An investigational therapeutic vaccine, Vvax001, has demonstrated promising results in treating high-grade precancerous cervical lesions caused by human papillomavirus type 16 (HPV16). The Phase II clinical trial, published in Clinical Cancer Research, indicates that Vvax001 could offer a non-surgical alternative for women with cervical intraepithelial neoplasia grade 3 (CIN3), a condition that, if untreated, progresses to cervical cancer in approximately one-third of cases within 10 years.
The study, led by Dr. Refika Yigit, an oncological gynecologist at University Medical Centre Groningen in the Netherlands, aimed to evaluate Vvax001 as a potential alternative to the standard-of-care loop excision, which is associated with complications. Vvax001 is a modified, non-replicating Semliki Forest virus vaccine that expresses the HPV16 oncogenic E6 and E7 proteins.
Study Design and Results
The Phase II trial involved 18 patients with HPV16-positive CIN3 who received three doses of Vvax001, administered three weeks apart. Patients were monitored via colposcopy, with a final biopsy conducted 19 weeks post-immunization. The results showed that nine of the 18 patients experienced regression: six to low-grade dysplasia and three with complete regression and no signs of dysplasia. Lesion size was significantly reduced in all but one patient within a month of completing vaccination.
"To the best of our knowledge, this response rate makes Vvax001 one of the most effective therapeutic vaccines for HPV16-associated CIN3 lesions reported to date," said Dr. Yigit. "If confirmed in a larger trial, our results could mean that at least half of the patients with CIN3 might be able to omit surgery and avoid all its possible side effects and complications."
HPV Clearance and Follow-Up
In the study, 10 of the 16 patients evaluated cleared HPV16, including all nine of those whose disease regressed. Two patients whose disease did not regress also cleared HPV16; however, their lesions harbored other HPV strains. After a median follow-up of 20 months, none of the patients experienced a recurrence.
Implications for Clinical Practice
The current standard of care for CIN3, loop excision, carries risks of adverse obstetric outcomes, cervical stenosis, and postoperative complications. Vvax001 offers a potential non-invasive alternative by targeting the E6 and E7 proteins, which are crucial in the development of HPV-associated tumors.
Study Limitations
Limitations of the study include a small sample size, limited follow-up time, and the absence of a control group for spontaneous regression due to ethical considerations. The study was supported by the Dutch Cancer Society (KWF) and ViciniVax.
