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Persistent HPV16 DNA in oral rinse signaled oropharyngeal cancer’s return

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Test isn’t ready for the clinic

HPV16 DNA was detected in oral rinses in just 54% of patients with HPV-OPC at diagnosis. This low sensitivity in the presence of gross disease calls into question the test’s utility as a biomarker for subclinical disease. The positive predictive value (PPV) of 83%, calculated based on five of six patients who had persistent HPV16 DNA detection and disease recurrence, requires further analysis.

First, the persistence criteria immediately eliminates the 46% of patients who had HPV-OPC but tested negative for HPV16 DNA at diagnosis. Second, the intent of the biomarker is early detection of local or locoregional recurrence, but only two of the patients had local or locoregional recurrence prompting surgical salvage.

Detection of HPV16 DNA had a median lead time of 7 months, but clinical utility of the test requires some assumptions about the natural course of HPV-OPC. First, local or locoregional recurrence must precede the spread of disease to distant sites; second, earlier surgical salvage must prevent systemic reseeding; and finally, the oral rinse test must be robust enough to warrant salvage surgery in the absence of measurable disease.

The operating characteristics of the HPV16 DNA oral rinse test (e.g., low sensitivity and low confidence in PPV) preclude clinical adoption. However, the high negative predictive value of the test may be useful as criteria to scale back surveillance visits and/or costly imaging, particularly during prospective trials.

Dr. Julie E. Bauman is director of the head and neck cancer section in the division of hematology-oncology at the University of Pittsburgh. Dr. Robert L. Ferris is chief, division of head and neck surgery at the University of Pittsburgh. Dr. Bauman and Dr. Ferris reported no conflicts of interest. These comments were taken from their editorial accompanying the study (JAMA Oncol. 2015 July 30 [doi:10.1001/jamaoncol.2015.2606]).


 

FROM JAMA ONCOLOGY

References

Patients with human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) who had human papillomavirus type 16 (HPV16) detected in oral rinses both at diagnosis and at any time after treatment were more likely to have OPC recurrence, according to a report published online in JAMA Oncology.

Detection of HPV16 DNA was frequent among patients at diagnosis (67 of 124 patients), but rare posttreatment (6 of 124 patients). Persistent HPV16 detection (at and after diagnosis) was associated with greater risk of disease recurrence (hazard ratio, 29.7) and death (HR, 23.5).

Electron micrograph of human papillomavirus (HPV). National Cancer Institute

Electron micrograph of human papillomavirus (HPV).

Approximately 10%-25% of patients with HPV-OPC experience progression after treatment, and surgical salvage is the most favorable treatment in these cases. However, surgery is not feasible for the significant proportion of HPV-OPC cases that have already spread to distant sites at the time of diagnosis.

“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,” wrote Dr. Eleni M. Rettig of the department of otolaryngology–head and neck surgery, Johns Hopkins University, Baltimore, and her colleagues (JAMA Oncol. 2015 July 30 [doi:10.1001/jamaoncol.2015.2524]).

“Detection of recurrent local or locoregional disease prior to distant spread is particularly desirable given the favorable response of HPV-OPC to surgical salvage,” the study authors observed.

The multisite, prospective cohort study evaluated 124 patients with HPV-related oropharyngeal carcinoma who had at least one posttreatment oral rinse sample. Most patients with HPV16 DNA detected at diagnosis had none detected after treatment (62 of 67 patients). Contrary to persistent HPV16 DNA detection, HPV16 detected at diagnosis was not significantly associated with disease-free or overall survival.

Based on the six patients who had posttreatment detection of HPV16 DNA in oral rinses, the sensitivity and specificity of predicting recurrence at 9-12 months were 43% and 100%, respectively. Considering only local disease recurrence, the sensitivity and specificity were 100% and 100%, respectively.

The median time from the first posttreatment detection of HPV16 DNA to recurrence was 7.0 months. That “clinically meaningful lead time” is important in evaluating HPV16 DNA detection in oral rinses as “a valuable tool for long-term posttreatment surveillance of HPV-OPC for local recurrence,” the investigators concluded.

Dr. Rettig reported having no disclosures. Several coauthors reported ties to industry sources.

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