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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
  1. Sepideh Farhat, MS*,
  2. Mayumi Nakagawa, MD, PhD and
  3. Anna-Barbara Moscicki, MD*
  1. *Department of Pediatrics, School of Medicine, University of California, San Francisco, CA; and
  2. University of Arkansas for Medical Sciences, Little Rock, AR.
  1. Address correspondence and reprint requests to Sepideh Farhat, MS, University of California, HSW 1419, 513 Parnassus Ave, San Francisco, CA 94143. E-mail: nozzaris{at}


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-γ) 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-γ 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.

  • CMI
  • Interferon gamma
  • ELISpot
  • HPV-16 E6 and E7
  • Persistent infection
  • Clearance

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  • This work was supported in part by the National Cancer Institute R01CA51323 and R01CA54053, NIH grant no. M01 RR01271, Maternal and Child Health Bureau Training grant no. MCJ000978, NCI K07 CA75974, and the Arkansas Biosciences Institute, the major component of the Tobacco Settlement Proceeds Act of 2000.