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

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Abstract

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.

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