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Curioso PAB, Correia Neto IJ, Souza LLD, Santos EDM, Santos-Silva AR, Vargas PA, Lopes MA. Comparative analysis of clinicopathological characteristics in young and elderly patients with oral squamous cell carcinoma: a retrospective study in Northeastern Brazil. Braz Oral Res 2024; 38:e138. [PMID: 39775426 DOI: 10.1590/1807-3107bor-2024.vol38.0138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 09/16/2024] [Indexed: 01/11/2025] Open
Abstract
The aim of this study was to perform a clinicopathological analysis of oral squamous cell carcinoma (OSCC) in young patients from the northeast of Brazil and compare with elderly individuals. This retrospective study reviewed 104 OSCC cases from 2000 to 2015, focusing on patients under 40 and over 60 at diagnosis. Forty-two patients under 40 years old (40.38%) and 62 patients over 60 years old (59.62%) were analyzed using descriptive statistics, chi-square, and Fisher's exact tests for clinicopathological factors, and Kaplan-Meier and Cox models for survival and prognostics. Most of the patients were male, with younger patients having lower rates of smoking (45.24%) and alcohol use (28.57%) compared to older patients (82.30% and 40.32%, respectively). Younger patients had a higher prevalence of tongue cancer and smaller tumors but faced more compromised surgical margins, perineural invasion, local recurrence, regional metastasis, distant metastasis, and second primary tumors. Statistical findings highlighted age-related differences in clinicopathological features and indicated that despite similar overall survival rates, younger patients had a poorer prognosis related to local recurrences, regional recurrences, and second tumors. Perineural invasion emerged as an independent prognostic factor. The study suggests that younger OSCC patients require personalized management strategies to address their higher risk of adverse outcomes, with an emphasis on the prognostic significance of perineural invasion.
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Affiliation(s)
- Pedro Augusto Bulhões Curioso
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Dnepartment of Oral Diagnosis, Piracicaba, SP, Brazil
| | - Ivan José Correia Neto
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Dnepartment of Oral Diagnosis, Piracicaba, SP, Brazil
| | - Lucas Lacerda de Souza
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Dnepartment of Oral Diagnosis, Piracicaba, SP, Brazil
| | | | - Alan Roger Santos-Silva
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Dnepartment of Oral Diagnosis, Piracicaba, SP, Brazil
| | - Pablo Agustin Vargas
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Dnepartment of Oral Diagnosis, Piracicaba, SP, Brazil
| | - Marcio Ajudarte Lopes
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Dnepartment of Oral Diagnosis, Piracicaba, SP, Brazil
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Synergistic association between underweight and type 2 diabetes on the development of laryngeal cancer: a national population-based retrospective cohort study. BMC Cancer 2022; 22:345. [PMID: 35351050 PMCID: PMC8966305 DOI: 10.1186/s12885-022-09403-9] [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: 11/03/2021] [Accepted: 03/07/2022] [Indexed: 11/15/2022] Open
Abstract
Background Although cigarette smoking is the most significant risk factor for laryngeal cancer, other risk factors might also be associated with the development of laryngeal cancer. We investigated whether underweight and type 2 diabetes are associated with laryngeal cancer in a Korean population. Methods A total of 9,957,059 participants (≥20 years) without prior history of cancer who underwent a National Health Insurance Service health checkup in 2009 were followed up until December 31, 2018. Newly diagnosed laryngeal cancer was identified using claim data, and underweight was defined as body mass index (BMI) < 18.5 kg/m2. A Cox proportional-hazards models with multivariable adjustment were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs). Results During the median follow-up period of 8.3 years, 3504 cases of laryngeal cancer occurred. Underweight was associated with increased risk of laryngeal cancer after adjusting for potential confounders (HR: 1.43, 95% CI: 1.22–1.69) compared to those who were not underweight. Underweight and type 2 diabetes were synergistically associated with higher risk of laryngeal cancer (HR: 2.33, 95% CI: 1.54–3.51), compared to those without either condition. This relationship was stronger in those with an age < 65 years (HR: 3.33, 95% CI: 1.88–5.87) and alcohol consumption (HR: 2.72, 95% CI: 1.64–4.53). Conclusions These results suggest that underweight may be a significant risk factor for laryngeal cancer and that underweight and type 2 diabetes might synergistically increase the risk of laryngeal cancer.
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Laryngeal cancers in paediatric and young adult patients: epidemiology, biology and treatment. Curr Opin Otolaryngol Head Neck Surg 2021; 30:145-153. [PMID: 34740227 DOI: 10.1097/moo.0000000000000766] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE OF REVIEW The aim of thi study was to review the recent literature on epidemiology, biology and treatment of laryngeal cancer in paediatric and young adult patients. RECENT FINDINGS Epidemiological studies reported that 2-10% of patients with laryngeal cancer are younger than 40-year-old, while the prevalence of laryngeal cancer remains unknown in the paediatric population. The development of laryngeal cancer in young adults is multifactorial and may be linked to common carcinogens (tobacco and alcohol), occupational factors, laryngopharyngeal reflux, immunosuppression, human papillomavirus infection and genetic polymorphism. A substantial number of cohort studies reported a significant lower proportion of drinkers and smokers in young populations with laryngeal cancer, supporting the higher prevalence of chromosomal losses or abnormalities predisposing to cancer in this group. The development of laryngeal cancer in paediatric patients is strongly associated with genetic syndromes with DNA repair abnormalities. The pathological, clinical and survival outcome differences between young and old patient groups vary significantly between studies, depending on epidemiological, genetic features and therapeutic strategies used. SUMMARY Paediatric and adult populations with laryngeal cancer present different clinical, pathological and survival outcomes. In the adult population, the patient age at the time of disease development underlies genetic and etiological differences with different mutation patterns between young and old patients, the latter being more frequently individuals with a history of tobacco and alcohol abuse. The differences between age groups regarding stage of cancer at initial presentation, as well as clinical and survival outcomes, are unclear, which may be due to demographic, ethnicity and population genetic differences.
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Rodrigues-Fernandes CI, Arboleda LPA, Vargas PA, Lopes MA, Santos-Silva AR. Oral leukoplakia in adolescents: Report of a rare case and review of the literature. Oral Oncol 2021; 122:105565. [PMID: 34673455 DOI: 10.1016/j.oraloncology.2021.105565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 10/01/2021] [Accepted: 10/04/2021] [Indexed: 12/01/2022]
Abstract
The aim of this report was to describe a rare case of leukoplakia in a young patient without any risk factors for squamous cell carcinoma. An 18-year-old male patient presented with an asymptomatic white lesion on the right lateral border of the tongue. Microscopic examination of the excisional biopsy specimen displayed hyperkeratosis and acanthosis without epithelial dysplasia, which were consistent with the clinical diagnosis of oral leukoplakia. The patient is undergoing systematic and regular evaluation, and after 28 months of follow-up, no recurrence has been observed. This report showed that, although uncommon, adolescents and/or young adults can also be affected by oral potentially malignant disorders. Therefore, dentists should be aware of this condition to establish the proper diagnosis and management.
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Affiliation(s)
- Carla Isabelly Rodrigues-Fernandes
- Department of Oral Diagnosis, Semiology and Pathology Areas, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
| | - Lady Paola Aristizabal Arboleda
- Department of Oral Diagnosis, Semiology and Pathology Areas, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Pablo Agustin Vargas
- Department of Oral Diagnosis, Semiology and Pathology Areas, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil; Department of Oral Biology and Oral Pathology, University of Pretoria, Pretoria, South Africa
| | - Márcio Ajudarte Lopes
- Department of Oral Diagnosis, Semiology and Pathology Areas, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
| | - Alan Roger Santos-Silva
- Department of Oral Diagnosis, Semiology and Pathology Areas, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil
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Kabagenyi F, Otiti J, Namwagala J, Kamulegeya A, Kalungi S. A descriptive study of human papilloma virus in upper aero-digestive squamous cell carcinoma at Uganda cancer institute assessed by P16 immunohistochemistry. CANCERS OF THE HEAD & NECK 2020; 5:10. [PMID: 32864169 PMCID: PMC7450959 DOI: 10.1186/s41199-020-00057-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/29/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cancer burden in sub-Saharan Africa is on the rise with one-third of cancers estimated to be caused by infectious agents. Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy in sub-Saharan Africa and includes tumors in the Upper Aero-digestive Tract (UADT). The established risk factors are tobacco and alcohol exposure with a recent recognition of the role of Human Papilloma Virus (HPV). The HPV related HNC is seen predominantly in the oropharynx, presents at a younger age and has a better prognosis. With a rapidly increasing incidence of these cancers in the developed world, it was important to study HPV in HNC in Uganda. The HPV can be detected using P16 immunohistochemistry as a surrogate marker thus making it suitable for screening. The study aimed at establishing the presence of HPV and the commonly affected sites in UADT squamous cell carcinoma (SCC) at Uganda Cancer Institute (UCI) using P16 immunohistochemistry. METHODOLOGY This was a cross sectional study in which 59 patients with histologically proven SCC from the oral cavity, oropharynx, larynx and hypopharynx were recruited. These patients' demographics and clinical data were collected. Tissue sections from retrieved histology samples were stained by Haematoxylin and Eosin to reconfirm SCC. Subsequently, P16 expression was determined using P16 immunohistochemistry. RESULTS Seventy-one patients were enrolled and 59 patients with confirmed SCC of the sites of interest were analyzed. The majority (79.7%) of the participants were male and over 50 years. 59.3% were tobacco smokers, 66.1% used alcohol, 52.2% used both. Only 27.1% used none of the substances. Only 27.1% of the participants were HIV positive. Most of the tumors were in the larynx (37.3%) and 64.4% were overall TNM stage 4. The overall prevalence of HPV in UADT SCC at UCI was 20.3, 95%CI 10.9-32.8. The oropharynx had the highest prevalence (30.8%). CONCLUSION The prevalence of HPV in UADT SCC at UCI is significant at 20.3%. The most affected site, is the oropharynx. Vigilant HPV screening of these sites with confirmation where possible is recommended.
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Affiliation(s)
- Fiona Kabagenyi
- Department of Ear, Nose and Throat, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
| | - Jeff Otiti
- Department of Surgery, Uganda Cancer Institute, P.O. Box 3935, Kampala, Uganda
| | - Justine Namwagala
- Department of Ear, Nose and Throat, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
| | - Adriane Kamulegeya
- Department of Oro-maxillofacial Surgery, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
| | - Sam Kalungi
- Department of Pathology, Mulago National Referral Hospital, P.O. Box 7272, Kampala, Uganda
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Morais-Faria K, Palmier NR, de Lima Correia J, de Castro Júnior G, Dias RB, da Graça Pinto H, Lopes MA, Ribeiro ACP, Brandão TB, Santos-Silva AR. Young head and neck cancer patients are at increased risk of developing oral mucositis and trismus. Support Care Cancer 2020; 28:4345-4352. [PMID: 31912359 DOI: 10.1007/s00520-019-05241-x] [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: 04/03/2019] [Accepted: 12/10/2019] [Indexed: 12/26/2022]
Abstract
OBJECTIVES To evaluate cancer treatment-related toxicities in young head and neck cancer (HNC) patients. MATERIAL AND METHODS A total of 44 patients were included in the present retrospective cohort study, which was designed to access oral toxicities of cancer treatment in young (< 45 years of age, Group I, n = 22) and old (> 58 years of age, Group II, n = 22) HNC patients with similar tumor stage and treatment protocols. Oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis were assessed during days 7th, 21st, and 35th of head and neck radiotherapy (HNRT) according to previously validated scales (World Health Organization criteria and the National Cancer Institute and Common Terminology Criteria for Adverse Events version 4.0). RESULTS Patients from both groups showed high incidence and severity of oral toxicities by the end of the HNRT with OM (81.9% (Group I); 63.6% (Group II)) and xerostomia (72.6% (Group I); 77.2% (Group II)) being the most prevalent toxicities. No differences regarding xerostomia, dysphagia, dysgeusia, and radiodermatitis incidences or severity could be observed between groups. However, higher incidences and severity of OM at 21st and 35th fractions (odds ratio = 2.22 and 5.71, respectively) and trismus at 21st and 35th fractions (odds ratio = 6.17 and 14.5, respectively) were observed throughout the treatment in young patients when compared to older patients (p < 0.01 and p < 0.05, respectively). CONCLUSION Young HNC patients are more affected by cancer treatment-related OM and trismus despite the similarities in clinical staging and treatment protocols with elderly patients.
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Affiliation(s)
- Karina Morais-Faria
- Dental Oncology Service, Instituto do Câncer do Estado de São Paulo, ICESP-FMUSP, São Paulo, Brazil
| | - Natalia Rangel Palmier
- Oral Diagnosis Department, Semiology Area, Piracicaba Dental School, UNICAMP, 901, Av. Limeira, Areão, Piracicaba, São Paulo, 13414-903, Brazil
| | - Jaqueline de Lima Correia
- Oral Diagnosis Department, Semiology Area, Piracicaba Dental School, UNICAMP, 901, Av. Limeira, Areão, Piracicaba, São Paulo, 13414-903, Brazil
| | - Gilberto de Castro Júnior
- Clinical Oncology Service, São Paulo State Cancer Institute (ICESP), School of Medicine of the University of São Paulo, São Paulo, Brazil
| | - Reinaldo Brito Dias
- Department of Maxillofacial Surgery, Prosthesis and Traumatology, USP, São Paulo, Brazil
| | | | - Marcio Ajudarte Lopes
- Oral Diagnosis Department, Semiology Area, Piracicaba Dental School, UNICAMP, 901, Av. Limeira, Areão, Piracicaba, São Paulo, 13414-903, Brazil
| | | | - Thaís Bianca Brandão
- Dental Oncology Service, Instituto do Câncer do Estado de São Paulo, ICESP-FMUSP, São Paulo, Brazil
| | - Alan Roger Santos-Silva
- Dental Oncology Service, Instituto do Câncer do Estado de São Paulo, ICESP-FMUSP, São Paulo, Brazil. .,Oral Diagnosis Department, Semiology Area, Piracicaba Dental School, UNICAMP, 901, Av. Limeira, Areão, Piracicaba, São Paulo, 13414-903, Brazil.
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Shoffel-Havakuk H, O'Dell K, Johns MM, Reder L, Popova M, Halperin D, Feldberg E, Lahav Y. The rising rate of nonsmokers among laryngeal carcinoma patients: Are we facing a new disease? Laryngoscope 2019; 130:E108-E115. [PMID: 31090946 DOI: 10.1002/lary.28067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 03/29/2019] [Accepted: 04/23/2019] [Indexed: 11/06/2022]
Abstract
OBJECTIVES/HYPOTHESIS Laryngeal squamous cell carcinoma (SCC) is strongly associated with tobacco smoking. With the rising awareness of tobacco's adverse health effects, we have witnessed a global decrease in tobacco use. Nevertheless, laryngeal SCC remains prevalent and includes a subset of patients lacking the traditional risk factors. STUDY DESIGN A two-center retrospective cohort. METHODS Medical records of patients diagnosed with laryngeal SCC between 2009 and 2016 were reviewed. Data collected included demographics, smoking status, and tumor site. Patients who have never smoked were designated as nonsmokers. RESULTS The study included 330 patients with laryngeal SCC, of whom 75 (22.7%) were nonsmokers; this rate was relatively similar for each of the two institutions independently (21.9% and 25%). There were 285 patients with glottic SCC and 45 with supraglottic SCC. All nonsmoking patients in this cohort had glottic SCC, representing 26.3% (75/285) of the glottic SCC cases. The rate of female patients was significantly higher among nonsmokers. Of the patients with glottic SCC, females represented 25.3% (19/75) of the nonsmokers compared with 12.4% (26/210) of the smokers (P = .008). Mean age at diagnosis was 60.2 ± 17.5 years for nonsmoking glottic SCC patients and 63.6 ± 12.4 years for smokers (P = .280). However, nonsmokers demonstrated a distinct age distribution pattern. Nonsmoking females with glottic SCC demonstrated a bimodal age distribution pattern; 73.7% (14/19) were age <40 years or >75 years at diagnosis. CONCLUSIONS The rate of laryngeal SCC in nonsmokers is higher than what has previously been reported, representing a growing proportion, and may suggest a shift in etiology. Knowing that laryngeal SCC in nonsmokers predominantly affects the glottis, and that females and age extremities are more vulnerable, the traditional screening paradigm should be revised. LEVEL OF EVIDENCE 4 Laryngoscope, 130:E108-E115, 2020.
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Affiliation(s)
- Hagit Shoffel-Havakuk
- Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Karla O'Dell
- USC Voice Center, Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California
| | - Michael M Johns
- USC Voice Center, Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California
| | - Lindsay Reder
- Department of Otolaryngology, Head and Neck Surgery, Southern California Permanente Medical Group, Los Angeles, California
| | - Margarita Popova
- USC Voice Center, Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California
| | - Doron Halperin
- Department of Otolaryngology-Head and Neck Surgery, Kaplan Medical Center, Rehovot, and the Hebrew University, Jerusalem, Israel
| | - Edit Feldberg
- Department of Pathology, Kaplan Medical Center, Rehovot, and the Hebrew University, Jerusalem, Israel
| | - Yonatan Lahav
- Department of Otolaryngology-Head and Neck Surgery, Kaplan Medical Center, Rehovot, and the Hebrew University, Jerusalem, Israel
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Ambele MA, Pepper MS, van Heerden MB, van Heerden WFP. Molecular profile of tongue cancer in an 18-year-old female patient with no recognizable risk factor. Laryngoscope Investig Otolaryngol 2019; 4:310-313. [PMID: 31236464 PMCID: PMC6580056 DOI: 10.1002/lio2.266] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 02/28/2019] [Accepted: 04/09/2019] [Indexed: 12/27/2022] Open
Abstract
Background The occurrence of oral tongue squamous cell carcinoma (TSCC) in nonsmoking young adults, especially females, has increased. Yet, there is no clear evidence to support the existence of any single determinant. This case reports the presence of TSCC in an 18-year-old female with no recognizable risk factor for oral cancer development. Methods Histological examination and p16 immunohistochemistry were performed. Formalin-fixed paraffin-embedded sections were prepared from resected tissue and DNA was extracted for molecular OncoScan analysis. Results Histological and immunochemical analysis showed a p16-negative poorly differentiated keratinizing squamous cell carcinoma. OncoScan analysis of this tumor revealed a high confidence TP53:p.R213*:c.637C>T somatic mutation as well as copy number alterations of chromosomal regions including gains of 1p, 3q, 5p, 7p, 8p, 8q, 11q, 15q, 17q, and 20p, and losses on 1p, 3p, 18q, and 22q. Conclusion The TP53:p.R213*:c.637C>T mutation detected is indicative of a genetic predisposition to cancer and it is the first to be reported in TSCC in a nonsmoking young adult. Level of Evidence Case report.
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Affiliation(s)
- Melvin A Ambele
- Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences Institute for Cellular and Molecular Medicine, University of Pretoria Pretoria South Africa.,Department of Oral Pathology and Oral Biology School of Dentistry, Faculty of Health Sciences, University of Pretoria Pretoria South Africa
| | - Michael S Pepper
- Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences Institute for Cellular and Molecular Medicine, University of Pretoria Pretoria South Africa
| | - Marlene B van Heerden
- Department of Oral Pathology and Oral Biology School of Dentistry, Faculty of Health Sciences, University of Pretoria Pretoria South Africa
| | - Willie F P van Heerden
- Department of Oral Pathology and Oral Biology School of Dentistry, Faculty of Health Sciences, University of Pretoria Pretoria South Africa
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Liu X, Gao XL, Liang XH, Tang YL. The etiologic spectrum of head and neck squamous cell carcinoma in young patients. Oncotarget 2018; 7:66226-66238. [PMID: 27528225 PMCID: PMC5323229 DOI: 10.18632/oncotarget.11265] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 08/08/2016] [Indexed: 02/05/2023] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC), accounting for more than 80% in head and neck malignancies, kills thousands of people a year in the world. Despite most of the patients are more than 45, and the occurrences of head and neck cancer shows a decreasing trend; however, horribly, the incidences of the patients under 45 years old is steadily increasing. Hence, it's of vital importance to get more pathogen information about risk factors of HNSCC in children and young adults. This review outlines the etiologic spectrum of HNSCC, especially oral/oropharyngeal squamous cell carcinoma, in patients under 45 years of age.
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Affiliation(s)
- Xin Liu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Xiao-Lei Gao
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Xin-Hua Liang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Ya-Ling Tang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.,Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China
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Miranda Galvis M, Santos-Silva AR, Freitas Jardim J, Paiva Fonseca F, Lopes MA, de Almeida OP, Lópes Pinto CA, Kaminagakura E, Sawazaki-Calone I, Speight PM, Kowalski LP. Different patterns of expression of cell cycle control and local invasion-related proteins in oral squamous cell carcinoma affecting young patients. J Oral Pathol Med 2017. [DOI: 10.1111/jop.12601] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Marisol Miranda Galvis
- Department of Oral Diagnosis; Piracicaba Dental School; University of Campinas; Piracicaba Brazil
| | - Alan Roger Santos-Silva
- Department of Oral Diagnosis; Piracicaba Dental School; University of Campinas; Piracicaba Brazil
- Academic Unit of Oral and Maxillofacial Pathology; School of Clinical Dentistry; The University of Sheffield; Sheffield UK
| | - Juscelino Freitas Jardim
- Department of Oral Diagnosis; Piracicaba Dental School; University of Campinas; Piracicaba Brazil
| | - Felipe Paiva Fonseca
- Department of Oral Surgery and Pathology; School of Dentistry; Universidade Federal de Minas Gerais; Belo Horizonte Brazil
| | - Marcio A. Lopes
- Department of Oral Diagnosis; Piracicaba Dental School; University of Campinas; Piracicaba Brazil
| | - Oslei Paes de Almeida
- Department of Oral Diagnosis; Piracicaba Dental School; University of Campinas; Piracicaba Brazil
| | | | - Estela Kaminagakura
- Departament of Bioscience and Oral Diagnosis; Science and Technology Institute; Universidade Estadual Paulista; São José dos Campos Brazil
| | - Iris Sawazaki-Calone
- Oral Pathology and Oral Medicine; Dentistry School; Western Paraná State University; Cascavel Brazil
| | - Paul M. Speight
- Academic Unit of Oral and Maxillofacial Pathology; School of Clinical Dentistry; The University of Sheffield; Sheffield UK
| | - Luiz Paulo Kowalski
- Department of Head and Neck Surgery and Otorhinolaryngology; A.C. Camargo Cancer Center; São Paulo Brazil
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Kim J, Kim S, Albergotti WG, Choi PA, Kaplan DJ, Abberbock S, Johnson JT, Gildener-Leapman N. Selection of Ideal Candidates for Surgical Salvage of Head and Neck Squamous Cell Carcinoma: Effect of the Charlson-Age Comorbidity Index and Oncologic Characteristics on 1-Year Survival and Hospital Course. JAMA Otolaryngol Head Neck Surg 2016; 141:1059-65. [PMID: 26447790 DOI: 10.1001/jamaoto.2015.2158] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
IMPORTANCE Salvage surgery for recurrent head and neck squamous cell carcinoma (HNSCC) carries substantial risks of morbidity and mortality. Risk factors for death within 1 year should be better defined. OBJECTIVES To report preoperative oncologic prognostic factors predictive of short-term (<1 year) survival after salvage surgery in patients with HNSCC, to assess whether preoperative age and comorbidity predicts 1-year mortality, and to report hospital courses after salvage surgery within 1 year. DESIGN, SETTING, AND PARTICIPANTS A retrospective medical record review of 191 patients with recurrent HNSCC treated with salvage surgery from January 1, 2003, through December 31, 2013, at a tertiary academic center. INTERVENTIONS Surgical salvage of HNSCC (larynx, oral cavity, oropharynx, or hypopharynx) with curative intent. MAIN OUTCOMES AND MEASURES Primary outcome was survival 1 year after salvage surgery. Secondary outcomes were length of inpatient hospital stay, days of admissions, and skilled nursing facility disposition within 1 year stratified by survival status. Presalvage Charlson-Age Comorbidity Index (CACI) was calculated. Associations among CACI, oncologic risk factors, and risk of death within 1 year after salvage surgery are investigated using multivariable analysis. RESULTS Of 191 patients studied, 53 (27.7%) died within 1 year after salvage surgery. Patients who died within 1 year had more total inpatient admissions (P < .001), longer total length of stay (P < .001), and higher risk of discharge to a skilled nursing facility (P < .001) and spent 17.3% (interquartile range, 5.2-36.3) of their remaining days in the hospital. Independent risk factors for death within 1 year are CACI (relative risk [RR], 1.43; 95% CI, 1.16-1.76), primary T3 or T4 stage (RR, 2.34; 95% CI, 1.27-4.31), and disease-free interval of less than 6 months (RR, 5.61; 95% CI, 1.78-16.7). CONCLUSIONS AND RELEVANCE Medical comorbidity and age as measured by the CACI, primary T3 or T4 stage, and short disease-free interval must be considered in selecting patients ideal for surgical salvage surgery for recurrent HNSCC. Patients with these risk factors should be more strongly considered for palliative measures.
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Affiliation(s)
- JeeHong Kim
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Seungwon Kim
- Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - William G Albergotti
- Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Phillip A Choi
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Shira Abberbock
- Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
| | - Jonas T Johnson
- Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Neil Gildener-Leapman
- Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Albany Medical College, Albany, New York
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Reddy RB, Bhat AR, James BL, Govindan SV, Mathew R, DR R, Hedne N, Illiayaraja J, Kekatpure V, Khora SS, Hicks W, Tata P, Kuriakose MA, Suresh A. Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer. PLoS One 2016; 11:e0147409. [PMID: 26808319 PMCID: PMC4726811 DOI: 10.1371/journal.pone.0147409] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 01/04/2016] [Indexed: 01/18/2023] Open
Abstract
The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05). The meta-analysis approach adopted in this study has identified candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance.
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Affiliation(s)
- Ram Bhupal Reddy
- Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Division of Medical Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India
| | - Anupama Rajan Bhat
- Strand Life Sciences, Kirloskar Business Park, Bangalore, Karnataka, India
| | - Bonney Lee James
- Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
| | | | - Rohit Mathew
- Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
| | - Ravindra DR
- Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
| | - Naveen Hedne
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
| | - Jeyaram Illiayaraja
- Department of Clinical Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
| | - Vikram Kekatpure
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
| | - Samanta S. Khora
- Division of Medical Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India
| | - Wesley Hicks
- Department of Head and Neck/Plastic & Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo, New York, United States of America
- Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, New York, United States of America
| | - Pramila Tata
- Strand Life Sciences, Kirloskar Business Park, Bangalore, Karnataka, India
| | - Moni A. Kuriakose
- Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, New York, United States of America
| | - Amritha Suresh
- Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
- Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India
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Zheng G, Peng C, Jia X, Gu Y, Zhang Z, Deng Y, Wang C, Li N, Yin J, Liu X, Lu M, Tang H, He Z. ZEB1 transcriptionally regulated carbonic anhydrase 9 mediates the chemoresistance of tongue cancer via maintaining intracellular pH. Mol Cancer 2015; 14:84. [PMID: 25890268 PMCID: PMC4404088 DOI: 10.1186/s12943-015-0357-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 04/02/2015] [Indexed: 12/29/2022] Open
Abstract
Background Chemoresistance is a major obstacle in successfully treating cancers, and the mechanisms responsible for drug resistance are still far from understood. Carbonic anhydrase 9 (CA9) has been shown to be upregulated in the drug-resistant tongue cancer cell line Tca8113/PYM and to be associated with drug resistance. However, the mechanisms regulating CA9 expression and its role in drug resistance remain unclear. Methods Bioinformatic and experimental analysis involving ChIP and luciferase reporter assays were used to validate Zinc finger E-box-binding homeobox 1 (ZEB1) as a transcriptional regulator of CA9. Gene expression and protein levels were evaluated by quantitative RT-PCR and western blotting, respectively. Sensitivity to chemotherapy was examined using the MTS assay and Hoechst staining and analysis caspase-3 activity to evaluate changes in apoptosis. Intracellular pH (pHi) was measured using fluorescent pH-indicator BCECF-AM. Protein expression in patient tissue samples was examined by immunohistochemistry and survival of tongue cancer patients from which these samples were derived was also analyzed. Results ZEB1 bound to the promoter of CA9 to positively regulate CA9 expression in tongue cancer cells. Knockdown of CA9 using short interfering RNA (siRNA) abolished the chemoresistance resulting from ZEB1 overexpression in Tca8113 and SCC-25 cells, and CA9 overexpression attenuated chemosensitivity induced by ZEB1 knockdown in Tca8113/PYM cells. CA9 knockdown also prevented maintenance of pHi mediated by overexpression of ZEB1 in Tca8113 and SCC-25 cells following chemotherapy, associated with increased apoptosis and caspase-3 activation. Conversely, ectopic expression of CA9 suppressed decrease in pHi mediated by ZEB1 knockdown in Tca8113/PYM cells following chemotherapy, accompanied by decreased apoptosis and caspase-3 activation. Importantly, a positive correlation was observed between ZEB1 and CA9 protein expression in tongue cancer tissues, and expression of these proteins associated with a poor prognosis for patients. Conclusion Our finding that tumor cells regulate pHi in response to chemotherapy provides new insights into mechanisms of drug resistance during cancer treatment. Identification of the ZEB1–CA9 signaling axis as a biomarker of poor prognosis in tongue cancer will be valuable in future development of therapeutic strategies aimed at improving treatment efficacy, especially in terms of drug resistance associated with this disease.
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Affiliation(s)
- Guopei Zheng
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Cong Peng
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Xiaoting Jia
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Yixue Gu
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Zhijie Zhang
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Yingen Deng
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Chengkun Wang
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Nan Li
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Jiang Yin
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Xiaorong Liu
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Minying Lu
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
| | - Hailin Tang
- Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, East Dongfeng Road 651#, Guangzhou, 510060, Guangdong, China.
| | - Zhimin He
- Cancer Hospital and Cancer Research Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
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15
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Fonseca FP, Coletta RD, Azevedo MB, Prado Ribeiro AC, Pires Soubhia AM, Miyahara GI, Carlos R, Farthing P, Hunter KD, Speight PM, Vargas PA, Almeida OP, Lopes MA, Santos-Silva AR. Stromal myofibroblasts in squamous cell carcinoma of the tongue in young patients - a multicenter collaborative study. Oral Surg Oral Med Oral Pathol Oral Radiol 2014; 118:483-9. [PMID: 25240996 DOI: 10.1016/j.oooo.2014.07.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 07/11/2014] [Accepted: 07/21/2014] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The purpose of this study was to evaluate the presence of myofibroblasts, frequently associated with a more aggressive neoplastic behavior, in oral tongue squamous cell carcinoma (TSCC) of young patients and to compare with the distribution observed in older patients. STUDY DESIGN Tumor samples from 29 patients younger than 40 years old affected by TSCC were retrieved and investigated for the presence of stromal myofibroblasts by immunohistochemical reactions against α smooth muscle actin, and the results obtained were compared to TSCC cases affecting older patients. RESULTS No positive reaction could be found in the stromal areas devoid of neoplastic tissue, whereas myofibroblasts were present in 58.6% of the lesions in young patients and in 75.9% of the older ones. No significant difference was found when comparing the invasive front and the overall stroma of both groups, and no correlation could be obtained with stromal α smooth muscle actin expression, higher tumor grades or clinical stage (P > .05). CONCLUSION There was no significant difference between the presence of stromal myofibroblasts of TSCC affecting young and old individuals.
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Affiliation(s)
- Felipe Paiva Fonseca
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil
| | - Ricardo Della Coletta
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil
| | - Marina Barbosa Azevedo
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil
| | - Ana Carolina Prado Ribeiro
- Service of Dental Oncology, Instituto do Cancer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
| | - Ana Maria Pires Soubhia
- Department of Pathology and Clinical Propedeutic, Univ Estadual Paulista (UNESP), Araçatuba Dental School, Araçatuba, Brazil
| | - Glauco Issamu Miyahara
- Department of Pathology and Clinical Propedeutic, Univ Estadual Paulista (UNESP), Araçatuba Dental School, Araçatuba, Brazil
| | - Roman Carlos
- Centro Clinico de Cabeza y Cuello, Guatemala City, Guatemala
| | - Paula Farthing
- Academic Unit of Oral and Maxillofacial Pathology, The University of Sheffield, School of Clinical Dentistry, Sheffield, UK
| | - Keith D Hunter
- Academic Unit of Oral and Maxillofacial Pathology, The University of Sheffield, School of Clinical Dentistry, Sheffield, UK
| | - Paul M Speight
- Academic Unit of Oral and Maxillofacial Pathology, The University of Sheffield, School of Clinical Dentistry, Sheffield, UK
| | - Pablo Agustin Vargas
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil
| | - Oslei Paes Almeida
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil
| | - Marcio Ajudarte Lopes
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil
| | - Alan Roger Santos-Silva
- Department of Oral Diagnosis, University of Campinas (UNICAMP), Piracicaba Dental School, Piracicaba, Brazil.
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Woods RSR, O’Regan EM, Kennedy S, Martin C, O’Leary JJ, Timon C. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review. World J Clin Cases 2014; 2:172-193. [PMID: 24945004 PMCID: PMC4061306 DOI: 10.12998/wjcc.v2.i6.172] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 04/21/2014] [Accepted: 05/19/2014] [Indexed: 02/05/2023] Open
Abstract
Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.
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Chun SH, Jung CK, Won HS, Kang JH, Kim YS, Kim MS. Divergence of P53, PTEN, PI3K, Akt and mTOR expression in tonsillar cancer. Head Neck 2014; 37:636-43. [DOI: 10.1002/hed.23643] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 12/18/2013] [Accepted: 02/21/2014] [Indexed: 02/06/2023] Open
Affiliation(s)
- Sang Hoon Chun
- Division of Medical Oncology; Department of Internal Medicine; Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Republic of Korea
| | - Chan-Kwon Jung
- Department of Hospital Pathology; Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Republic of Korea
| | - Hye Sung Won
- Division of Medical Oncology; Department of Internal Medicine; Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Republic of Korea
| | - Jin-Hyoung Kang
- Division of Medical Oncology; Department of Internal Medicine; Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Republic of Korea
| | - Yeon-Sil Kim
- Department of Radiation Oncology; Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Republic of Korea
| | - Min-Sik Kim
- Department of Otorhinolaryngology; Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Republic of Korea
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Tongue squamous cell carcinoma in young nonsmoking and nondrinking patients: 3 clinical cases of orthodontic interest. Am J Orthod Dentofacial Orthop 2014; 145:103-7. [PMID: 24373660 DOI: 10.1016/j.ajodo.2012.09.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2011] [Revised: 09/01/2012] [Accepted: 09/01/2012] [Indexed: 11/23/2022]
Abstract
Oral squamous cell carcinoma traditionally affects older men who smoke and drink. A change in this profile has been reported because of an increased incidence in young nonsmoking and nondrinking patients. The purpose of this article was to describe a series of young nonsmoking and nondrinking patients diagnosed with tongue squamous cell carcinoma who had recently received orthodontic treatment or evaluation. Details regarding diagnosis, treatment, follow-up, and disease evolution are presented, with a review of the pertinent literature. Orthodontists often treat young adults, who have frequent dental appointments and long-term follow-ups. Thus, practitioners should pay special attention to young patients during dental consultations, since the incidence of malignant oral lesions in this segment of the population seems to be increasing.
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Troeltzsch M, Knösel T, Eichinger C, Probst F, Troeltzsch M, Woodlock T, Mast G, Ehrenfeld M, Otto S. Clinicopathologic features of oral squamous cell carcinoma: do they vary in different age groups? J Oral Maxillofac Surg 2014; 72:1291-300. [PMID: 24813775 DOI: 10.1016/j.joms.2014.01.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Revised: 01/06/2014] [Accepted: 01/09/2014] [Indexed: 01/09/2023]
Abstract
PURPOSE To analyze clinicopathologic parameters of oral squamous cell carcinoma (OSCC) in different age groups. We hypothesized that clinical and pathologic parameters of OSCCs will vary in different age groups. MATERIALS AND METHODS A retrospective cohort study was performed. All patients who were treated for a primary manifestation of OSCC at a single institution from 2001 to 2012 were reviewed and allocated to predefined age groups (predictor variable) as follows: young (≤40 years), middle-aged (40-80 years), and very elderly (≥80 years). The following outcome variables were recorded: demographic parameters, classic risk factors, tumor location and size, neck node involvement, histopathologic and therapeutic details, and association with human papillomavirus (HPV). The descriptive statistics were computed. Parametric and nonparametric tests were used for additional analysis. The significance level was set at P < .05. RESULTS We reviewed 739 patients and identified 11 (1.4%) young (mean age 34.2 ± 2.8 years) and 17 (2.3%) very elderly patients (mean age 83.1 ± 1.2 years). The predilection site for OSCC was the oral tongue (63%) in young patients, the floor of the mouth (52%) in middle-aged patients, and the alveolar process (60%) in very elderly patients. One patient in the young group (9%) and 8 patients in the very elderly group (47%) had been exposed to risk factors; however, all of the examined middle-aged patients had had such exposure. The association of OSCC with HPV was distributed equally among the age groups. No age-related differences in the histopathologic parameters of OSCC were found. CONCLUSIONS The features of OSCC that vary at different ages are the anatomic predilection site and the association with classic risk factors. HPV was not an age-related independent risk factor for OSCC development in the present study.
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Affiliation(s)
- Matthias Troeltzsch
- Resident, Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany.
| | - Thomas Knösel
- Consultant, Department of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Christina Eichinger
- Resident, Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Florian Probst
- Resident, Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Markus Troeltzsch
- Resident, Department of Oral and Maxillofacial Surgery, University of Göttingen, Göttingen, Germany
| | - Timothy Woodlock
- Medical Oncologist, Department of Medicine, Unity Health System and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
| | - Gerson Mast
- Consultant, Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Michael Ehrenfeld
- Professor and Chair, Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Sven Otto
- Consultant, Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany
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Bascones-Martínez A, Rodríguez-Gutierrez C, Rodríguez-Gómez E, Gil-Montoya JA, Gómez-Font R, González-Moles MÁ. Evaluation of p53, caspase-3, Bcl-2, and Ki-67 markers in oral squamous cell carcinoma and premalignant epithelium in a sample from Alava Province (Spain). Med Oral Patol Oral Cir Bucal 2013; 18:e846-50. [PMID: 23722133 PMCID: PMC3854075 DOI: 10.4317/medoral.18901] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 03/08/2013] [Indexed: 01/10/2023] Open
Abstract
Objectives: The objective of this study was to determine whether alterations in the expression of p53, caspase-3 Bcl-2, and ki-67 appear early in premalignant oral epithelium and show clonal behavior.
Study Design: Samples from 41 tumors with their adjacent non-tumor epithelia were immunohistochemically analyzed using monoclonal antibodies that recognize p53, caspase-3, Bcl-2, and Ki-67
Results: A statistically significant association was found between the expression in tumor and adjacent epithelium of p53, caspase-3, and Bcl-2 but not of k-67. A significant association was observed between the expression of ki-67 and p53 in both localizations. In non-tumor (premalignant) epithelium samples, there was a significant inverse relationship between the expressions of p53 and caspase-3 and a significant direct relationship between the expressions of p53 and Bcl-2.
Conclusions: Alterations in these proteins appear to operate in combination with premalignant epithelia to create hyperproliferative cell states that favor the acquisition of summative oncogenic errors that confer invasive capacity.
Key words:Cell cycle, apoptosis, p53, caspase-3, Bcl-2, Ki-67.
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Affiliation(s)
- Antonio Bascones-Martínez
- Department of Medicine and Bucofacial Surgery, Dental School, Complutense University of Madrid, Plaza Ramón y Cajal 3, Ciudad Universitaria, 28040-Madrid, Spain,
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An analysis of the epidemiological and etiological factors of oral tumors of young adults in a Central-Eastern European population. Pathol Oncol Res 2013; 19:353-63. [PMID: 23645516 DOI: 10.1007/s12253-013-9628-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Accepted: 03/18/2013] [Indexed: 01/27/2023]
Abstract
The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a doctor. The study is made difficult by incomparable patient selection criteria as well as by the question of the intraoral localisation of tumors as an independent risk factor.
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Differentiation of branchial cleft cysts and malignant cystic adenopathy of pharyngeal origin. AJR Am J Roentgenol 2012; 199:W216-21. [PMID: 22826424 DOI: 10.2214/ajr.11.8120] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVE There is an increasing incidence of head and neck cancers that present as neck masses in a nonsmoking nondrinking population. These masses can be confused with benign cystic neck masses. The purpose of this study was to determine imaging criteria to differentiate benign lateral neck cysts from malignant cystic adenopathy. MATERIALS AND METHODS A retrospective analysis of patients who underwent contrast-enhanced neck CT between July 2003 and July 2011 was performed. Patients were diagnosed with either a branchial cleft cyst or pharyngeal squamous cell cancer. Each examination was reviewed by a neuroradiologist, and, for each cyst or cystic lymph node, the anatomic level in the neck, dimensions, wall thickness, septations, homogeneity, extracapsular spread, calcifications, and fat stranding were recorded. Data analysis was performed using Student t tests and chi-square tests. RESULTS Twenty-one patients with branchial cleft cysts and 29 patients with squamous cell carcinoma met the inclusion criteria. Significant differences between the groups were found with regard to size, homogeneity, and extracapsular spread. Branchial cleft cysts were found to be larger on the long axis (p < 0.001), short axis (p < 0.001), and height (p < 0.001). They were less likely to have extracapsular spread (p = 0.044) or septations (p = 0.059) and more likely to be homogeneous (p < 0.001). CONCLUSION Misdiagnosis of malignant cysts in the neck may lead to delay in diagnosis, a violated neck, tumor spillage, and spread. Differences in radiographic criteria can guide clinical decision making in the patient with a neck mass. However, fine-needle aspiration may be necessary to confirm the diagnosis.
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van Monsjou HS, Lopez-Yurda MI, Hauptmann M, van den Brekel MWM, Balm AJM, Wreesmann VB. Oral and oropharyngeal squamous cell carcinoma in young patients: The Netherlands Cancer Institute experience. Head Neck 2012; 35:94-102. [DOI: 10.1002/hed.22935] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/15/2011] [Indexed: 12/29/2022] Open
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Lu M, Liu Z, Yu H, Wang LE, Li G, Sturgis EM, Johnson DG, Wei Q. Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck. Mol Carcinog 2012; 51 Suppl 1:E132-41. [PMID: 22344756 DOI: 10.1002/mc.21882] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Revised: 01/04/2012] [Accepted: 01/18/2012] [Indexed: 11/11/2022]
Abstract
Deregulated expression of most members of the E2F family has been detected in many human cancers. We examined the association of common single nucleotide polymorphisms (SNPs) of E2F transcription factors 1 and 2 (E2F1 and E2F2) with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,096 SCCHN patients and 1,090 cancer-free controls. We genotyped 10 selected SNPs in E2F1 and E2F2, including those at the near 5'-untranslated region (UTR), microRNA (miRNA)-binding sites at the near 3'-UTR and tagSNPs according to bioinformatics analysis. Although none of the selected SNPs alone was significantly associated with risk of SCCHN, there was a statistically significantly increased risk of SCCHN associated with the combined risk genotypes (i.e., rs3213182 AA, rs3213183 GG, rs3213180 GG, rs321318121 GG, rs2742976 GT+TT, rs6667575 GA+AA, rs3218203 CC, rs3218148 AA, rs3218211 CC, and rs3218123 GT+TT). Compared with those with 0-4 risk genotypes, an increased risk was observed for those who carried 5-8 risk genotypes (adjusted OR = 1.04; 95% CI = 0.86-1.26) and 9-10 risk genotypes (adjusted OR = 1.62; 95% CI = 1.14-2.30) in a dose-response manner (P = 0.045). Furthermore, the joint effect was more pronounced among patients with oropharyngeal cancer, younger adults (≤57 yr old), men, non-smokers, non-drinkers, and individuals with family history of cancer in first-degree relatives. Additionally, we also observed that those with 5-10 risk genotypes had an earlier SCCHN onset than those with 0-4 risk genotypes, particularly for non-smokers and/or non-drinkers. We concluded that E2F1 and E2F2 genetic variants may jointly play important roles in head and neck carcinogenesis.
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Affiliation(s)
- Meixia Lu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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van Monsjou H, van Velthuysen M, van den Brekel M, Jordanova E, Melief C, Balm A. Human papillomavirus status in young patients with head and neck squamous cell carcinoma. Int J Cancer 2011; 130:1806-12. [DOI: 10.1002/ijc.26195] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2010] [Accepted: 05/02/2011] [Indexed: 01/11/2023]
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[A case of maxillary sinus carcinoma of a 24-year-old man, holistic aspects of care]. Otolaryngol Pol 2011; 65:122-7. [PMID: 21735668 DOI: 10.1016/s0030-6657(11)70641-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The aim of this study is to report a carcinoma affecting the maxillary sinus of a 24-years old man. Malignant tumors of the nasal cavity and paranasal sinuses are rare and a very heterogeneous group of tumors. The most common is a squamous cell carcinoma. Sinonasal malignances usually present as a difficult diagnostic and therapeutic problem. The treatment depended on location, extension and histology of the tumor, clinical condition and the patient desire. It consisted of surgery, RT, surgery and postoperatory R, and concurrent QT and RT. The treatment should be assessed individually for each patient. The treatment of patients with paranasal neoplasms requires a multidisciplinary cooperation. High quality care requires the preparation of a team of professionals dedicated to their work. We observe generally human trends to restore well being in difficult situation. Patients transform the information about them or change the values system. Psychooncological help in this field reinforces natural mechanism of restoring well being, increasing positive emotions and patient's own activity.
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Sun L, Yao Y, Liu B, Lin Z, Lin L, Yang M, Zhang W, Chen W, Pan C, Liu Q, Song E, Li J. MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting BMI1. Oncogene 2011; 31:432-45. [PMID: 21725369 DOI: 10.1038/onc.2011.263] [Citation(s) in RCA: 213] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Chemotherapy has been reported to induce epithelial-mesenchymal transition (EMT) in tumor cells, which is a critical step in the process of metastasis leading to cancer spreading and treatment failure. However, the underlying mechanisms of chemotherapy-induced EMT remain unclear, and the involvement of microRNAs (miRNA) in this process is poorly understood. To address these questions, we established stable chemotherapy-resistant tongue squamous cell carcinoma (TSCC) cell lines CAL27-res and SCC25-res by exposing the parental CAL27 and SCC25 lines to escalating concentrations of cisplatin for 6 months. CAL27-res and SCC25-res cells displayed mesenchymal features with enhanced invasiveness and motility. MiRNA microarray illustrated that miR-200b and miR-15b were the most significantly downregulated microRNAs in CAL27-res cells. Ectopic expression of miR-200b and miR-15b with miRNA mimics effectively reversed the phenotype of EMT in CAL27-res and SCC25-res cells, and sensitized them to chemotherapy, but inhibition of miR-200b and miR-15b in the sensitive lines with anti-sense oligonucleotides induced EMT and conferred chemoresistance. Retrieving the expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a target for miR-200b and miR-15b, in the presence of the miRNA mimics by transfecting CAL27-res cells with pcDNA3.1-BMI1-carrying mutated seed sequences of miR-200b or miR-15b at its 3'-UTR recapitulated chemotherapy-induced EMT. In vivo, enforced miR-200b or miR-15b expression suppressed metastasis of TSCC xenografts established by CAL27-res cells. Clinically, reduced miR-200b or miR-15b expression was associated with chemotherapeutic resistance in TSCCs and poor patient survival. Our data suggest that reduced expression of miR-200b and miR-15b underscores the mechanisms of chemotherapy-induced EMT in TSCC, and may serve as therapeutic targets to reverse chemotherapy resistance in tongue cancers.
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Affiliation(s)
- L Sun
- Department of Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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