Kevin Chen

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.

&lt;p&gt;Supplementary methods found here.&lt;/p&gt;

Kaposi sarcoma (KS) is a serious AIDS-defining malignancy that can progress rapidly in the setting of profound immunosuppression. Non-adherence to antiretroviral therapy (ART) remains a major barrier to viral suppression, particularly among underserved populations. We present the case of a 36-year-old African American man who has sex with men (MSM), living in an underserved community, with a history of HIV/AIDS and late latent syphilis. The patient developed disseminated KS after six months of non-adherence to bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy). He presented with a CD4 count of 44 cells/µL and a viral load of 592,000 copies/mL. Clinical findings included multiple violaceous skin lesions, pulmonary reticulonodular infiltrates with pleural effusion, and lymphadenopathy. Biopsy confirmed KS. He was restarted on ART and prophylactic antibiotics upon discharge. This case highlights the severe consequences of ART non-adherence in a vulnerable population. Targeted interventions, including long-acting ART, behavioral support, and telehealth innovations, are essential to improve retention in care and prevent advanced HIV-related complications like KS.

&lt;p&gt;Supplementary Table S1. Patient-level characteristics of the HPV (+) OPSCC cohort&lt;/p&gt;