TY - JOUR
T1 - Concordance of p16INK4a and E6*I mRNA among HPV-DNA-Positive Oropharyngeal, Laryngeal, and Oral Cavity Carcinomas from the ICO International Study
AU - Mena, Marisa
AU - Wang, Xin
AU - Tous, Sara
AU - Quirós, Beatriz
AU - Clavero, Omar
AU - Alejo, Maria
AU - Morey, Francisca
AU - Taberna, Miren
AU - León i Vintró, Xavier
AU - Lloveras Rubio, Belén
AU - Alos, Llucìa
AU - Mehanna, Hisham
AU - Quint, Wim
AU - Pawlita, Michael
AU - Tommasino, Massimo
AU - Pavón, Miguel Angel
AU - Muñoz, Nubia
AU - De Sanjose, Silvia
AU - Bosch, Francesc Xavier
AU - Alemany, Laia
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Human papillomavirus
KW - Head and neck cancer
KW - Biomarkers
U2 - 10.3390/cancers14153787
DO - 10.3390/cancers14153787
M3 - Article
C2 - 35954451
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 15
ER -