Fluid Biomarkers in HPV and Non-HPV Related Oropharyngeal Carcinomas: From Diagnosis and Monitoring to Prognostication—A Systematic Review

Abstract

Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong

“…Research studies to generate more direct and indirect evidence on the protection offered by HPV vaccination would enhance an evidence-based decision of policy makers to broaden the scope of vaccination programs against other health needs. With the increase in HPV-associated OPSCC, the development of biomarker panels incorporating HPV DNA/mRNA testing for early cancer screening is an urgent priority [ 39 , 40 ]. Given the difference in epidemiology, available infrastructure, and quality of life issues, management guidelines and public health strategies developed in the West may not be the best for Asian patients [ 41 ].…”

Prognostic prediction models for oropharyngeal squamous cell carcinoma (OPSCC): a protocol for systematic review, critical appraisal and meta-analysis

“…[4][5][6] An increased incidence of OPSCC among men under 45 years of age has been reported recently. [6][7][8][9] Moreover, the death rate of OPSCC is rising by 2% worldwide per year, compared with other head and neck carcinomas, 10 with an estimated 86 742 new deaths in 2020. 4 Of note,…”