Circulating Tumor High Risk HPV DNA as the HPV-Specific Test in Oropharyngeal Squamous Cell Carcinoma Patients.

PURPOSE: The uses for circulating tumor high risk human papillomavirus DNA (ctHPVDNA) in the diagnostic work-up and treatment of HPV-associated oropharyngeal squamous cell carcinoma (HPV( +)OPSCC) patients are actively being investigated. We evaluated the concordance of ctHPVDNA with tissue-based HPV testing (p16 immunohistochemistry (IHC), DNA in situ hybridization (ISH), and/or RNA ISH) to assess its performance as a primary diagnostic test for patients' HPV status.

METHODS

We conducted a retrospective cross-sectional study of patients evaluated at a tertiary care multidisciplinary oropharyngeal cancer clinic with suspected HPV( +)OPSCC who underwent pre-treatment ctHPVDNA testing (HPV types 16, 18, 31, 33, 35) via the NavDx assay.

RESULTS

Of 236 patients with OPSCC, 190 (81%) had a positive ctHPVDNA result. 41 (17%) were negative, and 3 (1%) were indeterminate. Of the 190 patients with a positive ctHPVDNA result, 190 (100%) had positive tissue-based HPV testing. Of the 41 patients with a negative result, 34 (83%) had positive tissue-based HPV testing and 7 (17%) were negative. ctHPVDNA demonstrated a sensitivity of 85% (95% CI 79-89%), specificity of 100% (95% CI 59-100%), NPV of 17% (95% CI: 7-32%), and PPV of 100% (95% CI 98-100%).

CONCLUSION

The high specificity and PPV of ctHPVDNA indicate that in the setting of a positive result and high clinical suspicion, it may not be necessary for pathologists to test subsequent cytology or tissue specimens that are diagnostic for SCC for p16 or HPV. In the setting of a negative ctHPVDNA result, however, our findings indicate that HPV testing of a pathology specimen must still be performed.