Citation: Pillai, S.; Kwan, J.C.; Yaziji, F.; Yu, H.; Tran, S.D. Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers. Cancers 2023, 15, 3894. https:// doi.org/10.3390/cancers15153894 Academic Editor: Juan P. Rodrigo Received: 29 June 2023 Revised: 24 July 2023 Accepted: 27 July 2023 Published: 31 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Review Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers Sangeeth Pillai , Jan C. Kwan, Fares Yaziji, Hanwen Yu and Simon D. Tran * McGill Craniofacial Tissue Engineering and Stem Cell Laboratory, Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 0C7, Canada; sangeeth.pillai@mail.mcgill.ca (S.P.); jan.kwan@mail.mcgill.ca (J.C.K.); fares.yaziji@mail.mcgill.ca (F.Y.); han.w.yu@mail.mcgill.ca (H.Y.) * Correspondence: simon.tran@mcgill.ca Simple Summary: Head and neck cancers (HNCs) are a group of cancers that affect parts like the mouth, throat, and glands in the neck. These cancers are quite complex and can be challenging to detect and treat early. Microfluidic devices are miniature chips that use a small volume of biological samples and have helped in understanding these cancers better. They have revolutionized the way we diagnose and treat cancer. These devices have also allowed us to create models of individual patients’ cancers on a chip, which help develop personalized treatments. In this review, we will talk about how microfluidics has improved the screening of drugs for treating HNC and how it helps in detecting cancer early and in understanding how treatments work. We will also discuss the challenges we face in using these microfluidic technologies in real-life medical settings. Abstract: Head and neck cancers (HNCs) account for ~4% of all cancers in North America and encompass cancers affecting the oral cavity, pharynx, larynx, sinuses, nasal cavity, and salivary glands. The anatomical complexity of the head and neck region, characterized by highly perfused and innervated structures, presents challenges in the early diagnosis and treatment of these cancers. The utilization of sub-microliter volumes and the unique phenomenon associated with microscale fluid dynamics have facilitated the development of microfluidic platforms for studying complex biological systems. The advent of on-chip microfluidics has significantly impacted the diagnosis and treatment strategies of HNC. Sensor-based microfluidics and point-of-care devices have improved the detection and monitoring of cancer biomarkers using biological specimens like saliva, urine, blood, and serum. Additionally, tumor-on-a-chip platforms have allowed the creation of patient- specific cancer models on a chip, enabling the development of personalized treatments through high-throughput screening of drugs. In this review, we first focus on how microfluidics enable the development of an enhanced, functional drug screening process for targeted treatment in HNCs. We then discuss current advances in microfluidic platforms for biomarker sensing and early detection, followed by on-chip modeling of HNC to evaluate treatment response. Finally, we address the practical challenges that hinder the clinical translation of these microfluidic advances. Keywords: head and neck cancers; microfluidics; personalized medicine; biosensing; tumor-on-chip; high throughput screening 1. Introduction Head and neck cancers (HNCs) represent a heterogenous group of tumors originating from the head and neck regions which comprise the upper aerodigestive tract [1]. Even with an increasing awareness regarding human papilloma virus (HPV)-associated oral cancer and decline in tobacco use-related cancer, HNCs remain the seventh most common form of cancer with more than 650,000 new cases every year, killing nearly 300,000 people annually [2]. The recent increase in the incidence rates of HNCs is chiefly attributed to a rise in oropharyngeal cancer and their associated deaths [3]. These statistics point towards Cancers 2023, 15, 3894. https://doi.org/10.3390/cancers15153894 https://www.mdpi.com/journal/cancers