Resection Margins in Head and Neck Cancer Surgery: An Update of Residual Disease and Field Cancerization

Abstract

Surgery is one of the mainstays of head and neck cancer treatment, and aims at radical resection of the tumor with 1 cm tumor-free margins to obtain locoregional control. Surgical margins are evaluated by histopathological examination of the resection specimen. It has been long an enigma that approximately 10–30% of surgically treated head and neck cancer patients develop locoregional recurrences even though the resection margins were microscopically tumor-free. However, the origins of these recurrences have been elucidated by a variety of molecular studies. Recurrences arise either from minimal residual disease, cancer cells in the surgical margins that escape detection by the pathologist when examining the specimen, or from precancerous mucosal changes that may remain unnoticed. Head and neck tumors develop in mucosal precursor changes that are sometimes visible but mostly not, fueling research into imaging modalities such as autofluorescence, to improve visualization. Mostly unnoticed, these precancerous changes may stay behind when the tumor is resected, and subsequent malignant progression will cause a local relapse. This led to a clinical trial of autofluorescence-guided surgery, of which the results were reported in 2020. This review focuses on the most recent literature of the improved diagnosis of the resection margins of surgically treated head and neck cancer patients, the pathobiological origin of recurrent disease, and relevant biomarkers to predict local relapse. Directions for further research will be discussed, including potential options for improved and personalized treatment, based on the most recently published data.

Current Strategies for Tumor Photodynamic Therapy Combined With Immunotherapy

“…Anti-PD-1/PD-L1 antibodies have demonstrated excellent efficacy in tumor immunotherapy; however, the high cost of these antibodies adds to the financial burden of cancer patients ( 145 ). To address the high cost of anti-PD-L1 antibodies, Zhang and colleagues ( 146 ) extracted PD-1-expressing HEK293T cell membranes to replace anti-PD-L1 antibodies to bind PD-L1 on 4T1 cells.…”

The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer

“…Yan’s team also proved that the combination of PKA inhibitor and VCP inhibitor and M1 virus reduced the production of virus-induced PD-L1 + DC, MDSC, TAM and T-reg, thereby reduced tumor burden and improved the survival rate of mice, and eventually enhanced the oncolytic effect of M1 virus ( Lin et al, 2014 ; Li et al, 2016 ; Zhang et al, 2017 ). The CRISPR/Cas9 technology was used for high-throughput screening of tumor target genes, which provided us with new ideas for screening the key kinases for ORFV to exert oncolytic effects ( Pierik et al, 2021 ). We purchased the MCF-7 kinase knockout library cells constructed by CRISPR/Cas9, and infected the library cells with ORFV and used high-throughput sequencing to screen out a batch of candidate kinases related to the oncolysis of ORFV.…”

Open Questions in Cold Atmospheric Plasma Treatment in Head and Neck Cancer: A Systematic Review

“…Surgery combined with adjuvant radiation therapy and/or chemotherapy is the standard of care, but in these cases, patients often experience notable complications related to disease treatments, including different degrees of hoarseness or aphonia, dysphagia, dry mouth, aspiration, neck masses, and facial distortion after surgery [ 9 ]. Indeed, it is important to obtain tumor-free resection margins in patients with HNC [ 10 ], and to achieve this, surgeons usually remove the tumor with a margin of 10 mm of macroscopically normal tissue, thus creating a large surgical defect that needs free flap reconstruction in more than half of patients [ 11 ]. Moreover, adjuvant chemoradiation to control the local disease itself may induce many morbidities that affect the quality of life and prognosis [ 12 ], led by the development of different side effects, such as permanent dry mouth, burning mouth syndrome, osteoradionecrosis, dental caries, neurological damage, thyroid function impairment, trismus, fibrosis and eye, and skin damage, compromising the patients’ recovery, psychological health, and physiology [ 13 , 14 ].…”