Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study

Epidemiological studies have clearly established that human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Most cervical cancers and pre-cancers are HPV-positive. Not all pre-cancers progress to cancer; a significant number regress. The immunological basis for either spontaneous or treatment-mediated recovery from HPV-associated CIN is not clear. Currently, prophylactic vaccines are successfully inducing antibody responses in HPV negative patients. Therapeutic vaccines for HPV-positive patients with disease are needed. There is a need to understand the immunologic basis for the Cell-Mediated Immune (CMI) response and for histological regression to help the formulation of therapeutic vaccines. Four groups of women were identified for this cross-sectional study of CMI. Group 1 consisted of six women without cytological or histological diagnosis of CIN and with an HPV negative test (CIN (−)/HPV (−)). Group 2 included 31 women with a new histological diagnosis of CIN and HPV positive test (CIN (+)/HPV (+)). Groups 3 and 4 were selected from women who had undergone ablative or excisional treatment for CIN at the colposcopy clinic at least 6 months before the study. The women in groups 3 and 4 were (CIN (+)/HPV (+)) before CIN treatment. Group 3 consisted of 22 women without evidence of recurrence of CIN (Recur (−)), and group 4 included 10 with histological diagnosis of recurrent CIN (Recur (+)). In particular, we investigated CMI responses to synthetic peptides from the E6 and E7 oncoproteins of HPV-16. Compared to patients with disease recurrence (Recur (+), n = 10), the majority of individuals who remained recurrence-free post-treatment (Recur (−), n = 22) exhibited significant proliferative responses to synthetic peptides from the E6 ( P = 0.001) and the E7 ( P =