{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:18:08Z","timestamp":1787735888659,"version":"build-2784847793"},"reference-count":21,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Objectives: The endometrium and cervix share a common M\u00fcllerian origin and may exhibit overlapping biological responses to oncogenic stimuli. However, the clinical significance of preoperative cervical cytology in patients with endometrial cancer remains unclear. This study aimed to investigate the association between preoperative cervical smear cytology and clinicopathologic characteristics, with particular emphasis on advanced FIGO stage (III\u2013IV) as the primary outcome. Methods: This retrospective cohort study included 154 patients who underwent primary surgery for histologically confirmed endometrial cancer. Preoperative cervical smear cytology was classified according to the Bethesda System into four categories: normal, low-grade, high-grade, and malignant. For subgroup analyses, low-grade, high-grade, and malignant cytology results were combined and compared with normal cytology. FIGO stage was analyzed both as individual stages (IA\u2013IV) and as early-stage (I\u2013II) versus advanced-stage (III\u2013IV) disease, where appropriate. Continuous variables were summarized as mean \u00b1 standard deviation or median (interquartile range), while categorical variables were expressed as n (%). Group comparisons were performed using the Pearson chi-square test or Fisher\u2019s exact test, as appropriate, and a two-sided p value &lt; 0.05 was considered statistically significant. Results: A total of 154 patients with endometrial cancer were included in the analysis. Preoperative cervical smear cytology was normal in 140 patients (90.9%), low-grade in 6 (3.9%), high-grade in 3 (1.9%), and malignant in 5 (3.2%). Comparison across cytology categories demonstrated a significant association between smear cytology and FIGO stage (p &lt; 0.001), with high-grade and malignant cytology occurring more frequently in patients with advanced-stage disease. Vaginal cuff involvement was also significantly associated with smear cytology (p = 0.001), whereas no significant associations were observed for myometrial invasion, lymphovascular space invasion, cervical stromal involvement, tubo-ovarian involvement, omental involvement, or lymph node metastasis. Subgroup analysis comparing normal and abnormal cytology yielded similar findings, confirming significant associations with FIGO stage (p &lt; 0.001) and vaginal cuff involvement (p = 0.002). In a multivariable model additionally including cervical cytology, LVSI and deep myometrial invasion were independent predictors of advanced stage (AUC = 0.888), whereas cytology was not statistically significant after adjustment (OR 4.51, p = 0.076) and showed poor standalone diagnostic performance (AUC = 0.564, sensitivity 19.4%, specificity 93.5%). All patients with vaginal cuff involvement had advanced-stage disease (Fisher\u2019s exact p &lt; 0.001). The cytology\u2013FIGO stage association was not significant in postmenopausal (p = 0.065) or endometrioid-only (p = 1.00) subgroup analyses. Conclusions: Abnormal preoperative cervical smear cytology was significantly associated with advanced FIGO stage and vaginal cuff involvement in patients with endometrial cancer. These findings suggest that cervical cytological abnormalities may reflect overall disease extent rather than individual histopathological risk factors. Given the retrospective design and the limited number of patients with abnormal cytology, these findings should be interpreted cautiously and validated in larger prospective studies. However, cytology was not an independent predictor of advanced stage after multivariable adjustment and performed poorly as a standalone diagnostic marker, suggesting it should not be used alone to assess disease extent.<\/jats:p>","DOI":"10.3390\/jcm15176575","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:11:15Z","timestamp":1787731875000},"page":"6575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative Cervical Smear Cytology and Clinicopathologic Characteristics in Endometrial Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Kubra Cakar","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Diyarbakir Gazi Yasargil Training and Research Hospital, Diyarbakir 21070, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5300-6536","authenticated-orcid":false,"given":"Kevser","family":"Arkan","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Diyarbakir Gazi Yasargil Training and Research Hospital, Diyarbakir 21070, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli Tugce","family":"Sarisoy","sequence":"additional","affiliation":[{"name":"Merz Aesthetics GmbH, 60318 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1055-6585","authenticated-orcid":false,"given":"Sunullah","family":"Soysal","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Marmara University Hospital, Istanbul 34899, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","first-page":"51","article-title":"Synchronous Primary Malignancy of Female Genital Tract: A Report of Two Cases and Review of Literature","volume":"10","author":"Khoiwal","year":"2019","journal-title":"J. Midlife Health"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bichri, K., El Ghanmi, A., Kouhen, F., Hamdi, S., Fichtali, K., El Mansouri, F., El Bakkouri, J., and Ghazi, B. (2025). The Sibylline Relationship Between Human Papillomavirus and Endometrial Cancer: Scarcity of Strong Evidence Linking Both Conditions. Viruses, 17.","DOI":"10.3390\/v17050607"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00642","DOI":"10.1016\/j.crwh.2024.e00642","article-title":"Synchronous primary endometrial adenocarcinoma and primary squamous cell carcinoma of the cervix: A case report and literature review","volume":"43","author":"Bahall","year":"2024","journal-title":"Case Rep. Women\u2019s Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ygyno.2014.02.040","article-title":"Prevalence of Human Papillomavirus in endometrial cancer: A systematic review and meta-analysis","volume":"134","author":"Olesen","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/CEJ.0000000000000969","article-title":"The relationship between atypical glandular cells and malignancy risk: A retrospective single-center study","volume":"35","author":"Tao","year":"2026","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5083","DOI":"10.21873\/anticanres.16708","article-title":"HPV16 E6 Gene Transcripts in Primary Type II Endometrial Carcinomas","volume":"43","author":"Szewczuk","year":"2023","journal-title":"Anticancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/19396368.2023.2247517","article-title":"Prevalence of human papilloma virus and Chlamydia trachomatis in endometrial and cervical carcinoma: A comparative study in North Indian women","volume":"69","author":"Gautam","year":"2023","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/00006254-197203000-00001","article-title":"The secondary M\u00fcllerian system","volume":"27","author":"Lauchlan","year":"1972","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13027-025-00635-5","article-title":"The role of lipids and lipids lowering drugs in human papillomavirus (HPV) and HPV-associated cancers","volume":"20","author":"Shabani","year":"2025","journal-title":"Infect. Agent Cancer"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s12672-025-02169-z","article-title":"Immune microenvironment and molecular mechanisms in endometrial cancer: Implications for resistance and innovative treatments","volume":"16","author":"Chen","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xi, Q., Kage, H., Ogawa, M., Matsunaga, A., Nishijima, A., Sone, K., Kawana, K., and Oda, K. (2023). Genomic Landscape of Endometrial, Ovarian, and Cervical Cancers in Japan from the Database in the Center for Cancer Genomics and Advanced Therapeutics. Cancers, 16.","DOI":"10.1101\/2023.10.09.23296710"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, Y., Liu, N., Guo, X., Han, R., Bai, J., Zhong, J., and Wang, Q. (2025). The immune microenvironment in endometrial carcinoma: Mechanisms and therapeutic targeting. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1586315"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wu, P.J., Tsai, S.C., Huang, J.Y., Lee, M.S., Wang, P.H., and Lin, F.C. (2023). From Infection to Malignancy: Tracing the Impact of Human Papillomavirus on Uterine Endometrial Cancer in a Nationwide Population-Based Cohort Study. Viruses, 15.","DOI":"10.3390\/v15122314"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/mco.2017.1202","article-title":"Synchronous primary malignant neoplasms of the cervix and endometrium","volume":"6","author":"Lv","year":"2017","journal-title":"Mol. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/PGP.0b013e31826a62bb","article-title":"Cervical cytology in serous and endometrioid endometrial cancer","volume":"32","author":"Roelofsen","year":"2013","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1136\/ijgc-00009577-200505000-00017","article-title":"Abnormal cervical cytology: A risk factor for endometrial cancer recurrence","volume":"15","author":"Brown","year":"2005","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_19","first-page":"458","article-title":"Endometrial carcinoma: The relevance of cervical cytology","volume":"77","author":"DuBeshter","year":"1991","journal-title":"Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.3802\/jgo.2023.34.e85","article-title":"FIGO staging of endometrial cancer: 2023","volume":"34","author":"Berek","year":"2023","journal-title":"J. Gynecol. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1055\/a-1545-4279","article-title":"2020 WHO Classification of Female Genital Tumors","volume":"81","author":"Brambs","year":"2021","journal-title":"Geburtshilfe Frauenheilkd."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6575\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:27:00Z","timestamp":1787732820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":21,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15176575"],"URL":"https:\/\/doi.org\/10.3390\/jcm15176575","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}