According to results from a small phase 2 study, an investigational therapeutic HPV vaccine showed clinical effectiveness in patients with human papillomavirus (HPV)16-positive cervical intraepithelial neoplasia grade 3 (CIN3), the most severe pre-cancerous cervical dysplasia.

The results from this small phase 2 clinical are very encouraging, meaning we may have a new treatment for the pre-cancerous lesions that lead to cervical cancer.

I have reviewed other therapeutic cancer vaccines in development, all of which may provide oncologists with more tools to effectively treat different cancers. Of course, the HPV vaccine greatly decreases the risk of cervical cancer making it a true cancer prevention vaccine.

This post will examine the results of this study on the new therapeutic HPV vaccine, which was published in a peer-reviewed journal.

What is cervical dysplasia?

Cervical dysplasia is most commonly caused by the human papillomavirus (HPV). HPV is a common virus that is spread through sexual contact. There are many types of HPV, some of which can lead to cervical dysplasia or cancer.

Cervical dysplasia refers to abnormal changes in the cells on the surface of the cervix. The cervix is the lower part of the uterus (womb) that opens at the top of the vagina. The changes are not cancer, but they can lead to cancer of the cervix if not treated. This is why it’s considered “pre-cancerous.”

Dysplasia that is seen on a biopsy of the cervix is called cervical intraepithelial neoplasia (CIN). It is grouped into 3 categories:

• CIN1 —mild dysplasia
• CIN2 — moderate to marked dysplasia
• CIN3 — severe dysplasia to carcinoma in situ

Mild dysplasia may go away without treatment, although it should be monitored. CIN2 and CIN3 dysplasia that does not go away may require surgery or other interventional treatment.

Therapeutic HPV vaccine study

In a paper published on 24 January 2025 in Clinical Cancer Research, Refika Yigit, MD, University Medical Centre, Groningen, Netherlands, and colleagues reported the results of a small clinical trial using the therapeutic cancer vaccine, Vvax001. This open-label study was conducted at the University Medical Centre Groningen and enrolled patients between March 2021 and August 2023. Median age was 32.5 years, and 12 of 18 patients had a single HPV16 infection at baseline. 

Vvax001 vaccine, developed by ViciniVax a Dutch biopharmaceutical company, uses a modified version of the Semliki Forest virus that cannot replicate and encodes a fusion protein of the oncogenic proteins and tumor-specific antigens E6 and E7 of HPV16. The E6 and E7 proteins are key oncogenes in the development of HPV-associated tumors.

The vaccine trains the immune system to target both cancer and HPV16 tumor-specific antigens.

Here are the key results of the study:

• Vvax001 showed a reduction in CIN3 lesion size in 17 of 18 patients, with reductions evident as soon as 3 weeks after the last immunization.
• Six of the patients had a regression to a CIN1 lesion.
• Three had a complete regression (no dysplasia).
• 10 of 16 patients (eight with regression and eight non-regressors) exhibited HPV16 clearance 19 weeks after the last vaccination, including all eight patients with histopathologic regression, as well as two non-regressors. HPV16 clearance is important to the management of CIN3 dysplasia.
• The vaccines were safe and well-tolerated, with no reported grade >3 treatment-related adverse events. Besides local injection site reactions (which are common to most vaccines), swollen lymph nodes in groins, malaise/fatigue, and myalgia were observed, with all treatment-related adverse events resolved without intervention within a median of 3 days.

Summary

This is a small, early study, but it shows some good results for the therapeutic HPV vaccine to reduce CIN3 dysplasia. The vaccine is effective and has a strong safety profile. I do not know if the researchers are planning a larger phase 2 or 3 study, but given the positive results, I believe that they will proceed if possible.

Of course, there is powerful evidence that the HPV vaccine itself will prevent HPV infections which lead to cervical cancer. It’s better to prevent a disease rather than treat it.

Citations

• Eerkens AL, Esajas MD, Brummel K, Vledder A, van Rooij N, Plat A, Avalos Haro SB, Paijens ST, Slagter-Menkema L, Schuuring E, Werner N, Kosterink JGW, Kroesen BJ, Wilschut JC, Daemen T, Bart J, Nijman HW, de Bruyn M, Yigit R. Vvax001, a Therapeutic Vaccine for Patients with HPV16-positive High-grade Cervical Intraepithelial Neoplasia: a Phase II Trial. Clin Cancer Res. 2025 Jan 24. doi: 10.1158/1078-0432.CCR-24-1662. Epub ahead of print. PMID: 39849926.