Cervical Precancer Detection Using a Multivariate Statistical Algorithm Based on Laser‐Induced Fluorescence Spectra at Multiple Excitation Wavelengths

Abstract— A portable fluorimeter was developed and utilized to acquire fluorescence spectra from 381 cervical sites in 95 patients at 337, 380 and 460 nm excitation immediately prior to colposcopy. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired in vivo. Two full‐parameter algorithms were developed using tissue fluorescence emission spectra at all three excitation wavelengths (161 excitation‐emission wavelength pairs) for cervical precancer (squamous intraepithelial lesion [SIL]) detection: a screening algorithm that discriminates between SIL and non‐SIL with a sensitivity of 82 ± 1.4% and specificity of 68 ± 0.0%, and a diagnostic algorithm that differentiates high‐grade SIL from non‐high‐grade SIL with a sensitivity and specificity of 79 ± 2% and 78 ± 6%, respectively. Multivariate statistical analysis was also employed to reduce the number of fluorescence excitation‐emission wavelength pairs needed to redevelop algorithms that demonstrate a minimum decrease in classification accuracy. Two reduced‐parameter algorithms that employ fluorescence intensities at only 15 excitation‐emission wavelength pairs were developed: the screening algorithm differentiates SIL from non‐SIL with a sensitivity of 84 ± 1.5% and specificity of 65 ± 2% and the diagnostic algorithm discriminates high‐grade SIL from non‐high‐grade SIL with a sensitivity and specificity of 78 ± 0.7% and 74 ± 2%, respectively. Both the full‐parameter and reduced‐parameter screening algorithms discriminate between SIL and non‐SIL with a similar specificity (±5%) and a substantially improved sensitivity relative to Pap smear screening. A comparison of the full‐parameter and reduced‐parameter diagnostic algorithms to colposcopy in expert hands indicates that all three have a very similar sensitivity and specificity for differentiating high‐grade SIL from non‐high‐grade SIL.