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.
N1 - Funding Information:
We thank Godfrey Wilson for pathological assessment of the biopsies, Andrew Bailey for HPV testing, Garry Ashton for cryostat section preparation and Sharon Barker for providing clinical support. We also thank Galderma for providing imiquimod and Xenova for providing TA-CIN and TA-GW. Cancer Research UK supported the research of PLS. The Joseph Starkey fellowship from Wigan Cancer Research Fund, Cancer Research UK and University of Manchester supported SD and UW. RBSR was supported by grants from the National Cancer Institute (P50 CA098252 SPORE in Cervical Cancer and RO1 CA118790).
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)
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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 -