Circulating tumor HPV DNA, antibodies to HPV16 early proteins, and oral HPV16 DNA as biomarkers for HPV-related oropharyngeal cancer screening

Background: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening. Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men. Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E antibodies and ctHPVDNA using a droplet digital PCR (ddPCR)-based assay that measures circulating tumor tissue modified viral (TTMV)-HPV DNA (NavDx, Naveris, Inc.). We calculated frequency distributions of variables of interest and agreement between the biomarkers. Results: We enrolled 1045 subjects between April 2017 and April 2024. The 954 subjects with results for all three biomarkers were included in the analysis. The prevalence was 4.9% for oral HPV16 DNA, 0.7% for HPV16 E antibodies, and 0.5% for TTMV-HPV DNA. Conclusions: The low prevalence of all three biomarkers shows their potential to identify high-risk individuals eligible for further clinical HPV-related cancer screening.