Theranostics 2018; 8(11):3099-3110. doi:10.7150/thno.24599

Research Paper

Ultrahigh-resolution optical coherence microscopy accurately classifies precancerous and cancerous human cervix free of labeling

Xianxu Zeng1,2,†, Xiaoan Zhang3,†, Canyu Li2,4, Xiaofang Wang2,5, Jason Jerwick2, Tao Xu2,6, Yuan Ning2,7, Yihong Wang8, Linlin Zhang5, Zhan Zhang5, Yutao Ma6, Chao Zhou2,9,10,✉

1. Department of Pathology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
2. Department of Electrical and Computer Engineering, Lehigh University, Bethlehem PA 18015, USA.
3. Department of Imaging, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China.
4. Department of Gynecology and Obstetrics, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
5. Department of Clinical Laboratory, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
6. State Key Laboratory of Software Engineering, Wuhan University, Wuhan 430072, China.
7. Department of Precision Instrument Engineering, Tianjin University, Tianjin 300072, China.
8. Department of Pathology and Laboratory Medicine, Rhode Island Hospital/Warren Alpert Medical School of Brown University, Rhode Island 02912, USA
9. Department of Bioengineering, Lehigh University, Bethlehem PA 18015, USA.
10. Center for Photonics and Nanoelectronics, Lehigh University, Bethlehem PA 18015, USA.
† These authors contributed equally to this work.

Abstract

Cervical cancer remains the fourth most common cause of cancer worldwide and the third leading cause of cancer deaths for women in developing countries. Traditional screening tools, such as human papillomavirus and Pap tests, cannot provide results in real-time and cannot localize suspicious regions. Colposcopy-directed biopsies are invasive in nature and only a few sites of the cervix may be chosen for investigation. A non-invasive, label-free and real-time imaging method with a resolution approaching that of histopathology is desirable for early detection of the disease.

Methods: Ultrahigh-resolution optical coherence microscopy (OCM) is an emerging imaging technique used to obtain 3-dimensional (3-D) “optical biopsies” of biological samples with cellular resolution. In this study, 497 3-D OCM datasets from 159 specimens were collected from 92 patients.

Results: Distinctive patterns for normal cervix, squamocolumnar junction, ectropion, low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL) and invasive cervical lesions were clearly observed from OCM images, which matched well with corresponding histological slides. OCM images demonstrated a sensitivity of 80% (95% confidence interval, CI, 72%-86%) and a specificity of 89% (95% CI, 84%-93%) for detecting high-risk lesions (HSIL and invasive lesions) when blindly tested by three investigators. A substantial inter-observer agreement was observed (κ=0.627), which showed high diagnostic consistency among three investigators.

Conclusion: These results laid the foundation for future non-invasive optical evaluation of cervical tissue in vivo, which could lead to a less invasive and more effective screening and “see-and-treat” strategy for the management of cervical cancer.

Keywords: cervical cancer, optical biopsy, optical coherence tomography (OCT), optical coherence microscopy (OCM), screening

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How to cite this article:
Zeng X, Zhang X, Li C, Wang X, Jerwick J, Xu T, Ning Y, Wang Y, Zhang L, Zhang Z, Ma Y, Zhou C. Ultrahigh-resolution optical coherence microscopy accurately classifies precancerous and cancerous human cervix free of labeling. Theranostics 2018; 8(11):3099-3110. doi:10.7150/thno.24599. Available from http://www.thno.org/v08p3099.htm