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Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand
Arunee Dechaphunkul, Phatcharaporn Thongwatchara, Paramee Thongsuksai, Tanadech Dechaphunkul, Sarayut Lucien Geater
J Pathol Transl Med. 2022;56(3):126-133.   Published online February 28, 2022
DOI: https://doi.org/10.4132/jptm.2022.01.04
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  • 1 Crossref
AbstractAbstract PDF
Background
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC.
Methods
Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations.
Results
The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations.
Conclusions
The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

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  • An empirical review on the resistance mechanisms of epidermal growth factor receptor inhibitors and predictive molecular biomarkers in colorectal cancer
    Sankha Bhattacharya
    Critical Reviews in Oncology/Hematology.2023; 183: 103916.     CrossRef
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Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
J Pathol Transl Med. 2020;54(5):411-418.   Published online July 21, 2020
DOI: https://doi.org/10.4132/jptm.2020.06.22
  • 6,892 View
  • 172 Download
  • 18 Web of Science
  • 21 Crossref
AbstractAbstract PDF
Background
High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites.
Methods
Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method.
Results
During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively.
Conclusions
Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

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  • Risk factors for cervical lymph node metastasis in oropharyngeal cancer and its impact on prognosis
    Li Zhang, Zhilin Li, Jing Wang, Chen Wang, Shuxin Wen
    Brazilian Journal of Otorhinolaryngology.2025; 91(2): 101520.     CrossRef
  • Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis
    Meimei Cui, Jinling Cheng, Huijuan Cheng, Ming Zhao, Dan Zhou, Min Zhang, Jingjing Jia, Limei Luo
    Archives of Oral Biology.2024; 157: 105830.     CrossRef
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    R. P. Ekanayaka, W. M. Tilakaratne
    Oral Diseases.2024;[Epub]     CrossRef
  • Longitudinal Screening for Oral High-Risk Non-HPV16 and Non-HPV18 Strains of Human Papillomavirus Reveals Increasing Prevalence among Adult and Pediatric Biorepository Samples: A Pilot Study
    Jordan Jacobs, Eugene Chon, Karl Kingsley
    Vaccines.2024; 12(8): 895.     CrossRef
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    Kyung-Jin Min, Yung-Taek Ouh, Sangrak Bae, Yong-Bae Ji, Jae-Kwan Lee, Jae-Weon Kim, Kwang-Jae Cho, Dong-Hun Im
    Vaccines.2024; 12(10): 1110.     CrossRef
  • Prevalence of human papilloma virus in head and neck mucous squamous cell carcinoma and genotypes by location: an observational study
    Emilie Uhlrich, Jerzy Klijanienko, Joey Martin, Emmanuelle Jeannot, Anne Vincent-Salomon, Paul Freneaux, Christophe Le Tourneau, Olivier Choussy, Antoine Dubray-Vautrin
    European Journal of Cancer Prevention.2024;[Epub]     CrossRef
  • High-risk HPV Does not Appear to be an Important Risk Factor for Sinonasal Carcinomas in Turkish Population: A Tertiary Center Experience
    Evsen Apaydin Arikan, Levent Aydemir, Murat Ulusan, Dilek Yilmazbayhan, Yasemin Ozluk
    International Journal of Surgical Pathology.2023; 31(2): 124.     CrossRef
  • Practical Application of Circulating Tumor-Related DNA of Human Papillomavirus in Liquid Biopsy to Evaluate the Molecular Response in Patients with Oropharyngeal Cancer
    Agnieszka M. Mazurek, Tomasz W. Rutkowski
    Cancers.2023; 15(4): 1047.     CrossRef
  • The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma
    Seyed Keybud Katirachi, Mathias Peter Grønlund, Kathrine Kronberg Jakobsen, Christian Grønhøj, Christian von Buchwald
    Viruses.2023; 15(2): 451.     CrossRef
  • The Protective Role of Cranberries and Blueberries in Oral Cancer
    César Esquivel-Chirino, Mario Augusto Bolaños-Carrillo, Daniela Carmona-Ruiz, Ambar Lopéz-Macay, Fernando Hernández-Sánchez, Delina Montés-Sánchez, Montserrat Escuadra-Landeros, Luis Alberto Gaitán-Cepeda, Silvia Maldonado-Frías, Beatriz Raquel Yáñez-Ocam
    Plants.2023; 12(12): 2330.     CrossRef
  • Unusual cases of sinonasal malignancies: a letter to the editor on HPV-positive sinonasal squamous cell carcinomas
    Benedicte Bitsch Lauritzen, Sannia Sjöstedt, Jakob Myllerup Jensen, Katalin Kiss, Christian von Buchwald
    Acta Oncologica.2023; 62(6): 608.     CrossRef
  • Prevalence of human Papillomavirus associated oropharyngeal and oral squamous cell carcinoma in Asian countries: A systematic review and large-scale meta-analysis
    Yy Jean Tan, Ken Wong Siong Hou, Galvin Sim Siang Lin, Jasmine Lim Suk Wun, Wan Nor Amira Wan Ahmad Abdul Nasir, Lynn Wei Linn Ko
    Acta Marisiensis - Seria Medica.2023; 69(2): 77.     CrossRef
  • Top 100 most cited articles on human papillomavirus-induced head and neck squamous cell carcinoma: A bibliographic review
    Rahul Mohandas, Subhashree Mohapatra, Mary Oshin, ShubhangiSambhaji Hajare
    Journal of International Oral Health.2023; 15(3): 219.     CrossRef
  • Intracellular Toll-Like Receptors Modulate Adaptive Immune Responses in Head and Neck Cancer
    Sangeetha K. Nayanar, Deepak Roshan V.G., Shruthi Surendran, Göran Kjeller, Bengt Hasséus, Daniel Giglio
    Viral Immunology.2023; 36(10): 659.     CrossRef
  • Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea
    Hyun Woong Jun, Yong Bae Ji, Chang Myeon Song, Jae Kyung Myung, Hae Jin Park, Kyung Tae
    Frontiers in Surgery.2022;[Epub]     CrossRef
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    Oral Diseases.2022; 28(8): 2309.     CrossRef
  • Effect of National Oral Health Screening Program on the Risk of Head and Neck Cancer: A Korean National Population-Based
    Chan Woo Wee, Hyo-Jung Lee, Jae-Ryun Lee, Hyejin Lee, Min-Jeong Kwoen, Woo-Jin Jeong, Keun-Yong Eom
    Cancer Research and Treatment.2022; 54(3): 709.     CrossRef
  • Expression of p16, p53, and TLR9 in HPV-Associated Head and Neck Squamous Cell Carcinoma: Clinicopathological Correlations and Potential Prognostic Significance
    Shu Wang, Xibing Zhuang, Caixia Gao, Tiankui Qiao
    OncoTargets and Therapy.2021; Volume 14: 867.     CrossRef
  • The Role of Human Papilloma Virus in Dictating Outcomes in Head and Neck Squamous Cell Carcinoma
    Shane Brennan, Anne-Marie Baird, Esther O’Regan, Orla Sheils
    Frontiers in Molecular Biosciences.2021;[Epub]     CrossRef
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    Amanda F. Carlander, Kathrine K. Jakobsen, Simone K. Bendtsen, Martin Garset-Zamani, Charlotte D. Lynggaard, Jakob Schmidt Jensen, Christian Grønhøj, Christian von Buchwald
    Viruses.2021; 13(7): 1326.     CrossRef
  • The Prevalence of High- and Low-Risk Types of HPV in Patients with Squamous Cell Carcinoma of the Head and Neck, Patients with Chronic Tonsillitis, and Healthy Individuals Living in Poland
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    Diagnostics.2021; 11(12): 2180.     CrossRef
Human Papillomavirus Serologic Profiles of Selected Filipinos with Head and Neck Squamous Cell Carcinoma
Pia Marie Albano, Christianne Salvador, Jose Orosa, Sheryl Racelis, Modesty Leaño, Angelika Michel, John Donnie Ramos, Dana Holzinger, Michael Pawlita
J Pathol Transl Med. 2019;53(5):273-279.   Published online May 30, 2019
DOI: https://doi.org/10.4132/jptm.2019.05.12
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  • 1 Crossref
AbstractAbstract PDF
Background
The low prevalence of human papillomavirus (HPV) DNA and mRNA in biopsy samples of Filipinos with head and neck squamous cell carcinoma (HNSCC) has been reported previously. Here, the HPV serologic profiles of HNSCC cases were analyzed and associated with life-style and sexual practices.
Methods
Serum samples were collected between May 2012 and September 2013 from HNSCC patients (n = 22) in the northwest region of the Philippines, and age- and sex-matched clinically healthy controls. Antibodies to capsid and early oncoproteins of HPV16, 18, 31, 33, 45, 52, 58, 6, and 11 were analyzed using multiplex serology.
Results
Most of the cases were males with tumors of the oral cavity or larynx. Two of the cases tested positive for at least one of the early oncoproteins (E6, E7, E1, and/or E2) of HPV16, and 11 did not display reactivity to any HPV early or late oncoproteins. Of the controls, four tested positive for at least one of the HPV16 early oncoproteins, and 10 were non-reactive to all HPV types. Titers to HPV16 E6 or E7 of the seropositive cases and controls were considerably lower than those typically observed in economically developed countries.
Conclusions
The low HPV titers seen here are consistent with the results of molecular analyses for this population. Hence, the seropositivity of some of the HNSCC cases is likely an indication of prior exposure to the virus and not the presence of HPV-driven tumors.

Citations

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  • Social determinants of sex disparities in cancer in Southeast Asia
    Ma. Veronica Pia N. Arevalo, Ethan Angelo S. Maslog, Katherine Donatela Manlongat, Eric David B. Ornos, Imjai Chitapanarux, Michelle Ann B. Eala, Edward Christopher Dee
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The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma
Kyu Ho Kim, Lucia Kim, Suk Jin Choi, Jee Young Han, Joon Mee Kim, Young Chae Chu, Young-Mo Kim, In Suh Park, Joo Han Lim
Korean J Pathol. 2014;48(4):263-269.   Published online August 26, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.263
  • 7,682 View
  • 52 Download
  • 11 Crossref
AbstractAbstract PDF
Background

Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis.

Results

The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival.

Conclusions

These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

Citations

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  • Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma
    Yuxi Cheng, Zhengzheng Song, Xiaodan Fang, Zhangui Tang
    Clinical Epigenetics.2024;[Epub]     CrossRef
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    Samar M. Abdel Raouf, Taiseer R. Ibrahim, Lobna A. Abdelaziz, Mohamed I. Farid, Salem Y Mohamed
    Journal of Gastrointestinal Cancer.2021; 52(1): 90.     CrossRef
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    European Journal of Surgical Oncology.2020; 46(6): 1066.     CrossRef
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    Journal of Oral Pathology & Medicine.2018; 47(3): 240.     CrossRef
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    Cancer Cell International.2018;[Epub]     CrossRef
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    HuaNan Luo, Yuan Jiang, SiJing Ma, HuanHuan Chang, ChunXi Yi, Hui Cao, Ying Gao, HaiLi Guo, Jin Hou, Jing Yan, Ying Sheng, XiaoYong Ren
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Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma
Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim
Korean J Pathol. 2012;46(6):515-522.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515
  • 6,711 View
  • 46 Download
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AbstractAbstract PDF
Background

Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).

Methods

Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by in situ hybridization and amplification of the c-Met gene by fluorescence in situ hybridization.

Results

The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.

Conclusions

Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.

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Expressions of E-cadherin, Cortactin and MMP-9 in Pseudoepitheliomatous Hyperplasia and Squamous Cell Carcinoma of the Head and Neck: Their Relationships with Clinicopathologic Factors and Prognostic Implication
Tack Kune You, Kyoung Min Kim, Sang Jae Noh, Jun Sang Bae, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Ho Sung Park
Korean J Pathol. 2012;46(4):331-340.   Published online August 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.331
  • 7,791 View
  • 76 Download
  • 14 Crossref
AbstractAbstract PDF
Background

E-cadherin, cortactin, and matrix metalloproteinase (MMP)-9 have roles in tumor development or progression, but their expression has not been fully investigated in pseudoepitheliomatous hyperplasia (PEH) and squamous cell carcinoma (SCC) of the head and neck.

Methods

We evaluated the immunohistochemical expression of E-cadherin, cortactin, and MMP-9 in 29 cases of PEH and 97 cases of SCC. Additionally, we evaluated their relationship with clinicopathologic factors and prognostic implications in SCC.

Results

Thirty-five cases of SCC showed reduced expression of E-cadherin, whereas none of the PEH did. A total of 20 cases and 11 cases of SCC were immunoreactive for cortactin and MMP-9, respectively, whereas none of the PEH did. In SCC, reduced expression of E-cadherin was correlated with cortactin expression and invasion depth. Cortactin expression was correlated with differentiation, T classification, and recurrence and/or metastasis. MMP-9 expression was correlated with invasion depth. Cortactin expression was correlated with poor overall survival and relapse-free survival and it was an independent prognostic factor.

Conclusions

The reduced expression of E-cadherin and the expression of cortactin may be helpful for the differential diagnosis of PEH and SCC. Furthermore, cortactin expression in association with reduced E-cadherin expression is correlated with poor prognosis in SCC.

Citations

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Review Article
Basaloid Squamous Cell Carcinoma of the Upper Aerodigestive Tract.
Kyung Ja Cho
Korean J Pathol. 2010;44(1):1-8.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.1
  • 4,002 View
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AbstractAbstract PDF
Basaloid squamous cell carcinoma (BSCC) is an uncommon variant of squamous cell carcinoma (SCC), usually occurring in the larynx, hypopharynx, oropharynx and esophagus. BSCCs have been reported from various geographic areas, but esophageal BSCCs are more prevalent in Asia. The morphology of BSCC is quite characteristic, but BSCC occasionally needs to be differentiated from neuroendocrine carcinoma or adenoid cystic carcinoma. Human papillomavirus16-associated oropharyngeal SCC with poorly differentiated or basaloid features has recently been recognized as a new clinical entity with a different etiology and prognosis. Nonoropharyngeal BSCC appears to share etiologic factors, genetic alterations and an immunoprofile with conventional SCC of the upper aerodigestive tract. However, the divergent differentiation of BSCC into various non-basaloid, epithelial or mesenchymal elements suggests the participation of more mulipotential cells than in SCC. The biologic behavior of BSCC has been reported to be worse than or equal to that of SCC, yet the data including the increasing numbers of human papillomavirus-associated cases now require reanalysis. It is presently uncertain whether BSCC is a histogenetically or clinically unique disease entity.

Citations

Citations to this article as recorded by  
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