Written in Blood: Liquid Biopsies for Cervical Cancer Screening

Cervical cancer (CC) is one of the most common malignancies affecting women across the world. The major cause of CC is human papillomavirus (HPV) infection. Studies have shown that HPV infection is highly correlated (>99%) with the occurrence of CC. HPV testing is done on women infected with high-risk HPV types that correlate strongly to CC development, such as HPV types 16 and 18.  In conjunction with HPV testing, traditional CC screening (Pap test and visual inspection test) is done as standard practice against all HPV types. However, the Pap test and HPV testing are highly invasive techniques that require collection of cervical cells at annual intervals for at-risk women. In addition, such tests pose significant socio-economic challenges, especially in countries where the combination of inadequate infrastructure and inadequate medical expertise greatly reduce test accuracy. Recently, liquid biopsy has been extensively examined as an alternative to cancer screening and diagnostics.  Liquid biopsy is a non-invasive technique that screens for circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) in the blood. ctDNA are fragments of cell-free DNA, shed from cell death, that contain hallmark mutations of cancerous cells. CTCs are tumor cells that have metastasized from primary tumor sites and are released into the blood-stream. Due to advances in high-throughput sequencing, the analysis of CTC and ctDNA is possible. Liquid biopsies can also detect real-time molecular changes that occur in the cancer and provide a more complete tumor profile regarding the number of tumor DNA mutations.  Liquid biopsy provides an exciting alternative for patients who may be unwilling to undergo invasive, and often painful, CC and HPV screening. Furthermore, it may greatly reduce medical costs as no specialized training is required to obtain samples, and it allows health-care practitioners to perform more testing, effectively monitoring disease progression. This can enable more targeted approaches to CC treatment and dramatically improve patient outcomes.