PMID- 25688737
OWN - NLM
STAT- MEDLINE
DCOM- 20150513
LR  - 20220408
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 112
IP  - 6
DP  - 2015 Mar 17
TI  - Frequency and prognostic significance of p16(INK4A) protein overexpression and 
      transcriptionally active human papillomavirus infection in laryngeal squamous 
      cell carcinoma.
PG  - 1098-104
LID - 10.1038/bjc.2015.59 [doi]
AB  - BACKGROUND: Human papillomavirus (HPV) infection is a powerful prognostic 
      biomarker in a subset of head and neck squamous cell carcinomas, specifically 
      oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such 
      as the larynx, remains unconfirmed. METHODS: We evaluated a cohort of 324 
      laryngeal squamous cell carcinoma (LSCC) patients for the expression of 
      p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 
      and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and 
      HPV status were correlated with clinicopathological features and outcomes. 
      RESULTS: Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. 
      Females and node-positive patients were more likely to be p16 positive (P<0.05). 
      There were no other significant clinical or demographic differences between 
      p16-positive and -negative cases. There was no difference in overall survival 
      (OS) between p16-positive and -negative patients with 2-year survival of 79% in 
      each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically 
      significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 
      66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 
      0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all 
      of which were p16 IHC positive. There was no statistically significant difference 
      in OS between patients with HPV RNA ISH-positive tumours compared with -negative 
      tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 
      0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 
      0.19-2.03, P=0.43). CONCLUSIONS: p16 overexpression is infrequent in LSCC and the 
      proportion of cases with high-risk HPV transcripts is even lower. There are no 
      statistically significant correlations between p16 IHC or HPV RNA ISH status and 
      OS or disease outcomes.
FAU - Young, R J
AU  - Young RJ
AD  - 1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Sir 
      Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 
      Australia.
FAU - Urban, D
AU  - Urban D
AD  - 1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] 
      Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 
      Australia.
FAU - Angel, C
AU  - Angel C
AD  - 1] Sir Peter MacCallum Department of Oncology, University of Melbourne, 
      Melbourne, Australia [2] Department of Pathology, Peter MacCallum Cancer Centre, 
      Melbourne, Australia.
FAU - Corry, J
AU  - Corry J
AD  - Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, 
      Australia.
FAU - Lyons, B
AU  - Lyons B
AD  - Department of Surgery, St Vincent's Hospital, Melbourne, Australia.
FAU - Vallance, N
AU  - Vallance N
AD  - Department of Otorhinolaryngology, Monash Medical Centre, Melbourne, Australia.
FAU - Kleid, S
AU  - Kleid S
AD  - Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, 
      Australia.
FAU - Iseli, T A
AU  - Iseli TA
AD  - Department of Surgery, Melbourne University, Royal Melbourne Hospital, Melbourne, 
      Australia.
FAU - Solomon, B
AU  - Solomon B
AD  - 1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Sir 
      Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 
      Australia [3] Department of Medical Oncology, Peter MacCallum Cancer Centre, 
      Melbourne, Australia.
FAU - Rischin, D
AU  - Rischin D
AD  - 1] Sir Peter MacCallum Department of Oncology, University of Melbourne, 
      Melbourne, Australia [2] Department of Medical Oncology, Peter MacCallum Cancer 
      Centre, Melbourne, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150317
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA, Viral)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/biosynthesis/genetics
MH  - Carcinoma, Squamous Cell/genetics/metabolism/*virology
MH  - Cohort Studies
MH  - Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis/genetics
MH  - DNA, Viral/genetics
MH  - Female
MH  - Head and Neck Neoplasms/genetics/metabolism/*virology
MH  - Humans
MH  - Laryngeal Neoplasms/genetics/metabolism/*virology
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Viral/biosynthesis/genetics
MH  - Papillomaviridae/genetics/*metabolism
MH  - Papillomavirus Infections/genetics/*metabolism/virology
MH  - Prognosis
MH  - Prospective Studies
MH  - RNA, Messenger/genetics
MH  - RNA, Viral/genetics
MH  - Squamous Cell Carcinoma of Head and Neck
MH  - Transcription, Genetic
PMC - PMC4366899
EDAT- 2015/02/18 06:00
MHDA- 2015/05/15 06:00
PMCR- 2016/03/17
CRDT- 2015/02/18 06:00
PHST- 2014/09/24 00:00 [received]
PHST- 2014/11/18 00:00 [revised]
PHST- 2015/01/19 00:00 [accepted]
PHST- 2015/02/18 06:00 [entrez]
PHST- 2015/02/18 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
PHST- 2016/03/17 00:00 [pmc-release]
AID - bjc201559 [pii]
AID - 10.1038/bjc.2015.59 [doi]
PST - epublish
SO  - Br J Cancer. 2015 Mar 17;112(6):1098-104. doi: 10.1038/bjc.2015.59.