Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type
department or school: Medicine, Faculty of
department or school: Non UBC
department or school: Obstetrics and Gynaecology, Department of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
identifier citation: Cancers 16 (24): 4216 (2024)
contributor: Vancouver General Hospital
contributor: University of British Columbia. Division of Medical Oncology
creator: Horn, Lars-Christian
creator: Brambs, Christine E.
creator: Alfaraidi, Mona
creator: Gilks, C. Blake
creator: Hoang, Lien N.
creator: Singh, Naveena
creator: Hiller, Grit Gesine Ruth
creator: Hering, Kathrin
creator: McAlpine, Jessica N.
creator: Jamieson, Amy
creator: Aktas, Bahriye
creator: Dornhöfer, Nadja
creator: Höhn, Anne Kathrin
issued: 2025-01-10T17:36:29Z
issued: 2024-12-18
description: Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to highrisk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53, but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/90096
note: Citation: Horn, L.-C.; Brambs, C.E.;Gilks, B.; Hoang, L.; Singh, N.; Hiller,G.G.R.; Hering, K.; McAlpine, J.N.;Jamieson, A.; Alfaraidi, M.; et al.Molecular Subtypes of VulvarSquamous Cell Carcinoma: TheSignificance of HPV-Independent/p53Wild Type. Cancers 2024, 16, 4216.https://doi.org/10.3390/cancers16244216Academic Editor: XavierSastre-GarauReceived: 22 October 2024Revised: 11 December 2024Accepted: 12 December 2024Published: 18 December 2024Copyright: © 2024 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).ReviewMolecular Subtypes of Vulvar Squamous Cell Carcinoma: TheSignificance of HPV-Independent/p53 Wild TypeLars-Christian Horn 1,* , Christine E. Brambs 2 , Blake Gilks 3, Lien Hoang 3, Naveena Singh 3,Grit Gesine Ruth Hiller 1, Kathrin Hering 4, Jessica N. McAlpine 5 , Amy Jamieson 5, Mona Alfaraidi 3,6,Bahriye Aktas 7 , Nadja Dornhöfer 7 and Anne Kathrin Höhn 11 Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig,D-04103 Leipzig, Germany; ruth.hiller@uniklinik-leipzig.de (G.G.R.H.);annekathrin.hoehn@medizin.uni-leipzig.de (A.K.H.)2 Department of Obstetrics and Gynecology, Kantonsspital Luzern, 6004 Luzern, Switzerland;christine.brambs@luks.ch3 Department of Anatomical Pathology, Vancouver General Hospital, The University of British Columbia,Vancouver, BC V5Z 1M9, Canada; blake.gilks@vch.ca (B.G.); lien.hoang@vch.ca (L.H.);naveena.singh@vch.ca (N.S.); mona.alfaraidi@vch.ca (M.A.)4 Department of Radiotherapy and Radiation Oncology, University Hospital Leipzig,D-04103 Leipzig, Germany; kathrin.hering@medizin.uni-leipzig.de5 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of BritishColumbia, Vancouver, BC V5Z 1M9, Canada; jessica.mcalpine@vch.ca (J.N.M.); amy.jamieson@vch.ca (A.J.)6 Prince …
has type: Article
is shown at: 10.14288/1.0447725
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/cancers16244216
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: vulvar cancer
subject: squamous cell carcinoma
subject: p53
subject: p16
subject: human papillomavirus
subject: molecular
subject: classification
subject: prognosis
subject: radiation therapy
subject: surgery
type: Text
identifier URI: http://hdl.handle.net/2429/90096