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. 2021 Apr 22;13(9):2008.
doi: 10.3390/cancers13092008.

Raman Spectroscopy of Liquid-Based Cervical Smear Samples as a Triage to Stratify Women Who Are HPV-Positive on Screening

Damien Traynor  1   2 , Cara M Martin  3   4   5 , Christine White  3   4 , Stephen Reynolds  3   4 , Tom D'Arcy  6 , John J O'Leary  3   4   5 , Fiona M Lyng  1   2
Affiliations

Raman Spectroscopy of Liquid-Based Cervical Smear Samples as a Triage to Stratify Women Who Are HPV-Positive on Screening

Damien Traynor et al. Cancers (Basel). .

Abstract

The role of persistent high-risk human papillomavirus (HPV) infection in the development of cervical precancer and cancer is now well accepted, and HPV testing has recently been introduced for primary cervical screening. However, the low specificity of HPV DNA testing can result in large numbers of women with an HPV-positive result, and additional triage approaches are needed to avoid over-referral to colposcopy and overtreatment. The aim of this study was to assess Raman spectroscopy as a potential triage test to discriminate between transient and persistent HPV infection. HPV DNA status and mRNA status were confirmed in ThinPrep® cervical samples (n = 60) using the Cobas 4800 and APTIMA HPV test, respectively. Raman spectra were recorded from single-cell nuclei and subjected to partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 14). Sensitivity of 85% and specificity of 92% were achieved for the classification of transient and persistent HPV infection, and this increased to 90% sensitivity and 100% specificity when mean sample spectra were used instead of individual cellular spectra. This study showed that Raman spectroscopy has potential as a triage test for HPV-positive women to identify persistent HPV infection.

Keywords: HPV; Raman spectroscopy; ThinPrep; biomarkers; cervical cancer; cervical precancer; cytology; exfoliated cells.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Representative cervical cells from (a) unstained and (d) stained Pap smears (bar = 50 μm). Superficial cells (b) before and (e) after staining (bar = 20 μm) and intermediate cells (c) before and (f) after staining (bar = 20 μm).
Figure 2
Figure 2
(a) Mean spectra of samples with non-transcriptionally active HPV infection (green, n = 750 spectra) and transcriptionally active HPV infection (blue, n = 750 spectra); shading indicates the standard deviation; (b) latent variable (LV) score scatter plot of LV1 and LV2 of samples with non-transcriptionally active HPV infection (green) and transcriptionally active HPV infection (blue); (c) LV1 loadings; (d) PLSDA plot.
Figure 2
Figure 2
(a) Mean spectra of samples with non-transcriptionally active HPV infection (green, n = 750 spectra) and transcriptionally active HPV infection (blue, n = 750 spectra); shading indicates the standard deviation; (b) latent variable (LV) score scatter plot of LV1 and LV2 of samples with non-transcriptionally active HPV infection (green) and transcriptionally active HPV infection (blue); (c) LV1 loadings; (d) PLSDA plot.
See this image and copyright information in PMC

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