Penn Medicine to explore therapeutic strategies for HIV positive women at risk of cervical cancer

The introduction of antiretroviral drugs in Botswana over the last two decades has increased the life expectancies of people living with HIV—many of whom are women co-infected with the human papillomavirus virus (HPV)—considerably: from 39 years to the low 60s. As a result, this co-infected group of women is at a much higher risk of developing HPV-associated cervical cancer.

To better understand these co-infections and develop optimal prevention and therapeutic approaches, the Perelman School of Medicine at the University of Pennsylvania, under the departments of Radiation Oncology and Microbiology and the Botswana-UPenn Partnership, has received a $3.5 million U54 grant over five years from the National Cancer Institute (NCI).

The NCI's U54 program is an initiative developed to strengthen the capabilities of sub-Saharan African institutions by collaborating with partnering institutions/cancer centers.

A research consortium will be led by Stephen M. Hahn, MD, chair of Radiation Oncology at Perelman, Erle S. Robertson, PhD, a professor of Microbiology and leader of the Tumor Virology Program at the Abramson Cancer Center, Doreen Ramogola-Masire, MD, director of the woman's program, Botswana-UPenn Partnership, and Bagele Chilisa, PhD, of the University of Botswana, with collaborations among investigators in the departments of Microbiology, Radiation Oncology, the division of Infectious Diseases, Obstetrics and Gynecology, Penn's Annenberg School of Communication, as well the University of Botswana.

"This is a unique, collaborative grant among many departments, with researchers from both continents working towards new approaches to this emerging health issue in Botswana," said Hahn. "Penn has been working with the University of Botswana for over a decade now, and this grant builds off an already-strong partnership with the citizens and health care providers there."

The central research theme is to determine epidemiology, pathogenesis, behavioral, clinical, and immunological risk factors of HPV-associated cervical cancer in HIV positive women. The consortium will focus on three cohorts: co-infected women with no clinical signs of cervical cancer; women with precancerous lesions; and a third group who are being treated for cervical cancer. The overall goal is to translate the knowledge into effective prevention and treatment strategies that will lower the burden and associated illness and deaths from cervical cancer.

The rates of cervical cancer are high in sub-Saharan Africa, and women often present with advanced cervical cancer, the number one cause of cancer-related mortality in the region for women. Today in Botswana, it's estimated that every year 250 women are diagnosed with the cancer—many who are co-infected with HPV and HIV.

The grant will also support Ramogola-Masire's continued efforts in cervical cancer screening in Botswana, as well the telemedicine efforts with mobile phones. Back in Philadelphia, Roberston's virology lab will begin to sequence and analyze patient samples to study the viruses more closely, as well as identify other viral, bacterial and parasitic agents and their involvement as drivers in tumor formation. Often, his research has shown, there are many viral culprits linked to cancers.

"One of the interesting aspects of the consortium is having both basic science and clinical studies," said Robertson. "Such findings could enhance and inform the long-term therapeutic strategies for women at risk of cervical cancer in Botswana and other parts of sub-Sahara Africa. And because of a strong emphasis on mentoring and education, the grant will also allow us to build a sustained research infrastructure in Botswana."

Another key component of the grant is a Mentoring/Career Development Core led by Harvey Friedman, MD, director of the Botswana-UPenn Partnership, in collaboration with Oathokwa Nkomazana at the University of Botswana. The goals of the Core are to provide scientific and career development mentorship to University of Botswana medical trainees and junior faculty and offer pilot grants as a mechanism to mentor trainees and faculty on research questions of importance in Botswana.