Addressing Positive Multi-Cancer Early Detection Tests in Head and Neck Surgery: Experience with Head and Neck Work Up for High-Risk Referrals

Purpose/Objective(s) Multi-cancer early detection (MCED) tests offer population-based screening for cancer using minimally invasive blood-based sampling and are now commercially available on a self-pay basis. Patients may be identified as at risk for head and neck cancer (HNC) based on a positive signal and predicted site of origin. Detailed information about subsite of origin is not available. There are currently no consensus guidelines available for HNC providers to direct work up or surveillance for these patients. We report an early case series which highlights considerations when evaluating patients referred for a positive commercially obtained MCED test. Materials/Methods Retrospective chart review of patients referred to Otolaryngology-Head and Neck Surgery (Oto-HNS) with an at risk MCED result. Patients who were enrolled in unpublished prospective clinical trials were excluded. Results Three patients were identified as high risk for HNC and one patient had a positive lymphoma MCED test (mean age: 70.8 years, range: 50-87; 3 male). All were asymptomatic. Patient 1 was at risk for HNC on MCED and had an abnormal oropharyngeal exam, H&N CT, PET/CT, and was diagnosed with pT2N1M0 p16(+) oropharygeal squamous cell carcinoma (HPV(+)OPSCC). Patient 2 was at risk for HNC and had a neck mass on exam, abnormal H&N CT, abnormal PET/CT, tested positive for circulating tumor HPV DNA (ctHPVDNA), and was diagnosed with pT2N1M0 HPV(+)OPSCC. Patient 3 was at risk for HNC and lung on MCED, had a normal H&N exam, an indeterminate 8-9 mm deep lobe parotid mass on H&N CT, H&N MRI, and H&N US, and a thigh mass on PET/CT, and was diagnosed with high grade undifferentiated pleomorphic sarcoma of the thigh. Due to the small size of the parotid mass, location, patient age and pressing comorbidities, radiographic surveillance with MRI and exam in 6 months was recommended. Patient 4 was referred to Oto-HNS for a positive lymphoma MCED test for H&N exam, and had no abnormal findings on exam or PET/CT. This patient is undergoing surveillance with MRI and exam in 6 months. The average time from MCED test result to clinical diagnosis was 42 days (range: 26-56 days). Conclusion In this case series, 67% (2/3) of patients referred with a positive MCED result suggesting HNC were diagnosed with HPV(+)OPSCC. We recommend that positive H&N MCED results be . Currently, work up should include a thorough H&N examination including flexible laryngoscopy and focused CT imaging. The performance of tissue of origin classifiers for squamous malignancies may be less accurate, supporting the use of a PET/CT scan in this setting. ctHPVDNA may be a useful adjunct for indeterminate imaging and physical exam findings. For a patient with no cancer identified, development of clear guidelines are warranted.