Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes in women with cervical neoplasia

Infection with oncogenic human papillomavirus (HPV) types is associated wit h the development of cervical neoplasia (CIN), The E6 and E7 oncoproteins a re constitutively expressed in these lesions and are therefore putative tar gets for the immune response against HPV. The relation between HPV 16-speci fic memory cytotoxic T-cell precursor (mCTLp) activity to both oncoproteins and the natural course of cervical dysplasia was analyzed in 38 patients p articipating in a nonintervention cohort study of women with CIN and 11 HPV 16-positive cervical carcinoma patients. In a cross-sectional study at the end of follow-up prior to biopsy, 8 of 20 patients with a persistent HPV 1 6 infection had specific mCTLp against at least one of the two oncoproteins . By contrast, no specific mCTLp activity was detected in 11 HPV-negative p atients or in 7 patients who had cleared an HPV 16 infection at the end of follow-up. However, 5 of 11 cervical carcinoma patients showed mCTLp activi ty against the By protein only. This study demonstrates that HPV 16 oncogen e-specific mCTLp are present in women with HPV 16-positive CIN prior to any intervention, Since HPV-specific mCTLp were detected predominantly in wome n with high-grade lesions or invasive cervical carcinoma and not in women w ho cleared the virus, the role of naturally occurring mCTLp in the protecti on against HPV-associated cervical neoplasia remains to be established. (C) 2000 Wiley-Liss. Inc.