High E6 Gene Expression Predicts for Distant Metastasis and Cancer-Specific Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Abstract

elevated plus maze tests. The highly hippocampal-dependent object placement (OP) test (a.k.a. novel object location test) was used to assess spatial memory dependent on intact neural stem cell function. Two OP tests, one with 40 min retention interval, and one with a more challenging 70 min retention interval were performed. An object recognition (OR) test was used to test hippocampal-independent cognitive function. The results were determined based on previously validated pass/fail criteria. Differences among treatment groups were analyzed using a likelihood ratio test for chi-square distributions, and pairwise chi-square comparisons were used to assess pairwise differences. Results: The irradiation procedure was well tolerated by all animals and all groups performed similarly on the general behavior tasks. Table 1 shows the results for the OP and OR behavior tasks. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the OP 40 min task (P Z .039) and the OP 70 min task (P Z .030). In contrast, HSI mice did not perform significantly different from control mice at either the 40 min (P Z .956) or 70 min (P Z .459) retention interval and performed significantly better compared to WBRT mice in the OP 40 min task (P Z .032). No difference between groups was found in the hippocampal-independent OR task (P Z .699). Conclusion: The results of this study show that hippocampal-dependent spatial memory is clearly affected after WBRT, but preserved in animals receiving HSI, consistent with the result seen in the RTOG 0933 clinical trial in humans. As such, this animal model could prove a helpful tool for researchers exploring novel strategies for mitigating the adverse cognitive impairment of high-dose cranial irradiation.