Jennifer Webster-Cyriaque, DDS, PhD, Professor, School of Dentistry and School of Medicine, University of North Carolina, was a key member of the Oral HIV/AIDS Research Alliance (OHARA) which was funded by the National Institute for Dental and Cranial Research (NIDCR) and the National Institute of Allergy and Infectious Disease (NIAID). From 2006 to 2013, OHARA worked in collaboration with the ACTG Network to focus on oral opportunistic infection, including research specifically targeting the Human Papilloma Virus (HPV). In all, there were nine OHARA clinical trials that have contributed to the development of a comprehensive oral infection/disease database with HIV/AIDS correlates. An HIV/AIDS oral specimen bank of over 30,000 aliquots and over 1000 fungal aliquots was also developed and will provide valuable material for future epidemiologic and biological research questions.
“The ACTG Network is a special group of individuals all of whom are passionate about making a difference in the global HIV/AIDS epidemic. We had wonderful relationships with our clinical trials specialists and our ACTG colleagues, several of whom were part of the OHARA collaborative group,” said Dr. Webster-Cyriaque. “The ACTG Network was always very inclusive, making us a part of all relevant committees from leadership to laboratory. I have to say, working with the ACTG Network and with OHARA was overall a wonderful experience.”
OHARA provided the first opportunity for systematic clinical trials in the context of oral HIV/AIDS and provided important insights into oral natural history, oral diagnostics and potential low cost interventions. In order to answer oral objectives for HPV related trials, A5240, A5246 and A5272, Dr. Webster-Cyriaque, alongside the OHARA virology team, developed assays targeting the most common forms of HPV’s. They were then adapted into a quadrivalent vaccine, a multiplex quantitative assay for types 6, 11, 16 and 18. . A degenerate quantitative assay was developed and run in parallel that targeted a conservative region of the virus that would potentially pick up any oral HPV. These first experiments formed the basis of the point of care assay that is now being developed as a biochip with InSilixa Inc., a California based DNA testing firm. This is a collaborative effort with InSilixa Inc. under the National Institutes of Health grant #1R43DE025441-01 and it is sponsored by the NIDCR.
“This is exciting news because persistent detection of high risk HPV is the most significant risk factor for cancer development,” said Dr. Webster-Cyriaque. “This test will potentially allow quantitative point of care detection for HPV in oral and other compartments. The point of care aspect is particularly appealing and I am looking forward to harnessing the strength of the biochip.”
Opportunistic infections were critical to OHARA’s focus and the ACTG Network values everything learned during OHARA/ACTG clinical trials, as the mouth is a great monitor for systemic disease.
“We are very pleased that research conducted at our sites is now being furthered by other organizations. Understanding infectious disease pathogenesis in the oral cavity provides a window into lesions and maladies detected in the mouth, ” said Daniel Kuritzkes, MD, ACTG Network Chair and Co-Principal Investigator and Chief, Division of Infectious Diseases at Brigham and Women’s Hospital. “It is our hope that in the future patients will be administered a test like the one developed by Dr. Webster-Cyriaque by clinicians in order to assess current and future HPV risk.”
Dr. Webster-Cyriaque plans to continue her research by following lines of study that will help to better understand oral disease in the context of immune compromise and the different roles viruses play in the development of oral disease. She hopes to fully understand how the oral microbiota facilitate viral life cycles, influence systemic disease and work to develop interventions and diagnostics that result in improved quality of life for affected individuals. Additionally, she hopes to work with the ACTG Network in the future and to continue collaboration outside of the formal OHARA structure.