{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T21:17:18Z","timestamp":1775683038654,"version":"3.50.1"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aktuelle Urol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>\n      Zusammenfassung\n    <\/jats:title><jats:p>\n            Hintergrund Das Peniskarzinom ist eine seltene, v.a. im metastasierten Stadium jedoch h\u00e4ufig t\u00f6dliche Tumorerkrankung. Die meisten Daten zu Prognosefaktoren des Peniskarzinoms basieren auf kleinen Patientenkohorten, und selbst Metaanalysen sind hinsichtlich der Patientenzahlen meist eingeschr\u00e4nkt. Es fehlt an suffizienten Parametern, um das Metastasierungspotenzial der Tumoren vorhersagen zu k\u00f6nnen. Weiterhin unklar ist die Rolle des HPV-Status f\u00fcr die Prognoseabsch\u00e4tzung und in diesem Zusammenhang auch von p16INK4a.\n    <\/jats:p><jats:p>\n            Material und Methoden In dieser Studie wurden 236 Patienten aus einer internationalen multizentrischen Kohorte hinsichtlich der histologischen Subtypen, des HPV- und p16-Status sowie weiterer klinischer Parameter untersucht. Der HPV-Status wurde nur bei Nachweis von HPV mittels PCR sowie einem positiven p16-Status als HPV-positiv gewertet. Die statistische Analyse erfolgte mittels Kaplan-Meier-Methode sowie dem Log-rank-Test und einer uni- und multivariablen Analyse mittels Cox-Regressionsmodell.\n    <\/jats:p><jats:p>\n            Ergebnisse Ein positiver HPV-Status war weder f\u00fcr das metastasenfreie (MFS), noch das tumorspezifische (CSS) oder das Gesamt\u00fcberleben (OS) ein signifikanter Parameter. Bei p16-positiven Tumoren zeigte sich ein signifikant besseres MFS (p = 0,026), was sich ebenfalls in der Subgruppenanalyse der HPV-negativen Tumoren best\u00e4tigte (p = 0,037) ohne Unterschiede im CSS oder OS. Im \u201eUsual Type\u201c bestand ebenfalls eine positive Tendenz im MFS, jedoch ohne statistische Signifikanz (p = 0,070). p16-positive Tumoren waren in der multivariablen Cox-Regression mit einem hochsignifikant besseren MFS (Hazard Ratio 0,3; p = 0,004) assoziiert, w\u00e4hrend Patienten mit einem pT1b-Tumorstadium oder fortgeschrittener Lymphknotenmetastasierung ein signifikant schlechteres \u00dcberleben aufzeigten. In der multivariablen Analyse der HPV-negativen Tumoren war der p16-Status ebenfalls mit einem signifikanten Unterschied im MFS assoziiert (Hazard Ratio 0,2; p = 0,007).\n    <\/jats:p><jats:p>\n            Schlussfolgerung Der HPV-Status scheint nur von geringer prognostischer Relevanz zu sein, w\u00e4hrend der p16-Status eine wichtige Rolle in der Prognoseabsch\u00e4tzung einnimmt. So ist die Expression von p16INK4a mit einem signifikant besseren MFS assoziiert. Insbesondere in HPV-negativen Tumoren sollte der p16-Status hinsichtlich der prognostischen Wertigkeit und damit weiterf\u00fchrend auch hinsichtlich der Therapieentscheidung evaluiert werden.\n    <\/jats:p>","DOI":"10.1055\/a-2104-1270","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T22:30:31Z","timestamp":1691188231000},"page":"274-284","source":"Crossref","is-referenced-by-count":4,"title":["Bedeutung von HPV-Status und p16 f\u00fcr die Prognose des Peniskarzinoms"],"prefix":"10.1055","volume":"54","author":[{"given":"Jan Niklas","family":"Mink","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oybek","family":"Khalmurzaev","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"},{"name":"Abteilung f\u00fcr Urologie, N N Blokhin NMRCO, Moskva, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Pryalukhin","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Pathologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"},{"name":"Institut f\u00fcr Pathologie, Universit\u00e4tsklinikum Bonn, Bonn, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"H\u00f6lters","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Geppert","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie, Universit\u00e4tsklinikum Erlangen, Erlangen, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Lohse","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Virologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristof","family":"Bende","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie, Universit\u00e4tsklinikum Erlangen, Erlangen, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Pathologie, IPO-PORTO, Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Pathologie, IPO-PORTO, Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagen","family":"Loertzer","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Urologie und Kinderurologie, Westpfalz Klinikum Gmbh, Kaiserslautern, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Steffens","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, St-Antonius-Hospital gGmbH, Eschweiler, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Pathologie, IPO-PORTO, Porto, Portugal"},{"name":"Portuguese Oncology Institute of Porto, Research Center (CI-IPOP), Porto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiko","family":"Wunderlich","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Urologie und Kinderurologie, St. Georg Klinikum Eisenach, Eisenach, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Heinzelbecker","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Bohle","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Pathologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"St\u00f6ckle","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vsevolod","family":"Matveev","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Urologie, N N Blokhin NMRCO, Moskva, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arndt","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie, Universit\u00e4tsklinikum Erlangen, Erlangen, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0873-8128","authenticated-orcid":false,"given":"Kerstin","family":"Junker","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Urologie und Kinderurologie, Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes, Homburg, Deutschland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00345-008-0302-z","article-title":"Penile cancer: epidemiology, pathogenesis and prevention","volume":"27","author":"MCG Bleeker","year":"2009","journal-title":"World J Urol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e34874","DOI":"10.2196\/34874","article-title":"Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study","volume":"8","author":"L Fu","year":"2022","journal-title":"JMIR Public Health Surveill"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1097\/MOU.0000000000000581","article-title":"Penile cancer epidemiology and risk factors: a contemporary review","volume":"29","author":"A Douglawi","year":"2019","journal-title":"Curr Opin Urol"},{"key":"ref4","first-page":"4620","article-title":"E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway","volume":"56","author":"SN Boyer","year":"1996","journal-title":"Cancer Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"6439","DOI":"10.1074\/jbc.273.11.6439","article-title":"The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells","volume":"273","author":"AL Talis","year":"1998","journal-title":"J Biol Chem"},{"key":"ref6","first-page":"102","article-title":"Noninfectious Penile Lesions","volume":"97","author":"JMH Teichman","year":"2018","journal-title":"Am Fam Physician"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nrm1987","article-title":"Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all","volume":"7","author":"J Gil","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/0092-8674(95)90385-2","article-title":"The retinoblastoma protein and cell cycle control","volume":"81","author":"RA Weinberg","year":"1995","journal-title":"Cell"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1097\/JTO.0b013e3182a46c0c","article-title":"CDKN2A\/p16 inactivation mechanisms and their relationship to smoke exposure and molecular features in non-small-cell lung cancer","volume":"8","author":"KW Tam","year":"2013","journal-title":"J Thorac Oncol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"ZC09","DOI":"10.7860\/JCDR\/2014\/9251.4949","article-title":"Promoter hypermethylation profile of tumour suppressor genes in oral leukoplakia and oral squamous cell carcinoma","volume":"8","author":"GS Asokan","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3390\/jcm7090241","article-title":"A Review of HPV-Related Head and Neck Cancer","volume":"7","author":"K Kobayashi","year":"2018","journal-title":"J Clin Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1002\/ijc.31139","article-title":"Does HPV status influence survival after vulvar cancer?","volume":"142","author":"CL Rasmussen","year":"2018","journal-title":"Int J Cancer"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.juro.2011.10.149","article-title":"p16(INK4a) is a marker of good prognosis for primary invasive penile squamous cell carcinoma: a multi-institutional study","volume":"187","author":"S Gunia","year":"2012","journal-title":"J Urol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4081\/aiua.2020.1.11","article-title":"Prognostic value of p16INK4a overexpression in penile cancer","volume":"92","author":"M Pereira-Louren\u00e7o","year":"2020","journal-title":"Arch Ital Urol Androl"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1177\/10732748211033544","article-title":"Role of P16 Expression in the Prognosis of Patients With Laryngeal Cancer: A Single Retrospective Analysis","volume":"28","author":"E Allegra","year":"2021","journal-title":"Cancer Control"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s00428-019-02566-0","article-title":"Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma","volume":"475","author":"S H\u00f6lters","year":"2019","journal-title":"Virchows Arch"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1128\/jcm.33.4.901-905.1995","article-title":"Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes","volume":"33","author":"MV Jacobs","year":"1995","journal-title":"J Clin Microbiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.molonc.2007.08.005","article-title":"Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7","volume":"1","author":"D Lindquist","year":"2007","journal-title":"Mol Oncol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.juro.2014.08.087","article-title":"Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome","volume":"193","author":"RS Djajadiningrat","year":"2015","journal-title":"J Urol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1002\/ijc.21961","article-title":"Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival","volume":"119","author":"AP Lont","year":"2006","journal-title":"Int J Cancer"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.humpath.2014.12.004","article-title":"Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas","volume":"46","author":"SM Bezerra","year":"2015","journal-title":"Hum Pathol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/1097-0142(20010615)91:12<2315::AID-CNCR1263>3.0.CO;2-C","article-title":"Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy","volume":"91","author":"AL Bezerra","year":"2001","journal-title":"Cancer"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1055\/a-0664-0316","article-title":"Role of p16(INK4A) in detection of human papillomavirus DNA and stratification of cancer-specific mortality on the basis of long term follow-up data of 34 patients with invasive penile cancer","volume":"50","author":"J Br\u00fcndl","year":"2019","journal-title":"Aktuelle Urol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/S1470-2045(18)30682-X","article-title":"Prevalence of human papillomavirus DNA and p16(INK4a) in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis","volume":"20","author":"TB Olesen","year":"2019","journal-title":"Lancet Oncol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.semradonc.2021.04.001","article-title":"Epidemiology of HPV Related Malignancies","volume":"31","author":"N Scott-Wittenborn","year":"2021","journal-title":"Semin Radiat Oncol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1055\/a-1032-8086","article-title":"Knowledge of German-speaking urologists regarding the association between penile cancer and human papilloma virus: results of a survey of the European PROspective Penile Cancer Study (E-PROPS)","volume":"53","author":"S Lebentrau","year":"2022","journal-title":"Aktuelle Urol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"Doc09","DOI":"10.3205\/cto000091","article-title":"Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer","volume":"11","author":"C Wittekindt","year":"2012","journal-title":"GMS Curr Top Otorhinolaryngol Head Neck Surg"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.3390\/ijms18071591","article-title":"The Role of p16(INK4a) Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer","volume":"18","author":"D D\u2019Arcangelo","year":"2017","journal-title":"Int J Mol Sci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1038\/modpathol.3800220","article-title":"Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior","volume":"17","author":"K Nilsson","year":"2004","journal-title":"Mod Pathol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.juro.2014.08.120","article-title":"Lack of P16ink4a over expression in penile squamous cell carcinoma is associated with recurrence after lymph node dissection","volume":"193","author":"DH Tang","year":"2015","journal-title":"J Urol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00428-010-1007-4","article-title":"Alterations in the tumor suppressor gene p16(INK4A) are associated with aggressive behavior of penile carcinomas","volume":"458","author":"M Poetsch","year":"2011","journal-title":"Virchows Arch"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1023\/a:1023243102230","article-title":"Predictive pathological factors of lymph nodes involvement in the squamous cell carcinoma of the penis","volume":"34","author":"V Ficarra","year":"2002","journal-title":"Int Urol Nephrol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/S0022-5347(05)66450-6","article-title":"Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer","volume":"165","author":"JW Slaton","year":"2001","journal-title":"J Urol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/s0022-5347(01)65471-5","article-title":"Prognostic factors in carcinoma of the penis: multivariate analysis of 145 patients treated with amputation and lymphadenectomy","volume":"156","author":"A Lopes","year":"1996","journal-title":"J Urol"}],"container-title":["Aktuelle Urologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2104-1270.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T22:31:11Z","timestamp":1691188271000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2104-1270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":34,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2023,8,4]]},"published-print":{"date-parts":[[2023,8]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2104-1270","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0001-7868","1438-8820"],"issn-type":[{"value":"0001-7868","type":"print"},{"value":"1438-8820","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}