Abstract
Introduction: Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of death by cancer in women worldwide. Over 85% of annual cervical cancer deaths occur in developing parts of the world and other low-resource populations where it is the leading cause of death from cancer among women chronically infected by at least one oncogenic type of human papillomavirus.
Background/Significance: Pap smear cytologic screening and current therapies for pre-cancerous low-grade lesions are costly, invasive and not feasible for use as therapy in low-resource settings. Inexpensive and validated alternative screening methods such as visual inspection with acetic acid (VIA) and a promising new HPV-DNA test (careHPV™, Qiagen), suggest the feasibility of implementing a single visit “screen-treat-prevent” public health care model in low-resource settings. However, there remains an unmet and urgent global need for an alternative therapy to serve as the “treatment arm” of a combined strategy that integrates screening with a safe, effective and affordable treatment for cervical dysplasia to prevent progression to cervical cancer.
Purpose/Approach: Our aim is to create a non-invasive therapy specifically for use in a “screen-treat-prevent” public health care model that can be readily implemented even in a remote village in Sub-Saharan Africa, without benefit of electricity, running water, clinical work-space or formally trained medical personnel. Such a therapy should be inexpensive, easily self-administered and curative as a single dose therapy (assume no follow-up). We used an approach derived from a fundamental principle of synthetic biology—a “bottoms up” approach—employing highly sophisticated material science research instrumentation and technologies to engineer a “low tech” alternative therapy that represents an unconventional and innovative solution to an urgent global health challenge.
Results: Our preliminary studies demonstrate the feasibility of controlled delivery of decoy peptide in situ to the cervical transformation zone in a transgenic mouse strain (K14E6) in which the high-risk type HPV16 E6 oncoprotein synergizes with 17 -estradiol to induce disease in situ that closely mimics the multi-stage development of human cervical cancer. Stable peptide-containing biopolymer formulations were created with properties that allow them to be solid phase at room temperature for ease of targeted application to the ectocervix, instantly melt at body temperature, adhere to mucosa and enhance peptide penetration across cervical mucosa. Penetration of decoy peptide across multiple layers of cervical squamous epithelium occurred in a dose- and time-dependent manner.
Social Impact: The ability to offer women a health care solution that encompasses a “screen-treat-prevent” approach requiring minimal medical supervision is at once powerful and empowering. Advancement in modern western medicine should aim at producing more equity rather than disparity. Studies have shown that women are often caregivers of the communities to which they belong, so that when they achieve improvements in their own health, the quality of life of the community as a whole improves significantly. This study hopes to add to the effort of continuing to enable and empower women all over the world to take stewardship of their own health for the betterment of the community at large.
Controlled topical delivery of biopolymer drug formulations represents an affordable and effective therapy for cervical dysplasia aimed at reducing cervical cancer incidence and mortality. Optimization of drug delivery using biopolymer formulations in a mouse model of human multi-stage cervical cancer will lay the groundwork for future human clinical trials.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A48.
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