Zhigang Kang, Nisha Nagarsheth, Christian Hinrichs and Liang Cao

• Submitter: Zhigang Kang (Biologist, bioinformatician, chemist, technician)
• email: zhigang.kang@nih.gov

In a retrospective study, we previously demonstrated that HPV ctDNA could be used as a noninvasive marker for tumor HPV genotyping and disease monitoring. To explore the clinical value of HPV ctDNA for companion diagnosis, we prospectively collected plasma samples from HPV associated cancer patients and tested in two independent laboratories for both genotyping and quantitation of HPV 16 and HPV18 ctDNA. The quantitative results of 66 plasma samples from two sites were significantly associated (R2 =0.9998). 59 cases (61%) of the total 97 tested cases were positive for HPV16 and HPV 18 ctDNA. Among 41 patients who have FFPE slides sent for HPV genotyping, 75% (27/36) tissue-HPV-positive cases were found HPV ctDNA positive, 100% (5/5) tissue-HPV-negative cases were found HPV ctDNA negative. Importantly, among 56 patients who do not have FFPE sample available for HPV typing, 57.1% (32) cases were found positive for HPV16 and HPV18 ctDNA. Our current studies illustrate that HPV ctDNA genotyping is highly accurate and reproducible and may be used as an alternative companion diagnostic, especially when tumor tissue is not accessible.