Abstract
Oropharyngeal squamous cell carcinoma (OPSCC) represents the most common HPV-related malignancy in the United States with increasing incidence. There is heterogeneity between the behavior and response to treatment of HPV-positive oropharyngeal squamous cell carcinoma that may be linked to the tumor virome. In this prospective study, a pan-pathogen microarray (PathoChip) was used to determine the virome of early stage, p16-positive OPSCC and neck metastasis treated with transoral robotic surgery (TORS) and neck dissection. The virome findings of primary tumors and neck lymph nodes were correlated with clinical data to determine if specific organisms were associated with clinical outcomes. A total of 114 patients were enrolled in the study. Double-stranded DNA viruses, specifically Papillomaviridae, showed the highest hybridization signal (viral copies) across all viral families in the primary and positive lymph node samples. High hybridization signals were also detected for signatures of Baculoviridae, Reoviridae, Siphoviridae, Myoviridae, and Polydnaviridae in most of the cancer specimens, including the lymph nodes without cancer present. Across all HPV signatures, HPV16 and 18 had the highest average hybridization signal index and prevalence. To our knowledge, this is the first study that has identified the viral signatures of OPSCC tumors. This will serve as a foundation for future research investigating the role of the virome in OPSCC. Further investigation into the OPSCC microbiome and its variations may allow for improved appreciation of the impact of microbial dysbiosis on risk stratification, oncologic outcomes, and treatment response which has been shown in other cancer sites.
Highlights
Head and neck squamous cell carcinomas (HNSCCs), including oropharyngeal squamous cell carcinoma (OPSCC), are classically associated with risk factors such as tobacco and alcohol use [1]
Further investigation into the Oropharyngeal squamous cell carcinoma (OPSCC) microbiome and its variations may allow for improved appreciation of the impact of microbial dysbiosis on risk stratification, oncologic outcomes, and treatment response which has been shown in other cancer sites
We evaluated the virome for a more homogeneous group of p16-positive, T1 or T2 tonsil squamous cell carcinomas with no positive lymph nodes or a single positive level 2 lymph node
Summary
Head and neck squamous cell carcinomas (HNSCCs), including oropharyngeal squamous cell carcinoma (OPSCC), are classically associated with risk factors such as tobacco and alcohol use [1]. Human papillomavirus (HPV) has emerged as one of the primary causes of carcinogenesis for the majority of OPSCCs in North America and Europe [2]. Important clinical differences exist between HPV-positive and HPV-negative OPSCC which impact treatment decisions. HPV-positive OPSCCs have a higher incidence amongst younger patients with higher performance status, lower tobacco consumption, and higher socioeconomic www.oncotarget.com status [3, 4]. The survival advantage of HPV-positivity persists even after adjusting for confounders [8], suggesting a difference in the tumor biology between HPV-positive and -negative OPSCCs
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