PURPOSE

Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. In this study, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia (CIN) grade 3 (CIN3).

PATIENTS AND METHODS

Patients with newly diagnosed HPV16-positive CIN3 were eligible for participation. Patients received three immunizations of Vvax001 (5 × 107 infectious particles) at a 3-week interval. Up to 19 weeks after the last immunization, patients were monitored for regression of CIN3 by colposcopy. A colposcopy-guided biopsy was taken at the last visit, and a standard-of-care loop excision was performed only in case of remaining CIN grade 2/CIN3. Histopathologic response rates, HPV16 clearance, treatment-related adverse events, and vaccine-induced immune responses were assessed.

RESULTS

A total of 18 patients were enrolled and fully immunized. Colposcopic examination revealed a reduction in CIN3 lesion sizes in 17/18 (94%) patients already evident from 3 weeks onward after the last immunization. A histopathologic complete response (regression to CIN grade 1 or no dysplasia) was observed in 9/18 patients (50%) and HPV16 clearance in 10/16 patients (63%). Vvax001 did not induce clearance of other HPV types. To date, no recurrences have been observed, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious adverse events were observed.

CONCLUSIONS

Treatment with Vvax001 is safe and feasible and shows preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions.