Persistent HPV16 in Oral Rinses Signals Poor Prognosis for HPV-Positive Oropharyngeal Carcinoma

Persistent HPV16 in Oral Rinses Signals Poor Prognosis for HPV-Positive Oropharyngeal Carcinoma
Persistent HPV16 in Oral Rinses Signals Poor Prognosis for HPV-Positive Oropharyngeal Carcinoma

CHICAGO, IL—Although infrequent, detection of human papillomavirus (HPV)16 DNA in oral rinses following treatment for HPV-positive oropharyngeal carcinoma (HPV-OPC) “is strongly associated with poor prognosis, highly predictive of recurrence—perhaps more so of local recurrence—and is a potential tool for long-term tumor surveillance,” a study concluded at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting.

These results corroborate findings from two previous smaller, more heterogenous cohorts, said Eleni Marie Rettig, MD of the Johns Hopkins School of Medicine, Department of Otolaryngology-Head and Neck Surgery in Baltimore, MD.

HPV now causes most of the oropharyngeal carcinomas in the United States, she said, and greater than 90% are HPV16. Although HPV-positive oropharyngeal carcinoma (HPV-OPC) has a favorable prognosis, approximately 10% to 25% of HPV-OPC cases progress, most within 2 to 3 years after treatment. HPV16 detection in oral rinses is strongly associated with HPV-OPC and is detected in up to two-thirds of patients with HPV-OPC. Its value as a prognostic biomarker, however, is unclear, said Dr. Rettig.

The objective of the HOTSPOT study was to determine association of HPV16 DNA detection in post-treatment oral rinses with recurrence and survival after treatment for HPV-OPC.

The study enrolled 151 patients with incident HPV-OPC treated with curative intent from October 2009 through May 2013 at four centers. Oral rinses were collected at baseline (diagnosis) and post-therapy at 9, 12, 18, and 24 months after diagnosis and evaluated for 36 types of HPV DNA—13 of which were high risk—in exfoliated cells using PCR amplification with PGMY09/11 primer.

Of the enrolled patients, 124 (79%) had one or more post-treatment oral rinse (median: 3). The study population was 90% male, 58% were never-smokers, 85% were married, 98% were white, 65% had small tumors (T1-T2), 70% had advanced nodal disease (N2b-N3), and 64% had received radiation-based primary treatment.

At the time of diagnosis, 67 patients (54%) had HPV16 and 27 patients (22%) had other high-risk HPV. Post-treatment, six patients (5%) had HPV16, five patients persistent (4%) and one patient (1%) newly detected, and 17 patients (14%) had other high-risk HPV, seven patients (6%) persistent and 12 patients (10%) newly detected. A total of 93% cleared HPV16 DNA and 74% cleared other high-risk HPV prevalence post-treatment.

At a median follow-up of 33 months, there were 14 recurrences and six deaths, Dr. Rettig reported. All five patients with persistent oral HPV16 recurred and three died of their disease.The 2-year disease-free survival rate was 92% (95% CI: 94, 100) and the 2-years overall survival rate, 98% (95% CI: 93, 99).

There was no association of oral HPV16 DNA with survival at diagnosis; however, there was a strong association for persistent, post-treatment oral HPV16 DNA.

Median time from earliest post-treatment oral HPV16 DNA detection to recurrence was 7 months (range: 3-11 months).

“Among 108 patients with a post-treatment oral rinse collected 9 to 12 months after diagnosis, detection of persistent oral HPV16 DNA had 100% positive predictive value (3/3), 96% negative predictive value (4/108), 43% sensitivity (3/7) and 100% specificity (104/104) for predicting recurrence between 12 to 24 months,” Dr. Rettig said.

The study results raise two important questions, she said: “What does HPV16 DNA in oral rinses represent?” and “Does it have clinical relevance as a surveillance tool?”


1. Rettig EM, Wentz A, Posner MR, et al. Prognostic implication of persistent HPV16 DNA detection in oral rinses for HPV-positive oropharyngeal carcinoma. J Clin Oncol. 2015;33:(suppl; abstr 6005).

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