When Maria Aprile was 25, she went to her doctor for her annual cervical cancer screening. Like millions of women, she didn’t think much of it.
But then she received a notification from her doctor that “abnormalities were noted,” and she needed to return to the office for a colposcopy, a diagnostic procedure to examine the cervix for disease.
As a woman in a long term partnership, questions about HPV exposure, past sexual partners, and the process of an invasive biopsy felt “terrifying.” After the colposcopy confirmed a CIN 2 lesion, a growth that can become cancerous if not treated, Aprile was fearful at the prospect of one day facing cervical cancer.
Plus, she now had to face enduring — and paying for — a LEEP procedure, which is an outpatient surgical procedure to cut lesions out of the cervix. She had a severe anxiety reaction to the colposcopy, throwing up during the procedure, so facing a more invasive LEEP was daunting.
But before her LEEP procedure was scheduled, a coordinator for a clinical trial offered at Michigan Medicine contacted Aprile and suggested she might be a good candidate to participate.
The Frantz Viral Therapeutics trial is testing whether a vaginal insert can eliminate the abnormal cells and clear the cancer causing HPV infection. If successful, it would provide a non-surgical, topical alternative to surgical interventions for CIN 2 or 3 cervical lesions. It’s currently enrolling patients at four sites: Michigan Medicine, Cleveland Clinic, MD Anderson Cancer Center, and Florida Gynecologic Oncology. There is no cure for HPV currently.
If the medication is proven effective and then approved by the FDA, it could replace an invasive LEEP procedure with a prescription topical treatment that a woman would receive from her doctor, without needing the surgery.
Aprile was considered a good candidate for the trial, and she jumped at the chance.
“They told me that their study was on a medication that could help women not need certain procedures,” said Aprile, who lives in Ann Arbor. “If I could help other women to not have to go through everything that I went through, that would make my experience all worth it.”
Michigan Medicine’s FRANTZ trial principal investigator, Diane Harper, MD, MPH, MS, a professor in the Department of Family Medicine and a member of Michigan Medicine's Rogel Cancer Center echoed that sentiment.
“If you have a CIN 2 or 3 lesion, you need to get treated. But we hope this trial will help us figure out if using a vaginal drug can cure the HPV and the diseased tissue,” said Harper.
Participating in the FRANTZ clinical trial
The site coordinator walked Aprile through why she might be a candidate, and why they were doing the trial. She was Aprile’s point person throughout her experience, always available to answer questions, explain what would happen, and coordinate her care with Harper, who Aprile says was completely available to her and supportive every step of the way.
“The LEEP procedure is an excisional procedure, like taking off a mole,” Harper said. “We go in and cut out a small ice cream scoop of tissue in the cervix. Depending on how deep we must go in, it’s associated with a shorter cervix because we remove the tissue. Sometimes, if a woman wants to get pregnant afterward, the integrity of the tissue might not be as strong, which can cause issues like early delivery.”
It’s important to note that this procedure does not cure the HPV.
“I’ve seen a patient who had five different LEEP procedures,” Harper said, due to the persistent presence of HPV infection causing recurring lesions.
Investigators hope to find a better way
The trial requires four in person clinic visits: one at the beginning, one at six weeks, one at 17 weeks, and a final visit at 40 weeks for follow up. All other visits are done via telehealth, and patients are reimbursed for their time, plus the cost of care is fully covered.
After a person is accepted into the trial, they will receive either the trial drug or a placebo, and take it as a vaginal insert for three, five-day courses for a total of 15 days of medication.
At week 17, all participants receive a LEEP procedure as standard of care. At the end of the trial, an analysis will determine if the medication was effective at eliminating the lesions and curing the HPV. Waiting 17 weeks for a LEEP to remove precancerous cells isn’t a concern, Harper notes, because it typically takes 10 years for a CIN 2 or 3 lesion to develop into cervical cancer.
In a phase 1 trial 68% of women who received the topical treatment cleared their CIN2/3 lesions and half of the participants who had clearance of their lesions also tested negative for HPV. About 300,000 women in the United States are diagnosed with these lesions every year, so the need is huge.
“That is a really great advancement,” Harper said. “LEEP doesn’t always clear HPV, so if we can cure HPV for some women with this drug while causing precancerous cells to disintegrate, that would be significant.”
Caring support, in pursuit of science
Like many of her generation, Aprile received the Gardasil vaccine for HPV as an adolescent. Upon reviewing her records with Harper, she learned that the vaccine protected her against some strains of HPV, but not the ones Aprile contracted that caused her lesion.
As someone who grew up understanding the risks of sexually transmitted infections and always seeking to maintain safe behavior, hearing that she had an HPV-caused abnormal Pap was concerning.
“I just felt really scared and worried,” she said. “Growing up, my mom wanted me to be educated on good sex health and making sure that I was careful. She would talk about STIs and highlight HPV, saying I should be careful because men don't know if they have the virus. The people who tend to suffer from it are women, it wasn't something men needed to think about.”
Participating in the clinical trial has helped Aprile feel empowered about this turn in her health.
“(The study team) has taught me a lot, and I don’t feel afraid about it anymore, I just feel good about it. It was better to go through this (with the team) and to feel like I have a really good team,” she said. “I just want women to have appropriate health care and not go through these things alone.”
“This is a really important trial,” Harper said. “Hundreds of thousands of women each year must go to colposcopy after their abnormal cervical cancer screening that is only partially covered by insurance – over 80% of women have a significant out of pocket cost to get the colposcopy done.
“When a precancer is diagnosed they undergo LEEP procedures which requires another invasive speculum exam – all cost shared with insurance companies requiring even more out of pocket for women to pay out. If this medication proves to be effective, treating these lesions would be just like treating any other infection. And, if it fails, then we still have surgery as a back-up option.”
Find out more here about the FRANTZ trial or by calling 800-865-1125.
