{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:14:31Z","timestamp":1790468071765,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K17274"],"award-info":[{"award-number":["JP21K17274"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.<\/jats:p>","DOI":"10.3390\/ijms25021212","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T03:33:41Z","timestamp":1705635221000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictive Value of Various Atypical Cells for the Detection of Human Papillomavirus in Cervical Smears"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-9670","authenticated-orcid":false,"given":"Kaori","family":"Okayama","sequence":"first","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, 1-7-1 Tonyamachi, Takasaki-shi 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Kakinuma","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, 1-7-1 Tonyamachi, Takasaki-shi 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2787-4184","authenticated-orcid":false,"given":"Koji","family":"Teruya","sequence":"additional","affiliation":[{"name":"Department of Health and Welfare, Faculty of Health Sciences, Kyorin University, 5-4-1 Shimorenjaku, Mitaka-shi 181-8621, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizue","family":"Oda","sequence":"additional","affiliation":[{"name":"Genki Plaza Medical Center for Health Care, 3-6-5 Iidabashi, Chiyoda-ku 102-0072, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Fujii","sequence":"additional","affiliation":[{"name":"Genki Plaza Medical Center for Health Care, 3-6-5 Iidabashi, Chiyoda-ku 102-0072, Tokyo, Japan"},{"name":"Department of Medical Technology, Faculty of Health Sciences, Kyorin University, 5-4-1 Shimorenjaku, Mitaka-shi 181-8621, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, 1-7-1 Tonyamachi, Takasaki-shi 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-844X","authenticated-orcid":false,"given":"Toshiyuki","family":"Sasagawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa Medical University, 1-1 Uchinadadaigaku, Kahoku-gun 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6152-3217","authenticated-orcid":false,"given":"Mitsuaki","family":"Okodo","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Sciences, Kyorin University, 5-4-1 Shimorenjaku, Mitaka-shi 181-8621, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.virol.2013.04.023","article-title":"Cross-roads in the classification of papillomaviruses","volume":"445","year":"2013","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.vaccine.2006.05.115","article-title":"HPV in the etiology of human cancer","volume":"24","author":"Gissmann","year":"2006","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2018.09.062","article-title":"Human oncoviruses: Mucocutaneous manifestations, pathogenesis, therapeutics, and prevention: Papillomaviruses and Merkel cell polyomavirus","volume":"81","author":"Haley","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"F55","DOI":"10.1016\/j.vaccine.2012.06.083","article-title":"The biology and life-cycle of human papillomaviruses","volume":"30","author":"Doorbar","year":"2012","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/path.4424","article-title":"Are 20 human papillomavirus types causing cervical cancer?","volume":"234","author":"Arbyn","year":"2014","journal-title":"J. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/S0140-6736(07)61416-0","article-title":"Human papillomavirus and cervical cancer","volume":"370","author":"Schiffman","year":"2007","journal-title":"Lancet"},{"key":"ref_7","first-page":"CD008587","article-title":"Cytology versus HPV testing for cervical cancer screening in the general population","volume":"8","author":"Koliopoulos","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.vaccine.2006.05.117","article-title":"Clinical applications of HPV testing: A summary of meta-analyses","volume":"24","author":"Arbyn","year":"2006","journal-title":"Vaccine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"K29","DOI":"10.1016\/j.vaccine.2008.06.019","article-title":"Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries","volume":"26","author":"Cuzick","year":"2008","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/annonc\/mdt538","article-title":"Cervical cancer screening: On the way to a shift from cytology to full molecular screening","volume":"25","author":"Dijkstra","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_11","unstructured":"World Health Organization (2023, October 16). New Recommendations for Screening and Treatment to Prevent Cervical Cancer. Available online: https:\/\/www.who.int\/news\/item\/06-07-2021-new-recommendations-for-screening-and-treatment-to-prevent-cervical-cancer."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1001\/jama.288.14.1749","article-title":"Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: Comparison of sensitivity, specificity, and frequency of referral","volume":"288","author":"Kulasingam","year":"2002","journal-title":"Jama"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1365-2303.2004.00179.x","article-title":"Can we detect cervical human papillomavirus (HPV) infection by cytomorphology alone? Diagnostic value of non-classic cytological signs of HPV effect in minimally abnormal Pap tests","volume":"16","author":"Bollmann","year":"2005","journal-title":"Cytopathology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1002\/jmv.25775","article-title":"Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential","volume":"92","author":"Okodo","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/jmv.25017","article-title":"Uniplex E6\/E7 PCR method detecting E6 or E7 genes in 39 human papillomavirus types","volume":"90","author":"Okodo","year":"2018","journal-title":"J. Med. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Okayama, K., Sasagawa, T., Teruya, K., Oda, M., Fujii, M., Kimura, H., and Okodo, M. (2021). Profiles of Human Papillomavirus Detection of the Multinucleated Cells in Cervical Smears. Microorganisms, 9.","DOI":"10.3390\/microorganisms9081575"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1001\/jama.1985.03350310071027","article-title":"Cytologic manifestations of cervical and vaginal infections: I. Epithelial and inflammatory cellular changes","volume":"253","author":"Kiviat","year":"1985","journal-title":"Jama"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nayar, R., and Wilbur, D.C. (2015). The Bethesda System for Reporting Cervical Cytology: Definitions, Criteria, and Explanatory Notes, Springer.","DOI":"10.1007\/978-3-319-11074-5"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.25259\/CMAS_03_08_2021","article-title":"The Pap smear in inflammation and repair","volume":"19","author":"Kamal","year":"2022","journal-title":"CytoJournal"},{"key":"ref_20","first-page":"82","article-title":"Frequency of epithelial giant cells in smears with Papillomavirus","volume":"86","author":"Shirata","year":"1994","journal-title":"Pathologica"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/GME.0000000000002125","article-title":"Cytological characteristics of premalignant cervical epithelial lesions in postmenopausal women based on endocrine indices and parakeratosis","volume":"30","author":"Sugisawa","year":"2023","journal-title":"Menopause"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/dc.23674","article-title":"The significance of parakeratosis alone in cervicovaginal cytology of Turkish women","volume":"45","author":"Kir","year":"2017","journal-title":"Diagn. Cytopathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1067\/mob.2002.126640","article-title":"The significance of hyperkeratosis\/parakeratosis on otherwise normal Papanicolaou smears","volume":"187","author":"Zahn","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_24","unstructured":"Lee, C., and Laimins, L.A. (2007). The Papillomaviruses, Springer."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2144\/00291bm09","article-title":"Preparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris (HotSHOT)","volume":"29","author":"Truett","year":"2000","journal-title":"Biotechniques"},{"key":"ref_26","unstructured":"International Agency for Research on Cancer (2012). A Review of Human Carcinogens: Personal Habits and Indoor Combustions, World Health Organization."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Okayama, K., Kakinuma, M., Tajima, S., Nagasawa, N., Ishii, Y., Oda, M., Kimura, H., and Okodo, M. (2023). Optimal Papanicolaou Smear Conditions for Manual Microdissection of Single Target Cells. Microorganisms, 11.","DOI":"10.3390\/microorganisms11112700"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:45:44Z","timestamp":1760103944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,19]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25021212"],"URL":"https:\/\/doi.org\/10.3390\/ijms25021212","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,19]]}}}