The goal was to find nonsurgical ways to treat precancerous lesions caused by HPV. “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,” says Prof. Cornelia Trimble, M.D. “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.”
High-grade cervical lesions, termed CIN2/3, occur most often in women 40 or younger. Because the lesions can progress to cancer, they are usually removed by surgery, freezing or laser. The procedures are successful in removing the precancerous areas in approximately 80% of women. Low-grade dysplasia, are usually monitored by physicians rather than immediately removed because they pose less of a risk for cancer and usually regress on their own.
METHOD: the scientists used vaccine VGX-3100, originally developed by University of Pennsylvania scientist David Weiner, Ph.D., engineered to teach immune system cells to recognize precancerous and cancerous cells. Those cells are coated with proteins linked to an infection with 2 strains of HPV – 16 and 18 – that cause cervical cancer.
~from 2011 – 2013, 167 women, 18 to 55 yo were recruited, with newly diagnosed, high-grade precancerous cervical lesions. The women were randomly assigned to receive either 3 doses of the vaccine or saline injections over a 12-wk period at 36 hospitals and private gynecology practices in the U.S. and 6 other countries.
~After each of the injections, the women got a small electric pulse at the arm site of the injection. Cells near the electric pulse open their pores increasing the likelihood that the vaccine will be taken up by immune system cells.
RESULTS: Of 114 women who received at least 1 vaccine dose, 55 (48.2%) had a regression of their precancerous lesion ie lesions disappeared or converted to low-grade lesions, vs 30% who received saline injections. Of the 114, 107 received all 3 vaccine doses, and 53 of them 49.5% had regression of their lesions. Of the 40 in the saline group, 36 got all three injections, and 30.6% had regression of their lesions.
13 women dropped out of the study after enrollment. 2 patients discontinued the study because of pain at the injection site. Skin redness was more common in the vaccine group compared with saline.
Among women who completed all 3 injections, 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. “In many of these women, the vaccine not only made their lesions disappear, but it also cleared the virus from their cervix,” says Trimble. “In most unvaccinated patients whose lesions went away, the virus was still present, and many still had low-grade lesions.”
After 12 weeks, doctors surgically removed lesions that did not regress and took biopsies of each study participant’s cervix. In the surgically removed lesions, scientists found miniscule cancers in 2 of the women who received the vaccine. These microinvasive cancers are rarely diagnosed by a biopsy but are found in surgical specimens.
Those 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,” says Trimble.
They are now working to identify biomarkers from cervical tissue that can predict which lesions are more likely to persist and eventually progress to cancer. The research team will be monitoring this initial group of study participants to see whether they have fewer recurrences than unvaccinated patients. Trimble is also studying other types of vaccines to prevent the progression of high-grade cervical lesions to cancer.
http://www.hopkinsmedicine.org/news/media/releases/vaccine_clears_some_precancerous_cervical_lesions_in_clinical_trial
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