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Oral HPV DNA Persistence After Head and Neck Cancer Treatment Linked to Disease Progression

NEW YORK (GenomeWeb) – Persistent traces of human papilloma virus DNA after treatment for HPV-positive head and neck cancer is linked to an increased recurrence risk, a new study has found.

Head and neck cancers affect some 53,000 people in the US each year, according to the National Cancer Institute, and HPV has been implicated in many of those cases. In general, patients with HPV-positive tumors have higher survival rates than those with HPV-negative tumors.

A team of MD Anderson Cancer Center-led researchers collected oral rinse samples from nearly 400 patients with head and neck squamous cell carcinomas at diagnosis and as their treatments progressed. As they reported today in JAMA Oncology, the researchers found that viral load in patients' oral samples broadly decreased as they underwent therapy. But some patients' viral loads persisted despite treatment, which was linked to an increased risk of cancer recurrence and death, the researchers reported.

"Our data suggest that a subset of patients with HPV-positive HNSCC at high risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment," MD Anderson's Maura Gillison and her colleagues write in their paper.

The researchers enrolled 396 patients with oral cavity, oropharyngeal, or unknown primary HNSCC in their study. They tested the patients' tumors for the presence of 13 high-risk HPV types using an mRNA expression test and found 202 patients had HPV-positive tumors.

At the same time, the researchers collected oral rinse samples from patients at diagnosis, after surgery, and at six months. Additionally, patients who underwent radiotherapy provided weekly oral rinse samples. The researchers tested these samples — a total of 2,922 oral rinse samples — for the presence of HPV using a multiplex PCR-based approach. 

At diagnosis, patients with HPV-positive tumors were significantly more likely to have oral rinse samples positive for HPV than were patients with HPV-negative tumors. In particular, the researchers reported that the detection of any oral HPV DNA had a sensitivity of 84 percent, a specificity of 88 percent, a positive predictive value of 88 percent, and a negative predictive value of 84 percent for the diagnosis of an HPV-positive tumor.

The prevalence of oral HPV DNA, though, went down after treatment, the researchers reported. Prior to treatment, the prevalence of HPV DNA in oral rinses that matched that of HPV in the tumor sample was 69 percent. But after primary surgical resection, it was about 14 percent. Its prevalence fell similarly for patients who underwent radiotherapy, going from 85 percent before treatment to 9 percent after radiotherapy.

As expected, overall and recurrence-free survival was higher for patients with HPV-positive tumors than with HPV-negative tumors. Patients with HPV-positive tumors had a two-year overall survival of 91 percent, as compared to 75 percent for patients with HPV-negative tumors.

But for a subset of patients with HPV-positive tumors — about 14 percent — the prevalence of oral HPV DNA didn't decline with treatment. These patients were more likely to recurrent disease, with about 45 percent experiencing disease recurrence within two years. Additionally, this subset had a lower two-year overall survival of 68 percent.

These patients, the researchers noted, might benefit from increased surveillance or adjuvant therapy.

The researchers added that their findings suggest that oral rinses to detect HPV DNA in head and neck cancer patients might be helpful. They cautioned, though, that its clinical utility might be limited by the need to identify tumor-type infections.

"Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations," the researchers added.