{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:11:12Z","timestamp":1789265472217,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of General Surgery and Medical\u2013Surgical Specialty at the University of Catania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The possible association between human papillomavirus (HPV) infection and negative pregnancy outcomes has been debated in the literature, with conflicting results from clinical trials. While some authors support a link between HPV and miscarriage, others argue that the mere detection of the virus does not necessarily indicate a causal relationship with negative pregnancy outcomes. In this study, we conducted a prospective, controlled investigation of the potential association between HPV infection and miscarriage. Our study included 59 women who had experienced a miscarriage and 57 women who had undergone voluntary termination of pregnancy (TOP) within the 12th week of gestation. We assessed HPV prevalence, maternal age, and HPV genotype in both groups and evaluated the relationship between these factors and pregnancy outcome. Unlike previous studies that only identified HPV in cases of abortion, we also correlated the positivity of chorionic villi with gestational age in both groups. We found a close correlation between positive chorionic villi and very early gestational age, with all 13 cases of virus-positive chorionic villi in the miscarriage group occurring in gestational periods of less than 8 + 5 weeks (&lt;60 days) (RR = 28.6). Our analysis showed no correlation between HPV infection and maternal age or viral genotypes. The results suggest that the presence of HPV alone is not enough to cause spontaneous abortion, but a high viral load in early pregnancy may increase the risk of negative outcomes. These findings have important implications for the management of HPV infection during pregnancy and may provide a rationale for the use of HPV vaccines to reduce the incidence of spontaneous abortion and infertility due to preclinical spontaneous abortions.<\/jats:p>","DOI":"10.3390\/diagnostics13091659","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T01:06:28Z","timestamp":1683594388000},"page":"1659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Papillomavirus Infection as Potential Cause of Miscarriage in the Early Gestational Age: A Prospective Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1557-1538","authenticated-orcid":false,"given":"Maria Teresa","family":"Bruno","sequence":"first","affiliation":[{"name":"Department of General Surgery and Medical Surgery Specialties, Gynecological Clinic, University of Catania, 95123 Catania, Italy"},{"name":"Multidisciplinary Research Center in Papillomavirus Pathology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-0932","authenticated-orcid":false,"given":"Salvatore","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgery Specialties, Gynecological Clinic, University of Catania, 95123 Catania, Italy"},{"name":"Multidisciplinary Research Center in Papillomavirus Pathology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Scalia","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Clinical Virology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Clinical Virology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Di Pasqua","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgery Specialties, Gynecological Clinic, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Boemi","sequence":"additional","affiliation":[{"name":"Multidisciplinary Research Center in Papillomavirus Pathology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Marzio","family":"Panella","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgery Specialties, Gynecological Clinic, University of Catania, 95123 Catania, Italy"},{"name":"Multidisciplinary Research Center in Papillomavirus Pathology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgery Specialties, Gynecological Clinic, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2014, October 12). World Cancer Report 2014. Available online: https:\/\/publications.iarc.fr."},{"key":"ref_2","first-page":"376","article-title":"Prevalence genotypes and distribution of human papillomavirus infection in women with abnormal cervical cytology in Catania, Italy","volume":"38","author":"Bruno","year":"2016","journal-title":"G. Ital. Di Ostet. E Ginecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa021641","article-title":"Epidemiologic classification of human papillomavirus types associated with cervical cancer","volume":"348","author":"Bosch","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F","article-title":"Human papillomavirus is a necessary cause of invasive cervical cancer worldwide","volume":"189","author":"Walboomers","year":"1999","journal-title":"J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1017\/S0950268814000636","article-title":"The prevalence and risk of human papillomavirus infection in pregnant women","volume":"142","author":"Liu","year":"2014","journal-title":"Epidemiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1002\/ijc.23762","article-title":"Prevalence, incidence and clearance of human papillomavirus infection among young primiparous pregnant women in Kampala, Uganda","volume":"123","author":"Banura","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Castellsagu\u00e9, X., Drudis, T., Ca\u00f1adas, M.P., Gonc\u00e9, A., Ros, R., P\u00e9rez, J.M., Quintana, M.J., Mu\u00f1oz, J., Albero, G., and de Sanjos\u00e9, S. (2009). Human papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: A prospective study in Spain. BMC Infect. Dis., 9.","DOI":"10.1186\/1471-2334-9-74"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejogrb.2009.03.024","article-title":"Adeno-associated virus and human papillomavirus types in cervical samples of pregnant and non-pregnant women","volume":"145","author":"Freitas","year":"2009","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1006\/viro.2001.1135","article-title":"Display of complete life cycle of human papillomavirustype 16 in cultured placental trophoblasts","volume":"290","author":"Liu","year":"2001","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/humrep\/dem404","article-title":"Placental infection with human papillomavirus is associated with spontaneous preterm delivery","volume":"23","author":"Gomez","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1080\/01443615.2018.1454408","article-title":"Human papillomavirus in foetal and maternal tissues from miscarriage cases","volume":"38","author":"Pereira","year":"2018","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3086036","DOI":"10.1155\/2016\/3086036","article-title":"Human papillomavirus infection as a possible cause of spontaneous abortion and spontaneous preterm delivery","volume":"2016","author":"Ambuhl","year":"2016","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1023\/A:1007975005433","article-title":"Human papillomavirus is more prevalent in first trimester spontaneously aborted products of conception compared to elective specimens","volume":"14","author":"Hermonat","year":"1997","journal-title":"Virus Genes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.placenta.2007.08.005","article-title":"Multiple human papillomavirus types replicate in 3A trophoblasts","volume":"29","author":"You","year":"2008","journal-title":"Placenta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.virol.2003.08.020","article-title":"Infection, replication, and cytopathology of human papillomavirus type 31 in trophoblasts","volume":"316","author":"You","year":"2003","journal-title":"Virology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00404-013-2711-5","article-title":"HPV-16 exposed mouse embryos: A potential model for pregnancy wastage","volume":"287","author":"Hong","year":"2013","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/carcin\/bgp281","article-title":"Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells","volume":"31","author":"Boulenouar","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s10815-006-9030-8","article-title":"Human papilloma virus DNA exposure and embryo survival is stage-specific","volume":"23","author":"Henneberg","year":"2006","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1023\/A:1014736805127","article-title":"Human papillomavirus and blastocyst apoptosis","volume":"19","author":"Calinisan","year":"2002","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_20","first-page":"337","article-title":"Human papillomavirus in the cervix and placenta","volume":"96","author":"Eppel","year":"2000","journal-title":"Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bruno, M.T., Caruso, S., Bica, F., Arcidiacono, G., and Boemi, S. (2021). Evidence for HPV DNA in the placenta of women who resorted to elective abortion. BMC Pregnancy Childbirth, 21.","DOI":"10.1186\/s12884-021-03937-9"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"662753","DOI":"10.1155\/2021\/6627531","article-title":"Progression of CIN1\/LSIL HPV Persistent of the Cervix: Actual Progression or CIN3 Coexistence","volume":"2021","author":"Bruno","year":"2021","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1093\/infdis\/jiaa054","article-title":"Association between maternal human papillomavirus infection and adverse pregnancy outcomes: Systematic review and meta-analysis","volume":"221","author":"Niyibizi","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.ejogrb.2013.07.002","article-title":"Human papillomavirus infection and spontaneous abortion: A case\u2013control study performed in Mexico","volume":"170","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_25","first-page":"343","article-title":"Recurrent miscarriage and cervical human papillomavirus infection","volume":"70","author":"Ticconi","year":"2013","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"683","DOI":"10.3760\/cma.j.issn.0366-6999.20121625","article-title":"Does human papillomavirus infection do harm to in-vitro fertilization outcomes and subsequent pregnancy outcomes?","volume":"126","author":"Yang","year":"2013","journal-title":"Chin. Med. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/j.1600-0412.2011.01189.x","article-title":"Prevalence of human papillomavirus in spontaneously aborted products of conception","volume":"90","year":"2011","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.ajog.2006.05.049","article-title":"Placental inflammation and viral infection are implicated in second trimester pregnancy loss","volume":"195","author":"Srinivas","year":"2006","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_29","first-page":"907","article-title":"Mass screening for human papillomavirus type 16 infection in infertile couples","volume":"45","author":"Tanaka","year":"2000","journal-title":"J. Reprod. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tognon, M., Tagliapietra, A., Magagnoli, F., Mazziotta, C., Oton-Gonzalez, L., Lanzillotti, C., Vesce, F., Contini, C., Rotondo, J.C., and Martini, F. (2020). Investigation on Spontaneous Abortion and Human Papillomavirus Infection. Vaccine, 8.","DOI":"10.3390\/vaccines8030473"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/infdis\/jiq056","article-title":"Evidence of human papillomavirus in the placenta","volume":"203","author":"Weyn","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1080\/14767058.2017.1297403","article-title":"High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: A case-control study in a tertiary center, Egypt","volume":"31","author":"Mosbah","year":"2018","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Foresta, C., Patassini, C., Bertoldo, A., Menegazzo, M., Francavilla, F., Barzon, L., and Ferlin, A. (2011). Mechanism of human papillomavirus binding to human spermatozoa and fertilizing ability of infected spermatozoa. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015036"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.fertnstert.2015.09.018","article-title":"Spontaneous fertility and in vitro fertilization outcome: New evidence of human papillomavirus sperm infection","volume":"105","author":"Garolla","year":"2016","journal-title":"Fertil Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/BF02765781","article-title":"Transfection of the inner cellmass and lack of a unique DNA sequence affecting the uptake ofexogenous DNA by sperm as shown by dideoxy sequencing analogues","volume":"14","author":"Cabrera","year":"1997","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.fertnstert.2003.08.020","article-title":"Possible role of bacterial and viral infections in miscarriages","volume":"81","author":"Matovina","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/0092623X.2019.1586019","article-title":"Sexual Behavior of Women with Diagnosed HPV","volume":"45","author":"Caruso","year":"2019","journal-title":"J. Sex Marital. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12985-022-01822-1","article-title":"Possible role of negative human papillomavirus E6\/E7 mRNA as a predictor of regression of cervical intraepithelial neoplasia 2 lesions in hr-HPV positive women","volume":"19","author":"Bruno","year":"2022","journal-title":"Virol. J."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/9\/1659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:31:32Z","timestamp":1760124692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/9\/1659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["diagnostics13091659"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13091659","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]}}}