Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine

Cancer Gene Ther. 2006 Jun;13(6):592-7. doi: 10.1038/sj.cgt.7700937.

Abstract

Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico, a women dies every 2 h, and since 1990 the statistics have shown that the numbers of deaths are increasing. We conducted a phase II clinical trial to evaluate the potential use of the MVA E2 recombinant vaccinia virus in treating high-grade lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four female patients with high degree lesions were treated either with an MVA E2 therapeutic vaccine or with conization. Thirty-four women received the therapeutic vaccine, at a total of 10(7) virus particles per dose injected directly into the uterus once every week over a 6-week period. Twenty control patients were treated with conization. By colposcopy, 19 patients out of 34 showed no lesion, in three patients the lesions were reduced by 85-90%, in eight other lesions had reduced by 60%, and in four more patients, they were reduced by 25%. Histological analysis showed total elimination of high-grade lesions in 20 out of 34 patients after treatment with MVA E2. Eleven patients had a 50% reduction in lesion size. In two other patients, the lesion was reduced to CIN 2 and in one more patient the lesion was reduced to low grade (CIN 1). All patients developed antibodies against the MVA E2 vaccine, and generated a specific cytotoxic response against papilloma-transformed cells. DNA viral load was significantly reduced in MVA E2-treated patients. Conization eliminated the lesions in 80% of the patients, but patients did not develop cytotoxic activity specific against cancer cells and did not eliminate the papillomavirus. In addition, three patients treated with conization had recurrence of lesions 1 year later. These results show that therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of high-grade lesion.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Cancer Vaccines / therapeutic use
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / therapy*
  • Cervical Intraepithelial Neoplasia / virology
  • Colposcopy
  • Demography
  • Female
  • Humans
  • Middle Aged
  • Papillomaviridae / immunology
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / immunology
  • Papillomavirus Vaccines
  • Patient Selection
  • Treatment Outcome
  • Uterine Cervical Neoplasms / prevention & control*
  • Vaccines, DNA / therapeutic use*
  • Vaccinia virus / immunology*
  • Viral Load

Substances

  • Cancer Vaccines
  • Papillomavirus Vaccines
  • Vaccines, DNA