{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:49:01Z","timestamp":1790092141767,"version":"4.0.1"},"reference-count":42,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Urologic Oncology: Seminars and Original Investigations"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1016\/j.urolonc.2017.10.010","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T06:04:12Z","timestamp":1509689052000},"page":"433-439","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["Insight into novel biomarkers in penile cancer: Redefining the present and future treatment paradigm?"],"prefix":"10.1016","volume":"36","author":[{"given":"Kamran","family":"Zargar-Shoshtari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe E.","family":"Spiess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.urolonc.2017.10.010_bib1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1067\/mcp.2001.113989","article-title":"Biomarkers and surrogate endpoints: preferred definitions and conceptual framework","volume":"69","year":"2001","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.urolonc.2017.10.010_bib2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1464-410X.2010.09770.x","article-title":"Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma","volume":"108","author":"Kirrander","year":"2011","journal-title":"BJU Int"},{"key":"10.1016\/j.urolonc.2017.10.010_bib3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaad.2012.05.029","article-title":"Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: correlation with pathologic subtypes, p16(INK4a) expression, and prognosis","volume":"68","author":"Ferrandiz-Pulido","year":"2013","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/bjc.2012.583","article-title":"The etiologic role of human papillomavirus in penile cancers: a study in Vietnam","volume":"108","author":"Do","year":"2013","journal-title":"Br J Cancer"},{"key":"10.1016\/j.urolonc.2017.10.010_bib5","doi-asserted-by":"crossref","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":"Tang","year":"2015","journal-title":"J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib6","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1007\/s00345-013-1024-4","article-title":"The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection","volume":"31","author":"Liu","year":"2013","journal-title":"World J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib7","first-page":"471","article-title":"C-reactive protein and malignancy: clinico-pathological association and therapeutic implication","volume":"32","author":"Wang","year":"2009","journal-title":"Chang Gung Med J"},{"key":"10.1016\/j.urolonc.2017.10.010_bib8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaad.2012.12.973","article-title":"Two major pathways of penile carcinogenesis: HPV-induced penile cancers overexpress p16ink4a, HPV-negative cancers associated with dermatoses express p53, but lack p16ink4a overexpression","volume":"69","author":"Mannweiler","year":"2013","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1126\/science.2157286","article-title":"Association of human papillomavirus types 16 and 18 E6 proteins with p53","volume":"248","author":"Werness","year":"1990","journal-title":"Science"},{"key":"10.1016\/j.urolonc.2017.10.010_bib10","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.clgc.2015.12.019","article-title":"Clinical significance of p53 and p16(ink4a) status in a contemporary North American penile carcinoma cohort","volume":"14","author":"Zargar-Shoshtari","year":"2016","journal-title":"Clin Genitourin Cancer"},{"key":"10.1016\/j.urolonc.2017.10.010_bib11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12885-015-1268-z","article-title":"The role of histologic subtype, p16(INK4a) expression, and presence of human papillomavirus DNA in penile squamous cell carcinoma","volume":"15","author":"Steinestel","year":"2015","journal-title":"BMC Cancer"},{"key":"10.1016\/j.urolonc.2017.10.010_bib12","doi-asserted-by":"crossref","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":"Djajadiningrat","year":"2015","journal-title":"J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib13","doi-asserted-by":"crossref","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":"Bezerra","year":"2015","journal-title":"Hum Pathol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib14","doi-asserted-by":"crossref","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":"Poetsch","year":"2011","journal-title":"Virch Arch"},{"issue":"53","key":"10.1016\/j.urolonc.2017.10.010_bib15","first-page":"e1","article-title":"Implications for human papillomavirus in penile cancer","volume":"32","author":"Flaherty","year":"2014","journal-title":"Urol Oncol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib16","doi-asserted-by":"crossref","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":"Lont","year":"2006","journal-title":"Int J Cancer"},{"key":"10.1016\/j.urolonc.2017.10.010_bib17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.urology.2007.03.003","article-title":"Do proliferating cell nuclear antigen and MIB-1\/Ki-67 have prognostic value in penile squamous cell carcinoma?","volume":"70","author":"Guimaraes","year":"2007","journal-title":"Urology"},{"key":"10.1016\/j.urolonc.2017.10.010_bib18","first-page":"2167","article-title":"Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the penis","volume":"27","author":"Papadopoulos","year":"2007","journal-title":"Anticancer Res"},{"key":"10.1016\/j.urolonc.2017.10.010_bib19","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1442-2042.2007.01694.x","article-title":"Clinical usage of the squamous cell carcinoma antigen in patients with penile cancer","volume":"14","author":"Touloupidis","year":"2007","journal-title":"Int J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1046\/j.1464-410X.2003.04315.x","article-title":"Squamous cell carcinoma antigen: a role in the early identification of nodal metastases in men with squamous cell carcinoma of the penis","volume":"92","author":"Laniado","year":"2003","journal-title":"BJU Int"},{"key":"10.1016\/j.urolonc.2017.10.010_bib21","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.urology.2007.07.013","article-title":"Squamous cell carcinoma antigen correlates with tumor burden but lacks prognostic potential for occult lymph node metastases in penile cancer","volume":"70","author":"Hungerhuber","year":"2007","journal-title":"Urology"},{"key":"10.1016\/j.urolonc.2017.10.010_bib22","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/j.juro.2008.07.040","article-title":"The value of squamous cell carcinoma antigen in the prognostic evaluation, treatment monitoring and followup of patients with penile cancer","volume":"180","author":"Zhu","year":"2008","journal-title":"J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib23","doi-asserted-by":"crossref","first-page":"bar026","DOI":"10.1093\/database\/bar026","article-title":"International Cancer Genome Consortium Data Portal\u2014a one-stop shop for cancer genomics data","volume":"2011","author":"Zhang","year":"2011","journal-title":"Database (Oxford)"},{"key":"10.1016\/j.urolonc.2017.10.010_bib24","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/ijc.11389","article-title":"A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16\/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5-8","volume":"107","author":"Hafkamp","year":"2003","journal-title":"Int J Cancer"},{"key":"10.1016\/j.urolonc.2017.10.010_bib25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0022-5347(05)64836-7","article-title":"p53 as a new prognostic factor for lymph node metastasis in penile carcinoma: analysis of 82 patients treated with amputation and bilateral lymphadenectomy","volume":"168","author":"Lopes","year":"2002","journal-title":"J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0022-5347(05)65389-X","article-title":"Immunoexpression of p53 protein and proliferating cell nuclear antigen in penile carcinoma","volume":"167","author":"Martins","year":"2002","journal-title":"J Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib27","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1136\/jclinpath-2011-200429","article-title":"Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis","volume":"65","author":"Gunia","year":"2012","journal-title":"J Clin Pathol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib28","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1464-410X.2007.06908.x","article-title":"The prognostic significance of p53, Ki-67, epithelial cadherin and matrix metalloproteinase-9 in penile squamous cell carcinoma treated with surgery","volume":"100","author":"Zhu","year":"2007","journal-title":"BJU Int"},{"key":"10.1016\/j.urolonc.2017.10.010_bib29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/1471-2407-13-223","article-title":"High CRP values predict poor survival in patients with penile cancer","volume":"13","author":"Steffens","year":"2013","journal-title":"BMC Cancer"},{"key":"10.1016\/j.urolonc.2017.10.010_bib30","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1471-2490-13-53","article-title":"Elevated C-reactive protein values predict nodal metastasis in patients with penile cancer","volume":"13","author":"Al Ghazal","year":"2013","journal-title":"BMC Urol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib31","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/bju.13379","article-title":"Clinical significance of preoperative C-reactive protein and squamous cell carcinoma antigen levels in patients with penile squamous cell carcinoma","volume":"118","author":"Li","year":"2016","journal-title":"BJU Int"},{"key":"10.1016\/j.urolonc.2017.10.010_bib32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1464-410X.2005.05584.x","article-title":"Expression of Ki-67 in squamous cell carcinoma of the penis","volume":"96","author":"Berdjis","year":"2005","journal-title":"BJU Int"},{"key":"10.1016\/j.urolonc.2017.10.010_bib33","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1136\/jclinpath-2011-200638","article-title":"The prognostic value of Ki-67 expression in penile squamous cell carcinoma","volume":"65","author":"Stankiewicz","year":"2012","journal-title":"J Clin Pathol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib34","doi-asserted-by":"crossref","first-page":"E383","DOI":"10.1111\/j.1464-410X.2012.11735.x","article-title":"Ki-67, mini-chromosome maintenance 2 protein (MCM2) and geminin have no independent prognostic relevance for cancer-specific survival in surgically treated squamous cell carcinoma of the penis","volume":"112","author":"May","year":"2013","journal-title":"BJU Int"},{"key":"10.1016\/j.urolonc.2017.10.010_bib35","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1128\/jvi.64.2.723-730.1990","article-title":"The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties","volume":"64","author":"Gage","year":"1990","journal-title":"J Virol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib36","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.urology.2005.10.026","article-title":"E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients","volume":"67","author":"Campos","year":"2006","journal-title":"Urology"},{"key":"10.1016\/j.urolonc.2017.10.010_bib37","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1007\/s13277-014-2864-2","article-title":"Pathologic and imunohistochemical characterization of tumoral inflammatory cell infiltrate in invasive penile squamous cell carcinomas: Fox-P3 expression is an independent predictor of recurrence","volume":"36","author":"Vassallo","year":"2015","journal-title":"Tumour Biol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib38","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.humpath.2015.01.018","article-title":"Immunohistochemical expression of ARID1A in penile squamous cell carcinomas: a tissue microarray study of 112 cases","volume":"46","author":"Faraj","year":"2015","journal-title":"Hum Pathol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.urolonc.2017.05.002","article-title":"Experimental validation of the complement protein C3a down expression in the plasma of patients with squamous cell carcinoma of the penis","author":"Ornellas","year":"2017","journal-title":"Urol Oncol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.urology.2016.02.006","article-title":"Overexpression of insulin-like growth factor-1 receptor is associated with penile cancer progression","volume":"92","author":"Ball","year":"2016","journal-title":"Urology"},{"key":"10.1016\/j.urolonc.2017.10.010_bib41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.humpath.2016.09.003","article-title":"Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort","volume":"59","author":"Cocks","year":"2017","journal-title":"Hum Pathol"},{"key":"10.1016\/j.urolonc.2017.10.010_bib42","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1158\/0008-5472.CAN-15-1004","article-title":"Genomic profiling of penile squamous cell carcinoma reveals new opportunities for targeted therapy","volume":"75","author":"McDaniel","year":"2015","journal-title":"Cancer Res"}],"container-title":["Urologic Oncology: Seminars and Original Investigations"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1078143917305471?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1078143917305471?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:14:09Z","timestamp":1761041649000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1078143917305471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["S1078143917305471"],"URL":"https:\/\/doi.org\/10.1016\/j.urolonc.2017.10.010","relation":{},"ISSN":["1078-1439"],"issn-type":[{"value":"1078-1439","type":"print"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Insight into novel biomarkers in penile cancer: Redefining the present and future treatment paradigm?","name":"articletitle","label":"Article Title"},{"value":"Urologic Oncology: Seminars and Original Investigations","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.urolonc.2017.10.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}