Page 90 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 4
Author
Gain of 3q26/hTERC
per outcome group (using study threshold)
Progression in gain-negative group
Test properties
Prediction of persistence/ progression vs regression
Prediction of progression vs regression/ persistence
Obermann, 2013
Li, 2014
Ravaioli, 2017
Regression: 16/67 3/54 Persistence: 15/55
Progression: 7/10
Regression: 4/42 NR
Persistence/ progression:
19/32 PPV 82%
Regression: 0/2 1/5 Persistence: 2/4
Progression: 1/2
NPV 75% NAe
Sens 70%
Spec 76%
PPV 30%
NPV 94%
(progression vs regression)
Sens 35% Spec 76% PPV 58% NPV 54%
Sens 59% Spec 90%
asensitivity, bspecificity, cpositive predictive value, dnegative predictive value, enot applicable
Summary and appraisal
All studies identify 3q26/hTERC gain as a potential prognostic marker in cervical precancerous lesions. 3q26/hTERC gain seems more frequent in persistent or progressive lesions, but positive predictive values are generally low: patients with 3q26/hTERC gain often show disease regression during follow-up. Negative predictive values are consistently higher: absence of 3q26/hTERC gain seems to be a strong predictor of disease regression.
Nevertheless, several limitations of the individual studies and their review must be noted. Patient populations were generally small. Most studies included only patients with low-grade lesions, which limits the evidence on the prognostic properties of 3q26/hTERC gain in high-grade lesions. The baseline diagnosis was not determined uniformly: some studies included patients based on cytology, whereas others included only histologically confirmed lesions. Furthermore, follow- up periods and methods differed: both cytology and histology was applied. Regarding the FISH analysis, the different studies did not apply a similar signal interpretation method and threshold for gain. Another important limitation in the interpretation of the study results is that HPV testing was not performed or reported in most studies. It is therefore unclear whether all lesions were HPV-induced. This limits the applicability of the study results to high-grade lesions, which are usually HPV positive. Moreover, HPV genotype is an individual predictor in the natural history of CIN lesions. As such, information on HPV status would improve the interpretation of the study data.
Despite all limitations, 3q26/hTERC analysis has been consistently identified as a prognostic marker in cervical precancerous lesions, with a high negative predictive value in mostly low-grade lesions. As such, evidence indicates a potential predictive role of 3q26/hTERC gain in the natural prognosis of cervical dysplasia, but clinical applicability is yet limited and the evidence on the
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