{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:16:42Z","timestamp":1775827002306,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a substantial proportion of women with established infection are managed conservatively, often with prolonged follow-up and associated psychological burden. Interest has therefore grown in supportive interventions that may facilitate viral clearance during routine clinical management. Methods: This retrospective cohort study included 239 women with confirmed cervical Human papillomavirus infection followed at a tertiary referral center between February 2023 and August 2025. Participants were classified into a treatment group receiving oral Papivir\/Pavirona\u00ae twice daily for six months (n = 119) and a control group managed with routine clinical follow-up alone (n = 120). Human papillomavirus DNA testing and cervical cytology were evaluated at baseline and at 6 and 12 months. Results: Human papillomavirus clearance rates were significantly higher in the Papivir\/Pavirona\u00ae group compared with controls at both 6 and 12 months. Cytological regression was also more frequent in the treatment group at both time points. In multivariate logistic regression analysis, Papivir\/Pavirona\u00ae use emerged as the only independent predictor of both Human papillomavirus clearance and cytological regression, while demographic, reproductive, behavioral, and virological baseline characteristics were not significantly associated with outcomes. Conclusions: Papivir\/Pavirona\u00ae supplementation was associated with increased Human papillomavirus clearance and cytological regression rates in women with cervical Human papillomavirus infection, suggesting a potential supportive role alongside standard clinical follow-up.<\/jats:p>","DOI":"10.3390\/v18040455","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:55:12Z","timestamp":1775807712000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Oral Papivir\/Pavirona\u00ae Supplementation with HPV DNA Clearance"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0446-2870","authenticated-orcid":false,"given":"Betul","family":"Gungor Serin","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4329-1376","authenticated-orcid":false,"given":"Bilal Esat","family":"Temiz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haticegul","family":"Tuncer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammed Onur","family":"Atakul","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9298-2720","authenticated-orcid":false,"given":"Ali Can","family":"Gunes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8920-1444","authenticated-orcid":false,"given":"Taylan","family":"Onat","sequence":"additional","affiliation":[{"name":"Sincan Training and Research Hospital, Ankara 06930, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1377-2651","authenticated-orcid":false,"given":"Utku","family":"Akgor","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-1417","authenticated-orcid":false,"given":"Derman","family":"Basaran","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zafer Selcuk","family":"Tuncer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4221-4459","authenticated-orcid":false,"given":"Murat","family":"Gultekin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","first-page":"552028","article-title":"Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation","volume":"8","author":"Li","year":"2020","journal-title":"Front. Public Health"},{"key":"ref_2","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2024). Global Cancer Observatory: Cancer Tomorrow, International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.fr\/tomorrow."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Legaki, E., Lappa, T., Prasoula, K.L., Kardasi, Z., Kalampokas, E., Kalampokas, T., Roubelakis, M.G., Charvalos, E., and Gazouli, M. (2026). HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020803"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.1016\/S2214-109X(19)30482-6","article-title":"Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis","volume":"8","author":"Legaki","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0140-6736(24)01097-3","article-title":"Causal attribution of human papillomavirus genotypes to invasive cervical cancer worldwide: A systematic analysis of the global literature","volume":"404","author":"Wei","year":"2024","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zheng, L.L., Chen, S.F., Yang, F., Wang, W.H., Xu, C., and Zheng, L.Y. (2023). High-risk HPV prevalence and genotype distribution among women in Liaocheng, Shandong Province, China from 2016 to 2022. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1145396"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2537","DOI":"10.1002\/rmv.2537","article-title":"Human papillomavirus infection: Epidemiology, biology, host interactions, cancer development, prevention, and therapeutics","volume":"34","author":"Wolf","year":"2024","journal-title":"Rev. Med. Virol."},{"key":"ref_8","unstructured":"World Health Organization (2020). Human Papillomavirus (HPV) and Cervical Cancer, World Health Organization."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110991","DOI":"10.1016\/j.isci.2024.110991","article-title":"Global pattern of persistent human papillomavirus infection in female genital tract: An update system review and meta-analysis","volume":"27","author":"Zhao","year":"2024","journal-title":"iScience"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bowden, S.J., Doulgeraki, T., Bouras, E., Markozannes, G., Athanasiou, A., Grout-Smith, H., Kechagias, K.S., Ellis, L.B., Zuber, V., and Chadeau-Hyam, M. (2023). Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: An umbrella review and follow-up Mendelian randomisation studies. BMC Med., 21.","DOI":"10.1186\/s12916-023-02965-w"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.62347\/GGVR2248","article-title":"Risk factors for persistent infection of high-risk HPV in patients with cervical intraepithelial neoplasia","volume":"17","author":"Wang","year":"2025","journal-title":"Am. J. Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1136\/ijgc-2022-003703","article-title":"Updates on cervical cancer prevention","volume":"33","author":"Fernandes","year":"2023","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41388-025-03310-6","article-title":"Ubiquitin and ubiquitin-like proteins in HPV-driven carcinogenesis","volume":"44","author":"Wootton","year":"2025","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, S., Hong, X., Wei, Z., Xie, M., Li, W., Liu, G., Guo, H., Yang, J., Wei, W., and Zhang, S. (2019). Ubiquitination of the HPV Oncoprotein E6 Is Critical for E6\/E6AP-Mediated p53 Degradation. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02483"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41417-023-00682-3","article-title":"HPV E6\/E7: Insights into their regulatory role and mechanism in signaling pathways in HPV-associated tumor","volume":"31","author":"Peng","year":"2024","journal-title":"Cancer Gene Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e29685","DOI":"10.1002\/jmv.29685","article-title":"High-risk HPV oncoproteins E6 and E7 and their interplay with the innate immune response: Uncovering mechanisms of immune evasion and therapeutic prospects","volume":"96","author":"Calati","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.3390\/cimb46060370","article-title":"Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1alpha Axis","volume":"46","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"189292","DOI":"10.1016\/j.bbcan.2025.189292","article-title":"Exploring the metabolic alterations in cervical cancer induced by HPV oncoproteins: From mechanisms to therapeutic targets","volume":"1880","author":"Gore","year":"2025","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_19","unstructured":"Centers for Disease Control and Prevention (2026, April 02). Chapter 11: Human Papillomavirus, Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book), Available online: https:\/\/www.cdc.gov\/pinkbook\/hcp\/table-of-contents\/chapter-11-human-papillomavirus.html."},{"key":"ref_20","unstructured":"World Health Organization (2020). Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem, World Health Organization."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/LGT.0000000000000562","article-title":"2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors","volume":"24","author":"Perkins","year":"2020","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/17437199.2020.1762106","article-title":"Emotional response to testing positive for human papillomavirus at cervical cancer screening: A mixed method systematic review with meta-analysis","volume":"15","author":"McBride","year":"2021","journal-title":"Health Psychol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e291","DOI":"10.1016\/S2666-5247(23)00257-4","article-title":"Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: Review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement","volume":"5","author":"Mitra","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"881902","DOI":"10.3389\/fonc.2022.881902","article-title":"AHCC((R)) Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections","volume":"12","author":"Smith","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2147\/DDDT.S123340","article-title":"Human papillomavirus (HPV): Systemic treatment with Gene-Eden-VIR\/Novirin safely and effectively clears virus","volume":"11","author":"Polansky","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Porcaro, G., Pavone-Cossut, M.R., Moretti, S., Bilotta, G., Aragona, C., and Unfer, V. (2025). Oral Treatment with EGCG, Folic Acid, Vitamin B12, and Hyaluronic Acid Improves HPV Clearance and Counteracts Its Persistence: A Clinical Study. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115251"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ferrari, F.A., Magni, F., Bosco, M., Biancotto, G., Zorzato, P.C., Lagan\u00e0, A.S., Chiantera, V., Raffaelli, R., Franchi, M., and Uccella, S. (2023). The Role of Micronutrients in Human Papillomavirus Infection, Cervical Dysplasia, and Neoplasm. Healthcare, 11.","DOI":"10.3390\/healthcare11111652"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.31557\/APJCP.2022.23.4.1285","article-title":"Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial","volume":"23","author":"Ayatollahi","year":"2022","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Guitian, M., Reina, G., and Carlos, S. (2025). The Role of Nutrition in HPV Infection and Cervical Cancer Development: A Review of Protective Dietary Factors. Cancers, 17.","DOI":"10.3390\/cancers17183020"},{"key":"ref_30","first-page":"2097","article-title":"Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression-independent manner in HPV-positive human cervical cancer-derived cells","volume":"19","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ferreira, M., Gomes, D., Neto, M., Passarinha, L.A., Costa, D., and Sousa, \u00c2. (2023). Development and Characterization of Quercetin-Loaded Delivery Systems for Increasing Its Bioavailability in Cervical Cancer Cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030936"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Koppikar, S.J., Choudhari, A.S., Suryavanshi, S.A., Kumari, S., Chattopadhyay, S., and Kaul-Ghanekar, R. (2010). Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassiacauses apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-210"},{"key":"ref_33","first-page":"140","article-title":"The role and mechanism of cinnamaldehyde in cancer","volume":"32","author":"Peng","year":"2024","journal-title":"J. Food Drug Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.biopha.2017.10.147","article-title":"Glycyrrhizin induces reactive oxygen species-dependent apoptosis and cell cycle arrest at G(0)\/G(1) in HPV18(+) human cervical cancer HeLa cell line","volume":"97","author":"Farooqui","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1016\/j.sjbs.2022.01.054","article-title":"Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+ Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway","volume":"29","author":"Ahmad","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10732748211001808","DOI":"10.1177\/10732748211001808","article-title":"Therapeutic Potential of Selenium and Selenium Compounds in Cervical Cancer","volume":"28","author":"Jablonska","year":"2021","journal-title":"Cancer Control"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Golara, A., Koz\u0142owski, M., Guzik, P., Kwiatkowski, S., and Cymbaluk-P\u0142oska, A. (2023). The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310887"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.31557\/APJCP.2019.20.5.1433","article-title":"The Relationship between the Serum Level of Selenium and Cervical Intraepithelial Neoplasia: A Comparative Study in a Population of Nigerian Women","volume":"20","author":"Obhielo","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Miyoshi, N., Tanabe, H., Suzuki, T., Saeki, K., and Hara, Y. (2020). Applications of a Standardized Green Tea Catechin Preparation for Viral Warts and Human Papilloma Virus-Related and Unrelated Cancers. Molecules, 25.","DOI":"10.3390\/molecules25112588"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1080\/01635581.2022.2093922","article-title":"Green Tea Polyphenols Cause Apoptosis and Autophagy in HPV-16 Subgene-Immortalized Human Cervical Epithelial Cells via the Activation of the Nrf2 Pathway","volume":"74","author":"Tang","year":"2022","journal-title":"Nutr. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.287.16.2114","article-title":"The 2001 Bethesda System: Terminology for reporting results of cervical cytology","volume":"287","author":"Solomon","year":"2002","journal-title":"JAMA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s12935-022-02677-w","article-title":"Potential mechanisms of quercetin in cancer prevention: Focus on cellular and molecular targets","volume":"22","author":"Asgharian","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/oxfordjournals.jncimonographs.a003477","article-title":"Chapter 3: Cofactors in human papillomavirus carcinogenesis\u2014Role of parity, oral contraceptives, and tobacco smoking","volume":"2003","author":"Castellsague","year":"2003","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mark, Z.A., Yu, L., Castro, L., Gao, X., Rodriguez, N.R., Sutton, D., Scappini, E., Tucker, C.J., Wine, R., and Yan, Y. (2024). Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094902"},{"key":"ref_45","first-page":"42","article-title":"Impact of smoking exposure on human papillomavirus clearance among Chinese women: A follow-up propensity score matching study","volume":"21","author":"Ma","year":"2023","journal-title":"Tob. Induc. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:05:37Z","timestamp":1775822737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["v18040455"],"URL":"https:\/\/doi.org\/10.3390\/v18040455","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]}}}