Experimental HPV vaccine shrinks high-grade precancerous cervical lesions

A novel vaccine that targets HPV type 16 (HPV16) has shown clinical activity against HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3) in a phase II trial, substantially reducing lesion size.

Named Vvax001, the vaccine is based on the Semliki Forest virus that cannot replicate and produces the oncogenic E6 and E7 proteins that are expressed exclusively by HPV16-infected cells.

A total of 18 patients (median age 32.5 years) with HPV16-positive CIN3 received three doses of Vvax001 in the trial. The vaccine was administered at 3-week intervals. During each treatment visit, each patient received two intramuscular shots of 1 mL, one into each upper leg.

Colposcopic examination results revealed a significant reduction in CIN3 lesion sizes in 17 patients (94 percent) as early as 3 weeks after the last immunization. Histopathological complete response (regression to CIN1 or no dysplasia) was observed in nine patients (50 percent), and HPV16 clearance occurred in 10 of 16 evaluable patients (63 percent). [Clin Cancer Res 2025;doi:10.1158/1078-0432.CCR-24-1662]

According to principal investigator Dr Refika Yigit from the University Medical Centre Groningen in Groningen, Netherlands, effective CIN3 management hinges on the clearance of HPV16. In the cohort, eight patients who showed CIN3 regression and two who did not were cleared of HPV16. Yigit noted the eradication of HPV16 through the vaccine therefore has the potential to prevent disease recurrence among both regressors and nonregressors.

Meanwhile, the nine patients whose lesions did not regress all underwent loop excision surgery. Given that no residual disease was detected in four of these patients, Yigit underscored the possibility that the delayed surgical intervention might have allowed for spontaneous regression of the lesions.

The median disease-free survival was 20 months, with the longest being 30 months. “To date, no recurrences have been observed,” she noted.

In terms of safety, Vvax001 was safe and well tolerated. None of the patients experienced grade >3 treatment-related adverse events (AEs). The most common AEs were local injection site reactions, swollen lymph nodes in groins, malaise/fatigue, and myalgia, all of which resolved without intervention within a median of 3 days.

“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,” Yigit said.

She highlighted the clinical implications of the findings, saying that nearly all premalignant cervical lesions and cervical cancers are linked to HPV infection, with HPV16 being the most common strain.

CIN3 represents a significant precancerous condition where cells have begun to exhibit abnormal changes indicating an increased risk of malignancy, the investigator explained. Without treatment, approximately one-third of these cases progress to cervical cancer within a decade, and roughly half within 30 years, she added.

“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,” Yigit said.

The study had several limitations, including limited follow-up time, small sample size, and lack of a control group for spontaneous regression due to ethical concerns.