Abstract

MP-Seq as a powerful clinical tool for the management of cancer patients

David Smith, Professor, Mayo Clinic

Human papillomavirus (HPV) is responsible for the development of most cervical cancers. It is also found in 85% of anal cancers, and over half of penile, vulvar and vaginal cancers. HPV is also responsible for the dramatic increase in the incidence of orpharyngeal squamous cell carcinoma (OPSCC) which are cancers of the base of the tongue, tonsils and larynx. The model for how HPV causes cancer was developed from several decades of study analyzing cervical cancer where HPV is found to be integrated into the human genome in most of these cancers. We wanted to test whether that model was a valid for OPSCC so we utilized the powerful technique of mate-pair next generation sequencing (MP-Seq). This technique provides information about the physical status of HPV in each OPSCC but also provides information about genome-wide changes in these cancers. Using MP-Seq we have found that HPV only integrates into the genome in about 30% of OPSCCs. HPVs role in the development of OPSCC is therefore most likel different than what is found in cervical cancer and this virus may play different roles in the development of different OPSCCs. Each OPSCC also had multiple genomic rearrangements observed by MP-Seq and we are currently using this information to derive cancer-specific PCR primers for each OPSCC. These will then be used with digital droplet PCR (ddPCR) to follow the individual cancers response to therapy using liquid biopsy. Our results demonstrate the power of MP-Seq as a powerful clinical tool to both characterize OPSCCs and to monitor patients using ddPCR after surgery.