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Yang L, Yu L, Shi G, Yang L, Wang Y, Han R, Huang F, Qian Y, Duan X. Radiomic features of dynamic contrast-enhanced MRI can predict Ki-67 status in head and neck squamous cell carcinoma. Magn Reson Imaging 2025; 116:110276. [PMID: 39571922 DOI: 10.1016/j.mri.2024.110276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/10/2024] [Accepted: 11/13/2024] [Indexed: 11/29/2024]
Abstract
PURPOSE This study aimed to investigate the potential of radiomic features derived from dynamic contrast-enhanced MRI (DCE-MRI) in predicting Ki-67 and p16 status in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS A cohort of 124 HNSCC patients who underwent pre-surgery DCE-MRI were included and divided into training and test set (7:3), further subgroup analysis was performed for 104 cases with oral squamous cell carcinoma (OSCC). Radiomics features were extracted from DCE images. The least absolute shrinkage and selection operator (LASSO) was used for radiomics features selection, and receiver operating characteristics analysis for predictive performance assessment. The nomogram's performance was evaluated using decision curve analysis (DCA). RESULTS Ten DCE-MRI features were identified to build the predictive model of HNSCC, demonstrating excellent predictive value for Ki-67 status in both the training set (AUC of 0.943) and test set (AUC of 0.801). The nomograms based on the predictive model showed good fit in the calibration curves (p > 0.05), and DCA indicated its high clinical usefulness. In subgroup analysis of OSCC, fourteen features were selected to build the predictive model for Ki-67 status with an AUC of 0.960 in training set and 0.817 in test set. No features could be included to establish a model to predict p16 status. CONCLUSION The radiomics model utilizing DCE-MRI features could effectively predict Ki-67 status in HNSCC patients, offering potential for noninvasive preoperative prediction of Ki-67 status.
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Affiliation(s)
- Lu Yang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China
| | - Longwu Yu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui Province, China
| | - Guangzi Shi
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China
| | - Lingjie Yang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China
| | - Yu Wang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China
| | - Riyu Han
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China
| | - Fengqiong Huang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China
| | - Yinfeng Qian
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui Province, China.
| | - Xiaohui Duan
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong, China.
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Liu XY, Hanjing S, Zhang BH, Luo XY. Expression of p16 and Ki67 in laryngeal squamous cell carcinoma and their clinical significance. Front Oncol 2024; 14:1430830. [PMID: 39376982 PMCID: PMC11456525 DOI: 10.3389/fonc.2024.1430830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/29/2024] [Indexed: 10/09/2024] Open
Abstract
Objective The objective of this study is to assess the prognostic value of Ki67 and p16 proteins in laryngeal cancer. Materials and methods This retrospective cohort analysis comprised 260 patients diagnosed with laryngeal cancer. Immunohistochemistry (IHC) was employed to assess the expression levels of p16 and Ki67, and their correlation with the survival time of laryngeal cancer patients was analyzed. Results The Ki67 index level exhibited a significant association with the prognosis of laryngeal cancer. Patients with higher Ki67 index levels demonstrated shorter survival times, more severe pathological classification, and higher tumor stages (P < 0.05). Conversely, no significant differences in prognostic characteristics of laryngeal cancer were observed in the p16 (-/+) population (P > 0.05). The median survival times for patients with Ki67 index levels of 0-35%, 36-70%, and 70-100% were 3.54 years, 2.10 years, and 1.92 years, respectively. After adjusting for age, smoking, alcohol consumption, pathological classification, surgical intervention, recurrence, and metastasis, the risk of death for patients with Ki67 index levels of 70-100% was 2.0504 times higher than that of patients with Ki67 index levels of 0-35% (95% CI: 1.2997-3.2345, P = 0.0020). Conclusion The Ki67 index level is strongly associated with survival time and the risk of death in laryngeal cancer, making it a valuable prognostic indicator. However, the prognostic value of p16 levels in laryngeal cancer is limited. These findings provide important insights for prognosis evaluation and treatment decision-making in patients with laryngeal cancer.
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Affiliation(s)
| | | | | | - Xian-Yang Luo
- Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
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Ye Z, Xiao M, Zhang Y, Zheng A, Zhang D, Chen J, Du F, Zhao Y, Wu X, Li M, Chen Y, Deng S, Shen J, Zhang X, Wen Q, Zhang J, Xiao Z. Identification of tumor stemness and immunity related prognostic factors and sensitive drugs in head and neck squamous cell carcinoma. Sci Rep 2024; 14:15962. [PMID: 38987626 PMCID: PMC11236973 DOI: 10.1038/s41598-024-66196-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/28/2024] [Indexed: 07/12/2024] Open
Abstract
The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.
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Affiliation(s)
- Zhihua Ye
- Department of Medical Oncology Center, Zhongshan People's Hospital, Zhongshan, Guangdong, China
| | - Mintao Xiao
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Yinping Zhang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Anfu Zheng
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Duoli Zhang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Jie Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Shuai Deng
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Xinyi Zhang
- School of Data Science, The Chinese University of Hong Kong, Shenzhen, China
| | - Qinglian Wen
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Junkai Zhang
- Department of Medical Oncology Center, Zhongshan People's Hospital, Zhongshan, Guangdong, China.
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China.
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China.
- Department of Pharmacology, School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, 621000, Sichuan, China.
- Gulin Traditional Chinese Medicine Hospital, Luzhou, China.
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Wang CW, Biswas PK, Islam A, Chen MK, Chueh PJ. The Use of Immune Regulation in Treating Head and Neck Squamous Cell Carcinoma (HNSCC). Cells 2024; 13:413. [PMID: 38474377 PMCID: PMC10930979 DOI: 10.3390/cells13050413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open
Abstract
Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.
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Affiliation(s)
- Che-Wei Wang
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan; (C.-W.W.); (A.I.)
- Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan;
| | - Pulak Kumar Biswas
- Institute of Molecular Medicine, National Cheng Kung University, Tainan 70101, Taiwan;
| | - Atikul Islam
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan; (C.-W.W.); (A.I.)
| | - Mu-Kuan Chen
- Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan;
| | - Pin Ju Chueh
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan; (C.-W.W.); (A.I.)
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Gallus R, Rizzo D, Rossi G, Mureddu L, Galli J, Artuso A, Bussu F. p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker? Pathogens 2024; 13:100. [PMID: 38392838 PMCID: PMC10892421 DOI: 10.3390/pathogens13020100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 01/21/2024] [Accepted: 01/22/2024] [Indexed: 02/25/2024] Open
Abstract
Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an oncosuppressor protein involved in cell cycle arrest, with a prognostic impact on other cancers, has been widely used in the head and neck region as a surrogate marker of HPV infection. Published papers and recent meta-analyses seem to minimize the biological role of HPV in the context of LSCC's cancerogenesis, and to disprove the reliability of p16ink4a as a surrogate prognostic marker in this context, while still highlighting its potential role as an independent predictor of survival. Unfortunately, the available literature, in particular during the last two decades, is often not focused on its potential role as an independent biomarker and few relevant data are found in papers mainly focused on HPV. The available data suggest that future research should focus specifically on p16ink4a, taking into account both its potential inactivation and overexpression, different patterns of staining, and immunohistochemistry cutoffs, and should focus not on its potential role as a surrogate marker but on its independent role as a predictor of survival.
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Affiliation(s)
- Roberto Gallus
- Otolaryngology, Mater Olbia Hospital, 07026 Olbia, Italy; (R.G.); (A.A.)
| | - Davide Rizzo
- U.O.C. Otorinolaringoiatria, Azienda Ospedaliero Universitaria di Sassari, Viale San Pietro, 43, 07100 Sassari, Italy; (D.R.); (F.B.)
- Otolaryngology Division, Department of Medicine, Surgery and Pharmacology, University of Sassari, Viale San Pietro, 43, 07100 Sassari, Italy
| | - Giorgia Rossi
- Unit of Otorhinolaryngology and Head-Neck Surgery, “A. Gemelli” Hospital Foundation IRCCS, 00168 Rome, Italy; (G.R.); (J.G.)
| | - Luca Mureddu
- U.O.C. Otorinolaringoiatria, Azienda Ospedaliero Universitaria di Sassari, Viale San Pietro, 43, 07100 Sassari, Italy; (D.R.); (F.B.)
| | - Jacopo Galli
- Unit of Otorhinolaryngology and Head-Neck Surgery, “A. Gemelli” Hospital Foundation IRCCS, 00168 Rome, Italy; (G.R.); (J.G.)
- Department of Head-Neck and Sensory Organs, Catholic University of Sacred Heart, 00168 Rome, Italy
| | - Alberto Artuso
- Otolaryngology, Mater Olbia Hospital, 07026 Olbia, Italy; (R.G.); (A.A.)
| | - Francesco Bussu
- U.O.C. Otorinolaringoiatria, Azienda Ospedaliero Universitaria di Sassari, Viale San Pietro, 43, 07100 Sassari, Italy; (D.R.); (F.B.)
- Otolaryngology Division, Department of Medicine, Surgery and Pharmacology, University of Sassari, Viale San Pietro, 43, 07100 Sassari, Italy
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Lee HP, Lee CC. Prognostic stratification of oropharyngeal cancer patients in a betel nut chewing and low HPV area. J Otolaryngol Head Neck Surg 2023; 52:27. [PMID: 37081578 PMCID: PMC10116661 DOI: 10.1186/s40463-023-00632-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 02/23/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND This study aimed to establish a simple predictive model for oropharyngeal cancer (OPC) in an area with a relatively low prevalence of human papillomavirus (HPV) and frequent betel nut chewing. METHODS A total of 116 patients with OPC were recruited from the clinical research database of a referral cancer center between 2013 and 2018. Patient characteristics-including age, gender, tumor stage, differentiation, and treatment modality-were extracted from the database. Patients diagnosed after 2018 were staged using the 7th AJCC staging system to explore the impact of extra-nodal tumor extension (ENE) on survival. Immunohistochemical analysis was performed for p16, epidermal growth factor receptor (EGFR), p53, and programmed cell death ligand 1 (PD-L1). ENE status was evaluated by pathological analysis or radiological features. Primary outcome was disease-specific overall survival (OS). Univariate and multivariate Cox regression were used to establish a predictive model. RESULTS Mean age was 57.3 ± 9.9 years; 103 patients (88.8%) were male. P16 positive OPC was positively associated with higher PD-L1 and a tonsillar sub-site and negatively associated with betel nut chewing and cigarette smoking. In Cox regression, age, p16 status, EGFR, cT4, ENE, and cigarette smoking were significantly associated with OS. In survival tree analysis, cT stage was the most important risk stratification parameter, followed by EGFR expression and p16 status. Patients with cT4 stage or high EGFR were classified as the high-risk group and had poorest OS. CONCLUSIONS Due to the low prevalence of HPV and popularity of betel nut chewing in Asia, the relative importance of prognostic predictors for OPC are not identical to Western countries. Identification of significant prognostic biomarkers may improve treatment. Trial registration This study was registered and approved by the Institutional Review Board (IRB) of Kaohsiung Veterans General Hospital (VGHKS19-CT9-07; date of approval: Aug 9, 2019).
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Affiliation(s)
- Huai-Pao Lee
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
| | - Ching-Chih Lee
- Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, No.386, Dazhong 1St Rd., Zuoying Dist., Kaohsiung City, 81362, Taiwan (R.O.C.).
- School of Medicine, National Defense Medical Center, Taipei, Taiwan.
- Department of Otolaryngology, Head and Neck Surgery, Tri-Service General Hospital, Taipei, Taiwan.
- Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Current state of play for HPV-positive oropharyngeal cancers. Cancer Treat Rev 2022; 110:102439. [DOI: 10.1016/j.ctrv.2022.102439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 07/13/2022] [Accepted: 07/17/2022] [Indexed: 01/22/2023]
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Bagher Ebadian H, Siddiqui F, Ghanem A, Zhu S, Lu M, Movsas B, Chetty IJ. Radiomics outperforms clinical factors in characterizing human papilloma virus (HPV) for patients with oropharyngeal squamous cell carcinomas. Biomed Phys Eng Express 2021; 8. [PMID: 34781281 DOI: 10.1088/2057-1976/ac39ab] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/15/2021] [Indexed: 11/11/2022]
Abstract
Purpose:To utilize radiomic features extracted from CT images to characterize Human Papilloma Virus (HPV) for patients with oropharyngeal cancer squamous cell carcinoma (OPSCC).Methods:One hundred twenty-eight OPSCC patients with known HPV-status (60-HPV+ and 68-HPV-, confirmed by immunohistochemistry-P16-protein testing) were retrospectively studied. Radiomic features (11 feature-categories) were extracted in 3D from contrast-enhanced (CE)-CT images of gross-tumor-volumes using 'in-house' software ('ROdiomiX') developed and validated following the image-biomarker-standardization-initiative (IBSI) guidelines. Six clinical factors were investigated: Age-at-Diagnosis, Gender, Total-Charlson, Alcohol-Use, Smoking-History, and T-Stage. A Least-Absolute-Shrinkage-and-Selection-Operation (Lasso) technique combined with a Generalized-Linear-Model (Lasso-GLM) were applied to perform regularization in the radiomic and clinical feature spaces to identify the ranking of optimal feature subsets with most representative information for prediction of HPV. Lasso-GLM models/classifiers based on clinical factors only, radiomics only, and combined clinical and radiomics (ensemble/integrated) were constructed using random-permutation-sampling. Tests of significance (One-way ANOVA), average Area-Under-Receiver-Operating-Characteristic (AUC), and Positive and Negative Predictive values (PPV and NPV) were computed to estimate the generalization-error and prediction performance of the classifiers.Results:Five clinical factors, including T-stage, smoking status, and age, and 14 radiomic features, including tumor morphology, and intensity contrast were found to be statistically significant discriminators between HPV positive and negative cohorts. Performances for prediction of HPV for the 3 classifiers were: Radiomics-Lasso-GLM: AUC/PPV/NPV=0.789/0.755/0.805; Clinical-Lasso-GLM: 0.676/0.747/0.672, and Integrated/Ensemble-Lasso-GLM: 0.895/0.874/0.844. Results imply that the radiomics-based classifier enabled better characterization and performance prediction of HPV relative to clinical factors, and that the combination of both radiomics and clinical factors yields even higher accuracy characterization and predictive performance.Conclusion:Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results in support of the role of radiomic features towards characterization of HPV in patients with OPSCC.
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Affiliation(s)
- Hassan Bagher Ebadian
- Department of Radiation Oncology , Henry Ford Hospital, 2799 West Grand Blvd., Detroit, Detroit, Michigan, 48202, UNITED STATES
| | - Farzan Siddiqui
- Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, Michigan, 48202, UNITED STATES
| | - Ahmed Ghanem
- Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, Michigan, 48202, UNITED STATES
| | - Simeng Zhu
- Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, Michigan, 48202, UNITED STATES
| | - Mei Lu
- Henry Ford Hospital, 2799 West Grand Blvd., Detroit, Michigan, 48202, UNITED STATES
| | - Benjamin Movsas
- Dept of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, 48202, UNITED STATES
| | - Indrin J Chetty
- Dept of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202-2689, USA, Detroit, Michigan, 48202, UNITED STATES
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Prognostic Significance of a Scoring System Combining p16, Smoking, and Drinking Status in a Series of 131 Patients with Oropharyngeal Cancers. Int J Otolaryngol 2021; 2021:8020826. [PMID: 34531914 PMCID: PMC8440106 DOI: 10.1155/2021/8020826] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/31/2021] [Indexed: 01/17/2023] Open
Abstract
Background Tobacco and alcohol are two main risk factors associated with head and neck squamous cell carcinoma (HNSCC). Studies showed that human papillomavirus (HPV) plays a role in the etiology of this cancer. HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients present in general a better response to conventional therapy and better overall survival (OS). However, OSCC is a heterogeneous disease regarding treatment. This study aimed to identify more effective prognostic factors associated with a poor clinical outcome for OSCC patients to improve treatment selection. Materials and Methods OSCC patients diagnosed between 2007 and 2017, in two Belgian hospitals, were included. Demographic and clinicopathologic data were extracted from medical records. HPV status was determined through p16 immunohistochemistry. Univariable and multivariable Cox proportional hazard regression analyses allowed to identify variables prognostic for OS and recurrence-free survival (RFS). Kaplan–Meier survival curves have been assessed for survival. Results The study included 131 patients. Statistics showed that monotherapies were significantly associated with a shorter OS; p16 overexpression was significantly associated with a weak consumption of tobacco or alcohol, and a high p16 expression was significantly associated with both longer RFS and OS. The study validated that tobacco and alcohol consumption were significantly correlated with poorer RFS and poorer OS. Only p16 expression trended to be significant for RFS when compared to smoking and drinking habits, while p16 upregulation and alcohol use were both vital for OS indicating that p16 is an independent and significant prognostic factor in OSCC patients. Finally, a scoring system combining p16, tobacco, and alcohol status was defined and was significantly associated with longer RFS and longer OS for nonsmoker and nondrinker p16-positive OSCC patients. Conclusions This study confirmed that the overexpression of the p16 protein could be viewed as a factor of good prognosis for RFS and OS of OSCC patients. The prognostic significance of a scoring system combining p16 expression, smoking, and drinking status was evaluated and concluded to be a more effective tool to determine therapeutic orientations based on the risk factors for better treatment relevance and survival.
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Mitsuda J, Tsujikawa T, Yoshimura K, Saburi S, Suetsugu M, Kitamoto K, Takenaka M, Ohmura G, Arai A, Ogi H, Itoh K, Hirano S. A 14-Marker Multiplexed Imaging Panel for Prognostic Biomarkers and Tumor Heterogeneity in Head and Neck Squamous Cell Carcinoma. Front Oncol 2021; 11:713561. [PMID: 34490110 PMCID: PMC8417535 DOI: 10.3389/fonc.2021.713561] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 07/15/2021] [Indexed: 01/10/2023] Open
Abstract
Recent advances made in treatment for head and neck squamous cell carcinoma (HNSCC) highlight the need for new prediction tools to guide therapeutic strategies. In this study, we aimed to develop a HNSCC-targeting multiplex immunohistochemical (IHC) panel that can evaluate prognostic factors and the intratumor heterogeneity of HNSCC. To identify IHC-based tissue biomarkers that constitute new multiplex IHC panel, a systematic review and meta-analysis were performed to analyze reported IHC biomarkers in laryngeal and pharyngeal SCC in the period of 2008–2018. The Cancer Genome Atlas (TCGA) and Reactome pathway databases were used to validate the prognostic and functional significance of the identified biomarkers. A 14-marker chromogenic multiplex IHC panel including identified biomarkers was used to analyze untreated HNSCC tissue. Forty-five high-quality studies and thirty-one candidate tissue biomarkers were identified (N = 7062). Prognostic validation in TCGA laryngeal and pharyngeal SCC cohort (N = 205) showed that β-catenin, DKK1, PINCH1, ADAM10, and TIMP1 were significantly associated with poor prognosis, which were related to functional categories such as immune system, cellular response, cell cycle, and developmental systems. Selected biomarkers were assembled to build a 14-marker panel, evaluating heterogeneity and polarized expression of tumor biomarkers in the tissue structures, which was particularly related to activation of Wnt/β-catenin pathway. Integrated IHC analysis based on a systemic review and meta-analysis provides an in situ proteomics tool to assess the aggressiveness and intratumor heterogeneity of HNSCC.
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Affiliation(s)
- Junichi Mitsuda
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takahiro Tsujikawa
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.,Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, United States
| | - Kanako Yoshimura
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Sumiyo Saburi
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masaho Suetsugu
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kayo Kitamoto
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mari Takenaka
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Gaku Ohmura
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akihito Arai
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Ogi
- Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.,SCREEN Holdings Co., Ltd., Kyoto, Japan
| | - Kyoko Itoh
- Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shigeru Hirano
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
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11
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Große-Thie C, Maletzki C, Junghanss C, Schmidt K. Long-term survivor of metastatic squamous-cell head and neck carcinoma with occult primary after cetuximab-based chemotherapy: A case report. World J Clin Cases 2021; 9:7092-7098. [PMID: 34540964 PMCID: PMC8409182 DOI: 10.12998/wjcc.v9.i24.7092] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/06/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cancer of unknown primary (CUP) is a histological proven malignant tumor whose origin cannot be detected despite careful examination. Most cervical lymph node metastases in CUP (80%) will originate from head and neck sites, and 15% show infiltration of squamous carcinoma cells. The survival rates of CUP are poor: The 5-year-survival rate ranges from 10% to 15%. First-line treatment recommendation for advanced, inoperable squamous cell carcinoma of head/neck (HNSCC) was cetuximab plus platinum-fluorouracil chemotherapy until recently, when checkpoint inhibitors proved clinically beneficial therapies.
CASE SUMMARY Here, we report a case of a 42-year-old female patient with cervical and abdominal lymph node and distant bone metastases of an occult primary of the head and neck (squamous cell carcinoma, human papillomavirus positive). The cancer was diagnosed during pregnancy 10 years ago, and after giving birth, the patient was treated with cetuximab plus platinum-fluorouracil chemotherapy achieving complete remission (CR). CR lasted 26 mo when new metastases (abdominal lymph node, lumbar vertebral body) emerged. Both manifestations were irradiated. From then on, the patient has not received any further treatment, and her disease has remained controlled. Ten years after the initial cancer diagnosis, the patient is still alive and in good health, representing an exceptional case of HNSCC.
CONCLUSION This case illustrates the exceptional clinical course and benefits of combined therapy approaches in advanced metastatic HNSCC with occult primary.
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Affiliation(s)
- Christina Große-Thie
- Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock 18057, Germany
| | - Claudia Maletzki
- Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock 18057, Germany
| | - Christian Junghanss
- Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock 18057, Germany
| | - Kathie Schmidt
- Department of Medicine, Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock 18057, Germany
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12
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Bagher-Ebadian H, Zhu S, Siddiqui F, Lu M, Movsas B, Chetty IJ. Technical Note: On the development of an outcome-driven frequency filter for improving Radiomics-based modeling of Human Papilloma Virus (HPV) in patients with oropharyngeal squamous cell carcinomas. Med Phys 2021; 48:7552-7562. [PMID: 34390003 DOI: 10.1002/mp.15159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/08/2021] [Accepted: 08/03/2021] [Indexed: 11/11/2022] Open
Abstract
PURPOSE To implement an outcome-driven frequency filter for improving radiomics-based modeling of human papilloma virus (HPV) for patients with oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS One hundred twenty-eight OPSCC patients with known HPV status (60-HPV+ and 68-HPV-, confirmed by immunohistochemistry-P16 protein testing) were retrospectively studied. A 3D Discrete Fourier Transform was applied on contrast-enhanced CT images of patient gross tumor volumes (GTV's) to transform intensity distributions to the frequency domain and estimate frequency power spectrums of HPV- and HPV+ patient cohorts. Statistical analyses were performed to rank frequency bands contributing towards prediction of HPV status. An outcome-driven frequency filter was designed accordingly and applied to GTV frequency information. 3D Inverse-Discrete-Fourier-Transform was applied to reconstruct HPV-related frequency-filtered images. Radiomics features (11 feature-categories) were extracted from pre- and post- frequency filtered images using our previously published 'ROdiomiX' software. Least-Absolute-Shrinkage-and-Selection-Operation (Lasso) combined with a Generalized-Linear-Model (Lasso-GLM) was developed to identify and rank feature subsets with optimal information for prediction of HPV+/-. Radiomics-based Lasso-GLM classifiers (pre- and post-frequency filtered) were constructed and validated using a random permutation sampling and nested cross-validation techniques. Average Area Under Receiver Operating Characteristic (AUC), and Positive and Negative Predictive values (PPV, NPV) were computed to estimate generalization error and prediction performance. RESULTS Among 192 radiomic features, 15 features were found to be statistically significant discriminators between HPV+/- cohorts on post-frequency filtered CE-CT images; 14 such radiomic features were observed on pre-frequency filtered datasets. Discriminant features included tumor morphology and intensity contrast. Performances for prediction of HPV for the pre- and post-frequency filtered Lasso-GLM classifiers were: AUC/PPV/NPV = 0.789/0.755/0.805 and 0.850/0.808/0.877 respectively. Nested-CV performances for prediction of HPV for the pre- and post-frequency filtered Lasso-GLM classifiers were: AUC/PPV/NPV = 0.814/0.725/0.877 and 0.890/0.820/0.911 respectively. CONCLUSION Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results on the importance of frequency analysis prior to radiomic feature extraction toward enhancement of model performance for characterizing HPV in patients with OPSCC. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Hassan Bagher-Ebadian
- Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI, 48202, USA
| | - Simeng Zhu
- Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI, 48202, USA
| | - Farzan Siddiqui
- Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI, 48202, USA
| | - Mei Lu
- Department of Public Health, Henry Ford Health System, Michigan, MI, 48202, USA
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI, 48202, USA
| | - Indrin J Chetty
- Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI, 48202, USA
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13
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Gadsden NJ, Fulcher CD, Li D, Shrivastava N, Thomas C, Segall JE, Prystowsky MB, Schlecht NF, Gavathiotis E, Ow TJ. Palbociclib Renders Human Papilloma Virus-Negative Head and Neck Squamous Cell Carcinoma Vulnerable to the Senolytic Agent Navitoclax. Mol Cancer Res 2021; 19:862-873. [PMID: 33495400 DOI: 10.1158/1541-7786.mcr-20-0915] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/06/2020] [Accepted: 01/19/2021] [Indexed: 02/06/2023]
Abstract
We demonstrate that inhibition of cyclin-dependent kinases 4/6 (CDK4/6) leads to senescence in human papillomavirus (HPV)-negative (-) head and neck squamous cell carcinoma (HNSCC), but not in HPV-positive (+) HNSCC. The BCL-2 family inhibitor, navitoclax, has been shown to eliminate senescent cells effectively. We evaluated the efficacy of combining palbociclib and navitoclax in HPV- HNSCC. Three HPV- HNSCC cell lines (CAL27, HN31, and PCI15B) and three HPV+ HNSCC cell lines (UPCI-SCC-090, UPCI-SCC-154, and UM-SCC-47) were treated with palbociclib. Treatment drove reduced expression of phosphorylated Rb (p-Rb) and phenotypic evidence of senescence in all HPV- cell lines, whereas HPV+ cell lines did not display a consistent response by Rb or p-Rb and did not exhibit morphologic changes of senescence in response to palbociclib. In addition, treatment of HPV- cells with palbociclib increased both β-galactosidase protein expression and BCL-xL protein expression compared with untreated controls in HPV- cells. Co-expression of β-galactosidase and BCL-xL occurred consistently, indicating elevated BCL-xL expression in senescent cells. Combining palbociclib with navitoclax led to decreased HPV- HNSCC cell survival and led to increased apoptosis levels in HPV- cell lines compared with each agent given alone. IMPLICATIONS: This work exploits a key genomic hallmark of HPV- HNSCC (CDKN2A disruption) using palbociclib to induce BCL-xL-dependent senescence, which subsequently causes the cancer cells to be vulnerable to the senolytic agent, navitoclax.
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Affiliation(s)
| | - Cory D Fulcher
- Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Daniel Li
- Medical Student, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Nitisha Shrivastava
- Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Carlos Thomas
- Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Jeffrey E Segall
- Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.,Department of Anatomy and Structural Biology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Michael B Prystowsky
- Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
| | - Nicolas F Schlecht
- Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.,Division of Oral Health and Society, Faculty of Dentistry, McGill University, Montreal, Canada.,Department of Epidemiology and Population Health, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.,Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Evripidis Gavathiotis
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York.,Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York
| | - Thomas J Ow
- Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York. .,Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
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14
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Rezaei M, Mohajerani H, Moslemi H, Shafiei S, Tabrizi MAA, Tabrizi R. Does P16 Protein Expression Affect Treatment Prognosis in Oral Squamous Cell Carcinoma - A Comparative Study. Ann Maxillofac Surg 2021; 11:17-20. [PMID: 34522648 PMCID: PMC8407645 DOI: 10.4103/ams.ams_321_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 01/18/2021] [Accepted: 01/25/2021] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION P16 is an independent and reliable surrogate for the detection of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC). The aim of this study was to assess the P16 expression as a marker for HPV infection in OSCC and its impact on the treatment outcome. METHODS AND MATERIALS A cross-sectional study was conducted on patients with a definite diagnosis of OSCC. Patients were assigned into two groups with and without recurrence or metastasis. Tumour resection was performed in the same manner for all patients. P16 expression was evaluated by immunohistochemical staining. Independent t-test and Chi-square tests were used to find significant differences in age, gender, stage of the disease, tumour size, lymph node involvement, and P16 expression between the two groups. RESULTS Of 50 patients, 37 did not show any recurrence or metastasis (group 1), while 13 had a relapse (group 2). There was no significant difference for age, gender distribution, stage of the disease, or lymph node involvement between the two groups (P > 0.05). A significant difference in tumour size was noted between the two groups (P = 0.001). The mean expression of P16 was 38.92 ± 24.36 in group 1 and 51.54 ± 33.63 in group 2. No significant difference was found between the two groups for the mean expression of P16 (P = 0.23). DISCUSSION A review of the recent literature revealed that the HPV role in OSCC treatment is controversial. According to the results of this study, there was no significant difference in terms of P16 expression between OSCC patients with and without recurrence or metastasis.
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Affiliation(s)
- Mitra Rezaei
- Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Virology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Mohajerani
- Department of Oral and Maxillofacial Surgery, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Moslemi
- Department of Oral and Maxillofacial Surgery, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shervin Shafiei
- Department of Oral and Maxillofacial Surgery, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amir Alizadeh Tabrizi
- Department of Oral and Maxillofacial Surgery, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Tabrizi
- Department of Oral and Maxillofacial Surgery, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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15
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Prognostic Correlation of an Autophagy-Related Gene Signature in Patients with Head and Neck Squamous Cell Carcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2020; 2020:7397132. [PMID: 33456497 PMCID: PMC7785385 DOI: 10.1155/2020/7397132] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 11/25/2020] [Accepted: 12/10/2020] [Indexed: 02/07/2023]
Abstract
Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan–Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients' overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.
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16
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Brouwer AF, He K, Chinn SB, Mondul AM, Chapman CH, Ryser MD, Banerjee M, Eisenberg MC, Meza R, Taylor JMG. Time-varying survival effects for squamous cell carcinomas at oropharyngeal and nonoropharyngeal head and neck sites in the United States, 1973-2015. Cancer 2020; 126:5137-5146. [PMID: 32888317 DOI: 10.1002/cncr.33174] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/13/2020] [Accepted: 08/05/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND Anatomical site is strongly associated with head and neck cancer etiology, and etiology and patient sociodemographic characteristics are prognostic factors for survival. It is not known whether the effects of these predictors persist over the postdiagnosis period or are strongest proximal to the time of diagnosis. METHODS Using survival times and causes of death for 180,434 patients with head and neck cancer in the Surveillance, Epidemiology, and End Results cancer registry (1973-2015), the empirical cumulative incidences of cancer-specific death and other-cause death were calculated with a competing risks framework, and the time-dependent effects (hazard ratios) of anatomical tumor site (oropharynx, oral cavity, or hypopharynx/larynx), age, sex, race, and year of diagnosis on cancer-specific death and other-cause death, stratified by tumor stage, were estimated. RESULTS All effects were significantly time-varying (P < .001). Patients with nonoropharyngeal cancer had a higher hazard of cancer-specific death but a similar cumulative fraction of deaths because of a higher rate of death from other causes. Cancer-specific survival has not changed for patients with nonoropharyngeal cancer over the past decades but has improved since 2000 for patients with oropharyngeal cancer. The effects of age and sex on cancer survival were strongest proximal to the diagnosis, whereas the effect of race persisted over time. CONCLUSIONS Recent improvements in survival for patients with oropharyngeal cancer may be due more to an increasing fraction of cancers attributable to human papillomavirus than to increasing treatment effectiveness. The prognostic strength of anatomical site and other predictors changes over the postdiagnosis period. LAY SUMMARY It is generally assumed that the effects of tumor and personal characteristics on the survival of patients with head and neck cancer are fixed over time, but this study shows that many factors are most important only in the first few years after diagnosis. Also, recent improvements in the survival of patients with head and neck cancer appear to benefit only patients with cancers of the oropharynx. The improvements may be due more to an increasing fraction of cancers caused by human papillomavirus (which generally have better outcomes) than to advances in head and neck cancer treatment overall.
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Affiliation(s)
- Andrew F Brouwer
- Department of Epidemiology, University of Michigan, Ann Arbor, Michigan
| | - Kevin He
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Steven B Chinn
- Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan
| | - Alison M Mondul
- Department of Epidemiology, University of Michigan, Ann Arbor, Michigan
| | - Christina H Chapman
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Marc D Ryser
- Department of Population Health Sciences, Duke University, Durham, North Carolina.,Department of Mathematics, Duke University, Durham, North Carolina
| | - Mousumi Banerjee
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Marisa C Eisenberg
- Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.,Department of Mathematics, University of Michigan, Ann Arbor, Michigan.,Department of Complex Systems, University of Michigan, Ann Arbor, Michigan
| | - Rafael Meza
- Department of Epidemiology, University of Michigan, Ann Arbor, Michigan
| | - Jeremy M G Taylor
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
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17
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Wang H, Zhang Y, Bai W, Wang B, Wei J, Ji R, Xin Y, Dong L, Jiang X. Feasibility of Immunohistochemical p16 Staining in the Diagnosis of Human Papillomavirus Infection in Patients With Squamous Cell Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis. Front Oncol 2020; 10:524928. [PMID: 33324540 PMCID: PMC7724109 DOI: 10.3389/fonc.2020.524928] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 09/10/2020] [Indexed: 12/24/2022] Open
Abstract
Human papillomavirus (HPV) is a risk factor for squamous cell carcinoma of the head and neck (HNSCC). This study aimed to investigate the feasibility of IHC- p16INK4a (p16) as an alternative modality for diagnosing HPV infection. We searched PubMed, EMBASE, Web of Science, and Cochrane library for studies that evaluated the diagnostic accuracy of IHC-p16 staining. A total of 30 studies involving 2,963 patients were included from 2007 to 2019. The combined sensitivity was 0.94 (95% CI: 0.92–0.95); specificity, 0.90 (95% CI: 0.89–0.91); positive likelihood ratio (LR), 6.80 (95% CI: 5.63–8.21); negative LR, 0.10 (95% CI: 0.07–0.16); diagnostic odds ratio, 85.98 (95% CI: 55.57–133.03); and area under the curve value, 0.9550. Subgroup analysis showed that the IHC-p16 test was more consistent with the in situ hybridization (ISH) test and has greater diagnostic value for oropharyngeal squamous cell carcinoma. The diagnostic efficacy of IHC-p16 varied among countries. In conclusion, IHC-p16 has high sensitivity and specificity for diagnosing HPV infection in HNSCC. The consistency of IHC-p16 findings with those of ISH indicate that their combination can be used to improve the specificity of diagnosis.
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Affiliation(s)
- Huanhuan Wang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.,Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.,NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
| | - Yuyu Zhang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.,Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.,NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
| | - Wei Bai
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Bin Wang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.,Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.,NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
| | - Jinlong Wei
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.,Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.,NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
| | - Rui Ji
- Department of Biology, Valencia College, Orlando, FL, United States
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Lihua Dong
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.,Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.,NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
| | - Xin Jiang
- Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.,Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.,NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China
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18
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Sastre-Garau X, Harlé A. Pathology of HPV-Associated Head and Neck Carcinomas: Recent Data and Perspectives for the Development of Specific Tumor Markers. Front Oncol 2020; 10:528957. [PMID: 33312940 PMCID: PMC7701329 DOI: 10.3389/fonc.2020.528957] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 10/19/2020] [Indexed: 12/23/2022] Open
Abstract
A significant subset of carcinomas developed in the head and neck (H&NCs) are associated with specific human papillomaviruses (HPV) genotypes. In particular, 40–60% of oropharyngeal carcinoma cases are linked to HPV. Epidemiological studies have demonstrated that HPV oral infections are predominantly sexually transmitted and are more frequent among men (10–18%) than women (3.6–8.8%). Although there is a large diversity of HPV genotypes associated with H&NCs, HPV16 lineage represents 83% of the reported cases. The prognostic value of HPV as a biological parameter is well recognized. However, the use of HPV DNA as a diagnostic and/or predictive marker is not fully developed. Recent data reporting the physical state of the HPV genome in tumors have shown that HPV DNA integration into the tumor cell genome could lead to the alteration of cellular genes implicated in oncogenesis. Most importantly, HPV DNA corresponds to a tumor marker that can be detected in the blood of patients. Profile of the HPV DNA molecular patterns in tumor cells using New Genome Sequencing-based technologies, allows the identification of highly specific tumor markers valuable for the development of innovative diagnostic and therapeutic approaches. This review will summarize recent epidemiological data concerning HPV-associated H&NCs, the genomic characterization of these tumors, including the presence of HPV DNA in tumor cells, and will propose perspectives for developing improved care of patients with HPV-associated H&NCs, based on the use of viral sequences as personalized tumor markers and, over the longer term, as a therapeutic target.
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Affiliation(s)
- Xavier Sastre-Garau
- Service de Pathologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France
| | - Alexandre Harlé
- Université de Lorraine, CNRS UMR7039 CRAN, service de Biopathologie, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France
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19
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Hashmi AA, Younus N, Naz S, Irfan M, Hussain Z, Shaikh ST, Ali J, Faridi N, Najam J, Shoaib M, Hashmi SK. p16 Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma: Association With Prognostic Parameters. Cureus 2020; 12:e8601. [PMID: 32676240 PMCID: PMC7362654 DOI: 10.7759/cureus.8601] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background p16 is a tumor suppressor gene, over expression of which is considered as a surrogate marker of oncogenic human papillomavirus (HPV) infection. Moreover, p16 over expression correlates with good prognosis in head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to evaluate the frequency of p16 overexpression in HNSCC in our setup and its association with clinicopathologic parameters. Methods We performed p16 immunohistochemistry (IHC) on 144 cases of HNSCC. Association of p16 overexpression with various clinicopathologic parameters including T-stage, N-stage, grade, recurrence status, and risk factors was evaluated. Results p16 over expression was noted in 22.9% (33 cases), while 21.5% (31 cases) were focal positive and 55.6% (80 cases) were negative for p16 over expression. On the basis of percentage of expression; > 70% p16 expression was noted in 4.9% (7 cases), 9% (13 cases) showed 51% - 70% p16 expression, 9% (13 cases) revealed 11%-50% p16 expression, while 77.1% cases revealed no expression or < 10% p16 expression. Significant association of p16 expression was noted with nodal metastasis and extranodal spread while no significant association of p16 was noted with other prognostic parameters and risk factors. Conclusion Our data revealed that high expression (> 50%) of p16 is low in oropharyngeal squamous cell carcinoma in our setup. These finding suggest a low prevalence of HPV as a cause of HNSCC in our population. Moreover, p16 expression was found to be associated with some good prognostic parameters like lack of nodal metastasis, however, no significant association was noted with overall disease-free survival.
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Affiliation(s)
- Atif A Hashmi
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Naila Younus
- Pathology, HITEC Institute of Medical Sciences, Taxila, PAK
| | - Samreen Naz
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Muhammad Irfan
- Epidemiology and Public Health, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Zubaida Hussain
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Sara T Shaikh
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Javaria Ali
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Naveen Faridi
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Javeria Najam
- Medicine, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Maira Shoaib
- Medicine, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Shumaila K Hashmi
- Pathology, Combined Military Hospital (CMH) Multan Institute of Medical Sciences, Karachi, PAK
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20
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Janecka-Widła A, Mucha-Małecka A, Majchrzyk K, Halaszka K, Przewoźnik M, Słonina D, Biesaga B. Active HPV infection and its influence on survival in head and neck squamous-cell cancer. J Cancer Res Clin Oncol 2020; 146:1677-1692. [PMID: 32372145 PMCID: PMC7256081 DOI: 10.1007/s00432-020-03218-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 04/11/2020] [Indexed: 01/04/2023]
Abstract
Purpose HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients. Methods Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors. Results Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%, p = 0.000; DFS 93.0% vs. 53.35%, p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence. Conclusions High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.
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Affiliation(s)
- Anna Janecka-Widła
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland.
| | - Anna Mucha-Małecka
- Department of Radiotherapy, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Kaja Majchrzyk
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Krzysztof Halaszka
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Marcin Przewoźnik
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland
| | - Dorota Słonina
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland.,Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland
| | - Beata Biesaga
- Department of Tumour Pathology, Maria Sklodowska-Curie Institute - Oncology Center, Cracow Branch, Cracow, Poland.,Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland
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21
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Buexm LA, Soares-Lima SC, Brennan P, Fernandes PV, de Souza Almeida Lopes M, Nascimento de Carvalho F, Santos IC, Dias LF, de Queiroz Chaves Lourenço S, Ribeiro Pinto LF. Hpv impact on oropharyngeal cancer patients treated at the largest cancer center from Brazil. Cancer Lett 2020; 477:70-75. [PMID: 32087309 DOI: 10.1016/j.canlet.2020.02.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 01/16/2020] [Accepted: 02/14/2020] [Indexed: 12/24/2022]
Abstract
Oropharyngeal squamous cell carcinoma (OSCC) is a fatal and highly incident disease. Although tobacco and alcohol consumption are the main risk factors associated with OSCC, a recent significant increase in OSCC HPV16 positive cases in high-income countries has been observed. However, it is not clear whether this change is also present in low- and middle-income countries. In this study, we evaluated HPV16 prevalence in 346 OSCC cases diagnosed in the largest Brazilian oncology public hospital by using the combination of two techniques, HPV16 E6 detection by qPCR and p16 immunohistochemistry. In total, 11.9% of cases were HPV16 E6 positive, 9.2% were p16 positive and 6.1% were positive in both analyses. There was a predominance of keratinizing-SCC, with only four HPV-positive cases showing basaloid-like or non-keratinizing-SCC. HPV infection had no impact on disease-free or overall survival, while alcohol use was an independent prognostic factor for overall survival. Most cases reported a high frequency of tobacco (94.6%) and alcohol consumption (88.2%), were of low education level, and typically presented at advanced clinical stages, indicating that the profile of Brazilian OSCC patients has not changed.
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Affiliation(s)
- Luisa Aguirre Buexm
- Oncology Graduate Program, Molecular Carcinogenesis Program, Research Center, Brazilian National Cancer Institute. Rua André Cavalcanti, 37, Centro, 20231-050, Rio de Janeiro, Brazil.
| | - Sheila Coelho Soares-Lima
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute. Rua André Cavalcanti, 37, Centro, 20231-050, Rio de Janeiro, Brazil.
| | - Paul Brennan
- International Agency for Research on Cancer. 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France.
| | - Priscila Valverde Fernandes
- Pathology Division, Brazilian National Cancer Institute, Rua Cordeiro da Graça, 156, Santo Cristo, 20220-400, Rio de Janeiro, Brazil.
| | - Monique de Souza Almeida Lopes
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute. Rua André Cavalcanti, 37, Centro, 20231-050, Rio de Janeiro, Brazil.
| | - Flávia Nascimento de Carvalho
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute. Rua André Cavalcanti, 37, Centro, 20231-050, Rio de Janeiro, Brazil.
| | - Izabella Costa Santos
- Department of Head and Neck Surgery, Cancer Hospital I, Brazilian National Cancer Institute, Praça da Cruz Vermelha, 23, Centro, 20230-130, Rio de Janeiro, Brazil.
| | - Luiz Fernando Dias
- Department of Head and Neck Surgery, Cancer Hospital I, Brazilian National Cancer Institute, Praça da Cruz Vermelha, 23, Centro, 20230-130, Rio de Janeiro, Brazil.
| | - Simone de Queiroz Chaves Lourenço
- Department of Pathology, Dental School, Fluminense Federal University, Rua Mario Santos Braga, 30, Centro, 24040-110, Niterói, Brazil.
| | - Luis Felipe Ribeiro Pinto
- Molecular Carcinogenesis Program, Brazilian National Cancer Institute. Rua André Cavalcanti, 37, Centro, 20231-050, Rio de Janeiro, Brazil.
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22
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Bagher-Ebadian H, Lu M, Siddiqui F, Ghanem AI, Wen N, Wu Q, Liu C, Movsas B, Chetty IJ. Application of radiomics for the prediction of HPV status for patients with head and neck cancers. Med Phys 2020; 47:563-575. [PMID: 31853980 DOI: 10.1002/mp.13977] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 10/28/2019] [Accepted: 11/22/2019] [Indexed: 12/19/2022] Open
Abstract
PURPOSE To perform radiomic analysis of primary tumors extracted from pretreatment contrast-enhanced computed tomography (CE-CT) images for patients with oropharyngeal cancers to identify discriminant features and construct an optimal classifier for the characterization and prediction of human papilloma virus (HPV) status. MATERIALS AND METHODS One hundred and eighty seven patients with oropharyngeal cancers with known HPV status (confirmed by immunohistochemistry-p16 protein testing) were retrospectively studied as follows: Group A: 95 patients (19HPV- and 76HPV+) from the MICAII grand challenge. Group B: 92 patients (52HPV- and 40HPV+) from our institution. Radiomic features (172) were extracted from pretreatment diagnostic CE-CT images of the gross tumor volume (GTV). Levene and Kolmogorov-Smirnov's tests with absolute biserial correlation (>0.48) were used to identify the discriminant features between the HPV+ and HPV- groups. The discriminant features were used to train and test eight different classifiers. Area under receiver operating characteristic (AUC), positive predictive and negative predictive values (PPV and NPV, respectively) were used to evaluate the performance of the classifiers. Principal component analysis (PCA) was applied on the discriminant feature set and seven PCs were used to train and test a generalized linear model (GLM) classifier. RESULTS Among 172 radiomic features only 12 radiomic features (from 3 categories) were significantly different (P < 0.05, |BSC| > 0.48) between the HPV+ and HPV- groups. Among the eight classifiers trained and applied for prediction of HPV status, the GLM showed the highest performance for each discriminant feature and the combined 12 features: AUC/PPV/NPV = 0.878/0.834/0.811. The GLM high prediction power was AUC/PPV/NPV = 0.849/0.731/0.788 and AUC/PPV/NPV = 0.869/0.807/0.870 for unseen test datasets for groups A and B, respectively. After eliminating the correlation among discriminant features by applying PCA analysis, the performance of the GLM was improved by 3.3%, 2.2%, and 1.8% for AUC, PPV, and NPV, respectively. CONCLUSIONS Results imply that GTV's for HPV+ patients exhibit higher intensities, smaller lesion size, greater sphericity/roundness, and higher spatial intensity-variation/heterogeneity. Results are suggestive that radiomic features primarily associated with the spatial arrangement and morphological appearance of the tumor on contrast-enhanced diagnostic CT datasets may be potentially used for classification of HPV status.
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Affiliation(s)
| | - Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Farzan Siddiqui
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA
| | - Ahmed I Ghanem
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA.,Department of Clinical Oncology, Alexandria University, Alexandria, Egypt
| | - Ning Wen
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA
| | - Qixue Wu
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA
| | - Chang Liu
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA
| | - Indrin J Chetty
- Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA
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23
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A non-oropharyngeal squamous cell carcinoma and the pitfalls of HPV testing: A case report. OTOLARYNGOLOGY CASE REPORTS 2019. [DOI: 10.1016/j.xocr.2019.100129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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24
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Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, Le QT, Lee NY, Leidner R, Lewis RL, Licitra L, Mehanna H, Mell LK, Raben A, Sikora AG, Uppaluri R, Whitworth F, Zandberg DP, Ferris RL. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 2019; 7:184. [PMID: 31307547 PMCID: PMC6632213 DOI: 10.1186/s40425-019-0662-5] [Citation(s) in RCA: 470] [Impact Index Per Article: 78.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 07/02/2019] [Indexed: 02/06/2023] Open
Abstract
Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a ≥ 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score ≥ 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S.
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Affiliation(s)
- Ezra E W Cohen
- Moores Cancer Center, University of California San Diego, San Diego, CA, USA
| | - R Bryan Bell
- Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA
| | - Carlo B Bifulco
- Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA
| | - Barbara Burtness
- Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA
| | - Maura L Gillison
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | | | - Nancy Y Lee
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Rom Leidner
- Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA
| | | | - Lisa Licitra
- Fondazione IRCCS Istituto Nazionale dei Tumori Milan and University of Milan, Milan, Italy
| | - Hisham Mehanna
- Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, UK
| | - Loren K Mell
- Moores Cancer Center, University of California San Diego, San Diego, CA, USA
| | - Adam Raben
- Helen F. Graham Cancer Center, Newark, DE, USA
| | | | - Ravindra Uppaluri
- Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA
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25
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Tian S, Switchenko JM, Jhaveri J, Cassidy RJ, Ferris MJ, Press RH, Pfister NT, Patel MR, Saba NF, McDonald MW, Higgins KA, Yu DS, Curran WJ, Gillespie TW, Beitler JJ. Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base. Cancer 2019; 125:2782-2793. [PMID: 31012957 DOI: 10.1002/cncr.32115] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 02/22/2019] [Accepted: 03/05/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND The prognostic relevance of human papillomavirus (HPV) status in patients with nonoropharyngeal (OPX) squamous cell cancer (SCC) of the head and neck is controversial. In the current study, the authors evaluated the impact of high-risk HPV status on overall survival (OS) in patients with non-OPX SCC using a large database approach. METHODS The National Cancer Data Base was queried to identify patients diagnosed from 2004 through 2014 with SCC of the OPX, hypopharynx (HPX), larynx, and oral cavity (OC) with known HPV status. Survival was estimated using Kaplan-Meier methods; distributions were compared using log-rank tests. Propensity score-matching and inverse probability of treatment weighing (IPTW) methods were used; cohorts were matched based on age, sex, Charlson-Deyo score, clinical American Joint Committee on Cancer (AJCC) group stage, treatments received, and anatomic subsite. Propensity analyses were stratified by group stage of disease. RESULTS A total of 24,740 patients diagnosed from 2010 through 2013 were analyzed: 1085 patients with HPX, 4804 with laryngeal, 4,018 with OC, and 14,833 with OPX SCC. The percentages of HPV-positive cases by disease site were 17.7% for HPX, 11% for larynx, 10.6% for OC, and 62.9% for OPX. HPV status was found to be prognostic in multiple unadjusted and propensity-adjusted non-OPX populations. HPV positivity was associated with superior OS in patients with HPX SCC with a hazard ratio (HR) of 0.61 (P < .001 by IPTW), in patients with AJCC stage III to IVB laryngeal SCC (HR, 0.79; P = .019 by IPTW), and in patients with AJCC stage III to IVB OC SCC (HR, 0.78; P = .03 by IPTW). CONCLUSIONS Positive high-risk HPV status appears to be associated with longer OS in multiple populations of patients with non-OPX head and neck disease (HPX, locally advanced larynx, and OC). If prospectively validated, these findings have implications for risk stratification.
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Affiliation(s)
- Sibo Tian
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Jeffrey M Switchenko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Heath, Emory University, Atlanta, Georgia
| | - Jaymin Jhaveri
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Richard J Cassidy
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Matthew J Ferris
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Robert H Press
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Neil T Pfister
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Mihir R Patel
- Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, Georgia
| | - Nabil F Saba
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Mark W McDonald
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Kristin A Higgins
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - David S Yu
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Walter J Curran
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Theresa W Gillespie
- Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Jonathan J Beitler
- Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.,Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, Georgia.,Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
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26
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Sánchez Barrueco A, González Galán F, Villacampa Aubá JM, Díaz Tapia G, Fernández Hernández S, Martín-Arriscado Arroba C, Cenjor Español C, Almodóvar Álvarez C. p16 Influence on Laryngeal Squamous Cell Carcinoma Relapse and Survival. Otolaryngol Head Neck Surg 2019; 160:1042-1047. [PMID: 30642220 DOI: 10.1177/0194599818821910] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE (1) To identify p16 protein in laryngeal squamous cell carcinoma (LSCC) specimens and to correlate it with the presence of human papillomavirus (HPV) found in these specimens from a previous study. (2) To analyze p16 impact on 10-year overall and disease-free survival. STUDY DESIGN Retrospective case series with oncologic database chart review. SETTING Academic tertiary care hospital. SUBJECTS A total of 123 samples of LSCC (taken from the glottis only) from patients treated with primary surgical resection between 1977 and 2005. METHODS p16 protein expression was analyzed through immunohistochemistry and compared with the presence of HPV established in our previous studies. Results were compared with histologic, clinicopathologic, and survival parameters, with a 10-year follow-up. RESULTS Of the samples, 39.02% were positive for p16, but only 11.38% were positive for both p16 and HPV. The p16+ cohort showed a significant improvement in disease-free survival ( P = .0022); statistical significance was not achieved for overall survival. p16+ cases had fewer relapses over time, with no relapses after a 2-year follow-up. Age at the time of diagnosis and tobacco consumption were the only epidemiologic factors that influenced overall survival. CONCLUSION The expression of p16 protein was a beneficial prognostic factor for disease-free survival among patients with LSCC of the glottis, with no relapses after a 2-year follow-up.
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Affiliation(s)
- Alvaro Sánchez Barrueco
- 1 ENT and Cervicofacial Surgery Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Fernando González Galán
- 1 ENT and Cervicofacial Surgery Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | | | - Gonzalo Díaz Tapia
- 1 ENT and Cervicofacial Surgery Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | | | | | - Carlos Cenjor Español
- 1 ENT and Cervicofacial Surgery Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
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27
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Götz C, Bischof C, Wolff KD, Kolk A. Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis. Mol Clin Oncol 2019; 10:17-28. [PMID: 30655973 PMCID: PMC6313947 DOI: 10.3892/mco.2018.1749] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 08/09/2018] [Indexed: 12/16/2022] Open
Abstract
The current controversial discussion on the disease-specific survival of patients with human papillomavirus (HPV)-positive (+) and -negative (-) squamous cell carcinoma (SCC) of the head neck region was the motivation for the present meta-analysis. Different detection methods for HPV are available, though these often lack sensitivity. As a consequence, there may be false interpretation of HPV positivity. A bias concerning HPV status and therefore also survival rates is serving a non-durable relevance in the discussion of tailored therapies. A literature search was performed via the online database PubMed/NCBI, and data extraction and statistical analysis were conducted. A total of 139 studies published between 2004 and 2014 were evaluated in the present meta-analysis. The HPV detection methods, patient characteristics, tumor localizations and stages, as well as (neo-) adjuvant therapies and survival times were analyzed. The average incidence rates of HPV+ patients with oropharyngeal tumors were higher than those of patients with cancers of other regions of the head and neck. Upon evaluating the results of different detection methods no significant differences were identified. We have compared the HPV incidence rates of each detection method, when studies have used more than one. Regarding overall survival, the pooled adjusted hazard ratio (HR) for oropharyngeal SCC was 0.31 [95% confidence interval (CI)=0.27-0.36]. Unfortunately, only 3 equivalent studies were available on nonoropharyngeal tumors, for which the pooled adjusted HR was 1 (95% CI=0.73-1.36). Overall, the evaluation demonstrated that the survival rates reported in numerous studies were not evaluated multifactorially and important confounders were excluded from the statistics. The HPV detection methods used were often not sufficient in representing HPV positivity. In addition, oropharyngeal and oral SCCs were assessed together in the localization. The widely differing number of HPV+ patients in each of the various studies may be explained by insufficient detection methods and by a lack of localization distinction. The considerations of a tailored therapy according to HPV status should be rejected based on the present information. The previously published studies should be read critically and do not represent a basis for therapeutic decisions.
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Affiliation(s)
- Carolin Götz
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Clara Bischof
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Klaus-Dietrich Wolff
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Andreas Kolk
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
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Abrahão R, Anantharaman D, Gaborieau V, Abedi-Ardekani B, Lagiou P, Lagiou A, Ahrens W, Holcatova I, Betka J, Merletti F, Richiardi L, Kjaerheim K, Serraino D, Polesel J, Simonato L, Alemany L, Agudo Trigueros A, Macfarlane TV, Macfarlane GJ, Znaor A, Robinson M, Canova C, Conway DI, Wright S, Healy CM, Toner M, Cadoni G, Boccia S, Gheit T, Tommasino M, Scelo G, Brennan P. The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study. Int J Cancer 2018; 143:32-44. [PMID: 29405297 DOI: 10.1002/ijc.31294] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 01/19/2018] [Accepted: 01/23/2018] [Indexed: 01/23/2023]
Abstract
Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.
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Affiliation(s)
- Renata Abrahão
- Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
| | - Devasena Anantharaman
- Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
| | - Valérie Gaborieau
- Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
| | - Behnoush Abedi-Ardekani
- Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France
| | - Pagona Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
| | - Areti Lagiou
- Department of Public Health and Community Health, School of Health Professions, Athens University of Applied Sciences, Athens, Greece
| | - Wolfgang Ahrens
- Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
- Institute of Statistics, Faculty of Mathematics and Computer Science, University Bremen, Bremen, Germany
| | - Ivana Holcatova
- Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University of Prague, Prage, Czech Republic
| | - Jaroslav Betka
- Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University of Prague, Prague, Czech Republic
| | - Franco Merletti
- Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Lorenzo Richiardi
- Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy
| | | | - Diego Serraino
- Unit of Cancer Epidemiology, Aviano National Cancer Institute, IRCCS, Aviano, Italy
| | - Jerry Polesel
- Unit of Cancer Epidemiology, Aviano National Cancer Institute, IRCCS, Aviano, Italy
| | - Lorenzo Simonato
- Department of Cardiovascular and Thoracic Sciences, University of Padova, Padova, Italy
| | - Laia Alemany
- Institut Català d'Oncologia, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain
- CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | | | - Tatiana V Macfarlane
- Epidemiology Group, University of Aberdeen, Aberdeen, United Kingdom
- Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
| | - Gary J Macfarlane
- Epidemiology Group, University of Aberdeen, Aberdeen, United Kingdom
| | - Ariana Znaor
- Cancer Surveillance Section, International Agency for Research on Cancer, Lyon, France
| | - Max Robinson
- Center for Oral Health Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom
| | - Cristina Canova
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
| | - David I Conway
- School of Medicine, Dentistry, and Nursing, University of Glasgow, Glasgow, United Kingdom
| | - Sylvia Wright
- Department of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom
| | - Claire M Healy
- Trinity College School of Dental Science, Dublin, Ireland
| | - Mary Toner
- Trinity College School of Dental Science, Dublin, Ireland
| | - Gabriella Cadoni
- Institute of Othorinolaringoiatry, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy
| | - Stefania Boccia
- Section of Hygiene - Institute of Public Health, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy
| | - Tarik Gheit
- Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France
| | - Massimo Tommasino
- Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France
| | - Ghislaine Scelo
- Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
| | - Paul Brennan
- Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
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Anayannis NV, Schlecht NF, Ben-Dayan M, Smith RV, Belbin TJ, Ow TJ, Blakaj DM, Burk RD, Leonard SM, Woodman CB, Parish JL, Prystowsky MB. Association of an intact E2 gene with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome in HPV16 positive head and neck squamous cell carcinoma. PLoS One 2018; 13:e0191581. [PMID: 29451891 PMCID: PMC5815588 DOI: 10.1371/journal.pone.0191581] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 01/08/2018] [Indexed: 11/18/2022] Open
Abstract
To assess the relationship of E2 gene disruption with viral gene expression and clinical outcome in human papillomavirus (HPV) positive head and neck squamous cell carcinoma, we evaluated 31 oropharyngeal and 17 non-oropharyngeal HPV16 positive carcinomas using two PCR-based methods to test for disruption of E2, followed by Sanger sequencing. Expression of HPV16 E6, E7 and E2 transcripts, along with cellular ARF and INK4A, were also assessed by RT-qPCR. Associations between E2 disruption, E2/E6/E7 expression, and clinical outcome were evaluated by Kaplan-Meier analysis for loco-regional recurrence and disease-specific survival. The majority (n = 21, 68%) of HPV16 positive oropharyngeal carcinomas had an intact E2 gene, whereas the majority of HPV16 positive non-oropharyngeal carcinomas (n = 10, 59%) had a disrupted E2 gene. Three of the oropharyngeal tumors and two of the non-oropharyngeal tumors had deletions within E2. Detection of an intact E2 gene was associated with a higher DNA viral load and increased E2/E6/E7, ARF and INK4A expression in oropharyngeal tumors. Oropharyngeal carcinomas with an intact E2 had a lower risk of loco-regional recurrence (log-rank p = 0.04) and improved disease-specific survival (p = 0.03) compared to tumors with disrupted E2. In addition, high E7 expression was associated with lower risk of loco-regional recurrence (p = 0.004) as was high E6 expression (p = 0.006). In summary, an intact E2 gene is more common in HPV16 positive oropharyngeal than non-oropharyngeal carcinomas; the presence of an intact E2 gene is associated with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome compared to patients with a disrupted E2 gene in oropharyngeal cancer.
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Affiliation(s)
- Nicole V. Anayannis
- Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
| | - Nicolas F. Schlecht
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Medicine (Oncology), Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, United States of America
| | - Miriam Ben-Dayan
- Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
| | - Richard V. Smith
- Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
| | - Thomas J. Belbin
- Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Discipline of Oncology, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
| | - Thomas J. Ow
- Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
| | - Duk M. Blakaj
- The James Cancer Center, Ohio State University, Columbus, OH, United States of America
| | - Robert D. Burk
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Pediatrics (Genetics), Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Microbiology & Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
- Department of Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
| | - Sarah M. Leonard
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Ciaran B. Woodman
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Joanna L. Parish
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Michael B. Prystowsky
- Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
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30
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Elhalawani H, Ger RB, Mohamed ASR, Awan MJ, Ding Y, Li K, Fave XJ, Beers AL, Driscoll B, Hormuth II DA, van Houdt PJ, He R, Zhou S, Mathieu KB, Li H, Coolens C, Chung C, Bankson JA, Huang W, Wang J, Sandulache VC, Lai SY, Howell RM, Stafford RJ, Yankeelov TE, van der Heide UA, Frank SJ, Barboriak DP, Hazle JD, Court LE, Kalpathy-Cramer J, Fuller CD. Dynamic contrast-enhanced magnetic resonance imaging for head and neck cancers. Sci Data 2018; 5:180008. [PMID: 29437167 PMCID: PMC5810424 DOI: 10.1038/sdata.2018.8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 12/18/2017] [Indexed: 02/05/2023] Open
Abstract
Dynamic myraidpro contrast-enhanced magnetic resonance imaging (DCE-MRI) has been correlated with prognosis in head and neck squamous cell carcinoma as well as with changes in normal tissues. These studies implement different software, either commercial or in-house, and different scan protocols. Thus, the generalizability of the results is not confirmed. To assist in the standardization of quantitative metrics to confirm the generalizability of these previous studies, this data descriptor delineates in detail the DCE-MRI digital imaging and communications in medicine (DICOM) files with DICOM radiation therapy (RT) structure sets and digital reference objects (DROs), as well as, relevant clinical data that encompass a data set that can be used by all software for comparing quantitative metrics. Variable flip angle (VFA) with six flip angles and DCE-MRI scans with a temporal resolution of 5.5 s were acquired in the axial direction on a 3T MR scanner with a field of view of 25.6 cm, slice thickness of 4 mm, and 256×256 matrix size.
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31
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Sun G, Dong X, Tang X, Qu H, Zhang H, Zhao E. The prognostic value of HPV combined p16 status in patients with anal squamous cell carcinoma: a meta-analysis. Oncotarget 2017; 9:8081-8088. [PMID: 29487716 PMCID: PMC5814283 DOI: 10.18632/oncotarget.23545] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 12/15/2017] [Indexed: 12/25/2022] Open
Abstract
Human papillomavirus (HPV) DNA and p16 expression have been identified to be related to the progression of anal squamous cell carcinoma (ASCC). However, the prognostic relevance of combined detection, particularly HPV-/p16+ and HPV+/p16- signatures, is unknown. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Data were collected from studies comparing overall survival (OS) and disease-free survival (DFS) / disease-specific survival (DSS) / relapse-free survival (RFS) / progression-free survival (PFS) in ASCC patients with HPV and p16 status. The electronic databases of MEDLINE and EMBASE were searched from their inception till 31 May 2017. Study-specific risk estimates were pooled using a fixed-effects model for OS and DFS/DSS/RFS/PFS. Four studies involving a total of 398 ASCC cases were included in this meta-analysis. The pooled results showed that HPV+/p16+ cancers were significantly associated with improved OS (HR = 0.30, 95% CI: 0.17-0.51) and DFS/DSS/RFS/PFS (HR = 0.23, 95% CI: 0.14-0.36). However, patients with HPV-/p16+ or HPV+/p16- do not have a comparably good prognosis compared with HPV+/p16+ patients. The meta-analysis indicated that concomitant detection of HPV-DNA and p16 expression may be of prognostic or therapeutic utility in the evaluation of factors contributing to ASCC. Testing tumor specimens for HPV-DNA and p16 expression might indirectly affect treatment decisions.
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Affiliation(s)
- Guorui Sun
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
| | - Xiaoyuan Dong
- Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
| | - Xiaolong Tang
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
| | - Hui Qu
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
| | - Hao Zhang
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
| | - Ensheng Zhao
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China
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32
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Chen SC, Chang PMH, Wang HJ, Tai SK, Chu PY, Yang MH. PD-L1 expression is associated with p16 INK4A expression in non-oropharyngeal head and neck squamous cell carcinoma. Oncol Lett 2017; 15:2259-2265. [PMID: 29434933 PMCID: PMC5776927 DOI: 10.3892/ol.2017.7564] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 08/15/2017] [Indexed: 12/31/2022] Open
Abstract
PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C-reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD-L1 was overexpressed in 32.1% (34/106) and p16INK4A in 20.8% (22/106) of patients. The expression of PD-L1 was associated with p16INK4A expression (P<0.01) but was not associated with levels of systemic inflammatory factors. Tumor stage was determined to be a significant prognostic value (stage I/II vs. III/IV, P=0.03), however, PD-L1, p16INK4A or other clinicopathological factors were not. The current study identified an association between PD-L1 and p16INK4A expression in non-OPHNSCC. This may facilitate the development of anti-PD1/PDL1 therapies to treat patients with head and neck cancer.
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Affiliation(s)
- San-Chi Chen
- Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Faculty of Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C.,Institute of Clinical Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C
| | - Peter Mu-Hsin Chang
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Faculty of Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C.,Institute of Clinical Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C
| | - Hsiao-Jung Wang
- Division of Experimental Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C
| | - Shyh-Kuan Tai
- Faculty of Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C.,Department of Otolaryngology, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C
| | - Pen-Yuan Chu
- Faculty of Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C.,Department of Otolaryngology, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C
| | - Muh-Hwa Yang
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Institute of Clinical Medicine, National Yang Ming University, Taipei 11217, Taiwan, R.O.C.,Genome Research Center, National Yang Ming University, Taipei 11217, Taiwan, R.O.C
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33
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Albers AE, Qian X, Kaufmann AM, Coordes A. Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype. Sci Rep 2017; 7:16715. [PMID: 29196639 PMCID: PMC5711807 DOI: 10.1038/s41598-017-16918-w] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 11/19/2017] [Indexed: 02/07/2023] Open
Abstract
Consistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV-/p16-, 6.7% for HPV-/p16+ and 7.3% for HPV+/P16-. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV-/p16+ HNSCC was intermediate while HPV+/p16- and HPV-/p16- had the shortest survival outcomes. The clearly distinct survival of HPV-/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.
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Affiliation(s)
- Andreas E Albers
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany.
| | - Xu Qian
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Andreas M Kaufmann
- Clinic for Gynecology, Charité - Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Annekatrin Coordes
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
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34
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Eden MM, Tompkins J, Verheijde JL. Reliability and a correlational analysis of the 6MWT, ten-meter walk test, thirty second sit to stand, and the linear analog scale of function in patients with head and neck cancer. Physiother Theory Pract 2017; 34:202-211. [DOI: 10.1080/09593985.2017.1390803] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Melissa M. Eden
- Physical Medicine and Rehabilitation, Mayo Clinic, Phoenix, AZ, USA
| | - James Tompkins
- Physical Medicine and Rehabilitation, Mayo Clinic, Phoenix, AZ, USA
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Höpken M, Reitmajer M, Silling S, Maune S, Brockmann M, Schildgen O. Novel DNA CHIP detects human papillomaviruses in tonsillar tumors. Future Virol 2017. [DOI: 10.2217/fvl-2017-0053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: In this study, the novel VisionArray HPV assay was compared with the LCD CHIP array for the detection of HPVs in tonsillar carcinoma. Materials & methods: A Panel of tonsillar tumors and control samples containing know HPV isolates were tested with the VisonArry HPV Assay (Zytovision, Bremerhaven, Germany) and the Chipron MycoDirect LCD Assay (Chipron, Berlin, Germany). Results: While both assays enabled the discrimination between low-risk, intermediate and high-risk types, the LCD CHIP assay had a better laboratory performance and was more comfortable in its usage. However, both arrays delivered comparable results. Conclusion: Both assays are appropriate tools for the detection of clinically relevant HPV strains in tonsillar tumors. However, if the LCD CHIP array is established, the more complex workflow required for the VisionArray HPV assay could restrain diagnostic labs from a change to this novel assay despite its good quality.
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Affiliation(s)
- Merle Höpken
- Kliniken der Stadt Köln gGmbH, Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie, Professur für Hals-, Nasen-, und Ohrenheilkunde der Privaten Universität Witten/Herdecke, Cologne, Germany
| | - Markus Reitmajer
- Kliniken der Stadt Köln gGmbH, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Institut für Pathologie, Cologne, Germany
| | - Steffi Silling
- Institut für Virologie, Universität zu Köln, Cologne, Germany
| | - Steffen Maune
- Kliniken der Stadt Köln gGmbH, Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie, Professur für Hals-, Nasen-, und Ohrenheilkunde der Privaten Universität Witten/Herdecke, Cologne, Germany
| | - Michael Brockmann
- Kliniken der Stadt Köln gGmbH, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Institut für Pathologie, Cologne, Germany
| | - Oliver Schildgen
- Kliniken der Stadt Köln gGmbH, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Institut für Pathologie, Cologne, Germany
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36
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Kadletz L, Heiduschka G, Wolf A, Haug-Lettenbichler A, Poyntner L, Primosch T, Rogatsch H, Formanek M, Stadler M, Kenner L, Eckel HE, Brunner M. Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma. Laryngoscope 2017; 128:1075-1082. [DOI: 10.1002/lary.26815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/23/2017] [Accepted: 06/30/2017] [Indexed: 12/29/2022]
Affiliation(s)
- Lorenz Kadletz
- Department of Otorhinolaryngology and Head and Neck Surgery; Medical University of Vienna; Vienna Austria
| | - Gregor Heiduschka
- Department of Otorhinolaryngology and Head and Neck Surgery; Medical University of Vienna; Vienna Austria
| | - Axel Wolf
- Department of Otorhinolaryngology and Head and Neck Surgery; Medical University of Graz; Graz Austria
| | - Anna Haug-Lettenbichler
- Department of Otorhinolaryngology and Head and Neck Surgery; Medical University of Innsbruck; Innsbruck Austria
| | - Lukas Poyntner
- Department of Otorhinolaryngology; Hospital Feldkirch; Feldkirch Austria
| | - Thomas Primosch
- Department of Otorhinolaryngology; Klinikum Klagenfurt; Klagenfurt Austria
| | | | - Michael Formanek
- Department of Otorhinolaryngology, Hospital of St. John of God, Department of Otolaryngology and Phonetics; Sigmund Freud University, Medical School; Vienna Austria
| | - Matthias Stadler
- Department of Otorhinolaryngology; Hospital Barmherzige Schwestern; Linz Austria
| | - Lukas Kenner
- Institute of Pathology; Medical University of Vienna; Vienna Austria
| | - Hans E. Eckel
- Department of Otorhinolaryngology; Klinikum Klagenfurt; Klagenfurt Austria
| | - Markus Brunner
- Department of Otorhinolaryngology and Head and Neck Surgery; Medical University of Vienna; Vienna Austria
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37
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Taib BG, Rylands J, Povall S, Jones TM, Taylor-Robinson D. Protocol: systematic review of the association between socio-economic status and survival in adult head and neck cancer. Syst Rev 2017; 6:151. [PMID: 28768525 PMCID: PMC5541745 DOI: 10.1186/s13643-017-0545-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Accepted: 07/18/2017] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Head and neck cancer incidence is increasing worldwide. Despite overall improvements in survival, numerous studies suggest worse survival in more disadvantaged populations; however, this literature has not been systematically reviewed. The aim of this review is to investigate whether lower compared to higher socioeconomic status (SES) influences survival in head and neck squamous cell cancer (HNSCC) and explore possible explanations for any relationship found. METHOD A systematic strategy will be used to identify articles, appraise their quality and extract data. Online databases including MEDLINE, Web of Knowledge, ESBCO Host and Scopus will be used to locate observational studies of adults with a primary diagnosis of head and neck cancer in EU15+ countries (15 members of the EU, Australia, Canada, Norway, USA and New Zealand) where the outcomes report associations between SES and survival. This will be augmented by searching for grey literature and through reference lists. Data will be extracted using a standardised form. Study quality will be assessed using the Newcastle Ottawa scale and where possible meta-analysis of the pooled data will be conducted. DISCUSSION This review will quantify the association between SES and survival outcomes for adult head and neck cancer patients in developed countries. The results will help identify gaps in the literature and therefore direct further novel research in the field. Ultimately, this will inform public policy and strategies to reduce the inequalities in HNSCC survival. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016037019 .
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Affiliation(s)
- Bilal G. Taib
- Postgraduate Centre, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP UK
| | - Joseph Rylands
- Aintree University Hospital, Longmoor Lane, Liverpool, L9 7AL UK
| | - Sue Povall
- Institute of Psychology, Health and Society, University of Liverpool, Waterhouse building, Liverpool, L69 3BX UK
| | - Terry M. Jones
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 200 London Road, Liverpool, L3 9GA UK
| | - David Taylor-Robinson
- Institute of Psychology, Health and Society, University of Liverpool, Waterhouse building, Liverpool, L69 3BX UK
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38
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Matched computed tomography segmentation and demographic data for oropharyngeal cancer radiomics challenges. Sci Data 2017; 4:170077. [PMID: 28675381 PMCID: PMC5497772 DOI: 10.1038/sdata.2017.77] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 04/12/2017] [Indexed: 11/28/2022] Open
Abstract
Cancers arising from the oropharynx have become increasingly more studied in the past few years, as they are now epidemic domestically. These tumors are treated with definitive (chemo)radiotherapy, and have local recurrence as a primary mode of clinical failure. Recent data suggest that ‘radiomics’, or extraction of image texture analysis to generate mineable quantitative data from medical images, can reflect phenotypes for various cancers. Several groups have shown that developed radiomic signatures, in head and neck cancers, can be correlated with survival outcomes. This data descriptor defines a repository for head and neck radiomic challenges, executed via a Kaggle in Class platform, in partnership with the MICCAI society 2016 annual meeting.These public challenges were designed to leverage radiomics and/or machine learning workflows to discriminate HPV phenotype in one challenge (HPV status challenge) and to identify patients who will develop a local recurrence in the primary tumor volume in the second one (Local recurrence prediction challenge) in a segmented, clinically curated anonymized oropharyngeal cancer (OPC) data set.
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39
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Chen H, Li Y, Long Y, Tang E, Wang R, Huang K, Xie C, Chen G. Increased p16 and p53 protein expression predicts poor prognosis in mucosal melanoma. Oncotarget 2017; 8:53226-53233. [PMID: 28881806 PMCID: PMC5581105 DOI: 10.18632/oncotarget.18367] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 05/10/2017] [Indexed: 12/14/2022] Open
Abstract
Primary mucosal melanoma (MM) is a rare, and aggressive, neoplasm with a poor prognosis. To date, few prognostic markers of MM have been well-defined. The aim of this study is to clarify the prognostic value of p53 and p16 proteins in predicting the clinical outcome of Chinese patients with MM. A total of 59 MM samples were contained from biopsy specimens, and, expressions of p53 and p16 proteins were assessed by immunohistochemistry. Cox regression analysis was performed to investigate the association of these proteins with the overall survival of MM patients. Increased p16 expression was significantly associated with reduced survival at three years (P=0.039). Increased p53 expression correlates with reduced one-year (P=0.025), and, two-year survival (P=0.037). Increased p53 and p16 protein expression may be helpful prognostic indicators for the management of these patients.
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Affiliation(s)
- Hanbin Chen
- Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yangyang Li
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yin Long
- Center for Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Yangpu, Shanghai, China
| | - Erjiang Tang
- Center for Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Yangpu, Shanghai, China
| | - Rongrong Wang
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Kate Huang
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Congying Xie
- Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Guorong Chen
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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40
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Vital D, Holzmann D, Huber GF, Soyka MB, Moch H, Zimmermann DR, Ikenberg K. p16 INK4a : A surrogate marker of high-risk human papillomavirus infection in squamous cell carcinoma of the nasal vestibule. Head Neck 2017; 39:1392-1398. [PMID: 28371015 DOI: 10.1002/hed.24767] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 01/15/2017] [Accepted: 02/08/2017] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND The purpose of this study was to analyze the role of p16INK4a and the prevalence of human papillomavirus (HPV) in squamous cell carcinoma (SCC) of the nasal vestibule. METHODS Patients diagnosed from 1995 to 2014 were included in this study. Assessment of p16INK4a and HPV-DNA polymerase chain reaction (PCR) was performed and analyzed with respect to baseline, clinicopathological, and outcome parameters. The p16INK4a positivity was defined as unequivocal nuclear and cytoplasmic staining of ≥70% of the cells, whereas 50%-69% was considered to be a "borderline" result. RESULTS There were 46 patients with SCCs of the nasal vestibule, of whom 31 (67.4%) were available for p16INK4a and 30 (65.2%) for analysis of HPV. Expression of p16INK4a was present in 19.4% and showed coincidence with high-risk HPV (P < .001). Neither p16INK4a nor HPV-DNA had significant impact on outcome. CONCLUSION Significant immunoreactivity for p16INK4a was present in about one-fifth of the samples and figured as a surrogate marker of high-risk HPV infection. There was no influence on outcome.
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Affiliation(s)
- Domenic Vital
- Department of Otorhinolaryngology, Head and Neck Surgery, Zurich University Hospital and University of Zurich, Frauenklinikstrasse 24, CH-8091, Zurich, Switzerland
| | - David Holzmann
- Department of Otorhinolaryngology, Head and Neck Surgery, Zurich University Hospital and University of Zurich, Frauenklinikstrasse 24, CH-8091, Zurich, Switzerland
| | - Gerhard F Huber
- Department of Otorhinolaryngology, Head and Neck Surgery, Zurich University Hospital and University of Zurich, Frauenklinikstrasse 24, CH-8091, Zurich, Switzerland
| | - Michael B Soyka
- Department of Otorhinolaryngology, Head and Neck Surgery, Zurich University Hospital and University of Zurich, Frauenklinikstrasse 24, CH-8091, Zurich, Switzerland
| | - Holger Moch
- Department of Pathology and Molecular Pathology, Zurich University Hospital and University of Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland
| | - Dieter R Zimmermann
- Department of Pathology and Molecular Pathology, Zurich University Hospital and University of Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland
| | - Kristian Ikenberg
- Department of Pathology and Molecular Pathology, Zurich University Hospital and University of Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland
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41
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Abstract
The pathology laboratory has a central role in providing human papillomavirus (HPV) tests for patients with head and neck cancer. There is an extensive literature around HPV testing and a large number of proprietary HPV tests, which makes the field difficult to navigate. This review provides a concise contemporary overview of the evidence around HPV testing in head and neck cancer and signposts key publications, guideline documents and the most commonly used methods in clinical practice.
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Affiliation(s)
- Max Robinson
- Oral Pathology, Centre for Oral Health Research, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK.
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42
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Verma G, Vishnoi K, Tyagi A, Jadli M, Singh T, Goel A, Sharma A, Agarwal K, Prasad SC, Pandey D, Sharma S, Mehrotra R, Singh SM, Bharti AC. Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers. Cancer Med 2017; 6:591-604. [PMID: 28155253 PMCID: PMC5345654 DOI: 10.1002/cam4.983] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Revised: 09/29/2016] [Accepted: 11/07/2016] [Indexed: 12/12/2022] Open
Abstract
Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings. We examined a total of 31 prospective and 30 formalin-fixed, paraffin-embedded tissues from treatment-naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 + PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c-Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP-1 and NF-κB lacking involvement of STAT3 that strongly correlated with HPV-positive tumors. Presence of STAT3/pSTAT3 with NF-κB irrespective of the presence or absence of AP-1 members was present in HPV-negative lesions. Expression of pSTAT3 strongly correlated with all the AP-1/NF-κB members (except JunD), its upstream activator pEGFRY1092 , and HPV infection-related negative regulator p16. Overall, we show a simple combination of AP-1, NF-κB, and STAT3 members' expression that may serve as molecular signature of HPV-positive lesions or more broadly the tumors that show better prognosis.
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Affiliation(s)
- Gaurav Verma
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
- School of BiotechnologyBanaras Hindu UniversityVaranasiUttar PradeshIndia
- Molecular Oncology LaboratoryDepartment of ZoologyUniversity of DelhiDelhiIndia
| | - Kanchan Vishnoi
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
- School of BiotechnologyBanaras Hindu UniversityVaranasiUttar PradeshIndia
- Molecular Oncology LaboratoryDepartment of ZoologyUniversity of DelhiDelhiIndia
| | - Abhishek Tyagi
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
| | - Mohit Jadli
- Molecular Oncology LaboratoryDepartment of ZoologyUniversity of DelhiDelhiIndia
| | - Tejveer Singh
- Molecular Oncology LaboratoryDepartment of ZoologyUniversity of DelhiDelhiIndia
| | - Ankit Goel
- Subharti Dental CollegeMeerutUttar PradeshIndia
| | | | | | - Subhash Chandra Prasad
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
| | - Durgatosh Pandey
- Department of OncosurgeryDr. Bheem Rao Ambedkar Institute‐Rotary Cancer HospitalAll India Institute Of Medical SciencesNew DelhiIndia
| | - Shashi Sharma
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
| | - Ravi Mehrotra
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
| | | | - Alok Chandra Bharti
- Division of Molecular OncologyInstitute of Cytology & Preventive Oncology (ICMR)NoidaUttar PradeshIndia
- Molecular Oncology LaboratoryDepartment of ZoologyUniversity of DelhiDelhiIndia
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43
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Kofler B, Borena W, Manzl C, Dudas J, Wegscheider AS, Jansen-Dürr P, Schartinger V, Riechelmann H. Sensitivity of tumor surface brushings to detect human papilloma virus DNA in head and neck cancer. Oral Oncol 2017; 67:103-108. [PMID: 28351563 DOI: 10.1016/j.oraloncology.2017.02.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 01/31/2017] [Accepted: 02/13/2017] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Human papilloma virus (HPV) induced head and neck squamous cell carcinoma (HNSCC) represents a distinct tumor subset. We questioned how accurately a brushing from the tumor surface detects HPV in patients with HNSCC. MATERIALS AND METHODS Brushings from the tumor surface were compared with HPV DNA isolation from formalin-fixed and paraffin-embedded (FFPE) tumor biopsies, which served as the reference standard. In both matrices, HPV DNA was detected using a commercially available test kit. In addition, p16 was assessed in tumor biopsies by immunohistochemistry (IHC). The tumors were considered p16 positive if 70% or more of cancer cells expressed p16. RESULTS 93 patients with HNSCC were included. Sensitivity and specificity of the brush test were 83% (95%CI: 67-92%) and 85% (95%CI: 72-93%). Results of p16 IHC were concordant with FFPE samples DNA determinations in 73/93 patients. In 53 patients (57%) the tumor was located in the oropharynx and in 40 patients (43%) the tumor was located in the non-oropharynx region. Sensitivity and specificity of the brush test in patients with oropharyngeal cancer was higher with 86% (95%CI: 70-95%) and 89% (95%CI: 65-99%). CONCLUSION Superficial brushes from the tumor surface may be used to identify HPV positive HNSCC.
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Affiliation(s)
- Barbara Kofler
- Department of Otorhinolaryngology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
| | - Wegene Borena
- Division of Virology, Department of Hygiene, Microbiology, Social Medicine, Medical University of Innsbruck, Peter-Mayr-Strasse 4b, 6020 Innsbruck, Austria
| | - Claudia Manzl
- Department of Pathology, Medical University of Innsbruck, Müllerstrasse 44, 6020 Innsbruck, Austria
| | - Jozsef Dudas
- Department of Otorhinolaryngology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Anne-Sophie Wegscheider
- Department of Pathology, Medical University of Innsbruck, Müllerstrasse 44, 6020 Innsbruck, Austria
| | - Pidder Jansen-Dürr
- Institute for Biomedical Ageing Research, Medical University of Innsbruck, Rennweg 10, 6020 Innsbruck, Austria
| | - Volker Schartinger
- Department of Otorhinolaryngology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
| | - Herbert Riechelmann
- Department of Otorhinolaryngology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
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44
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Ben‐Dayan MM, Ow TJ, Belbin TJ, Wetzler J, Smith RV, Childs G, Diergaarde B, Hayes DN, Grandis JR, Prystowsky MB, Schlecht NF. Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma. Cancer Med 2017; 6:397-407. [PMID: 28102032 PMCID: PMC5313649 DOI: 10.1002/cam4.961] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 10/14/2016] [Accepted: 10/21/2016] [Indexed: 12/17/2022] Open
Abstract
We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC.
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Affiliation(s)
- Miriam M. Ben‐Dayan
- Department of PathologyAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
| | - Thomas J. Ow
- Department of PathologyAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
- Department of Otorhinolaryngology‐Head and Neck SurgeryAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
| | - Thomas J. Belbin
- Department of PathologyAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
- Dicipline of OncologyFaculty of MedicineMemorial University of NewfoundlandSt. John'sNewfoundland
| | - Joshua Wetzler
- Department of PathologyAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
| | - Richard V. Smith
- Department of Otorhinolaryngology‐Head and Neck SurgeryAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
| | - Geoffrey Childs
- Department of PathologyAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
| | - Brenda Diergaarde
- Department of EpidemiologyUniversity of Pittsburgh Cancer InstitutePittsburghPennsylvania
| | - D. Neil Hayes
- Department of Otolaryngology/Head and Neck Cancer SurgeryUniversity of North CarolinaChapel HillNorth Carolina
| | - Jennifer R. Grandis
- Departments of Otolaryngology Head and Neck SurgeryUniversity of CaliforniaSan FranciscoCalifornia
- Department of Clinical and Translational Science InstituteUniversity of CaliforniaSan FranciscoCalifornia
| | - Michael B. Prystowsky
- Department of PathologyAlbert Einstein College of MedicineMontefiore Medical CenterBronxNew York
| | - Nicolas F. Schlecht
- Departments of Epidemiology & Population Health and MedicineAlbert Einstein College of MedicineBronxNew York
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Meshman J, Wang PC, Chin R, John MS, Abemayor E, Bhuta S, Chen AM. Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx. Am J Otolaryngol 2017; 38:31-37. [PMID: 27751621 DOI: 10.1016/j.amjoto.2016.09.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 09/25/2016] [Indexed: 10/20/2022]
Abstract
PURPOSE To evaluate the prognostic significance of p16 expression among patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HSCC). METHODS The medical records of all patients with locally advanced, non-metastatic LSCC/HSCC were reviewed. p16INK4A (p16) protein expression was evaluated on pathological specimens by immunohistochemistry (IHC), and the Kaplan-Meier method was used to estimate overall survival (OS) and locoregional control (LRC). In select cases, p16 expression was correlated to high-risk and low-risk HPV genotypes using in situ hybridization (ISH). RESULTS Thirty-one patients (23 LSCC; 8 HSCC) were identified. Seventeen (54.8%) patients were p16 negative; 14 (45.2%) were p16-positive. The primary treatment modality was radiation therapy for 22 (71.0%) patients and surgery for 9 (29.0%). Nineteen (61.3%) patients were evaluated for high-risk HPV and low-risk HPV genotypes by IHC, of whom 2 (10.5%) patients were positive for high-risk HPV and 1 (5.3%) was positive for low-risk HPV. For high-risk HPV, the positive predictive value (PPV), sensitivity, and specificity of p16 was 20.0%, 100%, and 52.9%. There was no significant difference in the 2-year actuarial rates of OS (91% vs. 64%, p=0.34) or LRC (51% vs. 46%, p=0.69) between the p16-positive and p-16 negative patients. CONCLUSION In this small cohort of 31 LSCC and HSCC patients, p16 was not a significant predictive of either LRC or OS. Furthermore, p16 was poorly correlated with HPV genotyping as identified by ISH.
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46
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Ragin C, Liu JC, Jones G, Shoyele O, Sowunmi B, Kennett R, Groen HJM, Gibbs D, Blackman E, Esan M, Brandwein MS, Devarajan K, Bussu F, Chernock R, Chien CY, Cohen MA, Samir EM, Mikio S, D'Souza G, Funchain P, Eng C, Gollin SM, Hong A, Jung YS, Krüger M, Lewis J, Morbini P, Landolfo S, Rittà M, Straetmans J, Szarka K, Tachezy R, Worden FP, Nelson D, Gathere S, Taioli E. Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients. Carcinogenesis 2016; 38:218-229. [PMID: 28025390 DOI: 10.1093/carcin/bgw203] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Indexed: 12/13/2022] Open
Abstract
The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.
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Affiliation(s)
- Camille Ragin
- Cancer Prevention and Control Program, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
- Department of Epidemiology & Biostatistics, Temple University, College of Public Health, Philadelphia, PA, USA
| | - Jeffrey C Liu
- Department of Otolaryngology, Temple University; and Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Gieira Jones
- Department of Epidemiology & Biostatistics, Temple University, College of Public Health, Philadelphia, PA, USA
| | - Olubunmi Shoyele
- Department of Pathology and Laboratory Medicine, Western Connecticut Health Network, Danbury Hospital, Danbury, CT, USA
| | - Bukola Sowunmi
- Cancer Prevention and Control Program, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
| | - Rachel Kennett
- Cancer Prevention and Control Program, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
| | - Harry J M Groen
- Department of Epidemiology & Biostatistics, Temple University, College of Public Health, Philadelphia, PA, USA
| | - Denise Gibbs
- Cancer Prevention and Control Program, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
| | - Elizabeth Blackman
- Cancer Prevention and Control Program, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
- Department of Epidemiology & Biostatistics, Temple University, College of Public Health, Philadelphia, PA, USA
| | - Michael Esan
- Cancer Prevention and Control Program, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
| | - Margaret S Brandwein
- Department of Pathology and Anatomical Sciences, SUNY at the University at Buffalo, Buffalo, NY, USA
| | - Karthik Devarajan
- Department of Biostatistics, Fox Chase Cancer Center - Temple Health, Philadelphia, PA, USA
| | - Francesco Bussu
- Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Rome, Italy
| | - Rebecca Chernock
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
| | - Chih-Yen Chien
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Marc A Cohen
- Department of Surgery, Head and Neck Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - El-Mofty Samir
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
| | - Suzuki Mikio
- Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Gypsyamber D'Souza
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Pauline Funchain
- Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA
| | - Charis Eng
- Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA
| | - Susanne M Gollin
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA USA
| | - Angela Hong
- Central Clinical School, The University of Sydney, Sydney, NSW, Australia
| | - Yuh-S Jung
- Department of Otolaryngology, Research Institute and Hospital, National Cancer Center, Gyeonggi-do, Korea
| | - Maximilian Krüger
- Department of Oral and Maxillofacial Surgery - Plastic Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - James Lewis
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, 37232, USA
| | - Patrizia Morbini
- Department of Molecular Medicine, Unit of Pathology, University of Pavia, and à IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
| | - Santo Landolfo
- Department of Sciences of Public Health and Pediatrics, University of Turin, Turin, Italy
| | - Massimo Rittà
- Department of Sciences of Public Health and Pediatrics, University of Turin, Turin, Italy
| | - Jos Straetmans
- Department of Otorhinolaryngology-Head and Neck Surgery, GROW Institute, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Krisztina Szarka
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Hungary
| | - Ruth Tachezy
- Department of Immunology, Institute of Hematology and Blood Transfusion National Reference Laboratory for Papillomaviruses, Prague, Czech Republic
| | - Francis P Worden
- Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Deborah Nelson
- Department of Epidemiology & Biostatistics, Temple University, College of Public Health, Philadelphia, PA, USA
| | - Samuel Gathere
- Non Communicable Diseases Research Programme, Kenya Medical Research Institute, Nairobi, Kenya
| | - Emanuela Taioli
- Departments of Population Health Science and Policy, of Thoracic Surgery, and Institute For Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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47
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Prigge ES, Arbyn M, von Knebel Doeberitz M, Reuschenbach M. Diagnostic accuracy of p16 INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int J Cancer 2016; 140:1186-1198. [PMID: 27859245 DOI: 10.1002/ijc.30516] [Citation(s) in RCA: 181] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 10/12/2016] [Accepted: 11/03/2016] [Indexed: 12/12/2022]
Abstract
The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta-analysis to determine the diagnostic accuracy of p16INK4a immunohistochemistry (IHC) to identify HPV-induced OPSCC. We identified all studies that performed p16INK4a IHC (index test) and HPV E6/E7 mRNA detection using an amplification-based method (gold standard to indicate a transforming relevance of HPV) in OPSCC. Testing with one or more comparator tests (HPV DNA PCR, HPV DNA in situ hybridization (ISH) and p16INK4a IHC/HPV DNA PCR combined testing) was an optional criterion for inclusion. Among 1,636 retrieved studies 24 fulfilled the inclusion criteria. The pooled sensitivity of p16INK4a IHC, HPV DNA PCR, HPV DNA ISH and p16INK4a IHC/HPV DNA PCR combined testing was 94% (95%-confidence interval (CI) 91-97%), 98% (CI 94-100%), 85% (CI 76-92%) and 93% (CI 87-97%), respectively. The pooled specificity was 83% (CI 78-88%), 84% (CI 74-92%), 88% (CI 78-96%) and 96% (CI 89-100%), respectively. p16INK4a IHC/HPV DNA PCR combined testing was as sensitive as either p16INK4a IHC or HPV DNA PCR alone but significantly more specific than either separate test. In conclusion, p16INK4a IHC is highly sensitive but moderately specific to diagnose HPV-transformed OPSCC when used as a single test. Combined p16INK4a IHC and HPV DNA PCR testing significantly enhances specificity while maintaining high sensitivity. This diagnostic test combination thus represents an attractive testing strategy for the reliable diagnosis of HPV-induced OPSCC in the clinical setting and may constitute an inclusion criterion for future therapeutic trials.
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Affiliation(s)
- Elena-Sophie Prigge
- Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany
| | - Marc Arbyn
- Belgian Cancer Centre and Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, B1050, Belgium.,University of Antwerp, Antwerp, Belgium
| | - Magnus von Knebel Doeberitz
- Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany
| | - Miriam Reuschenbach
- Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany
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48
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Pattle SB, Utjesanovic N, Togo A, Wells L, Conn B, Monaghan H, Junor E, Johannessen I, Cuschieri K, Talbot S. Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma. Genes Chromosomes Cancer 2016; 56:185-198. [DOI: 10.1002/gcc.22425] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 10/11/2016] [Accepted: 10/12/2016] [Indexed: 12/13/2022] Open
Affiliation(s)
- Samuel B. Pattle
- Division of Infection and Pathway Medicine; The University of Edinburgh, Little France Crescent, Scotland
| | - Natasa Utjesanovic
- Division of Infection and Pathway Medicine; The University of Edinburgh, Little France Crescent, Scotland
| | - Athena Togo
- Department of Otolaryngology, The Laurieston Building; NHS Lothian, Edinburgh
| | - Lucy Wells
- Western General Hospital; The Edinburgh Cancer Centre; NHS Lothian, Edinburgh
| | - Brendan Conn
- Department of Pathology; Royal Infirmary of Edinburgh; NHS Lothian, Edinburgh
| | - Hannah Monaghan
- Department of Pathology; Royal Infirmary of Edinburgh; NHS Lothian, Edinburgh
| | - Elizabeth Junor
- Western General Hospital; The Edinburgh Cancer Centre; NHS Lothian, Edinburgh
| | | | - Kate Cuschieri
- Scottish HPV Reference Laboratory; Royal Infirmary of Edinburgh; NHS Lothian, Edinburgh
| | - Simon Talbot
- Division of Infection and Pathway Medicine; The University of Edinburgh, Little France Crescent, Scotland
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49
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Sailer V, Holmes EE, Gevensleben H, Goltz D, Dröge F, de Vos L, Franzen A, Schröck F, Bootz F, Kristiansen G, Schröck A, Dietrich D. PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma. Oncotarget 2016; 7:75827-75838. [PMID: 27716615 PMCID: PMC5342781 DOI: 10.18632/oncotarget.12417] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 09/20/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients. RESULTS PITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010). METHODS Quantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy). CONCLUSIONS PITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.
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Affiliation(s)
- Verena Sailer
- Weill Medical College of Cornell University and New York Presbyterian Hospital, Department of Pathology and Laboratory Medicine, New York, NY, USA
- Weill Medical College of Cornell University and New York Presbyterian Hospital, Englander Institute for Precision Medicine, New York, NY, USA
| | - Emily Eva Holmes
- Institute of Pathology, University Hospital of Bonn, Bonn, Germany
| | | | - Diane Goltz
- Institute of Pathology, University Hospital of Bonn, Bonn, Germany
| | - Freya Dröge
- Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Luka de Vos
- University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, Bonn, Germany
| | - Alina Franzen
- University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, Bonn, Germany
| | - Friederike Schröck
- Department of Addictive Disorders and Addiction Medicine, LVR Hospital Bonn, Bonn, Germany
| | - Friedrich Bootz
- University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, Bonn, Germany
| | - Glen Kristiansen
- Institute of Pathology, University Hospital of Bonn, Bonn, Germany
| | - Andreas Schröck
- University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, Bonn, Germany
| | - Dimo Dietrich
- Institute of Pathology, University Hospital of Bonn, Bonn, Germany
- University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, Bonn, Germany
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50
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Ou P, Gear K, Rahnama F, Thomas S, Nagappan R, Kee D, Waldvogel-Thurlow S, Jain R, McIvor N, Izzard M, Douglas R. Human papillomavirus and oropharyngeal squamous cell carcinoma: a New Zealand cohort study. ANZ J Surg 2016; 88:E278-E283. [DOI: 10.1111/ans.13759] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 04/04/2016] [Accepted: 07/18/2016] [Indexed: 12/17/2022]
Affiliation(s)
- Peter Ou
- Department of Surgery; The University of Auckland; Auckland New Zealand
| | - Kim Gear
- Department of Oto-rhinolaryngology; Head and Neck Surgery, Auckland District Health Board; Auckland New Zealand
| | - Fahimeh Rahnama
- Department of Virology and Anatomical Pathology; LabPLUS, Auckland District Health Board; Auckland New Zealand
| | - Stephen Thomas
- Department of Virology and Anatomical Pathology; LabPLUS, Auckland District Health Board; Auckland New Zealand
| | - Radhika Nagappan
- Department of Virology and Anatomical Pathology; LabPLUS, Auckland District Health Board; Auckland New Zealand
| | - Dennis Kee
- Department of Virology and Anatomical Pathology; LabPLUS, Auckland District Health Board; Auckland New Zealand
| | | | - Ravi Jain
- Department of Surgery; The University of Auckland; Auckland New Zealand
| | - Nick McIvor
- Department of Oto-rhinolaryngology; Head and Neck Surgery, Auckland District Health Board; Auckland New Zealand
| | - Mark Izzard
- Department of Oto-rhinolaryngology; Head and Neck Surgery, Auckland District Health Board; Auckland New Zealand
| | - Richard Douglas
- Department of Surgery; The University of Auckland; Auckland New Zealand
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