Saliva HPV16 DNA Detection Potential for Long-Term Oropharyngeal Carcinoma Surveillance

HPV16 DNA is detected infrequently post-treatment in patients with oropharyngeal carcinoma, but may be predictive of disease recurrence

medwireNews: Study findings suggest that a positive oral rinse for human papillomavirus type 16 (HPV16) DNA after treatment for HPV-related oropharyngeal carcinoma (HPV-OPC) may indicate an increased risk of recurrence.

HPV-OPC generally has a “favourable prognosis”, say the researchers, but it can recur in 10% to 25% of patients. They add that although the presence of HPV DNA in oral rinses has been linked with HPV-OPC, “its potential as a prognostic Biomarker is unclear”.

Before treatment with curative intent, 54% of 124 patients included in this prospective study tested positive for HPV16 in their saliva rinse but this fell to 5% of patients after treatment, with five of the six patients testing positive at both timepoints.

Both 2-year disease-free survival and overall survival were significantly worse in the patients with persistent oral HPV16 DNA than those without, with hazard ratios of 29.7 and 23.5, respectively.

Gypsyamber D’Souza, from Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, USA, and co-authors also report in JAMA Oncology that all five patients with persistent HPV16 DNA experienced recurrence, three of whom had at least some local disease.

By contrast, recurrent disease was recorded in just nine (8%) of 119 patients who did not have persistent HPV16 DNA, and all but one of these individuals had regional or distant recurrence.

“[W]e observed a clinically meaningful lead time from first positive posttreatment oral rinse result to diagnosis of recurrence (median, 7months)”, they write.

“Therefore, HPV16 DNA detection in oral rinses may prove a valuable tool for long-term posttreatment surveillance of HPV-OPC for local recurrence.”

Persistent HPV16 DNA detection 9 to 12 months after treatment was 100% specific and 43% sensitive for recurrence, with positive and negative predictive values (PPV/NPV) of 100% and 96%, respectively. And when considering only patients whose recurrence included some local disease, the specificity and PPV remained at 100%, while the sensitivity and NPV increased to 100%.

“We hypothesize that the persistent presence of oral HPV16 DNA represents in most cases integrated or episomal viral DNA in persistent or microscopic disease that may not yet be detectable by conventional methods”, the researchers write.

Poor sensitivity for regional and distant recurrence is “not surprising”, they add, as tumours distant to the primary site would not be expected to shed tumour cells into an oral rinse.

“A potential strategy to increase sensitivity for recurrence overall is to combine oral rinses with plasma-based testing for HPV16 biomarkers, such as HPV16 DNA or antibodies to HPV16 antigens, which has also be shown to be sensitive for HPV-OPC and is less anatomically constrained”, the researchers add.

Reference

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. JAMA Oncol 2015; Advance online publication 30 July. doi:10.1001/jamaoncol.2015.2524

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