{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:50:23Z","timestamp":1771660223871,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human papillomavirus (HPV) is a well\u2010established mucosotropic carcinogen, but its impact on urothelial neoplasm is unclear. We aimed to clarify the clinical and pathological features of HPV\u2010related urothelial carcinoma (UC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tissue samples of 228 cases of UC were obtained from the bladder, upper and lower urinary tract, and metastatic sites to construct a tissue microarray. The samples were analyzed for the presence of HPV by a highly sensitive and specific mRNA in situ hybridization (RISH) technique (RNAscope) with a probe that can detect 18 varieties of high\u2010risk HPV. We also conducted immunohistochemistry (IHC) for a major HPV capsid antibody and DNA\u2010PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The HPV detection rates varied among the methods; probably due to low HPV copy numbers in UC tissues and the insufficient specificity and sensitivity of the IHC and PCR assays. The RISH method had the highest accuracy and identified HPV infection in 12 (5.2%) of the cases. The histopathological analysis of the HPV\u2010positive UC showed six cases of usual type UC, five cases of UC with squamous differentiation (UC_SqD), and one case of micropapillary UC. The HPV detection rate was six\u2010fold higher in the cases of UC_SqD than in the other variants of UC (odds ratio [OR] =8.9, <jats:italic>p<\/jats:italic> = 0.002). In addition, HPV infection showed a significant association with tumor grade (OR =9.8, <jats:italic>p<\/jats:italic> = 0.03) and stage (OR =4.7, <jats:italic>p<\/jats:italic> = 0.03) of UC. Moreover, the metastatic rate was higher in HPV\u2010positive than in negative UC (OR =3.4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data indicate that although the incidence of HPV infection in UC is low, it is significantly associated with squamous differentiation and poor prognosis. Furthermore, our observations show that RNAscope is an ideal method for HPV detection in UC compared with the other standard approaches such as IHC and PCR assays.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4091","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T05:40:06Z","timestamp":1624513206000},"page":"5534-5544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Detection of HPV infection in urothelial carcinoma using RNAscope: Clinicopathological characterization"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-8437","authenticated-orcid":false,"given":"Fidele Y.","family":"Musangile","sequence":"first","affiliation":[{"name":"Department of Human Pathology Wakayama Medical University Wakayama 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