HPV Vaccine ‘Very Promising’ for Nixing Precancerous Lesions

An experimental therapeutic human papillomavirus (HPV) vaccine showed promise in inducing regression of precancerous cervical lesions as well as viral clearance in patients with cervical intraepithelial neoplasia type 3 (CIN3), according to a small phase II, nonrandomized study.

“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,” said Refika Yigit, MD, principal investigator and oncological gynecologist at University Medical Centre Groningen, Groningen, the Netherlands, in a press release.

The findings, published in Clinical Cancer Research, suggest the vaccine may be “one of the most effective therapeutic vaccines for HPV16-associated CIN3 lesions reported to date,” Yigit added.

The rSFVeE6,7 vaccine (Vvax001) targets tumor-specific antigens E6 and E7, which are over-expressed in HPV16 — the infection most commonly linked to premalignant and malignant cervical lesions. The vaccination was previously shown to be safe and to induce robust cellular immune responses in 12 participants with a history of CIN2 or CIN3 in a phase I trial. 

The current study included 18 participants with newly diagnosed HPV16-positive CIN3 (median age, 32.5 years) who received three Vvax001 immunizations at 3-week intervals. The primary endpoint, histopathologic regression, defined as regression of CIN3 lesions to CIN1 or no dysplasia, was assessed by biopsy at 19 weeks after the last vaccination.

Regression was achieved in nine participants (50%) , three of whom had a complete regression (no dysplasia), and six others who regressed to CIN1. Immunogenicity, assessed by measuring HPV16 E6- and E7-specific T-cell responses in peripheral blood at baseline, and at weeks 1, 3, 11 and 19 weeks, was observed in all nine regressors (100%).

Colposcopic imaging also showed a reduction in lesion size in 17 of the 18 patients (94%). In addition, HPV clearance, a secondary endpoint, was observed in 63% of the 16 study participants whose data was available at the time of the analysis. 

Vaccination appeared to be safe, with no grade 2 or higher treatment-related adverse events. Besides local injection site reactions such as pain, swelling, erythema, and bruising, other reactions included swollen lymph nodes in groins, malaise/fatigue, and myalgia. All treatment-related adverse events resolved without intervention within a median time of 3 days (range 1-52 days), the study authors wrote.

For the nine participants without regression, loop excision of the transformation zone (LETZ) was performed, with no residual disease and a decrease in lesion size on colposcopy in 4 patients, the researchers reported, suggesting that a longer follow-up period may yield better results. “It could be that, in these patients, the time after the last immunization was too short to eradicate the full lesion,” the authors wrote.

No disease recurrences were observed either among regressors or among nonregressors who underwent a LETZ, with the longest follow-up extending to 30 months.

The authors noted that the study’s observed histopathologic regression rate of 50% “far exceeds” spontaneous regression rates reported for CIN3, which range from 1.3% to 30% within 2-24 months after the initial biopsy. 

While there are multiple similar vaccine strategies currently under investigation, and some promising results have been presented at meetings, this is the first study to go to publication, said Kimberly Levinson, MD, MPH, director of Johns Hopkins Gynecologic Oncology, Baltimore, Maryland, who was not involved in the research.

The results are “very promising” and have potentially important and exciting clinical implications, although, “larger, randomized studies are needed to evaluate this strategy further,” Levinson told Medscape Medical News.

And while the primary endpoint of histopathologic regression is important, “because this addresses the immediate risk of progression to cervical cancer”, it is the combination of that plus viral clearance that determines vaccine efficacy, she explained. “Long-term viral clearance is an important outcome because even if the changes in the tissue regress, if HPV 16 is still present, it can continue to cause changes in the future.”