Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia

No clinical evidence of vulvar lesion, i.e. 100% reduction of primary lesion size

Vulvar lesions will be described, measured with calipers, mapped and photographed. The digital photos will be analyzed with a computer program (ImageJ) to calculate the total lesion size in cm². Results will be classified as: no response (NR, reduction in lesion size of 25% or less), weak partial response (wPR, 26-75% reduction), strong partial response (stPR, 76%-99% reduction) and Complete response (CR, 100% reduction).

At baseline punch biopsies will be taken from the affected areas. The site of the initial biopsy will be photodocumented to ensure that the follow-up biopsy at 6 months is taken from the same site. Histologic results will be classified as response (R): complete disappearance of usual type VIN or reduction to VIN1,or no response (NR). All biopsy samples will be analysed independently by two experienced gynecologic pathologists unaware of the treatment allocation

The number, types and extent of surgical procedures will be recorded. The extent of surgery will be recorded as total operated lesion size (in cm², as measured on pre-operative photograph) and relative operated lesion size (percentage of operated lesion size compared with the original pretreatment lesion size)

HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.

Vulvar lesions will be described, measured with calipers, mapped and photographed. The digital photos will be analyzed with a computer program (ImageJ) to calculate the total lesion size in cm². Results will be classified as: no response (NR, reduction in lesion size of 25% or less), weak partial response (wPR, 26-75% reduction), strong partial response (stPR, 76%-99% reduction) and Complete response (CR, 100% reduction).

The number, types and extent of surgical procedures will be recorded. The extent of surgery will be recorded as total operated lesion size (in cm², as measured on pre-operative photograph) and relative operated lesion size (percentage of operated lesion size compared with the original pretreatment lesion size)

HPV status will be measured with the qualitative cobas® HPV Test, Roche, and the the APTIMA ® HPV assay, Gen-Probe.

Change from baseline in "Cervical Dysplasia Distress" score at 6 months

Change from Baseline in "Cervical Dysplasia Distress" score at 12 months

Change from Baseline "Fear of Progression" score at 6 months.

Change from Baseline "Fear of Progression" score at 12 months.

Change from baseline "Sexual activity" score at 6 months

Change from baseline "Sexual activity" score at 12 months

Histochemical analysis of immune cells from vulvar biopsy samples will be performed at baseline and at 6 months. Frozen sections will be prepared and stained with corresponding cell markers. Immune cell populations will be quantified as number of cells per square millimetre and will be compared between the two treatment groups. The following markers and their primary antibodies will be analysed: CD1a, marker for Langerhans cells, CD94, marker for natural killer cells, CD4, marker for T-helper cells, CD8, marker for cytotoxic T-cells and CD207, marker for immature dendritic cells expressing Langerin.

Detailed photos of the overall vulva will be taken. Photos will be compared to photos taken at baseline and judged by 4 independent, blinded observers for aesthetic results.

Detailed photos of the overall vulva will be taken. Photos will be compared to photos at baseline and judged by 4 independent, blinded observers for aesthetic results.

Change of VAS score for pain and pruritus from baseline to 6 months. VAS will be assessed at baseline, 1,2 ,3,4,5 and 6 months.