{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:29:04Z","timestamp":1787689744107,"version":"build-2784847793"},"reference-count":12,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of cervical cancer are caused by persistent infection with oncogenic high-risk human papillomavirus (HPV). This malignancy usually exhibits a gradual development through well-defined precursor stages, known as cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3, before evolving into invasive carcinoma. In diagnostic practice, several biomarkers have been implemented to improve the detection of high-risk cervical lesions. p16 and Ki-67 greatly aid in identifying HPV-driven dysplasia, but they cannot always reliably distinguish progressive lesions from regressive or transient HPV infections. These limitations highlight the need for novel biomarkers with better predictive accuracy to complement current screening and diagnostic algorithms. ROMO1 has become a possible marker of a high-ROS, high-risk tumor phenotype in a number of cancers. Although oxidative stress, HPV, and cervical carcinogenesis have been linked, nothing is known about ROMO1\u2019s involvement in cervical neoplasia. There is currently a lack of thorough information regarding the expression of ROMO1 in normal vs. precancerous lesions and in cervical cancer, as well as on whether or not its expression is correlated with the severity of the disease. In order to define ROMO1 expression throughout the course of cervical squamous neoplastic development, the current study was created. Methods: We performed immunohistochemical analysis of ROMO1 expression on cervical tissue samples from three groups: healthy cervix (n = 30), cervical intraepithelial neoplasia (CIN) (n = 41), and invasive cervical carcinoma (n = 205). ROMO1 expression in invasive carcinoma was evaluated using an H-score scale. Results: ROMO1 expression was basal in all normal cervix samples (0\/30 cases). In contrast, CIN lesions showed 100% ROMO1 expression in the suprabasal layers of abnormal cells in all CIN cases. In invasive cervical carcinomas, ROMO1 expression was heterogeneous. In our cancer cohort (n = 205), ROMO1 H-score showed no significant association with the following: FIGO stage I vs. II vs. III (p = 0.25); histologic grade G1 vs. G2 vs. G3 (p = 0.46); lymphovascular invasion (no vs. yes; p = 0.80); nodal status N0 vs. N1 (p = 0.67); patient age (\u226450 y vs. &gt;50 y; p = 0.38). However, ROMO1 expression did vary by histologic subtype (AC vs. ASC vs. SCC; p = 0.02), with SCC enriched for strong staining compared to AC\/ASC. With regard to tumor stage (pT stage), pT2a tumors exhibited significantly lower ROMO1 (pT1b1\u2013pT2b; p = 0.035) than pT1b1 (p = 0.04). No other clinicopathologic variable remained significant. Notably, ROMO1 expression was highest in stage I tumors and declined in more advanced stages of cervical carcinoma. Conclusions: These results show a clear pattern of ROMO1 expression across the cervical neoplasia spectrum: it is attenuated in invasive tumors (with a peak in early-stage illness), significantly raised in pre-cancerous CIN lesions, and negligible in normal epithelium. The idea that oxidative stress may be the primary cause of early malignant transformation in the cervix is supported by the noticeable overexpression of ROMO1 in early lesions. For the detection of early-stage cervical carcinoma and high-grade precancerous lesions, ROMO1 may be a useful auxiliary biomarker.<\/jats:p>","DOI":"10.3390\/diagnostics16010024","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T08:35:27Z","timestamp":1766392527000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ROMO1 as a Diagnostic Biomarker in Cervical Neoplasia: Evidence from Normal, Pre-Invasive, and Invasive Lesions"],"prefix":"10.3390","volume":"16","author":[{"given":"Eva","family":"Tsoneva","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Specialized Hospital for Active Treatment of Obstetrics and Gynaecology \u201cDr. Shterev\u201d, 1330 Sofia, Bulgaria"},{"name":"Faculty of Medicine, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-5585","authenticated-orcid":false,"given":"Polina","family":"Damyanova","sequence":"additional","affiliation":[{"name":"Department of General and Clinical Pathology, Heart and Brain Center of Clinical Excellence, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metodi V.","family":"Metodiev","sequence":"additional","affiliation":[{"name":"Life Sciences Laboratory, School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-7999","authenticated-orcid":false,"given":"Velizar","family":"Shivarov","sequence":"additional","affiliation":[{"name":"Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-3742","authenticated-orcid":false,"given":"Mariela","family":"Vasileva-Slaveva","sequence":"additional","affiliation":[{"name":"Bulgarian Breast and Other Gynecological Cancers Association, 1750 Sofia, Bulgaria"},{"name":"Department of Breast Surgery, \u201cDr. Shterev\u201d Hospital, 1750 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-7874","authenticated-orcid":false,"given":"Zornitsa","family":"Gorcheva","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Haematology and Gastroenterology, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonka","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Hospital \u201cSaint Anna\u201d, Medical University\u2014\u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavor","family":"Kornovski","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Hospital \u201cSaint Anna\u201d, Medical University\u2014\u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-3095","authenticated-orcid":false,"given":"Stoyan","family":"Kostov","sequence":"additional","affiliation":[{"name":"Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria"},{"name":"Department of Gynecology, Hospital \u201cSaint Anna\u201d, Medical University\u2014\u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4830-6159","authenticated-orcid":false,"given":"Stanislav","family":"Slavchev","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Hospital \u201cSaint Anna\u201d, Medical University\u2014\u201cProf. Dr. Paraskev Stoyanov\u201d, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Pathology Laboratory, Saint Marina University Hospital, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-382X","authenticated-orcid":false,"given":"Angel","family":"Yordanov","sequence":"additional","affiliation":[{"name":"Department of Gynaecological Oncology, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-1887","authenticated-orcid":false,"given":"Rafa\u0142","family":"Watrowski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Helios Hospital M\u00fcllheim, 79379 M\u00fcllheim, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, November 07). 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