TY - JOUR
T1 - Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia
AU - Daayana, S.
AU - Elkord, E.
AU - Winters, U.
AU - Pawlita, M.
AU - Roden, R.
AU - Stern, P. L.
AU - Kitchener, H. C.
PY - 2010/3
Y1 - 2010/3
N2 - Background: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.
AB - Background: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.
KW - Imiquimod
KW - T regulatory cells
KW - Therapeutic HPV vaccination
KW - Vulval intraepithelial neoplasia (VIN)
UR - http://www.scopus.com/inward/record.url?scp=77950370339&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6605611
DO - 10.1038/sj.bjc.6605611
M3 - Article
C2 - 20234368
AN - SCOPUS:77950370339
SN - 0007-0920
VL - 102
SP - 1129
EP - 1136
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -