A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer

Abstract

Cervical cancer remains one of the leading causes of death among women in developing countries. Without resources to support Pap smear cytology and colposcopy, cost-effective approaches which enable single-visit "see-and-treat" protocols offer the potential to reduce morbidity and mortality due to this preventable disease. We carried out a pilot clinical study in Shanxi province, China, to evaluate a low-cost, high-resolution microendoscope (HRME) imaging system which enables evaluation of epithelial cell morphology in vivo. HRME images were obtained at discrete sites on the cervix in 174 women, in addition to visual inspection with acetic acid (VIA) and colposcopic examination. Of 69 sites appearing abnormal on colposcopy, only 12 showed high-grade disease (CIN2+) on pathology. Quantification of the nuclear-to-cytoplasm ratio by HRME enabled an ad hoc threshold to be defined, which correctly classified all 12 sites as abnormal, whilst classifying 38 of the remaining 57 pathology normal sites as normal. All patients with biopsy confirmed high-grade disease also tested positive for high-risk human papilloma virus (HPV) DNA and were classified as abnormal by HRME. Among the remaining patients who tested positive for HPV but were either normal by colposcopy or showed <CIN2 on pathology, only 6 of 32 (18.8%) were classified as abnormal by HRME. Visual examination techniques for cervical cancer screening may overestimate the prevalence of precancerous lesions, leading to unnecessary treatment, expense, and patient stress. The results of this study suggest that evaluation of suspicious lesions by HRME may assist in ruling out immediate cryotherapy, thus increasing the efficiency of current see-and-treat programs.

Figures

Figure 1

(Left) Design of the pre-screening phase of the study. The study was designed to accrue an estimated 100 patients with cervical precancerous lesions, and 100 normal patients. (Right) Design of the HRME evaluation study. A total of 174 patients were recruited to the study from the pre-screening phase.

Figure 2

(a) Photograph of the high-resolution microendoscope (HRME) system and (b–d) demonstration of the imaging procedure. (b) Proflavine is applied using a cotton-tipped swab; (c) the fiber-optic probe is placed in gentle contact with the cervix; and (d) a high-resolution image is displayed on a laptop computer in real time. (e) Colposcopic view of an aceto-white cervical lesion at 5 o'clock (arrow), and (f) resulting HRME image. Histologic diagnosis of this site was normal, consistent with the HRME image which shows small, evenly spaced nuclei. (g) Colposcopic view of another aceto-white cervical lesion at 12 o'clock (arrow), and (h) resulting HRME image. Histologic diagnosis of this site was CIN3, consistent with the HRME image which shows large, crowded, pleomorphic nuclei. HRME image scale bars = 100 µm.

Figure 3

(a) Individual N/C ratio values measured at each of the 69 sites with a pathology diagnosis, as well as the 95 colposcopically normal sites imaged. The dashed line represents a post-hoc threshold at the lowest value which correctly classified all 12 CIN2+ sites as “neoplastic”. (b) Mean ± standard error values for N/C ratios at each pathology grade.