Human Papilloma Virus Analysis of HPV FISH patterns in low and high grade Cervical Intraepithelial Neoplasia


  • V.M.M. van Meegen



Human Papilloma Virus is the most common sexually transmitted infection, with anestimated 80% of sexually active men and women acquiring an infection at some pointin their lifetime. 10-20% of infected individuals can not clear this infection effectivelyand consequentially are at risk for progression of Cervical Intraepithelial Neoplasia(CIN) to cancer. Presence of HPV can be determined using PCR and/or (Fluorescence) InSitu Hybridization. The aim of the performed experiments was to determine the generalFISH patterns that are specifically linked to low grade and high grade CIN lesions and toinvestigate whether or not these patterns could be used to grade these lesions.12 formalin fixed and paraffin embedded sections from one patient and 30 formalin fixedand paraffin embedded sections from different patients where used to perform a FISHprocedure and to analyze the general FISH hybridization pattern for CIN 1,2 and 3. For theanalysis 3 distinct patterns for the physical status of the virus were determined: episomal,integrated and mixed pattern. Also the presence of replication, load and the ratio betweenbasal load and superficial load was analyzed to determine the general pattern.Results show that load and physical status of the virus are not associated with the severityof the lesions. High loads are present in both high and low grade lesions. Also physicalstatus of the virus is not different for the sections, episomal and mixed patterns are foundin low and high grades. Only integrated pattern is a marker for severity, as this is only foundin CIN 3. Presence of replication is most common in CIN 1, this might contribute to correctgrading. The ratio between the load in the Basal layer and the load in the superficial layeris the most informative discriminant of severity: <0.5 for CIN 1, 0.5<load<1 for CIN 2 and 1for CIN 3. Based on these results it is possible to classify the severity of the lesion


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