PMID- 14506739
OWN - NLM
STAT- MEDLINE
DCOM- 20031107
LR  - 20220321
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 107
IP  - 3
DP  - 2003 Nov 10
TI  - A subset of head and neck squamous cell carcinomas exhibits integration of HPV 
      16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in 
      p53 exons 5-8.
PG  - 394-400
AB  - Besides well-known risk factors such as tobacco use and alcohol consumption, 
      oncogenic human papillomavirus (HPV) infection also has recently been suggested 
      to promote head and neck tumorigenesis. HPV is known to cause cancer by 
      inactivation of cell cycle regulators p53 and pRb via expression of viral 
      oncoproteins E6 and E7. This indicates that p53 mutations are not a prerequisite 
      in HPV-induced tumor development. However, discrepancy exists with respect to the 
      frequency of head and neck squamous cell carcinomas (HNSCC) harboring DNA of 
      oncogenic HPV and the fraction of these tumors showing p53 mutations. In our 
      study, we examined the frequency of HNSCC demonstrating HPV 16/18 integration as 
      identified by fluorescence in situ hybridization (FISH) and investigated their 
      p53 (mutation) status by immunohistochemistry and single-strand conformation 
      polymorphism (SSCP) analysis of exons 5-8. Paraffin-embedded, archival biopsy 
      material from 27 premalignant mucosal lesions and 47 cases of HNSCC were 
      analyzed. Ten of the 47 (21%) HNSCC unequivocally exhibited HPV 16 integration, 
      including 8 of 12 (67%) tonsillar carcinomas. This is supported by the 
      immunohistochemical detection of p16(INK4A) overexpression in all 10 HPV-positive 
      tumors. Although FISH is considered to be less sensitive than PCR-based methods 
      for HPV detection, our data clearly demonstrate clonal association of HPV with 
      these tumors, as illustrated by the presence of integrated HPV 16 in both the 
      primary tumor and their metastases in 2 patients. In contrast, HPV 16/18 DNA 
      could not be detected in the premalignant lesions. In 30 of 47 (64%), HNSCC 
      accumulation of p53 was observed, including 8 of the 10 HPV-positive carcinomas. 
      However, in none of the latter cases could mutations in exons 5-8 be identified, 
      except for a polymorphism in codon 213 of exon 6 in one patient. Evaluation of 
      clinical data revealed a significant inverse relation between tobacco use with or 
      without alcohol consumption, and HPV positivity of the tumors.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Hafkamp, Harriet C
AU  - Hafkamp HC
AD  - Research Institute GROW, Department of Otorhinolaryngology and Head and Neck 
      Surgery, University Hospital Maastricht, Maastricht, The Netherlands.
FAU - Speel, Ernst J M
AU  - Speel EJ
FAU - Haesevoets, Annick
AU  - Haesevoets A
FAU - Bot, Fredrik J
AU  - Bot FJ
FAU - Dinjens, Winand N M
AU  - Dinjens WN
FAU - Ramaekers, Frans C S
AU  - Ramaekers FC
FAU - Hopman, Anton H N
AU  - Hopman AH
FAU - Manni, Johannes J
AU  - Manni JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA, Viral)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/chemistry/pathology/*virology
MH  - Cyclin-Dependent Kinase Inhibitor p16/*analysis
MH  - DNA, Viral/analysis
MH  - Exons
MH  - Female
MH  - Head and Neck Neoplasms/chemistry/pathology/*virology
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Papillomaviridae/*genetics
MH  - Precancerous Conditions/virology
MH  - Risk Factors
MH  - Tumor Suppressor Protein p53/*analysis
MH  - *Virus Integration
EDAT- 2003/09/25 05:00
MHDA- 2003/11/08 05:00
CRDT- 2003/09/25 05:00
PHST- 2003/09/25 05:00 [pubmed]
PHST- 2003/11/08 05:00 [medline]
PHST- 2003/09/25 05:00 [entrez]
AID - 10.1002/ijc.11389 [doi]
PST - ppublish
SO  - Int J Cancer. 2003 Nov 10;107(3):394-400. doi: 10.1002/ijc.11389.