{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:28:52Z","timestamp":1783636132871,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["252984, 263943, and 271386"],"award-info":[{"award-number":["252984, 263943, and 271386"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.<\/jats:p>","DOI":"10.3390\/ijms22063242","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T12:55:07Z","timestamp":1616417707000},"page":"3242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7096-2713","authenticated-orcid":false,"given":"Mar\u00eda Lourdes","family":"Garza-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Centro Universitario Contra el C\u00e1ncer, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-2803","authenticated-orcid":false,"given":"Mariel Araceli","family":"Oyervides-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnologico de Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey 64849, Mexico"},{"name":"Departamento de Bioqu\u00edmica y Medicina Molecular, Facultad de Medicina, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro Monterrey, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6614-1266","authenticated-orcid":false,"given":"Antonio Al\u00ed","family":"P\u00e9rez-Maya","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Medicina Molecular, Facultad de Medicina, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro Monterrey, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3444-9565","authenticated-orcid":false,"given":"Celia Nohem\u00ed","family":"S\u00e1nchez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Medicina Molecular, Facultad de Medicina, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro Monterrey, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Berlanga-Garza","sequence":"additional","affiliation":[{"name":"Departamento de Ginecolog\u00eda y Obstetricia, Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Antonio-Macedo","sequence":"additional","affiliation":[{"name":"Departamento de Ginecolog\u00eda y Obstetricia, Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lezmes Dionicio","family":"Vald\u00e9s-Chapa","sequence":"additional","affiliation":[{"name":"Departamento de Ginecolog\u00eda y Obstetricia, Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Vidal-Torres","sequence":"additional","affiliation":[{"name":"Departamento de Ginecolog\u00eda y Obstetricia, Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Vidal-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Centro Universitario Contra el C\u00e1ncer, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Cristina","family":"P\u00e9rez-Ibave","sequence":"additional","affiliation":[{"name":"Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Centro Universitario Contra el C\u00e1ncer, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero S\/N, Mitras Centro, Nuevo Le\u00f3n 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7472-9844","authenticated-orcid":false,"given":"V\u00edctor","family":"Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Av. Morones Prieto 3000, Colonia Los Doctores, Nuevo Le\u00f3n 64710, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","unstructured":"Wold Health Organization (2021, February 09). Cervical Cancer: Overview. Available online: https:\/\/www.who.int\/health-topics\/cervical-cancer#tab=tab_1."},{"key":"ref_2","unstructured":"(2020, December 10). Human Papillomavirus and Related Diseases in Mexico. Available online: http:\/\/www.hpvcentre.net\/statistics\/reports\/MEX.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11451","DOI":"10.1128\/JVI.78.21.11451-11460.2004","article-title":"Mechanisms of Human Papillomavirus-Induced Oncogenesis","volume":"78","author":"Baldwin","year":"2004","journal-title":"J. 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