Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening: Removing the Confounder of Discordance

Abstract

BackgroundSubjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation.MethodsWithin a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn’s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease.ResultsConventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation.ConclusionsHistology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool.

Vibrational spectroscopy of biofluids for disease screening or diagnosis: translation from the laboratory to a clinical setting

“…In the handling of some biofluids such as blood, there remain challenges to be overcome [98]. Whilst there is a large body of compelling evidence to support the application of vibrational spectroscopy to biofluids such as blood to triage patients for particular conditions such as myocardial infarction [99,100], the integration of these techniques into standard clinical practice remains some way off [101] and definitive clinical trials are needed to define their true diagnostic accuracy [102]. The enormous advantage of a real-time analytical monitoring device is that in the face of emerging disease such as neurodegeneration, one could take simple medications to slow down the progress of the pathology [103].…”

The performance of multimodal hyperspectral spectroscopy in the detection of precancerous cervical lesions

“…The reflectance range is wider (350-900 nm) [7,8]. In addition to a xenon light source, the spectroscopy device features a monochromatic system, which is controlled by a computerized system and projects the wavelengths of the light above the cervix through an optical fiber [9,10]. The working principle of MHS is the transmission of monochromatic light through a media (solution) onto the cytoplasm of the cervix.…”

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

“…Another study revealed the potential of ATR-FTIR in segregating benign from malignant brain tumors identifying relevant biomarkers at the same time [184]. A third study has demonstrated that ATR-FTIR spectroscopy of cervical liquid-based cytology is better in identifying underlying atypia or disease than conventional screening when compared with histology [185].…”