title: Potential value of in situ cellular immune response in HPV subtype 16 and 18 positive cervical cancer.
abstract: There is no doubt that the association between infection of the cervical epithelium by carcinogenic Human Papilloma Virus (HPV), particularly types 16 and 18, and cervical cancer (CC) is responsible for the activation of the immune response (IR). Research on tumor infiltrating lymphocytes at the primary tumor site could give us important information on how the immune cells are fighting against cancer.
  
  
  OBJECTIVE
  The aims of our study were to assess HPV status and to evaluate the significance of in situ cellular IR in CC.
  
  
  METHODS
  We performed a two-step retrospective analysis of IR in 18 CC: evaluation of HPV 16 and 18 infections by in situ hybridization and immune biomarkers (CD20, CD3, CD45) by immunohistochemistry. Immune cell profile, densities (assigned scores "0" if no inflammatory infiltrate, "1+" low, "2+" intense), tissue distribution and classical negative prognosis factors in relationship with survival and relapse were further assessed.
  
  
  RESULTS
  We successfully demonstrated HPV 16 and/or 18 in all cases. We reported statistical significant correlations (p<0.005) between CD3, CD20, CD45 and survival (r=0.800), relapse (r=-0.892), clinical stage (r=-0.914), tumor size (r=-1) as well as the association between survival and CC subtype (r=0.548), FIGO stage (r=-0.914), tumor size (r=-0.800) and grading (r=0.61).
  
  
  CONCLUSIONS
  The density of different immune cells is significantly involved in guiding prognosis of the CC in high-risk 16 and 18 HPV positive women; low cellular densities for CD3, CD20 and CD45 meaning limited immune response reflect negative disease outcomes promoting local relapse and decreased survival in such settings.
authors.affiliation: "Grigore T. Popa" University of Medicine and Pharmacy, Iassy, Romania; codrina_ancuta@yahoo.com.
authors.forename: Eugen
authors.initials: E
authors.lastname: Ancuţa
authors.forename: Stefan
authors.initials: S
authors.lastname: Buţureanu
authors.forename: Florin
authors.initials: F
authors.lastname: Zugun-Eloae
authors.forename: Carmen Rodica
authors.initials: CR
authors.lastname: Anton
authors.forename: Codrina
authors.initials: C
authors.lastname: Ancuţa
authors.forename: Damian
authors.initials: D
authors.lastname: Diţescu
authors.forename: Emil
authors.initials: E
authors.lastname: Anton
mesh_terms: D004279:DNA, Viral / Q000032:analysis; D005260:Female; D052162:Human papillomavirus 16 / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral