Peripheral Surrogates of Tumor Burden to Guide Chemotherapeutic and Immunotherapeutic Strategies for HPV-associated Malignancies

With the rapid adoption of immunotherapy into clinical practice for HPV-associated malignancies, assessing tumor burden using "liquid biopsies" would further our understanding of clinical outcomes mediated by immunotherapy and allow for tailoring of treatment based on real-time tumor dynamics. In this review, we examine translational studies on peripheral surrogates of tumor burden derived from peripheral blood in HPV-associated malignancies, including levels and methylation of circulating tumor DNA (ctDNA), miRNA derived from extracellular vesicles, circulating tumor cells (CTCs), and HPV-specific antibodies and T cell responses. We review their utility as prognostic and predictive biomarkers of response to chemotherapy and radiation, with a focus on how they may inform and guide immunotherapies to treat locally advanced and metastatic HPV-associated malignancies. We also highlight unanswered questions that must be addressed to translate and integrate these peripheral tumor biomarkers into the clinic.