Promote HPV screening rate with a non-invasive HPV POC cartridge

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 DESCRIPTION (provided by applicant): Persistent infection by HPV causes cancers, and can be prevented - About 79 million American women are infected with HPV with about 14 million becoming newly infected each year. In 2010, there were 11,818 American women diagnosed with cervical cancer, and 3939 cervical cancer deaths. Persistent infection by HPV is a necessary factor in the pathologic process which may lead to cervical cancer development. Cervical cancer is a major fatal malignancy among women, causing about 275,000 deaths annually worldwide, mostly in developing countries. Cervical cancer is also a highly preventable disease if detected at its precancerous stages and treated by ablative procedures. The current HPV tests do not screen for persistent HPV infection - HPV testing has a clinical role in identifying individuals with an increased risk of an HPV-associated cervical precancer or cancer. Four tests are currently approved by the Food and Drug Administration (FDA) for detecting clinically significant levels of any of 13-14 high-risk HPV types: (1) the Qiagen Digene Hybrid capture(r) 2 (HC2, Qiagen, Gaithersburg, MD), (2) the Hologic-Genprobe Cervista(r) HPV (Hologics, Bedford, MA), (3) the Hologic-Genprobe APTIMA(r) HPV (Hologics, Bedford, MA), and (4) the Roche cobas(r) 4800 HPV test (Roche Molecular Systems, Pleasanton, CA). But the FDA approved indication of these tests is high-risk HPV infection, not persistent high risk HPV infection. Studies have shown that more than 90% of new HPV infections, including those with high-risk types, clear or become undetectable within two years, and clearance usually occurs in the first 6 months after infection. One of the key features of cervical cancer is its slow progression from normal cervical tissue, to precancerous (or dysplastic) changes in the tissue, to invasive cancer. The average time for progression of cervical intraepithelial neoplasia (CIN 3) to invasive cancer has been estimated to be 10 to 15 years, and there is a small subset of rapidly progressive cervical cancers which are diagnosed within 3 years of a confirmed negative Pap test. Hence, most high risk HPV infections will be cleared by body's immune system in 6 months, and only a smaller percentage of high risk HPV infections become persistent and develop into invasive cervical cancer after 10 to 15 years. A positive hrHPV result from the current FDA approved Roche's cobas HPV DNA test immediately calls for a colposcopy, while most hrHPV infections will not become persistent. However, it is difficult to conduct a follow-up test 6 months after the first positive hrHPV infection, because the current HPV tests are not easily accessible, unfriendly and invasive. Persistent infection with high-risk HPV is the most important risk factor for cervical cancer precursors and invasive cervical cancer. Cervical cancer is primarily a disease among unscreened or rarely screened women. Only less than 0.015% of HPV infection will lead to invasive cervical cancer, therefore a more clinically relevant screening test would detect persistent high-risk HPV infection, not just high-risk HPV infection. Discomfort and inconvenience are two major barriers of the follow up test to confirm persistent infection. Therefore, a self-administered HPV POC test on non-invasive samples such as urine and saliva along with education can significantly improve the HPV screening rate, and one HPV test in a woman's lifetime can decrease cancer mortality by 48% as compared to standard of care. The ultimate goal of this SBIR effort is to increase the HPV screening rate by demonstrating a non-invasive POC HPV test enabled by a smartphone mounted with a PocketLab. In the following Phase II study, the HPV test panel will be expanded to HPV 16/18 DNA, a pool of 12 other hrHPV DNA, E6/E7 oncoproteins, and the system control and reagent delivery will be replaced by a palm-sized PocketLab. This proposed SBIR Phase I study will demonstrate a smartphone-based HPV screening device to detect hrHPV DNA and oncoproteins E6/E7 from non-invasive specimens such as urine, saliva and swabs. All four FDA approved HPV DNA tests are intended for use by trained laboratory personnel who are proficient in performing real-time PCR assays in a well equipped clinical diagnostics laboratory. These tests require access to sophisticated and expensive lab equipment which is not widely available in developing countries, and several manual processing steps which increase the chances for contaminations. The proposed HPV PocketLab cartridge integrates the sample processing, target amplification, and detection steps of the HPV amplification assay and immunoassay into a single inexpensive, disposable cartridge that contains all necessary lyophilized reagents and requires no manual steps other than sample loading.