Multiple imputation and clinico-serological models to predict human papilloma virus (HPV) status in oropharyngeal carcinoma: An alternative when tissue is unavailable
Jianjun Ren, Wei Xu, Jie Su (Susie), Xue Ren, Bayardo Perez-Ordonez,Kevin Boyd, Dangxiao Cheng, Zhuo Chen, Noemi Bender, Tim Waterboer,Shao Hui Huang (Sophie), Yu Zhao, Geoffrey Liu
Sichuan University, China
University of Toronto, Canada
Shanghai University of Finance and Economics, China
University Health Network, Canada
German Cancer Research Center (DKFZ), Germany
: J Otol Rhinol
Abstract
Aim: In epidemiological studies, determination of human papilloma virus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) may depend on the availability of clinical testing, and/or tumor tissue access. We aimed to identify alternative methods for estimating HPV status to improve the quality of such datasets. Method: We developed multi-modal prediction models for HPV status and prognosis by combining both clinico-epidemiologic variables and either serological multiplex assays of HPV or multiple imputation of HPV status. Sensitivity, specificity and accuracy between these methods and either p16 immunostaining or survival were assessed. Results: When comparing to a reference of tumor tissue p16 immunostaining in 783 OPC patients, the model incorporating a composite of 20 HPV serological antibodies and clinical factors (c-index: 0.96) performed better than using this composite HPV serology (c-index: 0.92) or imputation (c-index: 0.86) alone. However, the model containing a single HPV 16E6 antibody combined with clinical variables performed extremely well (c-index: 0.95). When defining HPV status by composite HPV, HPV 16E6 serology, multiple imputation, or through p16 immunostaining, each of these definitions demonstrated improved overall and progression-free survival in HPV-positive OPC patients, when compared to HPV-negative patients (adjusted hazard ratios between 0.25 and 0.63). Conclusion: Our study strongly suggests that when blood samples are available, a model that utilizes a single HPV 16E6 antibody combined with several clinical features has excellent performance characteristics to estimate HPV status. When no blood or tumor tissue is available, multiple imputations remain a viable, but suboptimal option. Recent Publications 1. Ren J, Wang J, Zhao Y, et al. (2018) Could aspiration pepsin be used as a marker of gastric reflux? Chest 153(4):107 2. Ren J J, Yu Z, Yang F L, Lv D, Hung S, Zhang J, et al. (2015) Effects of Bifidobacterium breve feeding strategy and delivery modes on experimental allergic rhinitis mice. PLoS ONE 10(10): e0140018. 3. Jian-jun Ren, Yu Zhao, Jing Wang, et al. (2017) Pepsin A as a marker of laryngopharyngeal reflux detected in chronic rhinosinusitis patients. Otolaryngology–Head and Neck Surgery 156(5):893-900. 4. Ren J J, Zhao Y, Ren X, et al. (2017) Is reflux symptom index reliable in chronic rhinosinusitis patients to assess their reflux status? Kaohsiung J Med Sci. 33(6):318-319. 5. Jian-Jun Ren, Yu Zhao, Ming-Juan Liu, Guo Liu and Fei Chen (2015) Langerhans cell sarcoma arising from the root of tongue: a rare case, Int J Clin Exp Pathol. 8(11):15312-15315.
Biography
Jianjun Ren is currently doing the researches of HPV related to head and neck cancer patients’ outcomes; the correlation between laryngopharyngeal reflux and rhinosinusitis; Artificial intelligence in the field of ENT medicine, etc, by using molecular biology, biochemistry, epidemiology, pharmacogenomics and computer science, etc.
E-mail: juneent2016@163.com
