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PurposeTo characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations.Experimental designTumor RNA-sequencing data from over 800 patients with head and neck squamous cell carcinoma (HNSCC) and cervical cancer, including a prospective validation cohort, was analyzed to study the impact of B-cell gene expression on overall survival (OS). A novel murine model of HPV+ HNSCC was used to study the effects of PD-1 blockade and radiotherapy on B-cell activation, differentiation, and clonality including analysis by single-cell RNA-sequencing and B-cell receptor (BCR)-sequencing. Human protein microarray was then used to quantify B-cell-mediated IgG and IgM antibodies to over 16,000 proteins in the serum of patients treated on a clinical trial with PD-1 blockade.ResultsRNA-sequencing identified CD19 and IGJ as novel B-cell prognostic biomarkers for 3-year OS (HR, 0.545; P < 0.001). PD-1 blockade and radiotherapy enhance development of memory B cells, plasma cells, and antigen-specific B cells. BCR-sequencing found that radiotherapy enhances B-cell clonality, decreases CDR3 length, and induces B-cell somatic hypermutation. Single-cell RNA-sequencing identified dramatic increases in B-cell germinal center formation after PD-1 blockade and radiotherapy. Human proteome array revealed enhanced IgG and IgM antibody responses in patients who derived clinical benefit but not those with progressive disease after treatment with PD-1 blockade.ConclusionsThese findings establish a key role for B cells in patient outcomes and responses to PD-1 blockade in HPV-associated squamous cell carcinomas and demonstrate the need for additional diagnostics and therapeutics targeting B cells.

OBJECTIVE:The incidence and survivorship of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) are increasing. Presence of HPV DNA and epigenetic alterations in salivary rinses are independently associated with clinical prognosis. We evaluated the utility of a combined panel in detecting disease recurrence during surveillance. We also assessed the assay's applicability in screening for HPV+ OPSCC. STUDY DESIGN:Retrospective cohort study. SETTING:Two tertiary academic hospitals. SUBJECTS AND METHODS:Forty-nine patients with posttreatment OPSCC were enrolled. Separately, 21 treatment-naive patients and 40 controls were included in the screening analysis. Salivary rinses were obtained from these cohorts and biomarker levels were quantified. Receiver operative characteristic (ROC) curves and multivariate logistic models were used to assess performance of biomarker combinations. RESULTS:Eight patients (16.3%) in the posttreatment cohort developed locoregional recurrence. Recurrence was associated with alcohol use (odds ratio [OR], 6.12; 95% confidence interval [CI], 0.26-3.79) and advanced nodal disease (OR, 2.21; 95% CI, 1.52-3.01). A panel of HPV DNA and methylated EDNRB improved detection of recurrent disease (area under the curve [AUC], 0.88) compared to single markers (AUC, 0.69-0.78). Positive biomarkers preceded clinical detection by 2.4 ± 1.6 months and was associated with nearly 40-fold risk of recurrence (OR, 36.4; 95% CI, 1.15-45.22). Within the screening analysis, single biomarkers demonstrated moderate sensitivity and specificity (AUC, 0.59-0.83) in the detection of primary disease. A panel combining HPV DNA markers with methylated EDNRB and methylated PAX5 improved AUC to 0.93. CONCLUSION:Detection of high-risk HPV DNA or aberrant hypermethylation in oral rinses is associated with presence and recurrence of OPSCC. Targeting both markers in saliva may have utility in long-term surveillance.

Introduction  Postoperative pain management and opioid use following endoscopic skull base surgery (ESBS) is not well understood. A subset of patients requires additional opioid prescription (AOP) in the postoperative period. The objective of this study is to describe the incidence of AOP, as well as evaluate patient and surgical characteristics that may predict additional pain management requirements following ESBS. Methods  A retrospective review of cases undergoing ESBS between November 2016 and August 2018 was performed. We reviewed patients' sociodemographic and clinical data, and Controlled Substance Utilization Review and Evaluation System (CURES) records. Stepwise multivariable logistic regressions were performed to evaluate the factors associated with AOP within 60 days following surgery. Results  A total of 42 patients were identified. Indications for ESBS included intracranial mass (64.2%), sinonasal malignancy (23.8%), and skull base reconstruction (9.5%). AOP were recorded in nine patients (21.4%). There were no significant differences in operative factors, including approach, lesion location, or perioperative analgesia between the two cohorts. On multivariable logistic regression, we found that younger age (odds ratio [OR]: 0.891, 95% confidence interval [CI]: 0.79–1.00, p  = 0.050), comorbid depression (OR: 86.48, 95% CI: 1.40–5,379.07, p  = 0.034), and preoperative opioid use (OR: 104.45, 95% CI: 1.41–7,751.10, p  = 0.034) were associated with additional prescriptions postoperatively. Conclusion  The requirement for extended postoperative opioid pain control is common after ESBS. Patient demographics including age and psychosocial factors, such as depression may predict the need for AOP after ESBS. These results suggest that patient-driven factors, rather than surgical characteristics, may determine the need for prolonged pain control requirements after ESBS. [ABSTRACT FROM AUTHOR]