Head and neck squamous cell carcinoma (HNSCC) manifests in the mucosal epithelial lining of the oral cavity, oropharynx, hypopharynx, nasopharynx or larynx and has a tremendous disease burden worldwide. Smoking and alcohol consumption were once major risk factors, but HPV-associated infection has emerged as the major contributor to HNSCC occurrence in developed countries. Circulating biomarker evaluations in biofluids, also known as liquid biopsy, are an attractive alternative for cancer screening as they are minimally invasive, potentially low cost, and easily repeatable on a serial basis. This review summarizes the current knowledge and potential of assessing circulating blood and salivary HPV DNA and HPV antibodies for the surveillance of HPV-positive HNSCC. Additionally, the biological underpinnings of the presence and relevance of circulating HPV DNA is discussed.