Presence of Oral HPV After Treatment of HNSCC May Predict Recurrence

An increasing number of patients with oropharyngeal head and neck squamous cell carcinoma (HNSCC) have human papillomavirus (HPV) associated cancer. Although HPV-positive oropharyngeal cancers are generally less aggressive than HPV-negative tumors, around 20% of HPV-positive patients experience cancer progression and death within 5 years. Thus, markers to identify patients at risk for recurrence are needed. Several retrospective studies have suggested that presence of oral HPV-16 DNA following curative treatment may be associated with detection of subclinical cancer. In a recently published prospective cohort study of 396 newly diagnosed patients with oral cavity or oropharyngeal HNSCC, outcomes after completion of primary treatment were correlated to presence or absence of HPV DNA in oral rinse samples collected before, during, and after therapy.

Prior to treatment, the majority of patients in the HPV-positive cohort tested positive for HPV DNA (84.2%), while relatively few patients (12.4%) in the HPV-negative cohort had detectable DNA. Presence of oral HPV DNA was determined to have an 81% sensitivity and a 100% specificity for detection of HPV-positive HNSCC. Oral HPV DNA detection at diagnosis in patients with HPV-positive HNSCC was associated with stage T3 or T4 tumors, while presence of oral HPV DNA in patients with HPV-negative tumors was associated with male sex and higher lifetime number of sexual partners.

Among HPV-positive tumors, the prevalence of oral tumor-type HPV decreased significantly following surgical resection (69.2% vs 13.7%, P<.001) or primary radiotherapy (85% vs 9%, P<.001). For patients who required adjuvant radiotherapy following surgery, prevalence decreased from 70% to 38% after surgery and then decreased to 1% after radiotherapy (P<.001). No decrease in nontumor type HPV was observed following any treatment. Median time to clearance was 42 days, and current smoking was the only factor associated with reduced clearance of tumor-type HPV DNA (HR 0.49, P = .01).

Persistence of oral tumor-type HPV DNA among patients with HPV-positive HNSCC was associated with a significant reduction in 2-year overall survival (OS) rates compared to patients without oral HPV DNA (68% vs 95%; HR 6.61, P = .003). A similar association between presence of HPV DNA and poorer outcomes was seen in terms of 2-year recurrence-free survival (55% vs 88%; HR 3.71, P<.001), as well as rates of local and regional recurrence. Presence of HPV DNA and higher viral loads at diagnosis did not impact outcomes.

The authors concluded that presence of oral tumor-type HPV DNA in patients with HNSCC following primary treatment is associated with increased risk of recurrence and death, and that this may be used as a marker for patients who need close observation or adjuvant therapy. Importantly, presence of nontumor-type HPV DNA did not impact outcomes, reflecting that patients may have an ongoing HPV infection, regardless of tumor status.

JAMA Oncol. 2019 May 2. [Epub ahead of print.]
Persistence of oral-HPV-Predicts-Risk-of-HNSCC-Recurrence

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