New, lower-cost tests that target high-risk human papillomavirus (HR-HPV) have been developed for cervical cancer screening in lower-resource settings but large, population-based screening studies are lacking. Women ages 25 to 65 years and living in rural China (n ¼ 7,543) self-collected a cervicovaginal specimen, had 2 cervical specimens collected by a clinician, and underwent visual inspection after acetic acid (VIA). The self-and one clinician-collected specimens underwent HR-HPV DNA testing by careHPV (QIAGEN) and Hybrid Capture 2 (HC2; QIAGEN) and the other clinician-collected specimen was tested for HPV16, 18, and 45 E6 using OncoE6 (Arbor Vita Corporation). Women who screened positive for any test and a random sample of those negative on all tests underwent colposcopic evaluation. The percent test positive was 1.8% for HPV E6 oncoprotein, between 14% and 18% for HR-HPV DNA testing, and 7.3% for VIA. The sensitivity for cervical intraepithelial neoplasia grade 3 or more severe (CIN3 þ ; n ¼ 99) was 53.5% for OncoE6, 97.0% for both careHPV and HC2 testing of the clinician-collected specimen, 83.8% for careHPV testing and 90.9% for HC2 testing of the self-collected specimen, and 50.5% for VIA. OncoE6 had the greatest positive predictive value (PPV), at 40.8% for CIN3 þ , compared with the other tests, which had a PPV of less than 10%. OncoE6 tested 70.3% positive for HPV16, 18, or 45-positive CIN3 þ and tested negative for all HPV16-, 18-, or 45-negative CIN3 þ (P < 0.0001). HPV E6 oncoprotein detection is useful for identifying women who have cervical precancer and cancer. Cancer Prev Res; 6(9); 938-48. Ó2013 AACR.

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Purpose: Although tumor necrosis factor^related apoptosis-inducing ligand (TRAIL) and agonistic antibodies targeting its receptors are promising cancer therapies because of their tumor selectivity, many tumors are resistant toTRAIL-based therapies.We examined whether the nonsteroidal anti-inflammatory drug aspirin sensitized cancer cells toTRAIL agonists in vitro and in vivo and investigated the underlying mechanism. Experimental Design: The effects of aspirin on sensitivity toTRAIL agonists and expression of apoptosis regulators was determined in human breast cancer cell lines and xenograft tumors. The specific role of survivin depletion in the TRAIL-sensitizing effects of aspirin was determined by silencing survivin. Results: Aspirin sensitized human breast cancer cells, but not untransformed human mammary epithelial cells, to TRAIL-induced caspase activation and apoptosis by a cyclooxygenase-2î ndependent mechanism. Aspirin also sensitized breast cancer cells to apoptosis induced by a human agonisticTRAIL receptor-2 monoclonal antibody (lexatumumab). Aspirin treatment led to G 1 cell cycle arrest and a robust reduction in the levels of the antiapoptotic protein survivin by inducing its proteasomal degradation, but did not affect the levels of many other apoptosis regulators. Silencing survivin with small interfering RNAs sensitized breast cancer cells toTRAILinduced apoptosis, underscoring the functional role of survivin depletion in theTRAIL-sensitizing actions of aspirin. Moreover, aspirin acted synergistically with TRAIL to promote apoptosis and reduce tumor burden in an orthotopic breast cancer xenograft model. Conclusions: Aspirin sensitizes transformed breast epithelial cells to TRAIL-based therapies in vitro and in vivo by a novel mechanism involving survivin depletion. These findings provide the first in vivo evidence for the therapeutic utility of this combination.