To date, there are no good preclinical models for HPV disease. Dr. Trimble’s lab has developed methods to query the cervical mucosal microenvironment at a molecular level, in very small human tissue specimens. Dr. Trimble’s lab has designed and conducted a series of early phase, investigator-initiated clinical trials testing immunotherapies to treat incipient malignancies caused by HPV. Insights gained from longitudinal subject-matched tissue specimens have informed the design and choice of vaccine for each subsequent clinical trial. Data derived from longitudinal, prospectively-obtained, subject-matched specimens obtained from their protocol participants will be discussed.