title: Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.
abstract: OBJECTIVE
  This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18.
  
  
  METHODS
  A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints.
  
  
  RESULTS
  All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)).
  
  
  CONCLUSIONS
  Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix.
authors.affiliation: Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Sonja Izquierdo
authors.initials: SI
authors.lastname: Meyer
authors.forename: Katrine
authors.initials: K
authors.lastname: Fuglsang
authors.forename: Jan
authors.initials: J
authors.lastname: Blaakaer
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000187:drug effects* / Q000472:pathogenicity; D052161:Human papillomavirus 18 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000517:prevention & control*
chemical_list: D053918:Papillomavirus Vaccines
keywords: Cervical cancer; cellular immunity; cervical intraepithelial neoplasia; human papillomavirus; immunity; vaccination