{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:43:29Z","timestamp":1791848609946,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In recent years, many studies have highlighted the possible close correlation between human diseases and definite patterns of microbial organisms colonizing various organs. Even at sites traditionally considered sterile, such as the upper female reproductive tract (FRT), it is now well-recognized as hosting a low biomass of different bacterial phyla. Additionally, the data from recent studies highlight a possible link between lower and upper FRT dysbiosis with a potential predisposition to cervical and ovarian cancer. Acinetobacter, chlamydia, increased mycoplasma, and lactobacillary scarcity in the upper FRT have all been linked to a predisposition to ovarian cancer. Additionally, a high-diversity vaginal community state type (CST) is linked to the presence and persistence of high-risk human papillomavirus (HPV), resulting in decreased cellular p53 activity and a reduction in the immune activity of T lymphocytes, resulting in cervical and ovarian cancer predisposition. While these findings are still far from being clarified in all aspects, in patients with multiple risk factors for ovarian cancer, a Lactobacillus crispatus treatment with a product with a proven ability to restore a favorable CST should be considered as an add-on therapy.<\/jats:p>","DOI":"10.3390\/ijms232416019","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T03:55:39Z","timestamp":1671162939000},"page":"16019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ovarian Microbiota, Ovarian Cancer and the Underestimated Role of HPV"],"prefix":"10.3390","volume":"23","author":[{"given":"Massimiliano","family":"Cazzaniga","sequence":"first","affiliation":[{"name":"Scientific & Research Department, Velleja Research, 20125 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cardinali","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Infermi Hospital, AUSL Romagna, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-8675","authenticated-orcid":false,"given":"Francesco","family":"Di Pierro","sequence":"additional","affiliation":[{"name":"Scientific & Research Department, Velleja Research, 20125 Milano, Italy"},{"name":"Digestive Endoscopy Unit and Gastroenterology, Fondazione Poliambulanza, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-9115","authenticated-orcid":false,"given":"Alexander","family":"Bertuccioli","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61122 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The Human Intestinal Microbiome in Health and Disease","volume":"375","author":"Lynch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.3389\/fimmu.2019.02387","article-title":"Uterine Immunity and Microbiota: A Shifting Paradigm","volume":"10","author":"Agostinis","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41585-020-0286-z","article-title":"The microbiome and gynaecological cancer development, prevention and therapy","volume":"17","author":"Ilhan","year":"2020","journal-title":"Nat. Rev. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41467-017-00901-0","article-title":"The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases","volume":"8","author":"Chen","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.resmic.2017.04.001","article-title":"The role of lactic acid production by probiotic Lactobacillus species in vaginal health","volume":"168","author":"Tachedjian","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ajog.2018.11.1089","article-title":"Ecological dynamics of the vaginal microbiome in relation to health and disease","volume":"220","author":"Greenbaum","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/1471-0528.14631","article-title":"The role of the vaginal microbiome in gynaecological cancer","volume":"125","author":"Champer","year":"2017","journal-title":"BJOG: Int. J. Obstet. Gynaecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ijgo.13878","article-title":"Cancer of the ovary, fallopian tube, and peritoneum: 2021 update","volume":"155","author":"Berek","year":"2021","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/CEJ.0000000000000217","article-title":"Ovarian cancer: Epidemiology and risk factors","volume":"26","year":"2017","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_12","first-page":"41","article-title":"Ovarian Cancer: A Heterogeneous Disease","volume":"85","author":"Leary","year":"2017","journal-title":"Pathobiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s11912-021-01079-x","article-title":"The Microbiome and Gynecologic Cancer: Current Evidence and Future Opportunities","volume":"23","author":"Chambers","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13027-022-00465-9","article-title":"Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?","volume":"17","author":"Dellino","year":"2022","journal-title":"Infect. Agents Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3390\/microbiolres13040069","article-title":"Lactobacillus crispatus M247: Characteristics of a Precision Probiotic Instrument for Gynecological and Urinary Well-Being","volume":"13","author":"Bertuccioli","year":"2022","journal-title":"Microbiol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/S1470-2045(19)30340-7","article-title":"Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: A case-control study","volume":"20","author":"Reisel","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.semcancer.2021.07.013","article-title":"Microbes in gynecologic cancers: Causes or consequences and therapeutic potential","volume":"86","author":"Wahid","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s10020-021-00295-2","article-title":"The role of the microbiome in ovarian cancer: Mechanistic insights into oncobiosis and to bacterial metabolite signaling","volume":"27","author":"Sipos","year":"2021","journal-title":"Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1038\/s41598-018-38031-2","article-title":"The biodiversity Composition of Microbiome in Ovarian Carcinoma Patients","volume":"9","author":"Zhou","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1007\/s10096-012-1570-5","article-title":"Viral and bacterial aetiologies of epithelial ovarian cancer","volume":"31","author":"Shanmughapriya","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1006\/gyno.1996.0316","article-title":"Prevalence of Mycoplasma Conserved DNA in Malignant Ovarian Cancer Detected Using Sensitive PCR\u2013ELISA","volume":"63","author":"Chan","year":"1996","journal-title":"Gynecol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36225","DOI":"10.18632\/oncotarget.16717","article-title":"The ovarian cancer oncobiome","volume":"8","author":"Banerjee","year":"2017","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gulve, N., and Rudel, T. (2019). Chlamydia trachomatis and human herpesvirus 6 infections in ovarian cancer\u2014Casual or causal?. PLOS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008055"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19935","DOI":"10.1038\/s41598-019-56448-1","article-title":"Detection and genotyping of CMV and HPV in tumors and fallopian tubes from epithelial ovarian cancer patients","volume":"9","author":"Paradowska","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1186\/1743-422X-10-343","article-title":"Human papillomavirus genotyping and integration in ovarian cancer Saudi patients","volume":"10","author":"Hafez","year":"2013","journal-title":"Virol. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nakamura, M., Obata, T., Daikoku, T., and Fujiwara, H. (2019). The Association and Significance of p53 in Gynecologic Cancers: The Potential of Targeted Therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215482"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-0-387-68969-2_9","article-title":"Role of p53 and Rb in Ovarian Cancer","volume":"622","author":"Corney","year":"2008","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1600-065X.2008.00622.x","article-title":"Antigen-specific immunotherapy of cervical and ovarian cancer","volume":"222","author":"Hung","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18538","DOI":"10.1073\/pnas.0509182102","article-title":"Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+\/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer","volume":"102","author":"Sato","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1056\/NEJMoa020177","article-title":"Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer","volume":"348","author":"Zhang","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zeppa, S.D., Sisti, D., Amatori, S., Gervasi, M., Agostini, D., Piccoli, G., Bertuccioli, A., Rocchi, M.B., Stocchi, V., and Sestili, P. (2020). High-intensity Interval Training Promotes the Shift to a Health-Supporting Dietary Pattern in Young Adults. Nutrients, 12.","DOI":"10.3390\/nu12030843"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3233\/MNM-140008","article-title":"The Mediterranean Diet in the era of globalization: The need to support knowledge of healthy dietary factors in the new socio-economical framework","volume":"7","author":"Bertuccioli","year":"2014","journal-title":"Mediterr. J. Nutr. Metab."},{"key":"ref_33","first-page":"621","article-title":"Oral administration of Lactobacillus crispatus M247 to papillomavirus-infected women: Results of a preliminary, uncontrolled, open trial","volume":"73","author":"Criscuolo","year":"2021","journal-title":"Minerva Obstet. Gynecol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Di Pierro, F., Polzonetti, V., Patrone, V., and Morelli, L. (2019). Microbiological Assessment of the Quality of Some Commercial Products Marketed as Lactobacillus crispatus-Containing Probiotic Dietary Supplements. Microorganisms, 7.","DOI":"10.3390\/microorganisms7110524"},{"key":"ref_35","first-page":"4935","article-title":"A naturally-inspired, curcumin-based lecithin formulation (Meriva\u00ae formulated as the finished product Algocur\u00ae) alleviates the osteo-muscular pain conditions in rugby players","volume":"21","author":"Zacconi","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_36","first-page":"286","article-title":"A novel lecithin-based delivery form of Boswellic acids as complementary treatment of radiochemotherapy-induced cerebral edema in patients with glioblastoma multiforme: A longitudinal pilot experience","volume":"63","author":"Simonetti","year":"2019","journal-title":"J. Neurosurg. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3389\/fonc.2019.00173","article-title":"From Bench to Bedside: Evaluation of AHCC Supplementation to Modulate the Host Immunity to Clear High-Risk Human Papillomavirus Infections","volume":"9","author":"Smith","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"881902","DOI":"10.3389\/fonc.2022.881902","article-title":"AHCC\u00ae Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections","volume":"12","author":"Smith","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/01635581.2018.1380203","article-title":"Active Hexose Correlated Compound (AHCC) Inhibits the Proliferation of Ovarian Cancer Cells by Suppressing Signal Transducer and Activator of Transcription 3 (STAT3) Activation","volume":"70","author":"Choi","year":"2017","journal-title":"Nutr. Cancer"},{"key":"ref_40","first-page":"172","article-title":"Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus","volume":"66","author":"Bertuccioli","year":"2020","journal-title":"Minerva Gastroenterol. Dietol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16019\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:32Z","timestamp":1760146952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":40,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232416019"],"URL":"https:\/\/doi.org\/10.3390\/ijms232416019","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]}}}