{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:32:57Z","timestamp":1773822777220,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Squamous cell carcinoma (SCC) of the penis accounts for approximately 95% of penile cancers and is associated with substantial morbidity and mortality. SCC typically develops in uncircumcised men, most commonly affecting the foreskin or glans. While slow-growing, early detection is crucial to improve survival outcomes. Risk factors include advanced age, lack of circumcision, poor hygiene, HPV infection (types 16 and 18), chronic inflammation, and smoking. Methods: We conducted a retrospective, single-center study at IRCCS Hospital \u201cG. Pascale\u201d of Naples, Italy, involving 59 patients treated between January 2015 and January 2023. The inclusion criteria were surgically treated primary tumors, confirmed SCC pathology, and pathologically verified inguinal lymph node metastasis (ILNM). We analyzed clinical variables including lymph node involvement, lymphovascular invasion (LVI), spongiosum corpus involvement (SCI), HPV infection, and tumor differentiation. Univariate and multivariate logistic regression analyses were performed to determine independent predictors of ILNM. Results: The mean age of patients was 66.67 \u00b1 13.97 years. ILNM was confirmed in 24 patients (40.6%), while 35 (59.3%) had no lymph node involvement. Univariate analysis identified lymph node involvement at diagnosis (p = 0.005), LVI (p = 0.003), and SCI (p = 0.003) as significant predictors of ILNM. These factors were confirmed in the multivariate analysis, with lymph node involvement (p = 0.004), LVI (p = 0.025), and SCI (p = 0.028) as independent predictors. Conclusions: Lymph node status, LVI, and SCI are significant predictors of ILNM in penile SCC. Identifying these factors can aid in risk stratification, optimizing surgical decisions, and potentially reducing unnecessary morbidity. Further large-scale studies are recommended to validate these findings and refine prognostic models.<\/jats:p>","DOI":"10.3390\/jcm14092921","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T12:04:33Z","timestamp":1745409873000},"page":"2921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictors of Inguinal Lymph Node Metastasis in Penile Squamous Cell Carcinoma: Insights from a Single-Center Retrospective Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4109-3683","authenticated-orcid":false,"given":"Francesco","family":"Passaro","sequence":"first","affiliation":[{"name":"Uro-Gynecological Department, IRCCS, Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-0356","authenticated-orcid":false,"given":"Luigi","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale Salerno, ASL Salerno-DS66, Via Vernieri, 84124 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Tufano","sequence":"additional","affiliation":[{"name":"Uro-Gynecological Department, IRCCS, Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"La Rocca","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8625-1703","authenticated-orcid":false,"given":"Claudio","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-132X","authenticated-orcid":false,"given":"Biagio","family":"Barone","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Surgical Sciences, AORN Sant\u2019Anna e San Sebastiano, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Urology, A.O.R.N.A. Cardarelli, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo","family":"Amicuzi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelangelo","family":"Olivetta","sequence":"additional","affiliation":[{"name":"Urology Unit G. Fucito, Hospital and University Hospital, 84085 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Mastrangelo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Reccia","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Surgical Sciences, AORN dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4315-7660","authenticated-orcid":false,"given":"Felice","family":"Crocetto","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-7930","authenticated-orcid":false,"given":"Lorenzo","family":"Romano","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6340-4403","authenticated-orcid":false,"given":"Francesco Paolo","family":"Calace","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Surgical Sciences, AORN dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1175-8637","authenticated-orcid":false,"given":"Lorenzo","family":"Spirito","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9706-8516","authenticated-orcid":false,"given":"Celeste","family":"Manfredi","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5282-2335","authenticated-orcid":false,"given":"Davide","family":"Arcaniolo","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"De Palma","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Turco","sequence":"additional","affiliation":[{"name":"Department of Urology, Ospedale del Mare, ASL NA1 Centro, 80147 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Sciorio","sequence":"additional","affiliation":[{"name":"Urology Unit, A. Manzoni General Hospital, 23900 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo Maria","family":"Altieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u201cV. Tiberio\u201d, University of Molise, 86100 Campobasso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennaro","family":"Mattiello","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Surgical Sciences, AORN Sant\u2019Anna e San Sebastiano, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0552-4829","authenticated-orcid":false,"given":"Ernesto","family":"di Mauro","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale Salerno, ASL Salerno-DS66, Via Vernieri, 84124 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-8385","authenticated-orcid":false,"given":"Giuseppe","family":"Celentano","sequence":"additional","affiliation":[{"name":"Urology Unit, Clinica Mediterranea, 80122 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sisto","family":"Perdon\u00e0","sequence":"additional","affiliation":[{"name":"Uro-Gynecological Department, IRCCS, Fondazione \u201cG. Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","unstructured":"(2025, April 18). EAU Guidelines on Penile Cancer\u2014Uroweb. Available online: https:\/\/uroweb.org\/guidelines\/penile-cancer."},{"key":"ref_2","first-page":"646","article-title":"The Diagnosis and Treatment of Penile Cancer","volume":"115","author":"Erbersdobler","year":"2018","journal-title":"Dtsch. \u00c4rztebl. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1590\/abd1806-4841.20175009","article-title":"Penile Squamous Cell Carcinoma: A Review of the Literature and Case Report Treated with Mohs Micrographic Surgery","volume":"92","author":"Marchionne","year":"2017","journal-title":"An. Bras. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s11670-012-0090-2","article-title":"Lymph Node Metastases and Prognosis in Penile Cancer","volume":"24","author":"Zhu","year":"2012","journal-title":"Chin. J. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Salazar-M-Messias, I., Sotelo, R., Subir\u00e1-Rios, D., Elbalka, S., Medina, L.G., Corona-Montes, V.E., Saba, A.S.S., Hidaka, A.K., and Tobias-Machado, M. (2023). Techniques, Outcomes, and Complications of Minimally Invasive Inguinal Lymphadenectomy in Cancer of the Penis: An International Clinical Review. AME Med. J., 8.","DOI":"10.21037\/amj-23-8"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Borque-Fernando, \u00c1., Gaya, J.M., Esteban-Esca\u00f1o, L.M., G\u00f3mez-Rivas, J., Garc\u00eda-Baquero, R., Agreda-Casta\u00f1eda, F., Gallioli, A., Verri, P., Ortiz-Vico, F.J., and Amir-Nicolau, B.F. (2023). Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer. Cancers, 15.","DOI":"10.3390\/cancers15030616"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s40487-020-00135-z","article-title":"Recent Advances in the Management of Penile Cancer: A Contemporary Review of the Literature","volume":"9","author":"Stecca","year":"2021","journal-title":"Oncol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1590\/s1677-5538.ibju.2021.0613","article-title":"Analysis of the Related Risk Factors of Inguinal Lymph Node Metastasis in Patients with Penile Cancer: A Cross-Sectional Study","volume":"48","author":"Jia","year":"2022","journal-title":"Int. Braz. J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Amicuzi, U., Grillo, M., Stizzo, M., Olivetta, M., Tammaro, S., Napolitano, L., Reccia, P., De Luca, L., Rubinacci, A., and Della Rosa, G. (2024). Exploring the Multifactorial Landscape of Penile Cancer: A Comprehensive Analysis of Risk Factors. Diagnostics, 14.","DOI":"10.3390\/diagnostics14161790"},{"key":"ref_10","unstructured":"Penis Carcinoma\u2014An Overview (2025, April 18). ScienceDirect Topics. Available online: https:\/\/www.sciencedirect.com\/topics\/medicine-and-dentistry\/penis-carcinoma."},{"key":"ref_11","first-page":"91","article-title":"Penile Carcinoma and HPV Infection (Review)","volume":"20","author":"Iorga","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kori, M., and Arga, K.Y. (2020). Pathways Involved in Viral Oncogenesis: New Perspectives from Virus-Host Protein Interactomics. Biochim. Biophys. Acta BBA\u2014Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165885"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/cid\/ciw354","article-title":"Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-World Experience","volume":"63","author":"Garland","year":"2016","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4111\/icu.2019.60.2.127","article-title":"Microbiology of Smegma: Prospective Comparative Control Study","volume":"60","author":"Chung","year":"2019","journal-title":"Investig. Clin. Urol."},{"key":"ref_15","first-page":"559","article-title":"Risk Factors and Prevalence of Penile Cancer","volume":"63","author":"Morrison","year":"2018","journal-title":"West Indian Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Crocetto, F., Arcaniolo, D., Napolitano, L., Barone, B., La Rocca, R., Capece, M., Caputo, V.F., Imbimbo, C., De Sio, M., and Calace, F.P. (2021). Impact of Sexual Activity on the Risk of Male Genital Tumors: A Systematic Review of the Literature. Int. J. Environ. Res. Public. Health, 18.","DOI":"10.3390\/ijerph18168500"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.urology.2011.12.048","article-title":"Clinical and Pathologic Factors of Prognostic Significance in Penile Squamous Cell Carcinoma in a North American Population","volume":"79","author":"Bethune","year":"2012","journal-title":"Urology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/jso.20414","article-title":"Prognostic Factors in Node-Positive Carcinoma of the Penis","volume":"93","author":"Pandey","year":"2006","journal-title":"J. Surg. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tufano, A., Napolitano, L., Barone, B., Pezone, G., Alvino, P., Cilio, S., Buonerba, C., Canciello, G., Passaro, F., and Perdon\u00e0, S. (2024). Preoperative Albumin-to-Alkaline Phosphatase Ratio as an Independent Predictor of Lymph Node Involvement in Penile Cancer. Medicina, 60.","DOI":"10.3390\/medicina60030414"},{"key":"ref_20","first-page":"13428","article-title":"Preoperative Platelet-to-Lymphocyte Ratio as a Predictor of Inguinal Lymph Node Metastasis in Penile Cancer","volume":"97","author":"Passaro","year":"2025","journal-title":"Arch. Ital. Urol. E Androl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.juro.2017.11.121","article-title":"Differences in Survival Associated with Performance of Lymph Node Dissection in Patients with Invasive Penile Cancer: Results from the National Cancer Database","volume":"199","author":"Correa","year":"2018","journal-title":"J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1515\/jbcpp-2023-0038","article-title":"Inguinal Lymphadenectomy in Penile Cancer Patients: A Comparison between Open and Video Endoscopic Approach in a Multicenter Setting","volume":"34","author":"Bada","year":"2023","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1046\/j.1464-410X.2001.00380.x","article-title":"Lymphadenectomy for Squamous Cell Carcinoma of the Penis. Part 1: Diagnosis of Lymph Node Metastasis","volume":"88","author":"Horenblas","year":"2001","journal-title":"BJU Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.urology.2016.06.033","article-title":"Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis","volume":"96","author":"Winters","year":"2016","journal-title":"Urology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.1016\/j.urology.2010.04.008","article-title":"Prognostic Factors in Penile Cancer","volume":"76","author":"Ficarra","year":"2010","journal-title":"Urology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1590\/s1677-5538.ibju.2020.0959","article-title":"Prognostic Predictors of Lymph Node Metastasis in Penile Cancer: A Systematic Review","volume":"47","author":"Zekan","year":"2021","journal-title":"Int. Braz. J. Urol. Off. J. Braz. Soc. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.eururo.2010.08.015","article-title":"Prognostic Factors for Occult Inguinal Lymph Node Involvement in Penile Carcinoma and Assessment of the High-Risk EAU Subgroup: A Two-Institution Analysis of 342 Clinically Node-Negative Patients","volume":"58","author":"Graafland","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.2147\/CMAR.S206579","article-title":"Predictors of Inguinal Lymph Node Metastasis in Penile Cancer Patients: A Meta-Analysis of Retrospective Studies","volume":"11","author":"Hu","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1016\/j.juro.2010.02.025","article-title":"Long-Term Followup of Penile Carcinoma with High Risk for Lymph Node Invasion Treated with Inguinal Lymphadenectomy","volume":"183","author":"Marconnet","year":"2010","journal-title":"J. Urol."},{"key":"ref_30","first-page":"774","article-title":"Squamous Cell Carcinoma of the Penis: Predicting Nodal Metastases by Histologic Grade, Pattern of Invasion and Clinical Examination","volume":"29","author":"Alkatout","year":"2011","journal-title":"Urol. Oncol. Semin. Orig. Investig."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/2921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:25Z","timestamp":1760030425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/2921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,23]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14092921"],"URL":"https:\/\/doi.org\/10.3390\/jcm14092921","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,23]]}}}