Small viral changes can have a significant impact on the ability of a virus to infect other people and to cause more severe disease.
Dr. Krystle Kuhs, Associate Professor in Epidemiology at the University of Kentucky College of Public Health, and colleagues, led a study to ask the question of whether changes within the human papillomavirus (HPV) genome could potentially influence the aggressiveness of HPV-driven oropharyngeal cancer (HPV-OPC) - a type of throat cancer caused by oral HPV infection, with rapidly increasing incidence in the US.
In the first study to sequence the HPV viral genome in HPV-OPC, Dr. Kuhs and colleagues found 8 viral changes that were associated with poorer patient survival. Median survival was 4 years for patients with 1 or more of the 8 viral changes compared to 19 years for patients without. Results of this study were recently published in Annals of Oncology.
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HPV-OPC, a type of throat cancer caused by oral HPV infection, has increased in incidence by more than 200% over the past several decades. Approximately 90% of HPV-OPCs are caused by one HPV type -- HPV16.
While most patients with HPV-OPC survive, treatment is often associated with severe and permanent side effects. Given the high survival rates, there has been a recent push to de-escalate treatment for HPV-OPC patients to reduce treatment-related side effects.
However, a major barrier to treatment de-escalation is that a subset of patients has more aggressive cancers and poorer survival outcomes. Currently, there are no ways to identify this subset of patients prior to treatment.
Dr. Krystle Kuhs, Associate Professor in the University of Kentucky College of Public Health and co-leader of the Cancer Prevention and Control Research Program at the Markey Cancer Center, led a study to ask the question of whether small genetic differences between HPV16 viruses could explain why a subset of HPV-OPC patients have more aggressive tumors and whether these viral differences could help identify patients with poor prognosis prior to treatment.
To carry out this, Dr. Kuhs led a multi-institutional study with intramural investigators from the National Cancer Institute (NCI), part of the National Institutes of Health, UK Healthcare’s Markey Cancer Center, Vanderbilt University Medical Center and the University of Pittsburgh Medical Center. Using novel technology developed at the NCI’s Cancer Genomics Research Laboratory, the group conducted the first large study to sequence the HPV16 viral genome in HPV-OPC.
“Through this research, we analyzed 384 HPV16+ tumors and found eight genetic differences called single nucleotide polymorphisms (SNPs) within the HPV16 viral genome that were strongly associated with patient survival,” says Kuhs.
“For HPV-OPC patients with at least one high-risk HPV16 SNP, median survival was 4 years versus 19 years for patients without a high-risk HPV16 SNP. Including HPV16 SNP information improved the ability to predict HPV-OPC patient survival above traditional risk factors such as age, cancer stage, treatment and smoking history alone.”
The results of the study suggest that HPV16 whole genome sequencing may help identify HPV-OPC patients with poor prognoses prior to treatment and may help clinicians better tailor treatment for HPV-OPC patients.
Furthermore, this may allow HPV-OPC patients with good prognosis to safely receive de-escalated treatment and improve their quality of life. In addition, this could also open new treatment possibilities for those HPV-OPC patients who are currently failing standard treatment protocols.
Yet, Dr. Kuhs cautioned that while these results are exciting, “It is important to note that this is just the first of many studies that need to be done before considering moving this testing in to the clinic.”
“This is the first study to show that genetic variation within theHPV16 genome may impact prognosis among patients with HPV-OPC. Large viral genome studies have helped us to understand the role of HPV genetic variants in carcinogenesis and risk of precancer and cancer, and now we find viral SNPs can further contribute to more aggressive cancers,” said Dr. Lisa Mirabello, Senior Investigator at NCI. “Additional studies are needed to elucidate how these viral SNPs contribute to more aggressive disease.”
As a result of this research, the best way to treat HPV-OPC is to prevent it from happening in the first place.
“HPV infection causes six distinct types of cancers which include HPV-OPC, cervical, anal, vulvar, vaginal and penile cancer. HPV vaccination can prevent these cancers,” says Kuhs. “When people hear HPV, they think cervical cancer in women. However, for HPV-OPC, 85% of cases occur among men and the number of cases of HPV-OPC currently outnumber cervical cancer cases in the US. Therefore, it’s important for men (and women) to be vaccinated.”
Part of the University of Kentucky College of Public Health’s (CPH) mission is to conduct robust research and collaborate with partners to solve some of the major public health challenges in the Commonwealth of Kentucky and beyond – to create a healthier community, state, and world for everyone.
Kentucky has one of the highest rates of OPC and lowest HPV vaccination rates in the country. As a result, research focused on preventing HPV-OPC through vaccination and improving patients’ quality of life once they develop HPV-OPC is a public health priority for the Commonwealth of Kentucky and beyond.
Annals of Oncology, the journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, provides rapid and efficient peer-review publications on innovative cancer treatments or translational work related to oncology and precision medicine.
To review the full publication in the Science Direct “Annals of Oncology” journal, visit here. For 50 days of free access follow this link here.
