IADR Abstract Archives
Significance of HPV and Circadian Clock Dysregulation in Oral Cancer
Objectives: Oral Cancer (OC) is a deadly disease with a 5-year disease-survival of a dismal 57%, due to late diagnosis. HPV infection is a key risk factor for OC within North American populations, including Saskatchewan. Additionally, our group and others have found that dysregulation of the circadian clock mechanism is prominent in OC but the exact roles remain unclear. Our group has also showed that antacid medications i.e. Proton Pump Inhibitors (PPIs) may improve OC outcome by effective inhibition of the gastric Vacuolar-H+-ATPases. Objectives: Our aim is to elucidate the differential actions of PPIs on the HPV(+) vs. HPV(-) carcinoma-derived cell lines and the links with clock genes dysregulation in OC. Our aim is also to improve diagnosis and prognosis of OC using novel salivary tests that detect HPV and circadian clock profiles.
Methods: We use an automated, programmable USB device (VolTRAX, Nanopore Technologies) that allows the separate sample and library preparation processes to be performed sequentially. Diagnosis of HPV is performed in less than one day by combining the VolTRAX device with the MinION Nanopore sequencer, allowing fully automated sequencing. We are also using melatonin saliva measurements to evaluate circadian clock dysregulation in OC patients. HPV and circadian clock salivary profiles are then correlated with HPV and clock genes expression within OC biopsies. Finally, the action of PPIs on HPV and clock genes expression in relation to disease outcome is examined in animal models and patient cohorts.
Results: Our data suggest that circadian clock is dysregulated in OC and this dysregulation correlates with OC outcome and biological characteristics. HPV status is also found directly related to OC outcome. Rapid identification of HPV infection (HPV16 E6 and E7 oncoproteins), HPV-DNA integration and detection of clock genes dysregulation in saliva are novel indicators of OC prognosis. The effects of PPIs can also be monitored by evaluating HPV and circadian clock status.
Conclusions: We suggest that a comprehensive, real-time HPV analysis and a saliva-based evaluation of circadian clock dysregulation can enhance diagnosis and prognosis of OC. These studies can also improve monitoring of OC patients, prior and after antacid medication and/or routine therapeutic approaches.
Methods: We use an automated, programmable USB device (VolTRAX, Nanopore Technologies) that allows the separate sample and library preparation processes to be performed sequentially. Diagnosis of HPV is performed in less than one day by combining the VolTRAX device with the MinION Nanopore sequencer, allowing fully automated sequencing. We are also using melatonin saliva measurements to evaluate circadian clock dysregulation in OC patients. HPV and circadian clock salivary profiles are then correlated with HPV and clock genes expression within OC biopsies. Finally, the action of PPIs on HPV and clock genes expression in relation to disease outcome is examined in animal models and patient cohorts.
Results: Our data suggest that circadian clock is dysregulated in OC and this dysregulation correlates with OC outcome and biological characteristics. HPV status is also found directly related to OC outcome. Rapid identification of HPV infection (HPV16 E6 and E7 oncoproteins), HPV-DNA integration and detection of clock genes dysregulation in saliva are novel indicators of OC prognosis. The effects of PPIs can also be monitored by evaluating HPV and circadian clock status.
Conclusions: We suggest that a comprehensive, real-time HPV analysis and a saliva-based evaluation of circadian clock dysregulation can enhance diagnosis and prognosis of OC. These studies can also improve monitoring of OC patients, prior and after antacid medication and/or routine therapeutic approaches.