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Staibano P, Au M, Xie M, Gupta MK, Young JEMT, Zhang H. Return to work and self-reported swallowing following transoral robotic surgery for early-stage oropharyngeal squamous cell carcinoma: A retrospective cohort study. Oral Oncol 2024; 159:107033. [PMID: 39278148 DOI: 10.1016/j.oraloncology.2024.107033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/28/2024] [Accepted: 09/09/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND Treatment de-intensification, including transoral robotic surgery (TORS), may outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Early return to work (RTW) improves quality of life in oncology patients. Our objective was to compare the RTW time in OPSCC patients undergoing primary TORS or chemoradiotherapy (CRT). We investigated the role of treatment modality on self-reported swallowing function. METHODS All patients were adults diagnosed with early-stage (T1-2, N0-2) OPSCC and treated via primary TORS or CRT. We performed 1:1 exact case matching based on tumor stage and subsite. We collected RTW outcomes for all patients. We also reported MD Anderson Dysphagia Index (MDADI) scores up to 24 months from the end of treatment. We performed statistical analyses and comparison of RTW and MDADI outcomes based on treatment group. RESULTS Overall, 26 patients undergoing primary TORS and 25 undergoing primary CRT were included. We found a significant improvement in RTW in TORS patients compared to CRT (TORS: 54 days (1.8 months), IQR: 30.8; CRT: 164 days (5.4 months), IQR: 109; W=587, p = 9.28e-08) independent of HPV status, tonsillar subsite, and radiotherapy alone. Primary TORS had a 16.2-fold (95 % CI: 5.78-45.5) higher likelihood of returning to work than primary CRT patients. Primary TORS also had better MDADI scores within two years of treatment. CONCLUSIONS In OPSCC, primary TORS accelerated RTW and improved swallowing when compared to primary CRT. The potential economic advantage of returning to work sooner should be discussed when reviewing treatment options with patients.
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Affiliation(s)
- Phillip Staibano
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
| | - Michael Au
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Michael Xie
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Michael K Gupta
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - James Edward Massey Ted Young
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Han Zhang
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
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Cabibi D, Giannone AG, Quattrocchi A, Lo Coco R, Formisano E, Porcasi R, Benfante V, Comelli A, Capra G. High-Risk HPV CISH Detection in Cervical Biopsies with Weak and/or Focal p16 Immunohistochemical Positivity. Int J Mol Sci 2024; 25:5354. [PMID: 38791395 PMCID: PMC11121605 DOI: 10.3390/ijms25105354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/19/2024] [Accepted: 05/10/2024] [Indexed: 05/26/2024] Open
Abstract
In cervical biopsies, for diagnosis of Human Papilloma Virus (HPV) related conditions, the immunohistochemical staining for p16 has a diagnostic value only if diffusely and strongly positive, pattern named "block-like". "Weak and/or focal (w/f) p16 expression" is commonly considered nonspecific. In our previous study, we demonstrated the presence of high-risk HPV (hrHPV) DNA by LiPa method in biopsies showing w/f p16 positivity. The aim of the present study was to investigate the presence of hrHPV-DNA by CISH in the areas showing w/f p16 expression. We assessed the presence of hrHPV16, 18, 31, 33, 51 by CISH in a group of 20 cervical biopsies showing w/f p16 expression, some with increased Ki67, and in 10 cases of block-like expression, employed as control. The immunohistochemical p16 expression was also assessed by digital pathology. hrHPV-CISH nuclear positivity was encountered in 12/20 cases of w/f p16 expression (60%). Different patterns of nuclear positivity were identified, classified as punctate, diffuse and mixed, with different epithelial distributions. Our results, albeit in a limited casuistry, show the presence of HPV in an integrated status highlighted by CISH in w/f p16 positive cases. This could suggest the necessity of a careful follow-up of the patients with "weak" and/or "focal" immunohistochemical patterns of p16, mainly in cases of increased Ki67 cell proliferation index, supplemented with molecular biology examinations.
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Affiliation(s)
- Daniela Cabibi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Antonino Giulio Giannone
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Alberto Quattrocchi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Roberta Lo Coco
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Eleonora Formisano
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Rossana Porcasi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Viviana Benfante
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy
| | - Albert Comelli
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy
| | - Giuseppina Capra
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
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Midorikawa S, Mizukami H, Kudoh K, Takeuchi Y, Sasaki T, Kushibiki H, Wang Z, Itakura Y, Murakami K, Kudo N, Nagaki T, Wakasa T, Nakamura Y, Matsubara A. Diabetes can increase the prevalence of EBV infection and worsen the prognosis of nasopharyngeal carcinoma. Pathology 2024; 56:65-74. [PMID: 38071160 DOI: 10.1016/j.pathol.2023.09.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 09/13/2023] [Accepted: 09/27/2023] [Indexed: 01/24/2024]
Abstract
Epstein‒Barr virus (EBV) infection is a primary oncogenic factor of nasopharyngeal carcinoma (NPC) that elicits epithelial-mesenchymal transition (EMT). Although diabetic patients are more susceptible to various infectious diseases, the pathological association with virus-related NPC has not yet been clarified. Herein, we evaluated the influence of diabetes on the clinicopathological changes of 70 patients with NPC. Disease-specific survival (DSS) modified by viral infection was also analysed. The proportion of NPC patients with diabetes was 32.9% (23/70 cases), and 91.3% (21/23 cases) were infected with EBV detected by EBER-I in situ hybridisation. NPC with diabetes showed an effect on EMT evaluated by immunostaining for E-cadherin and vimentin, which was correlated with HbA1c levels. Receiver operating characteristic (ROC) curve analysis determined a HbA1c level of 6.5% as the cut-off value for primary disease death at 2 years [area under the curve (AUC) 0.76; sensitivity 0.64; and specificity 0.81]. High HbA1c levels (≥6.5%) significantly increased the number of lymph node metastases in NPC compared to low HbA1c levels (<6.5%, p<0.01). Diabetic NPC patients had a significantly poorer prognosis than all non-diabetic patients (DSS, 72 months vs not reached, p<0.05). Diabetic EBV-positive NPC patients had a significantly poorer prognosis than non-diabetic EBV-positive patients (DSS, 35 months vs not reached, p<0.01). Multivariate analysis using the Cox proportional hazards model also suggested that HbA1c ≥6.5% was a significant factor in poor prognosis, with a hazard ratio of 6.84 (p<0.05). Collectively, our results revealed for the first time a high prevalence of EBV infection, poor prognosis and the importance of proper glycaemic control in diabetic NPC patients.
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Affiliation(s)
- Shin Midorikawa
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan; Department of Otolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hiroki Mizukami
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
| | - Kazuhiro Kudoh
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Yuki Takeuchi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Takanori Sasaki
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hanae Kushibiki
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Zhenchao Wang
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Yuko Itakura
- Department of Pathology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan
| | - Kotaro Murakami
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Naomi Kudo
- Department of Otolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Takahiko Nagaki
- Department of Otolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Tomoko Wakasa
- Department of Diagnostic Pathology, Kindai University Nara Hospital, Nara, Japan
| | - Yasuhiro Nakamura
- Division of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
| | - Atsushi Matsubara
- Department of Otolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
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Murphy RM, Tasoulas J, Porrello A, Carper MB, Tsai YH, Coffey AR, Kumar S, Zeng PYF, Schrank TP, Midkiff BR, Cohen S, Salazar AH, Hayward MC, Hayes DN, Olshan A, Gupta GP, Nichols AC, Yarbrough WG, Pecot CV, Amelio AL. Tumor Cell Extrinsic Synaptogyrin 3 Expression as a Diagnostic and Prognostic Biomarker in Head and Neck Cancer. CANCER RESEARCH COMMUNICATIONS 2022; 2:987-1004. [PMID: 36148399 PMCID: PMC9491693 DOI: 10.1158/2767-9764.crc-21-0135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 04/15/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022]
Abstract
Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV) yet biomarkers for stratifying oropharyngeal head and neck squamous cell carcinoma (HNSC) patient risk are limited. We used immunogenomics to identify differentially expressed genes in immune cells of HPV(+) and HPV(-) squamous carcinomas. Candidate genes were tested in clinical specimens using both quantitative RT-PCR and IHC and validated by IHC using the Carolina Head and Neck Cancer Study (CHANCE) tissue microarray of HNSC cases. We performed multiplex immunofluorescent staining to confirm expression within the immune cells of HPV(+) tumors, receiver operating characteristic (ROC) curve analyses, and assessed survival outcomes. The neuronal gene Synaptogyrin-3 (SYNGR3) is robustly expressed in immune cells of HPV(+) squamous cancers. Multiplex immunostaining and single cell RNA-seq analyses confirmed SYNGR3 expression in T cells, but also unexpectedly in B cells of HPV(+) tumors. ROC curve analyses revealed that combining SYNGR3 and p16 provides more sensitivity and specificity for HPV detection compared to p16 IHC alone. SYNGR3-high HNSC patients have significantly better prognosis with five-year OS and DSS rates of 60% and 71%, respectively. Moreover, combining p16 localization and SYNGR3 expression can further risk stratify HPV(+) patients such that high cytoplasmic, low nuclear p16 do significantly worse (Hazard Ratio, 8.6; P = 0.032) compared to patients with high cytoplasmic, high nuclear p16. SYNGR3 expression in T and B cells is associated with HPV status and enhanced survival outcomes of HNSC patients.
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Affiliation(s)
- Ryan M. Murphy
- Graduate Curriculum in Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jason Tasoulas
- Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Alessandro Porrello
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Miranda B. Carper
- Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Yi-Hsuan Tsai
- Bioinformatics Core, Lineberger Comprehensive Cancer Center, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Alisha R. Coffey
- Bioinformatics Core, Lineberger Comprehensive Cancer Center, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Sunil Kumar
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Technology Development, Naveris Inc., Natick, Massachusetts
| | - Peter YF. Zeng
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada
| | - Travis P. Schrank
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Bentley R. Midkiff
- Pathology Services Core, Lineberger Comprehensive Cancer Center, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Stephanie Cohen
- Pathology Services Core, Lineberger Comprehensive Cancer Center, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Ashley H. Salazar
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Michele C. Hayward
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - D. Neil Hayes
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Center for Cancer Research, University of Tennessee Health Sciences, Memphis, Tennessee
| | - Andrew Olshan
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Gaorav P. Gupta
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina
| | - Anthony C. Nichols
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Department of Oncology, University of Western Ontario, London, Ontario, Canada
| | - Wendell G. Yarbrough
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina
- Department of Pathology and Lab Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Chad V. Pecot
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Antonio L. Amelio
- Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Cancer Cell Biology Program, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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5
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Current state of play for HPV-positive oropharyngeal cancers. Cancer Treat Rev 2022; 110:102439. [DOI: 10.1016/j.ctrv.2022.102439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 07/13/2022] [Accepted: 07/17/2022] [Indexed: 01/22/2023]
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De Keukeleire SJ, Vermassen T, De Meulenaere A, Deron P, Huvenne W, Duprez F, Creytens D, Van Dorpe J, Rottey S, Ferdinande L. Tumour infiltrating lymphocytes in oropharyngeal carcinoma: prognostic value and evaluation of a standardised method. Pathology 2021; 53:836-843. [PMID: 34217516 DOI: 10.1016/j.pathol.2021.03.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 03/12/2021] [Accepted: 03/22/2021] [Indexed: 01/04/2023]
Abstract
Tumour infiltrating lymphocytes (TILs) have been described as a biomarker for the host immune response against the tumour with prognostic properties. The International Immuno-Oncology Biomarkers Working Group (IBWG) proposed a standardised method for quantifying TILs in solid tumours to improve consistent and reproducible scoring. In this study, the methodology was tested in a retrospective population of oropharyngeal squamous cell carcinoma (OPSCC). TIL quantification was performed on 92 OPSCC samples (2004-2013) by four independent observers as described by the IBWG. Interobserver variability was assessed and results were correlated with clinicopathological variables and survival. TIL evaluation turned out to be challenging in OPSCC due to heterogeneity of TILs distribution, presence of pre-existing lymphoid tissue, surface ulceration or erosion and insufficient amount of intertumoural stroma in biopsies. Nonetheless, interobserver variability proved to be good to excellent. High stromal TILs (TILstr) and intratumoural TILs (TILtum) were both correlated to favourable overall survival and multivariate analysis showed TILstr to be the sole independent prognostic factor in OPSCC. The IBWG-proposed TIL quantification method is feasible and reproducible in OPSCC and provides valuable prognostic information regarding clinicopathological characteristics and overall survival. The use of this standardised methodology may facilitate implementation of TILs scoring as a prognostic biomarker in OPSCC.
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Affiliation(s)
| | - Tijl Vermassen
- Ghent University Hospital, Department of Medical Oncology, Ghent, Belgium; Ghent University Hospital, Drug Research Unit Ghent, Ghent, Belgium
| | | | - Philippe Deron
- Ghent University Hospital, Department of Head and Neck Surgery, Ghent, Belgium
| | - Wouter Huvenne
- Ghent University Hospital, Department of Head and Neck Surgery, Ghent, Belgium
| | - Fréderic Duprez
- Ghent University Hospital, Department of Radiation Oncology, Ghent, Belgium
| | - David Creytens
- Ghent University Hospital, Department of Pathology, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Jo Van Dorpe
- Ghent University Hospital, Department of Pathology, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Sylvie Rottey
- Ghent University Hospital, Department of Medical Oncology, Ghent, Belgium; Ghent University Hospital, Drug Research Unit Ghent, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Liesbeth Ferdinande
- Ghent University Hospital, Department of Pathology, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
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Hoffmann M, Quabius ES. Relevance of Human Papillomaviruses in Head and Neck Cancer-What Remains in 2021 from a Clinician's Point of View? Viruses 2021; 13:v13061173. [PMID: 34207440 PMCID: PMC8235461 DOI: 10.3390/v13061173] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 12/12/2022] Open
Abstract
Human papillomaviruses (HPV) cause a subset of head and neck cancers (HNSCC). HPV16 predominantly signs responsible for approximately 10% of all HNSCC and over 50% of tonsillar (T)SCCs. Prevalence rates depend on several factors, such as the geographical region where patients live, possibly due to different social and sexual habits. Smoking plays an important role, with non-smoking patients being mostly HPV-positive and smokers being mostly HPV-negative. This is of unparalleled clinical relevance, as the outcome of (non-smoking) HPV-positive patients is significantly better, albeit with standard and not with de-escalated therapies. The results of the first prospective de-escalation studies have dampened hopes that similar superior survival can be achieved with de-escalated therapy. In this context, it is important to note that the inclusion of p16INK4A (a surrogate marker for HPV-positivity) in the 8th TMN-classification has only prognostic, not therapeutic, intent. To avoid misclassification, highest precision in determining HPV-status is of utmost importance. Whenever possible, PCR-based methods, still referred to as the "gold standard”, should be used. New diagnostic antibodies represent some hope, e.g., to detect primaries and recurrences early. Prophylactic HPV vaccination should lead to a decline in HPV-driven HNSCC as well. This review discusses the above aspects in detail.
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Affiliation(s)
- Markus Hoffmann
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, Christian-Albrechts-University Kiel, D24105 Kiel, Germany;
- Quincke-Forschungszentrum (QFZ), Medical Faculty, Christian-Albrechts-University Kiel, D24105 Kiel, Germany
- Correspondence: ; Tel.: +49-431-500-21701; Fax: +49-431-500-19028
| | - Elgar Susanne Quabius
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, Christian-Albrechts-University Kiel, D24105 Kiel, Germany;
- Quincke-Forschungszentrum (QFZ), Medical Faculty, Christian-Albrechts-University Kiel, D24105 Kiel, Germany
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8
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Lifsics A, Groma V, Cistjakovs M, Skuja S, Deksnis R, Murovska M. Identification of High-Risk Human Papillomavirus DNA, p16, and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas. Viruses 2021; 13:v13061008. [PMID: 34072187 PMCID: PMC8229053 DOI: 10.3390/v13061008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 05/21/2021] [Accepted: 05/25/2021] [Indexed: 01/16/2023] Open
Abstract
Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.
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Affiliation(s)
- Andrejs Lifsics
- Department of otolaryngology, Riga Stradiņš University, Pilsoņu 13, LV-1002 Riga, Latvia
- Correspondence:
| | - Valerija Groma
- Institute of Anatomy and Anthropology, Riga Stradiņš University, Kronvalda blvd 9, LV-1010 Riga, Latvia; (V.G.); (S.S.)
| | - Maksims Cistjakovs
- Institute of Microbiology and Virology, Riga Stradiņš University, Rātsupītes 5, LV-1067 Riga, Latvia; (M.C.); (M.M.)
| | - Sandra Skuja
- Institute of Anatomy and Anthropology, Riga Stradiņš University, Kronvalda blvd 9, LV-1010 Riga, Latvia; (V.G.); (S.S.)
| | - Renars Deksnis
- Department of Head and Neck Surgery, Oncology Centre of Latvia, Riga Eastern University Hospital, Hipokrāta 2, LV-1038 Riga, Latvia;
| | - Modra Murovska
- Institute of Microbiology and Virology, Riga Stradiņš University, Rātsupītes 5, LV-1067 Riga, Latvia; (M.C.); (M.M.)
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9
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Su Y, Zeng Z, Rong D, Yang Y, Wu B, Cao Y. PSMC2, ORC5 and KRTDAP are specific biomarkers for HPV-negative head and neck squamous cell carcinoma. Oncol Lett 2021; 21:289. [PMID: 33732365 PMCID: PMC7905686 DOI: 10.3892/ol.2021.12550] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 01/07/2021] [Indexed: 12/11/2022] Open
Abstract
The prognosis of patients with human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is poorer than those with HPV-positive HNSCC. The present study aimed to identify novel and specific biomarkers of HPV-negative HNSCC using bioinformatics analysis and associated experiments. The gene expression profiles of HPV-negative HNSCC tissues and corresponding clinical data were downloaded from The Cancer Genome Atlas database and used in a weighted gene co-expression network analysis. Genes in clinically significant co-expression modules were used to construct a protein-protein interaction (PPI) network. The genes demonstrating a high degree score in the PPI network and a high correlation with tumor grade were considered hub genes. The diagnostic value of the hub genes associated with HPV-negative and HPV-positive HNSCC was analyzed using differential expression gene (DEG) analysis, immunohistochemical (IHC) staining and a receiver operating characteristic (ROC) curve analysis. Seven genes [Serrate RNA effector molecule (SRRT), checkpoint kinase 2 (CHEK2), small nuclear ribonucleoprotein polypeptide E (SNRPE), proteasome 26S subunit ATPase 2 (PSMC2), origin recognition complex subunit 5 (ORC5), S100 calcium binding protein A7 and keratinocyte differentiation associated protein (KRTDAP)] were demonstrated to be hub genes in clinically significant co-expression modules. DEG, IHC and ROC curve analyses revealed that SRRT, CHEK2 and SNRPE were significantly upregulated in HPV-negative and HPV-positive HNSCC tissues compared with in adjacent tissues, and these genes demonstrated a high diagnostic value for distinguishing HNSCC tissues. However, PSMC2, ORC5 and KRTDAP were the only differentially expressed genes identified in HPV-negative HNSCC tissues, and these genes demonstrated a high diagnostic value for HPV-negative HNSCC. PSMC2, ORC5 and KRTDAP may therefore serve as novel and specific biomarkers for HPV-negative HNSCC, potentially improving the diagnosis and treatment of patients with HPV-negative HNSCC.
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Affiliation(s)
- Yushen Su
- Clinical Medical School, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
| | - Zhirui Zeng
- School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
| | - Dongyun Rong
- Clinical Medical School, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China.,Public Health School, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
| | - Yushi Yang
- School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China.,Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Bei Wu
- Department of Obstetrics and Gynecology, 925 Hospital of The Joint Logistics Support Force of The Chinese People's Liberation Army, Guiyang, Guizhou 550004, P.R. China
| | - Yu Cao
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
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