Abstract 3330: Circulating HPV DNA as a biomarker for metastatic cervical cancer detection, genotyping and monitoring

Purpose: Circulating cell-free (cf) human papillomavirus (HPV) DNA is a unique tumor marker for metastatic cervical cancers. We developed a method to genotype and quantify blood circulating HPV DNA in patients with metastatic cervical cancer for patient selection, treatment monitoring, as well as informing data on an experimental T cell therapy. Patients and Methods: we developed a digital droplet (dd) PCR method for HPV genotyping and quantification with cfDNA. In a retrospective study, HPV cfDNA was measured in serum samples from nine metastatic cervical cancer patients received tumor-infiltrating lymphocyte (TIL) immunotherapy. cfDNA data were aligned with the tumor HPV data, drug treatment, and clinical outcome. In a HPV screening, the genotyping and DNA copy number of HPV cfDNA from 47 cervical cancer patients were measured and the allele frequencies were determined in relative to total genomic cfDNA of each patient. Results: The ddPCR assay is highly sensitive, specific, and capable of accurate quantification of both HPV16 and HPV18 cfDNA. In the clinical validation, we detected HPV cfDNA from 19/19 (100%) patients with HPV-positive metastatic and recurrent cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients’ tumors was correctly identified in 87/87 (100%) sequential patient serum samples. Our data showed the use of HPV cfDNA for pharmacokinetic studies, effectiveness on an investigational therapy, and patient monitoring. In three patients who experienced objective responses, a transient HPV cfDNA peak was detected 2-3 days after TIL immunotherapy and a persistent clearance of HPV cfDNA was observed in only two patients with a complete response (CR). Among the HPV positive cases, the median HPV cfDNA allele frequency is above 30% of genomic single copy genes in these cervical cancer patients. Conclusions: We developed and validated a highly sensitive and specific HPV cfDNA genotyping and quantification method. As a promising non-invasive tumor marker, HPV cfDNA may have value in detecting the efficacy of therapeutic agents and monitoring cervical cancer patients in remission. The cfDNA based HPV genotyping is currently being evaluated for patient selection in an experimental T-cell therapy against a specific HPV antigen. HPV cfDNA may also be a potential biomarker for early diagnosis of cervical cancer. Citation Format: Zhigang Kang, Sanja Stevanović, Christian Hinrichs, Liang Cao. Circulating HPV DNA as a biomarker for metastatic cervical cancer detection, genotyping and monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3330.