Concordance of p16INK4a and E6*I mRNA among HPV-DNA-Positive Oropharyngeal, Laryngeal, and Oral Cavity Carcinomas from the ICO International Study
Mena, Marisa (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. Instituto de Salud Carlos III)
Wang, Xin (Institut d'Investigació Biomèdica de Bellvitge)
Tous, Sara (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. Instituto de Salud Carlos III)
Quirós, Beatriz (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. Instituto de Salud Carlos III)
Clavero, Omar (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. Instituto de Salud Carlos III)
Alejo, María (Hospital General de l'Hopitalet. Pathology Department)
Morey, Francisca (Institut d'Investigació Biomèdica de Bellvitge)
Taberna, Miren (Institut d'Investigació Biomèdica de Bellvitge)
León i Vintró, Xavier (Institut d'Investigació Biomèdica Sant Pau)
Lloveras Rubio, Belén (Hospital del Mar. Pathology Department)
Alos, Llucìa (Hospital Clínic i Provincial de Barcelona)
Mehanna, Hisham (Institute of Head and Neck Studies and Education. University of Birmingham)
Quint, Wim (DDL Diagnostic Laboratory)
Pawlita, Michael (Division of Molecular Diagnostics of Oncogenic Infections. Research Program Infection. Inflammation and Cancer. German Cancer Research Center (DKFZ))
Tommasino, Massimo (Infections and Cancer Biology Group. International Agency for Research on Cancer (IARC))
Pavón, Miguel Angel (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. Instituto de Salud Carlos III)
Muñoz, Nubia (National Cancer Institute)
De Sanjose, Silvia (ISGlobal)
Bosch, Francesc Xavier (Universitat Oberta de Catalunya)
Alemany, Laia (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. Instituto de Salud Carlos III)

Fecha:	2022
Resumen:	Background: Tests or test algorithms for diagnosing HPV-driven oral cavity and laryngeal head and neck carcinomas (HNC) have not been yet validated, and the differences among oral cavity and laryngeal sites have not been comprehensively evaluated. We aimed to assess the utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC) and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16 immunohistochemistry, taking E6*I mRNA detection as the reference standard. Methods: Formalin-fixed paraffin-embedded OCC, OPC, and LC carcinomas were collected from pathology archives in 29 countries. All samples were subjected to histopathological evaluation, DNA quality control, and HPV-DNA detection. All HPV-DNA-positive samples (including 78 OCC, 257 OPC, and 51 LC out of 3680 HNC with valid HPV-DNA results) were also tested for p16 immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16: (a) >25%, (b) >50%, and (c) ≥70%. The concordance of p16 and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was assessed. Results: A total of 78 OCC, 257 OPC, and 51 LC were HPV-DNA-positive and further tested for p16 and E6*I mRNA. The percentage of concordance between p16 (cutoff ≥ 70%) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was 79. 5% (95% CI 69. 9-89. 1%), 82. 1% (95% CI 77. 2-87. 0%), and 56. 9% (95% CI 42. 3-71. 4%), respectively. A p16 cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16 cutoffs, the percentage of discordant cases was higher for HPV16- than HPV-non16-positive cases. Conclusions: The diagnostic algorithm of HPV-DNA testing followed by p16 immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16 expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. Our study provides new insights into the use HPV-DNA, p16, and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16 cutoffs to be used. More studies are warranted to clarify the role of p16 and HPV status in both OPC and non-OPC HNC.
Ayudas:	Ministerio de Ciencia e Innovación 08/1535 Ministerio de Ciencia e Innovación PI11/02096 Ministerio de Ciencia e Innovación PI11/02104 Instituto de Salud Carlos III CB06/02/007 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1085 European Commission 282562
Nota:	Altres ajuts: Generalitat de Catalunya (CERCA Programme); European Regional Development Fund (FEDER "A way to build Europe"); Asociación Española Contra el Cancer; Stichting Pathologie Ontwikkeling en Onderzoek (SPOO) foundation (The Netherlands); Sanofi Pasteur MSD and Merck & Co, Inc.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Human papillomavirus ; Head and neck cancer ; Biomarkers
Publicado en:	Cancers, Vol. 14 Núm. 15 (august 2022) , p. 3787, ISSN 2072-6694

DOI: 10.3390/cancers14153787
PMID: 35954451

12 p, 2.6 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
Artículos > Artículos de investigación
Artículos > Artículos publicados