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Project PI17/00772; Valor de la deteccion del ARNm de los biomarcadores CDKN2A, MKi67, TOP2A en la prevencion secundaria del cancer de cuello de utero, funded by Instituto de Salud Carlos III and co-funded by the European Union (ERDF) A way to make Europe. ISGlobal receives support from the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019-2023 Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

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Martinez Puchol, AnabelAuthorDel Pino MAuthorMarimon LAuthorDiaz-Mercedes SAuthorRodrigo-Calvo MtAuthorAjami TAuthorMartinez AAuthorReig OAuthorRibal MjAuthorCorral-Molina JmAuthorRibera-Cortada IAuthor

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Article

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

Publicated to:American Journal Of Surgical Pathology. 46 (8): 1071-1077 - 2022-08-01 46(8), DOI: 10.1097/pas.0000000000001885

Authors: Guerrero, Jose; Trias, Isabel; Veloza, Luis; del Pino, Marta; Garcia, Adriana; Marimon, Lorena; Diaz-Mercedes, Sherley; Rodrigo-Calvo, Maria T; Alos, Silvia; Ajami, Tarek; Parra-Medina, Rafael; Martinez, Antonio; Reig, Oscar; Ribal, Maria J; Corral-Molina, Juan M; Ordi, Jaume; Ribera-Cortada, Inmaculada; Rakislova, Natalia

Affiliations

August Pi & Sunyer Biomed Res Inst IDIBAPS, Barcelona, Spain - Author
Hlth Sci Univ Fdn, Res Inst, Dept Pathol, Bogota, Colombia - Author
Hosp Clin Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain - Author
Lausanne Univ, Lausanne Univ Hosp, Inst Pathol, Lausanne, Switzerland - Author
NULL - Author
Univ Barcelona, Dept Pathol, Barcelona, Spain - Author
Univ Barcelona, Inst Gynecol Obstet & Neonatol, Fac Med, Hosp Clin,August Pi & Sunyer Biomed Res Inst IDIB, Barcelona, Spain - Author
Univ Barcelona, Inst Hematol & Oncol Dis, Hosp Clin Barcelona, Barcelona, Spain - Author
Univ Barcelona, Urooncol Unit, Barcelona, Spain - Author
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Abstract

Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83?y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPV-associated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPV-associated HSIL.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

associationclassificationdermatosesdifferentiated penile intraepithelial neoplasiahpvhuman-papillomaviruslesionsmutationsp16p16(ink4a)p53pathologyvariantsAgedAged, 80 and overAlcohol consumptionArticleCarcinoma in situCell junctionCigarette smokingClinical featureCyclin dependent kinase inhibitor 2aCyclin-dependent kinase inhibitor p16Differentiated penile intraepithelial neoplasiaEpidermisErythemaFemaleGeneticsGiant condyloma acuminatumHistopathologyHpvHumanHuman tissueHumansImiquimodImmunohistochemistryInvasive carcinomaKeratinocyteKi 67 antigenLichen sclerosus et atrophicusMajor clinical studyMaleMetabolismNeurodermatitisP16P53PapillomaviridaePapillomavirus infectionPapillomavirus infectionsPathologyPenile cancerPenile intraepithelial neoplasiaPenile neoplasmsPenis tumorPhimosisPrepuceProtein p16Protein p53Skin neoplasmsSkin tumorSquamous intraepithelial lesionsSquamous-cell carcinomaTumor suppressor protein p53UlcerVery elderlyVirus dnaVulva tumorVulvar neoplasms

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal American Journal Of Surgical Pathology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 15/213, thus managing to position itself as a Q1 (Primer Cuartil), in the category Surgery. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.29, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-27, the following number of citations:

  • WoS: 2
  • Scopus: 3
  • Europe PMC: 1

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-27:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 13.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 13 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Australia; Colombia; Switzerland; United States of America.