Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV‐related oropharyngeal cancer and cancer of unknown primary

A biomarker that is useful for the detection of human papillomavirus (HPV)‐related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in‐house droplet digital polymerase chain reaction. Seventy‐four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI] = 66‐92) and 100% (95% CI = 88‐100), 85% (95% CI = 69‐94) and 94% (95% CI = 73‐100), and 93% (95% CI = 81‐99) and 97% (95% CI = 84‐100), respectively, for HPV16‐related OPC, while those were 20% (95% CI = 1‐72) and 100% (95% CI = 3‐100), 0% (95% CI = 0‐52) and 100% (95% CI = 3‐100), and 100% (95% CI = 54‐100) and 100% (95% CI = 16‐100), respectively, for HPV16‐related CUP. The sensitivity of ctHPV16DNA for HPV16‐related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume and HPV16 copy number per tumor genome in patients with HPV16‐related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16‐related OPC, while further studies are required for HPV16‐related CUP. What's new? A minimally‐invasive biomarker that allows the detection of human papillomavirus (HPV)‐related oropharyngeal cancer and cancer of unknown primary is indispensable. Here, the authors show that circulating tumour HPV DNA (ctHPVDNA) correlates with the tumour burden and HPV copy number per tumour genome in HPV‐related oropharyngeal cancer and cancer of unknown primary. Neither oral HPV DNA nor mRNA exhibits such a correlation. ctHPVDNA outperforms oral HPV DNA and mRNA in detecting HPV‐related oropharyngeal cancer and in distinguishing HPV‐related cancer of unknown primary from HPV‐unrelated cancers. ctHPVDNA emerges as a potentially useful biomarker for HPV‐related oropharyngeal cancer and cancer of unknown primary.