title: Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine.
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.
authors.affiliation: Hospital de Gineco Obstetricia, Instituto Mexicano del Seguro Social (IMSS), and FES Zaragoza, National Autonomous University of México, Mexico City, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: García-Hernández
authors.forename: J L
authors.initials: JL
authors.lastname: González-Sánchez
authors.forename: A
authors.initials: A
authors.lastname: Andrade-Manzano
authors.forename: M L
authors.initials: ML
authors.lastname: Contreras
authors.forename: S
authors.initials: S
authors.lastname: Padilla
authors.forename: C C
authors.initials: CC
authors.lastname: Guzmán
authors.forename: R
authors.initials: R
authors.lastname: Jiménez
authors.forename: L
authors.initials: L
authors.lastname: Reyes
authors.forename: G
authors.initials: G
authors.lastname: Morosoli
authors.forename: M L
authors.initials: ML
authors.lastname: Verde
authors.forename: R
authors.initials: R
authors.lastname: Rosales
mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000627:therapeutic use; D003127:Colposcopy; D003710:Demography; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology; D053918:Papillomavirus Vaccines; D018579:Patient Selection; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000276:immunology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000628:therapy* / Q000821:virology
chemical_list: D019496:Cancer Vaccines; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA