Mate pair sequencing of oropharyngeal squamous cell carcinomas reveals that HPV integration occurs much less frequently than in cervical cancer

• Published in: Journal of clinical virology 2014-03, Vol.59 (3), p.195-200
• Main Authors: Gao, Ge, Johnson, Sarah H, Kasperbauer, Jan L, Eckloff, Bruce W, Tombers, Nicole M, Vasmatzis, George, Smith, David I
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Allergy and Immunology; Alphapapillomavirus - genetics; Base Sequence; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - virology; DNA, Viral - genetics; Female; HPV integration; Humans; Infectious Disease; Male; Mate pair sequencing; Middle Aged; Molecular Sequence Data; OPSCC; Oropharyngeal Neoplasms - chemistry; Oropharyngeal Neoplasms - epidemiology; Oropharyngeal Neoplasms - genetics; Oropharyngeal Neoplasms - virology; Papillomavirus Infections - epidemiology; Papillomavirus Infections - genetics; Papillomavirus Infections - virology; Sequence Analysis, DNA - methods; Uterine Cervical Neoplasms; Virus Integration - genetics
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2013.12.006

Abstract 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. Study design 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. Conclusion 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.