A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions.
The aim of this study was to investigate the capacity of an HPV16 E6/E7 synthetic overlapping long-peptide vaccine to stimulate the HPV16-specific T-cell response, to enhance the infiltration of HPV16-specific type 1 T cells into the lesions of patients with HPV16+ high-grade cervical squamous intraepithelial lesion (HSIL) and HPV clearance. This was a placebo-controlled randomized phase II study in patients with HPV16-positive HSIL. HPV16-specific T-cell responses were determined pre- and post-vaccination by ELISPOT, proliferation assay and cytokine assays in PBMC and HSIL-infiltrating lymphocytes, and delayed-type hypersensitivity skin tests. Motivational problems of this patient group to postpone treatment of their premalignant lesions affected the inclusion rates and caused the study to stop prematurely. Of the accrued patients, 4 received a placebo and 5 received 1-2 vaccinations. Side effects mainly were flu-like symptoms and injection site reactions. A strong HPV-specific IFNγ-associated T-cell response was detected by ELISPOT in all vaccinated patients. The outcome of the skin tests correlated well with the ELISPOT analysis. The cytokine profile associated with HPV16-specific proliferation varied from robust type 1 to dominant type 2 responses. No conclusions could be drawn on vaccine-enhanced T-cell infiltration of the lesion, and there was no HPV clearance at the time of LEEP excision. Thus, vaccination of HSIL patients results in increased HPV16-specific T-cell immunity. Further development of this type of treatment relies on the ability to motivate patients and in the reduction in the side effects.
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands. p.j.de_vos_van_steenwijk@lumc.nl
Peggy J
PJ
de Vos van Steenwijk
Tamara H
TH
Ramwadhdoebe
Margriet J G
MJ
Löwik
Caroline E
CE
van der Minne
Dorien M A
DM
Berends-van der Meer
Lorraine M
LM
Fathers
A Rob P M
AR
Valentijn
Jaap
J
Oostendorp
Gert Jan
GJ
Fleuren
Bart W J
BW
Hellebrekers
Marij J P
MJ
Welters
Mariette I
MI
van Poelgeest
Cornelis J M
CJ
Melief
Gemma G
GG
Kenter
Sjoerd H
SH
van der Burg
D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D012097:Repressor Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000628:therapy / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy / Q000821:virology*
D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16