Abstract 6523: A case of stage I HPV-mediated oropharyngeal squamous cell carcinoma (SCC) diagnosed using a multi-cancer early detection (MCED) test
Authors: Vittone Janet , Feygin Julia , Carey Jason 
Published: April 2023

There are no routine screening tests for head and neck (H&N) cancers, which account for approximately 4% of all cancers in the US. Risk factors for oropharyngeal cancer include smoking and human papillomavirus (HPV) infection. An MCED test that uses a cell-free DNA-based targeted methylation assay and machine learning classifiers to detect a shared cancer signal and predict the cancer signal origin (CSO) is available as a complement to existing single-cancer screening tests. If a cancer signal is detected, the positive result is reported with 1 or 2 CSO prediction(s). We report here a tonsil cancer case detected using an MCED test and review the CSO-guided diagnostic journey. An asymptomatic 74-year-old White male (BMI: 29.9 kg/m2) with history of chronic lymphocytic leukemia (CLL; Rai stage 0; 13q, CD38, and ZAP-70 negative; no treatment was needed) 17 years prior and papillary thyroid cancer (stage IVa; pT3N1bM0; thyroidectomy and radiation therapy; no recurrence) 8 years prior was screened using the MCED test. Patient had an elevated PSA level (9-10 ng/mL) and was a nonsmoker. Fifteen days after a blood sample was collected for analysis, a positive test result (CSO prediction=H&N) was communicated to the patient (Day 1). PET showed abnormal uptake in the right tonsil (Day 28). The patient was referred for an ENT consult and underwent a right lymph node biopsy (Day 54). The biopsy showed invasive moderately differentiated SCC, non-keratinizing, forming a 3 × 2.1 × 1.2 cm mass (Day 57). Patient underwent right tonsillectomy (the surgical margins were negative for invasive or in situ carcinoma) and lymph node dissection (Day 57). The cancer was diagnosed as HPV-mediated p16+, pT2, pN1, cM0 (stage I) SCC of the oropharynx (Day 57). No chemotherapy or radiation was required due to the early stage of detection. The patient will follow-up with ENT and radiation oncology. The MCED test detected a cancer signal and predicted an accurate CSO for an asymptomatic individual with stage I HPV-mediated oropharyngeal SCC. Notably, despite a history of CLL and an elevated PSA level, the test accurately predicted CSO leading to a directed workup diagnosing asymptomatic cancer in less than 2 months, while the cancer was still at stage I. In the case-control Circulating Cell-free Genome Atlas study, the MCED test sensitivity to detect a cancer signal was 63% in stage I H&N cancer. The use of this MCED test led to detection of cancer in a patient with CLL history and treatment (surgery without complications and without chemotherapy or radiation) with curative intent.

Citation Format: Janet Vittone, Julia Feygin, Jason Carey. A case of stage I HPV-mediated oropharyngeal squamous cell carcinoma (SCC) diagnosed using a multi-cancer early detection (MCED) test [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6523.