{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T23:19:31Z","timestamp":1791674371485,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Korean Society for Cytopathology","award":["2019-01."],"award-info":[{"award-number":["2019-01."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Infections with multiple human papilloma virus (HPV) types have been reported, but their role in cervical carcinogenesis has not been fully elucidated. In this study, 236 cases with multiple HPV infection were examined and compared to 180 cases with single HPV infection. HPV genotyping was performed with cervico-vaginal swab specimens using multiplex (real-time) polymerase chain reaction (PCR). In multiple HPV infection, the most prevalent HPV genotype was HPV 53, followed by HPV 16, 58, 52, and 68. HPV 33, 35, 39, 51, 52, 53, 58, and 68 were high-risk-HPV (HR-HPV) genotypes that were more frequently detected in multiple HPV infection compared to that in single HPV infection. The association between multiple HPV infection and high-grade SIL (HSIL) was significantly stronger compared to that of single HPV infection and HSIL (p = 0.002). Patients with multiple HPV infection displayed persistent and longer duration of the HPV infection compared to patients with single HPV infection. Multiple HPV infections have distinct clinicopathologic characteristics. Since it is associated with persistent HPV infection, HSIL, and different HR-HPV strains in contrast to single HPV infection, the presence of multiple HPV infection should be reported; close follow up is warranted.<\/jats:p>","DOI":"10.3390\/v13071342","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T21:56:52Z","timestamp":1626127012000},"page":"1342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Multiple Human Papilloma Virus (HPV) Infections Are Associated with HSIL and Persistent HPV Infection Status in Korean Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Moonsik","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1857-813X","authenticated-orcid":false,"given":"Nora Jee-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6167-4998","authenticated-orcid":false,"given":"Ji Yun","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-1064","authenticated-orcid":false,"given":"Ji Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1136\/jcp.55.4.244","article-title":"The causal relation between human papillomavirus and cervical cancer","volume":"55","author":"Bosch","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"D499","DOI":"10.1093\/nar\/gkw879","article-title":"The Papillomavirus Episteme: A major update to the papillomavirus sequence database","volume":"45","author":"Li","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.virol.2010.02.002","article-title":"Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments","volume":"401","author":"Bernard","year":"2010","journal-title":"Virology"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/1471-0528.13071","article-title":"HPV-negative carcinoma of the uterine cervix: A distinct type of cervical cancer with poor prognosis","volume":"122","author":"Soveral","year":"2015","journal-title":"BJOG"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1016\/j.celrep.2019.02.004","article-title":"A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms of Cervical Carcinogenesis","volume":"26","author":"He","year":"2019","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pvr.2018.10.001","article-title":"Single type infection of human papillomavirus as a cause for high-grade cervical intraepithelial neoplasia and invasive cancer in Japan","volume":"6","author":"Sakamoto","year":"2018","journal-title":"Papillomavirus Res."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/sj.bjc.6601024","article-title":"Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: A meta-analysis","volume":"89","author":"Clifford","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Oyervides-Munoz, M.A., Perez-Maya, A.A., Sanchez-Dominguez, C.N., Berlanga-Garza, A., Antonio-Macedo, M., Valdez-Chapa, L.D., Cerda-Flores, R.M., Trevino, V., Barrera-Saldana, H.A., and Garza-Rodriguez, M.L. (2020). Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women. Viruses, 12.","DOI":"10.3390\/v12040380"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bruno, M.T., Scalia, G., Cassaro, N., and Boemi, S. (2020). Multiple HPV 16 infection with two strains: A possible marker of neoplastic progression. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06946-7"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/jmv.25331","article-title":"Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing, China","volume":"91","author":"Li","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3346\/jkms.2012.27.9.1091","article-title":"Prevalence and distribution of human papillomavirus infection in Korean women as determined by restriction fragment mass polymorphism assay","volume":"27","author":"Lee","year":"2012","journal-title":"J. Korean Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/488S2a","article-title":"HPV: The global burden","volume":"488","author":"Crow","year":"2012","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/j.1469-0691.2010.03387.x","article-title":"Single and multiple human papillomavirus infections in cervical abnormalities in Portuguese women","volume":"17","author":"Pista","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1093\/infdis\/jiq139","article-title":"Human papillomavirus infection with multiple types: Pattern of coinfection and risk of cervical disease","volume":"203","author":"Chaturvedi","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1097\/IGC.0b013e31829e9fb4","article-title":"Multiple-type human papillomavirus (HPV) infections: A cross-sectional analysis of the prevalence of specific types in 309,000 women referred for HPV testing at the time of cervical cytology","volume":"23","author":"Dickson","year":"2013","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1158\/1055-9965.EPI-09-0983","article-title":"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_20","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1093\/infdis\/jiq131","article-title":"Persistence of concurrent infections with multiple human papillomavirus types: A population-based cohort study","volume":"203","author":"Campos","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.virusres.2006.12.017","article-title":"Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women","volume":"125","author":"Gargiulo","year":"2007","journal-title":"Virus Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1158\/1055-9965.EPI-06-0129","article-title":"Human papillomavirus infections with multiple types and risk of cervical neoplasia","volume":"15","author":"Trottier","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/cncy.21789","article-title":"Infections with multiple high-risk HPV types are associated with high-grade and persistent low-grade intraepithelial lesions of the cervix","volume":"125","author":"Pellegrini","year":"2017","journal-title":"Cancer Cytopathol."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","unstructured":"Senapati, R., Nayak, B., Kar, S.K., and Dwibedi, B. (2017). HPV genotypes co-infections associated with cervical carcinoma: Special focus on phylogenetically related and non-vaccine targeted genotypes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187844"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0140-6736(09)61248-4","article-title":"Efficacy of human papillomavirus (HPV)-16\/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): Final analysis of a double-blind, randomised study in young women","volume":"374","author":"Paavonen","year":"2009","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/oxfordjournals.jncimonographs.a003476","article-title":"Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia","volume":"2003","author":"Schiffman","year":"2003","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/LGT.0b013e318287d329","article-title":"2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors","volume":"17","author":"Massad","year":"2013","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc2050","article-title":"The natural history of cervical HPV infection: Unresolved issues","volume":"7","author":"Woodman","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1016\/j.vaccine.2006.05.031","article-title":"Chapter 6: Epidemiology and transmission dynamics of genital HPV infection","volume":"24","author":"Burchell","year":"2006","journal-title":"Vaccine"},{"key":"ref_31","first-page":"615","article-title":"Risk Factors for High-Risk Type Human Papillomavirus Infection among Mexican-American Women","volume":"8","author":"Giuliano","year":"1999","journal-title":"Cancer Epidemiol. Prev. Biomark."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Soto-De Leon, S., Camargo, M., Sanchez, R., Munoz, M., Perez-Prados, A., Purroy, A., Patarroyo, M.E., and Patarroyo, M.A. (2011). Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014705"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/ijc.22527","article-title":"Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update","volume":"121","author":"Smith","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_34","first-page":"1267","article-title":"Prevalence and Genotype Analysis of High Risk-human Papillomavirus Infection in Busan Women","volume":"29","author":"Kang","year":"2019","journal-title":"J. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104","DOI":"10.15430\/JCP.2016.21.2.104","article-title":"Human Papillomavirus Prevalence and Type Distribution Among 968 Women in South Korea","volume":"21","author":"So","year":"2016","journal-title":"J. Cancer Prev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1128\/JCM.00087-13","article-title":"Multiple human papillomavirus infections with high viral loads are associated with cervical lesions but do not differentiate grades of cervical abnormalities","volume":"51","author":"Schmitt","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/ijc.10708","article-title":"Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer","volume":"102","author":"Bachtiary","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gallegos-Bolanos, J., Rivera-Dominguez, J.A., Presno-Bernal, J.M., and Cervantes-Villagrana, R.D. (2017). High prevalence of co-infection between human papillomavirus (HPV) 51 and 52 in Mexican population. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3519-7"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/jmv.1085","article-title":"Detection of multiple human papillomavirus types in the lower genital tract correlates with cervical dysplasia","volume":"64","author":"Fife","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1086\/324579","article-title":"Cervical coinfection with human papillomavirus (HPV) types as a predictor of acquisition and persistence of HPV infection","volume":"184","author":"Rousseau","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1016\/j.vaccine.2005.09.002","article-title":"Immune responses to human papillomavirus","volume":"24","author":"Stanley","year":"2006","journal-title":"Vaccine"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Baasland, I., Romundstad, P.R., Eide, M.L., and Jonassen, C.M. (2019). Clinical performance of Anyplex II HPV28 by human papillomavirus type and viral load in a referral population. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210997"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/7\/1342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:29:10Z","timestamp":1760164150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/7\/1342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,12]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["v13071342"],"URL":"https:\/\/doi.org\/10.3390\/v13071342","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,12]]}}}