Investigative vaccine eradicates precancerous lesions in some women

by Bruce Sylvester: Researchers report that a genetically engineered vaccine, VGX-3100/ Inovio Pharmaceuticals,  appears to eradicate high-grade precancerous cervical lesions in some women. The findings from a phase 2b trial were published online on Sept. 17, 2015 in The Lancet.

“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 lead author Cornelia Trimble, M.D., professor at the Johns Hopkins University School of Medicine in Baltimore. “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.”

Between 2011 and 2013, the researchers scientists enrolled 167 women, ages 18 to 55, with newly diagnosed, high-grade precancerous cervical lesions.

They randomized the subjects to three doses of the vaccine or placebo saline injections, and over a 12-week period.

Following each injection, the subjects received a small electric pulse at the injection site. Cells near an electric pulse open their pores, Trimble explained, thereby increasing the possibility that the vaccine will be absorbed by immune system cells.

Of 114 subjects who received at least one vaccine dose, 55 (48.2 percent) achieved regression of their precancerous lesion (conversion to low-grade lesions), compared with 12 of 40 subjects (30 percent) who received placebo.

Of the 114 vacccine-treated treated subjects, 107 received all three vaccine doses, and 53 of them (49.5 percent) achieved regression of their lesions. Of the 40 subjects in the placebo group, 36 received three injections, and 11 (30.6 percent) achieved regression of their lesions.

Thirteen subjects dropped out of the study following enrollment.

Among those who received all three injections, the investigators found no trace of HPV in the cervixes of 56 of those who received the vaccine, compared with nine of those who received the placebo.

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

Trimble noted that  virus clearance is a important since persistent HPV infection is a major risk factor for cervical lesion recurrence.

In a related Comment  in The Lancet,  senior investigators at the U.S. National Cancer Institute Division of Cancer Epidemiology & Genetics, Mark Schiffman, MD and Nicolas Wentzensen, MD, wrote,  “The current trial represents a major breakthrough and proof-of-principle that therapeutic HPV vaccination is feasible. More broadly, the trial shows that it is possible to boost immune clearance of HPV among women who initially failed to control infection.”