Introduction

Every year 604,000 women are diagnosed with cervical cancer and 342,000 die from it worldwide. The overall goal of our cervical cancer SPORE is, in the next 5 years, to better reach and protect the next generation of women from oncogenic HPV infection, and to develop novel vaccines improve treatment outcomes of patients with persistent HPV infection, HPV-associated precancer, and cervical cancer. Vaccines represent the most cost-effective and successful public health intervention. We include four vaccine projects in this SPORE program based upon the success of prophylactic HPV vaccination for primary prevention of cervical cancer, and advances in understanding of cellular immunology, including the mechanisms of spontaneous viral clearance and the impact of HIV.

The intent of the Cervical Cancer SPORE Program in the next 5 years is to develop novel vaccines to improve treatment outcomes of patients with HPV- associated cervical cancer and its precursor lesions, and to better reach and protect the next generation of women from oncogenic HPV infection and its sequelae.

Therefore, there are three overarching goals in this SPORE: 1) PRIMARY PREVENTION to reduce the global incidence of cervical cancer by improving access to prophylactic vaccination through the development of a low-cost, thermostable RG1-VLP formulation that needs to be administered only once to effectively prevent infection by all oncogenic HPV types (Project 1), 2) SECONDARY PREVENTION by eliminating persistent HPV infection (Project 2) and associated precancer lesions (Project 3) using innovative therapeutic HPV vaccines, and 3) Improving CANCER TREATMENT of advanced cervical cancer to adjuvant standard of care by targeting minimal residual disease with an innovative therapeutic HPV vaccination after chemoradiation (Project 4). This program is supported by an Administrative/Communication Core (Core A), a Biostatistics/Bioinformatics Core (Core B), a Tissue/Pathology/Immunology Core (Core C), and innovates and renews membership through a Developmental Research Program (DRP) and a Career Enhancement Program (CEP). Our investigators with expertise in molecular and cellular biology, virology, immunology, pathology, medical and surgical oncology, and epidemiology of cervical cancer continue to work as a team withthe primary long-term goal of rapidly translating scientific advances made in the laboratory into novel cost-effective preventive and therapeutic strategies to reduce cervical cancer incidence, morbidity, and mortality worldwide.

Our Vision

Our vision is that the Cervical Cancer SPORE support translational academic research that does not readily fit into other funding categories or commercial endeavors. This is particularly important for cervical cancer, which has reached ‘orphan disease’ status in the US, and for which the introduction of vaccines to low-resource settings has little to attract traditional commercial entities. The Cervical Cancer SPORE thus fosters the creative and productive use of NCI extramural funding to further its translational mission to reduce the burden of cervical cancer, while uncovering fundamental principles that underpin HPV virology and cancer immunobiology.

We do this in the uniquely collaborative manner that has made the SPORE mechanism and our program so successful and effective. An example is the union of JHU and UAB to access diverse demographics and to ensure that the clinical development of the most promising HPV vaccines benefits all populations, including those most underserved and those most at risk. Critically, our SPORE has also successfully leveraged multiple industry collaborations, which are important for rapid translation and to successfully bring new treatments to patients. We have also utilized governmental organizations, such as NCI’s NExT (RAID) and PREVENT (RAPID) mechanisms and the CP-Net Cooperative group, to facilitate translation. This collaboration between multiple academic, industrial, and governmental organizations within and outside of the US is critical to the success of our program and driving the development of interventions for widespread clinical implementation.