Research Focus

I am a cancer prevention researcher and molecular epidemiologist. My main research focus is human papillomavirus (HPV)-related cancers.  Approximately, 5% of all cancers worldwide are related to HPV infection. In addition to causing nearly cervical cancer, HPV infection is also responsible for a proportion of non-cervical cancers including anal, penile, vulvar, vaginal and a type of head and neck cancer called oropharyngeal cancer. Importantly, in the US, the incidence of HPV-associated cancers at non-cervical sites is increasing; yet, the underlying cause of this increase or how to control it is unclear.

HPV-driven Oropharyngeal Cancer (HPV-OPC)

Early Detection. The incidence of HPV-OPC has increased by more than 200% in the past few decades. Kentucky is at the epicenter of this emerging epidemic with some of the highest rates of HPV-driven cancers in the country. In the US, the number of OPC cases, 85% of which occur in men, already out-number cervical cancer cases in women. Unlike cervical cancer where the introduction of effective screening methods has significantly reduced cervical cancer mortality, there are no screening methods for early detection of OPC.

HPV16 E6 antibody positivity has been shown to be a promising early biomarker for identifying those at highest-risk for developing HPV-OPC. HPV16 E6 antibodies are present in approximately 90% of patients who develop HPV-OPC and are present in the blood more than 10 years prior to OPC diagnosis. We are currently conducting a clinical study to evaluate HPV16 E6 antibodies as a potential screening tool among people living with HIV (PLWH). PLWH are 1.5 to 4 times more likely to develop HPV-OPC than their HIV-negative counterparts, develop HPV-OPC at younger ages (51 versus 60) and have a less favorable cancer prognoses. Supported by an R01 from the National Institute for Dental and Craniofacial Research (R01 DE029650) and in partnership with the Tennessee Center for AIDS Research and HIV Comprehensive Care Clinic, 3,000 men aged 40+ living with HIV are being screened for HPV16 E6 antibodies. Both HPV16 E6 seropositive and seronegative men will undergo yearly head and neck screening exams to determine whether men with HPV16 E6 antibodies will be more likely to have persistent oral HPV infection and to develop HPV-OPC.

Biomarkers of HPV-OPC Prognosis. Although treatment for HPV-OPC is often curative, it is associated with severe morbidity. A large portion of my research is also focused on developing biomarkers to identify patients at low risk of recurrence who would benefit from de-escalated treatment protocols. Supported by a grant from the National Cancer Institute (K07CA218247), I am building a large clinical cohort of HPV-OPC patients with tumor, blood and oral rinses specimens. Using this cohort, I am conducting the first large-scale HPV genome sequencing study in HPV-OPC in collaboration with the University of Pittsburgh Cancer Institute and the National Cancer Institute. Preliminary analyses of the data suggest that HPV-OPC patient prognosis is strongly associated with HPV genetic variation and may be a potential tool to risk stratify patients prior to treatment. We are currently working to expand this study across the commonwealth of Kentucky to validate these early findings.

Early Onset Oral Tongue Cancer (OTC)

I also have a strong interest in oral tongue cancer (OTC), a rapidly increasing subset of head and neck cancer for which no underlying cause has been identified. The increase in oral tongue cancers is primarily occurring within young (<50 years of age) white males and females. Despite the rapid increase in incidence of early onset oral tongue cancer in the US, few studies have been performed to evaluate risk factors, prognosis, and survival.

We recently conducted the largest US-based study to assess risk factors and prognosis associated with early onset oral tongue cancer. Compared to typical onset patients, early onset patients had a better prognosis.  We also found that early onset oral tongue cancer patients were less likely to report tobacco use, and if they did, were more likely than typical onset patients to use snuff. However, snuff use was only reported in 11% of early onset cases, suggesting that additional, yet to be identified risk factors are contributing to the rise in these cancers. To better understand whether early onset OTC is a distinct molecular subset of OTC, we recently established a consortium of 227 OTC specimens with existing whole exome sequencing data across 7 institutions and the TCGA. We identified 8 cancer driver genes, 3 of which had not been previously reported.  Additionally, this study was the first to show that early onset OTC has a significantly lower mutational burden than typical onset OTC even after stratifying by tobacco use suggesting that early onset OTC may be a unique molecular subset of OTC. We are currently working to expand this study across the ORIEN network to better understand the unique molecular signature of early onset OTC and to also identify potential infectious factors.

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