The largest study of its kind has found some intriguing clues as to why some patients with cancer of the base of the tongue or tonsils caused by the human papillomavirus (HPV) develop metastatic disease and do poorly, despite the generally favorable prognosis for individuals with this virus-associated disease.
The findings of a team from Dana-Farber Cancer Institute, published in the journal JCI Insight, don’t fully answer the question, but the researchers say they may help guide treatment of certain patients. In analyzing tumor DNA patterns of patients with metastatic HPV-linked oropharyngeal cancer (OPC), the investigators found that individuals whose tumors contained a commonly altered molecular signaling pathway had significantly better survival.
Overall, cancers of the head and neck have been decreasing in the United States, mainly because people smoke less, but cancers of the oropharynx (tongue base and tonsils) are increasing. These cancers are most often diagnosed in young to middle-aged men who don’t have traditional risk factors, such as smoking: in these patients, the cancer is frequently driven by the HPV virus, which may have been transmitted from a sexual partner. Oropharyngeal cancer associated with HPV infection has a better outlook than cancer caused by smoking, and often can be cured with surgery, radiation, and/or chemotherapy.
However, a minority of patients with HPV-associated oropharyngeal cancer, estimated at 10 to 15 percent, will develop spread of their cancer to distant organs or have a recurrence, jeopardizing chances of a cure. “We know that clinically they are a distinct entity, but until now we really didn’t have any information about the distinct molecular landscape of these patients,” said Glenn Hanna, MD, of Dana-Farber’s Center for Head and Neck Oncology, first author of the study.
In search of genomic clues that might serve as biomarkers, the researchers studied the cases of 52 patients with HPV-associated, metastatic oropharyngeal cancer treated at Dana-Farber/Harvard Cancer Center from 2011 to 2018. DNA sequencing data was available for 81 percent of patients, making this the largest genomically profiled cohort of metastatic HPV-positive OPC patients to date, the researchers said. These data were then compared with genomic profiles of HPV OPC patients who, unlike the metastatic patients, were deemed curable.
While no major differences distinguishing curable from metastatic HPV-positive OPC jumped out of the data, there were some notable findings. For one thing, metastatic patients whose tumor cells contained alterations of the PI3K signaling pathway had significantly better survival than those with no aberrations of the pathway. “This becomes all the more relevant in that this pathway has actionable therapeutic targets” – that is, drugs that inhibit the PI3K pathway, the researchers said. None of the patients with metastatic disease had received PI3K inhibitors; Hanna said it would be worth trying the drugs in this group of patients.
Another observation from the analysis was poorer survival of patients whose oropharyngeal cancer had spread only to the lungs, compared with those who had metastatic spread to other organs and tissues. The latter category of patients had a median survival of 61 months, compared with 29 months for patients whose cancer had spread only to the lungs. “As a result of these findings, I might think about being more aggressive in treating patients like this, for example with combination chemotherapy up front or enrolling them in a clinical trial right away,” said Hanna.
Senior authors of the report are Robert Haddad, MD, chief of head and neck oncology, and Laura MacConaill, PhD, scientific director of the Center for Cancer Genome Discovery at Dana-Farber.
No NIH or specific grant funding to disclose.