{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T09:25:13Z","timestamp":1772616313517,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Cervical cancer is fourth the most common cancer in women worldwide. Due to the prevalence of human papillomavirus (HPV) in the population (80\u201390%), scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, In Situ Hybridization (ISH) assays that use automated signal-detecting methods in formalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. Objectives and Methods: To evaluate automatic signal detection of ISH assay for detecting HPV DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Results: Our findings showed a significant relation was confirmed between ISH III level and HPV outcome (positive\/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = \u22127961.82 CI95 [\u221217,230.00; \u2212199.21], p = 0.005. Conclusions: Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology.<\/jats:p>","DOI":"10.3390\/cancers16203485","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T04:45:35Z","timestamp":1729485935000},"page":"3485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of Automatic Signal Detection of In Situ Hybridization for Detecting HPV DNA in Cervical Tissue Derived from Patients with Cervical Intraepithelial Neoplasia"],"prefix":"10.3390","volume":"16","author":[{"given":"Marcin","family":"Przybylski","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, District Public Hospital, 60-479 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8291-3879","authenticated-orcid":false,"given":"Sonja","family":"Millert-Kali\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, District Public Hospital, 60-479 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4718-9747","authenticated-orcid":false,"given":"Mateusz","family":"de Mezer","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-9920","authenticated-orcid":false,"given":"Monika","family":"Krzy\u017caniak","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, University Clinical Hospital in Poznan, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Kurzawa","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, University Clinical Hospital in Poznan, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-0451","authenticated-orcid":false,"given":"Jakub","family":"\u017burawski","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-763X","authenticated-orcid":false,"given":"Robert","family":"Jach","sequence":"additional","affiliation":[{"name":"Department of Gynecological Endocrinology, Jagiellonian University Medical College, 31-008 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-5731","authenticated-orcid":false,"given":"Dominik","family":"Pruski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, District Public Hospital, 60-479 Poznan, Poland"},{"name":"Gynecology Specialised Practise, 60-408 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1001\/jama.2023.13174","article-title":"Cervical Cancer Screening: A Review","volume":"330","author":"Perkins","year":"2023","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fitzpatrick, M.B., Hahn, Z., Mandishora, R.S.D., Dao, J., Weber, J., Huang, C., Sahoo, M.K., Katzenstein, D.A., and Pinsky, B.A. (2020). Whole-Genome Analysis of Cervical Human Papillomavirus Type 35 from rural Zimbabwean Women. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-63882-z"},{"key":"ref_4","first-page":"595","article-title":"Human papillomavirus vaccines and vaccine implementation","volume":"4","author":"Alemany","year":"2008","journal-title":"Women\u2019s Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chen, Z., Schiffman, M., Herrero, R., DeSalle, R., Anastos, K., Segondy, M., Sahasrabuddhe, V.V., Gravitt, P.E., Hsing, A.W., and Burk, R.D. (2011). Evolution and taxonomic classification of human papillomavirus 16 (HPV16)-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020183"},{"key":"ref_6","first-page":"894","article-title":"Comparison of the effectiveness of cytodiagnostics, molecular identification of HPV HR and CINtecPLUS test to identify LG SIL and HG SIL","volume":"83","author":"Rokita","year":"2012","journal-title":"Ginekol. Pol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mazurec, K., Trzeszcz, M., Mazurec, M., Streb, J., Halon, A., and Jach, R. (2023). Triage Strategies for Non-16\/Non-18 HPV-Positive Women in Primary HPV-Based Cervical Cancer Screening: p16\/Ki67 Dual Stain vs. Cytology. Cancers, 15.","DOI":"10.3390\/cancers15205095"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/S1470-2045(22)00294-7","article-title":"Accuracy and effectiveness of HPV mRNA testing in cervical cancer screening: A systematic review and meta-analysis","volume":"23","author":"Arbyn","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00404-010-1771-z","article-title":"Evaluation of two commercialised in situ hybridisation assays for detecting HPV-DNA in formalin-fixed, paraffin-embedded tissue","volume":"284","author":"Montag","year":"2011","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/PAI.0b013e3182a501a2","article-title":"Automated in situ hybridization for human papilloma virus","volume":"22","author":"Cohen","year":"2014","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/ijc.20862","article-title":"HPV in situ hybridization: Impact of different protocols on the detection of integrated, H.P.V","volume":"115","author":"Hopman","year":"2005","journal-title":"Int. J. Cancer."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1111\/iju.12509","article-title":"Recurrence and progression in patients with non-muscle invasive bladder cancer: Prognostic models including multicolor fluorescence in situ hybridization molecular grading","volume":"21","author":"Lodde","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1262\/jrd.18002","article-title":"Expression profiling of mouse placental lactogen II and its correlative genes using a cDNA microarray analysis in the developmental mouse placenta","volume":"53","author":"Ishida","year":"2007","journal-title":"J. Reprod. Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1128\/JCM.01299-07","article-title":"Evaluation of a commercialized in situ hybridization assay for detecting human papillomavirus DNA in tissue specimens from patients with cervical intraepithelial neoplasia and cervical carcinoma","volume":"46","author":"Guo","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00266-020-01949-y","article-title":"Injection of Aquafilling\u00ae for Breast Augmentation Causes Inflammatory Responses Independent of Visible Symptoms","volume":"45","author":"Chalcarz","year":"2021","journal-title":"Aesthet. Plast. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"362371","DOI":"10.5603\/GP.2020.0075","article-title":"COLPOSCOPY 2020\u2014COLPOSCOPY PROTOCOLS: A Summary of the Clinical Experts Consensus Guidelines of the Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynaecologists and Obstetricians","volume":"91","author":"Jach","year":"2020","journal-title":"Ginekol. Pol."},{"key":"ref_17","first-page":"97","article-title":"Colposcopy Standards: Guidelines for Endocervical Curettage at Colposcopy","volume":"27","author":"Massad","year":"2023","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/LGT.0000000000000337","article-title":"The New ASCCP Colposcopy Standards","volume":"21","author":"Wright","year":"2017","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Przybylski, M., Pruski, D., Millert-Kali\u0144ska, S., Krzy\u017caniak, M., de Mezer, M., Frydrychowicz, M., Jach, R., and \u017burawski, J. (2023). Expression of E4 Protein and HPV Major Capsid Protein (L1) as A Novel Combination in Squamous Intraepithelial Lesions. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010225"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.2174\/0113892010264673231111082438","article-title":"Immunohistochemical Expression of the SERPINA3 Protein in Uterine Fibroids","volume":"25","author":"Markowska","year":"2024","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13027-020-00310-x","article-title":"Multiplex HPV RNA in situ hybridization\/p16 immunohistochemistry: A novel approach to detect papillomavirus in HPV-related cancers. A novel multiplex ISH\/IHC assay to detect HPV","volume":"15","author":"Ronchi","year":"2020","journal-title":"Infect. Agent. Cancer"},{"key":"ref_22","first-page":"2168","article-title":"Detection of high-risk human papillomavirus subtypes in cervical glandular neoplasia by in situ hybridization","volume":"6","author":"Sheng","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_23","first-page":"993","article-title":"Human Papillomavirus Types and Localization in Adenocarcinoma and Adenosquamous Carcinoma of the Uterine Cervix: A study by in Situ DNA Hybridization","volume":"48","author":"Tase","year":"1988","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s004280100439","article-title":"Expression of cyclin-dependent kinase inhibitors p16MTS1, p21WAF1, and p27KIP1 in HPV-positive and HPV-negative cervical adenocarcinomas","volume":"439","author":"Riethdorf","year":"2001","journal-title":"Virchows Archiv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1177\/002215540205001014","article-title":"HPV DNA detection by in situ hybridization with catalyzed signal amplification on thin-layer cervical smears","volume":"50","author":"Samama","year":"2002","journal-title":"J. Histochem. Cytochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.5603\/GP.2019.0011","article-title":"Sensitivity and specificity of HR HPV E6\/E7 mRNA test in detecting cervical squamous intraepithelial lesion and cervical cancer","volume":"90","author":"Pruski","year":"2019","journal-title":"Ginekol. Pol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zappacosta, R., Colasante, A., Viola, P., D\u2019Antuono, T., Lattanzio, G., Capanna, S., Gatta, D.M., and Rosini, S. (2013). Chromogenic in situ hybridization and p16\/Ki67 dual staining on formalin-fixed paraffin-embedded cervical specimens: Correlation with HPV-DNA test, E6\/E7 mRNA test, and potential clinical applications. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/453606"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13000-021-01072-9","article-title":"Accuracy of HPV E6\/E7 mRNA examination using in situ hybridization in diagnosing cervical intraepithelial lesions","volume":"16","author":"Hui","year":"2021","journal-title":"Diagn. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pruski, D., Millert-Kali\u0144ska, S., \u0141agiedo, M., Sikora, J., Jach, R., and Przybylski, M. (2023). Effect of HPV Vaccination on Virus Disappearance in Cervical Samples of a Cohort of HPV-Positive Polish Patients. J. Clin. Med., 12.","DOI":"10.3390\/jcm12247592"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1016\/j.ygyno.2013.04.100","article-title":"Efficacy of the human papillomavirus vaccination in women aged 20\u201345 years with high-grade cervical intraepithelial neoplasia treated by loop electrosurgical excision procedure","volume":"130","author":"Kim","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ghelardi, A., Marrai, R., Bogani, G., Sopracordevole, F., Bay, P., Tonetti, A., Lombardi, S., Bertacca, G., and Joura, E.A. (2021). Surgical treatment of vulvar HSIL: Adjuvant HPV vaccine reduces recurrent disease. Vaccines, 9.","DOI":"10.3390\/vaccines9020083"},{"key":"ref_32","first-page":"8102","article-title":"The analysis of human papillomavirus DNA in penile cancer tissue by in situ hybridization","volume":"15","author":"Takamoto","year":"2018","journal-title":"Oncol. Lett."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/20\/3485\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:13:25Z","timestamp":1760112805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/20\/3485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":32,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["cancers16203485"],"URL":"https:\/\/doi.org\/10.3390\/cancers16203485","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,15]]}}}