Recombinant HPV type 11 [GST]

High-risk human papillomavirus (HPV) types 16/18 have been associated with Barrett's dysplasia (BD)/esophageal adenocarcinoma (EAC). Nevertheless, no data exist in relation to serological analysis for HPV antibodies in BD/EAC with site-specific viral DNA status. We prospectively examined antibodies to multiple HPV types in 438 patients representing hospital/reflux controls and Barrett's metaplasia (BM)/BD/intramucosal EAC. Antibody responses to HPV6/11/16/18/31/33/45/52/58 were analyzed using multiplex serology, including antibodies to E6/E7/E1/E2 and L1 antigens. Seropositivity for individual HPV proteins was infrequent in both cases and controls and was <= 10.2%. There was no difference in the seroprevalence of antibodies to any HPV antigen/antibody combination between reclassified cases (BD/EAC) and controls (hospital/reflux/BM) or between HPV16 or HPV18 DNA cases and controls, respectively. Among HPV16 DNA-positive BD/EAC cases, antibodies to HPV16 E7 were significantly more prevalent (3/26, 11.5%) than in hospital and reflux controls plus BM (5/328, 1.5%) (adjusted OR = 10.12, 95% CI: 1.61-63.73,P = 0.014). Among HPV18 DNA-positive cases, antibodies to HPV18 E1 were present in 3/6 (50%) cases versus 5/328 (1.5%) controls (adjusted OR = 44.28, 95% CI: 6.10-321.47,P = 0.0002). Although antibodies against HPV were generally uncommon in cases and controls, immune responses against two early proteins of HPV16/18 were significantly more frequent in viral DNA-positive BD/intramucosal EAC.

Introduction: The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx). Materials and methods: We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 317 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2. Results: Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P < 0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65). Conclusion: The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.