UNC Lineberger researchers are working on a test that could provide a less invasive option for monitoring patients at risk for cervical cancer.

UNC Lineberger’s Gaorav Gupta, MD, PhD, and Shivani Sud, MD, are launching a pilot study of a test to monitor patients at risk for cervical cancer by tracking levels of human papillomavirus, or HPV, in the blood or urine.

Cervical cancer is the second most common cancer caused by infection with HPV in the United States, according to the Centers for Disease Control and Prevention. HPV causes nearly all cervical cancer cases.

Gaorav Gupta, MD, PhD.

“The biggest question is: How can we determine who is at greatest risk of developing cervical cancer?” said Gupta, who is an assistant professor in the UNC School of Medicine Department of Radiation Oncology. “What we’re hypothesizing is that our blood test may be able to do this in a less invasive way and potentially decrease the need for frequent cervical tissue biopsies.”

Already, UNC Lineberger researchers have developed a blood test that detects fragments of HPV’s genetic material released into the blood by dying cancer cells.

Building upon previous studies

In previous studies, researchers evaluated whether they could use this blood test to monitor for recurrence of oropharyngeal cancer, a type of head and neck cancer that’s also linked to HPV infection. Each year, about 13,500 cases of oropharyngeal cancer and 10,900 cases of cervical cancer are estimated to be caused by HPV in the United States, according to CDC data.

In preliminary results released at the American Society for Radiation Oncology Annual Meeting in 2018, they found they could accurately use the test to monitor patients after treatment to see if patients remained cancer-free or developed recurrence.

Launching a pilot study

Researchers will use the seed grant awarded by UNC Lineberger to launch a pilot study to track HPV levels in urine as well as in blood before and after pre-cancerous cervical lesions have been removed. That is the first step to see if a blood or urine test could be used to track HPV levels to detect cervical cancer after an initial Pap smear revealed an abnormal finding.

“Our hypothesis is that the amount of HPV signal in the blood or urine may be reflective of the amount of abnormality in the cervix,” Gupta said. “If this hypothesis is confirmed, it suggests that we may be able to use the blood or urine test to identify patients whose immune system may be naturally clearing their cervical pre-cancer, and possibly spare them additional biopsies.”

Doctors typically need to run additional tests, including biopsies, to monitor patients who have pre-cancerous changes in the cervix caused by HPV infection. These tests can have certain risks.

“Current cervical cancer screening practices are very resource intensive, and on the whole, they’re probably more invasive than they need to be,” Gupta said.

Opportunities for expanding screening capabilities

Researchers envision multiple potential future applications for the test.

They are interested in studying whether the test could be used to monitor and personalize treatment for patients who have biopsy-confirmed cervical pre-cancer due to HPV infection.

Shivani Sud, MD.

“We hypothesize that our biomarker blood test will improve risk stratification and enable personalized treatment decisions, while potentially decreasing the need for frequent cervical biopsies and their associated risks,” said Sud, who is a radiation oncology resident in the UNC School of Medicine.

Potentially, the test could also be used as a primary screening test for cervical cancer — especially in countries or settings where cultural barriers could prevent a woman from receiving a Pap test.

“Where there are scarce personnel and sociocultural barriers, the western cervical cancer screening model — which involves multiple visits, pelvic exams and biopsies —  cannot be easily implemented,” Sud said. “A blood or urine test could expand screening capabilities for women in low resource settings.”

Collaborative efforts at UNC

Gupta and Sud are working with a team of researchers from the UNC School of Medicine, including Lisa Rahangdale, MD, MPH in the Department of Obstetrics & Gynecology, Ashley Weiner, MD, PhD in the Department of Radiation Oncology, and Nerlyne Desravines, MD, a fellow in the UNC School of Medicine Department of Obstetrics and Gynecology.

“We’re leveraging the strengths in cervical dysplasia screening here at UNC,” Gupta said. “This is a synergistic collaboration between radiation oncology, the cancer center and the gynecologic oncology screening program. With the support of this Lineberger seed grant, we are able to launch this feasibility pilot clinical study looking at whether a novel, less invasive test may help tailor the intensity of cervical cancer screening that an individual person needs.”

“Furthermore, this seed grant awarded to a resident and faculty mentor highlights our education mission and focus on training future generations of physicians to translate new discoveries into clinical practice to benefit our patients,” Sud added.