Therapeutic Vaccine Clears HPV in One-Third of Cervical Precancers

The results from a new clinical trial of a potential new immune-based therapy to treat precancers in the cervix were very positive. 

A therapeutic vaccine completely eliminated both the lesion and the underlying human papillomavirus (HPV) infection in a third of women enrolled in this clinical trial, which was published on April 4, 2019. 

The therapeutic vaccine Tipapkinogen Sovacivec injects a specific protein that triggers an immune system response to attack high-risk HPV types that cause nearly all cervical cancer precursors, known as cervical intraepithelial neoplasia, or CIN. 

These researchers noted that the Tipapkinogen Sovacivec vaccine is completely different from Gardasil 9 which is the vaccine given to prevent HPV infection. 

The primary difference is Gardasil 9 prevents HPV infection from occurring, while Tipapkinogen Sovacivec clears tissue already infected with HPV. 

With this vaccine, the researchers found that it not only eliminated the lesions but also eliminated the HPV infection. 

"It actually treats the cause of the disease, which is HPV," said Diane Harper, M.D., M.P.H., M.S., professor of family medicine and obstetrics and gynecology at Michigan Medicine, in a press release.

This new study published in Gynecologic Oncology enrolled 192 women diagnosed with CIN received the vaccine were more than twice as likely as those who received placebo to see their CIN eliminated, regardless of the type of HPV infection. 

The results were more positive in the more-severe CIN 3. 

At least 15 percent and as much as 36 percent of those who got the vaccine saw their CIN3 eliminated, while none of the women in the placebo group did. 

Researchers showed that long-term follow-up was better for those who received the vaccine over placebo, with more women in the vaccine group remaining completely clear of HPV. 

"There are very few products trying to cure women who already have an HPV infection," says Dr. Harper. 

"This is the first time we've seen something with this success rate that is relatively easy to implement." 

Cervical precancerous lesions are divided into three grades of severity:

• CIN 1 lesions generally clear up on their own,
• CIN 2 lesions often clear up on their own, but can also progress to CIN 3 lesions,
• CIN 3 is the most severe. It's a very slow-growing disease, though: fewer than half of CIN 3 lesions will have become cancer within 30 years.

"But we have no way to determine which women with CIN 3 will progress to cancer and which women will not. So we treat all women with CIN 2 or 3 as if they are likely to develop cancer," Dr. Harper says. 

The typical treatment procedure for CIN2 or CIN3 involves removing a cone-shaped piece of the cervix, called a LEEP or a cone. This results in scarring and a shortened cervix, which can cause problems during childbirth and lead to increased risk of cesarean section. 

In addition, women who have this procedure have a very high risk of developing cervical cancer over the next 20 years if they do not continue to be screened. 

"The surgical procedure removes all the tissue that is headed towards cancer, but it doesn't remove all the HPV. You're not home-free. You still have HPV," says Dr. Harper. 

Women who received the vaccine injections reported sometimes-severe reactions at the injection site. 

Dr. Harper says that was expected because the vaccine is designed to trigger the immune system. An immune reaction is likely to inflame the skin. 

The study looked only at cervical lesions, but HPV is linked to several other types of cancer, including head and neck cancer and anal cancer.

Additional clinical trials are needed before seeking approval for Tipapkinogen Sovacivec from the U.S Food and Drug Administration. No trials are currently available. 

Additional study authors: Pekka Nieminen, Gilbert Donders, Mark H. Einstein, Francisco Garcia, Warner K. Huh, Mark H. Stoler, Katerina Glavini, Gemma Attley, Jean-Marc Limacher, Berangere Bastien, Elizabeth Calleja

The funding was provided by F Hoffmann-La Roche LTD. Roche, who sold the compound to Transgene. Transgene facilitated the data analysis with Dr. Harper. 

Reference: Gynecologic Oncology, doi: 10.1016/j.ygyno.2019.03.250; published online April 4, 2019