Cervical cancer is largely preventable, but not in every case.
While most cases are driven by human papillomavirus (HPV) and can be addressed through vaccination and early detection, a small subset of patients develops cervical cancer without any evidence of HPV. These rare cancers are harder to detect, more difficult to treat, and often associated with worse outcomes.
The Ojesina Lab is focused on understanding why. By studying how genetic changes interact with viruses and bacteria inside tumors, the team is working to uncover what sets these cancers apart and how that knowledge could lead to better care. “If we say we want to cure all cervical cancer, we need to address not just the common types,” said Akinyemi I. Ojesina, MD, PhD, Assistant Professor in the Department of Obstetrics & Gynecology.
His lab focuses on the cervical cancers that fall outside standard prevention strategies: HPV-independent disease, which accounts for about five percent of cases, and extrachromosomal HPV-related cervical cancer, in which HPV triggers cancer without integrating into the genome. While HPV vaccination has proven effective at preventing most cervical cancers, Dr. Ojesina’s work addresses critical gaps for patients whose disease cannot be prevented through vaccination alone.
“Screening Is Only a Snapshot”
Inside the Ojesina Lab, researchers examine the biological drivers that distinguish these rare cancers from more common forms of the disease.
In HPV-independent cancers, his team identified several mutations occurring in genes that are part of the cell cycle, one of the main systems that controls how cells grow. The lab will soon begin testing cyclin-dependent kinase inhibitors to explore whether slowing cell proliferation could offer a new treatment approach.
To better understand the tumor environment, the team also studies the role of microbes, including both viruses and bacteria. They use PathSeq, a computational subtraction tool that Dr. Ojesina co-developed as a trainee, to analyze cervical cancer sequencing data.
“We’re trying to understand the relative abundance of the good and bad bacteria so we can see how they affect how cancer develops and how, potentially, cancer responds to therapy,” Dr. Ojesina said.
The researchers are also expanding upon recently published work examining tumor microbes and host genes in triple negative breast cancer (TNBC). Dr. Ojesina says they’re currently conducting similar studies in cervical cancer tissue.
The Ojesina Lab studied correlative and survival relationships between host gene expression and microbial transcript abundance in TNBC. They identified relatively higher abundance of Hafnia and Shewanella in the tumors from women of African ancestry, and Erwinia and Serratia in the tumors from women of European ancestry.
Dr. Ojesina explained the aim of the study on TNBC: “We wanted to see whether there were certain bacteria that were correlated to the host gene expression, meaning when the bacterium is high, or it’s abundant, the gene is also highly expressed, and vice versa."
His work also highlights the limits of prevention tools. While HPV screening and vaccination remain the primary ways to prevent cervical cancer, Dr. Ojesina emphasized that screening does not capture the full picture. Women between ages 25 and 65 should be tested for HPV every three to five years, and both girls and boys can be vaccinated as young as nine years old.
“I think one of the things that might be a misconception is that people think that once you get screened, you’re done,” Dr. Ojesina says. “But screening is only a snapshot.”
Postdoctoral Researcher Golya Shahrokhi, PhD, added: “There are many unknowns about cervical cancers. Most of the time people are thinking having HPV vaccination may reduce the cervical cancer diagnosis, which is true, but there are other factors that need to come under consideration.”
The Patient Who Changed Everything
Dr. Ojesina’s interest in women’s health goes back to the first patient he encountered after graduating from medical school in Nigeria. He was working at University College Hospital Ibadan, the same hospital where he trained, when he met the woman he calls “B.”
B was a high school science teacher. She was intelligent—brilliant, Dr. Ojesina says—and a fantastic conversationalist. Then, “something would just switch” in her demeanor and he would remember that B had breast cancer that had metastasized to her brain. People with metastatic cancer may experience cognitive or behavioral changes that interfere with their personality, speech, or vision.
When B started to pull out her infusion line in the middle of the night, Dr. Ojesina was always the one asked to put the line back in. It became so consistent that he began to wake up minutes before 3 a.m., when he’d get the daily phone call to check on B.
During his time caring for B, Dr. Ojesina met her younger sister, who also had breast cancer, and both of their daughters. They had questions for him. Who was at risk for cancer? What could they do? He answered as many questions as he could.
“One of the things that I valued, particularly as a young physician, was the opportunity to talk to people and take time to explain” situations that patients were going through, he says.
In 1998, B passed away. She was 42 years old. Dr. Ojesina still thinks of her as changing the course of his life.
Closing Gaps with Curiosity and Persistence
That experience continues to shape how Dr. Ojesina approaches his work today, including how he mentors early-career scientists in his lab. One of Dr. Ojesina’s passions is helping young researchers—he’s always looking for more to join his lab— to pursue work they’re deeply interested in so they remain curious and persistent.
Postdoctoral Researcher Sunday Negedu, PhD, joined the lab in October and is currently working to identify molecular markers of extrachromosomal HPV-associated cervical cancer.
Dr. Negedu feels fortunate that through his work he may one day help identify therapeutic targets for cervical cancer. He’s inspired every day by Dr. Ojesina’s ideas, his lab mates, and former patients he has encountered through research.
“These are ordinary people. If you meet them on the street, you don’t know they even have a disease. But meeting them within that space and seeing the pain they go through—each day I tell myself ‘we’ve got to stop cancer,’” Dr. Negedu said.
Meanwhile, Dr. Shahrokhi is focused on germline and non-inherited mutations that may be associated with cervical cancer development. She is also studying HPV-independent disease, which has not been heavily investigated and has a small sample size. She’s currently looking at the genetic differences in tumors of people with HPV-positive and HPV-independent cancer.
There’s been significant progress in understanding the disease, which gives Dr. Shahrokhi optimism about the future. She’s grateful to be able to do impactful work in the supportive environment of Dr. Ojesina’s lab.
“It feels like I’m working with my family,” she said.
Learn more about the Ojesina Lab.