Cancer Research and Treatment

Original Articles

Head and Neck cancer

Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01): Yun-Gyoo Lee, Eun Joo Kang, Bhumsuk Keam, Jin-Hyuk Choi, Jin-Soo Kim, Keon Uk Park, Kyoung Eun Lee, Hyo Jung Kim, Keun-Wook Lee, Min Kyoung Kim, Hee Kyung Ahn, Seong Hoon Shin, Hye Ryun Kim, Sung-Bae Kim, Hwan Jung Yun; Cancer Res Treat. 2022;54(1):109-117. Published online April 27, 2021; DOI: https://doi.org/10.4143/crt.2020.1329

Purpose
Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods
Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results
Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion
Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.

Citations

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Circulating tumor DNA determines induction chemotherapy response in HPV associated oropharyngeal squamous cell carcinoma: A pilot study
Zachary M. Huttinger, Emile Gogineni, Sujith Baliga, Dukagjin M. Blakaj, Priyanka Bhateja, Marcelo Bonomi, Stephen Y. Kang, Matthew O. Old, Nolan B. Seim, Kyle K. VanKoevering, Amit Agrawal, Enver Ozer, James W. Rocco, Catherine T. Haring
Oral Oncology.2025; 161: 107179. CrossRef
Treatment patterns, outcomes, healthcare resource utilization, and costs associated with locally advanced squamous cell carcinoma of the head and neck in Japan
Kenichi Nibu, Makoto Tahara, Noriko Yoshimi, Ramzi Argoubi, Vanessa Rascon-Velasco, Makan Rahshenas, Sarah Bobiak, Ember Lu
Frontiers in Oncology.2025;[Epub] CrossRef
Neoadjuvant Chemotherapy for Oropharyngeal Cancer Treatment De-Escalation: From Historical Failures to Contemporary HPV-Driven Paradigms
Alvaro Sanabria, Juan P. Rodrigo, Anna Luíza Damaceno Araújo, Luiz P. Kowalski
Cancers.2025; 18(1): 23. CrossRef
Clinical decision pathway and management of locally advanced head and neck squamous cell carcinoma: A multidisciplinary consensus in Asia-Pacific
Ye Guo, Torahiko Nakashima, Byoung Chul Cho, Darren W.-T. Lim, Muh-Hwa Yang, Pei-Jen Lou, June Corry, Jin Ching Lin, Guo Pei Zhu, Kyung Hwan Kim, Bin Zhang, Zhiming Li, Ruey-Long Hong, Junice Yi Siu Ng, Ee Min Tan, Yan Ping Liu, Con Stylianou, Carmel Spit
Oral Oncology.2024; 148: 106657. CrossRef
Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for locally advanced head and neck squamous cell carcinoma
Ping Han, Faya Liang, Pan Song, Taowei Wu, Yangyang Li, Ming Gao, Peiliang Lin, Jianming Fan, Xiaoming Huang
Holistic Integrative Oncology.2024;[Epub] CrossRef
Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience
Hyun Bang, Hyeon-Jong Kim, Seung Lee, Hyun Shim, Jun Hwang, Woo Bae, Ik-Joo Chung, Sang-Hee Cho
Oncology Letters.2024;[Epub] CrossRef
Role of induction chemotherapy in advanced‐stage olfactory neuroblastoma
Sung‐Woo Cho, Bhumsuk Keam, Keun‐Wook Lee, Ji‐Won Kim, Doo Hee Han, Hyun Jik Kim, Jeong‐Whun Kim, Dong‐Young Kim, Chae‐Seo Rhee, Yun Jung Bae, Ji‐Hoon Kim, Keun‐Yong Eom, Hong‐Gyun Wu, Yong Hwy Kim, Chae‐Yong Kim, Sun Ha Paek, Hyojin Kim, Tae‐Bin Won
International Forum of Allergy & Rhinology.2024; 14(12): 1882. CrossRef
Intra-Arterial Chemotherapy for Locally Advanced Oral Cavity Cancer
B. B. Vyzhigina, M. A. Kropotov, B. I. Dolgushin, D. A. Safarov, I. V. Pogrebnyakov, S. B. Alieva
Journal of oncology: diagnostic radiology and radiotherapy.2024; 7(3): 62. CrossRef
Response to induction chemotherapy as a prognostic indicator in locally advanced head and neck squamous cell carcinoma
Francesca Huwyler, Roland Giger, Ruben Bill, Daniel Rauch, Simon Haefliger
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Response to induction chemotherapy in sinonasal malignancies: A single‐institutional experience
Sarah C. Nyirjesy, Rachel Fenberg, Margaret A. Heller, Ryan T. Judd, Michael M. Li, Brandon Koch, Marcelo Bonomi, Ricardo L. Carrau, Kyle K. VanKoevering
Head & Neck.2023; 45(6): 1445. CrossRef
Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives
Michaela Svajdova, Pavol Dubinsky, Tomas Kazda, Branislav Jeremic
Cancers.2022; 14(21): 5385. CrossRef

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Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma: Liyuan Dai, Qigen Fang, Peng Li, Junfu Wu, Xu Zhang; Cancer Res Treat. 2020;52(1):109-116. Published online May 30, 2019; DOI: https://doi.org/10.4143/crt.2019.202

Abstract PDF PubReader ePub

Purpose
The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design.
Materials and Methods
Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method.
Results
Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS.
Conclusion
NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

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Clinicopathological Analysis and Survival Outcomes of Radiation‐Induced Oral Squamous Cell Carcinoma: A Systematic Review and Meta‐Analysis
Anne Evelyn Oliveira Moura, Carla Isabelly Rodrigues‐Fernandes, Ana Gabriela Costa Normando, Danielle Machado Farias, Márcio Ajudarte Lopes, Pablo Agustin Vargas, Alan Roger Santos‐Silva, Fábio de Abreu Alves, Luiz Paulo Kowalski, Danyel Elias da Cruz Per
Journal of Oral Pathology & Medicine.2026; 55(4): 448. CrossRef
γ-Catenin (JUP) in Cancer: Contradictory Functions and Therapeutic Potential
Jessica Alejandra Zapata García
Ciencia y Frontera.2026; 3(1): 51. CrossRef
Impact of prior cancer history on the prognosis of extranodal NK/T-cell lymphoma
Qian Wang, Tao Huang, Xudong Wei, Niraj Babu
PLOS ONE.2024; 19(10): e0311094. CrossRef
Oral Squamous Cell Carcinoma and Concomitant Primary Tumors, What Do We Know? A Review of the Literature
Mohammed Badwelan, Hasan Muaddi, Abeer Ahmed, Kyungjun T. Lee, Simon D. Tran
Current Oncology.2023; 30(4): 3721. CrossRef
Secondary Oral Cancer after Systemic Treatment of Hematological Malignancies and Oral GVHD: A Systematic Review
Aleksandra Janowiak-Majeranowska, Jakub Osowski, Bogusław Mikaszewski, Alan Majeranowski
Cancers.2022; 14(9): 2175. CrossRef
Orocutaneous Fistula Formation in Free Flap Reconstruction for Oral Squamous Cell Carcinoma
Qigen Fang, Junhui Yuan, Wei Du, Liyuan Dai, Xu Zhang, Ruihua Luo
Frontiers in Oncology.2022;[Epub] CrossRef
Survival Significance of Number of Positive Lymph Nodes in Oral Squamous Cell Carcinoma Stratified by p16
Peng Li, Qigen Fang, Yanjie Yang, Defeng Chen, Wei Du, Fei Liu, Ruihua Luo
Frontiers in Oncology.2021;[Epub] CrossRef
Significance of depth of invasion determined by MRI in cT1N0 tongue squamous cell carcinoma
Chunmiao Xu, Junhui Yuan, Liuqing Kang, Xiaoxian Zhang, Lifeng Wang, Xuejun Chen, Qi Yao, Hailiang Li
Scientific Reports.2020;[Epub] CrossRef
Significance of SUV Max for Predicting Occult Lymph Node Metastasis and Prognosis in Early-Stage Tongue Squamous Cell Carcinoma
Chunmiao Xu, Hailiang Li, Dongjie Seng, Fei Liu
Journal of Oncology.2020; 2020: 1. CrossRef
Lingual Lymph Node Metastasis in cT1-2N0 Tongue Squamous Cell Carcinoma: Is It an Indicator for Elective Neck Dissection
Wenli Yang, Minglei Sun, Qiaoyan Jie, Haixia Zhou, Peng Zhang, Juanfang Zhu
Frontiers in Oncology.2020;[Epub] CrossRef
Significance of PET-CT for Detecting Occult Lymph Node Metastasis and Affecting Prognosis in Early-Stage Tongue Squamous Cell Carcinoma
Guo Zhao, Jianli Sun, Kai Ba, Yunxiang Zhang
Frontiers in Oncology.2020;[Epub] CrossRef
Feasibility of Submandibular Gland Preservation in cT1-2N0 Squamous Cell Carcinoma in the Floor of the Mouth
Wei Du, Qigen Fang, Shanting Liu, Defeng Chen, Ruihua Luo, Xu Zhang
Frontiers in Oncology.2020;[Epub] CrossRef
Impact of submandibular gland preservation in neck management of early-stage buccal squamous cell carcinoma on locoregional control and disease-specific survival
Bo Gu, Qigen Fang, Yao Wu, Wei Du, Xu Zhang, Defeng Chen
BMC Cancer.2020;[Epub] CrossRef

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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection: Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon; Cancer Res Treat. 2019;51(3):1052-1063. Published online October 24, 2018; DOI: https://doi.org/10.4143/crt.2018.411

Abstract PDF Supplementary Material PubReader ePub

Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

Citations

Citations to this article as recorded by

TrkA Expression as a Novel Prognostic Biomarker in Oral Squamous Cell Carcinoma
Aleksandra Ciarka, Filip Skowronek, Przemysław Miłosz, Michał Kunc, Robert Burdach, Monika Sakowicz-Burkiewicz, Barbara Jereczek-Fossa, Anna Starzyńska, Rafał Pęksa
International Journal of Molecular Sciences.2025; 26(14): 6847. CrossRef
Role of NTRK Fusion Genes in the Tumor Immune Microenvironment of HPV (+/−) Cervical Cancer
Qiongying Wang, Chan Zhang, Shijia Liu, Wangshu Li, Wenjuan Wei, Aziz ur Rehman Aziz, Han Lu, Daqing Wang
Journal of Medical Virology.2025;[Epub] CrossRef
NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population
Lilibeth Stephania Escoto-Vasquez, Javier Portilla-Robertson, Josué Orlando Ramírez-Jarquín, Luis Fernando Jacinto-Alemán, Alejandro Alonso-Moctezuma, Carla Monserrat Ramírez-Martínez, Osmar Alejandro Chanes-Cuevas, Fabiola Salgado-Chavarria
Dentistry Journal.2024; 12(10): 327. CrossRef
Accuracy of magnetic resonance imaging in the assessment of depth of invasion in tongue carcinoma: A systematic review and meta-analysis
Kondajji Ramachandra Vijayalakshmi, Vanshika Jain
National Journal of Maxillofacial Surgery.2023; 14(3): 341. CrossRef
CYLD Alterations in the Tumorigenesis and Progression of Human Papillomavirus–Associated Head and Neck Cancers
Zhibin Cui, Hyunseok Kang, Jennifer R. Grandis, Daniel E. Johnson
Molecular Cancer Research.2021; 19(1): 14. CrossRef
Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer
Zijian Chen, Zenghong Huang, Yanxin Luo, Qi Zou, Liangliang Bai, Guannan Tang, Xiaolin Wang, Guangwen Cao, Meijin Huang, Jun Xiang, Huichuan Yu
Journal of Translational Medicine.2021;[Epub] CrossRef
Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
Cancer Research and Treatment.2021; 53(4): 1174. CrossRef
Clinical Significance of Trk Receptor Expression as a New Therapeutic Target in Hepatocellular Carcinoma
Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park, Sang Yun Ha
Pathology & Oncology Research.2020; 26(4): 2587. CrossRef
Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro‐oncogenic phenotype in HNSCC
Daniel E. Gracilla, Praveen Kumar Korla, Ming‐Tsung Lai, An‐Jen Chiang, Wen‐Shiung Liou, Jim Jinn‐Chyuan Sheu
Molecular Oncology.2020; 14(12): 3065. CrossRef
NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
Eun Kyung Kim, Yoon Ah Cho, Mi-kyoung Seo, Hyunmi Ryu, Byoung Chul Cho, Yoon Woo Koh, Sun Och Yoon
Scientific Reports.2019;[Epub] CrossRef
Characterization of head and neck squamous cell carcinoma arising in young patients: Particular focus on molecular alteration and tumor immunity
Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Head & Neck.2019; 41(1): 198. CrossRef

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Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same: Vishal Sahu, Lokesh Nigam, Vertica Agnihotri, Abhishek Gupta, Shashank Shekhar, Naidu Subbarao, Suman Bhaskar, Sharmistha Dey; Cancer Res Treat. 2019;51(1):313-325. Published online May 9, 2018; DOI: https://doi.org/10.4143/crt.2018.105

Abstract PDF Supplementary Material PubReader ePub

Purpose
The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same.
Materials and Methods
Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors.
Results
We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket.
Conclusion
In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

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Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma
Liyuan Dai, Qigen Fang, Peng Li, Junfu Wu, Xu Zhang
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International Journal of Molecular Sciences.2020; 21(20): 7524. CrossRef

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The Role of E-cadherin/β-catenin Complex and Cyclin D1 in Head and Neck Squamous Cell Carcinoma: Nam Yong Do, Sung Yong Park, Sung Chul Lim; Cancer Res Treat. 2004;36(1):72-78. Published online February 29, 2004; DOI: https://doi.org/10.4143/crt.2004.36.1.72

Abstract PDF PubReader ePub

Purpose

To determine the relationship between expression pattern of E-cadherin, β-catenin and cyclin D1, and clinicopathologic parameters in patients with head and neck squamous cell carcinomas (HNSCC).

Materials and Methods

The authors evaluated the immunohistochemical expression pattern of E-cadherin, β-catenin in relationship with cyclin D1 overexpression, degree of histologic differentiation, clinical stage, and nodal status in 146 head and neck squamous cell carcinomas (HNSCC). The authors also evaluated the expression of E-cadherin/β-catenin complex, E-cadherin/cyclin D1, and β-catenin/cyclin D1 double staining with confocal laser scanning microscope.

Results

Aberrant expressions in 78% of E-cadherin, 77% of β-catenin, and 69% of cyclin D1 in the HNSCC were observed. There was correlation of aberrant expression of E-cadherin and nodal status. Cyclin D1 overexpression was also correlated to clinical stage and nodal status. Significant relation was observed between E-cadherin and β-catenin expression patterns. Co-expression of E-cadherin and β-catenin was significantly detected. However, there was no correlation of cyclin D1 overexpression with E-cadherin or β-catenin expression patterns.

Conclusion

These results suggest that aberrant expression of E-cadherin, E-cadherin/β-catenin complex, and cyclin D1 may be involved in clinical stage and/or nodal status, and analysis of the pattern of E-cadherin, cyclin D1, and E-cadherin/β-catenin complex may be good prognostic marker of HNSCC.

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Pilomatrix carcinoma of the right postauricular region
Shabiah Martin, Jana DeJesus, Ann Jacob, Teah Qvavadze, Claudio Guerrieri, Rachel Hudacko, Thaddeus Boucree
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Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal expansion in head and neck squamous cell carcinoma
Khushdeep Shergill, Arijit Sen, Hari Janardanan Pillai
Journal of the Korean Association of Oral and Maxillofacial Surgeons.2018; 44(4): 182. CrossRef
Prognostic Significance of Cyclin D1 and E-cadherin Expression in Laryngeal Squamous Cell Carcinoma
Rehab Allah Ahmed, Abd El-Aty Shawky, Rasha Hamdy Hamed
Pathology & Oncology Research.2014; 20(3): 625. CrossRef

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