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1. Effectiveness of SARS-CoV-2 primary vaccines and boosters in patients with type 2 diabetes mellitus in Hungary (HUN-VE 4 Study)

Author

Miklos Kasler, Gábor Sütő, Gergő A Molnár, Gyorgy Rokszin, Zoltan Kiss, István Wittmann, István Kenessey, Zoltan Voko, Andras Weber, Peter Nagy, Dávid Nagy, György Surján, Orsolya Surján, Mihály Pálosi, and Cecília Müller

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary.Research design and methods Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model.Results A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the ‘healthy’ controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14–120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65–100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65–100 years: 89.1 (88.1–89.9)% with Pfizer-on-Pfizer, controls 65–100 years old: 86.9 (85.8–88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65–100 years: 88.3 (87.2–89.2)% with Pfizer-on-Sinopharm, controls 65–100 years old: 87.8 (86.8–88.7)% with Pfizer-on-Sinopharm).Conclusions Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection.

Published
2024
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2. Waning of SARS-CoV-2 Vaccine Effectiveness in COPD Patients: Lessons from the Delta Variant

Author

Lörinc Polivka, Istvan Valyi-Nagy, Zoltan Szekanecz, Krisztina Bogos, Hajnalka Vago, Anita Kamondi, Ferenc Fekete, Janos Szlavik, György Surjan, Orsolya Surjan, Peter Nagy, Zsuzsa Schaff, Zoltan Kiss, Cecilia Müller, Miklos Kasler, and Veronika Müller

Subjects
COVID-19, COPD, vaccine effectiveness, VE, waning, Medicine
Abstract

Although the COVID-19 pandemic is profoundly changing, data on the effect of vaccination and duration of protection against infection and severe disease can still be advantageous, especially for patients with COPD, who are more vulnerable to respiratory infections. The Hungarian COVID-19 registry was retrospectively investigated for risk of infection and hospitalization by time since the last vaccination, and vaccine effectiveness (VE) was calculated in adults with COPD diagnosis and an exact-matched control group during the Delta variant of concern (VOC) wave in Hungary (September–December 2021). For the matching, sex, age, major co-morbidities, vaccination status, and prior infection data were obtained on 23 August 2021. The study population included 373,962 cases divided into COPD patients (age: 66.67 ± 12.66) and a 1:1 matched group (age: 66.73 ± 12.67). In both groups, the female/male ratio was 52.2:47.7, respectively. Among the unvaccinated, there was no difference between groups in risk for infection or hospitalization. Regarding vaccinated cases, in the COPD group, a slightly faster decline in effectiveness was noted for hospitalization prevention, although in both groups, the vaccine lost its significant effect between 215 and 240 days after the last dose of vaccination. Based on a time-stratified multivariate Cox analysis of the vaccinated cases, the hazard was constantly higher in the COPD group, with an HR of 1.09 (95%: 1.05–1.14) for infection and 1.87 (95% CI: 1.59–2.19) for hospitalization. In our study, COPD patients displayed lower vaccine effectiveness against SARS-CoV-2 infection and hospitalization but a similar waning trajectory, as vaccines lost their preventive effect after 215 days. These data emphasize revaccination measures in the COPD patient population.

Published
2023
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3. Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor

Author

Beatrix Kotlan, Szabolcs Horvath, Klara Eles, Vanda K. Plotar, Gyorgy Naszados, Katalin Czirbesz, Miri Blank, Emil Farkas, Laszlo Toth, Jozsef Tovari, Andras Szekacs, Yehuda Shoenfeld, Maria Godeny, Miklos Kasler, and Gabriella Liszkay

Subjects
B lymphocytes, glycosphingolipids (GSLs), immune regulation, immunoglobulin, metastatic melanomas, natural antibody, Immunologic diseases. Allergy, RC581-607
Abstract

There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose two solid tumor types, with variable to considerable B cell infiltration. The strategy we set up with invasive breast carcinoma, showing medullary features, has been introduced and standardized in metastatic melanoma. After detecting B lymphocytes by immunohistochemistry, VH-JH, Vκ-Jκ immunoglobulin rearranged V region genes were amplified by RT-PCR, from TIL-B cDNA. Immunoglobulin variable-region genes of interest were cloned, sequenced, and subjected to a comparative DNA analysis. Single-chain variable (scFv) antibody construction was performed in selected cases to generate a scFv library and to test tumor binding capacity. DNA sequence analysis revealed an overrepresented VH3-1 cluster, represented both in the breast cancer and the melanoma TIL-B immunoglobulin repertoire. We observed that our previously defined anti GD3 ganglioside-binder antibody-variable region genes were present in melanoma as well. Our antibody fragments showed binding potential to disialylated glycosphingolipids (GD3 ganglioside) and their O acetylated forms on melanoma cancer cells. We conclude that our results have a considerable tumor immunological impact, as they reveal the power of TIL-B cells to recognize strong tumor-associated glycosphingolipid structures on melanomas and other solid tumors. As tumor-derived gangliosides affect immune cell functions and reduce the B lymphocytes' antibody production, we suspect an important B lymphocyte and cancer cell crosstalk mechanism. We not only described the isolation and specificity testing of the tumor infiltrating B cells, but also showed the TIL-B cells' highly tumor-associated GD3 ganglioside-revealing potential in melanomas. The present data help to identify new cancer-associated biomarkers that may serve for novel cancer diagnostics. The two-direction regulation mechanism between immune B cells and the tumor could eventually be developed into an innovative cancer treatment strategy.

Published
2019
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4. Analysis of Gyimes Csango population samples on a high-resolution genome-wide basis

Author

Zsolt Bánfai, Gergely Büki, Valerián Ádám, Katalin Sümegi, András Szabó, Kinga Hadzsiev, Krisztián Erős, Ferenc Gallyas, Attila Miseta, Miklós Kásler, and Béla Melegh

Subjects
DNA microarray, Ancestry, Population structure, Csango, Allele frequency, Haplotype, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background The Csangos are an East-Central European ethnographic group living mainly in east of Transylvania in Romania. Traditionally, ethnography distinguishes three Csango subpopulations, the Moldavian, Gyimes and Burzenland Csangos. In our previous study we found that the Moldavian Csangos have East Asian/Siberian Turkic ancestry components that might be unique in the East-Central European region and might help to better understand the history of Hungarian speaking ethnic groups of the area. Since then, we obtained further Csango samples from Moldavia and from a distinct region of Gyimes, which two Csango subgroups are traditionally different since they live in a degree of isolation not only from other people but also from each other. Here we present the first genomic analysis of Gyimes Csangos, which intended to compare the genetic makeup of these two Csango subgroups using both allele-frequency and haplotype-based methods. The main goal of the study was to investigate the genetic isolation of the Csangos on a genome-wide SNP basis and to assess the isolation of Gyimes Csangos, which in contrast to the Moldavians was not yet studied. Results Our results show that these two Csango groups show slight differences from each other. We confirmed the genetic isolation of Moldavian Csangos and revealed that Gyimes Csangos have a similar, but detectably weaker isolation. In the case of Gyimes Csangos we detected also a stronger East European or presumably Asian derived ancestry. Conclusion The Gyimes Csangos show a degree of genetic isolation comparable to that of the Moldavians. The Asian ancestry that differentiates the Moldavian Csango people from the other East-Central European populations may be present in the Gyimes Csangos in an even higher degree, since Gyimes Csango individuals show a more significant share from that ancestry component.

Published
2024
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5. Characterization of Danube Swabian population samples on a high-resolution genome-wide basis

Author

Zsolt Bánfai, Erzsébet Kövesdi, Katalin Sümegi, Gergely Büki, András Szabó, Lili Magyari, Valerián Ádám, Ferenc Pálos, Attila Miseta, Miklós Kásler, and Béla Melegh

Subjects
Genome-wide data, Population genetics, Swabians, Ethnic group, Admixture, Haplotype, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcső-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3–6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. Results Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. Conclusion This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.

Published
2023
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6. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin Jaiswal, Michael Curran, Tina C. Albershardt, Anshika Bajaj, Jacob F. Archer, Rebecca S. Reeves, Lisa Y. Ngo, Peter Berglund, Jan ter Meulen, Caroline Denis, Hormas Ghadially, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Robert W. Wilkinson, Nicolai Wagtmann, Yannis Morel, Pascale Andre, Michael B. Atkins, Matteo S. Carlino, Antoni Ribas, John A. Thompson, Toni K. Choueiri, F. Stephen Hodi, Wen-Jen Hwu, David F. McDermott, Victoria Atkinson, Jonathan S. Cebon, Bernie Fitzharris, Michael B. Jameson, Catriona McNeil, Andrew G. Hill, Eric Mangin, Malidi Ahamadi, Marianne van Vugt, Mariëlle van Zutphen, Nageatte Ibrahim, Georgina V. Long, Robyn Gartrell, Zoe Blake, Ines Simoes, Yichun Fu, Takuro Saito, Yingzhi Qian, Yan Lu, Yvonne M. Saenger, Sadna Budhu, Olivier De Henau, Roberta Zappasodi, Kyle Schlunegger, Bruce Freimark, Jeff Hutchins, Christopher A. Barker, Jedd D. Wolchok, Taha Merghoub, Elena Burova, Omaira Allbritton, Peter Hong, Jie Dai, Jerry Pei, Matt Liu, Joel Kantrowitz, Venus Lai, William Poueymirou, Douglas MacDonald, Ella Ioffe, Markus Mohrs, William Olson, Gavin Thurston, Cristian Capasso, Federica Frascaro, Sara Carpi, Siri Tähtinen, Sara Feola, Manlio Fusciello, Karita Peltonen, Beatriz Martins, Madeleine Sjöberg, Sari Pesonen, Tuuli Ranki, Lukasz Kyruk, Erkko Ylösmäki, Vincenzo Cerullo, Fabio Cerignoli, Biao Xi, Garret Guenther, Naichen Yu, Lincoln Muir, Leyna Zhao, Yama Abassi, Víctor Cervera-Carrascón, Mikko Siurala, João Santos, Riikka Havunen, Suvi Parviainen, Akseli Hemminki, Angus Dalgleish, Satvinder Mudan, Mark DeBenedette, Ana Plachco, Alicia Gamble, Elizabeth W. Grogan, John Krisko, Irina Tcherepanova, Charles Nicolette, Pooja Dhupkar, Ling Yu, Eugenie S. Kleinerman, Nancy Gordon, Italia Grenga, Lauren Lepone, Sofia Gameiro, Karin M. Knudson, Massimo Fantini, Kwong Tsang, James Hodge, Renee Donahue, Jeffrey Schlom, Elizabeth Evans, Holm Bussler, Crystal Mallow, Christine Reilly, Sebold Torno, Maria Scrivens, Cathie Foster, Alan Howell, Leslie Balch, Alyssa Knapp, John E. Leonard, Mark Paris, Terry Fisher, Siwen Hu-Lieskovan, Ernest Smith, Maurice Zauderer, William Fogler, Marilyn Franklin, Matt Thayer, Dan Saims, John L. Magnani, Jian Gong, Michael Gray, George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H. Schreiber, Sofia R. Gameiro, Paul E. Clavijo, Clint T. Allen, James W. Hodge, Kwong Y. Tsang, Jane Grogan, Nicholas Manieri, Eugene Chiang, Patrick Caplazi, Mahesh Yadav, Patrick Hagner, Hsiling Chiu, Michelle Waldman, Anke Klippel, Anjan Thakurta, Michael Pourdehnad, Anita Gandhi, Ian Henrich, Laura Quick, Rob Young, Margaret Chou, Andrew Hotson, Stephen Willingham, Po Ho, Carmen Choy, Ginna Laport, Ian McCaffery, Richard Miller, Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhiu Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James West, Bryan A. Irving, Ritika Jaini, Matthew Loya, Charis Eng, Melissa L. Johnson, Alex A. Adjei, Mateusz Opyrchal, Suresh Ramalingam, Pasi A. Janne, George Dominguez, Dmitry Gabrilovich, Laura de Leon, Jeannette Hasapidis, Scott J. Diede, Peter Ordentlich, Scott Cruickshank, Michael L. Meyers, Matthew D. Hellmann, Pawel Kalinski, Amer Zureikat, Robert Edwards, Ravi Muthuswamy, Nataša Obermajer, Julie Urban, Lisa H. Butterfield, William Gooding, Herbert Zeh, David Bartlett, Olga Zubkova, Larissa Agapova, Marina Kapralova, Liudmila Krasovskaia, Armen Ovsepyan, Maxim Lykov, Artem Eremeev, Vladimir Bokovanov, Olga Grigoryeva, Andrey Karpov, Sergey Ruchko, Alexandr Shuster, Danny N. Khalil, Luis Felipe Campesato, Yanyun Li, Adam S. Lazorchak, Troy D. Patterson, Yueyun Ding, Pottayil Sasikumar, Naremaddepalli Sudarshan, Nagaraj Gowda, Raghuveer Ramachandra, Dodheri Samiulla, Sanjeev Giri, Rajesh Eswarappa, Murali Ramachandra, David Tuck, Timothy Wyant, Jasmin Leshem, Xiu-fen Liu, Tapan Bera, Masaki Terabe, Birgit Bossenmaier, Gerhard Niederfellner, Yoram Reiter, Ira Pastan, Leiming Xia, Yang Xia, Yangyang Hu, Yi Wang, Yangyi Bao, Fu Dai, Shiang Huang, Elaine Hurt, Robert E. Hollingsworth, Lawrence G. Lum, Alfred E. Chang, Max S. Wicha, Qiao Li, Thomas Mace, Neil Makhijani, Erin Talbert, Gregory Young, Denis Guttridge, Darwin Conwell, Gregory B. Lesinski, Rodney JM Macedo Gonzales, Austin P. Huffman, Ximi K. Wang, Ran Reshef, Andy MacKinnon, Jason Chen, Matt Gross, Gisele Marguier, Peter Shwonek, Natalija Sotirovska, Susanne Steggerda, Francesco Parlati, Amani Makkouk, Mark K. Bennett, Ethan Emberley, Tony Huang, Weiqun Li, Silinda Neou, Alison Pan, Jing Zhang, Winter Zhang, Netonia Marshall, Thomas U. Marron, Judith Agudo, Brian Brown, Joshua Brody, Christopher McQuinn, Matthew Farren, Hannah Komar, Reena Shakya, Thomas Ludwug, Y. Maurice Morillon, Scott A. Hammond, John W. Greiner, Pulak R. Nath, Anthony L. Schwartz, Dragan Maric, David D. Roberts, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Deborah J. Wong, Manish Patel, Gerald Falchook, Shubham Pant, Patrick A. Ott, Melinda Whiteside, Amita Patnaik, John Mumm, Filip Janku, Ivan Chan, Todd Bauer, Rivka Colen, Peter VanVlasselaer, Gail L. Brown, Nizar M. Tannir, Martin Oft, Jeffrey Infante, Evan Lipson, Ajay Gopal, Sattva S. Neelapu, Philippe Armand, Stephen Spurgeon, John P. Leonard, Rachel E. Sanborn, Ignacio Melero, Thomas F. Gajewski, Matthew Maurer, Serena Perna, Andres A. Gutierrez, Raphael Clynes, Priyam Mitra, Satyendra Suryawanshi, Douglas Gladstone, Margaret K. Callahan, James Crooks, Sheila Brown, Audrey Gauthier, Marc Hillairet de Boisferon, Andrew MacDonald, Laura Rosa Brunet, William T. Rothwell, Peter Bell, James M. Wilson, Fumi Sato-Kaneko, Shiyin Yao, Shannon S. Zhang, Dennis A. Carson, Cristina Guiducci, Robert L. Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Tomoko Hayashi, Ezra E. W. Cohen, David Schaer, Yanxia Li, Julie Dobkin, Michael Amatulli, Gerald Hall, Thompson Doman, Jason Manro, Frank Charles Dorsey, Lillian Sams, Rikke Holmgaard, Krishnadatt Persaud, Dale Ludwig, David Surguladze, John S. Kauh, Ruslan Novosiadly, Michael Kalos, Kyla Driscoll, Hardev Pandha, Christy Ralph, Kevin Harrington, Brendan Curti, Wallace Akerley, Sumati Gupta, Alan Melcher, David Mansfield, David R. Kaufman, Emmett Schmidt, Mark Grose, Bronwyn Davies, Roberta Karpathy, Darren Shafren, Katerina Shamalov, Cyrille Cohen, Naveen Sharma, James Allison, Tala Shekarian, Sandrine Valsesia-Wittmann, Christophe Caux, Aurelien Marabelle, Brian M. Slomovitz, Kathleen M. Moore, Hagop Youssoufian, Marshall Posner, Poonam Tewary, Alan D. Brooks, Ya-Ming Xu, Kithsiri Wijeratne, Leslie A. A. Gunatilaka, Thomas J. Sayers, John P. Vasilakos, Tesha Alston, Simon Dovedi, James Elvecrog, Iwen Grigsby, Ronald Herbst, Karen Johnson, Craig Moeckly, Stefanie Mullins, Kristen Siebenaler, Julius SternJohn, Ashenafi Tilahun, Mark A. Tomai, Katharina Vogel, Eveline E. Vietsch, Anton Wellstein, Martin Wythes, Stefano Crosignani, Joseph Tumang, Shilpa Alekar, Patrick Bingham, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, JunLi Feng, Kim Frederix, Samantha Greasley, Jie Guo, James Hardwick, Stephen Kaiser, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Kevin Ryan, Stephanie Scales, Jay Srirangam, Jim Solowiej, Al Stewart, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Xianxian Zheng, Gregory Driessens, Bruno Gomes, Manfred Kraus, Chunxiao Xu, Yanping Zhang, Giorgio Kradjian, Guozhong Qin, Jin Qi, Xiaomei Xu, Bo Marelli, Huakui Yu, Wilson Guzman, Rober Tighe, Rachel Salazar, Kin-Ming Lo, Jessie English, Laszlo Radvanyi, Yan Lan, Michael Postow, Yasin Senbabaoglu, Billel Gasmi, Hong Zhong, Cailian Liu, Daniel Hirschhorhn-Cymerman, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Yusuke Nakamura, Hongtao Liu, Xiaoming Ju, Rachelle Kosoff, Kimberly Ramos, Brandon Coder, Robert Petit, Michael Princiotta, Kyle Perry, Jun Zou, Ainhoa Arina, Christian Fernandez, Wenxin Zheng, Michael A. Beckett, Helena J. Mauceri, Yang-Xin Fu, Ralph R. Weichselbaum, Whitney Lewis, Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Dongyun Wu, Jin Li, Xiaoling Liang, Xiangjun Zhou, Jinlin Hou, Raffit Hassan, Thierry Jahan, Scott J. Antonia, Hedy L. Kindler, Evan W. Alley, Somayeh Honarmand, Weiqun Liu, Meredith L. Leong, Chan C. Whiting, Nitya Nair, Amanda Enstrom, Edward E. Lemmens, Takahiro Tsujikawa, Sushil Kumar, Lisa M. Coussens, Aimee L. Murphy, Dirk G. Brockstedt, Sven D. Koch, Martin Sebastian, Christian Weiss, Martin Früh, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geissler, Frank Griesinger, Jens Kollmeier, Alexandros Papachristofilou, Fatma Doener, Mariola Fotin-Mleczek, Madeleine Hipp, Henoch S. Hong, Karl-Josef Kallen, Ute Klinkhardt, Claudia Stosnach, Birgit Scheel, Andreas Schroeder, Tobias Seibel, Ulrike Gnad-Vogt, Alfred Zippelius, Ha-Ram Park, Yong-Oon Ahn, Tae Min Kim, Soyeon Kim, Seulki Kim, Yu Soo Lee, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Shari Pilon-Thomas, Amy Weber, Jennifer Morse, Krithika Kodumudi, Hao Liu, John Mullinax, Amod A. Sarnaik, Luke Pike, Andrew Bang, Tracy Balboni, Allison Taylor, Alexander Spektor, Tyler Wilhite, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal Aizer, Elizabeth Buchbinder, Mark Awad, Leena Ghandi, Jonathan Schoenfeld, Elizabeth Lessey-Morillon, Lisa Ridnour, Neil H. Segal, Manish Sharma, Dung T. Le, Robert L. Ferris, Andrew D. Zelenetz, Ronald Levy, Izidore S. Lossos, Caron Jacobson, Radhakrishnan Ramchandren, John Godwin, A. Dimitrios Colevas, Roland Meier, Suba Krishnan, Xuemin Gu, Jaclyn Neely, John Timmerman, Claire I. Vanpouille-Box, Silvia C. Formenti, Sandra Demaria, Erik Wennerberg, Aranzazu Mediero, Bruce N. Cronstein, Michael P. Gustafson, AriCeli DiCostanzo, Courtney Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A. Gastineau, Bruce D. Johnson, Allan B. Dietz, Cameron MacDonald, Mark Bucsek, Guanxi Qiao, Bonnie Hylander, Elizabeth Repasky, William J. Turbitt, Yitong Xu, Andrea Mastro, Connie J. Rogers, Sita Withers, Ziming Wang, Lam T. Khuat, Cordelia Dunai, Bruce R. Blazar, Dan Longo, Robert Rebhun, Steven K. Grossenbacher, Arta Monjazeb, William J. Murphy, Scott Rowlinson, Giulia Agnello, Susan Alters, David Lowe, Nicole Scharping, Ashley V. Menk, Ryan Whetstone, Xue Zeng, Greg M. Delgoffe, Patricia M. Santos, Jian Shi, Greg Delgoffe, Misako Nagasaka, Ammar Sukari, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Natalie Collins, Robert Manguso, Hans Pope, Yashaswi Shrestha, Jesse Boehm, W. Nicholas Haining, Kyle R. Cron, Ayelet Sivan, Keston Aquino-Michaels, Marco Orecchioni, Davide Bedognetti, Wouter Hendrickx, Claudia Fuoco, Filomena Spada, Francesco Sgarrella, Gianni Cesareni, Francesco Marincola, Kostas Kostarelos, Alberto Bianco, Lucia Delogu, Jessica Roelands, Sabri Boughorbel, Julie Decock, Scott Presnell, Ena Wang, Franco M. Marincola, Peter Kuppen, Michele Ceccarelli, Darawan Rinchai, Damien Chaussabel, Lance Miller, Andrew Nguyen, J. Zachary Sanborn, Charles Vaske, Shahrooz Rabizadeh, Kayvan Niazi, Steven Benz, Shashank Patel, Nicholas Restifo, James White, Sam Angiuoli, Mark Sausen, Sian Jones, Maria Sevdali, John Simmons, Victor Velculescu, Luis Diaz, Theresa Zhang, Jennifer S. Sims, Sunjay M. Barton, Angela Kadenhe-Chiweshe, Filemon Dela Cruz, Andrew T. Turk, Christopher F. Mazzeo, Andrew L. Kung, Jeffrey N. Bruce, Darrell J. Yamashiro, Eileen P. Connolly, Jason Baird, Marka Crittenden, David Friedman, Hong Xiao, Rom Leidner, Bryan Bell, Kristina Young, Michael Gough, Zhen Bian, Koby Kidder, Yuan Liu, Emily Curran, Xiufen Chen, Leticia P. Corrales, Justin Kline, Ethan G. Aguilar, Jennifer Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Suzan Lazo, Roderick Bronson, Anthony Letai, Richard S. Kornbluth, Sachin Gupta, James Termini, Elizabeth Guirado, Geoffrey W. Stone, Christina Meyer, Laura Helming, Nicholas Wilson, Robert Hofmeister, Natalie J. Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A. Fuertes Marraco, Daniel E. Speiser, Tara S. Abraham, Bo Xiang, Michael S. Magee, Scott A. Waldman, Adam E. Snook, Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Barbara Dolegowska, Teresa Starzynska, Leo Chan, Srinivas Somanchi, Kelsey McCulley, Dean Lee, Nico Buettner, Feng Shi, Paisley T. Myers, Stuart Curbishley, Sarah A. Penny, Lora Steadman, David Millar, Ellen Speers, Nicola Ruth, Gabriel Wong, Robert Thimme, David Adams, Mark Cobbold, Remy Thomas, Mariam Al-Muftah, Michael KK Wong, Michael Morse, Joseph I. Clark, Howard L. Kaufman, Gregory A. Daniels, Hong Hua, Tharak Rao, Janice P. Dutcher, Kai Kang, Yogen Saunthararajah, Vamsidhar Velcheti, Vikas Kumar, Firoz Anwar, Amita Verma, Zinal Chheda, Gary Kohanbash, John Sidney, Kaori Okada, Shruti Shrivastav, Diego A. Carrera, Shuming Liu, Naznin Jahan, Sabine Mueller, Ian F. Pollack, Angel M. Carcaboso, Alessandro Sette, Yafei Hou, Hideho Okada, Jessica J. Field, Weiping Zeng, Vincent FS Shih, Che-Leung Law, Peter D. Senter, Shyra J. Gardai, Nicole M. Okeley, Jennifer G. Abelin, Abu Z. Saeed, Stacy A. Malaker, Jeffrey Shabanowitz, Stephen T. Ward, Donald F. Hunt, Pam Profusek, Laura Wood, Dale Shepard, Petros Grivas, Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig, Manuel Schmidt, Julian P. Sefrin, Lars Hillringhaus, Valeria Lifke, Alexander Lifke, Anna Skaletskaya, Jose Ponte, Thomas Chittenden, Yulius Setiady, Eva Sivado, Vincent Thomas, Meddy El Alaoui, Sébastien Papot, Charles Dumontet, Mike Dyson, John McCafferty, Said El Alaoui, Praveen K. Bommareddy, Andrew Zloza, Frederick Kohlhapp, Ann W. Silk, Sachin Jhawar, Tomas Paneque, Jenna Newman, Pedro Beltran, Felicia Cao, Bang-Xing Hong, Tania Rodriguez-Cruz, Xiao-Tong Song, Stephen Gottschalk, Hugo Calderon, Sam Illingworth, Alice Brown, Kerry Fisher, Len Seymour, Brian Champion, Emma Eriksson, Jessica Wenthe, Ann-Charlotte Hellström, Gabriella Paul-Wetterberg, Angelica Loskog, Ioanna Milenova, Magnus Ståhle, Justyna Jarblad-Leja, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Sharad Goyal, Ann Silk, Janice Mehnert, Nashat Gabrail, Jennifer Bryan, Daniel Medina, Leah Mitchell, Kader Yagiz, Fernando Lopez, Daniel Mendoza, Anthony Munday, Harry Gruber, Douglas Jolly, Steven Fuhrmann, Sasa Radoja, Wei Tan, Aldo Pourchet, Alan Frey, Ian Mohr, Matthew Mulvey, Robert H. I. Andtbacka, Merrick Ross, Sanjiv Agarwala, Kenneth Grossmann, Matthew Taylor, John Vetto, Rogerio Neves, Adil Daud, Hung Khong, Stephanie M. Meek, Richard Ungerleider, Scott Welden, Maki Tanaka, Matthew Williams, Sigrun Hallmeyer, Bernard Fox, Zipei Feng, Christopher Paustian, Carlo Bifulco, Sadia Zafar, Otto Hemminki, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Tameem Ansari, Srividya Sundararaman, Diana Roen, Paul Lehmann, Anja C. Bloom, Lewis H. Bender, Ian B. Walters, Jay A. Berzofsky, Fanny Chapelin, Eric T. Ahrens, Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Alexander Scholz, Danhui Zhang, Gilson Baia, Yann Chong Tan, Jeremy Sokolove, Dongkyoon Kim, Kevin Williamson, Xiaomu Chen, Jillian Colrain, Gregg Espiritu Santo, Ngan Nguyen, Wayne Volkmuth, Norman Greenberg, William Robinson, Daniel Emerling, Charles G. Drake, Daniel P. Petrylak, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Tuyen Vu, Dwayne Campogan, Heather Haynes, James B. Trager, Nadeem A. Sheikh, David I. Quinn, Peter Kirk, Murali Addepalli, Thomas Chang, Ping Zhang, Marina Konakova, Katsunobu Hagihara, Steven Pai, Laurie VanderVeen, Palakshi Obalapur, Peiwen Kuo, Phi Quach, Lawrence Fong, Deborah H. Charych, Jonathan Zalevsky, John L. Langowski, Yolanda Kirksey, Ravi Nutakki, Shalini Kolarkar, Rhoneil Pena, Ute Hoch, Stephen K. Doberstein, John Cha, Zach Mallon, Myra Perez, Amanda McDaniel, Snjezana Anand, Darrin Uecker, Richard Nuccitelli, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, Ariana N. Renrick, Menaka Thounaojam, Portia Thomas, Samuel Pellom, Anil Shanker, Duafalia Dudimah, Alan Brooks, Yu-Lin Su, Tomasz Adamus, Qifang Zhang, Sergey Nechaev, Marcin Kortylewski, Spencer Wei, Clark Anderson, Chad Tang, Jonathan Schoenhals, Efrosini Tsouko, John Heymach, Patricia de Groot, Joe Chang, Kenneth R. Hess, Adi Diab, Padmanee Sharma, David Hong, James Welsh, Andrea J. Parsons, Jardin Leleux, Stephane Ascarateil, Marie Eve Koziol, Dina Bai, Peihong Dai, Weiyi Wang, Ning Yang, Stewart Shuman, Liang Deng, Patrick Dillon, Gina Petroni, David Brenin, Kim Bullock, Walter Olson, Mark E. Smolkin, Kelly Smith, Carmel Nail, Craig L. Slingluff, Meenu Sharma, Faisal Fa’ak, Louise Janssen, Hiep Khong, Zhilan Xiao, Yared Hailemichael, Manisha Singh, Christina Vianden, Willem W. Overwijk, Andrea Facciabene, Pierini Stefano, Fang Chongyung, Stavros Rafail, Michael Nielsen, Peter Vanderslice, Darren G. Woodside, Robert V. Market, Ronald J. Biediger, Upendra K. Marathi, Kevin Hollevoet, Nick Geukens, Paul Declerck, Nathalie Joly, Laura McIntosh, Eustache Paramithiotis, Magnus Rizell, Malin Sternby, Bengt Andersson, Alex Karlsson-Parra, Rui Kuai, Lukasz Ochyl, Anna Schwendeman, James Moon, Weiwen Deng, Thomas E. Hudson, Bill Hanson, Chris S. Rae, Joel Burrill, Justin Skoble, George Katibah, Michele deVries, Peter Lauer, Thomas W. Dubensky, Xin Chen, Li Zhou, Xiubao Ren, Charu Aggarwal, Drishty Mangrolia, Roger Cohen, Gregory Weinstein, Matthew Morrow, Joshua Bauml, Kim Kraynyak, Jean Boyer, Jian Yan, Jessica Lee, Laurent Humeau, Sandra Oyola, Susan Duff, David Weiner, Zane Yang, Mark Bagarazzi, Douglas G. McNeel, Jens Eickhoff, Robert Jeraj, Mary Jane Staab, Jane Straus, Brian Rekoske, Glenn Liu, Marit Melssen, William Grosh, Nikole Varhegyi, Nadejda Galeassi, Donna H. Deacon, Elizabeth Gaughan, Maurizio Ghisoli, Minal Barve, Robert Mennel, Gladice Wallraven, Luisa Manning, Neil Senzer, John Nemunaitis, Masahiro Ogasawara, Shuichi Ota, Kaitlin M. Peace, Diane F. Hale, Timothy J. Vreeland, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Guy T. Clifton, Mark O. Hardin, Anne Toms, Na Qiao, Jennifer Litton, George E. Peoples, Elizabeth A. Mittendorf, Lila Ghamsari, Emilio Flano, Judy Jacques, Biao Liu, Jonathan Havel, Vladimir Makarov, Timothy A. Chan, Jessica B. Flechtner, John Facciponte, Stefano Ugel, Francesco De Sanctis, George Coukos, Sébastien Paris, Agnes Pottier, Laurent Levy, Bo Lu, Federica Cappuccini, Emily Pollock, Richard Bryant, Freddie Hamdy, Adrian Hill, Irina Redchenko, Hussein Sultan, Takumi Kumai, Valentyna Fesenkova, Esteban Celis, Ingrid Fernando, Claudia Palena, Justin M. David, Elizabeth Gabitzsch, Frank Jones, James L. Gulley, Mireia Uribe Herranz, Hiroshi Wada, Atsushi Shimizu, Toshihiro Osada, Satoshi Fukaya, Eiji Sasaki, Milad Abolhalaj, David Askmyr, Kristina Lundberg, Ann-Sofie Albrekt, Lennart Greiff, Malin Lindstedt, Dallas B. Flies, Tomoe Higuchi, Wojciech Ornatowski, Jaryse Harris, Sarah F. Adams, Todd Aguilera, Marjan Rafat, Laura Castellini, Hussein Shehade, Mihalis Kariolis, Dadi Jang, Rie vonEbyen, Edward Graves, Lesley Ellies, Erinn Rankin, Albert Koong, Amato Giaccia, Reham Ajina, Shangzi Wang, Jill Smith, Mariaelena Pierobon, Sandra Jablonski, Emanuel Petricoin, Louis M. Weiner, Lorcan Sherry, John Waller, Mark Anderson, Alison Bigley, Chantale Bernatchez, Cara Haymaker, Harriet Kluger, Michael Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Tagliaferri, Patrick Hwu, Mario Snzol, Michael Hurwitz, Theresa Barberi, Allison Martin, Rahul Suresh, David Barakat, Sarah Harris-Bookman, Charles Drake, Alan Friedman, Sara Berkey, Stephanie Downs-Canner, Robert P. Edwards, Tyler Curiel, Kunle Odunsi, Tullia C. Bruno, Brandon Moore, Olivia Squalls, Peggy Ebner, Katherine Waugh, John Mitchell, Wilbur Franklin, Daniel Merrick, Martin McCarter, Brent Palmer, Jeffrey Kern, Dario Vignali, Jill Slansky, Anissa S. H. Chan, Xiaohong Qiu, Kathryn Fraser, Adria Jonas, Nadine Ottoson, Keith Gordon, Takashi O. Kangas, Steven Leonardo, Kathleen Ertelt, Richard Walsh, Mark Uhlik, Jeremy Graff, Nandita Bose, Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Amitabha Chaudhuri, Yu Chen, Jing Lin, Yun-bin Ye, Chun-wei Xu, Gang Chen, Zeng-qing Guo, Andrey Komarov, Alex Chenchik, Michael Makhanov, Costa Frangou, Yi Zheng, Carla Coltharp, Darryn Unfricht, Ryan Dilworth, Leticia Fridman, Linying Liu, Milind Rajopadhye, Peter Miller, Fernando Concha-Benavente, Julie Bauman, Sumita Trivedi, Raghvendra Srivastava, James Ohr, Dwight Heron, Uma Duvvuri, Seungwon Kim, Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman, Edward Stack, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Douglas Marks, Bret Taback, Basil Horst, Laura Hix Glickman, David B. Kanne, Kelsey S. Gauthier, Anthony L. Desbien, Brian Francica, Justin L. Leong, Leonard Sung, Ken Metchette, Shailaja Kasibhatla, Anne Marie Pferdekamper, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, John Tallarico, Steven Bender, Chudi Ndubaku, Sarah M. McWhirter, Elena Gonzalez Gugel, Charles J. M. Bell, Adiel Munk, Luciana Muniz, Nina Bhardwaj, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nathalie Scholler, Catherine Yin, Pien Van der Meijs, Andrew M. Prantner, Cecile M. Krejsa, Leia Smith, Brian Johnson, Daniel Branstetter, Paul L. Stein, Juan C. Jaen, Joanne BL Tan, Ada Chen, Timothy Park, Jay P. Powers, Holly Sexton, Guifen Xu, Steve W. Young, Ulrike Schindler, Wentao Deng, David John Klinke, Hannah M. Komar, Gregory Serpa, Omar Elnaggar, Philip Hart, Carl Schmidt, Mary Dillhoff, Ming Jin, Michael C. Ostrowski, Madhuri Koti, Katrina Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Charles Graham, Andrew Craig, Julie-Ann Francis, Beatrix Kotlan, Timea Balatoni, Emil Farkas, Laszlo Toth, Mihaly Ujhelyi, Akos Savolt, Zoltan Doleschall, Szabolcs Horvath, Klara Eles, Judit Olasz, Orsolya Csuka, Miklos Kasler, Gabriella Liszkay, Eytan Barnea, Collin Blakely, Patrick Flynn, Reid Goodman, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Brian West, Paul R. Kunk, Joseph M. Obeid, Kevin Winters, Patcharin Pramoonjago, Edward B. Stelow, Todd W. Bauer, Osama E. Rahma, Adam Lamble, Yoko Kosaka, Fei Huang, Kate A. Saser, Homer Adams, Christina E. Tognon, Ted Laderas, Shannon McWeeney, Marc Loriaux, Jeffery W. Tyner, Brian J. Druker, Evan F. Lind, Zhuqing Liu, Shanhong Lu, Lawrence P. Kane, Gulidanna Shayan, Julia Femel, Ryan Lane, Jamie Booth, Amanda W. Lund, Anthony Rodriguez, Victor H. Engelhard, Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Rachidi Saleh, Shaoli Sun, Jennifer Wu, Bei Liu, Zihai Li, Zachary S. Morris, Emily I. Guy, Clinton Heinze, Jasdeep Kler, Monica M. Gressett, Lauryn R. Werner, Stephen D. Gillies, Alan J. Korman, Hans Loibner, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Paul M. Harari, Paul M. Sondel, Erica Huelsmann, Joseph Broucek, Dorothee Brech, Tobias Straub, Martin Irmler, Johannes Beckers, Florian Buettner, Elke Schaeffeler, Matthias Schwab, Elfriede Noessner, Alison Wolfreys, Andre Da Costa, John Silva, Andrea Crosby, Ludovicus Staelens, Graham Craggs, Annick Cauvin, Sean Mason, Alison M. Paterson, Andrew C. Lake, Caroline M. Armet, Rachel W. O’Connor, Jonathan A. Hill, Emmanuel Normant, Ammar Adam, Detlev M. Biniszkiewicz, Scott C. Chappel, Vito J. Palombella, Pamela M. Holland, Annette Becker, Manmohan R. Leleti, Eric Newcomb, Joanne B. L. Tan, Suthee Rapisuwon, Arash Radfar, Kellie Gardner, Geoffrey Gibney, Michael Atkins, Keith R. Rennier, Robert Crowder, Ping Wang, Russell K. Pachynski, Rosa M. Santana Carrero, Sarai Rivas, Figen Beceren-Braun, Scott Anthony, Kimberly S. Schluns, Deepali Sawant, Maria Chikina, Hiroshi Yano, Creg Workman, Elise Salerno, Ileana Mauldin, Donna Deacon, Sofia Shea, Joel Pinczewski, Thomas Gajewski, Stefani Spranger, Brendan Horton, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Raj K. Puri, Randy F. Sweis, Riyue Bao, Jason Luke, Marie-Nicole Theodoraki, Frances-Mary Mogundo, Haejung Won, Dayson Moreira, Chan Gao, Xingli Zhao, Priyanka Duttagupta, Jeremy Jones, Massimo D’Apuzzo, and Sumanta Pal

Subjects
0301 basic medicine, Pharmacology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cancer, Immunotherapy, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Molecular Medicine, Immunology and Allergy, Medicine, business
Abstract

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Published
2016
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7. Human papilloma virus status evaluation and survival description in selected oropharyngeal and laryngeal squamous cell carcinoma patients from Hungary

Author

Eniko, Reka Fejer, Zoltan, Abram, Jiahe, Zs Egyed, Septimiu, Voidazan, Erika, Toth, Zoltan, Szentirmay, and Miklos, Kasler

Subjects
Adult, Aged, 80 and over, Male, Squamous Cell Carcinoma of Head and Neck, Middle Aged, Oropharyngeal Neoplasms, Head and Neck Neoplasms, Carcinoma, Squamous Cell, Humans, Female, Neoplasm Recurrence, Local, Laryngeal Neoplasms, Papillomaviridae, Aged, Neoplasm Staging, Retrospective Studies
Abstract

Many patients with oropharyngeal squamous cell carcinomas do not have any of the traditional risk factors associated with head and neck squamous cell cancers (HNSCC). Epidemiologic and molecular studies have identified human papillomavirus (HPV) as a causative agent, viral tumors presenting a better survival and being important risk factors together with the long established ones, tobacco and alcohol consumption, in head and neck cancers. The purpose of this study was to establish the incidence of HPV-associated HNSCCs, to identify the most frequent HPV type and to evaluate the overall survival and recurrence rates of HPV-positive cases in comparison with HPV-negative HNSCCs.A retrospective analysis from the database of the National Institute of Oncology from Budapest was performed and the following parameters were analyzed: age, age at diagnosis, gender, primary tumor location, tumor histopathology, TNM stage, HPV status, date of recurrence, last visit and date of death.Out of 81 patients with HNSCCs 55 (67.9%) were male and 26 (32.1%) female. HNSCCs were more frequent in men (2.11:1) and the majority of the patients (81.7%) were diagnosed in advanced stages (TNM III and IV). HPV status was evaluated in nearly half (48.14%) of the patients and HNSCCs were positive for HPV in 43.6% of the cases. These were more frequent in patients over 50 years (76.66%), in men (76.47%) and in oropharyngeal location (94.1%). HPV-16 type was associated with malignancy in 82.35% of the cases. Disease recurrence was more frequent in HPV-negative (31.81%) vs HPV-positive cases (29.41%) and mortality rate was inferior in HPV-positive 33.33% vs negative (38.09%) tumors (p=0.52).In Hungary HNSCCs are more frequent in men than in women. HPV positivity is higher in men vs women and in oropharyngeal vs laryngeal location. Overall survival rate was superior in HPV-positive vs HPV-negative cases. Disease recurrence was more frequent in HPV-negative vs HPV-positive cases.

Published
2016

8. Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015

Author

Erik Wennerberg, Gabriele Madonna, Gennaro Ciliberto, Michele Minopoli, Caroline Dutriaux, Matthew Wongchenko, Elisabetta Gambale, David F. Stroncek, Céleste Lebbé, Ani S. Balmanoukian, Gianluca Di Monta, Vincenzo Ingangi, Soldano Ferrone, Ivan Marquez-Rodas, Giuseppe Masucci, Janis M. Taube, Simona Mastroeni, Gerardo Bott, Franck Pagès, Jonathan M. Pitt, Judit Olasz, Elisabetta Panza, Paola Michelozzi, Daniil Stoyakovskiy, Stéphane Dalle, Mario Sznol, John M. Kirkwood, Keith T. Flaherty, Maria Capuano, Amalia Azzariti, Edward Cha, Peter Boasberg, Maria Godeny, Angela Gismondi, Ornella Franzese, Giusy Gentilcore, Jean-Jacques Grob, Olivier Michielin, Adina Elena Stanciu, Giuseppe Cirino, Julien Fourcade, Nelofer Syed, Giuseppe Ercolano, Caroline Robert, Ascierto Paolo Antonio, Christine K. Gause, Silviu Voinea, Adeeb Rahman, Anne Caignard, Camila Flores, Cristina Fortes, Yuya Yoshimoto, Angela Sandru, Andras Szollar, Monica Cantile, Frederic Lehmann, Maria Libera Ascierto, Sacha Gnjatic, Marco Tucci, Rosa Russo, Giuseppina Liguori, Valeria De Biasio, David Ross Kaufman, Mary Ruisi, Ewa Kalinka-Warzocha, Phillip Wong, Rosaria Falcon, Vincenzo Faiola, Nicole Richie, Lars Ny, Miri Blank, Paola De Cicco, Anna Passarelli, Jean-François Baurain, Guido Kroemer, Claudio Jommi, Francesca Capone, Maria Teresa Fierro, Tracee L. McMiller, Lev V. Demidov, Alessandro Testori, Omid Hamid, Marone Ugo, Annamaria Anniciello, Andrew J. Park, Fara De Murtas, RuthAnn Gordan, Emil Farkas, David Hogg, Alessandra Di Paolo, Mark Maurer, Yangyang Wang, Mario Mandalà, Rodabe N. Amaria, Massimiliano Di Marzo, Stefania Guida, Luigi Fattore, Veronica Huber, Ludmila Danilova, Luigi Aurisicchio, Gabriella Aquino, Domenico Mallardo, Catriona M. McNeil, Stephanie Anne Kronenberg, Consiglia Carella, Theresa S. Pritchard, Katia Bifulco, Michaela Semeraro, Carlo M. Croce, David P. Enot, Laurence Zitvogel, Marcella Occelli, Benjamin Weide, Magdalena Thurin, Margherita Cerrone, Naiyer A. Rizvi, Blessing Agunwamba, Stella D'Oronzo, Sarah Jegou, Stucci Stefania, Drew M. Pardoll, Vito Michele Garrisi, Haidong Tang, Szabolcs Horvath, Hong Wang, Benjamin Brady, Antonio Doronzo, Claudia Marino, Xian He, Michael A. Davies, Hexiao Wang, Isabelle Rooney, Orsolya Csuka, Maurizio Nudo, Lance Leopold, Jeffrey S. Wasser, Sabino Strippoli, Silvia Ch Formenti, MariaLaura Foddai, Michael A. Postow, Robert H.I. Andtbacka, Paul Lorigan, Tommy Andersson, Naoko Imai, Ari VanderWalde, Mariaelena Capone, Ilsung Chang, Laura Lattanzio, Carmen Loquai, Arantxa Sancho, Christine Horak, Federica Sallusto, Timea Balatoni, Maha Ayyoub, Angela Santoni, Alessio Caggiati, Anna Lisa De Presbiteris, Henrik Schmidt, Paola Savoia, Pontus Berglund, Igor Puzanov, Aurélien Marabelle, Ana Carrizossa Anderson, Hassane M. Zarour, Maria Wolodarski, Patrick Hwu, Joel Jiang, Pio Zeppa, Jeffrey A. Sosman, Eugenio Fernandez, Susan Costantini, Marcus Ballinger, Luc Thomas, Leslie Cope, Rolf Kiessling, Christophe Borg, Francesca Platini, Florian Stratica, Tilman T. Rau, Craig L. Slingluff, Paolo A. Ascierto, Angela Ianaro, Harriet M. Kluger, Stephen Hodi, Tara C. Gangadhar, Claire Vanpouille-Box, Caroline Flament, Hearn J. Cho, Mannavola Francesco, Takahiro Yamazaki, Charles G. Drake, Jason J. Luke, Miklos Kasler, Linda Pan, Caracò Corrado, Alfonso Berrocal, Angel Rivera, Vera Hirsh, Eduardo J. Patriarca, Giovanni Di Giulio, Antonello Pessi, Helena Stabile, Helene Hardy, Tucci Marco, Ralph Venhaus, Maria Luisa Di Cecilia, Catherine A. Harwood, Jonathan Cebon, Anna Maria Anniciello, Grant A. McArthur, Carlo Baldi, Ahmad A. Tarhini, Shelley Coleman, Gil Bar-Sela, Axel Hauschild, Byoung S. Kwon, Maria Paula Roberti, Sabin Cinca, Tiziana Cocco, Valeria Sorrentino, Jeffrey Wallin, Rosa Camerlingo, Sandra Demaria, Jedd D. Wolchok, Isabel Poschke, Alessandro Lugli, Michael B. Atkins, Andrea Cavalcanti, Laura Marra, Rosamaria Pinto, Adam D. Cohen, Michele Maio, Weiyi Peng, Rosario Guarrasi, David Enot, Antoni Ribas, Oscar Alabiso, Chiara Armogida, Silvestris Franco, Jessica C. Hassel, Rita Mancini, Michele Guida, Silvia C. Formenti, Andrea P. Sponghini, Imma Maida, Alba Zappalà, Charlotte M. Proby, Alan J. Korman, Yibing Yan, Matias Chacon, Haiying Xu, Carolin Blattner, Maria-Paula Roberti, Lisa Chen, James Larkin, Ryan J. Sullivan, Madonna Gabriele, Nadege Vimond, Cosmo Di Donna, Farnaz Moradi, Manish R. Patel, Sylvie Rusakiewicz, Francesca Passarelli, Luis de la Cruz-Merino, Nicolas Jacquelot, Roberta Miceli, Viktor Umansky, Akos Savolt, David Rondonotti, Gabriella Liszkay, Jianda Yuan, Stefani Spranger, Yufan Zhao, Yehuda Shoenfeld, Todd M. Bauer, Claus Garbe, Joe-Marc Chauvin, Achim A. Jungbluth, Cristiana Lo Nigro, Alexander M. Lesokhin, Gabriella Guida, Brigitte Dréno, Cindy Sanders, Jeffrey S. Weber, Janet Maleski, Chris Cheadle, Romain Daillère, Isabella Sperduti, Michaele Maio, Claudia Felici, Parneet K. Cheema, Concetta Ragone, Johan Hansson, Klara Eles, Victoria Atkinson, Speiser Daniel, Daniel O. Koralek, Zhaojun Sun, Debora Malpicci, Elena Marra, Rickard Linnskog, Jeffrey Chou, Yang Wang, Eugenia Panaitescu, F. Stephen Hodi, Anthony J. Olszanski, Chiara Botti, Nicola Mozzillo, Anna Ferretta, Paul B. Chapman, Michaë la Semeraro, Belinda Palermo, Francesco Sabbatino, Neil H. Segal, Yago Pico de Coaña, Tseng-hui Timothy Chen, Ornella Pagliano, John B. A. G. Haanen, Huibin Yue, Emilia Caputo, Alan E. Berger, Simona De Summa, Nikoletta Lendvai, Paola Queirolo, Francesco Mannavola, Thomas F. Gajewski, Michele De Tursi, Paola Nisticò, Karen Briscoe, Karmele Mujika Eizmendi, Maria Vincenza Carrier, Passarelli Anna, Laurent Mortier, Crescenzo D'Alterio, Jorge Camarero, Licia Rivoltini, Pietro Quaglino, Davide Quaresmini, Marie Vétizou, Anna Maria Di Giacomo, Chandra Prakash Prasad, Riccardo Bono, Vichnou Poirier-Colame, David Smith, Capone Mariaelena, Giosuè Scognamiglio, Margaret K. Callahan, Vashisht Gopal Yennu Nanda, Fabiola Gilda Cordaro, George J. Netto, Madalina Bolovan, Federica Fratangelo, Josep Malvehy, Robert A. Anders, Karsten A. Pilones, Vincenzo C. Battarra, Karin Leandersson, Maria Letizia Motti, Yang Xin Fu, Tim Crook, Sarah Nataraj, Alastair M. Thompson, Franco Silvestris, Carolina Cauchi, Georgina V. Long, Holbrook E Kohrt, Giuseppe Pirozzi, Celeste Fusciello, Marco Carlo Merlano, François Aubin, Mozzillo Nicola, Giuseppe Cirin, Stefania Scala, Suzanne L. Topalian, Alexander M.M. Eggermont, Antonio Marra, Jinshui Fan, Reinhard Dummer, Federica Zito Marino, Amanda Ralabate, Matthew M. Burke, Piotr Rutkowski, Gerardo Botti, Stefano Pepe, Ivor Caro, and Stefania Tommasi

Subjects
0301 basic medicine, business.industry, MEDLINE, General Medicine, medicine.disease, Bridge (interpersonal), General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, Medical emergency, business
Published
2016

9. The Porto European Cancer Research Summit 2021

Author

Ulrik Ringborg, Anton Berns, Julio E. Celis, Manuel Heitor, Josep Tabernero, Joachim Schüz, Michael Baumann, Rui Henrique, Matti Aapro, Partha Basu, Regina Beets‐Tan, Benjamin Besse, Fátima Cardoso, Fátima Carneiro, Guy vanden Eede, Alexander Eggermont, Stefan Fröhling, Susan Galbraith, Elena Garralda, Douglas Hanahan, Thomas Hofmarcher, Bengt Jönsson, Olli Kallioniemi, Miklós Kásler, Eva Kondorosi, Jan Korbel, Denis Lacombe, José Carlos Machado, José M. Martin‐Moreno, Francoise Meunier, Péter Nagy, Paolo Nuciforo, Simon Oberst, Júlio Oliveiera, Maria Papatriantafyllou, Walter Ricciardi, Alexander Roediger, Bettina Ryll, Richard Schilsky, Grazia Scocca, Raquel Seruca, Marta Soares, Karen Steindorf, Vincenzo Valentini, Emile Voest, Elisabete Weiderpass, Nils Wilking, Amanda Wren, and Laurence Zitvogel

Subjects
Cancer Mission, cancer research/care/prevention continuum, clinical/prevention trials, comprehensive cancer centres, infrastructures for translational cancer research, outcomes research, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high‐quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures – namely translational research, clinical/prevention trials and outcomes research – were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next‐generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health‐related quality‐of‐life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU‐wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost.

Published
2021
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10. Genome-wide autosomal, mtDNA, and Y chromosome analysis of King Bela III of the Hungarian Arpad dynasty

Author

Chuan-Chao Wang, Cosimo Posth, Anja Furtwängler, Katalin Sümegi, Zsolt Bánfai, Miklós Kásler, Johannes Krause, and Béla Melegh

Subjects
Medicine, Science
Abstract

Abstract The ancient Hungarians, “Madzsars”, established their control of the Carpathian Basin in the late ninth century and founded the Hungarian Kingdom around 1000AD. The origin of the Magyars as a tribal federation has been much debated in the past. From the time of the conquest to the early fourteenth century they were ruled by descendants of the Arpad family. In order to learn more about the genetic origin of this family, we here analyzed the genome of Bela III one of the most prominent members of the early Hungarian dynasty that ruled the Hungarian Kingdom from 1172 to 1196. The Y-Chromosome of Bela III belongs to haplogroup R1a-Z2123 that is today found in highest frequency in Central Asia, supporting a Central Asian origin for the ruling lineage of the Hungarian kingdom. The autosomal DNA profile of Bela III, however, falls within the genetic variation of present-day east European populations. This is further supported through his mtDNA genome that belongs to haplogroup H, the most common European maternal lineage, but also found in Central Asia. However, we didn’t find an exact haplotype match for Bela III. The typical autosomal and maternal Central Eastern European ancestry among Bela III autosomes might be best explained by consecutive intermarriage with local European ruling families.

Published
2021
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11. The genetic legacy of the Hunyadi descendants

Author

Endre Neparáczki, Luca Kis, Zoltán Maróti, Bence Kovács, Gergely I.B. Varga, Miklós Makoldi, Pamjav Horolma, Éva Teiszler, Balázs Tihanyi, Péter L. Nagy, Kitti Maár, Attila Gyenesei, Oszkár Schütz, Eszter Dudás, Tibor Török, Vesna Pascuttini-Juraga, Ivančica Peharda, László Tamás Vizi, Gábor Horváth-Lugossy, and Miklós Kásler

Subjects
Ancient genomes, Hunyadi, Corvinus, Hungarian Nobel family, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

The Hunyadi family is one of the most influential families in the history of Central Europe in the 14th–16th centuries. The family’s prestige was established by Johannes Hunyadi, a Turk-beater who rose to the position of governor of the Kingdom of Hungary. His second son, Matthias Hunyadi, became the elected ruler of the Kingdom of Hungary in 1458. The Hunyadi family had unknown origin. Moreover, Matthias failed to found a dynasty because of lacking a legitimate heir and his illegitimate son Johannes Corvinus was unable to obtain the crown. His grandson, Christophorus Corvinus, died in childhood, thus the direct male line of the family ended.In the framework of on interdisciplinary research, we have determined the whole genome sequences of Johannes Corvinus and Christophorus Corvinus by next-generation sequencing technology. Both of them carried the Y-chromosome haplogroup is E1b1b1a1b1a6a1c ∼, which is widespread in Eurasia. The father-son relationship was verified using the classical STR method and whole genome data. Christophorus Corvinus belongs to the rare, sporadically occurring T2c1+146 mitochondrial haplogroup, most frequent around the Mediterranean, while his father belongs to the T2b mitochondrial haplogroup, widespread in Eurasia, both are consistent with the known origin of the mothers. Archaeogenomic analysis indicated that the Corvinus had an ancient European genome composition.Based on the reported genetic data, it will be possible to identify all the other Hunyadi family member, whose only known grave site is known, but who are resting assorted with several other skeletons.

Published
2022
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12. Comparison of Cancer Survival Trends in Hungary in the Periods 2001–2005 and 2011–2015 According to a Population-Based Cancer Registry

Author

István Kenessey, Georgina Szőke, Mária Dobozi, István Szatmári, András Wéber, György Fogarassy, Péter Nagy, Miklós Kásler, Csaba Polgár, and Ágnes Vathy-Fogarassy

Subjects
mortality, survival, incidence, oncology, cancer registry, trend, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Pathology, RB1-214
Abstract

Background: Assessment of population-based cancer survival may provide the most valuable feedback about the effectiveness of oncological surveillance and treatment.Aims: Based on the database of the Hungarian National Cancer Registry, standardized incidence rates of lung, breast, colorectal, prostate and cervical cancer were compared to standardized mortality data of the Hungarian Central Statistical Office in the period between 2001 and 2015. Then survival analysis was performed on cleansed database.Results: The incidence of colorectal, breast and prostate cancer increased, while standardized rates of lung and cervical cancer declined. The survival of colorectal, breast and prostate cancer showed improvement. Contrarily, lung cancer exhibited a mild decline, while that of cervical cancer did not change significantly. In earlier stages survival was improved among almost every studied tumor type, while in advanced stages improvement was not observed. Comparison of stage distribution revealed that in the 2011–2015 period colorectal, breast and prostate cancer cases were diagnosed at earlier stages, while lung and cervical cancer patients were typically discovered at more advanced stages.Discussion: The outcome of advanced cancer treatments is better in earlier stages, which highlighted the importance of screening network. However, growth of oncological treatment costs with longer patient survival imposes a constantly increasing burden on society.

Published
2022
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13. Effectiveness and Waning of Protection With Different SARS-CoV-2 Primary and Booster Vaccines During the Delta Pandemic Wave in 2021 in Hungary (HUN-VE 3 Study)

Author

Zoltán Vokó, Zoltán Kiss, György Surján, Orsolya Surján, Zsófia Barcza, István Wittmann, Gergő Attila Molnár, Dávid Nagy, Veronika Müller, Krisztina Bogos, Péter Nagy, István Kenessey, András Wéber, Lőrinc Polivka, Mihály Pálosi, János Szlávik, György Rokszin, Cecília Müller, Zoltán Szekanecz, and Miklós Kásler

Subjects
booster vaccine, delta variant, vaccine effectiveness, sinopharm, sputnik-V, janssen, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundIn late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered for the vulnerable population starting from August 2021.MethodsThe nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations in the prevention of SARS-CoV-2 infection, Covid-19 related hospitalization and mortality during the Delta wave, compared to an unvaccinated control population without prior SARS-CoV-2 infection.ResultsThe study population included 8,087,988 individuals who were 18–100 years old at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14–120 days after primary immunization in the 16–64 and 65–100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65–100 years, we found high, 88.1%–92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%–95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%–75.3% and 72.9%–100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14–120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed a moderate decline over time, while booster vaccine types restored effectiveness up to almost 100%, except for the Sinopharm booster.ConclusionsThe HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines, and this is the first study to provide clear and comparable effectiveness results for six different vaccine types after primary immunization against severe during the Delta pandemic wave.

Published
2022
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14. Modern Breast Cancer Surgery 1st Central-Eastern European Professional Consensus Statement on Breast Cancer

Author

Zoltán Mátrai, Péter Kelemen, Csaba Kósa, Róbert Maráz, Attila Paszt, Gábor Pavlovics, Ákos Sávolt, Zsolt Simonka, Dezső Tóth, Miklós Kásler, Andrey Kaprin, Petr Krivorotko, Ferenc Vicko, Piotr Pluta, Agnieszka Kolacinska-Wow, Dawid Murawa, Jerzy Jankau, Slawomir Ciesla, Daniel Dyttert, Martin Sabol, Andrii Zhygulin, Artur Avetisyan, Alexander Bessonov, and György Lázár

Subjects
breast cancer, surgery, consensus statement, oncoplastic surgery, oncology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Pathology, RB1-214
Abstract

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

Published
2022
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15. Nationwide Effectiveness of First and Second SARS-CoV2 Booster Vaccines During the Delta and Omicron Pandemic Waves in Hungary (HUN-VE 2 Study)

Author

Zoltán Kiss, István Wittmann, Lőrinc Polivka, György Surján, Orsolya Surján, Zsófia Barcza, Gergő Attila Molnár, Dávid Nagy, Veronika Müller, Krisztina Bogos, Péter Nagy, István Kenessey, András Wéber, Mihály Pálosi, János Szlávik, Zsuzsa Schaff, Zoltán Szekanecz, Cecília Müller, Miklós Kásler, and Zoltán Vokó

Subjects
SARS-CoV2 infection, booster vaccine, 4th vaccine, omicron variant (SARS-CoV-2), delta variant (B.1.617.2), vaccine effectiveness, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundIn Hungary, the pandemic waves in late 2021 and early 2022 were dominated by the Delta and Omicron SARS-CoV-2 variants, respectively. Booster vaccines were offered with one or two doses for the vulnerable population during these periods.Methods and FindingsThe nationwide HUN-VE 2 study examined the effectiveness of primary immunization, single booster, and double booster vaccination in the prevention of Covid-19 related mortality during the Delta and Omicron waves, compared to an unvaccinated control population without prior SARS-CoV-2 infection during the same study periods. The risk of Covid-19 related death was 55% lower during the Omicron vs. Delta wave in the whole study population (n=9,569,648 and n=9,581,927, respectively; rate ratio [RR]: 0.45, 95% confidence interval [CI]: 0.44–0.48). During the Delta wave, the risk of Covid-19 related death was 74% lower in the primary immunized population (RR: 0.26; 95% CI: 0.25–0.28) and 96% lower in the booster immunized population (RR: 0.04; 95% CI: 0.04–0.05), vs. the unvaccinated control group. During the Omicron wave, the risk of Covid-19 related death was 40% lower in the primary immunized population (RR: 0.60; 95% CI: 0.55–0.65) and 82% lower in the booster immunized population (RR: 0.18; 95% CI: 0.16–0.2) vs. the unvaccinated control group. The double booster immunized population had a 93% lower risk of Covid-19 related death compared to those with only one booster dose (RR: 0.07; 95% CI. 0.01–0.46). The benefit of the second booster was slightly more pronounced in older age groups.ConclusionsThe HUN-VE 2 study demonstrated the significantly lower risk of Covid-19 related mortality associated with the Omicron vs. Delta variant and confirmed the benefit of single and double booster vaccination against Covid-19 related death. Furthermore, the results showed the additional benefit of a second booster dose in terms of SARS-CoV-2 infection and Covid-19 related mortality.

Published
2022
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16. Genome-Wide Marker Data-Based Comparative Population Analysis of Szeklers From Korond, Transylvania, and From Transylvania Living Non-Szekler Hungarians

Author

Valerián Ádám, Zsolt Bánfai, Katalin Sümegi, Gergely Büki, András Szabó, Lili Magyari, Attila Miseta, Miklós Kásler, and Béla Melegh

Subjects
population genetics, identical by descent, Transylvania, Szeklers, genome-wide data, Genetics, QH426-470
Abstract

Genome-wide genotype data from 48 carefully selected population samples of Transylvania-living Szeklers and non-Szekler Hungarians were analyzed by comparative analysis. Our analyses involved contemporary Hungarians living in Hungary, other Europeans, and Eurasian samples counting 530 individuals altogether. The source of the Szekler samples was the commune of Korond, Transylvania. The analyzed non-Szekler Hungarian samples were collected from villages with a history dating back to the era of the Árpád Dynasty. Population structure by principal component analysis and ancestry analysis also revealed a great within-group similarity of the analyzed Szeklers and non-Szekler Transylvanian Hungarians. These groups also showed similar genetic patterns with each other. Haplotype analyses using identity-by-descent segment discovering tools showed that average pairwise identity-by-descent sharing is similar in the investigated populations, but the Korond Szekler samples had higher average sharing with the Hungarians from Hungary than non-Szekler Transylvanian Hungarians. Average sharing results showed that both groups are isolated compared to other Europeans, and pointed out that the non-Szekler Transylvanian Hungarian inhabitants of the investigated Árpád Age villages are more isolated than investigated Szeklers from Korond. This was confirmed by our autozygosity analysis as well. Identity-by-descent segment analyses and 4-population tests also confirmed that these Hungarian-speaking Transylvanian ethnic groups are strongly related to Hungarians living in Hungary.

Published
2022
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17. Towards a cancer mission in Horizon Europe: recommendations

Author

Anton Berns, Ulrik Ringborg, Julio E. Celis, Manuel Heitor, Neil K. Aaronson, Nancy Abou‐Zeid, Hans‐Olov Adami, Kathi Apostolidis, Michael Baumann, Alberto Bardelli, René Bernards, Yvonne Brandberg, Carlos Caldas, Fabien Calvo, Caroline Dive, Angelika Eggert, Alexander Eggermont, Carolina Espina, Frederik Falkenburg, Jérôme Foucaud, Douglas Hanahan, Ulrike Helbig, Bengt Jönsson, Mette Kalager, Sakari Karjalainen, Miklós Kásler, Pamela Kearns, Klas Kärre, Denis Lacombe, Francesco deLorenzo, Françoise Meunier, Gerd Nettekoven, Simon Oberst, Péter Nagy, Thierry Philip, Richard Price, Joachim Schüz, Eric Solary, Peter Strang, Josep Tabernero, and Emile Voest

Subjects
cancer mission, cancer research/care/prevention continuum, comprehensive cancer centres, European healthcare systems, patient empowerment, science policy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research–care–prevention continuum has the potential to achieve in 2030 a 10‐year cancer‐specific survival for 75% of patients diagnosed in European Union (EU) member states with a well‐developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high‐quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science‐driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC‐like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long‐term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans‐border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence‐based advice.

Published
2020
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18. Booster Vaccination Decreases 28-Day All-Cause Mortality of the Elderly Hospitalized Due to SARS-CoV-2 Delta Variant

Author

Veronika Müller, Lorinc Polivka, Istvan Valyi-Nagy, Alexandra Nagy, Zoltan Szekanecz, Krisztina Bogos, Hajnalka Vago, Anita Kamondi, Ferenc Fekete, Janos Szlavik, Jeno Elek, György Surján, Orsolya Surján, Péter Nagy, Zsuzsa Schaff, Cecília Müller, Zoltan Kiss, and Miklós Kásler

Subjects
SARS-CoV-2 infection, delta variant, vaccine effectiveness, mortality, hospitalization, elderly, Medicine
Abstract

(1) Background: SARS-CoV-2 infections are associated with an increased risk of hospital admissions especially in the elderly (age ≥ 65 years) and people with multiple comorbid conditions. (2) Methods: We investigated the effect of additional booster vaccinations following the primary vaccination series of mRNA, inactivated whole virus, or vector vaccines on infections with the SARS-CoV-2 delta variant in the total Hungarian elderly population. The infection, hospital admission, and 28-day all-cause mortality of elderly population was assessed. (3) Results: A total of 1,984,176 people fulfilled the criteria of elderly including 299,216 unvaccinated individuals, while 1,037,069 had completed primary vaccination and 587,150 had obtained an additional booster. The primary vaccination series reduced the risk of infection by 48.88%, the risk of hospital admission by 71.55%, and mortality by 79.87%. The booster vaccination had an additional benefit, as the risk of infection, hospital admission, and all-cause mortality were even lower (82.95%; 92.71%; and 94.24%, respectively). Vaccinated patients needing hospitalization suffered significantly more comorbid conditions, indicating a more vulnerable population. (4) Conclusions: Our data confirmed that the primary vaccination series and especially the booster vaccination significantly reduced the risk of the SARS-CoV-2 delta-variant-associated hospital admission and 28-day all-cause mortality in the elderly despite significantly more severe comorbid conditions.

Published
2022
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20. Revealing the Genetic Impact of the Ottoman Occupation on Ethnic Groups of East-Central Europe and on the Roma Population of the Area

Author

Zsolt Bánfai, Béla I. Melegh, Katalin Sümegi, Kinga Hadzsiev, Attila Miseta, Miklós Kásler, and Béla Melegh

Subjects
population genetics, genome-wide data, population structure, ancestry estimation, admixture, East-Central Europe, Genetics, QH426-470
Abstract

History of East-Central Europe has been intertwined with the history of Turks in the past. A significant part of this region of Europe has been fallen under Ottoman control during the 150 years of Ottoman occupation in the 16–17th centuries. The presence of the Ottoman Empire affected this area not only culturally but also demographically. The Romani people, the largest ethnic minority of the East-Central European area, share an even more eventful past with Turkish people from the time of their migration throughout Eurasia and they were a notable ethnic group in East-Central Europe in the Ottoman era already. The relationship of Turks with East-Central European ethnic groups and with regional Roma ethnicity was investigated based on genome-wide autosomal single nucleotide polymorphism data. Population structure analysis, ancestry estimation, various formal tests of admixture and DNA segment analyses were carried out in order to shed light to the conclusion of these events on a genome-wide basis. Analyses show that the Ottoman occupation of Europe left detectable impact in the affected East-Central European area and shaped the ancestry of the Romani people as well. We estimate that the investigated European populations have an average identity-by-descent share of 0.61 with Turks, which is notable, compared to other European populations living in West and North Europe far from the affected area, and compared to the share of Sardinians, living isolated from these events. Admixture of Roma and Turks during the Ottoman rule show also high extent.

Published
2019
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21. High prevalence of germline STK11mutations in Hungarian Peutz-Jeghers Syndrome patients

Author

Szilvia Solyom, Edith Olah, Marietta Eva Kovacs, Anne Lise Børresen-Dale, János Papp, and Miklos Kasler

Subjects
Adult, Male, lcsh:Internal medicine, congenital, hereditary, and neonatal diseases and abnormalities, lcsh:QH426-470, Adolescent, Peutz-Jeghers Syndrome, STK11, Protein Serine-Threonine Kinases, Biology, Polymerase Chain Reaction, White People, Germline, Frameshift mutation, Exon, Germline mutation, AMP-Activated Protein Kinase Kinases, Genetics, Humans, Point Mutation, Genetics(clinical), RNA, Messenger, Multiplex ligation-dependent probe amplification, Allele, lcsh:RC31-1245, Child, Frameshift Mutation, Alleles, Germ-Line Mutation, Genetics (clinical), Hungary, Point mutation, Exons, Sequence Analysis, DNA, Middle Aged, Molecular biology, lcsh:Genetics, Codon, Nonsense, Child, Preschool, Female, RNA Splice Sites, Gene Deletion, Research Article
Abstract

Background Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the STK11/LKB1 tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in STK11/LKB1 and their association to disease phenotype. Methods Mutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations. Results Thirteen different pathogenic mutations in STK11, including a high frequency of large genomic deletions (38%, 5/13), were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes (SBNO2 and GPX4), located upstream of STK11, with a possible modifier effect. The majority of the point mutations (88%, 7/8) can be considered novel. Quantification of the STK11 transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3. Conclusions A combination of sensitive techniques may assure a high (100%) STK11 mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.

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