A team of University of South Carolina scientists led by assistant research professor Carolyn Banister and associate professor Phillip Buckhaults has discovered a new subtype of cervical cancer that affects 8 percent of patients.
Unlike most cervical cancers — which are primarily driven by human papillomavirus — this subtype is initiated by the virus, but HPV oncogene expression eventually disappears and does not sustain the cancer’s growth. This finding suggests that patients with this subtype may respond better to alternative treatments that target their tumors’ unique genetic structure, which is different than most cervical cancers. The study was published online Jan. 6 in the journal Oncotarget.
“Cervical cancer patients are currently treated as a uniform group based on chemotherapy and radiation regimens that help the largest percentage of people; however, one third of these patients are not helped by standard therapies,” Banister said. “We have discovered the existence of a subgroup of cervical cancers with very different genetic features. These women may benefit from alternative treatments that are not usually given to cervical cancer patients.”
HPV vaccines have been available since 2006 and act as effective tools to prevent cervical cancer. However, because many people remain unvaccinated and some cervical cancer patients do not respond to standard treatment, identifying the most effective treatment options remains an important goal.
Congress designated January as Cervical Health Awareness Month, and the American Cancer Society estimated that nearly 13,000 American women would be diagnosed with invasive cervical cancer in 2016, with more than 4,000 women dying from the disease. According to 2013 data from the S.C. Department of Health and Environmental Control, South Carolina ranked 15th in the nation for cervical cancer incidence and 12th for cervical cancer deaths. Across the state, inpatient hospitalizations related to cervical cancer cost more than $6.6 million in 2014.
The researchers from the University of South Carolina College of Pharmacy and School of Medicine discovered this new subtype by analyzing data from 255 cervical cancer samples in The Cancer Genome Atlas, a large-scale federally funded project launched in 2005 by the National Cancer Institute and National Human Genome Research Institute. Their analysis revealed that the samples fell into two categories: an HPV-active class (high expression rates of two HPV cancer genes) and an HPV-inactive class (low or zero expression rates of the two HPV cancer genes).
Previous studies by the University of South Carolina’s Lucia Pirisi-Kim Creek research group had identified an HPV-inactive class in head and neck cancers and suggested that a similar mechanism could exist in cervical cancer. This research confirmed that suspicion and discovered molecular genetic mechanisms that drive the evolution of HPV-inactive cervical cancers.
The researchers also examined the frequency of mutations across all human genes in the samples. They found that 19 cancer driver genes had significantly higher mutation rates in the HPV-inactive class than in the HPV-active class.
These differences indicate that these mutated genes replace functions normally provided by the HPV cancer genes in regulating tumor cell growth. For example, HPV-inactive tumors were 17 times more likely to contain TP53 gene mutations — which are common in other cancer types — than HPV-active cervical cancers. The authors suggest that administering therapies targeting TP53 mutations may boost clinical outcomes for patients with HPV-inactive tumors.
“Physicians managing cervical cancer patients should test for HPV oncogene expression in these tumors and consider personalized treatment depending on HPV activity,” Banister said. “We predict that immune checkpoint inhibitor therapy will be more effective for HPV-active tumors than HPV-inactive tumors. In contrast, because of the high incidence of TP53 mutations in the HPV-inactive class, these tumors may be less responsive to the standard cisplatin chemotherapy and more sensitive to other chemotherapies such as dasatinib.”
According to the ACS, Hispanic and African-American women are more likely to develop cervical cancer than whites in the United States, and Banister will be conducting genomic sequencing research at the University to explore the underlying reason for this racial disparity.
The University of South Carolina researchers involved in this study were Carolyn E. Banister, Phillip J. Buckhaults, Kim E. Creek, Lucia Pirisi and Changlong Liu. The study was supported by funding provided from the National Institutes of Health grants U01CA158428 and R21CA201853.