Mar 09, 2023
By Jimmy O’Hara, Conquer Cancer
In Colombia, lung cancer is among the most frequent types of cancer and is the second leading cause of cancer-related death in patients with male sex characteristics. Here, patients often present with additional diseases that are linked to lung cancer diagnoses, including human papillomavirus (HPV). Despite the harmful effects and negative reputation of HPV, the infection could help doctors more effectively guide the course of care for patients with certain types of lung cancers. Oncologists can look to HPV levels to determine how effective immunotherapy may be for patients. Luis Leonardo Rojas Puentes, MD, MSc, of the Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center in Bogotá, Colombia, is uncovering how providers can leverage HPV to predict treatment response and personalize immunotherapy for patients.
“The cost of lung cancer treatments, such as immunotherapy, is high and finding new predictive biomarkers for these therapies is necessary, particularly in low-income communities. Response to HPV could modify the immune response to lung tumors and predict checkpoint inhibitors’ outcomes,” said Dr. Rojas. “We postulate HPV infection as a prognostic factor in patients with lung adenocarcinoma treated with immunotherapy.”
Immunity Matters: Improving Treatment
Supported by a 2018 Global Oncology Young Investigator Award (GO YIA) from Conquer Cancer, the ASCO Foundation, Dr. Rojas assessed HPV infection in tumor tissue from patients with lung cancer. He used GO YIA funding to access laboratory equipment and related materials for testing. Dr. Rojas used genomic sequencing techniques to measure levels of HPV genetic material and evaluate the presence of HPV mRNA, a messenger-like molecule that tells the body how to make proteins. HPV infections can build immune system capacity in patients and may signal the likely outcomes of immunotherapy for patients with lung tumors.
“We found that HPV infection was a prognostic factor in patients with lung adenocarcinoma treated with immunotherapy. Patients with HPV infection showed better survival results for immunotherapy compared with [patients who were] HPV-negative, even after adjusting for other factors, such as PDL-1 expression,” said Dr. Rojas. “Also, the overall response to immunotherapy was better in [patients who were] HPV-positive.”
Dr. Rojas believes that patients with HPV experience a more favorable response to immunotherapy because HPV conducts a form of damage control. HPV can strengthen the immune system by minimizing the body’s protective response to its presence. This process can benefit patients with lung cancer who are HPV-positive because their bodies may have a heightened capacity to endure immunotherapy. Dr. Rojas’s findings can help oncologists to individualize treatment options for patients.
“We postulate that HPV infection modifies tumoral immune response by decreasing damage response and genomic repair mechanisms that result in incremental mutational loads. These incremental mutational loads, in turn, could induce the production of more cancer-related epitopes and increase immune response,” said Dr. Rojas. “Finding differences in the immune response of patients with lung cancer and HPV infection may help [providers] to better select which patients may benefit more from therapies, such as checkpoint inhibitors, and propose other treatment alternatives based on the state of HPV infection.”
Early Support From IDEA
Five years before his GO YIA research, Dr. Rojas received an International Development and Education Award (IDEA) from ASCO and Conquer Cancer.
The IDEA program facilitates the exchange of knowledge between early-career oncologists in low- and middle-income countries (LMICs) and other ASCO members. IDEA recipients are paired with an ASCO member mentor, provided with support to attend the ASCO Annual Meeting, and immersed in a post-Meeting visit to their mentor’s institution.
During his IDEA experience, Dr. Rojas expanded his professional network, increased his confidence in sharing research, and learned best practices for writing grant applications and study designs. These program benefits laid the foundation for his promising GO YIA project.
“The IDEA experience showed me the alternatives and resources that ASCO promotes for research, particularly in LMICs where economic and technological resources are scarce,” said Dr. Rojas. “The IDEA experience encouraged me to think about cancer causes that explain the differences between patient populations.”
Future Research
Next steps for Dr. Rojas include studying immunotherapy response in a larger sample size of patients with lung cancer and HPV infection. This will help connect the dots as to why this patient population generally responds better to immunotherapy.
“If we could expand our sample and perform other analyses to evaluate immune response, we could explain these differences in immunotherapy responses,” said Dr. Rojas.
Dr. Rojas credits the foundation-building impact of Conquer Cancer support for providing him with the resources to advance this vital work.
“The GO YIA experience [not only] gave me tools to learn how to write a grant and a research article for high-impact journals, but [also gave me] the experience of sharing with other researchers who are interested in the development of lung cancer research,” said Dr. Rojas.