Label-free tissue proteomics can classify oral squamous cell carcinoma from healthy tissue in a stage-specific manner

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.Peer reviewe

Presentation of second primary cancers in young laryngeal carcinoma patients

Background: Laryngeal squamous cell carcinoma (LSCC) is rare in the young. Objectives: We characterized the clinical behavior of LSCC and assessed the presentation of second primary tumors (SPCs) in this patient population. Materials and methods: Data from the Finnish Cancer Registry (FCR) were used to identify an epidemiological series of LSCC patients diagnosed at the age of 40 years or under, during 1953-2012 in Finland. Data regarding primary treatment, survival, and SPCs were available. To further characterize the comorbidity and lifestyle factors of young patients with LSCC, institutional data were collected of patients treated at the Helsinki University Hospital during 1967-2012. Results: We identified 151 patients, with a mean follow-up of 252 months. The 10-year overall survival (OS) was 75% and the disease-specific survival was 84%. SPCs were diagnosed in 26% (n = 39), with a median delay of 28 years. Of the 35 patients in the institutional series from Helsinki, 22 (63%) were current or former smokers. LSCC recurred in 28% of patients. Conclusions and Significance: The delay to SPCs in young patients was significantly longer compared with the general LSCC population. As factors underlying this phenomenon cannot be identified by this retrospective study, further studies are warranted.Peer reviewe

Inflammation parameters predict fatal outcome in male COVID-19 patients in a low case-fatality area - a population-based registry study

Background Male sex predicts case-fatality in SARS-CoV-2 (COVID-19) - a phenomenon linked to systemic inflammation. We compared sex-related associations of inflammation parameters and outcome in a population-based setting with low case-fatality prior to wide use of immunosuppressives. Methods A population-based quality registry with laboratory-confirmed COVID-19 cases of specialized hospitals of the Capital Province of Finland were analysed to compare inflammatory parameters by sex during the first COVID-19 wave February-June 2020. Results Altogether, 585 hospitalized patients (54% males) were included. Males required more often intensive care unit (ICU) treatment (26.9 vs. 17.5%) and had higher 90-d case-fatality (14.9 vs. 7.8%) compared with females. Highest association with case-fatality in males was seen for high neutrophil counts (median; interquartile range) (8.70; 7.10-9.10 vs. 5.60; 3.90-7.80) (E9/l), low monocyte (0.50; 0.20-1.50 vs. 0.70; 0.50-0.90) (E9/l) and lymphocyte (0.90; 0.70-1.40 vs. 1.50; 1.10-2.00) (E9/l) counts, and high levels of d-dimer (3.80; 1.80-5.30 vs. 1.10; 0.60-2.75) (mg/l) and C-reactive protein (CRP) (190; 85.5-290 vs. 77.0; 49.0-94.0) (mg/l). In females, low lymphocyte (0.95; interquartile range 0.60-1.28 vs. 1.50; 1.10-2.00) (E9/l) and thrombocyte counts (196; 132-285 vs. 325; 244-464) (E9/l) and high CRP values (95.0; 62.0-256 vs. 66.0; 42.5-89.0) (mg/l) were associated with case-fatality. In multivariable analysis for males, lymphocyte cut-off 0.85 (E9/l) (OR 0.02; 95% CI 0.002-0.260), d-dimer cut-off 1.15 (mg/l) (OR 7.29; 1.01-52.6) and CRP cut-off 110 (mg/l) (OR 15.4; 1.87-127) were independently associated with case-fatality. In female multivariable analysis, CRP cut-off 81 (mg/l) (OR 7.32; 1.44-37.2) was the only inflammatory parameter associated with case-fatality. Conclusions COVID-19 results in higher inflammation parameter levels in male vs. female patients irrespective of outcome. This study suggests that low lymphocyte, high d-dimer and high CRP cut-off values may serve as potential markers for risk stratification in male patients.Peer reviewe

Accuracy of preoperative MRI to assess lateral neck metastases in papillary thyroid carcinoma

Primary treatment of papillary thyroid carcinoma (PTC) with lateral lymph node metastasis is surgery, but the extent of lateral neck dissection remains undefined. Preoperative imaging is used to guide the extent of surgery, although its sensitivity and specificity for defining the number and level of affected lymph nodes on the lateral neck is relatively modest. Our aim was to assess the role of preoperative magnetic resonance imaging (MRI) in predicting the requisite levels of neck dissection in patients with regionally metastatic PTC, with a focus on Levels II and V. All patients with PTC and lateral neck metastasis who had undergone neck dissection at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland from 2013 to 2016 and had a preoperative MRI available were retrospectively reviewed. A head and neck radiologist re-evaluated all MRIs, and the imaging findings were compared with histopathology after neck dissection. In the cohort of 39 patients, preoperative MRI showed concordance with histopathology for Levels II and V as follows: sensitivity of 94 and 67%, specificity of 20 and 91%, positive predictive value of 56 and 75%, and negative predictive value of 75 and 87%, respectively. In PTC, MRI demonstrated fairly high specificity and negative predictive value for Level V metastasis, and future studies are needed to verify our results to omit prophylactic dissection of this level. Routine dissection of Level II in patients with regionally metastatic PTC needs to be considered, as MRI showed low specificity.Peer reviewe

Mass spectrometry-based lipidomics of oral squamous cell carcinoma tissue reveals aberrant cholesterol and glycerophospholipid metabolism - A Pilot study

Lipid metabolic reprogramming is one hallmark of cancer. Lipid metabolism is regulated by numerous enzymes, many of which are targeted by several drugs on the market. We aimed to characterize the lipid alterations in oral squamous cell carcinoma (OSCC) as a basis for understanding its lipid metabolism, thus identifying potential therapeutic targets. We compared lipid species, classes, and glycerophospholipid (GPL) fatty acid species between paired tumor tissue and healthy oral tongue mucosa samples from 10 OSCC patients using a QExactive mass spectrometer. After filtering the 1370 lipid species identified, we analyzed 349 species: 71 were significantly increased in OSCC. The GPL metabolism pathway was most represented by the lipids differing in OSCC (P = .005). Cholesterol and the GPLs phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols were most significantly increased in OSCC tissue (FC 1.8, 2.0, 2.1, and 2.3 and, P = .003, P = .005, P = .002, P = .007). In conclusion, we have demonstrated a shift in the lipid metabolism in these OSCC samples by characterizing the detailed landscape. Predominantly, cholesterol and GPL metabolism were altered, suggesting that interactions with sterol regulatory binding proteins may be involved. The FA composition changes of the GPLs suggest increased de novo lipogenesis.Peer reviewe

Male predominance in disease severity and mortality in a low Covid-19 epidemic and low case-fatality area - a population-based registry study

Background Men reportedly suffer from a more severe disease and higher mortality during the global SARS-CoV-2 (Covid-19) pandemic. We analysed sex differences in a low epidemic area with low overall mortality in Covid-19 in a population based setting with patients treated in specialized healthcare. Methods We entered all hospitalized laboratory-confirmed Covid-19 cases of all specialized healthcare hospitals of the Capital Province of Finland, into a population-based quality registry and described demographics, severity and case-fatality by sex of the first Covid-19 wave February-June 2020. Results Altogether 5471 patients (49% male) were identified. Patients hospitalized in the specialist healthcare (N = 585, 54% male, OR 1.25; 95% CI 1.05-1.48) were of the same age. Men had less asthma and thyroid insufficiency and more coronary artery disease compared to women. Mean time from symptom onset to diagnosis was at least one day longer for men (p=.005). Men required intensive care unit (ICU) more often (27% vs. 17%) with longer lengths-of-stays at ICU. Male sex associated with significantly higher case-fatality at 90-days (15% vs. 8%) and all excess male deaths occurring after three weeks from onset. Men with fatal outcomes had delays in both Covid-19 testing and hospital admission after a positive test. The delays in patients with the most severe and fatal outcomes differed markedly by sex. In multivariable analysis, male sex associated independently with case-fatality (OR 2.37; 95% CI 1.22-4.59). Conclusions Male sex associated with higher disease severity and case-fatality. Late presentation of male fatal cases could represent different treatment-seeking behaviour or disease progression by sex.Peer reviewe

Newly detected DNA viruses in juvenile nasopharyngeal angiofibroma (JNA) and oral and oropharyngeal squamous cell carcinoma (OSCC/OPSCC)

PurposeApproximately 20% of cancers are estimated to have a viral etiology. We aimed to investigate whether DNA of 8 human parvoviruses [bocavirus 1-4 (HBoV1-4), parvovirus B19 (B19V), protoparvoviruses (bufa-, tusa-, and cutavirus)] and 13 human polyomaviruses (HPyV) can be detected in oropharyngeal and oral cavity squamous cell carcinoma (OPSCC/OSCC), and in juvenile nasopharyngeal angiofibroma (JNA) tissue samples.MethodsFresh samples of seven JNA tissues and ten paired tissues of OSCC/OPSCC tumor and adjacent healthy tissues were collected. DNA extraction and real-time PCRs were performed to detect HBoV1-4, B19V, bufa- tusa- and cutavirus, and HPyV genomes.ResultsJNA specimens were negative for all parvoviruses tested, whereas one JNA sample was Merkel cell polyomavirus (MCPyV) DNA positive. The OSCC/OPSCC samples were negative for the human protoparvoviruses, HBoV1-4, and all human polyomaviruses, except for one patient that was MCPyV DNA positive in both healthy and tumor tissues. Seven OSCC/OPSCC patients were positive for B19V DNA, three of them in both healthy and cancerous tissues and three in only healthy tissues. Three of the B19V DNA-positive patients harbored viral genotype 1, three genotype 2, and one genotype 3B.ConclusionsThese are the first reports of MCPyV and B19V DNA being detected in JNA and OPSCC. The significance of viral DNA positivity is unclear. B19V DNA is known to remain in the tissues lifelong, however, it is of interest that there are some patients with B19 DNA in healthy tissue, but not in the corresponding cancer tissue.Peer reviewe

In situ hybridization for high-risk HPV E6/E7 mRNA is a superior method for detecting transcriptionally active HPV in oropharyngeal cancer

Current human papillomavirus (HPV) detection methods in oropharyngeal squamous cell carcinoma (OPSCC) have varying sensitivity and specificity. We aimed to compare different HPV-detection methods against the test used in clinical practice, ie, p16 immunohistochemistry (IHC) and to evaluate whether another HPV-detection test additional to p16 IHC would be worthwhile in OPSCC specimens. The study cohort comprised 357 consecutive OPSCC patients during two time periods: 2000-2009 and 2012-2016. From tumor tissue slides, HPV mRNA via in situ hybridization (ISH), HPV DNA via ISH and HPV DNA via polymerase chain reaction (PCR) were detected. The results of these methods were compared with p16 IHC results. Additionally, clinicopathological factors were compared with the methods studied. The sensitivity of HPV mRNA ISH, HPV DNA ISH and HPV DNA PCR were 93.4%, 86.3%, and 83.5%, respectively. The corresponding specificity was 92.4%, 95.3%, and 89.1%, respectively. The negative predictive value for p16 IHC was highest (89.0%) when using mRNA ISH, and followed by DNA ISH (83.5%). ISH for high-risk HPV E6/E7 mRNA was found to be a highly specific and sensitive method for detecting HPV in OPSCC. As p16 protein may be overexpressed due to HPV-independent mechanisms, all p16 IHC positive OPSCCs should be considered for retesting using mRNA ISH in order to verify transcriptionally active HPV. This is especially critical when considering de-escalated treatment approaches for patients with HPV-positive tumors and still maintaining favorable outcomes for this subgroup of patients. (C) 2019 Elsevier Inc. All rights reserved.Peer reviewe

Pysy lähelläni : opas pienten lasten vanhemmille seksuaalisuuden vahvistamiseksi parisuhteessa

Opinnäytetyö toteutui kehittämistyönä Metropolia AMK:n sekä Kymenlaakson AMK:n yhteisessä hankkeessa ”Positiivisen mielenterveyden edistäminen pikkulapsiperheissä”. Opinnäytetyön tarkoituksena oli luoda opas 3–5-vuotiaiden lasten vanhemmille sekä vastata kehittämistehtäviin. Oppaan tavoitteena oli auttaa vanhempia vahvistamaan ja ylläpitämään seksuaalisuhdettaan kuormittavien ruuhkavuosien aikana. Opinnäytetyön kehittämistehtävät olivat 1) Millainen on hyvä opas? 2) Miten pienten lasten vanhempien parisuhde ja seksuaalisuhde muuttuu vanhemmaksi tulon myötä? 3) Miten pienten lasten vanhemmat voivat ylläpitää ja edistää parisuhteensa seksuaalisuutta? Opinnäytetyön tavoitteena oli lisätä vanhempien ymmärrystä heidän seksin merkityksestä heidän parisuhteelleen sekä siten edistää koko perheen positiivista mielenterveyttä. Vanhemmaksi tuleminen on suuri muutos parisuhteelle, ja aiheuttaa suhteelle tietynlaisen kriisin. Erityisesti muuttunut ajankäyttö ja yhteisen ajan väheneminen kuormittavat suhdetta. Tutkimamme aineiston perusteella keinoiksi vahvistaa seksuaalisuutta kumppaneiden välillä nousivat tunneyhteyden parantaminen, fyysisen läheisyyden lisääminen sekä seksuaalisen nautinnon parantaminen. Suhteeseen panostaminen ja suhteen säännöllinen hoitaminen ovat tärkeää, ja ne heijastuvat kumppaneiden väliseen seksuaalisuuteen. Opinnäytetyön tuloksena syntyi opas ”Pysy lähelläni” -Oppaalla ei vielä ole jakelukanavaa, joten erityisesti opinnäytetyön hyödynnettävyyttä voitaisiin vielä kehittää. Oppaan teoreettista viitekehystä luodessa kävi ilmi, että Suomessa on tutkittu niukasti noin 3–5-vuotiaiden lasten vanhempien seksuaalista tyytyväisyyttä ja siihen vaikuttavia tekijöitä. Jatkotutkimuksissa olisi mielenkiintoista selvittää aihetta tarkemmin myös Suomessa.The final project was part of ongoing project of Metropolia University of Applied Sciences and Kymenlaakso University of Applied Sciences. The Project is aiming to promote positive mental health in families that has young children. The final project was development project and the purpose was to design a guide for the parents of young children and answer the research questions. Aim of the guide was to give parents of young children tools to strength and maintain their sexual relationship when life is hectic. The research questions that guided the final project were: 1) What qualities a good guide has? 2) How does the transition to parenthood change the young children’s parents’ relationship and sexual relationship? 3) How could the parents of young children maintain and strengthen sexuality in parental relationship? Aim of the final project was to make parents understand the influence of their satisfying sexual relationship for the positive mental health of the whole family unit. At the transition to parenthood, the relationship between parents goes under a lot of pressure. This is caused by the lack of shared free time and independence of parents. Based on the research it seems that to avoid this crisis, parents of young children should increase their intimacy, emotional intimacy and sexual satisfaction. Parents should make effort for the relationship and take care of it. Product of The final project was a guide named as “Stay Close”. The guide still hasn’t any distribution channel. For that reason, usability of the final project is something that needs to be developed. There weren’t that many studies of subject in Finland, so it would be interesting to study how parents of young children experience their sexual parental relationship in Finland