Cell-mediated immune responses to human papillomavirus 16 E6 and E7 antigens as measured by interferon gamma enzyme-linked immunospot in women with cleared or persistent human papillomavirus infection

Int J Gynecol Cancer. 2009 May;19(4):508-12. doi: 10.1111/IGC.0b013e3181a388c4.


Cell-mediated immune responses have been thought to be important in the control of human papillomavirus (HPV) infections. We examined cell-mediated immune responses to HPV-16 E6 and E7 in the peripheral blood using interferon gamma (IFN-gamma) enzyme-linked immunospot assay (Cellular Technology Ltd, Cleveland, Ohio) in women with HPV-16 infection who showed clearance and compared these women to women with HPV-16 persistence. Women participating in a longitudinal study of cervical HPV were recruited once cervical HPV-16 infection was detected by polymerase chain reaction. Four groups of women were examined: (1) persistent, (2) intermittent, (3) transient, and (4) cleared. Ninety-six samples from 55 women were compared. Comparing IFN-gamma enzyme-linked immunospot to the HPV-16 clearance of 10 women with recent persistence, none had response to either E6 or E7; of 24 women with recent clearance, 14 had E6 and 8 had E7 response. Women with intermittent persistence behaved similarly to the clearance group than recent persistors: 50% were positive to E6 and 20% to E7. In summary, anti-E6 responses seem critical in the immediate control of HPV, and in some women, an immune tolerance eventually develops if HPV is not eliminated soon after infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, Viral / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / blood*
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear / immunology
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / virology
  • Repressor Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Interferon-gamma