In a small study, a self-administered vaginal insert containing the antimalarial agent artesunate resolved cervical intraepithelial neoplasia (CIN) 2/3 lesions in two-thirds of patients and cleared human papillomavirus (HPV) genotypes in nearly half of women whose lesions disappeared.
Ying Liu, Shanghai Xinhua News Agency
Artemisia annua plants yield the antimalarial artemisinin.
Among 28 women with biopsy-confirmed CIN 2/3 who used the inserts prior to a planned standard-of-care resection, histologic regression of lesions occurred in 19 patients. In 9 of the 19 women, there was clearance of baseline HPV genotypes.
These results were reported in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The study results were also published in Gynecologic Oncology.
An unexpected treatment
“The implications of having a safe, inexpensive, self-administered, shelf-stable, nonsurgical treatment for HPV intraepithelial disease, not only here in the U.S., but also extending to low-resource settings,” are self-evident, said study author Cornelia L. Trimble, MD, of Johns Hopkins University in Baltimore.
“This could change the entire landscape of care,” Dr. Trimble said in an interview. “Who’d have thunk that a freaking Chinese herbal medicine derived from the bark of a tree could have this effect?”
Artesunate is a derivative of artemisinin, an antimalarial isolated from the plant Artemisia annua, which is used in traditional Chinese medicine. According to the Centers for Disease Control and Prevention, intravenous artesunate is the first-line drug for treatment of severe malaria in the United States.
However, artesunate is neither approved by the Food and Drug Administration nor commercially available in the United States. The CDC provides artesunate to U.S. clinicians on an as-needed basis.
In addition to its antimalarial activity, artesunate has been shown to have a cytotoxic effect on squamous cells transformed by HPV in vitro. Dr. Trimble and colleagues are also testing a topical form of the drug for the treatment of vulvar intraepithelial neoplasia.
Patients, dosing, and efficacy
In the current study, Dr. Trimble and colleagues enrolled adult immunocompetent women with CIN 2/3, visible residual lesions, and detectable HPV. The patients were assigned sequentially to one of four treatment groups: one 5-day cycle of 50-mg inserts or one, two, or three 5-day cycles using 200-mg inserts.
The patients were instructed to place the inserts at bedtime using a vaginal applicator, followed by a tampon, and then remove the inserts in the morning.
In a modified intention-to-treat analysis including all women who received at least one dose of artesunate and who had endpoint data available, 19 of 28 (67.9%) had histologic regression of CIN lesions. Of the 19 patients, 9 (47.4%) had clearance of all HPV genotypes that had been present at baseline.
Dr. Cornelia L. Trimble
Asked how the investigators could distinguish between the treatment effect of the inserts and spontaneous clearance of lesions seen as part of the natural history of CIN in some patients, Dr. Trimble pointed to two observations suggesting an immunologic effect from treatment.
Specifically, although there was lesion regression to CIN 1 or less in all treatment groups, the patients who had only a single treatment cycle had a longer time to regression than those who received two or three cycles.
Additionally, among the nine patients who had viral clearance, three had clearance at the same study time point where histologic regression was observed. For the other six patients, the virus did not clear until several weeks following lesion regression.
These two observations suggest the therapeutic effect of artesunate is recognized by the immune system, which may stimulate a localized immune-mediated cytotoxic effect, Dr. Trimble said.