Turkish Researcher Dr. Refika Yiğit's Therapeutic HPV Vaccine Study

Responsible for approximately 5% of all cancers , human papillomavirus (HPV) remains a major public health issue worldwide. HPV vaccines fall into two categories: preventive and therapeutic. Preventive vaccines aim to stop infection; one of the most widely used is Gardasil 9. It provides strong protection against high-risk types and prevents many infections that cause cervical cancer. However, a therapeutic vaccine for people already infected and showing cellular changes was not yet available. Research has continued for many years, and this new study is considered one of the most tangible advances.

Therapeutic HPV16 Vaccine Found Safe and Effective Against Precancerous Cervical Lesions

Could precancerous cervical lesions be treated without surgery?

A new phase II trial led in the Netherlands by Dr. Refika Yiğit found the experimental therapeutic vaccine Vvax001 safe and effective in patients with human papillomavirus type 16 (HPV16)-positive cervical intraepithelial neoplasia (CIN3).

If confirmed in phase III trials, Vvax001 could offer a nonsurgical alternative for precancerous cervical lesions. The study was published on January 24, 2025, in Clinical Cancer Research .

The Link Between HPV16 and Cervical Cancer

Research shows that high-risk types such as HPV16 and HPV18 cause almost all cervical cancers. An earlier phase I trial found that targeting HPV16 E6 and/or E7 proteins with Vvax001 produced strong cytotoxic T-cell responses. The new phase II trial confirmed this activity and was described as demonstrating preclinical success.

What Is Cervical Intraepithelial Neoplasia (CIN)?

CIN describes precancerous patterns of abnormal cervical cell growth. These changes are not cancer but may become cervical cancer if untreated.

Severity is classified as CIN1, CIN2, or CIN3:

• CIN1 (Mild Dysplasia): Mild abnormalities usually need no treatment because the body can often resolve them itself.
• CIN2 and CIN3 (Moderate-to-Severe Dysplasia): These indicate more serious abnormalities. CIN2 and CIN3 may need treatment if they progress or do not resolve within 1-2 years. CIN3 is generally treated because of its high risk of progression to cervical cancer.

A Potentially Groundbreaking Study

The trial enrolled 18 newly diagnosed patients with HPV16-positive CIN3. They received three doses of Vvax001 at 3-week intervals and were monitored for 19 weeks after the final vaccination using colposcopy . A biopsy at the final visit assessed regression. Persistent CIN2/3 lesions were treated surgically as standard.

Researchers assessed histopathological response, HPV16 clearance, vaccine-related adverse effects, and immune responses.

Findings

• Lesion sizes decreased: Colposcopy showed that in 94% (17/18) of patients, CIN3 lesions decreased in size, visible as early as 3 weeks after the final vaccination.

• Complete disease regression rate: 50%: Histology showed that half the patients (50%; 9/18) had regression from CIN3 to CIN1 or complete disappearance.

• HPV16 clearance: 63%: Complete clearance of HPV16 occurred in 63% (10/16).

• No effect on other HPV types: The vaccine did not clear types other than HPV16.

• All patients remained disease-free: No recurrence has been observed so far. Average and longest disease-free periods were 20 and 30 months, respectively.

• No serious adverse effects: The vaccine caused no serious side effects.

Could This Provide a Nonsurgical Alternative for Precancerous Cervical Lesions?

Principal investigator Dr. Refika Yiğit, a gynecologic oncologist at University Medical Center Groningen, said:

“To our knowledge, Vvax001 appears to be among the most effective therapeutic vaccines targeting HPV16-associated CIN3. If confirmed in a larger trial, at least half of patients with CIN3 could avoid surgery and its side effects and complications.”

These encouraging findings could bring a revolutionary change in treatment. If phase III trials confirm them, Vvax001 could become an important option in gynecologic oncology.

Vvax001: Composition and Mechanism

Vvax001 is a Semliki Forest virus (SFV)-based RNA replicon cancer vaccine encoding HPV16 E6 and E7 oncoproteins. It contains replication-incompetent SFV replicon particles carrying HPV16-derived antigens. After IM administration, it induces E6 and E7 expression and stimulates innate and adaptive immunity, supporting recognition and elimination of HPV-infected cells.

When Might It Become Available?

Vvax001 has not yet been approved by any health authority. If phase III trials confirm efficacy and safety, it could become one of the first approved therapeutic HPV vaccines for precancerous cervical lesions. Strong clinical data may accelerate approval, with potential access within a few years.

Who Is Dr. Refika Yiğit?

Dr. Refika Yiğit studied medicine at KU Leuven from 1994-2001, specialized in obstetrics and gynecology there from 2002-2007, and completed further breast surgery training in 2007-2008. She worked at UMC St Radboud from 2008-2012 and The Royal Marsden NHS Foundation Trust in London from 2012-2013. Since 2013, she has worked at University Medical Center Groningen (UMCG) in gynecologic oncology, minimally invasive surgery, and robotic surgery.