{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:27:59Z","timestamp":1768688879469,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003758","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e ao Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico do Maranh\u00e3o","doi-asserted-by":"publisher","award":["IECT-FAPEMA-05796\/18 FAPEMA IECT 30\/2018 - IECT"],"award-info":[{"award-number":["IECT-FAPEMA-05796\/18 FAPEMA IECT 30\/2018 - IECT"]}],"id":[{"id":"10.13039\/501100003758","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/AGR\/04033\/2020, UIDB\/CVT\/00772\/2020, UIDB\/00511\/2020"],"award-info":[{"award-number":["UID\/AGR\/04033\/2020, UIDB\/CVT\/00772\/2020, UIDB\/00511\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Center of the Portuguese Oncology Institute of Porto","award":["PI86-CI-IPOP-66-2017"],"award-info":[{"award-number":["PI86-CI-IPOP-66-2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB\/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ER\u03b1) and beta (ER\u03b2), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ER\u03b1 and ER\u03b2 expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ER\u03b1, ER\u03b2 and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation.<\/jats:p>","DOI":"10.3390\/pathogens10101224","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T22:24:13Z","timestamp":1632695053000},"page":"1224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential Incidence of Tongue Base Cancer in Male and Female HPV16-Transgenic Mice: Role of Female Sex Hormone Receptors"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6726-4786","authenticated-orcid":false,"given":"Clariano Pires","family":"de Oliveira Neto","sequence":"first","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"}]},{"given":"Beatriz","family":"Medeiros-Fonseca","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6457-2356","authenticated-orcid":false,"given":"Diogo","family":"Est\u00eav\u00e3o","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"FMUP, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Ver\u00f3nica F.","family":"Mestre","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"given":"Nat\u00e1lia R.","family":"Costa","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"}]},{"given":"F\u00e1bio Evangelista","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Veterinary Sciences Department, State University of Maranh\u00e3o, S\u00e3o Luis 65081-400, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Veterinary Sciences Department, University of Tr\u00e1s-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8605-0054","authenticated-orcid":false,"given":"Margarida M. S. M.","family":"Bastos","sequence":"additional","affiliation":[{"name":"LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"FMUP, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, 4249-004 Porto, Portugal"},{"name":"Research Department of the Portuguese League against Cancer Regional Nucleus of the North (LPCC\u2014NRNorte), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-4364","authenticated-orcid":false,"given":"Diogo","family":"Assis","sequence":"additional","affiliation":[{"name":"Department of Morphology, Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2653-2262","authenticated-orcid":false,"given":"Ana","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"Department of Pathology, Instituto Portugues de Oncologia de Lisboa, NOVA Medical School, University NOVA of Lisbon, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"},{"name":"Pathology Department Portuguese Institute of Oncology Lisbon Franscisco Gentil, Rua Professor Lima Bastos, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-412X","authenticated-orcid":false,"given":"Fernanda","family":"Ferreira Lopes","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-2449","authenticated-orcid":false,"given":"Rui M.","family":"Gil da Costa","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"},{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"Department of Morphology, Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"},{"name":"UFMA University Hospital (HUUFMA), S\u00e3o Luis 65020-070, Brazil"}]},{"given":"Haissa O.","family":"Brito","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"},{"name":"Department of Morphology, Federal University of Maranh\u00e3o, S\u00e3o Luis 65080-805, Brazil"}]},{"given":"Luciane M. 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