Vaccine eradicates precancerous cervical lesions in half of women studied

Scientists used a genetically-engineered vaccine to successfully regress high-grade precancerous cervical lesions in almost one-half of women who received the vaccine in a phase IIb clinical trial.

The vaccine also cleared human papillomavirus (HPV) infection from the cervix in 40% of women, according to a study published online September 17, 2015 in The Lancet.

Despite the implementation of current vaccines to prevent HPV infection, precancerous cervical lesions are still common in women, most often in those age 40 or younger. However, current treatments to remove these lesions—cervical intraepithelial neoplasias grade 2 and 3 (CIN 2 and CIN 3)—involve ablative procedures, which can lead to long-term obstetrical complications in some instances.

“Every standard therapeutic option for women with these lesions destroys part of the cervix, which is particularly relevant for women of childbearing age, who may then be at risk for preterm birth due to a weakened cervix,” said the study’s first author Cornelia Trimble, MD, professor of gynecology and obstetrics, oncology, and pathology at the Johns Hopkins University School of Medicine, in Baltimore, MD. “A vaccine able to cure precancerous lesions could eventually be one way women can avoid surgery that is invasive and can also harm their fertility.”

For this trial, the scientists used a vaccine, VGX-3100, originally engineered to teach immune system cells to recognize precancerous and cancerous cells. Once injected, the vaccine stimulates the production of antigens that activate and direct T cells to target CIN 2 and CIN 3 caused by HPV types 16 and 18, which account for the majority of HPV-related cancers. The vaccine is made by Inovio Pharmaceuticals, which funded the clinical trial and was involved in authoring the study.

Between 2011 and 2013, the scientists recruited 167 women, ages 18 to 55, with newly diagnosed, high-grade precancerous cervical lesions. The women were randomized to receive 3 doses of either the vaccine or saline injections over a 12-week period. Study centers included 36 hospitals and private gynecology practices in the U.S. and in 6 other countries.

Each of the injections was accompanied by electroporation—tiny electric pulses at the site of the injection that cause cell membranes to open their pores, which increases the likelihood that the vaccine is taken up by immune system cells.

In the treatment group, 114 women received at least 1 vaccine dose. Of these, 55 (48.2%) had regression of CIN 2 or 3 lesions, compared with 12 (30%) of 40 who received saline injections. Of the 114 women in the vaccine group, 107 received all 3 doses. Of these, 53 (49.5%) had regression of their lesions. Of the 40 in the saline group, 36 got all 3 injections, and 11 of them (30.6%) had regression of their lesions.

“In many of these women, the vaccine not only made their lesions disappear, but it also cleared the virus from their cervix,” Dr. Trimble said. “In most unvaccinated patients whose lesions went away, the virus was still present, and many still had low-grade lesions.”

Specifically, scientists could find no trace of HPV in the cervixes of 56 of the 107 women who received the vaccine, compared with only 9 of 35 saline recipients.

Clearance of the virus is a “significant bonus” from receiving the vaccine because persistent HPV infection is a major risk factor for recurrence of cervical lesions, Dr. Trimble explained.

After 12 weeks, surgeons removed lesions that did not regress and took biopsies of each study participant’s cervix. The scientists found that patients whose lesions completely regressed after treatment had more T cells present in the tissue. “It’s important that T cells capable of recognizing HPV stay in the cervix and fight off any recurrence of the infection,” Dr. Trimble said.

“This is a great first step,” she added. “We showed that the vaccine may enable an immune response in a person whose immune system was initially not adequately engaged or was hampered in some way so as to let the lesion occur.”

In an accompanying commentary, Mark Schiffman, MD, MPH, and Nicolas Wentzensen, MD, PhD, of the Division of Cancer Epidemiology & Genetics at the National Cancer Institute in Bethesda, MD, wrote, “The results of the trial suggest that, if approved by regulatory authorities, women might try a course of vaccination to treat cervical precancers positive for HPV-16 or HPV-18, before undergoing conventional treatment that excises the cancer-prone cervical transformation zone.”

They added, “Therapeutic vaccination could become the proper treatment not only for women diagnosed with precancer, but for all women with HPV persistence past an accepted waiting period.”

The investigators are now working to identify biomarkers from cervical tissue that can predict which lesions are more likely to persist and eventually progress to cancer. It was once one of the most common causes of cancer death for American women, early detection has become key to recent increased cervical cancer survival rate. The research team will be monitoring this initial group of study participants to see whether they have fewer recurrences than unvaccinated patients.