Cervical cancer, often caused by persistent human papillomavirus (HPV) infections, remains a public health challenge worldwide despite falling diagnoses related to the success of the HPV vaccine in young adult women. More than 11,500 women in the U.S. are diagnosed with cervical cancer each year, and over 4,000 women die from it.
A randomized three-arm (compares three different groups) phase II trial led by Yale Cancer Center (YCC) researchers at Yale School of Medicine examined the efficacy of imiquimod suppositories — which contain a topical drug that stimulates an immune system response — alone and in combination with the 9-valent human papillomavirus (9vHPV) vaccine in patients with cervical intraepithelial neoplasia (CIN), grades 2 and 3. CIN is a precancerous condition in which an individual develops abnormal cells at the entrance of the uterus (the cervix). It’s often caused by HPV strains.
YCC researchers presented the study’s findings at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, California, on April 9. The results were simultaneously published in the journal Clinical Cancer Research.
A new treatment could be welcomed by women. Surgery is the standard treatment option for patients with CIN2 and CIN3, which can cause reproductive health complications.
In this study, YCC researchers investigated the efficacy of noninvasive immunomodulatory agents and vaccine treatments for women with CIN2 and CIN3. Women with CIN1, in which abnormal cells are the least severe, typically have a regression rate of over 90% over time and do not usually need surgery.
“With CIN1, we don’t do surgery; we advise the patients to come back and see us in 6 to 12 months, so we can repeat the pap smear,” said Alessandro Santin, MD, senior author of the study, professor of obstetrics, gynecology & reproductive sciences at YSM, and co-chief of the section of gynecologic oncology at YCC. “For CIN2 it is different," said Santin. “Our study shows that women with CIN2 have very high regression rates taking imiquimod. With the rate so high, it shows they don’t need surgery and can instead take this topical treatment.”
In this study, researchers randomly grouped 133 patients with CIN 2 (77%) and CIN 3 (23%) into three cohorts. One was treated with imiquimod, another combined the use of imiquimod with the protective shield of the 9vHPV vaccine, and a third group was monitored through clinical surveillance, serving as the control.
The results were positive, well-exceeding regression (reduction of abnormal cells) rates of past retrospective studies for women with CIN2: Ninety-five percent of those treated with imiquimod alone saw their condition regress to levels typically seen with CIN1 (lowest severity) or better, compared to the 79% in the surveillance group. The addition of the 9vHPV vaccine to imiquimod treatment resulted in an 84% regression rate, suggesting that the medication and HPV vaccine may impact the success of each other.
“The imiquimod treatment was patient-friendly and easy to use, since it could be applied by the patient without requiring an office visit,” said Sangini Sheth, MD, MPH, first author of the study, YSM associate professor of obstetrics, gynecology & reproductive sciences, and director of the Colposcopy and Cervical Dysplasia Program, Gynecologic Specialties. “It was also well-tolerated by the study participants, who experienced minimal side effects.”
The trial's results provide evidence for noninvasive procedures to potentially replace surgery as the best strategy for managing CIN2 and possibly CIN3. Santin would like to see future studies that investigate imiquimod for cervical intraepithelial neoplasia include a higher percentage of patients with CIN3.
In addition to Santin and Sheth, Stefania Bellone, Michelle Greenman, Levent Mutlu, Blair McNamara, Shefali Pathy, Mitchell Clark, Masoud Azodi, Gary Altwerger, Vaagn Andikyan, Gloria Huang, Elena Ratner, Daniel J Kim, Akiko Iwasaki, Angelique Levi, Natalia Buza, Pei Hui, Sean Flaherty, and Peter Schwartz were Yale co-authors.