Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia.

Daayana, S; Elkord, E; Winters, U; Pawlita, M

Abstract

Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure.
Methods: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed.
Results: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens.
Conclusion: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically.

Citation

Daayana, S., Elkord, E., Winters, U., & Pawlita, M. (2010). Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. British Journal of Cancer, 102(7), 1129-1136. https://doi.org/10.1038/sj.bjc.6605611

• Journal Article Type: Article
• Publication Date: Mar 1, 2010
• Deposit Date: Oct 11, 2011
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 102
• Issue: 7
• Pages: 1129-1136
• DOI: https://doi.org/10.1038/sj.bjc.6605611
• Publisher URL: http://dx.doi.org/ 10.1038/sj.bjc.6605611