{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:42:20Z","timestamp":1761864140537,"version":"3.37.3"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006081","name":"Lounais-Suomen Sy\u00f6p\u00e4yhdistys","doi-asserted-by":"publisher","award":["0"],"award-info":[{"award-number":["0"]}],"id":[{"id":"10.13039\/501100006081","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish Doctoral Programme in Oral Sciences","award":["0"],"award-info":[{"award-number":["0"]}]},{"name":"Dental Association of Turku","award":["0"],"award-info":[{"award-number":["0"]}]},{"DOI":"10.13039\/501100005634","name":"Suomen Hammasl\u00e4\u00e4k\u00e4riseura Apollonia","doi-asserted-by":"publisher","award":["0"],"award-info":[{"award-number":["0"]}],"id":[{"id":"10.13039\/501100005634","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish Women Dentists\u2019 Association","award":["0"],"award-info":[{"award-number":["0"]}]},{"DOI":"10.13039\/501100001658","name":"Minerva Foundation","doi-asserted-by":"publisher","award":["0"],"award-info":[{"award-number":["0"]}],"id":[{"id":"10.13039\/501100001658","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>This study was designed to investigate the invasion of human papillomavirus (HPV) positive human cervical carcinoma cell lines in human leiomyoma-based extracellular matrices in vitro<jats:italic>,<\/jats:italic> and to test the suitability of the model for studying the irradiation effects on the cancer cell invasion.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>HPV positive cervical carcinoma cell lines SiHa and CaSki, and HPV negative squamous cell carcinoma cell line HSC-3 were used. CaSki cells contain around 600 copies of HPV 16 virus in the genome, whereas SiHa have only 1\u20132 copies per cell. Cells were analyzed using two different human tumor derived extracellular matrix methods (3D myoma disc model, and Myogel Transwell invasion assay). Cultures were irradiated with 4\u2009Gy. Myoma invasion area and the depth of invasion were measured with ImageJ 1.51j8 software. Statistical analyses were performed with SPSS Statistics (IBM SPSS\u00ae Statistics 25).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>All cells invaded through Myogel coated Transwell membranes and within myoma discs. In myoma discs, a difference in the invasion depth (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001) but not in invasion area (<jats:italic>p<\/jats:italic>\u2009=\u20090.310) between the HPV positive cell lines was seen, since SiHa (less HPV) invaded slightly better than CaSki (more HPV). HSC-3 cells (HPV negative) invaded deepest (<jats:italic>p<\/jats:italic>\u2009=\u20090.048) than either of the HPV positive cell line cells. No difference was detected in the invasion area (<jats:italic>p<\/jats:italic>\u2009=\u20090.892) between HPV positive and HPV negative cells. The ionized radiation significantly reduced the invasion depth of HSC-3 (<jats:italic>p<\/jats:italic>\u2009=\u20090.008), SiHa (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001) and CaSki (<jats:italic>p<\/jats:italic>\u2009=\u20090.005). No significant effect on the invasion area was detected in any of the cell lines. However, a significant difference was observed between SiHa and CaSki in the reduction of the invasion depth after radiation (<jats:italic>p<\/jats:italic>\u2009=\u20090.013) as the reduction was greater with SiHa than CaSki.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Both solid and gelatinous human leiomyoma-based extracellular matrix models were suitable platforms to study the invasion of HPV positive cervical carcinoma cells in vitro. SiHa cells with less HPV copy number cells invaded slightly better and were slightly more sensitive to irradiation than CaSki cells with high HPV copy number. However, there was no drastic differences between the invasion properties of these carcinoma cells.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12985-020-01367-1","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T07:02:49Z","timestamp":1593500569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Human myoma tissue-based extracellular matrix models for testing the effects of irradiation on the HPV positive cells"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4808-4851","authenticated-orcid":false,"given":"Heidi","family":"Tuominen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Al-Samadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaana","family":"Rautava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"issue":"1737","key":"1367_CR1","doi-asserted-by":"publisher","first-page":"20160482","DOI":"10.1098\/rstb.2016.0482","volume":"373","author":"T Salo","year":"2018","unstructured":"Salo T, Dourado MR, Sundquist E, et al. Organotypic three-dimensional assays based on human leiomyoma\u2013derived matrices. Philos Trans R Soc B Biol Sci. 2018;373(1737):20160482. https:\/\/doi.org\/10.1098\/rstb.2016.0482.","journal-title":"Philos Trans R Soc B Biol Sci"},{"issue":"2","key":"1367_CR2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.yexcr.2016.04.003","volume":"344","author":"E Sundquist","year":"2016","unstructured":"Sundquist E, Renko O, Salo S, et al. Neoplastic extracellular matrix environment promotes cancer invasion in vitro. Exp Cell Res. 2016;344(2):229\u201340. https:\/\/doi.org\/10.1016\/j.yexcr.2016.04.003.","journal-title":"Exp Cell Res"},{"issue":"1","key":"1367_CR3","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1186\/s12885-015-1944-z","volume":"15","author":"T Salo","year":"2015","unstructured":"Salo T, Sutinen M, Hoque Apu E, et al. A novel human leiomyoma tissue derived matrix for cell culture studies. BMC Cancer. 2015;15(1):981. https:\/\/doi.org\/10.1186\/s12885-015-1944-z.","journal-title":"BMC Cancer"},{"issue":"3","key":"1367_CR4","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.2353\/ajpath.2009.081110","volume":"175","author":"S Nurmenniemi","year":"2009","unstructured":"Nurmenniemi S, Sinikumpu T, Alahuhta I, et al. A novel organotypic model mimics the tumor microenvironment. Am J Pathol. 2009;175(3):1281\u201391. https:\/\/doi.org\/10.2353\/ajpath.2009.081110.","journal-title":"Am J Pathol"},{"key":"1367_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/978-1-4939-7595-2_19","volume":"1731","author":"P \u00c5str\u00f6m","year":"2018","unstructured":"\u00c5str\u00f6m P, Heljasvaara R, Nyberg P, Al-Samadi A, Salo T. Human tumor tissue-based 3D in vitro invasion assays. Methods Mol Biol (Clifton, N.J.). 2018;1731:213\u201321. https:\/\/doi.org\/10.1007\/978-1-4939-7595-2_19.","journal-title":"Methods Mol Biol (Clifton, N.J.)"},{"key":"1367_CR6","doi-asserted-by":"publisher","unstructured":"Naakka E, Tuomainen K, Wistrand H, et al. Fully human tumor-based matrix in three-dimensional spheroid invasion assay. J Vis Exp. 2019;(147). https:\/\/doi.org\/10.3791\/59567.","DOI":"10.3791\/59567"},{"issue":"36","key":"1367_CR7","doi-asserted-by":"publisher","first-page":"60123","DOI":"10.18632\/oncotarget.17768","volume":"8","author":"A Al-Samadi","year":"2017","unstructured":"Al-Samadi A, Awad SA, Tuomainen K, et al. Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in in vitro and in vivo models. Oncotarget. 2017;8(36):60123\u201334. https:\/\/doi.org\/10.18632\/oncotarget.17768.","journal-title":"Oncotarget"},{"issue":"4","key":"1367_CR8","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.yexcr.2012.12.010","volume":"319","author":"S Teppo","year":"2013","unstructured":"Teppo S, Sundquist E, Vered M, et al. The hypoxic tumor microenvironment regulates invasion of aggressive oral carcinoma cells. Exp Cell Res. 2013;319(4):376\u201389. https:\/\/doi.org\/10.1016\/j.yexcr.2012.12.010.","journal-title":"Exp Cell Res"},{"issue":"1","key":"1367_CR9","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.yexcr.2015.06.012","volume":"336","author":"I Alahuhta","year":"2015","unstructured":"Alahuhta I, Aikio M, V\u00e4yrynen O, et al. Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment. Exp Cell Res. 2015;336(1):130\u201340. https:\/\/doi.org\/10.1016\/j.yexcr.2015.06.012.","journal-title":"Exp Cell Res"},{"issue":"2","key":"1367_CR10","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/cam4.24","volume":"1","author":"D Dayan","year":"2012","unstructured":"Dayan D, Salo T, Salo S, et al. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer. Cancer Med. 2012;1(2):128\u201340. https:\/\/doi.org\/10.1002\/cam4.24.","journal-title":"Cancer Med"},{"issue":"3","key":"1367_CR11","doi-asserted-by":"publisher","first-page":"e0120895","DOI":"10.1371\/journal.pone.0120895","volume":"10","author":"E Piril\u00e4","year":"2015","unstructured":"Piril\u00e4 E, V\u00e4yrynen O, Sundquist E, et al. Macrophages modulate migration and invasion of human tongue squamous cell carcinoma. Guan X-Y, ed. PLoS One. 2015;10(3):e0120895. https:\/\/doi.org\/10.1371\/journal.pone.0120895.","journal-title":"PLoS One"},{"issue":"1","key":"1367_CR12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.yexcr.2016.10.015","volume":"350","author":"J Korvala","year":"2017","unstructured":"Korvala J, Jee K, Porkola E, et al. MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro. Exp Cell Res. 2017;350(1):9\u201318. https:\/\/doi.org\/10.1016\/j.yexcr.2016.10.015.","journal-title":"Exp Cell Res"},{"issue":"1","key":"1367_CR13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.yexcr.2019.01.018","volume":"376","author":"O V\u00e4yrynen","year":"2019","unstructured":"V\u00e4yrynen O, \u00c5str\u00f6m P, Nyberg P, et al. Matrix metalloproteinase 9 inhibits the motility of highly aggressive HSC-3 oral squamous cell carcinoma cells. Exp Cell Res. 2019;376(1):18\u201326. https:\/\/doi.org\/10.1016\/j.yexcr.2019.01.018.","journal-title":"Exp Cell Res"},{"issue":"8","key":"1367_CR14","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1111\/jop.12272","volume":"44","author":"JH Kauppila","year":"2015","unstructured":"Kauppila JH, Korvala J, Siiril\u00e4 K, et al. Toll-like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue. J Oral Pathol Med. 2015;44(8):571\u20137. https:\/\/doi.org\/10.1111\/jop.12272.","journal-title":"J Oral Pathol Med"},{"issue":"5","key":"1367_CR15","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1111\/jop.12373","volume":"45","author":"LK M\u00e4kinen","year":"2016","unstructured":"M\u00e4kinen LK, Ahmed A, Hagstr\u00f6m J, et al. Toll-like receptors 2, 4, and 9 in primary, metastasized, and recurrent oral tongue squamous cell carcinomas. J Oral Pathol Med. 2016;45(5):338\u201345. https:\/\/doi.org\/10.1111\/jop.12373.","journal-title":"J Oral Pathol Med"},{"key":"1367_CR16","doi-asserted-by":"publisher","unstructured":"Giuliano AR, Nyitray AG, Kreimer AR, et al. EUROGIN 2014 roadmap: differences in HPV infection natural history, transmission, and HPV-related cancer incidence by gender and anatomic site of infection HHS public access. Int J Cancer Int J Cancer. 2015. https:\/\/doi.org\/10.1002\/ijc.29082.","DOI":"10.1002\/ijc.29082"},{"issue":"3","key":"1367_CR17","first-page":"361","volume":"119","author":"C Yee","year":"1985","unstructured":"Yee C, Krishnan-Hewlett I, Baker CC, Schlegel R, Howley PM. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol. 1985;119(3):361\u20136 http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/2990217. Accessed 20 May 2019.","journal-title":"Am J Pathol"},{"key":"1367_CR18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jviromet.2014.05.017","volume":"206","author":"R Raybould","year":"2014","unstructured":"Raybould R, Fiander A, Wilkinson GWG, Hibbitts S. HPV integration detection in CaSki and SiHa using detection of integrated papillomavirus sequences and restriction-site PCR. J Virol Methods. 2014;206:51\u20134. https:\/\/doi.org\/10.1016\/j.jviromet.2014.05.017.","journal-title":"J Virol Methods"},{"issue":"2","key":"1367_CR19","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/0042-6822(85)90164-3","volume":"145","author":"M Pater","year":"1985","unstructured":"Pater M, Pater A. Human papillomavirus types 16 and 18 sequences in carcinoma cell lines of the cervix. Virology. 1985;145(2):313\u20138.","journal-title":"Virology"},{"issue":"1","key":"1367_CR20","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa0912217","volume":"363","author":"KK Ang","year":"2010","unstructured":"Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24\u201335. https:\/\/doi.org\/10.1056\/NEJMoa0912217.","journal-title":"N Engl J Med"},{"issue":"15","key":"1367_CR21","doi-asserted-by":"publisher","first-page":"4791","DOI":"10.1158\/0008-5472.CAN-13-0587","volume":"73","author":"RJ Kimple","year":"2013","unstructured":"Kimple RJ, Smith MA, Blitzer GC, et al. Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res. 2013;73(15):4791\u2013800. https:\/\/doi.org\/10.1158\/0008-5472.CAN-13-0587.","journal-title":"Cancer Res"},{"issue":"8","key":"1367_CR22","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1080\/15384047.2015.1056410","volume":"16","author":"M Zhang","year":"2015","unstructured":"Zhang M, Rose B, Lee CS, Hong AM. In vitro 3-dimensional tumor model for radiosensitivity of HPV positive OSCC cell lines. Cancer Biol Ther. 2015;16(8):1231\u201340. https:\/\/doi.org\/10.1080\/15384047.2015.1056410.","journal-title":"Cancer Biol Ther"},{"issue":"3","key":"1367_CR23","doi-asserted-by":"publisher","first-page":"441","DOI":"10.4149\/neo_2018_170414N277","volume":"65","author":"M Ibragimova","year":"2018","unstructured":"Ibragimova M, Tsyganov M, Shpileva O, et al. HPV status and its genomic integration affect survival of patients with cervical cancer. Neoplasma. 2018;65(3):441\u20138. https:\/\/doi.org\/10.4149\/neo_2018_170414N277.","journal-title":"Neoplasma"},{"issue":"3","key":"1367_CR24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/ijc.10708","volume":"102","author":"B Bachtiary","year":"2002","unstructured":"Bachtiary B, Obermair A, Dreier B, et al. Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer. Int J Cancer. 2002;102(3):237\u201343. https:\/\/doi.org\/10.1002\/ijc.10708.","journal-title":"Int J Cancer"},{"issue":"5","key":"1367_CR25","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/S0360-3016(01)02796-1","volume":"52","author":"Y Harima","year":"2002","unstructured":"Harima Y, Sawada S, Nagata K, Sougawa M, Ohnishi T. Human papilloma virus (HPV) DNA associat human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy. Int J Radiat Oncol Biol Phys. 2002;52(5):1345\u201351. https:\/\/doi.org\/10.1016\/S0360-3016(01)02796-1.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"39","key":"1367_CR26","doi-asserted-by":"publisher","first-page":"66352","DOI":"10.18632\/oncotarget.18558","volume":"8","author":"P Li","year":"2017","unstructured":"Li P, Tan Y, Zhu LX, et al. Prognostic value of HPV DNA status in cervical cancer before treatment: a systematic review and meta-analysis. Oncotarget. 2017;8(39):66352\u20139. https:\/\/doi.org\/10.18632\/oncotarget.18558.","journal-title":"Oncotarget"},{"issue":"8699","key":"1367_CR27","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/0140-6736(90)92693-c","volume":"335","author":"G Riou","year":"1990","unstructured":"Riou G, Favre M, Jeannel D, Bourhis J, Le Doussal V, Orth G. Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA. Lancet (London, England). 1990;335(8699):1171\u20134. https:\/\/doi.org\/10.1016\/0140-6736(90)92693-c.","journal-title":"Lancet (London, England)"},{"issue":"11","key":"1367_CR28","doi-asserted-by":"publisher","first-page":"3935","DOI":"10.1002\/j.1460-2075.1992.tb05487.x","volume":"11","author":"T Crook","year":"1992","unstructured":"Crook T, Vousden KH. Properties of p53 mutations detected in primary and secondary cervical cancers suggest mechanisms of metastasis and involvement of environmental carcinogens. EMBO J. 1992;11(11):3935\u201340 http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/1327751. Accessed 12 Oct 2019.","journal-title":"EMBO J"},{"issue":"3\u20134","key":"1367_CR29","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/BF01540656","volume":"16","author":"MC Kibbey","year":"1994","unstructured":"Kibbey MC. Maintenance of the EHS sarcoma and Matrigel preparation. J Tissue Cult Methods. 1994;16(3\u20134):227\u201330. https:\/\/doi.org\/10.1007\/BF01540656.","journal-title":"J Tissue Cult Methods"},{"issue":"1","key":"1367_CR30","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.yexcr.2018.08.005","volume":"371","author":"O V\u00e4yrynen","year":"2018","unstructured":"V\u00e4yrynen O, Piippo M, J\u00e4ms\u00e4 H, et al. Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro. Exp Cell Res. 2018;371(1):151\u201361. https:\/\/doi.org\/10.1016\/j.yexcr.2018.08.005.","journal-title":"Exp Cell Res"},{"key":"1367_CR31","doi-asserted-by":"publisher","unstructured":"van Wyk HC, Roseweir A, Alexander P, et al. The relationship between tumor budding, tumor microenvironment, and survival in patients with primary operable colorectal cancer. Ann Surg Oncol. 2019. https:\/\/doi.org\/10.1245\/s10434-019-07931-6.","DOI":"10.1245\/s10434-019-07931-6"},{"issue":"10","key":"1367_CR32","doi-asserted-by":"publisher","first-page":"3712","DOI":"10.1002\/hed.25872","volume":"41","author":"AA M\u00e4kitie","year":"2019","unstructured":"M\u00e4kitie AA, Almangush A, Rodrigo JP, Ferlito A, Leivo I. Hallmarks of cancer: tumor budding as a sign of invasion and metastasis in head and neck cancer. Head Neck. 2019;41(10):3712\u20138. https:\/\/doi.org\/10.1002\/hed.25872.","journal-title":"Head Neck"},{"issue":"6","key":"1367_CR33","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1111\/his.13144","volume":"70","author":"M Seki","year":"2017","unstructured":"Seki M, Sano T, Yokoo S, Oyama T. Tumour budding evaluated in biopsy specimens is a useful predictor of prognosis in patients with cN0 early stage oral squamous cell carcinoma. Histopathology. 2017;70(6):869\u201379. https:\/\/doi.org\/10.1111\/his.13144.","journal-title":"Histopathology"},{"issue":"4","key":"1367_CR34","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/bjc.2017.425","volume":"118","author":"A Almangush","year":"2018","unstructured":"Almangush A, Pirinen M, Heikkinen I, M\u00e4kitie AA, Salo T, Leivo I. Tumour budding in oral squamous cell carcinoma: a meta-analysis. Br J Cancer. 2018;118(4):577\u201386. https:\/\/doi.org\/10.1038\/bjc.2017.425.","journal-title":"Br J Cancer"},{"issue":"2","key":"1367_CR35","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s00428-017-2212-1","volume":"472","author":"A Almangush","year":"2018","unstructured":"Almangush A, Leivo I, Siponen M, et al. Evaluation of the budding and depth of invasion (BD) model in oral tongue cancer biopsies. Virchows Arch. 2018;472(2):231\u20136. https:\/\/doi.org\/10.1007\/s00428-017-2212-1.","journal-title":"Virchows Arch"},{"issue":"2","key":"1367_CR36","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/his.12781","volume":"68","author":"A Almangush","year":"2016","unstructured":"Almangush A, Karhunen M, Hautaniemi S, Salo T, Leivo I. Prognostic value of tumour budding in oesophageal cancer: a meta-analysis. Histopathology. 2016;68(2):173\u201382. https:\/\/doi.org\/10.1111\/his.12781.","journal-title":"Histopathology"},{"issue":"7","key":"1367_CR37","doi-asserted-by":"publisher","first-page":"E112","DOI":"10.1177\/0145561319848669","volume":"98","author":"D Chatterjee","year":"2019","unstructured":"Chatterjee D, Bansal V, Malik V, et al. Tumor budding and worse pattern of invasion can predict nodal metastasis in oral cancers and associated with poor survival in early-stage tumors. Ear Nose Throat J. 2019;98(7):E112\u20139. https:\/\/doi.org\/10.1177\/0145561319848669.","journal-title":"Ear Nose Throat J"},{"issue":"6","key":"1367_CR38","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1002\/hed.25614","volume":"41","author":"Y Ebihara","year":"2019","unstructured":"Ebihara Y, Yoshida S, Nakahira M, et al. Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma. Head Neck. 2019;41(6):1809\u201315. https:\/\/doi.org\/10.1002\/hed.25614.","journal-title":"Head Neck"},{"issue":"2","key":"1367_CR39","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1177\/1066896914565022","volume":"23","author":"PV Angadi","year":"2015","unstructured":"Angadi PV, Patil PV, Hallikeri K, Mallapur MD, Hallikerimath S, Kale AD. Tumor budding is an independent prognostic factor for prediction of lymph node metastasis in oral squamous cell carcinoma. Int J Surg Pathol. 2015;23(2):102\u201310. https:\/\/doi.org\/10.1177\/1066896914565022.","journal-title":"Int J Surg Pathol"},{"issue":"2","key":"1367_CR40","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1002\/hed.25462","volume":"41","author":"Y Zhu","year":"2019","unstructured":"Zhu Y, Liu H, Xie N, et al. Impact of tumor budding in head and neck squamous cell carcinoma: a meta-analysis. Head Neck. 2019;41(2):542\u201350. https:\/\/doi.org\/10.1002\/hed.25462.","journal-title":"Head Neck"},{"issue":"6","key":"1367_CR41","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.22034\/APJCP.2017.18.6.1717","volume":"18","author":"N Satabongkoch","year":"2017","unstructured":"Satabongkoch N, Khunamornpong S, Pongsuvareeyakul T, et al. Prognostic value of tumor budding in early-stage cervical adenocarcinomas. Asian Pac J Cancer Prev. 2017;18(6):1717\u201322. https:\/\/doi.org\/10.22034\/APJCP.2017.18.6.1717.","journal-title":"Asian Pac J Cancer Prev"},{"issue":"2","key":"1367_CR42","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1002\/cjp2.95","volume":"4","author":"M Jesinghaus","year":"2018","unstructured":"Jesinghaus M, Strehl J, Boxberg M, et al. Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix. J Pathol Clin Res. 2018;4(2):93\u2013102. https:\/\/doi.org\/10.1002\/cjp2.95.","journal-title":"J Pathol Clin Res"},{"issue":"5","key":"1367_CR43","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1177\/0194599815592157","volume":"153","author":"MB Wang","year":"2015","unstructured":"Wang MB, Liu IY, Gornbein JA, Nguyen CT. HPV-positive oropharyngeal carcinoma. Otolaryngol Neck Surg. 2015;153(5):758\u201369. https:\/\/doi.org\/10.1177\/0194599815592157.","journal-title":"Otolaryngol Neck Surg"},{"issue":"6","key":"1367_CR44","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.oraloncology.2013.03.446","volume":"49","author":"R Nagel","year":"2013","unstructured":"Nagel R, Martens-de Kemp SR, Buijze M, Jacobs G, Braakhuis BJM, Brakenhoff RH. Treatment response of HPV-positive and HPV-negative head and neck squamous cell carcinoma cell lines. Oral Oncol. 2013;49(6):560\u20136. https:\/\/doi.org\/10.1016\/j.oraloncology.2013.03.446.","journal-title":"Oral Oncol"},{"issue":"3","key":"1367_CR45","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.radonc.2017.08.018","volume":"124","author":"K Schneider","year":"2017","unstructured":"Schneider K, Bol V, Gr\u00e9goire V. Lack of differences in radiation-induced immunogenicity parameters between HPV-positive and HPV-negative human HNSCC cell lines. Radiother Oncol. 2017;124(3):411\u20137. https:\/\/doi.org\/10.1016\/j.radonc.2017.08.018.","journal-title":"Radiother Oncol"},{"issue":"3","key":"1367_CR46","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.radonc.2013.06.011","volume":"108","author":"BS S\u00f8rensen","year":"2013","unstructured":"S\u00f8rensen BS, Busk M, Olthof N, et al. Radiosensitivity and effect of hypoxia in HPV positive head and neck cancer cells. Radiother Oncol. 2013;108(3):500\u20135. https:\/\/doi.org\/10.1016\/j.radonc.2013.06.011.","journal-title":"Radiother Oncol"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-020-01367-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-020-01367-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-020-01367-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T23:34:35Z","timestamp":1625009675000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-020-01367-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1367"],"URL":"https:\/\/doi.org\/10.1186\/s12985-020-01367-1","relation":{},"ISSN":["1743-422X"],"issn-type":[{"type":"electronic","value":"1743-422X"}],"subject":[],"published":{"date-parts":[[2020,6,30]]},"assertion":[{"value":"13 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The myomas have been obtained from routine surgical procedures after obtaining the patients\u2019 informed consent. The original study was approved by the Ethics Committee of the Oulu University Hospital (statement #8\/2006, amendment 19\/10\/2006 and statement #35\/2014, 28.4.2014).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"87"}}