Randomised Controlled Study on the Effects of Imiquimod, a TLR 7 Activating Agent,
on the HPV16-Specific Immune Response Following HPV16 E6/E.7 Synthetic Long
Peptides Vaccination in Women with HPV16 Positive High Grade Vulvar/Vaginal
Intraepithelial Neoplasia

1. Patients of 18 years and older.

2. Willing and able to comply with the protocol and to provide informed consent in accordance with institutional and regulatory guidelines.

3. Histological evidence of high grade VIN and/or VaIN, HPV16 positive.

4. Baseline laboratory findings; white blood cells (WBC) > 3,000 x 109/l, lymphocytes > 1,000 x 109/l, platelets > 100 x 109/l.

5. HIV- and HBV-negative.

6. Patients of child-bearing potential should test negative using a serum pregnancy test and agree to utilize effective contraception during the entire treatment and follow-up period of the study.

1. Known hypersensitivity to the vaccine or imiquimod or to any of the respective excipients.

2. Indication of a current active infectious disease of the vulva or other infections that need medical attention, other than HPV16.

3. VaIN lesions that are not distinguishable from a co-existing cervical intraepithelial neoplasia (CIN) lesion.

4. History of an autoimmune disease or other systemic intercurrent disease that might affect the immunocompetence of the patient, or patients receiving immunosuppressive therapy including transplant recipients.

5. History of a second malignancy except curatively treated low-stage tumours with a histology that can be differentiated from the vulvar, vaginal and cervical cancer type.

6. Radiotherapy, chemotherapy administered within 4 weeks prior to the enrolment visit.

7. Participation in a study with another investigational drug within 30 days prior to the enrolment in this study.

8. Any condition that in the opinion of the investigator could interfere with the conduct of the study.