RB1, p16, and Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma

• Published in: Head & neck pathology (Totowa, N.J.) N.J.), 2021-12, Vol.15 (4), p.1109-1118
• Main Authors: Berdugo, Jérémie, Rooper, Lisa M., Chiosea, Simion I.
• Format: Article
• Language: English
• Subjects: Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Dentistry; Disease-Free Survival; DNA, Viral - genetics; E2F1 Transcription Factor - genetics; Female; Genome, Viral; High-Throughput Nucleotide Sequencing; Humans; In Situ Hybridization, Fluorescence; Male; Medicine; Medicine & Public Health; Middle Aged; Oral and Maxillofacial Surgery; Original Paper; Oropharyngeal Neoplasms - mortality; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - virology; Otorhinolaryngology; Papillomaviridae - genetics; Pathology; RNA, Viral - genetics
• ISSN: 1936-0568; 1936-055X; 1936-0568
• DOI: 10.1007/s12105-021-01317-5

While P16 immunohistochemistry (IHC) is a well-established surrogate marker of Human Papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC), Retinoblastoma 1 (RB1) loss may lead to p16 overexpression in the absence of HPV. We determined the proportion of p16-positive/HPV-negative OSCC with RB1 loss and other alterations in RB1/p16 pathway, and tested RB1 IHC as a prognostic biomarker for OSCC, along with the 8th edition of AJCC staging manual. P16 and RB1 IHC and HPV DNA in situ hybridization (ISH) were performed on 257 OSCC. High risk HPV RNA ISH, RB1 fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) were done on p16-positive/HPV DNA ISH-negative OSCC. Disease free survival (DFS) was used as an endpoint. In the entire cohort and in p16-positive ( n  = 184) and p16-negative ( n  = 73) subgroups, AJCC 8th edition staging correlated with DFS ( p