July 31, 2015
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Persistent HPV16 DNA in oral rinses predicts oropharyngeal cancer recurrence

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The presence of HPV type 16 DNA in oral rinses following treatment for HPV-related oropharyngeal cancer corresponded with poor prognosis and may serve as a potential biomarker for long-term tumor surveillance and local recurrence, according to results of a prospective cohort study.

The incidence of HPV-related oropharyngeal carcinoma (HPV-OPC) has increased in the U.S. and despite its favorable prognosis, recurrence occurs in 10% to 25% of cases. Gypsyamber D’Souza, PhD, MS, associate professor of cancer epidemiology at Johns Hopkins Bloomberg School of Public Health, and colleagues sought to determine whether HPV DNA detection in oral rinses following treatment for HPV-OPC served as a prognostic biomarker for recurrence and survival.

The analysis included data from 124 patients (90% men) with incident HPV-OPC diagnosed between 2009 and 2013 who had one or more post-treatment oral rinses. The researchers collected rinse samples at diagnosis and at 9, 12, 18 and 24 months following treatment.

DFS, OS and the association of HPV DNA detection in oral rinses with survival rates served as the primary endpoints.

Median follow-up was 33 months (interquartile range, 24-41).

Sixty-seven patients (54%) had oral HPV type 16 (HPV16) at diagnosis. However, only six patients (5%) had detectable oral HPV16 following treatment, which included five patients who had persistent oral HPV16 since diagnosis.

Overall, 92% (95% CI, 94-100) of patients achieved 2-year DFS and 98% (95% CI, 93-99) achieved 2-year OS. Fourteen recurrences occurred in the population, resulting in six deaths.

The researchers associated persistent oral HPV16 DNA with worse DFS (HR = 29.7; 95% CI, 9-98.2) and OS (HR = 23.5; 95% CI, 4.7-116.9).

All five patients with persistent oral HPV16 DNA developed recurrent disease, including three cases of local disease involvement. Only nine patients (8%) without persistent oral HPV16 DNA experienced disease recurrence, with one case of local disease involvement.

The median time from earliest post-treatment oral HPV16 DNA detection to recurrence was 7 months (range, 3.7-10.9).

The researchers acknowledged the low number of deaths and recurrences and the infrequency of persistent oral HPV16 DNA detection as limitations to these findings. They also noted that the majority of patients in their study exhibited characteristics associated with improved prognosis, including higher incomes, higher likelihood of marriage and fewer pack-years of smoking.

“Our data suggest that persistent HPV16 DNA detection in post-treatment oral rinses, although uncommon, is associated with poor prognosis and may be predictive of disease recurrence, in particular local recurrence,” D’Souza and colleagues wrote. “Therefore, HPV16 DNA detection in oral rinses is a potentially useful tool for long-term tumor surveillance for the growing population of HPV-OPC survivors.”

A recurrence biomarker needs high sensitivity, high positive predictive value, accuracy for subclinical locoregional recurrence and a low number needed to treat, Julie E. Bauman, MD, MPH, director of the head and neck cancer section and thyroid cancer section in the division of hematology-oncology at the University of Pittsburgh School of Medicine, and Robert L. Ferris, MD, PhD, chief of the division of head and neck cancer surgery at the University of Pittsburgh Cancer Institute, wrote in an accompanying editorial.

“This pioneering study demonstrates an association between persistent oral HPV16 DNA detection and recurrence,” Bauman and Ferris wrote. “Operating characteristics, including low sensitivity, low confidence in the positive predictive value and high number needed to treat, preclude immediate clinical adoption. Incorporation of an HPV-specific biomarker in future surveillance guidelines will require improved sensitivity, perhaps realized in combination with serologic markers such as HPV16 DNA or E6 antibodies; narrowing of the CI for positive predictive value by the study of larger populations; and confirmation of significant lead time increasing the rate of successful surgical salvage. … The high negative predictive value of oral rinse HPV16 DNA detection raises the promise of deintensifying surveillance visits and/or costly imaging, particularly if on a prospective trial.” – by Cameron Kelsall

Disclosure: D’Souza reports prior institutional research funding from Merck. Please see the full study for a list of all other researchers’ relevant financial disclosures. Bauman and Ferris report no financial disclosures.