Concordance of p16(INK4a) and E6*I mRNA among HPV-DNA-Positive Oropharyngeal, Laryngeal, and Oral Cavity Carcinomas from the ICO International Study


Por: Mena, M, Wang, X, Tous, S, Quiros, B, Clavero, O, Alejo, M, Morey, F, Taberna, M, Vintro, XL, Rubio, BL, Alos, L, Mehanna, H, Quint, W, Pawlita, M, Tommasino, M, Pavon, MA, Munoz, N, De Sanjose, S, Bosch, FX, Alemany, L

Publicada: 1 ago 2022
Resumen:
Simple Summary 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(INK4a) immunohistochemistry, taking E6*I mRNA detection as the reference standard, was assessed in HPV-DNA-positive formalin-fixed paraffin-embedded samples from 29 countries. The concordance of p16(INK4a) and E6*I mRNA among 78, 257, and 51 HPV-DNA-positive OCC, OPC, and LC, respectively, was moderate to substantial in OCC and OPC but only fair in LC. A different p16(INK4a) expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. We concluded that the diagnostic algorithm of HPV-DNA testing followed by p16(INK4a) immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. Our study provides new insights into the use HPV-DNA, p16(INK4a), and HPV-E6*I mRNA for diagnosing an HPV-driven head and neck carcinoma. 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(INK4a) 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(INK4a) immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16(INK4a): (a) >25%, (b) >50%, and (c) >= 70%. The concordance of p16(INK4a) 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(INK4a) and E6*I mRNA. The percentage of concordance between p16(INK4a) (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(INK4a) cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16(INK4a) 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(INK4a) immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16(INK4a) 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(INK4a), and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16(INK4a) cutoffs to be used. More studies are warranted to clarify the role of p16(INK4a) and HPV status in both OPC and non-OPC HNC.

Filiaciones:
Mena, M:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

Wang, X:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

Tous, S:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

Quiros, B:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

Clavero, O:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

Alejo, M:
 Hosp Vic, Pathol Dept, Vic 08500, Spain

 Hosp Gen Hop, Pathol Dept, Barcelona 08908, Spain

Morey, F:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

Taberna, M:
 Catalan Inst Oncol ICO IDIBELL, Oncol Dept, ONCOBELL, Barcelona 08908, Spain

Vintro, XL:
 Hosp Santa Creu & Sant Pau, Otorhinolaryngol Dept, Barcelona 08026, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Madrid 28029, Spain

Rubio, BL:
 Hosp del Mar, Pathol Dept, Barcelona 08003, Spain

Alos, L:
 Hosp Clin Barcelona, Pathol Dept, Barcelona 08036, Spain

Mehanna, H:
 Univ Birmingham, Inst Head & Neck Studies & Educ, Birmingham B15 2TT, W Midlands, England

Quint, W:
 DDL Diagnost Lab, NL-2288 ER Rijswijk, Netherlands

Pawlita, M:
 German Canc Res Ctr, Res Program Infect Inflammat & Canc, Div Mol Diagnost Oncogen Infect, D-69120 Heidelberg, Germany

Tommasino, M:
 Int Agcy Res Canc IARC, Infect & Canc Biol Grp, F-69372 Lyon, France

Pavon, MA:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

Munoz, N:
 Natl Canc Inst, Bogota 111511, Colombia

De Sanjose, S:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

 ISGlobal, Barcelona 08036, Spain

Bosch, FX:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain

 Univ Oberta Catalunya, Barcelona 08035, Spain

Alemany, L:
 Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Barcelona 08908, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid 28029, Spain
ISSN: 20726694
Editorial
MDPI, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 14 Número: 15
Páginas:
WOS Id: 000839132200001
ID de PubMed: 35954451
imagen gold, Green Published, Gold, Green

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