Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide

Most human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN) lesions in normal women regress spontaneously, but a small number persist and may progress to invasive cancer. To evaluate the role of immunity to HPV and the outcome of CIN and associated HPV infection, we examined cell-mediated immune (CMI) responses to HPV 16 E6 and E7 peptides. One hundred thirty-six women with biopsy-confirmed CIN I or CIN II were followed for 1 year at 3 month intervals. Study subjects were 58% Hispanic, 36% African American, and 6% of other ethnicity, and were attending a municipal hospital colposcopy clinic. At each visit, cervical cytology and cervicovaginal lavage for HPV detection and typing was done, and blood was obtained for immunological studies. Lymphoproliferative CMI responses to HPV 16 E6 and E7 peptides were tested. An end point biopsy was done after the 1-year follow-up. The association between CMI responses to specific peptides and the outcome of disease was evaluated. CMI responses to E7 peptide (37-54) correlated significantly with regression of disease and with resolution of viral infection within 12 months. The protective effects of CMI to this peptide were not HPV type-specific. CMI responses to several other peptides also showed an association with regression, although not significant at present sample size. E7 peptide 37-54 contains one or more human T-cell epitopes. Identification and mapping of "protective" epitopes in the HPV E6 and E7 proteins could lead to the development of immunological assays to determine the risk of CIN and the development of immunotherapeutic protocols for the management of premalignant and malignant HPV-associated neoplasia and, ultimately, for the prevention of cancer.