{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:39:50Z","timestamp":1786700390146,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>High-risk human papillomavirus (HR-HPV) infection is the principal etiological factor in cervical cancer, with genotype distribution and cytological associations varying across populations. This retrospective study aimed to characterize the prevalence and genotype distribution of HR-HPV among 1747 Bulgarian women, including a subgroup of 1134 women with paired HPV polymerase chain reaction (PCR) and liquid-based cytology (LBC) results. The study population comprised women undergoing routine cervical screening (76.0%, n = 1328) and women tested because of clinical indications, including gynecological symptoms (24.0%, n = 419). The overall HR-HPV prevalence was 31.4% (549\/1747) and was significantly higher among women tested for clinical indications than among those undergoing routine screening. HPV16 was the most frequently detected genotype, followed by multiple HR-HPV infections and other genotypes, including HPV31, HPV51, HPV66, HPV18, HPV45, HPV56, HPV68, and HPV33. Cytological abnormalities were identified in 24.7% (280\/1134) of women with paired HPV and cytology results. HR-HPV positivity was strongly associated with abnormal cytology; however, 27.3% (233\/854) of women with negative cytology were also HR-HPV positive. Integrating HPV genotyping with cytology may improve risk stratification and support more targeted clinical management. Despite the increasing use of LBC and HPV co-testing, comparative data describing HR-HPV genotype distribution and its relationship with cytological findings in screening and symptomatic populations remain limited. These findings provide epidemiological evidence on HR-HPV infection patterns in Bulgarian women and establish a foundation for future studies evaluating genotype-specific risks, disease progression, and population-based surveillance strategies.<\/jats:p>","DOI":"10.3390\/microorganisms14081794","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:01Z","timestamp":1786698241000},"page":"1794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epidemiological Profile of High-Risk HPV in Cervical Samples for Liquid-Based Cytology: Insights from Screening and Symptomatic Cohorts"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2858-1970","authenticated-orcid":false,"given":"Antoanela","family":"Curici","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology and Histology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Synevo Romania, 021408 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-374X","authenticated-orcid":false,"given":"Denitsa","family":"Tsaneva-Damyanova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Virology, Medical University, 3 Bregalnitsa St., 9000 Varna, Bulgaria"},{"name":"Medical Diagnostics Laboratory Synevo Bulgaria, 24 Saborni Blvd., 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergana","family":"Nedelcheva","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Virology, Medical University, 3 Bregalnitsa St., 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-6956","authenticated-orcid":false,"given":"Luciana Alexandra","family":"Pavelescu","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology and Histology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Har\u0119\u017ca, D.A., Wilczy\u0144ski, J.R., and Paradowska, E. (2022). Human Papillomaviruses as Infectious Agents in Gynecological Cancers. Oncogenic Properties of Viral Proteins. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031818"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.30683\/1927-7229.2025.14.07","article-title":"Prevalence and Type Distribution of Human Papilloma Virus (HPV) in Oral, Oropharyngeal, Cervical, and Vulvovaginal Cancers","volume":"14","author":"Dholariya","year":"2025","journal-title":"J. Anal. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112289","DOI":"10.1016\/j.jtbi.2025.112289","article-title":"Human Papillomavirus Driving Cervical Cancer: A Mathematical Model with Persistent Infection, Cancer Progression, and Spontaneous Remission","volume":"617","author":"Hayashi","year":"2026","journal-title":"J. Theor. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104721","DOI":"10.1016\/j.critrevonc.2025.104721","article-title":"Novel Therapeutic Strategies for Targeting E6 and E7 Oncoproteins in Cervical Cancer","volume":"211","author":"Ranasinghe","year":"2025","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S1470-2045(10)70230-8","article-title":"Human Papillomavirus Genotype Attribution in Invasive Cervical Cancer: A Retrospective Cross-Sectional Worldwide Study","volume":"11","author":"Quint","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e29524","DOI":"10.1002\/jmv.29524","article-title":"Correlation between high-risk HPV infection and p16\/Ki-67 abnormalities in Pap samples in a South Eastern Europe cohort","volume":"96","author":"Shalaby","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_7","first-page":"25","article-title":"Prevalence of Human Papillomavirus Genotypes in Bulgarian Women with Atypical Cervical Lesions Examined by Colposcopy","volume":"49","author":"Kovachev","year":"2010","journal-title":"Akusherstvo Ginekol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s40291-025-00790-w","article-title":"Cell-Free HPV-DNA in Screening, Diagnosis, Prognosis, and Treatment Response Monitoring of Cervical Cancer","volume":"29","author":"Silva","year":"2025","journal-title":"Mol. Diagn. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4103\/joc.joc_53_26","article-title":"Cervical Cancer Screening in the Molecular Era: Integrating Cytology, Human Papillomavirus Testing, and Biomarkers","volume":"43","author":"Parvathy","year":"2026","journal-title":"J. Cytol."},{"key":"ref_10","first-page":"1728","article-title":"Spectrum of cervical precancerous and cancerous lesion in liquid-based cytology smears and its correlation with HPV typing","volume":"32","author":"Misra","year":"2025","journal-title":"J. Popul. Ther. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"332","DOI":"10.34297\/AJBSR.2022.15.002116","article-title":"New Quantitative PCR Technology for Screening Human Papillomavirus Test\u2014Identification of 25 Genotypes: A Molecular Epidemiology and Cross- Sectional Study","volume":"15","year":"2022","journal-title":"Am. J. Biomed. Sci. Res."},{"key":"ref_12","unstructured":"Thanasas, I., Lavranos, G., Gogou, P., and Paraskevis, D. (2020). Epidemiology of the HPV in Greece and Other Countries of the World. Zenodo (CERN Eur. Organ. Nucl. Res.)."},{"key":"ref_13","first-page":"1239","article-title":"Cervical Cancer (over-)Screening in Europe: Balancing Organised and Opportunistic Programmes","volume":"51","author":"Jolidon","year":"2022","journal-title":"Scand. J. Public Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100955","DOI":"10.1016\/j.lanmic.2024.100955","article-title":"Global Prevalence of Cervical Human Papillomavirus in Women Aged 50 Years and Older with Normal Cytology: A Systematic Review and Meta-Analysis","volume":"6","author":"Osmani","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1093\/eurpub\/ckae075","article-title":"Understanding the High-Risk Human Papillomavirus Prevalence and Associated Factors in the European Country with a High Incidence of Cervical Cancer","volume":"34","author":"Berza","year":"2024","journal-title":"Eur. J. Public Health"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ga\u0144czak, M., Miazgowski, T., Ko\u017cybska, M., Kotwas, A., Korze\u0144, M., Rudnicki, B., Nogal, T., Andrei, C.L., Ausloos, M., and Banach, M. (2020). Changes in Disease Burden in Poland between 1990-2017 in Comparison with Other Central European Countries: A Systematic Analysis for the Global Burden of Disease Study 2017. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226766"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.31557\/APJCP.2022.23.7.2477","article-title":"Genotype Distribution and Prevalence of High-Risk Human Papillomavirus Infection among Women in Samsun Province of Turkey","volume":"23","author":"Taskin","year":"2022","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_18","first-page":"351","article-title":"Detection of 14 Human Papillomavirus Genotypes in Cervical Samples in Women from a Central-Southern Area of Italy Showing Different Pap Test Results","volume":"32","author":"Zappacosta","year":"2009","journal-title":"New Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s00404-011-2155-8","article-title":"Prevalence and Risk Factors of HPV Infection among Women from Various Provinces of the World","volume":"285","author":"Vinodhini","year":"2011","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1002\/jmv.23652","article-title":"Prevalence of Human Papillomavirus Infection in Women in Some Cities and Regions of Bulgaria","volume":"85","author":"Kovachev","year":"2013","journal-title":"J. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1002\/jmv.25050","article-title":"Prevalence of Human Papillomavirus Infection in Women in Bulgaria: A 2017 Update","volume":"90","author":"Kovachev","year":"2018","journal-title":"J. Med. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.21873\/invivo.13314","article-title":"Detection of 14 High-Risk Human Papillomavirus (HPV) Genotypes Within the Italian Cervical Cancer Screening","volume":"37","author":"Cenci","year":"2023","journal-title":"In Vivo"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14794","DOI":"10.1002\/cam4.6109","article-title":"Diagnostic Value of High-Risk HPV Other than Type 16\/18 in High-Grade Cervical Neoplasia among Cytology-Negative Women: A Multicenter Retrospective Study","volume":"12","author":"Bai","year":"2023","journal-title":"Cancer Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/sj.bjc.6600688","article-title":"Human Papillomavirus Types in Invasive Cervical Cancer Worldwide: A Meta-Analysis","volume":"88","author":"Clifford","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"375","DOI":"10.37201\/req\/178.2026","article-title":"Associations between High-Risk Human Papillomavirus Genotypes: Evidence of HPV16 Predominance as a Monoinfection and Its No Stronger Link with High-Grade Lesions","volume":"39","year":"2026","journal-title":"Rev. Esp. Quimioter. Publ. Of. Soc. Esp. Quimioter."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"76","DOI":"10.31486\/toj.25.0082","article-title":"Comparative Distribution of High-Risk Human Papillomavirus (HPV) Genotypes in India vs World Health Organization Regions and Countries: Implications for HPV Vaccination","volume":"26","author":"Prabhakaran","year":"2026","journal-title":"Ochsner J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1093\/ajcp\/aqac073","article-title":"The Clinical Utility of Extended High-Risk HPV Genotyping in Women With ASC-US Cytology","volume":"158","author":"Jiang","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1159\/000442512","article-title":"Multiple Human Papilloma Virus Infections and Their Impact on the Development of High-Risk Cervical Lesions","volume":"59","author":"Salazar","year":"2015","journal-title":"Acta Cytol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/LGT.0000000000000487","article-title":"Distribution of High-Risk Human Papillomavirus Genotypes and Multiple Infections in Preneoplastic and Neoplastic Cervical Lesions of Unvaccinated Women: A Cross-Sectional Study","volume":"23","author":"Iacobone","year":"2019","journal-title":"J. Low. Genit. Tract. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1158\/1055-9965.EPI-09-0983","article-title":"Data from Concurrent Infection with Multiple Human Papillomavirus Types: Pooled Analysis of the IARC HPV Prevalence Surveys","volume":"19","author":"Vaccarella","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Keiffer, T.R., Soorya, S., and Sapp, M.J. (2021). Recent Advances in Our Understanding of the Infectious Entry Pathway of Human Papillomavirus Type 16. Microorganisms, 9.","DOI":"10.3390\/microorganisms9102076"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13027-025-00709-4","article-title":"Clinical Study on the Pathogenic Risks of Different Genotypes of High-Risk HPV Infection and Multiple Infections","volume":"20","author":"Song","year":"2025","journal-title":"Infect. Agents Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/infdis\/jiw074","article-title":"Incident Detection of High-Risk Human Papillomavirus Infections in a Cohort of High-Risk Women Aged 25-65 Years","volume":"214","author":"Winer","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tessandier, N., \u00c9lie, B., Bou\u00e9, V., Selinger, C., Rahmoun, M., Bernat, C., Grasset, S., Groc, S., Bedin, A., and B\u00e9n\u00e9teau, T. (2023). Viral and Immune Dynamics of HPV Genital Infections in Young Women. medRxiv.","DOI":"10.1101\/2023.05.11.23289843"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1097\/AOG.0b013e31818b0df2","article-title":"Prevalence of High-Risk Human Papillomavirus among Older Women","volume":"112","author":"Lindau","year":"2008","journal-title":"Obstet. Gynecol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Piana, A., Sotgiu, G., Cocuzza, C., Musumeci, R., Marras, V., Pischedda, S., Deidda, S., Muresu, E., and Castiglia, P. (2013). High HPV-51 Prevalence in Invasive Cervical Cancers: Results of a Pre-Immunization Survey in North Sardinia, Italy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063395"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Soylu, B., T\u00fcrk\u00e7\u00fc, G., A\u011fa\u00e7ayak, E., and F\u0131rat, U. (2026). Cytomorphological Reflections of HPV Positivity in Concurrent HPV Testing and Smear Specimens. Harran \u00dcniversitesi T\u0131p Fak\u00fcltesi Derg., 49\u201355. Advanced Online Publication.","DOI":"10.35440\/hutfd.1762809"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrclinonc.2012.16","article-title":"More Evidence Supporting Human Papillomavirus Testing","volume":"9","author":"Castle","year":"2012","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105657","DOI":"10.1016\/j.jcv.2024.105657","article-title":"Human Papillomavirus Negative High Grade Cervical Lesions and Cancers: Suggested Guidance for HPV Testing Quality Assurance","volume":"171","author":"Cuschieri","year":"2024","journal-title":"J. Clin. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/dc.25146","article-title":"High-Grade Squamous Intraepithelial Lesion Cervicovaginal Paps with Negative High-Risk HPV Testing, a Prospective Study with Histological Follow-Up","volume":"51","author":"Agoff","year":"2023","journal-title":"Diagn. Cytopathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1128\/JCM.01733-08","article-title":"RNA (E6 and E7) Assays versus DNA (E6 and E7) Assays for Risk Evaluation for Women Infected with Human Papillomavirus","volume":"47","author":"Cattani","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, J., Zhang, D., Yang, Z., Wang, X., and Wang, D. (2019). The Role of High-Risk HPV Genotyping in the Detection of High-Grade Intraepithelial Neoplasia or Cancer in Women with Negative Cytology but Positivity for HPV: A Hospital-Based Investigation in Northeastern China. Res. Sq. Am. J. Experts.","DOI":"10.21203\/rs.2.17764\/v1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"82","DOI":"10.17816\/clinpract64982","article-title":"Additional Diagnostic Capabilities in the Practice of a PAP-Test Using Liquid-Based Cytology","volume":"12","author":"Aksamentov","year":"2021","journal-title":"J. Clin. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bandeira, I.C., Comerlato, J., Bessel, M., Fernandes, B.V., Mota, G., Villa, L.L., De Souza, F.M.A., Pereira, G.F.M., and Wendland, E.M. (2024). Comparative Evaluation of HPV Genotyping: A Study on the Performance Concordance between Anyplex II HPV28 Detection and Linear Array Genotyping Tests in Nationwide Studies in Brazil. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0305122"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1128\/JCM.01305-06","article-title":"Pilot Study of a Commercialized Human Papillomavirus (HPV) Genotyping Assay: Comparison of HPV Risk Group to Cytology and Histology","volume":"44","author":"Castle","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0191824","DOI":"10.1128\/spectrum.01918-24","article-title":"Multi-Center Evaluation of the Alinity m HR HPV Assay with Liquid-Based Cytology Cervical Specimens in the United States","volume":"13","author":"Goldstein","year":"2025","journal-title":"Microbiol. Spectr."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/8\/1794\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:20:23Z","timestamp":1786699223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/8\/1794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["microorganisms14081794"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14081794","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}