New Study: Vaccine Holds Promise in Treating Cervical Pre-Cancer

Despite the availability of an effective preventive vaccine for the human papillomavirus (HPV), the virus that causes cervical cancer, many girls do not receive this vaccine and go on to contract HPV when they become sexually active. While many of these individuals will clear the virus with the help of their immune system, those who don’t are at high risk of developing cervical cancer.

HPV doesn’t cause cancer right away. It usually takes a few years of chronic infection. But along the way there can be characteristic signs that the virus is wreaking havoc. Abnormal cellular changes, called cervical intraepithelial neoplasia (CIN), can be detected with a Pap smear and other tests. These changes are given a grade from 1-3, depending on severity.

Currently, the only effective treatment option for patients with CIN2/3 is surgery to cut out the affected tissue. But since the procedure is invasive and incurs a risk of reproductive complications, other effective treatment options are badly needed.

A new study by researchers at Johns Hopkins University and published in the journal The Lancet shows that a vaccine designed to stimulate an immune response against HPV cures about half of patients of their pre-cancerous lesions.

The study, led by Connie Trimble, MD, at Hopkins, was a phase IIb trial that enrolled women with CIN2/3 from 36 sites in the U.S. and around the world. A total of 167 women received either the vaccine (n=125) or a placebo (n=42). At 36 weeks following the first dose, 48% of women receiving the vaccine showed regression of their pre-cancer compared to 30% in the control group. More impressive, in the vaccine group, 40% of women had no detectable HPV DNA in their system versus only 10% of women in the control group, suggesting that the HPV infection had been completely cleared in a large fraction of patients.

The vaccine, called VGX-3100, is made by the pharmaceutical company Inovio. It consists of a circle of DNA that has inserted into it two different genes from HPV-16 and HPV-18—two strains of the virus that cause the most trouble. The vaccine is administered intramuscularly. Once inside the body, the circle of DNA is taken up by normal cells, which present the viral proteins to the immune system. It appears to be well-tolerated, with only minor side effects. Xuefei Shen, PhD, a former CRI predoctoral fellow and now a senior scientist at Inovio, is a co-author on the paper.

This study suggests that women with cervical pre-cancer might try such a vaccine first, before having surgery, to see if their pre-cancer regresses. This would spare them having to undergo an invasive procedure that is not without reproductive risk.

CRI has a long history of supporting research that is helping to prevent and treat cervical cancer. In 1999, CRI provided funding to Ian Frazer, for work that led to the development of the HPV vaccine known as Gardasil®, approved by the FDA in 2006 for the prevention of cervical cancer. The development of this vaccine represents a huge contribution to public health. Yet for those women who were already infected at the time Gardasil became available, or who fail to take advantage of it when they are young, ways to treat existing HPV infections are badly needed. This study is a big step in the right direction.

Study: Cornelia L. Trimble, Matthew P. Morrow, Kimberly A. Kraynyak, Xuefei Shen, Michael Dallas, Jian Yan, Lance Edwards, R. Lamar Parker, Lynette Denny, Mary Giffear, Ami Shah Brown, Kathleen Marcozzi-Pierce, Divya Shah, Anna M. Slager, Albert J. Sylvester, Amir Khan, Kate E. Broderick, Robert J. Juba, Timothy A. Herring, Jean Boyer, Jessica Lee, Niranjan Y. Sardesai, David B. Weiner, Mark L. Bagarazzi. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. Published online September 17, 2015.