Silica (SiO2) micro- and nanostructures fabricated with pre-stressed thermoplastic shrink wrap film have been shown to yield far-field fluorescence signal enhancements over their planar or wrinkled counterparts. The SiO2 structures have previously been used for improved detection of fluorescently labelled proteins and DNA. In this work, we probe the mechanism responsible for the dramatic increases in fluorescence signal intensity. Optical characterization studies attribute the fluorescence signal enhancements to increased surface density and light scattering from the rough SiO2 structures. Using this information, we come up with a theoretical approximation for the enhancement factor based off the scattering effects alone. We show that increased deposition thickness of SiO2 yields improved fluorescence signal enhancements, with an optimal SiO2 thin layer achieved at 20 nm. Finally, we show that the SiO2 substrates serve as a suitable platform for disease diagnostics, and show improved limits of detection (LOD) for the human immunodeficiency virus type 1 (HIV-1) p24 antigen.