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Fluorescence In Situ Hybridization Testing for the Diagnosis of High-Grade Cervical Abnormalities: A Systematic Review

Earley, Amy BS1,2; Lamont, Jenny L. MS1,2; Dahabreh, Issa J. MD, MS3,4; Cowan, Janet PhD5; Feldman, Sarah MD, MPH6; Uhlig, Katrin MD, MS1,2,7

Journal of Lower Genital Tract Disease: July 2014 - Volume 18 - Issue 3 - p 218–227
doi: 10.1097/LGT.0000000000000007
Original Articles

Objective We examined the diagnostic performance of fluorescence in situ hybridization (FISH) tests on cervical cytology for precancerous lesions or cancer on cervical histology.

Materials and Methods A search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, and Scopus through September 3, 2013. Eleven studies examined FISH tests for telomerase RNA component gene (TERC), myelocytomatosis oncogene (MYC), or human papillomavirus (HPV) type 16 or 18 in samples exhibiting atypical squamous cells of unknown significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). None examined HPV-positive, cytologically normal samples. We extracted data on the sensitivity and specificity for high-grade cervical intraepithelial neoplasia (CIN 2+ or CIN 3+).

Results Fluorescence in situ hybridization test probes and thresholds varied across studies. Included populations were convenience samples. Only 1 study testing for TERC specified HPV status. In meta-analysis, FISH for TERC in LSIL (9 studies, 1,082 cases) had a summary sensitivity of 0.76 (95% confidence interval = 0.63–0.85) and a summary specificity of 0.78 (95% confidence interval = 0.57–0.91) for CIN 2+. Fluorescence in situ hybridization for TERC in ASC-US (3 studies, 839 cases) showed sensitivities ranging from 0.75 to 1.00 and specificities from 0.87 to 0.93 for CIN 2+. For CIN 3+, sensitivity and specificity appeared similar, although a small number of studies preclude firm conclusions. For FISH tests for HPV, we found only few studies with small sample sizes.

Conclusions The evidence on FISH testing is limited given the small number of studies for each cytology subgroup and the lack of studies in well-defined screening contexts stratifying participants by HPV status.

Fluorescence in situ hybridization testing on cervical cytology to screen for high-grade cervical intraepithelial neoplasia or cancer needs further investigation.

1Center for Clinical Evidence Synthesis and 2Institute of Clinical Research and Health Policy Study, Tufts Medical Center, Boston, MA; 3Center of Evidence-Based Medicine and 4Department of Health Services Policy & Practice, Program in Public Health, Brown University, Providence, RI; 5Division of Cytogenetics, Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA; 6Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham & Women’s Hospital, Boston, MA; and 7Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA

Reprint requests to: Katrin Uhlig, MD, MS, 800 Washington St, #391, Tufts Medical Center, Boston, MA 02111. E-mail:

This report is based on a Health Technology Assessment prepared by the Tufts Evidence-based Practice Center under contract with the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290 2007 10055 I).

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services.

No investigators have any affiliations or financial involvement (e.g., employment, consultancies, honoraria, stock options, expert testimony, grants or patents received or pending, or royalties) that conflict with material presented in this article.

Copyright © 2014 by the American Society for Colposcopy and Cervical Pathology