Mate pair sequencing of oropharyngeal squamous cell carcinomas reveals that HPV integration occurs much less frequently than in cervical cancer.
BACKGROUND
Human papillomavirus (HPV) is now recognized to be very important in the pathogenesis of oropharyngeal squamous cell carcinoma (OPSCC). It is not clear yet whether the physical status of HPV in OPSCC is similar to what is found in cervical cancer.


METHODS
We performed genome-wide mate pair next generation sequencing from 20 OPSCCs patients, thirteen of which were positive for HPV16 to determine the HPV physical status and its relationship to HPV oncogene E6 and E7 expression.


RESULTS
This high throughput approach detected HPV integration events and also determined the bridged HPV coverage in each sample. Two of the HPV16-positive OPSCCs had HPV integration and one of the HPV16-negative OPSCCs had an HPV26 integration. We mapped the site of integration in the HPV genome in all integration events and the integrations were located at E1, E5, E6 and L2 region respectively. One HPV positive OPSCC had two integration events but also had a very high bridged HPV coverage, while the other two just had HPV integrated into the human genome.


CONCLUSIONS
Our results are thus different from what is routinely observed in cervical cancer where HPV is almost always integrated into the human genome with loss of episomal HPV sequences. Thus more investigation should be carried out to study how episomal HPV alone can contribute to the development of most OPSCCs.
Division of Experimental Pathology, Mayo Clinic, Rochester, MN, United States.
Ge
G
Gao
Biomarker Discovery Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United States.
Sarah H
SH
Johnson
Division of Otolaryngology, Mayo Clinic, Rochester, MN, United States.
Jan L
JL
Kasperbauer
Mayo Medical Genome Facility, Mayo Clinic, Rochester, MN, United States.
Bruce W
BW
Eckloff
Division of Otolaryngology, Mayo Clinic, Rochester, MN, United States.
Nicole M
NM
Tombers
Biomarker Discovery Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United States.
George
G
Vasmatzis
Division of Experimental Pathology, Mayo Clinic, Rochester, MN, United States. Electronic address: smith.david@mayo.edu.
David I
DI
Smith
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D017422:Sequence Analysis, DNA / Q000379:methods*; D002583:Uterine Cervical Neoplasms; D016662:Virus Integration / Q000235:genetics*
D004279:DNA, Viral
HPV integration; Mate pair sequencing; OPSCC