PMID- 33830464
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220409
IS  - 1936-0568 (Electronic)
IS  - 1936-055X (Print)
IS  - 1936-055X (Linking)
VI  - 15
IP  - 4
DP  - 2021 Dec
TI  - RB1, p16, and Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma.
PG  - 1109-1118
LID - 10.1007/s12105-021-01317-5 [doi]
AB  - 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 < 0.01). RB1 IHC showed RB1 loss in p16-positive 
      OSCC only (79/184, 43%). RB1 loss by IHC is associated with a better DFS, without 
      providing additional prognostic information for patients with p16-positive OSCC. 
      HPV RNA ISH was positive in 12 of 14 HPV DNA ISH-negative cases. RB1 IHC showed 
      loss in 10 of 15 HPV DNA ISH-negative cases and in 1 of 2 HPV RNA ISH-negative 
      cases. Overall, only one case of p16-positive/HPV RNA ISH-negative OSCC showed 
      RB1 loss by IHC (1/184, 0.5%). Of the 10 p16-positive and HPV DNA ISH-negative 
      cases with RB1 loss by IHC, 2 had RB1 hemizygous deletion and 3 showed Chromosome 
      13 monosomy by FISH. No RB1 mutations were detected by NGS. Other molecular 
      alterations in p16-positive/HPV DNA ISH-negative cases included TP53 and TERT 
      mutations and DDX3X loss. HPV-independent RB1 inactivation rarely results in 
      false positive p16 IHC. RB1 inactivation by high risk HPV E7 oncoprotein may 
      co-exist with RB1 deletion. RB1 loss is a favorable prognosticator and occurs 
      exclusively in p16-positive OSCC. The 8th edition of the AJCC staging manual 
      satisfactorily predicts DFS of OSCC patients.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Berdugo, Jeremie
AU  - Berdugo J
AD  - Department of Pathology, University of Montreal, Montreal, QC, Canada.
FAU - Rooper, Lisa M
AU  - Rooper LM
AD  - Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, 
      USA.
FAU - Chiosea, Simion I
AU  - Chiosea SI
AUID- ORCID: 0000-0002-5766-8779
AD  - Department of Pathology, Presbyterian University Hospital, University of 
      Pittsburgh Medical Center, A610.3, 200 Lothrop St., Pittsburgh, PA, 15213, USA. 
      chioseasi@upmc.edu.
LA  - eng
PT  - Journal Article
DEP - 20210408
PL  - United States
TA  - Head Neck Pathol
JT  - Head and neck pathology
JID - 101304010
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA, Viral)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Carcinoma, Squamous Cell/mortality/*pathology/virology
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics
MH  - DNA, Viral/genetics
MH  - Disease-Free Survival
MH  - E2F1 Transcription Factor/*genetics
MH  - Female
MH  - Genome, Viral
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Oropharyngeal Neoplasms/mortality/*pathology/virology
MH  - Papillomaviridae/*genetics
MH  - RNA, Viral/genetics
PMC - PMC8633196
OTO - NOTNLM
OT  - AJCC 8th edition staging classification
OT  - Human papillomavirus
OT  - Oropharyngeal squamous cell carcinoma
OT  - P16
OT  - RB1
OT  - Retinoblastoma 1
COIS- No conflict of interest to disclose.
EDAT- 2021/04/09 06:00
MHDA- 2022/03/23 06:00
PMCR- 2022/04/08
CRDT- 2021/04/08 12:48
PHST- 2021/02/05 00:00 [received]
PHST- 2021/03/16 00:00 [accepted]
PHST- 2021/04/09 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/04/08 12:48 [entrez]
PHST- 2022/04/08 00:00 [pmc-release]
AID - 10.1007/s12105-021-01317-5 [pii]
AID - 1317 [pii]
AID - 10.1007/s12105-021-01317-5 [doi]
PST - ppublish
SO  - Head Neck Pathol. 2021 Dec;15(4):1109-1118. doi: 10.1007/s12105-021-01317-5. Epub 
      2021 Apr 8.