HPV DNA Tied to Increased Risk for Death from HPV-Positive Oral/Oropharyngeal Cancer

Results from a recent study suggest that a link exists between human papillomavirus (HPV) DNA and an increased risk for recurrence and death from HPV-positive oral or oropharyngeal cancer (JAMA Oncol. 2019 May 2. Epub ahead of print).

“Detection of persistent oral…HPV…DNA may be associated with recurrence of HPV-positive head and neck squamous cell carcinoma (HNSCC),” explained Carole Fakhry, MD, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, and colleagues, who conducted the study.

Dr Fakhry et al conducted a prospective, 2-institution study of 396 patients (median age, 59 years) with newly diagnosed oral cavity or oropharyngeal HNSCC between July 11, 2011, and May 7, 2016, to assess the dynamics of oral HPV DNA detection as well as the outcomes associated with HPV status in HNSCC.

They collected oral rinse samples at diagnosis, upon completion of primary therapy, and weekly during radiotherapy. In addition, the investigators evaluated purified tumor and oral rinse sample DNA for 37 HPV types, and quantified viral load by type-specific real-time polymerase chain reaction.

“Cancers were stratified by tumor HPV status, and HPV was classified as tumor type if identical to that detected in the tumor or nontumor type,” Dr Fakhry and her co-investigators explained.

The main end points of the study were the prevalence of HPV DNA before, during, and after therapy, and any relationships between tumor-type and nontumor-type oral HPV DNA detection and recurrence-free survival (RFS) and overall survival (OS).

Overall, 217 patients had oropharyngeal cancer, 170 had oral cavity cancer, and 9 had unknown primary HNSCC.

Findings demonstrated that the prevalence of oral HPV detection at diagnosis was higher in HPV-positive patients with HNSCC versus HPV-negative patients with HNSCC (24 of 194 [84.2%] vs 170 of 202 [12.4%], respectively; P <.001). Of note, oral HPV-16 DNA had an 81% sensitivity and a specificity of 100% for HPV-16-positive HNSCC.

During primary treatment, the prevalence and load of tumor-type HPV decreased significantly with odds ratio for probability of infection with each increasing month postdiagnosis (0.41; 95% CI, 0.33-0.52; P <.001), whereas those of nontumor types did not (1.01; 95% CI, 0.97-1.06; P = .62).

Notably, being a current smoker was significantly associated with a reduced clearance of tumor-type HPV DNA (hazard ratio [HR], 0.54; 95% CI, 0.32-0.93).

The OS at 2 years was significantly lower in HPV-positive patients with persistent detection of tumor-type HPV posttherapy versus those without detectable tumor-type DNA after therapy (68% vs 95%, respectively; adjusted HR, 6.61; 95% CI, 1.86-23.44; P = .003), as was RFS (55% vs 88%, respectively; adjusted HR, 3.72; 95% CI, 1.71-8.09; P <.001).

Ultimately, there were no relations observed for nontumor type HPV DNA in patients with HNSCC and positive or negative HPV status.

“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,” concluded Dr Fakhry and colleagues.—Hina Khaliq