An article in today’s New England Journal of Medicine reports some interesting and intriguing research that may help some women with a not uncommon pre-cancerous lesion of the vulva called vulvar intraepithelial neoplasia, or VIN.
By using proteins found in the cancer-causing human papilloma virus type 16 (HPV-16), the researchers were able to make a vaccine that actually led to an effective treatment for a small group of women with VIN, resulting in complete disappearance of the lesion in almost half of the women they treated.
You may have heard of HPV infections. These are the viruses that cause cervical cancer. Two of these viruses—types 16 and 18—are responsible for the majority of cervical cancers in the United States. They are also the viruses targeted by currently available vaccines which prevent infection with HPV thus reducing the risk of developing cervical cancer.
It turns out that the same viruses are also related to VIN, especially type 16 which causes over 75% of VIN. (VIN is a superficial lesion on the vulva which can actually last for many years.)
The problem is that the treatments for VIN are sometimes unsatisfactory, and the lesions can recur frequently after treatment. Topical medicines, surgery and laser treatments are commonly used. More recently, an antiviral medicine called imiquimod has been reported to be effective and less irritating. About 1 out of 65 VIN lesions can resolve spontaneously.
And, just like what can happen in the cervix where the HPV infection progresses on to cervical cancer, untreated VIN can become an actual vulvar cancer. Fortunately, this is uncommon.
In this current report, the doctors made a vaccine using cancer-causing proteins from the virus. They treated women with advanced pre-cancerous VIN by giving them the vaccine under the skin of the arm or leg every three weeks for a total of three to four injections. Side effects were tolerable, and frequently included a local reaction at the vaccination site in addition to flu like symptoms, chills and tiredness.
The responses in some of the women were remarkable: At one year, 6 of the 19 patients had a partial response to the vaccine. 9 of the patients (47%) had complete disappearance of the VIN, which lasted for at least another 12 months. As a result, 79% of the women responded to the vaccine. This compares to a complete response rate of 35% for lesions treated with imiquimod, according to the report.
Unfortunately, not all of the women had such positive responses to the vaccine. Two of the participants went on to develop cancer, and one of those women had shown a previous partial response to the vaccine.
The researchers also measured whether the women’s immune systems responded to the vaccine. All of the women in the study did have a response, and those with a complete resolution of their VIN at 3 months after treatment had much stronger responses compared to women who did not have a complete regression.
What’s interesting to me about this research is that it seems to work in a way that is different from what we have seen before.
We are all familiar with the typical types of vaccines, where the vaccine contains a protein from a virus or bacteria that is given to us when we aren’t sick with an infection and then prevents us from getting the same infection at a later date.
Here we have a situation where the woman is already infected with the virus, and her body has either not developed a response to the infection or become “tolerant” to the virus. That’s usually a situation where vaccination doesn’t work. Think of having the flu, then getting the flu vaccine. Basically, it’s too late.
That same theory carries over to the currently available cervical cancer vaccine. If a woman has already become sexually active and infected with HPV, then giving her the preventive vaccine isn’t going to be effective in reducing her risk of cervical cancer.
But, for some reason, in this trial giving a piece of the virus to stimulate the immune system after the infection had set in did work. What I don’t understand is how that happened. It just is not what one would ordinarily expect based on the science.
These doctors weren’t interested in making a prevention vaccine. What they developed, as they report, was a therapeutic vaccine.
Maybe I shouldn’t be so worried about how this happened, and just be glad that in fact it did happen.
The implications of this research are significant.
First, it may mean that this vaccine will be studied further (this was a very small, early stage trial) and eventually be available for wider use in the treatment of women with VIN.
But—perhaps more importantly—it raises the question of whether a similar approach could be used in women who have advanced pre-cancerous lesions in the cervix.
These researchers have actually previously reported studies using the same vaccine in women with either advanced or treated cervical cancer. In one study, they vaccinated women who had cervical cancer that was successfully treated surgically, and were able to induce an immune response to HPV-16 using this vaccine.
As they stated in that article, the results of the study “indicates the potential of this vaccine for the immunotherapy of HPV 16-induced progressive infections, lesions, and malignancies.”
In plain language, if this vaccine is effective in VIN, and it can demonstrate the ability to cause an immune response in women who have already been diagnosed with cervical cancer, then maybe it can also be effective in treating women who have pre-cancerous cervical lesions as well.
I suspect it will be some time before we know the rest of the story as to whether this vaccine is truly effective in treating women with VIN or whether it can improve the treatment for women with pre-cancerous lesions of the cervix. Patience is clearly going to be part of the process.
But if this theory holds up, then this report could be the foundation of a new approach to treating some not-uncommon pre-cancerous diseases. And that is very exciting news indeed.