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Abstract
Introduction Cervical cancer is the 4th most common cancer in women worldwide. Majority of cases are caused by human papillomavirus (HPV) infection and early detection is possible with cytology and/or HPV-DNA. However, cytology has a low sensitivity, and the HPV-DNA test has a low specificity in distinguishing transient from clinically significant HPV infections. Furthermore, there are limited non-invasive options for surveillance post-treatment. Liquid biopsy is a non-invasive approach aimed at addressing these limitations. This study aimed to demonstrate that HPV circulating tumour (ct)DNA levels in blood, urine, and vaginal swabs correlate with extent of disease.
Methods Using ddPCR, primers were designed to target the viral E7 oncogene sequence from high-risk HPV subtypes (hrHPV 16, 18 and 33). Samples were collected from patients with cervical dysplasia ranging from low to high grade (pre-cancer group, n=22) and patients with a new cervical cancer diagnosis (cancer group, n=23).
Results HPV ctDNA was detected in more cancer patients (13/23, 56.5%) than pre-cancer patients (1/22, 4.5%). Among the ctDNA-positive patients, the concentration was higher in the urine and vaginal swabs compared to blood. Furthermore, samples collected from cancer patients at multiple timepoints (n=7) showed that ctDNA decreased post-treatment.
Conclusion/Implications HPV ctDNA levels correlated to the extent of disease and was detectable in different liquid biopsy samples. Liquid biopsy has the potential to serve as a non-invasive complementary method to existing techniques both in screening and monitoring of cervical pre-cancer and cancer. Future work will explore other hrHPV subtypes and the performance of individual analytes.
