Search

Objective: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is a lethal disease with increasing incidence; however, technologies for early detection are limited. Nanomotors are synthetic nanostructures that can be powered by different mechanisms and functionalized for specific applications, such as biosensing. The objective of this investigation was to demonstrate an in vitro proof of concept for a novel nanomotor-based cancer detection approach toward in vivo detection of HPV-OPC., Study Design: In vitro cell line incubated with ultrasound-propelled nanomotors., Setting: Basic science and engineering laboratories., Subjects and Methods: Ultrasound-powered gold nanowire nanomotors were functionalized with graphene oxide and dye-labeled single-stranded DNA for the specific intracellular detection of HPV16 E6 mRNA transcripts. Nanomotors were incubated with HPV-positive or HPV-negative human OPC cells under static conditions or with an applied ultrasound field for 15 minutes. The resulting intracellular fluorescence was assessed with fluorescence microscopy and analysis software., Results: Nanomotors incubated with RNA extracted from HPV-positive OPC cells resulted in 60.7% of maximal fluorescence recovery, while incubation with RNA extracted from HPV-negative cells produced negligible fluorescence. Nanomotor incubation with intact HPV-negative cells produced minimal fluorescence (0.01 au), while incubation with HPV-positive cells produced a detectable signal (0.43 au) under static conditions and had 2.3-times greater intensity when powered with ultrasound., Conclusion: Acoustically powered nanomotors can successfully identify HPV16 E6 mRNA transcripts extracellularly and within intact cells. This work represents the first step toward a novel, practical approach to address the challenge of visually detecting HPV-OPC in real time.

Background: Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited., Methods: A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan-Meier and Cox proportional hazards methods., Results: The current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV-positive (80 patients). HPV-positive tumor status was associated with longer time to disease recurrence (P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09-0.58 [P = .002]), longer time to disease recurrence (≥ 1 year; aHR, 0.36; 95% CI, 0.18-0.74 [P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12-0.61 [P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04-0.56 [P = .005]) and distant (aHR, 0.19; 95% CI, 0.05-0.75 [P = .018]) metastatic disease recurrences., Conclusions: Surgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases., (© 2015 American Cancer Society.)