Page 95 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

histological specimen instead of cytology for the FISH analysis, which has been shown to be more
sensitive to the identification of cells with 3q gain.[12, 20] We however chose to perform FISH
analysis in biopsy material, as histology is the golden standard for a CIN diagnosis. A limitation
regarding the interpretation of the study results, is the effect of a diagnostic biopsy on the natural
history of the lesion. It is suggested that the biopsy itself may induce lesions regression. This
would limit the interpretation of any prognostic marker, and applies to all studies on the natural
history of CIN lesions. On the other hand, high-grade lesions are clinically diagnosed with a biopsy,
making the prognostic effect of a prognostic biomarker clinically applicable despite the effect of 4 the biopsy on regression itself. Another general limitation with regard to the interpretation and application of histological biomarkers in high-grade CIN is the possibility of false negative results
due to sampling error, in which the biopsy is not representative of the actual disease status. We therefore propose that histological biomarkers should be applied as part of a biomarker profile, which should also contain biomarkers that are independent of the disease histology. Examples are cytological, serological or epidemiological markers, such as HPV-genotype, immune markers and smoking status.
In conclusion, the results of the current review and pilot study show that the absence of 3q26 gain could potentially serve as a prognostic biomarker for the identification of CIN lesions with a high probability of disease regression, preferentially as part of a broader biomarker profile. As such, 3q26 staining could aid in the selection of women with low-grade lesions who would not need immediate colposcopic assessment and women with high-grade lesions who would not need immediate treatment. Both strategies could result in reduced costs, patient burden and side effects of surgical treatment. To confirm this hypothesis further research is necessary. Research should focus on identification of a generalized methodology for 3q26 gain testing and interpretation. Subsequently, its prognostic properties should be confirmed in a larger patient population. Moreover, assessment of the association between HPV and 3q26 gain is needed. Upon confirmation of its prognostic properties, 3q26 staining could be considered as part of a biomarker profile to triage women with high-grade lesions for conservative follow-up measures.
3q26 as a prognostic biomarker
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