Page 85 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

strategy was independently proven by means of a statistical analysis of spot counting in tissue sections.[18, 19] Lesions were classified are tetrasomic (copy number 4) in case a major fraction exhibited 4 copies, as aneusomic (copy number 3,4) in case a major fraction exhibited 3 copies and in case of minor fractions (copy number 2-4). Gain for the targets was noted when dysplastic areas were recognized with more than two copies for 3c or 3q. Subsequently, normal morphologic areas were analysed and consistently showed a disomy for 3c and 3q.
Outcome measures and criteria for biomarker performance 4 The outcome measure was defined as the correlation between 3q26 gain and disease persistence
of high-grade CIN. No previous biomarker performance values are available for HLA types. The
required test performance values include a high sensitivity and negative predictive value: lesions
that will not regress spontaneously must be identified, as treatment is necessary in these women. The actual values depend on the follow-up term of observational management. Lower values can be accepted when strict histological follow-up is implemented to identify persisting lesions at an early stage.
Outcome measure and statistical analysis
Quantitative variables were described as mean and ranges. Qualitative variables were described as frequency and percentage. Sensitivity, specificity, positive and negative predictive values were calculated from a 2x2 table. Sample size calculation was not feasible, due to the lack of comparable biomarker performance values and limitation of the study population by the availability of material.
Literature overview
Eight studies were identified that evaluated the predictive properties of 3q26/hTERC gain in cervical squamous lesions. [20-27] All studies assessed patients with cervical squamous intraepithelial lesions who were followed for a certain period of time, without immediate treatment, in order to evaluate the natural prognosis of the lesions. The main study features are displayed in table 1. Only two studies included patients with high-grade lesions. Heselmeyer- Haddad included patients with German PAP 3D cytology, which resembles CIN 1 or 2, of which the latter is interpreted as a high-grade lesion.[20] Ravaioli et al. included five patients with high- grade CIN.[27]
3q26 as a prognostic biomarker
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