Mouth Rinse May Predict Recurrence of HPV-Related Oral Cancer

Gypsyamber D’Souza, PhD

Gypsyamber D’Souza, PhD

Patients who have human papillomavirus 16 (HPV16) DNA in their saliva following treatment of their oropharyngeal cancer are more likely to have their cancer recur, and a simple mouth rinse can be used to detect it, a new study has found.

The presence of HPV16 DNA is common at diagnosis of HPV-related oropharyngeal carcinoma (HPV-OPC) but rare after treatment. HPV-OPC has a favorable prognosis; however, 10% to 25% of patients experience disease progression, usually within 2 years of treatment.

For this prospective cohort study, led by Gypsyamber D’Souza, PhD, researchers at the Johns Hopkins Bloomberg School of Public Health monitored 124 patients newly diagnosed with oropharyngeal cancer from 2009 through 2013. They collected oral rinse and gargle samples using 10 mL of mouthwash at the time of diagnosis as well as after treatment 9, 12, 18, and 24 months later.

HPV16 DNA was detected in 67 out of 124 of the participants testing positive. Of the 67 patients who had HPV16 DNA in their saliva at the time of diagnosis, five patients (7%) were found to still have traces of HPV16 in their oral rinses following treatment.

All five patients developed a local recurrence of oropharyngeal cancer, three of whom died from the disease.

“It’s a very small number so we have to be somewhat cautious,” said D’Souza, an associate professor in the Department of Epidemiology at the Bloomberg School and a member of the Sidney Kimmel Comprehensive Cancer Center, in a statement. However, “The fact that all of the patients with persistent HPV16 DNA in their rinses after treatment later had recurrence meant that this may have the potential to become an effective prognostic tool.”

Detection of HPV16 DNA at diagnosis was not associated with disease-free survival (DFS; P = .15) or overall survival (OS; P = .14). However, patients with persistent HPV16 DNA at diagnosis and after treatment had almost 30 times greater the risk of recurrence (hazard ratio [HR] = 29.7; 95% CI, 9.0-98.2) and more than 20 times greater risk of death (HR = 23.5; 95% CI, 4.7-116.9).

It is not known whether the presence of HPV16 DNA in the posttreatment rinse meant that the treatment did not completely eradicate the cancer in the first place or if the cancer returned.

Persistent HPV16 DNA detection remained associated with DFS and OS after adjustments were made for years of smoking cigarettes and tumor stage. Years of smoking was also correlated with worse DFS (HR = 1.4 [95% CI, 1.1-1.8]) per 10 pack-years, and OS (HR = 1.5 [95% CI, 1.1-2.1]).

A median of 7.0 months elapsed between posttreatment detection of oral HPV16 DNA and cancer recurrence (range, 3.7-10 months), the researchers found, thus offering a potential way for clinicians to detect recurrence before any other clinical signs or symptoms occur.

HPV is associated with several cancers including cervical and oral cancers. In the United States, the infection causes more than 70% of newly diagnosed oropharyngeal cancer and has been increasing in incidence.

HPV-related oropharyngeal cancer can typically be treated surgically, the authors noted, but the success rate decreases if the disease progresses and metastasizes to other parts of the body. Most of the recurrences in the study were localized.

“There is a need for clinically relevant biomarkers of disease recurrence to facilitate timely initiation of aggressive diagnostic investigation and subsequent salvage treatment to potentially improve outcomes for the growing population of HPV-OPC survivors,” the researchers wrote. “Detection of recurrent local or locoregional disease prior to distant spread is particularly desirable given the favorable response of HPV-OCP to surgical salvage.”

“It should be reassuring that most people who have been treated for HPV-related oropharyngeal cancers are cured, and there is no HPV16 DNA detected in their mouths,” said D’Souza, but among those that did recur, this was an important potential predictor.”

The researchers added that the study is limited by the infrequency of persistent oral HPV16 DNA detection and the small number of deaths and recurrences, but concluded that this kind of testing can potentially be a useful tool for long-term tumor surveillance, allowing for earlier detection of recurrence and an overall better prognosis.

“There was a lead time of several months between when we detected HPV16 DNA in the rinse and when they were diagnosed with recurrence,” noted D’Souza. “If we had known at the rinse time, it would have given a lead time for treatment.”

Rettig EM, Wentz A, Posner MR, et al. Prognostic implication of persistent human papillomavirus type 16 DNA detection in oral rinses for human papillomavirus-related oropharyngeal carcinoma [published online ahead of print July 30, 2015]. JAMA Oncol.