{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:39Z","timestamp":1785422739766,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010747","name":"CONCYTEC","doi-asserted-by":"publisher","award":["E041-2023-02"],"award-info":[{"award-number":["E041-2023-02"]}],"id":[{"id":"10.13039\/501100010747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010747","name":"CONCYTEC","doi-asserted-by":"publisher","award":["PE501083623-2023"],"award-info":[{"award-number":["PE501083623-2023"]}],"id":[{"id":"10.13039\/501100010747","id-type":"DOI","asserted-by":"publisher"}]},{"award":["E041-2023-02"],"award-info":[{"award-number":["E041-2023-02"]}],"id":[{"id":"https:\/\/ror.org\/05c7j7r25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PE501083623-2023"],"award-info":[{"award-number":["PE501083623-2023"]}],"id":[{"id":"https:\/\/ror.org\/05c7j7r25","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Universidad Peruana de Ciencias Aplicadas","award":["2025 C-020-2025"],"award-info":[{"award-number":["2025 C-020-2025"]}]},{"award":["2025 C-020-2025"],"award-info":[{"award-number":["2025 C-020-2025"]}],"id":[{"id":"https:\/\/ror.org\/047xrr705","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: HPV16 is the most prevalent high-risk genotype associated with cervical cancer, yet the genetic variability and immune potential of the replication protein E1 are less characterized in asymptomatic infections. We assessed HPV16 E1 diversity and predicted conserved T-cell epitopes. Methods: We conducted a descriptive cross-sectional study of cervical samples from women undergoing HPV screening. HPV was detected with universal primers and then HPV16-specific PCR. Thirty HPV16-positive samples underwent full-length E1 amplification and nanopore amplicon sequencing. Variability and phylogeny were analyzed with Clustal Omega and MEGA (maximum likelihood). MHC class I and II epitopes were predicted with the IEDB using HLA alleles representative of South American populations and evaluated for conservation, toxicity, allergenicity, and population coverage. Results: Mutations were detected in 14\/30 samples, while 16 sequences matched the reference (GenBank: NC_001526.3). European lineages (A1\u2013A3) predominated, with one sequence in the Asian-American lineage D. Seven highly conserved MHC I epitopes and 37 conserved MHC II epitopes were identified. Epitopes mapped to multiple regions across the E1 sequence. Predicted global coverage was 94.38% for MHC I, 83.75% for MHC II, and 99.09% combined. Conclusions: HPV16 E1 is highly conserved and contains candidate T-cell targets with broad predicted coverage, supporting evaluation for future vaccine or immunotherapy strategies.<\/jats:p>","DOI":"10.3390\/pathogens15050526","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:17:23Z","timestamp":1779203843000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variability and Conserved T-Cell Epitope Prediction of the HPV16 E1 Protein in Cervix Samples from Peru"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-4617","authenticated-orcid":false,"given":"Eliezer","family":"Bonifacio-Velez de Villa","sequence":"first","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-3190","authenticated-orcid":false,"given":"Miguel Angel","family":"Aguilar-Luis","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilmer","family":"Silva-Caso","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Becerra-Goicochea","sequence":"additional","affiliation":[{"name":"Oncology Unit, Hospital Regional Docente de Cajamarca, Cajamarca 06003, Peru"},{"name":"Professional Academic School of Obstetrics, Universidad Nacional de Cajamarca, Cajamarca 06003, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yordi","family":"Tarazona-Castro","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"},{"name":"Instituto de Investigacion de Enfermedades Infecciosas, Lima 15008, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deysi","family":"Aguilar-Luis","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5360-7314","authenticated-orcid":false,"given":"Dayana","family":"Denegri-Hinostroza","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Cornejo-Tapia","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9100-8547","authenticated-orcid":false,"given":"Ronald","family":"Aquino-Ortega","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6011-5040","authenticated-orcid":false,"given":"Juana","family":"del Valle-Mendoza","sequence":"additional","affiliation":[{"name":"Biomedicine Laboratory, Research Center of Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima 15087, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Denda, N., Maletin, N., Ra\u0161kovi\u0107, A., Prodanovi\u0107, D., Golu\u0161in, Z., Vu\u010dkovi\u0107, B., Nemet, M., and Kusturica, M.P. (2025). Knowledge and Attitudes about Human Papillomavirus Infection and Prevention Methods among Medical Science Students in Novi Sad, Serbia: A Cross-Sectional Study. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-21593-y"},{"key":"ref_2","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA. Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"West, N., Boz, V., Zanotta, N., Cason, C., Campisciano, G., Casuccio, A., Gianfrilli, D., Fasciana, T.M.A., Capra, G., and Salfa, M.C. (2025). Human Papillomavirus: An Old New History. Pathogens, 14.","DOI":"10.20944\/preprints202509.1506.v1"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jouya, S., Shahabinia, Z., Mazidimoradi, A., Allahqoli, L., Salehiniya, H., and Lee, D.-Y. (2026). Cervical Cancer Epidemiology: Global Incidence, Mortality, Survival, Risk Factors, and Equity in HPV Screening and Vaccination. J. Clin. Med., 15.","DOI":"10.3390\/jcm15031079"},{"key":"ref_5","unstructured":"(2026, January 17). International Agency for Research on Cancer Global Cancer Observatory: Cancer Today. Peru Fact Sheet. Available online: https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/populations\/604-peru-fact-sheet.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Galati, L., Di Bonito, P., Marinaro, M., Chiantore, M.V., and Gheit, T. (2024). HPV16 Phylogenetic Variants in Anogenital and Head and Neck Cancers: State of the Art and Perspectives. Viruses, 16.","DOI":"10.3390\/v16060904"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12985-024-02397-9","article-title":"The Potential Use of Therapeutics and Prophylactic mRNA Vaccines in Human Papillomavirus (HPV)","volume":"21","author":"Movahed","year":"2024","journal-title":"Virol. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2017.08.001","article-title":"HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis","volume":"170","author":"Mirabello","year":"2017","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Baedyananda, F., Sasivimolrattana, T., Chaiwongkot, A., Varadarajan, S., and Bhattarakosol, P. (2022). Role of HPV16 E1 in Cervical Carcinogenesis. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.955847"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, F., Fu, S., Zhang, C., Zhe, X., Li, H., Li, D., Shao, R., and Pan, Z. (2021). Analysis of Genetic Variation in Human Papillomavirus Type 16 E1 and E2 in Women with Cervical Infection in Xinjiang, China. BMC Med. Genom., 14.","DOI":"10.1186\/s12920-021-01120-9"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bonifacio-Velez de Villa, E., Aguilar-Luis, D., Denegri-Hinostroza, D., Aguilar-Luis, M.A., Silva-Caso, W., Tarazona-Castro, Y., Becerra-Goicochea, L., Aquino-Ortega, R., Cornejo-Tapia, A., and del Valle-Mendoza, J. (2025). Genetic Variability and Prediction of T Epitopes of the HPV16 E2 Gene in Asymptomatic Women from Cajamarca, Peru. Viruses, 17.","DOI":"10.3390\/v17111420"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.meegid.2018.07.002","article-title":"The Association of Human Papillomavirus Type 16 E2 Variations with Cervical Cancer in a Han Chinese Population","volume":"64","author":"Dai","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/tcmj.tcmj_134_24","article-title":"An Exploration of the Natural and Acquired Immunological Mechanisms to High-Risk Human Papillomavirus Infection and Unmasking Immune Escape in Cervical Cancer: A Concise Synopsis","volume":"37","author":"Mohammed","year":"2025","journal-title":"Tzu Chi Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Requena, D., M\u00e9dico, A., Chac\u00f3n, R.D., Ram\u00edrez, M., and Mar\u00edn-S\u00e1nchez, O. (2020). Identification of Novel Candidate Epitopes on SARS-CoV-2 Proteins for South America: A Review of HLA Frequencies by Country. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02008"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Carrillo-Ng, H., Becerra-Goicochea, L., Tarazona-Castro, Y., Pinillos-Vilca, L., del Valle, L.J., Aguilar-Luis, M.A., Tinco-Valdez, C., Silva-Caso, W., Martins-Luna, J., and Pe\u00f1a-Tuesta, I. (2021). Variations in Cervico-Vaginal Microbiota among HPV-Positive and HPV-Negative Asymptomatic Women in Peru. BMC Res. Notes, 14.","DOI":"10.1186\/s13104-020-05422-6"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.7150\/ijms.34279","article-title":"Human Papillomavirus Type 16 E1 Mutations Associated with Cervical Cancer in a Han Chinese Population","volume":"16","author":"Yao","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6272","DOI":"10.1038\/s41467-020-20075-6","article-title":"Analytical Validity of Nanopore Sequencing for Rapid SARS-CoV-2 Genome Analysis","volume":"11","author":"Bull","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"W502","DOI":"10.1093\/nar\/gkz452","article-title":"IEDB-AR: Immune Epitope Database\u2014Analysis Resource in 2019","volume":"47","author":"Dhanda","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1021\/acs.jafc.3c07143","article-title":"pLM4Alg: Protein Language Model-Based Predictors for Allergenic Proteins and Peptides","volume":"72","author":"Du","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Morozov, V., Rodrigues, C.H.M., and Ascher, D.B. (2023). CSM-Toxin: A Web-Server for Predicting Protein Toxicity. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020431"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.virol.2020.11.003","article-title":"Genetic Signatures for Lineage\/Sublineage Classification of HPV16, 18, 52 and 58 Variants","volume":"553","author":"Ou","year":"2021","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.pvr.2019.02.001","article-title":"Human Papillomavirus 16 Sub-Lineage Dispersal and Cervical Cancer Risk Worldwide: Whole Viral Genome Sequences from 7116 HPV16-Positive Women","volume":"7","author":"Clifford","year":"2019","journal-title":"Papillomavirus Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/bjc.2012.508","article-title":"HPV16 Genetic Variation and the Development of Cervical Cancer Worldwide","volume":"108","author":"Cornet","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1093\/infdis\/jiad204","article-title":"Human Papillomavirus 16 Lineage A Variants Associated with Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study","volume":"228","author":"Ferreira","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"del Valle-Mendoza, J., Becerra-Goicochea, L., Aguilar-Luis, M.A., Pinillos-Vilca, L., Carrillo-Ng, H., Silva-Caso, W., Palomares-Reyes, C., Taco-Masias, A.-A., Aquino-Ortega, R., and Tinco-Valdez, C. (2021). Genotype-Specific Prevalence of Human Papillomavirus Infection in Asymptomatic Peruvian Women: A Community-Based Study. BMC Res. Notes, 14.","DOI":"10.1186\/s13104-021-05588-7"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1002\/ijc.22481","article-title":"High Grade Cervical Lesions Are Caused Preferentially by Non-European Variants of HPVs 16 and 18","volume":"120","author":"Sichero","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"32535","DOI":"10.1038\/s41598-025-18455-3","article-title":"Genotype Distribution and Molecular Characterization of HPV in the Peruvian Amazon: Insights into Prevalence, Lineage Diversity, and Viral Integration","volume":"15","author":"Stosic","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kiamba, E.W., Goodier, M.R., and Clarke, E. (2025). Immune Responses to Human Papillomavirus Infection and Vaccination. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1591297"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7349","DOI":"10.1128\/JVI.74.16.7349-7361.2000","article-title":"Identification of Domains of the Human Papillomavirus Type 11 E1 Helicase Involved in Oligomerization and Binding to the Viral Origin","volume":"74","author":"Titolo","year":"2000","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rana, A., Yilmaz, G., Biswas-Fiss, E.E., and Biswas, S. (2025). Mechanisms of Viral DNA Replication of Human Papillomavirus: E2 Protein-Dependent Recruitment of E1 DNA Helicase to the Origin of DNA Replication. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094333"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7069","DOI":"10.1128\/JVI.78.13.7069-7078.2004","article-title":"Selection, Transmission, and Reversion of an Antigen-Processing Cytotoxic T-Lymphocyte Escape Mutation in Human Immunodeficiency Virus Type 1 Infection","volume":"78","author":"Allen","year":"2004","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e006721","DOI":"10.1136\/jitc-2023-006721","article-title":"Identification of HPV16 E1 and E2-Specific T Cells in the Oropharyngeal Cancer Tumor Microenvironment","volume":"11","author":"McInnis","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"126.28","DOI":"10.4049\/jimmunol.200.Supp.126.28","article-title":"HPV18 E1-Antigen Specific CD8+ T Cells Show Cross-Reactivity against Cells Expressing E1 from HPV16, 31, 33 and 53","volume":"200","author":"Amador","year":"2018","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1016\/S0140-6736(15)00239-1","article-title":"Safety, Efficacy, and Immunogenicity of VGX-3100, a Therapeutic Synthetic DNA Vaccine Targeting Human Papillomavirus 16 and 18 E6 and E7 Proteins for Cervical Intraepithelial Neoplasia 2\/3: A Randomised, Double-Blind, Placebo-Controlled Phase 2b Trial","volume":"386","author":"Trimble","year":"2015","journal-title":"Lancet"},{"key":"ref_35","unstructured":"Qiao, R., Tran, N.H., Shan, B., Ghodsi, A., and Li, M. (2020). Personalized Workflow to Identify Optimal T-Cell Epitopes for Peptide-Based Vaccines against COVID-19 2020. arXiv."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/526\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:30:17Z","timestamp":1779204617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["pathogens15050526"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15050526","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}