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Abstract Background Human papillomavirus high risk (HPV-HR) type 16 is a significant risk factor for head and neck cancers (HNC) independent of tobacco and alcohol. The purpose of this study was to determine whether antibody levels to the HPV-16 oncoproteins E6 and E7 measured in sera collected at baseline (BL) prior to treatment and at two post-treatment follow-up (FU) visits were associated with HNC risk factors or prognosis. Methods Presence of antibodies to HPV-16 E6 and E7 was evaluated in 109 newly diagnosed HNC cases with BL and FU blood samples, using the enzyme-linked immunosorbent assay (ELISA). Results HPV-16 E6 and/or E7 seropositive HNC cases were associated with higher risk in younger patients (≤ 55 years), more sexual partners (≥ 10), oropharyngeal cancer, worse stage at diagnosis, poorer grade, and nodal involvement. Between BL and FU (median = 8.3 months), there were decreased antibody levels for seropositive E6 (73% vs. 27%, p = 0.02) and seropositive E7 patients (65% vs. 35%, p = 0.09) with 5% of BL E6 and 35% of BL E7 seropositive patients converting to negative status at FU. Overall mortality (OM) was significantly worse among BL E6 seronegative patients than among BL seropositive patients (40.2% vs.13.6%, p = 0.01). There were no disease specific (DS) deaths among BL E6 seropositive vs. 24% in BL E6 seronegative patients (p = 0.01). BL E7 seronegative patients also had higher mortality than BL seropositive patients (OM: 38.2% vs. 20.0%, p = 0.04; DS: 22.5% vs. 5.6%, p = 0.07). Conclusion These findings are the first to follow post-treatment OD levels of HPV-16 E6 and E7 in HNC and suggest that these HPV antibodies may be potential prognostic markers of survival in HNC patients.

Abstract Background P16 and p53 protein expression, and high-risk human papillomavirus (HPV-HR) types have been associated with survival in head and neck cancer (HNC). Evidence suggests that multiple molecular pathways need to be targeted to improve the poor prognosis of HNC. This study examined the individual and joint effects of tumor markers for differences in predicting HNC survival. P16 and p53 expression were detected from formalin-fixed, paraffin-embedded tissues by immunohistochemical staining. HPV DNA was detected by PCR and DNA sequencing in 237 histologically confirmed HNC patients. Results Overexpression of p16 (p16+) and p53 (p53+) occurred in 38% and 48% of HNC tumors, respectively. HPV-HR was detected in 28% of tumors. Worse prognosis was found in tumors that were p53+ (disease-specific mortality: adjusted hazard ratios, HR = 1.9, 95% CI: 1.04-3.4) or HPV- (overall survival: adj. HR = 2.1, 1.1-4.3) but no association in survival was found by p16 status. Compared to the molecular marker group with the best prognosis (p16+/p53-/HPV-HR: referent), the p16-/p53+/HPV- group had the lowest overall survival (84% vs. 60%, p < 0.01; HR = 4.1, 1.7-9.9) and disease-specific survival (86% vs. 66%, p < 0.01; HR = 4.0, 1.5-10.7). Compared to the referent, the HRs of the other six joint biomarker groups ranged from 1.6-3.4 for overall mortality and 0.9-3.9 for disease-specific mortality. Conclusion The p16/p53/HPV joint groups showed greater distinction in clinical outcomes compared to results based on the individual biomarkers alone. This finding suggests that assessing multiple molecular markers in HNC patients will better predict the diverse outcomes and potentially the type of treatment targeted to those markers.

As medical schools have changed their curricula to address foundational and clinical sciences in a more integrated fashion, teaching methods such as concept mapping have been incorporated in small group learning settings. Methods that can assess students' ability to apply such integrated knowledge are not as developed, however. The purpose of this project was to assess the validity of scores on a focused version of concept maps called mechanistic case diagrams (MCDs), which are hypothesized to enhance existing tools for assessing integrated knowledge that supports clinical reasoning. The data were from the medical school graduating class of 2018 (N = 136 students). In 2014-2015 we implemented a total of 16 case diagrams in case analysis groups within the Mechanisms of Health and Disease (MOHD) strand of the pre-clinical curriculum. These cases were based on topics being taught during the lectures and small group sessions for MOHD. We created an overall score across all 16 cases for each student. We then correlated these scores with performance in the preclinical curriculum [as assessed by overall performance in MOHD integrated foundational basic science courses and overall performance in the Clinical and Professional Skills (CAPS) courses], and standardized licensing exam scores [United States Medical Licensing Exam (USMLE)] Step 1 (following core clerkships) and Step 2 Clinical Knowledge (at the beginning of the fourth year of medical school). MCD scores correlated with students' overall basic science scores (r = 0.46, p = 0.0002) and their overall performance in Clinical and Professional Skills courses (r = 0.49, p < 0.0001). In addition, they correlated significantly with standardized exam measures, including USMLE Step 1 (r = 0.33, p [less than or equal to] 0.0001), and USMLE Step 2 CK (r = 0.39, p < 0.0001). These results provide preliminary validity evidence that MCDs may be useful in identifying students who have difficulty in integrating foundational and clinical sciences.