HPV DNA and Outcomes After Primary Treatment for Oral and Oropharyngeal Squamous Cell Carcinomas


Key Points

  • Prevalence and viral load of tumor-type HPV DNA decreased rapidly with primary therapy.
  • Persistence of tumor-type HPV DNA was associated with poorer 2-year survival.

In a two-institution study reported in JAMA Oncology, Fakhry et al found that persistent detection of tumor-type human papillomavirus (HPV) DNA after primary treatment for oral and oropharyngeal squamous cell carcinomas was associated with poorer outcomes.

Study Details

The prospective study included 396 patients with newly diagnosed oral cavity or oropharyngeal head and neck squamous cell carcinoma treated at Ohio State University Columbus or Greater Baltimore Medical Center from July 2011 to May 2016. Oral rinse samples for HPV testing were prospectively collected at diagnosis and at completion of primary therapy.

Tumor-type HPV DNA was defined as the same HPV DNA type detected in the oral rinse sample and in the tumor at baseline.

Treatment Outcomes

Of the 396 patients, 202 (51.0%) had HPV-positive head and neck squamous cell carcinomas and 194 (49.0%) had HPV-negative head and neck squamous cell carcinomas. Most oropharyngeal cancers (187 of 217; 86.2%) and unknown primary head and neck squamous cell carcinomas (8 of 9; 88.9%) were HPV-positive; only 7 of 170 oral cavity cancers (4.1%) were HPV-positive. The prevalence of oral HPV DNA detection at diagnosis was 84.2% among patients with HPV-positive disease and 12.4% among those with HPV-negative head and neck squamous cell carcinoma (P < .001). Oral HPV-16 DNA had an 81% sensitivity and 100% specificity for HPV-16-positive head and neck squamous cell carcinoma.

Prevalence and load of tumor-type HPV DNA decreased during primary therapy, with an odds ratio (OR) for probability of infection of 0.41 (P < .001) with each additional month after diagnosis; the OR for nontumor-type was 1.01 (P = .62). Current smoking was associated with reduced clearance of tumor-type HPV DNA (hazard ratio [HR] = 0.54, 95% confidence interval [CI] =0.32–0.93).

Overall survival at 2 years was 68% among 21 HPV-positive patients with persistent detection of tumor-type HPV DNA after therapy vs 95% among 128 without detectable tumor-type DNA after therapy (adjusted HR = 6.61, P = .003). Two-year recurrence-free survival was 55% vs 88% (adjusted HR = 3.72, P < .001). No associations in outcomes were observed for nontumor-type HPV DNA among patients with HPV-positive or HPV-negative head and neck squamous cell carcinoma.

The investigators concluded, “Prevalence and viral load of tumor-type HPV DNA decreased rapidly with therapy, and persistent detection was associated with increased risk of recurrence and death. Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression.”

Maura L. Gillison, MD, PhD, of the Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by a grant from the Oral Cancer Foundation and The Ohio State University Comprehensive Cancer Center. For full disclosures of the study authors, visit

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