Lymphoproliferative responses to human papillomavirus (HPV) type 16 proteins E6 and E7: outcome of HPV infection and associated neoplasia

J Natl Cancer Inst. 1997 Sep 3;89(17):1285-93. doi: 10.1093/jnci/89.17.1285.


Background: Infection with human papillomavirus (HPV) type 16 (HPV16) is a major cause of high-grade cervical intraepithelial neoplasia (CIN). Experiments were planned to evaluate the role of cell-mediated immunity (e.g., lymphocyte proliferation) against HPV in the natural history of HPV-associated neoplasia and to identify antigenic sequences of the HPV16 proteins E6 and E7 against which an immune response may confer protection.

Methods: Forty-nine women with abnormal cervical cytology and biopsy-confirmed CIN were followed through one or more clinic visits. Lymphoproliferative responses of peripheral blood mononuclear cells to HPV16 E6 and E7 peptides were assessed in long-term (3-week) cultures. HPV DNA was detected in cervicovaginal lavage by means of polymerase chain reaction and Southern blotting. Disease status was determined by cervical cytologic examination and colposcopy. Reported P values are two-sided.

Results: Subjects with positive lymphoproliferative responses to E6 and/or E7 peptides were more likely to be HPV negative at the same clinic visit than were nonresponders (P = .039). Subjects who were negative for HPV and those with a low viral load were more likely to be responders than were those with a high viral load (P for trend = .037). Responses to N-terminal E6 peptide 369 were associated with absence of HPV infection at the same clinic visit (P = .015). Subjects with positive responses to E6 or E7 peptides at one clinic visit were 4.4 times more likely to be HPV negative at the next visit than were nonresponders (P = .142). Responses to E6 peptide 369 and/or E7 C-terminal peptide 109 were associated with an absence of HPV infection (P = .02 for both) and an absence of CIN (P = .04 and .02, respectively) at the next visit.

Conclusions: Lymphoproliferative responses to specific HPV16 E6 and E7 peptides appear to be associated with the clearance of HPV infection and the regression of CIN.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / immunology
  • Antigens, Viral, Tumor / immunology
  • Blotting, Southern
  • Cell Division
  • Cells, Cultured
  • Cervical Intraepithelial Neoplasia / immunology*
  • Cervical Intraepithelial Neoplasia / virology
  • Female
  • Humans
  • Leukocytes, Mononuclear / virology*
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / chemistry
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology*
  • Polymerase Chain Reaction
  • Repressor Proteins*
  • Tumor Cells, Cultured
  • Tumor Virus Infections / complications
  • Tumor Virus Infections / immunology*
  • Uterine Cervical Dysplasia / immunology*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / virology


  • Antigens, Viral
  • Antigens, Viral, Tumor
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins