Established and Emerging Optical Technologies for the Real-Time Detection of Cervical Neoplasia: A Review

Abstract

Cervical cancer remains a critically important problem for women, especially those women in the developing world where the case-fatality rate is high . There are an estimated 528,000 cases and 266,000 deaths worldwide. Established screening and detection programs in the developed world have lowered the mortality from 40/100,000 to 2/100,000 over the last 60 years. The standard of care has been and continues to be: a screening Papanicolaou smear with or without Human Papilloma Virus (HPV) testing; followed by colposcopy and biopsies and if the smear is abnormal; and followed by treatment if the biopsies show high grade disease (cervical intraepithelial neoplasia (CIN) grades 2 and 3 and Carcinoma- in-situ ). Low grade lesions (Pap smears with Atypical Cells of Uncertain Significance (ASCUS), Low Grade Squamous Intraepithelial Lesions (L G SIL), biopsies showing HPV changes or showing CIN 1) ; are usually fol lowed for two years and then treated if persistent. Treatment can be performed with loop excision, LASER, or cryotherapy. Loop excision yields a specimen which can be reviewed to establish the diagnosis more accurately. LASER vaporizes the lesion and cryotherapy leads to tissue destruction. Under long term study; loop excision, LASER, and cryotherapy have the same rate of cure. The stan dard of care is expensive and takes 6 - 12 weeks for the individual patient . During the last twenty years, new technologies that can view the cervix and even image the cervix with cellular resolution have been developed. These technol ogies could lead to a new paradigm in which diagnosis and treatment occurs at a single visit. These technologies include fluorescence and reflectance spec tros copy (probe or wide-field, whole cervix scanning approaches) and fluores cence confocal endomicroscopy or high resolution micro-endoscopy. Both technol ogies have received Federal Drug Administration (FDA) and have been com mer cialized. Research trials continue to show their remarkable performance. These technologies are reviewed and clinical trials are summarized. Emerging technologies are coming along that may compete with those already approved and include optical coherence tomography, optical coherence tomography with autofluorescence, diffuse optical microscopy, and dual mode micro-endoscopy. These technologies are also reviewed and where available, clinical data is reported. Optical technologies are ready to diffuse into clinical practice because they will save money and 3 or 4 visits in the developed world and offer the same standard of care to the developing world where more cervical cancer exists.