{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:11:40Z","timestamp":1792192300444,"version":"4.4.0"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Cooperatio Medical Diagnostics"],"award-info":[{"award-number":["Cooperatio Medical Diagnostics"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022761","name":"Fakultn\u00ed Thomayerova nemocnice","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022761","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016366","name":"V\u0161eobecn\u00e1 Fakultn\u00ed Nemocnice v Praze","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Penile carcinoma is a rare but psychosexually devastating malignancy associated with the worst prognosis among male-specific genitourinary malignancies (prostate, testicular, and penile cancer). In addition to loss of the organ itself, patients frequently suffer from chronic lymphedema following inguinal lymph node dissection. Despite advances in oncology, the prognosis of penile cancer has not substantially improved over the past half century, and the disease has long remained underrepresented in basic research, clinical trials, and patient advocacy initiatives. During the 2020s, however, the situation has begun to change, with an increasing number of large studies and the emergence of the first meta-analyses focused on penile carcinoma. Current morphological and molecular studies aim to identify features of aggressive disease that may guide treatment escalation or de-escalation and thereby improve patients\u2019 quality of life. This review summarizes recent advances in the field, with particular emphasis on prognostic parameters accessible by routine histopathological examination. In many settings, simple pathological biomarkers may provide greater clinical utility than expensive molecular analyses. Special attention is devoted to the interplay between morphology, HPV status, immune microenvironment, and molecular alterations. The review discusses histological grading, morphological subtypes, HPV status and its correlation with morphology and mutational profiles, the prognostic significance of tumor-infiltrating lymphocytes and PD-L1 expression, and particularly tumor budding, which is strongly associated with aberrant p53 status and adverse prognosis. Future perspectives include refinement of penile carcinoma classification into: 1) HPV-associated, 2) HPV-independent, p53 wild-type, and 3) HPV independent, p53-altered tumors. Additional parameters with potential to improve prognostic stratification include tumor budding and the subjectively assessed peritumoral lymphocytic rim (brisk versus non-brisk), both of which appear suitable for routine reporting alongside conventional staging and grading. To sum up: Morphology really matters even in the molecular era.<\/jats:p>","DOI":"10.3389\/fonc.2026.1890741","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:42:12Z","timestamp":1784695332000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From biology to morphology and treatment: the current role of pathology in penile cancer \u2014 a narrative review"],"prefix":"10.3389","volume":"16","author":[{"given":"Jan","family":"Hrudka","sequence":"first","affiliation":[{"name":"Department of Pathology, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette","family":"Zavillov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady","place":["Prague, Czechia"]},{"name":"Department of Urology, Third Faculty of Medicine, Charles University, Thomayer University Hospital","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hojn\u00fd","sequence":"additional","affiliation":[{"name":"Department Pathology, First Faculty of Medicine, Charles University, General University Hospital","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Waldauf","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care Medicine, Third Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radoslav","family":"Mat\u011bj","sequence":"additional","affiliation":[{"name":"Department of Pathology, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady","place":["Prague, Czechia"]},{"name":"Department Pathology, First Faculty of Medicine, Charles University, General University Hospital","place":["Prague, Czechia"]},{"name":"Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University, Thomayer University Hospital","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103481","article-title":"Penile cancer: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"9","author":"Muneer","year":"2024","journal-title":"ESMO Open"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2196\/34874","article-title":"Global pattern and trends in penile cancer incidence: Population-based study","volume":"8","author":"Fu","year":"2022","journal-title":"JMIR Public Health Surveill"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1457006","article-title":"Treatment approaches in advanced penile cancer: targeted therapies and immunotherapy","volume":"14","author":"Benjamin","year":"2024","journal-title":"Front Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41443-024-00842-5","article-title":"Long-term outcomes of penile squamous cell carcinoma in men age \u226450 years old compared with men >50 years old from a single tertiary referral centre: a propensity score matched analysis","volume":"37","author":"Pang","year":"2025","journal-title":"Int J Impot Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.02.027","article-title":"European association of urology-American society of clinical oncology collaborative guideline on penile cancer: 2023 update","volume":"83","author":"Brouwer","year":"2023","journal-title":"Eur Urol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-5347(17)44281-9","article-title":"Penile cancer: relation of extent of nodal metastasis to survival","volume":"137","author":"Srinivas","year":"1987","journal-title":"J Urol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-5347(17)35221-7","article-title":"Squamous cell carcinoma of the penis. 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