasheed O; Troiano, Giuseppe; Coletta, Ricardo D.; Salo, Tuula; Pirinen, Matti; Mäkitie, Antti A.; Leivo, Ilmo (BioMed Central, 2021)
    Abstract Background The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer. Methods Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Results TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56–2.84) and disease-free survival (HR 1.84, 95%CI 1.38–2.46). Conclusions The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.
  • Almangush, Alhadi; Alabi, Rasheed Omobolaji; Troiano, Giuseppe; Coletta, Ricardo D.; Salo, Tuula; Pirinen, Matti; Mäkitie, Antti A.; Leivo, Ilmo (2021)
    Background The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer. Methods Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Results TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56-2.84) and disease-free survival (HR 1.84, 95%CI 1.38-2.46). Conclusions The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.
  • Passador-Santos, F.; Gronroos, M.; Irish, J.; Gilbert, R.; Gullane, P.; Perez-Ordonez, B.; Makitie, A.; Leivo, I. (2016)
    Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).
  • Kainulainen, S.; Tornwall, J.; Koivusalo, A. M.; Suominen, A. L.; Lassus, Patrik (2017)
    Objectives: Glucocorticoids are widely used in association with major surgery of the head and neck to improve postoperative rehabilitation, shorten intensive care unit and hospital stay, and reduce neck swelling. This study aimed to clarify whether peri-and postoperative use of dexamethasone in reconstructive head and neck cancer surgery is associated with any advantages or disadvantages. Materials and methods: This prospective double-blind randomized controlled trial comprised 93 patients. A total dose of 60 mg of dexamethasone was administered to 51 patients over three days peri-and post-operatively. The remaining 42 patients served as controls. The main primary outcome variables were neck swelling, length of intensive care unit and hospital stay, duration of intubation or tracheostomy, and delay to start of possible radiotherapy. Complications were also recorded. Results: No statistical differences emerged between the two groups in any of the main primary outcome variables. However, there were more major complications, especially infections, needing secondary surgery within three weeks of the operation in patients receiving dexamethasone than in control patients (27% vs. 7%, p = 0.012). Conclusions: The use of dexamethasone in oral cancer patients with microvascular reconstruction did not provide a benefit. More major complications, especially infections, occurred in patients receiving dexamethasone. Our data thus do not support the use of peri-and postoperative dexamethasone in oropharyngeal cancer patients undergoing microvascular reconstruction. (C) 2016 Elsevier Ltd. All rights reserved.
  • de Oliveira Figueiredo, Rejane Augusta; Weiderpass, Elisabete; Tajara, Eloiza Helena; Strom, Peter; Carvalho, Andre Lopes; de Carvalho, Marcos Brasilino; Kanda, Jossi Ledo; Moyses, Raquel Ajub; Wunsch-Filho, Victor (2016)
    Introduction: Diabetes mellitus (DM (Diabetes Mellitus)) is directly associated with some cancers. However, studies on the association between diabetes mellitus and head and neck cancer (HNC (Head and Neck Cancer)) have rendered controversial results. The objective of this study was to evaluate the association between DM and HNC, as well as the impact of metformin use on the risk of HNC. Material and methods: This case-control study was conducted within the framework of the Brazilian Head and Neck Genome Project in 2011-2014. The study included 1021 HNC cases with histologically confirmed squamous cell carcinoma of the head and neck admitted to five large hospitals in Sao Paulo state. A total of 1063 controls were selected in the same hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. Results: Diabetic participants had a decreased risk of HNC (OR = 0.68; 95% CI: 0.49-0.95) than nondiabetic participants, and this risk was further decreased among diabetic metformin users (OR = 0.54; 95% CI: 0.29-0.99). Diabetic metformin users that were current smokers (OR = 0.13; 95% CI: 0.04-0.44) or had an alcohol consumption of >40 g/day (OR = 0.31; 95% CI: 0.11-0.88) had lower risk of HNC than equivalent non-diabetic participants. Conclusion: The risk of HNC was decreased among diabetic participants; metformin use may at least partially explain this inverse association. (C) 2016 Elsevier Ltd. All rights reserved.
  • Loimu, Venla; Seppälä, Tiina; Kapanen, Mika; Tuomikoski, Laura; Nurmi, Heidi; Makitie, Antti; Tenhunen, Mikko; Saarilahti, Kauko (2017)
    Background and purposes: Permanent xerostomia as a result of radiation-induced salivary gland damage remains a common side effect of radiotherapy (RT) of the head and neck. The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing the post-RT salivary gland function in patients with head and neck cancer (HNC). Materials and methods: In this prospective study, 20 HNC patients scheduled for bilateral neck chemoradiotherapy (CRT) with weekly cisplatin went through diffusion-weighted magnetic resonance imaging (DW-MRI) and salivary gland scintigraphy (SGS) prior to and at a mean of six months after completing the treatment. The changes in apparent diffusion coefficient (ADC) before and after treatment were compared with ejection fraction (EF) measured with SGS and the radiation dose absorbed by the salivary glands. Results: As a result of gustatory stimulation with ascorbic acid, the ADC showed a biphasic response with an initial increase and subsequent decrease. This pattern was seen both before and after RT. Post-RT ADC increased as a function of RT dose absorbed by the salivary glands. A moderate statistical correlation between pre- and post-RT ADCs at rest and EF measured with SGS was found. Conclusions: DW-MRI seems a promising tool for detection of physiological and functional changes in major salivary glands after RT. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Heinonen, T.; Loimu, V.; Saarilahti, K.; Saarto, T.; Mäkitie, A. (2018)
    Studies on palliative care of head and neck cancer (HNC) patients are scarce although the affected patient population is quite large. To evaluate the role of a specialised palliative-care pathway of HNC patients. Data on all HNC patients who were treated at the Helsinki University Hospital Palliative Care Center during 1 year were retrospectively reviewed. The analysis comprised 60 patients (49 males; mean age 67 years; range 28-88). All patients had a minimum follow-up of 1 year or until death. Fifty-nine (98%) out of the 60 patients died during the follow-up period. Median survival after diagnosis was 11 months (range 3 weeks-11.9 years) and after withholding disease-specific therapies 3 months (range 0-16). Thirty-three (55%) patients received palliative radiotherapy, 27 (45%) had PEG tube and 17 (28%) tracheostomy. Thirty-seven (66%) patients visited an emergency department (ED) (median 1.3 visits; range 0-6) and 21 (35%) were hospitalised at the university hospital during the palliative period. The most common severe complications were infection (also the most common reason for ED visits and hospitalisation), bleeding (four massive airway bleedings with one death), delirium and airway obstruction (one emergency tracheostomy). Twelve (35%) out of the 34 patients who were referred to specialised home care died at home as compared with three (12%) out of the 26 patients not supported by a specialised home-care team. Severe complications leading to an emergency unit visit and hospitalisation are common among HNC patients in their relatively short palliative period reflecting the need for early-integrated palliative care. Collaboration with a specialised palliative home-care team seems to increase end-of-life care at home.
  • Ilmarinen, Taru; Hammarstedt-Nordenvall, Lalle; Bäck, Leif; Mäkitie, Antti (2021)
    Purpose We assessed current policies and perceptions of enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT). A web-based survey was used to compare the timing and method of tube feeding within and between the five Nordic countries, covering a population of 27 million. Methods From each of the 21 Nordic university hospitals, one oncologist and one otorhinolaryngology-head and neck (ORL-HN) surgeon responded to a survey. The respondents were asked whether tube insertion before the onset of CRT, or during CRT as required (prophylactic vs. reactive) was preferred. The use of a pretreatment nutritional screening tool and the choice of feeding route (nasogastric vs. gastrostomy tube) were assessed. In total, we analyzed responses from 21 oncologists and 21 ORL-HN surgeons. Results A tendency was observed towards decreasing the use of a PEG tube. Of the 21 university hospitals, only 2 (10%) reported using a prophylactic PEG tube in over half of HNC patients undergoing definitive CRT. The preferred method for reactive tube feeding was by a NG tube in 14 of 21 (67%), and by a PEG in 7 of 21 (33%). In general, both oncologists and ORL-HN surgeons were content with their current policy. Conclusions The practices for enteral tube feeding in HNC management vary within and between the Nordic countries. We suggest that unified protocols for tube feeding should be developed for this patient population.
  • Baijens, Laura W. J.; Walshe, Margaret; Aaltonen, Leena-Maija; Arens, Christoph; Cordier, Reinie; Cras, Patrick; Crevier-Buchman, Lise; Curtis, Chris; Golusinski, Wojciech; Govender, Roganie; Eriksen, Jesper Grau; Hansen, Kevin; Heathcote, Kate; Hess, Markus M.; Hosal, Sefik; Klussmann, Jens Peter; Leemans, C. Rene; MacCarthy, Denise; Manduchi, Beatrice; Marie, Jean-Paul; Nouraei, Reza; Parkes, Claire; Pflug, Christina; Pilz, Walmari; Regan, Julie; Rommel, Nathalie; Schindler, Antonio; Schols, Annemie M. W. J.; Speyer, Renee; Succo, Giovanni; Wessel, Irene; Willemsen, Anna C. H.; Yilmaz, Taner; Clave, Pere (2021)
    Purpose To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. Methods Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. Results Twenty-four sections on HNC-specific OD topics. Conclusion This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.
  • Ruuskanen, Miia; Leivo, Ilmo; Minn, Heikki; Vahlberg, Tero; Haglund, Caj; Hagström, Jaana; Irjala, Heikki (BioMed Central, 2019)
    Abstract Background Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. Methods In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. Results We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). Conclusions TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.
  • Ruuskanen, Miia; Leivo, Ilmo; Minn, Heikki; Vahlberg, Tero; Haglund, Caj; Hagström, Jaana; Irjala, Heikki (2019)
    BackgroundNasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer.MethodsIn our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome.ResultsWe found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2(nucl) or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2(nucl)/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative).ConclusionsTLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.
  • Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemstrom, Karl; Paavonen, Timo; Toppila-Salmi, Sanna (2016)
    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (aeyen80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.
  • Al-Samadi, Ahmed; Poor, Benedek; Tuomainen, Katja; Liu, Ville; Hyytiäinen, Aini; Suleymanova, Ilida; Mesimäki, Karri; Wilkman, Tommy; Mäkitie, Antti; Saavalainen, Paivi; Salo, Tuula (2019)
    Objectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy. Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix "Myogel/fibrin" and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients' serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated. Results: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent. Conclusion: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients.
  • Dickinson, Amy; Saraswat, Mayank; Mäkitie, Antti; Silen, Robert; Hagström, Jaana; Haglund, Caj; Joenväärä, Sakari; Silen, Suvi (2018)
    Objectives: No prognostic or predictive biomarkers for oral squamous cell carcinoma (OSCC) exist. We aimed to discover novel proteins, altered in OSCC, to be further investigated as potential biomarkers, and to improve understanding about pathways involved in OSCC. Materials and Methods: Proteomic signatures of seven paired healthy and OSCC tissue samples were identified using ultra-definition quantitative mass spectrometry, then analysed and compared using Anova, principal component analysis, hierarchical clustering and OPLS-DA modelling. A selection of significant proteins that were also altered in the serum from a previous study (PMID: 28632724) were validated immunohistochemically on an independent cohort (n = 66) to confirm immunopositivity and location within tumour tissue. Ingenuity Pathways Analysis was employed to identify altered pathways. Results: Of 829 proteins quantified, 257 were significant and 72 were able to classify healthy vs OSCC using OPLS-DA modelling. We identified 19 proteins not previously known to be upregulated in OSCC, including prosaposin and alpha-taxilin. KIAA1217 and NDRG1 were upregulated in stage IVa compared with stage I tumours. Altered pathways included calcium signalling, cellular movement, haematological system development and function, and immune cell trafficking, and involved NF-kappa B and MAPK networks. Conclusions: We found a set of proteins reliably separating OSCC tumour from healthy tissue, and multiple proteins differing between stage I and stage IVa OSCC. These potential biomarkers can be studied and validated in larger cohorts.
  • Pehkonen, Henna; Lento, Mira; von Nandelstadh, Pernilla; Filippou, Artemis; Grenman, Reidar; Lehti, Kaisa; Monni, Outi (2018)
    Background: PPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-alpha 1 encoded by PPFIA1 contributes to the adhesive and invasive structures of cytoskeletal elements and is located at the invadosomes in cancer cells. However, the precise mechanism of liprin-alpha 1 function in cancer progression has remained elusive. Methods: Invasion regulating activity of liprin-alpha 1 was examined by analyzing the functions of squamous cell carcinoma of head and neck (HNSCC) cell lines in three-dimensional collagen I after RNAi mediated gene knockdown. Transcriptome profiling and Gene Set Enrichment Analysis from HNSCC and breast cancer cells were used to identify expression changes relevant to specific cellular localizations, biological processes and signaling pathways after PPFIA1 knockdown. The significance of the results was assessed by relevant statistical methods (Wald and Benjamini-Hochberg). Localization of proteins associated to liprin-alpha 1 was studied by immunofluorescence in 2D and 3D conditions. The association of PPFIA1 amplification to HNSCC patient survival was explored using The Cancer Genome Atlas data. Results: In this study, we show that liprin-alpha 1 regulates biological processes related to membrane microdomains in breast carcinoma, as well as protein trafficking, cell-cell and cell-substrate contacts in HNSCC cell lines cultured in three-dimensional matrix. Importantly, we show that in all these cancer cells liprin-alpha 1 knockdown leads to the upregulation of transmembrane protein CD82, which is a suppressor of metastasis in several solid tumors. Conclusions: Our results provide novel information regarding the function of liprin-alpha 1 in biological processes essential in cancer progression. The results reveal liprin-alpha 1 as a novel regulator of CD82, linking liprin-alpha 1 to the cancer cell invasion and metastasis pathways.
  • Pehkonen, Henna; Lento, Mira; von Nandelstadh, Pernilla; Filippou, Artemis; Grénman, Reidar; Lehti, Kaisa; Monni, Outi (BioMed Central, 2018)
    Abstract Background PPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-α1 encoded by PPF1A1 contributes to the adhesive and invasive structures of cytoskeletal elements and is located at the invadosomes in cancer cells. However, the precise mechanism of liprin-α1 function in cancer progression has remained elusive. Methods Invasion regulating activity of liprin-α1 was examined by analyzing the functions of squamous cell carcinoma of head and neck (HNSCC) cell lines in three-dimensional collagen I after RNAi mediated gene knockdown. Transcriptome profiling and Gene Set Enrichment Analysis from HNSCC and breast cancer cells were used to identify expression changes relevant to specific cellular localizations, biological processes and signaling pathways after PPFIA1 knockdown. The significance of the results was assessed by relevant statistical methods (Wald and Benjamini-Hochberg). Localization of proteins associated to liprin-α1 was studied by immunofluorescence in 2D and 3D conditions. The association of PPFIA1 amplification to HNSCC patient survival was explored using The Cancer Genome Atlas data. Results In this study, we show that liprin-α1 regulates biological processes related to membrane microdomains in breast carcinoma, as well as protein trafficking, cell-cell and cell-substrate contacts in HNSCC cell lines cultured in three-dimensional matrix. Importantly, we show that in all these cancer cells liprin-α1 knockdown leads to the upregulation of transmembrane protein CD82, which is a suppressor of metastasis in several solid tumors. Conclusions Our results provide novel information regarding the function of liprin-α1 in biological processes essential in cancer progression. The results reveal liprin-α1 as a novel regulator of CD82, linking liprin-α1 to the cancer cell invasion and metastasis pathways.
  • Kainulainen, Satu; Koivusalo, A. M.; Roine, R. P.; Wilkman, T.; Sintonen, H.; Törnwall, J.; Thoren, H.; Lassus, P. (2020)
    Purpose The aim of this study was to evaluate the long-term health-related quality of life (HRQoL) of head and neck cancer patients with microvascular surgery. Surgical treatment causes great changes in patient HRQoL. Studies focusing on long-term HRQoL after microvascular reconstruction for head and neck cancer patients are scarce. Methods We conducted a prospective study of 93 patients with head and neck cancer and microvascular reconstruction in Helsinki University Hospital Finland. HRQoL was measured using the 15D instrument at baseline and after a mean 4.9-years follow up. Results were compared with those of an age-standardized general population. Results Of the 93 patients, 61 (66%) were alive after follow-up; of these, 42 (69%) answered the follow-up questionnaire. The median time between surgery and HRQoL assessment was 4.9 years (range 3.7-7.8 years). The mean 15D score of all patients (n = 42) at the 4.9-years follow up was statistically significantly (p = 0.010) and clinically importantly lower than at baseline. The dimensions of "speech" and "usual activities" were significantly impaired at the end of follow up. There was a significant difference at the 4.9-years follow-up in the mean 15D score between patients and the general population (p = 0.014). After follow up, patients were significantly (p <0.05) worse off on the dimensions of "speech," "eating," and "usual activities." Conclusions Long-term HRQoL was significantly reduced in the whole patient cohort. Speech and usual activities were the most affected dimensions in head and neck cancer patients with microvascular reconstruction at the end of the 4.9-years follow up.
  • Jouhi, Lauri; Atula, Timo; Mäkitie, Antti; Keski-Santti, Harri (2019)
    PurposeOnly a minority of patients with oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed without regional metastasis (cN0). Studies focusing on the management of cN0 neck in OPSCC are scarce.MethodsWe reviewed all OPSCC patients treated at our institution with cN0 neck between 2000 and 2009. The treatment of neck and pattern of regional control was analyzed. Median follow-up was 5years (range 3.5-9.0) or until death.ResultsOf the total 313 OPSCC patients treated within the period, 56 (18%) presented with cN0 neck. Of them, 51 (91%) received completed treatment with curative intent: 46 (90%) underwent elective neck treatment with either neck dissection (chemo)radiotherapy (C)RT (n=23) or (C)RT (n=23). A regional recurrence occurred in three patients (6%) and they all had a p16-negative soft palate midline primary tumor. Two of these patients had received RT on the neck.Conclusions While the overall prognosis of OPSCC is generally favorable and regional recurrences are infrequent, soft palate tumors, that are usually p16 negative, may form an subgroup warranting more aggressive treatment despite the clinical appearance of early stage.
  • Mäkitie, Antti A.; Alabi, Rasheed Omobolaji; Orell, Helena; Youssef, Omar; Almangush, Alhadi; Homma, Akihiro; Takes, Robert P.; Lopez, Fernando; de Bree, Remco; Rodrigo, Juan P.; Ferlito, Alfio (2022)
    Introduction Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorexia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients. Methods We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC. Results A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to enhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome. Conclusion Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients.