Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring. Significance: Plasma DNA molecules originating from the liver, HCC and other cancers, placenta, and hematopoietic cells each harbor a set of characteristic plasma DNA end motifs. Such markers carry tissue-of-origin information and represent a new class of biomarkers in the nascent field of fragmentomics. This article is highlighted in the In This Issue feature, p. 627

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.

While the overall incidence of head and neck cancer is decreasing in the United States, recognized cases of oropharyngeal squamous cell carcinoma (OPSCC) are on the rise. This is predominantly owing to an epidemic of oropharyngeal cancer related to high-risk human papillomavirus (HPV). Prior studies cite a rising proportion of OPSCC cases related to HPV, with literature supporting 50% or greater being HPV-16 related.^1-3 Recently, oral HPV infection has been shown to have a prevalence of 7% in the general population with a bimodal distribution.⁴ Quiz Ref ID Oral HPV infection is more prevalent in the male compared with female population, with a prevalence ratio of 2.3 and a peak incidence of up to 10% in men aged 55 to 64 years. Within the general population, approximately 1% are infected with the high-risk subtype HPV-16.⁴ Quiz Ref ID In addition, both retrospective and prospective studies have demonstrated an improved overall survival in HPV-16–positive OPSCC vs HPV-16–negative OPSCC counterparts; an outcome believed to hold true for both surgical and nonsurgical treatment modalities.^2,5,6

A compact and dexterous magnetic resonance (MR)–safe soft robot enables MR imaging–guided transoral laser microsurgery.

This Viewpoint describes the precautions taken when treating patients in Hong Kong since the novel coronavirus disease 2019 (COVID-19) epidemic began in China.