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Lewis JS, Beadle B, Bishop JA, Chernock RD, Colasacco C, Kalicanin T, Krane JF, Lacchetti C, Moncur JT, Rocco JW, Schwartz MR, Seethala RR, Faquin WC. Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline Update. Arch Pathol Lab Med 2025; 149:e115-e150. [PMID: 40126379 DOI: 10.5858/arpa.2024-0388-cp] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2025] [Indexed: 03/25/2025]
Abstract
CONTEXT.— In 2018, an evidence-based guideline was published by the College of American Pathologists to develop recommendations for the testing, application, interpretation, and reporting of high-risk human papillomavirus and surrogate marker tests in head and neck carcinomas. Substantial new evidence has prompted a review, including data on human papillomavirus (HPV) in nonoropharyngeal anatomic sites, HPV global rates, p16 immunohistochemistry, and HPV testing performance in cytology specimens, and performance of p16 immunohistochemistry as a surrogate marker. OBJECTIVE.— To assess research published since the release of the original 2018 guideline and to update evidence-based recommendations for HPV testing in head and neck carcinomas. DESIGN.— The College of American Pathologists convened a panel of experts to update the guideline following the standards established by the National Academy of Medicine for developing trustworthy clinical practice guidelines. The expert panel defined the key questions and performed a systematic review of the literature. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, recommendations were updated on the basis of available evidence, certainty of that evidence, and key judgments. RESULTS.— Seven strong recommendations, 4 conditional recommendations, and 5 good practice statements are offered in the guideline update. CONCLUSIONS.— The updated guideline statements provide direction on the nature of HPV testing in various head and neck specimens (including key updates based on new research on sinonasal squamous cell carcinoma) and expanded guidance on specific scenarios and practice settings. The goal is to improve and standardize, where possible, HPV testing across diverse pathology practice settings and different countries.
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Affiliation(s)
- James S Lewis
- From Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona (Lewis)
- the Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee (Lewis)
| | - Beth Beadle
- the Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (Beadle)
| | - Justin A Bishop
- the Department of Pathology, UT Southwestern Medical Center, Dallas, Texas (Bishop)
| | - Rebecca D Chernock
- the Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri (Chernock)
| | - Carol Colasacco
- Pathology and Laboratory Quality Center for Evidence-Based Guidelines, College of American Pathologists, Northfield, Illinois (Colasacco, Kalicanin)
| | - Tanja Kalicanin
- Pathology and Laboratory Quality Center for Evidence-Based Guidelines, College of American Pathologists, Northfield, Illinois (Colasacco, Kalicanin)
| | - Jeffrey F Krane
- Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California (Krane)
| | - Christina Lacchetti
- Policy and Advocacy, American Society of Clinical Oncology, Alexandria, Virginia (Lacchetti)
| | - Joel T Moncur
- Office of the Director, The Joint Pathology Center, Silver Spring, Maryland (Moncur)
| | - James W Rocco
- the Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus (Rocco)
| | - Mary R Schwartz
- the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Schwartz)
| | - Raja R Seethala
- the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Seethala)
| | - William C Faquin
- the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston (Faquin)
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Zidar N, Thompson LDR, Agaimy A, Stenman G, Hellquist H, Nadal A, Mäkitie AA, Fernando L, Strojan P, Ferlito A. The impact of histopathology on prognosis of squamous cell carcinoma of the larynx: can we do better? Virchows Arch 2025:10.1007/s00428-025-04082-w. [PMID: 40140089 DOI: 10.1007/s00428-025-04082-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 03/14/2025] [Accepted: 03/18/2025] [Indexed: 03/28/2025]
Abstract
Despite decades of progress, laryngeal squamous cell carcinoma (SCC) is still associated with significant morbidity and mortality worldwide. Additional biomarkers are needed to apply precision medicine and predict the clinical course. We reviewed and summarised routinely reported histopathologic features (e.g. subtypes of laryngeal SCC) along with promising potential biomarkers not yet routinely assessed using international guidelines. These include extra- vs intratumoural vascular and perineural invasion, tumour budding, depth of invasion, and tumour-infiltrating lymphocytes. We also address the problem of specimen quality and type (open approach vs endoscopic surgery) and the related limitations. High-risk human papillomavirus infection is another controversial issue to be discussed, being rare in laryngeal SCC, with an indeterminate prognostic significance and less reliable p16 overexpression as a surrogate marker of HPV infection. Further studies are warranted to address the applicability and to see which of the described parameters may help to better stratify patients with laryngeal SCC and should therefore be included in the pathology report.
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Affiliation(s)
- Nina Zidar
- Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia.
| | | | - Abbas Agaimy
- Comprehensive Cancer Center (CCC) Erlangen-EMN, Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Göran Stenman
- Department of Pathology, Sahlgrenska Center for Cancer Research, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
| | - Henrik Hellquist
- Department of Biomedical Sciences and Medicine, ABC-RI, University of Algarve, Faro, Portugal
- Department of Cellular Pathology, Northern Lincolnshire and Goole NHS Foundation Trust, Lincoln, UK
| | - Alfons Nadal
- Department of Pathology, Hospital Clinic, Barcelona, Spain
- Department of Basic Clinical Practice, School of Medicine, Universitat de Barcelona, Barcelona, Spain
| | - Antti A Mäkitie
- Department of Otorhinolaryngology-Head and Neck Surgery, Research Program in Systems Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - López Fernando
- Department of Otolaryngology, ISPA, IUOPA, CIBERONC, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Spain
| | - Primož Strojan
- Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
| | - Alfio Ferlito
- University of Udine School of Medicine, Udine, Italy
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Krishnapura SG, Holliday D, Rohde SL. Papillary Squamous Cell Carcinoma of the Oropharynx Arising within Cleft Palate Surgical Scar. EAR, NOSE & THROAT JOURNAL 2025; 104:NP72-NP74. [PMID: 35522272 DOI: 10.1177/01455613221101086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
| | - Dean Holliday
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sarah L Rohde
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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Lewis JS. Human Papillomavirus in Sinonasal Tract Tumors-Another Head and Neck "Hot Spot" for Prognostically Favorable Viral Disease. Surg Pathol Clin 2024; 17:599-614. [PMID: 39489552 DOI: 10.1016/j.path.2024.07.002] [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] [Indexed: 11/05/2024]
Abstract
The sinonasal tract, while an uncommon site of SCC overall, is another "hot spot" for transcriptionally-active high-risk HPV-associated tumors. The accumulating data show that, across the world, the rate of HPV-associated SCC here is approximately 15% and, in the United States, closer to 30%. Patients have lower disease recurrence and better survival than HPV-independent SCC patients. Low-risk HPV also causes a smaller subset of sinonasal SCC, mostly through exophytic and inverted papillomas that transform into SCC. It is not known if these patients have better survival than patients with low-risk HPV-negative SCC. This article reviews the latest data on HPV in sinonasal tumors.
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Affiliation(s)
- James S Lewis
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
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Ghossein RA, Dogan S, Cohen MA, Katabi N, Xu B. Histologic spectrum and outcome of Human papillomavirus (HPV)-associated oral cavity squamous cell carcinoma: a single center experience and a survey of The Cancer Genome Atlas (TGCA) cohort. Virchows Arch 2024; 485:665-674. [PMID: 39289237 PMCID: PMC11875009 DOI: 10.1007/s00428-024-03837-1] [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: 03/04/2024] [Revised: 05/16/2024] [Accepted: 05/28/2024] [Indexed: 09/19/2024]
Abstract
While high-risk human papillomavirus (HPV) serves as an essential pathogen and an important prognostic and predictive biomarker for oropharyngeal squamous cell carcinoma, it occurs at low frequency (2.2-6%) in oral cavity squamous cell carcinoma (OCSCC). To date, the pathologic features of HPV-associated OCSCC (HPV( +)-OCSCC) have been sparsely reported and its prognosis is not well-defined. We herein described detailed clinicopathologic features and outcomes of a retrospective series of 27 HPV( +)-OCSCC, including 13 from Memorial Sloan Kettering Cancer Center (MSKCC) and 14 from The Cancer Genomic Atlas program (TCGA). The frequency of HPV positivity in OCSCC was 0.7% in MSKCC cohort and 4.9% in TCGA cohort. Although HPV( +)-OCSCC was predominantly non-keratinizing (in 81%) with various degree of maturation, its histologic spectrum was expanded to include keratinizing subtype (19%), adenosquamous carcinoma (7%), and papillary architecture (subtype, 7%). HPV( +)-OCSCC predominantly affected male patients (male:female ratio = 12.5:1) and (ex) smokers (77%). It might occur in mandibular mucosa, floor of mouth, tongue, retromolar trigone, buccal mucosa, maxillary mucosa, or hard palate. In oral cavity, positivity of HPV by RNA in situ hybridization was required, and p16 immunohistochemistry alone was insufficient to confirm the HPV + status. The positive predictive value of p16 immunopositivity in detecting HPV infection was 68%. HPV-positivity did not appear to affect outcomes, including disease specific survival and progression free survival in OCSCC.
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Affiliation(s)
- Ronald A Ghossein
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Snjezana Dogan
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Marc A Cohen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nora Katabi
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Bin Xu
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
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Abi-Saab T, Lozar T, Chen Y, Tannenbaum AP, Geye H, Yu M, Weisman P, Harari PM, Kimple RJ, Lambert PF, Lloyd RV, Hu R. Morphologic Spectrum of HPV-associated Sinonasal Carcinomas. Head Neck Pathol 2024; 18:67. [PMID: 39101976 PMCID: PMC11300749 DOI: 10.1007/s12105-024-01670-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 06/18/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND High-risk human papillomavirus (HR-HPV) infection has been increasingly recognized as a risk factor for sinonasal tract carcinomas. However the prevalence and prognostic significance of HPV-associated sinonasal carcinomas is not well known due to limited studies and inconsistency in HPV testing modalities in literatures. Morphologically, HPV-associated sinonasal carcinomas encompass a diverse group of tumors. HPV-associated sinonasal adenocarcinoma has not been reported. The purpose of this study was to determine the prevalence, morphologic spectrum and prognostic implication of HPV-associated sinonasal carcinomas. METHODS This cohort included 153 sinonasal carcinomas. Tissue microarrays were constructed. P16 immunohistochemistry and HR-HPV E6/7 in-situ Hybridization (ISH) were performed. Carcinomas were deemed HPV-associated based on a positive ISH testing. Clinicopathologic data was collected. RESULTS 28/153 (18%) sinonasal carcinomas were HPV-associated. HPV-associated carcinomas consisted of 26 (93%) squamous cell carcinomas and variants, 1 (3.5%) HPV-related multiphenotypic sinonasal carcinoma and 1 (3.5%) adenocarcinoma. The HPV-associated adenocarcinoma closely resembled HPV-associated endocervical adenocarcinoma morphologically. HPV-associated carcinomas occurred in 8 (29%) women and 20 (71%) men with a median age of 66 years old. HPV-associated carcinomas were predominantly located at nasal cavity. A trend toward improved overall survival and progression free survival in HPV-associated carcinomas patients was observed, yet without statistical significance. CONCLUSION Our study identifies a novel HPV-associated sinonasal adenocarcinoma subtype, highlights the broad morphologic spectrum of HPV-associated sinonasal carcinomas, and supports routine p16 testing during pathology practice regardless of tumor subtype followed by a confirmatory HR-HPV testing. This practice is critical for studying the clinical behavior of HPV-associated sinonasal carcinomas.
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Affiliation(s)
- Tarek Abi-Saab
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Taja Lozar
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Yi Chen
- Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Alex P Tannenbaum
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Heather Geye
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Menggang Yu
- Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Paul Weisman
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Paul M Harari
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Randall J Kimple
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Paul F Lambert
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Ricardo V Lloyd
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA
| | - Rong Hu
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA.
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA.
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Mizuno Y, Okada R, Kirimura S, Yoshimura R, Asakage T. A Case of Malignant Transformation of Recurrent Respiratory Papillomatosis That Was Effectively Treated with Pembrolizumab. Case Rep Oncol 2024; 17:734-740. [PMID: 40265104 PMCID: PMC12014013 DOI: 10.1159/000540009] [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: 05/24/2024] [Accepted: 06/20/2024] [Indexed: 04/24/2025] Open
Abstract
Introduction Recurrent respiratory papillomatosis (RRP) is a benign tumor caused by the human papillomavirus that mainly occurs in the larynx; the tumor is known to show malignant transformation in a small percentage of cases. In this report, we describe a case of rapidly growing cervical metastasis due to malignant transformation of RRP that was successfully treated with pembrolizumab. Case Presentation A 79-year-old man diagnosed as having laryngeal papilloma was referred to our department, and we resected the tumor by transoral laser microsurgery (TLM). Postoperative histopathology showed papillary lesions with mild cellular atypia, suggestive of papilloma. Six years later, the patient visited our hospital again with worsening hoarseness of the voice and an enlarged papillary lesion of the larynx. We performed a second TLM and postoperative histopathological examination revealed a papillary squamous cell carcinoma. In the early postoperative period, the patient developed a recurrence at the primary site and received radiotherapy (70 Gy). Three months after the completion of radiotherapy, a rapidly enlarging metastatic lymph node was observed in the right cervical region, and we performed neck dissection. Five months after the surgery, a rapidly enlarging mass appeared in the anterior cervical subcutaneous region, and the patient received palliative radiation. Since an immunohistochemical examination of a specimen obtained at the time of neck dissection showed high PD-L1 expression, with a combined positive score of 100, the patient was initiated on treatment with pembrolizumab 1 month later. Although the patient developed fever and a skin rash as adverse events, the tumor disappeared almost entirely within 3 weeks. Thereafter, we have observed no evidence of recurrence for over 1 year. Conclusion The PD-1/PD-L1 pathway has been implicated in the tumorigenesis of RRP. This pathway may also play an important role in the malignant transformation of RRPs. Therefore, evaluation of tumor PD-L1 expression is recommended in these cases.
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Affiliation(s)
- Yusuke Mizuno
- Department of Otorhinolaryngology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryuhei Okada
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Susumu Kirimura
- Department of Pathology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryoichi Yoshimura
- Department of Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takahiro Asakage
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
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Li F, Chen X. Contribution and underlying mechanisms of lncRNA TRPM2-AS in the development and progression of human cancers. Pathol Res Pract 2023; 251:154887. [PMID: 37871443 DOI: 10.1016/j.prp.2023.154887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 10/07/2023] [Accepted: 10/11/2023] [Indexed: 10/25/2023]
Abstract
Long-stranded non-coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides and do not code for proteins. They play a significant role in various biological processes, including epigenetics, cell cycle, and cell differentiation. Many studies have shown that the occurrence of human cancer is closely related to the abnormal expression of lncRNA. In recent years, lncRNAs have been a hot topic in cancer research. TRPM2-AS, a novel lncRNA, is aberrantly expressed in many human cancers, and its overexpression is strongly linked to poor clinical outcomes in patients. It has been demonstrated that TRPM2-AS acts as a ceRNA, participates in signaling pathways, and interacts with biological proteins and other molecular mechanisms to regulate gene expression. In addition, it can regulate the proliferation, migration, invasion, apoptosis, and treatment resistance of cancer cells. As a result, TRPM2-AS may be a potential target for cancer treatment and a possible biomarker for cancer prognosis. This review outlined the expression, biological processes, and molecular mechanisms of TRPM2-AS in various malignancies, and discussed potential therapeutic uses.
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Affiliation(s)
- Fei Li
- Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Xiuwei Chen
- Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
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Dehghani Nazhvani A, Farhadi A, Badiee P, Keshvari H, Ashraf MJ, Pakdel F, Farzinnia G. Aspergillus Species and Human Papillomavirus Infections in Epithelial Tumors of Nasal and Paranasal Cavities. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2023; 16. [DOI: 10.5812/ijcm-133155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/17/2022] [Accepted: 01/22/2023] [Indexed: 04/06/2025]
Abstract
Background: There are diverse lesions originating from the paranasal sinuses and nasal cavity. Tobacco use, alcohol consumption, and malnutrition have been identified to play a role in the development of head and neck carcinomas. Recently, fungi and viruses have been recognized as potential causes of nasal cavity and paranasal tumors. Objectives: This study aimed at specifying the prevalence of Aspergillus and human papillomavirus (HPV) infections in the epithelial tumors of nasal cavity and paranasal sinuses. Methods: In this cross-sectional study, 57 paraffin-embedded tissue samples of malignant and benign lesions of the paranasal sinuses and nasal cavity were evaluated for the presence of Aspergillus and HPV DNA by nested polymerase chain reaction (nPCR) technique with specific primers. Results: Despite the absence of angular hyphae (acute angle) of the fungus on histopathological slides, overall, 10 (17.54%) out of 57 paraffin-embedded samples were found to be positive for Aspergillus species. However, HPV-DNA was not found in any of the samples. Conclusions: Our data suggest that fungal infections (especially aspergillosis) as an etiological factor can be contributed to the development of sinonasal cancer and, therefore, they should be considered in the management of patients with sinonasal cancer. In addition, PCR can provide an alternative to culture-dependent identification methods.
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Li T, Wang Y, Xiang X, Chen C. Survival comparison of different histological subtypes of oropharyngeal squamous cell carcinoma: A propensity-matched score analysis based on SEER database. EAR, NOSE & THROAT JOURNAL 2022:1455613221136360. [PMID: 36317416 DOI: 10.1177/01455613221136360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023] Open
Abstract
OBJECTIVE The purpose of this study was to analyze the difference of survival rates in paitents with oropharyngeal keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), basaloid squamous cell carcinoma (BSCC), and papillary squamous cell carcinoma (PSCC). MATERIALS AND METHODS Patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2015 were collected from the SEER database. Cox proportional hazards models and Kaplan-Meier curves were used for survival analysis. Propensity score matching (PSM) was performed to adjust for the effect of confounding variables. Due to the small sample size of PSCC, this study did not perform PSM between it and other subtypes. RESULTS The 5-year cancer-specific survival (CSS) rate of PSCC was higher than that of KSCC, NKSCC, and BSCC (0.627 vs. 0.812 vs. 0.789 vs. 0.875, P < 0.05); And the CSS rate of KSCC was lower than that of other subtypes both before and after PSM. In addition, the 5-year and 10-year CSS rates of BSCC were not different from NKSCC (P > 0.05), but not as good as NKSCC in the long term (P = 0.028). After PSM, the 5-year, 10-year, and long-term prognosis of BSCC were significantly worse than those of NKSCC (P < 0.001). CONCLUSION The 5-year CSS of PSCC was better than the other three subtypes. The short-term prognosis of BSCC was not significantly different from NKSCC, but the long-term survival was lower than that of NKSCC, and the difference was more obvious after PSM. Meanwhile, the prognosis of KSCC was worst.
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Affiliation(s)
- Tao Li
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Hefei, China
- Wan Nan Medical College, Wuhu, China
| | - Yi Wang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Hefei, China
| | - Xianwang Xiang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Hefei, China
| | - Chuanjun Chen
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Hefei, China
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Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Hypopharynx, Larynx, Trachea and Parapharyngeal Space. Head Neck Pathol 2022; 16:31-39. [PMID: 35312977 PMCID: PMC9018940 DOI: 10.1007/s12105-021-01405-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/16/2021] [Indexed: 11/17/2022]
Abstract
In this article, we review the chapter on tumors of the larynx, hypopharynx, trachea and parapharyngeal space in the new edition of the WHO book, focusing on the new developments in comparison to the previous edition. Squamous cell carcinoma (SCC) and its variants are by far the most common malignancies at these locations, with very limited new insights. The most important is the introduction of new targeted treatment-checkpoint inhibitors, with a new task for pathologists, who may help to predict the response to treatment by analyzing the expression of targeted proteins in biopsy samples. Precancerous lesions remain a controversial topic and, similarly to other organs, it is acceptable to use the terms "dysplasia" or "squamous intraepithelial lesion" (SIL), but there is a slight difference between low-grade dysplasia and low-grade SIL: in the former, mild atypia must be present, while the latter also includes hyperplastic epithelium without atypia. Two approaches have been proposed: a two-tiered system with low- and high-grade dysplasia/SIL and a three-tiered system with an additional category, carcinoma in situ. We are still searching for reliable diagnostic markers to surpass the subjectivity in biopsy diagnosis, with a few potential candidate markers on the horizon, e.g., stem cell markers. Other tumors are rare at these locations, e.g., hematolymphoid, neuroendocrine and salivary gland neoplasms, and are no longer included in Chapter 3. They must be diagnosed according to criteria described in specific chapters. The same holds true for soft tissue tumors, with the exception of cartilaginous neoplasms, which are still included in Chapter 3.
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12
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HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol 2022; 19:306-327. [PMID: 35105976 PMCID: PMC8805140 DOI: 10.1038/s41571-022-00603-7] [Citation(s) in RCA: 472] [Impact Index Per Article: 157.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2022] [Indexed: 12/13/2022]
Abstract
Human papillomavirus (HPV)-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has one of the most rapidly increasing incidences of any cancer in high-income countries. The most recent (8th) edition of the UICC/AJCC staging system separates HPV+ OPSCC from its HPV-negative (HPV−) counterpart to account for the improved prognosis seen in the former. Indeed, owing to its improved prognosis and greater prevalence in younger individuals, numerous ongoing trials are examining the potential for treatment de-intensification as a means to improve quality of life while maintaining acceptable survival outcomes. In addition, owing to the distinct biology of HPV+ OPSCCs, targeted therapies and immunotherapies have become an area of particular interest. Importantly, OPSCC is often detected at an advanced stage owing to a lack of symptoms in the early stages; therefore, a need exists to identify and validate possible diagnostic biomarkers to aid in earlier detection. In this Review, we provide a summary of the epidemiology, molecular biology and clinical management of HPV+ OPSCC in an effort to highlight important advances in the field. Ultimately, a need exists for improved understanding of the molecular basis and clinical course of this disease to guide efforts towards early detection and precision care, and to improve patient outcomes. The incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is increasing rapidly in most developed countries. In this Review, the authors provide an overview of the epidemiology, molecular biology and treatment of HPV-positive OPSCC, including discussions of the role of treatment de-escalation and emerging novel therapies.
The incidence of human papillomavirus-associated oropharyngeal cancer (HPV+ OPSCC) is expected to continue to rise over the coming decades until the benefits of gender-neutral prophylactic HPV vaccination begin to become manifest. The incidence of HPV+ OPSCC appears to be highest in high-income countries, although more epidemiological data are needed from low- and middle-income countries, in which HPV vaccination coverage remains low. The substantially better prognosis of patients with HPV+ OPSCC compared to those with HPV– OPSCC has been recognized in the American Joint Committee on Cancer TNM8 staging guidelines, which recommend stratification by HPV status to improve staging. The molecular biology and genomic features of HPV+ OPSCC are similar to those of other HPV-associated malignancies, with HPV oncogenes (E6 and E7) acting as key drivers of pathogenesis. Treatment de-intensification is being pursued in clinical trials, although identifying the ~15% of patients with HPV+ OPSCC who have recurrent disease, and who therefore require more intensive treatment, remains a key challenge.
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13
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Zheng S, Magliocca KR, Reid MD, Kaka AS, Lubin D. Metastatic HPV-Mediated Adenocarcinoma Arising from a Base of Tongue Primary: A Case Report with Cytomorphology and Molecular Findings with Review of the Literature. Head Neck Pathol 2022; 16:893-901. [PMID: 35015191 PMCID: PMC9424432 DOI: 10.1007/s12105-021-01407-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 12/20/2021] [Indexed: 01/13/2023]
Abstract
Human papillomavirus (HPV)-mediated squamous cell carcinomas of the oropharynx are common, however only rare cases of HPV-mediated oropharyngeal adenocarcinoma have been reported to date. In this report, we describe a 50 year old nonsmoking male who originally presented with an enlarging neck mass. Fine needle aspiration cytology confirmed an HPV-mediated adenocarcinoma. Subsequent surgery identified a 0.7 cm base of tongue primary HPV-mediated carcinoma with focal glandular differentiation and a 4.0 cm cystic lymph node metastasis demonstrating entirely glandular differentiation. Next generation sequencing of the metastasis detected a pathogenic NOTCH1 mutation.
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Affiliation(s)
- Stephanie Zheng
- grid.411929.60000 0004 0441 5764Department of Pathology, Emory University Hospital Midtown, 550 Peachtree Street NE, Atlanta, GA 30308 USA
| | - Kelly R. Magliocca
- grid.411929.60000 0004 0441 5764Department of Pathology, Emory University Hospital Midtown, 550 Peachtree Street NE, Atlanta, GA 30308 USA
| | - Michelle D. Reid
- grid.411929.60000 0004 0441 5764Department of Pathology, Emory University Hospital Midtown, 550 Peachtree Street NE, Atlanta, GA 30308 USA
| | - Azeem S. Kaka
- grid.411929.60000 0004 0441 5764Department of Otolaryngology, Head and Neck Surgery, Emory University Hospital Midtown, 550 Peachtree Street NE, Atlanta, GA 30308 USA
| | - Daniel Lubin
- grid.411929.60000 0004 0441 5764Department of Pathology, Emory University Hospital Midtown, 550 Peachtree Street NE, Atlanta, GA 30308 USA ,grid.412162.20000 0004 0441 5844Pathology and Laboratory Medicine, Emory University Hospital, Room H-184, 1364 Clifton Road NE, Atlanta, GA 30322 USA
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14
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Grigolato R, Accorona R, Lombardo G, Corrocher G, Garagiola U, Massari F, Nicoli S, Rossi S, Calabrese L. Oral cancer in non-smoker non-drinker patients. Could comparative pet oncology help to understand risk factors and pathogenesis? Crit Rev Oncol Hematol 2021; 166:103458. [PMID: 34461267 DOI: 10.1016/j.critrevonc.2021.103458] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 08/03/2021] [Accepted: 08/22/2021] [Indexed: 01/16/2023] Open
Abstract
During the last decades there has been a progressive increase in proportion of incidence of oral cancer not related to a known etiologic factor, such as the so-called "oral cancer in young", a relevant tumor in non-smoker non-drinker (NSND) patients. The topic is matter of long standing debate, and adequate study models to analyze this entity are lacking. Spontaneous oral cancer in companion animals such as dogs and cats, presents more clinical and biological similarities with the human oral cancer than any other animal model. In our review we analyze how the study of spontaneous oral cancer in common pets can prospectively prove to be of double usefulness in unraveling the question about the origin of oral cancer in NSND patients, allowing both the analysis of environmental and behavioral risk factors, and the study of how carcinogenic viruses, chronic inflammation, and changes in immunity can influence pre-tumoral and tumoral microenvironment.
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Affiliation(s)
- Roberto Grigolato
- Division of Otorhinolaryngology, "San Maurizio" Hospital, Bolzano, Italy
| | - Remo Accorona
- Department of Otorhinolaryngology - Head and Neck Surgery, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
| | - Giorgio Lombardo
- School of Dentistry, Department of Surgery, Dentistry, Pediatrics, and Gynecology (DIPSCOMI), University of Verona, Verona, Italy
| | - Giovanni Corrocher
- School of Dentistry, Department of Surgery, Dentistry, Pediatrics, and Gynecology (DIPSCOMI), University of Verona, Verona, Italy
| | - Umberto Garagiola
- Biomedical, Surgical and Dental Sciences Department, Maxillofacial and Odontostomatology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | | | | | - Sabrina Rossi
- Department of Oncology and Hematology, Humanitas Cancer Center, Rozzano, Milano, Italy
| | - Luca Calabrese
- Division of Otorhinolaryngology, "San Maurizio" Hospital, Bolzano, Italy
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15
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Malignant Sinonasal Tumors: Update on Histological and Clinical Management. ACTA ACUST UNITED AC 2021; 28:2420-2438. [PMID: 34287240 PMCID: PMC8293118 DOI: 10.3390/curroncol28040222] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/28/2021] [Accepted: 06/29/2021] [Indexed: 02/03/2023]
Abstract
Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes. Due to the extreme rarity of these neoplasms, there are no standard and evidence-based therapeutic strategies, lacking prospective and large clinical trials. In fact, most studies are retrospective analyses. Surgery represents the mainstay of treatment of TuNSs for small and localized tumors allowing complete tumor removal. Locally advanced lesions require more demolitive surgery that should be always followed by adjuvant radio- or chemo-radiotherapy. Recurrent/metastatic disease requires palliative chemo- and/or radiotherapy. Many studies emphasize the role of specific genes mutations in the development of TuNSs like mutations in the exons 4-9 of the TP53 gene, in the exon 9 of the PIK3CA gene and in the promoter of the TERT gene. In the near future, this genetic assessment will have new therapeutic implications. Future improvements in the understanding of the etiology, biology, and clinical features of TuNSs are warranted to improve their management.
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Human Papillomavirus in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers (Basel) 2020; 13:cancers13010045. [PMID: 33561073 PMCID: PMC7796014 DOI: 10.3390/cancers13010045] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/19/2020] [Accepted: 12/21/2020] [Indexed: 12/18/2022] Open
Abstract
Simple Summary The causative role of human papillomavirus (HPV) in sinonasal squamous cell carcinoma (SNSCC) remains unclear and is hindered by small studies using variable HPV detection techniques. This meta-analysis aims to provide an updated overview of HPV prevalence in SNSCC stratified by detection method, anatomic subsite, and geographic region. From 60 eligible studies, an overall HPV prevalence was estimated at 26%. When stratified by detection method, HPV prevalence was lower when using multiple substrate testing compared to single substrate testing. Anatomic subsite HPV prevalence was higher in subsites with high exposure to secretion flow compared to low exposure subsites. HPV prevalence in SNSCC followed the global distribution of HPV+ oropharyngeal squamous cell carcinoma. Taken together, this meta-analysis further supports a role for HPV in a subset of SNSCCs. Abstract Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies (n = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7–31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5–28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6–41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5–50.2) vs. low-exposure (15.1%, 95% CI 7.3–28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9–41.5) vs. low (Africa) (13.1, 95% CI 6.5–24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.
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17
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Human papilloma virus related squamous cell carcinomas of the head and neck: diagnosis, clinical implications and detection of HPV. Pathology 2019; 52:179-191. [PMID: 31889547 DOI: 10.1016/j.pathol.2019.10.008] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 10/16/2019] [Indexed: 02/06/2023]
Abstract
High-risk human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck is reported most commonly in the oropharynx but can also uncommonly be found in other sites such as the anterior oral cavity and sinonasal tract. While HPV positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has been shown to have a more favourable prognosis than conventional smoking- and alcohol-related anterior oral cavity squamous cell carcinoma (OSCC), HPV positive SCC arising elsewhere in the head and neck region does not carry the same favourable prognosis. HPV-OPSCC often tends to present with large cystic metastases in the cervical lymph nodes, with a clinically and radiologically occult primary. Correct diagnosis of the initial biopsy/cytology specimen is critical for directing further investigations and management. In recognition of its distinct biological behaviour, the 8th edition of the American Joint Commission on Cancer (AJCC 8) has proposed a separate clinical and pathological staging system for HPV-OPSCC compared to that for a conventional primary OSCC or neck metastasis of similar size. The new AJCC staging does not apply to other HPV positive SCC of the head and neck. This review examines the current biology of HPV positive SCC, focusing on HPV-OPSCC. The value and pitfalls of current detection methods of HPV are discussed with an emphasis on the role of the pathologist in the diagnosis and management of HPV positive SCC of the head and neck.
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18
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The evolving landscape of HPV-related neoplasia in the head and neck. Hum Pathol 2019; 94:29-39. [DOI: 10.1016/j.humpath.2019.09.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 09/09/2019] [Indexed: 12/12/2022]
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19
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Transcriptionally Active HPV and Targetable EGFR Mutations in Sinonasal Inverted Papilloma. Am J Surg Pathol 2019; 44:340-346. [DOI: 10.1097/pas.0000000000001411] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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20
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Garcia JA, Best SR, Rooper LM. HPV RNA in-situ hybridization as a diagnostic aid in papillary laryngeal lesions. Laryngoscope 2019; 130:955-960. [PMID: 31283030 DOI: 10.1002/lary.28159] [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: 01/16/2019] [Revised: 05/23/2019] [Accepted: 06/11/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVES In the larynx, differentiating squamous papillomas from de-novo papillary squamous dysplasias or squamous cell carcinomas (SCC) has significant consequences for management. Overlapping clinical presentations and cytologic changes across the spectrum of papillary lesions presents diagnostic challenges for otolaryngologists and pathologists. In this study, we evaluate whether ribonucleic acid (RNA) in-situ hybridization (ISH) for low-risk and high-risk human papillomavirus (HPV) can help distinguish these lesions. METHODS We constructed tissue microarrays from 97 papillary laryngeal lesions, including 61 squamous papillomas, two papillomas with dysplasia, two SCCs-ex papilloma, 14 papillary squamous dysplasias, and 18 papillary SCCs identified at the Johns Hopkins Hospital between 2000 and 2017. We performed RNA ISH using probes for low-risk and high-risk HPV types. RESULTS Low-risk HPV RNA was identified in 55 benign papillomas (90%), two papillomas with dysplasia (100%), and two SCCs-ex papilloma (100%) but was absent in de-novo papillary dysplasias and SCCs (0%). High-risk HPV RNA ISH was positive only in four papillary SCC (22%). Overall, low-risk HPV RNA ISH was 90% sensitive and 89% specific for benign papillomas with a positive predictive value of 93% and negative predictive value of 84%. In contrast, high-risk HPV was 20% sensitive for SCC. CONCLUSION Low-risk HPV RNA ISH is a useful diagnostic adjunct for distinguishing laryngeal squamous papillomas from papillary squamous dysplasia and SCC. However, it is not entirely specific for benign processes as it is also retained in papillomas with dysplasia and SCCs-ex papilloma. Because high-risk HPV is rare in papillary laryngeal lesions, high-risk HPV RNA ISH has limited utility. LEVEL OF EVIDENCE Level 4 Laryngoscope, 130:955-960, 2020.
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Affiliation(s)
- Jordan A Garcia
- Department of Otolaryngology, The Johns Hopkins Hospital, Baltimore, Maryland, U.S.A
| | - Simon R Best
- Department of Otolaryngology, The Johns Hopkins Hospital, Baltimore, Maryland, U.S.A
| | - Lisa M Rooper
- Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.,Department of Oncology, The Johns Hopkins Hospital, Baltimore, Maryland, U.S.A
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21
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Andreasen S, Kiss K, Mikkelsen LH, Channir HI, Plaschke CC, Melchior LC, Eriksen JG, Wessel I. An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome. APMIS 2019; 127:240-264. [PMID: 30811708 DOI: 10.1111/apm.12901] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 10/08/2018] [Indexed: 12/12/2022]
Abstract
The head and neck region harbor numerous specialized tissues of all lineages giving rise to a plethora of different malignancies. In recent years, new types and subtypes of cancer has been described here due to the recognition of their histological and molecular characteristics. Some have been formally accepted in the most recent classifications from the World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) as distinct diseases due to characteristics in clinical presentation, outcome, and treatment. In particular, this applies to malignancies of the salivary gland, sinonasal tract, and oropharynx. In this overview, we present the most recent developments in the classification, histopathological characteristics, and molecular features of head and neck cancer. The clinical and radiological characteristics, outcome, and treatment options including perspectives for targeted therapies, are discussed.
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Affiliation(s)
- Simon Andreasen
- Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark.,Department of Pathology, Rigshospitalet, Copenhagen, Denmark
| | - Katalin Kiss
- Department of Pathology, Rigshospitalet, Copenhagen, Denmark
| | - Lauge Hjorth Mikkelsen
- Department of Pathology, Rigshospitalet, Copenhagen, Denmark.,Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark
| | - Hani Ibrahim Channir
- Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark
| | | | | | - Jesper Grau Eriksen
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Irene Wessel
- Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark
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22
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Virus-associated carcinomas of the head & neck: Update from the 2017 WHO classification. Ann Diagn Pathol 2019; 38:29-42. [DOI: 10.1016/j.anndiagpath.2018.10.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Accepted: 10/18/2018] [Indexed: 12/12/2022]
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23
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Jo VY, Krane JF, Pantanowitz L, Monaco SE. HPV‐associated neuroendocrine carcinomas of the head and neck in FNA biopsies: Clinicopathologic features of a rare entity. Cancer Cytopathol 2018; 127:26-34. [DOI: 10.1002/cncy.22075] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 08/29/2018] [Accepted: 09/18/2018] [Indexed: 01/05/2023]
Affiliation(s)
- Vickie Y. Jo
- Department of Pathology Brigham and Women’s Hospital and Harvard Medical School Boston Massachusetts
| | - Jeffrey F. Krane
- Department of Pathology Brigham and Women’s Hospital and Harvard Medical School Boston Massachusetts
| | - Liron Pantanowitz
- Department of Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania
| | - Sara E. Monaco
- Department of Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania
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24
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Serra A, Caltabiano R, Scalia G, Palmucci S, Di Mauro P, Cocuzza S. Papillary squamous cell carcinoma of the palatine tonsil: a rare cancer of the head and neck. ACTA OTORHINOLARYNGOLOGICA ITALICA 2018; 37:341-345. [PMID: 28530265 PMCID: PMC5584108 DOI: 10.14639/0392-100x-1281] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 07/12/2016] [Indexed: 11/23/2022]
Abstract
Papillary squamous neoplasms of the upper respiratory tract are rare variants of squamous cell carcinomas. They are characterised by an exophytic, papillary growth and generally have favourable prognosis. The tumour has been described in the upper aerodigestive tract. In this context, most common sites of involvement are the larynx and hypopharynx, and rarely the oral cavity and oropharynx. The limited studies and small number of published cases of papillary squamous cell carcinoma of the palatine tonsil led us to make a complete analysis of this tumour by analysing the clinical, histological, radiological, virological and therapeutic aspects that are not always present in the literature. A case of papillary squamous cell carcinoma of the palatine tonsil is reported. The lesion (T2N0M0) was located into the left palatine tonsil that hung towards the oral cavity. Both HPV 16 DNA and E6/E7 mRNA were detected in the lesion. The clinicopathological profile of the neoplasm is presented and a comprehensive review of recent literature was made by analysing all aspects of interest of this neoplasm.
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Affiliation(s)
- A Serra
- Department G.F. Ingrassia, ENT Section, University of Catania, Catania, Italy
| | - R Caltabiano
- Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Italy
| | - G Scalia
- Clinical Virology Unit, Central Laboratory, University Hospital "Policlinico Vittorio-Emanuele", and Department of Biomedical and Biotechnological Sciences, University of Catania, Italy
| | - S Palmucci
- Radiodiagnostic and Radiotherapy Unit, University Hospital "Policlinico Vittorio Emanuele", Catania, Italy
| | - P Di Mauro
- Department G.F. Ingrassia, ENT Section, University of Catania, Catania, Italy
| | - S Cocuzza
- Department G.F. Ingrassia, ENT Section, University of Catania, Catania, Italy
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25
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Tamaki A, Miles BA, Lango M, Kowalski L, Zender CA. AHNS Series: Do you know your guidelines? Review of current knowledge on laryngeal cancer. Head Neck 2017; 40:170-181. [PMID: 29076227 DOI: 10.1002/hed.24862] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Accepted: 05/22/2017] [Indexed: 11/07/2022] Open
Abstract
The following article is part of a series in an initiative by the American Head and Neck Society's Education Committee and will review clinical practice guidelines for head and neck oncology. The primary goal is to increase awareness of current best practices pertaining to head and neck surgery and oncology. This manuscript is a review of current knowledge in laryngeal cancer with a focus on anatomy, epidemiology, diagnosis, evaluation, and treatment.
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Affiliation(s)
- Akina Tamaki
- Ear, Nose, and Throat Institute, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Brett A Miles
- Department of Otolaryngology - Head and Neck Surgery, Icahn School of Medicine at Mount Sinai Medical Center, New York, New York
| | - Miriam Lango
- Department of Surgical Oncology, Division of Head and Neck Surgery, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, Pennsylvania
| | - Luiz Kowalski
- Head and Neck Surgery and Otorhinolaryngology Department, A C Camargo Cancer Center, Sao Paulo, Brazil
| | - Chad A Zender
- Ear, Nose, and Throat Institute, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, Ohio
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26
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Riener MO, Hoegel J, Iro H, Hartmann A, Agaimy A. IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis. Oncol Lett 2017; 14:1665-1670. [PMID: 28789393 DOI: 10.3892/ol.2017.6352] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 11/17/2016] [Indexed: 11/06/2022] Open
Abstract
Expression of p16 has been established as a good surrogate marker for high-risk human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) patients, and it has been associated with an improved prognosis, irrespective of the actual HPV status. Conversely, the human insulin-like growth factor II mRNA binding protein 3 (IMP3) has been related to aggressiveness in several types of tumors. The aim of the present study was to investigate and compare p16 and IMP3 as markers of favorable and unfavorable behavior, respectively, in head and neck SCC (HNSCC), with particular reference to the HPV status. Both markers were analyzed by immunohistochemical analysis of 156 HNSCC samples originating from the oropharynx (n=81), oral cavity (n=44), larynx (n=15), hypopharynx (n=10) and nasopharynx (n=6). The HPV status was examined in a randomly selected representative subcohort (n=38) using polymerase chain reaction. Of the 156 HNSCC samples, 81 (51.9%) and 54 (34.6%) were positive for IMP3 and p16, respectively. IMP3 expression (P=0.022), p16 expression (P<0.001) and the combination of these markers (P<0.001) were significantly associated with tumor site. In particular, 69/81 (85%) OPSCC samples were positive for either one or both markers compared with 36/75 (48%) SCC samples from other sites. p16 expression was significantly associated with HPV infection (P=0.017) and a trend towards a negative association between IMP3 expression and HPV infection was observed (P=0.053). The results of the present study suggested that IMP3 and p16 are more frequently expressed in OPSCC compared with other HNSCCs. The prognostic impact of IMP3 on OPSCC remains to be investigated in a larger series with an extended follow-up period.
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Affiliation(s)
- Marc-Oliver Riener
- Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany.,OptiPath, Pathology Joint Practice, Frankfurt D-60487, Germany
| | - Josef Hoegel
- Institute of Human Genetics, University Hospital Ulm, D-89081 Ulm, Germany
| | - Heinrich Iro
- Department of Otorhinolaryngology, Head & Neck Surgery, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital, D-91054 Erlangen, Germany
| | - Arndt Hartmann
- Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany
| | - Abbas Agaimy
- Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany
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27
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Abstract
Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.
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Affiliation(s)
- Lester D R Thompson
- Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, 5601 De Soto Avenue, Woodland Hills, CA 91367, USA.
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28
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López F, Williams MD, Cardesa A, Hunt JL, Strojan P, Rinaldo A, Nixon IJ, Rodrigo JP, Saba NF, Mendenhall WM, Quer M, Suárez C, Ferlito A. How phenotype guides management of non-conventional squamous cell carcinomas of the larynx? Eur Arch Otorhinolaryngol 2017; 274:2709-2726. [PMID: 28364287 DOI: 10.1007/s00405-017-4533-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 03/13/2017] [Indexed: 12/15/2022]
Abstract
Although the majority of laryngeal malignancies are the conventional squamous cell carcinomas (SCC), a wide variety of malignant epithelial tumors can affect the larynx. Current treatment guidelines are designed to guide clinicians in management of conventional laryngeal SCC. Less is known about the biological behavior and responsiveness to therapy and overall outcomes of other malignant epithelial lesions. Because a spectrum of disease biology is represented by these rare phenotypes, an understanding of the basic biology can help direct management to optimize clinical outcome in this group of patients. This review provides a critical analysis of literature relating to the diagnosis, management, and outcome of patients with non-conventional squamous malignant epithelial neoplasms of the larynx. Particular attention is paid to features which are at variance with the conventional SCC and how these impact on management of these rare tumors.
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Affiliation(s)
- Fernando López
- Department of Otolaryngology, Hospital Universitario Central de Asturias, Avenida de Roma s/n, 33011, Oviedo (Asturias), Spain. .,Instituto Universitario de Oncología del Principado de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, University of Oviedo, Oviedo, Spain.
| | - Michelle D Williams
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Antonio Cardesa
- Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Jennifer L Hunt
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Primož Strojan
- Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
| | | | - Iain J Nixon
- Departments of Surgery and Otolaryngology, Head and Neck Surgery, Edinburgh University, Edinburgh, UK
| | - Juan P Rodrigo
- Department of Otolaryngology, Hospital Universitario Central de Asturias, Avenida de Roma s/n, 33011, Oviedo (Asturias), Spain.,Instituto Universitario de Oncología del Principado de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, University of Oviedo, Oviedo, Spain
| | - Nabil F Saba
- Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | | | - Miquel Quer
- Department of Otolaryngology, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - Carlos Suárez
- Instituto Universitario de Oncología del Principado de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, University of Oviedo, Oviedo, Spain
| | - Alfio Ferlito
- International Head and Neck Scientific Group, Padua, Italy
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29
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Abstract
Human papillomavirus (HPV) is an essential causal factor in a subset of head and neck neoplasms, most notably oropharyngeal squamous cell carcinoma, for which HPV infection has important diagnostic, prognostic, and therapeutic implications. This article summarizes the current understanding of HPV-associated neoplasms of the head and neck, including the recently described carcinoma with adenoid cystic-like features. Salient clinical, gross, and microscopic features are discussed, and the utility of specific ancillary studies is highlighted.
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Affiliation(s)
- Aaron M Udager
- Department of Pathology, University of Michigan Health System, 2G309 UH, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5054, USA
| | - Jonathan B McHugh
- Department of Pathology, University of Michigan Health System, 2G332 UH, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5054, USA.
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30
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Westra WH, Lewis JS. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx. Head Neck Pathol 2017; 11:41-47. [PMID: 28247229 PMCID: PMC5340734 DOI: 10.1007/s12105-017-0793-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 02/02/2017] [Indexed: 12/14/2022]
Abstract
The changes for oropharyngeal lesions in the 2017 edition of the WHO/IARC Classification of Head and Neck Tumours reference book are dramatic and significant, largely due to the growing impact of high risk human papillomavirus (HPV). The upcoming edition divides tumours of the oral cavity and oropharynx into separate chapters, classifies squamous cell carcinomas (SCC) of the oropharynx on the basis of HPV status, abandons the practice of histologic grading for oropharyngeal SCCs that are HPV positive, recognizes small cell carcinoma of the oropharynx, and combines polymorphous low grade adenocarcinoma and cribriform adenocarcinoma of tongue and minor salivary glands under the single term "polymorphous adenocarcinoma." This review not only calls attention to these changes, but describes the rationale driving these changes and highlights their implications for routine clinical practice.
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Affiliation(s)
- William H Westra
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
- Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
- Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - James S Lewis
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA.
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31
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Stelow EB, Bishop JA. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Nasal Cavity, Paranasal Sinuses and Skull Base. Head Neck Pathol 2017; 11:3-15. [PMID: 28247233 PMCID: PMC5340732 DOI: 10.1007/s12105-017-0791-4] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 02/02/2017] [Indexed: 12/29/2022]
Abstract
The sinonasal tract remains an epicenter of a diverse array of neoplasia. This paper discusses changes to the WHO classification system of tumors involving this area. In particular, seromucinous hamartoma, NUT carcinoma, biphenotypic sinonasal sarcoma, HPV-related carcinoma with adenoid cystic features, SMARCB1-deficient carcinoma, and renal cell-like adenocarcinoma are discussed.
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Affiliation(s)
- Edward B. Stelow
- Department of Pathology, Anatomic Pathology, University of Virginia Health System, Jefferson Park Ave., Box 800214, Charlottesville, VA 22908 USA
| | - Justin A. Bishop
- Department of Pathology, Johns Hopkins University, Baltimore, MD USA
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32
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Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space. Head Neck Pathol 2017; 11:23-32. [PMID: 28247231 PMCID: PMC5340729 DOI: 10.1007/s12105-017-0788-z] [Citation(s) in RCA: 97] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 02/02/2017] [Indexed: 01/08/2023]
Abstract
Chapter 3 "Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space" of the World Health Organization (WHO) Blue Book 2017 "Classification of Head and Neck Tumours" shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial-mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate- and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.
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Toman J, Von Larson S, Umeno H, Kurita T, Furusaka T, Hasegawa H, Prasad ML, Sasaki CT. HPV-Positive Oropharyngeal Cancer Via p16 Immunohistochemistry in Japan. Ann Otol Rhinol Laryngol 2017; 126:152-158. [PMID: 27913709 DOI: 10.1177/0003489416681582] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Human papillomavirus (HPV) has emerged as a driving cause of head and neck cancer, but investigations outside the West are limited. A p16 immunohistochemistry is a commonly used biomarker for HPV cancers. We sought to investigate the pathology and rates of HPV head and neck oropharyngeal cancer in Japan via p16 immunohistochemistry at 2 institutions in Japan. METHODS Fifty-nine oropharyngeal specimens from 2 university hospitals in Japan were examined for morphology and p16 immunohistochemistry. The rate of p16 positivity was then determined, and the 2 groups were compared for differences in age, smoking history, gender, and stage of presentation and mortality. RESULTS The rate of p16 positivity among the oropharyngeal specimens was 29.5%. There were important differences in the pathology compared to morphology usually seen in the US. The patients with p16+ cancer tended to be younger. There was no significant difference in smoking status. Patients with p16+ cancers trended toward better survival. CONCLUSION There appears to be a geographical difference in HPV rates of oropharyngeal cancers with persistently lower rates in Asian countries when compared to Western Europe and the US. Conclusions about HPV head and neck squamous cell carcinoma (HNSCC) in Western countries may not be generalizable across the globe at this time.
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Affiliation(s)
- Julia Toman
- 1 Department of Surgery, Division of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut, USA
| | | | - Hirohito Umeno
- 3 Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka Japan
| | - Takashi Kurita
- 3 Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka Japan
| | - Tohru Furusaka
- 4 Department of Otolaryngology and Head & Neck Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Hisashi Hasegawa
- 4 Department of Otolaryngology and Head & Neck Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Manju L Prasad
- 5 Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Clarence T Sasaki
- 1 Department of Surgery, Division of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut, USA
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34
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Wenig BM. Squamous cell carcinoma of the upper aerodigestive tract: dysplasia and select variants. Mod Pathol 2017; 30:S112-S118. [PMID: 28060368 DOI: 10.1038/modpathol.2016.207] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2016] [Revised: 11/03/2016] [Accepted: 11/03/2016] [Indexed: 12/26/2022]
Abstract
Upper aerodigestive tract (UADT) mucosal premalignant lesions include non-keratinizing and keratinizing intraepithelial dysplasia. The keratinizing type of intraepithelial dysplasia represents the majority of UADT dysplasias. Historically, grading of UADT dysplasias has followed a three tier system to include mild, moderate and severe dysplasia. Recent recommendations have introduced a two tier grading scheme to including low-grade (ie, mild dysplasia) and high-grade (moderate and severe dysplasia/carcinoma in situ) providing for better consensus among pathologists in the interpretation of such dysplastic lesions. Squamous cell carcinoma is the most common malignant neoplasm of the UADT. Several variants of squamous cell carcinoma are recognized among which the more common types include papillary squamous cell carcinoma, verrucous carcinoma, spindle cell squamous cell carcinoma (sarcomatoid carcinoma) and basaloid squamous cell carcinoma. Each of these variants of squamous cell carcinoma poses diagnostic challenges and each correlates to specific therapy and prognosis. This review details the proposed update in the grading of UADT dysplasia to a two-tiered system as well as providing the key diagnostic features for select variants of squamous cell carcinoma.
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Affiliation(s)
- Bruce M Wenig
- Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA
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35
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Morphologic diversity in human papillomavirus-related oropharyngeal squamous cell carcinoma: Catch Me If You Can! Mod Pathol 2017; 30:S44-S53. [PMID: 28060372 DOI: 10.1038/modpathol.2016.152] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Revised: 07/05/2016] [Accepted: 07/05/2016] [Indexed: 01/19/2023]
Abstract
As the human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma epidemic has developed in the past several decades, it has become clear that these tumors have a wide variety of morphologic tumor types and features. For the practicing pathologist, it is critical to have a working knowledge about these in order to make the correct diagnosis, not to confuse them with other lesions, and to counsel clinicians and patients on their significance (or lack of significance) for treatment and outcomes. In particular, there are a number of pitfalls and peculiarities regarding HPV-related tumors and their nodal metastases that can easily result in misclassification and confusion. This article will discuss the various morphologic types and features of HPV-related oropharyngeal carcinomas, specific differential diagnoses when challenging, and, if established, the clinical significance of each finding.
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36
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37
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Allison DB, Maleki Z. HPV-related head and neck squamous cell carcinoma: An update and review. J Am Soc Cytopathol 2016; 5:203-215. [PMID: 31042510 DOI: 10.1016/j.jasc.2015.12.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2015] [Revised: 12/22/2015] [Accepted: 12/28/2015] [Indexed: 06/09/2023]
Abstract
This is a review of human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC). The epidemiology, pathology, clinical features, and risk factors of HPV-related HNSCC are discussed. HPV vaccines are also discussed.
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Affiliation(s)
- Derek B Allison
- Division of Cytopathology, Department of Pathology, The Johns Hopkins Hospital, 600 N. Wolfe Street/Pathology 412C, Baltimore, Maryland
| | - Zahra Maleki
- Division of Cytopathology, Department of Pathology, The Johns Hopkins Hospital, 600 N. Wolfe Street/Pathology 412C, Baltimore, Maryland.
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38
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Mahajan A. Practical issues in the application of p16 immunohistochemistry in diagnostic pathology. Hum Pathol 2016; 51:64-74. [DOI: 10.1016/j.humpath.2015.12.021] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 12/21/2015] [Accepted: 12/23/2015] [Indexed: 11/25/2022]
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39
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Abstract
The most common malignancy to involve the oral cavity and oropharynx is squamous cell carcinoma (SCC). Because these oral cancers share an origin from the squamous epithelium, the pathology of oral SCC might be expected to be uniform and its diagnosis repetitive. In reality, the morphologic diversity in SCC, along with the propensity for reactive processes of the oral cavity to mimic SCC histologically, renders its diagnosis one of the more challenging in surgical pathology. This article discusses variants of oral and oropharyngeal SCC and highlights those features that help distinguish human papillomavirus-related from human papillomavirus-unrelated SCC.
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40
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Lewis JS. Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus. Head Neck Pathol 2016; 10:60-67. [PMID: 26830402 PMCID: PMC4746138 DOI: 10.1007/s12105-016-0692-y] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 08/03/2015] [Indexed: 02/03/2023]
Abstract
The sinonasal tract is one of the least frequent sites for squamous cell carcinoma in the head and neck. However, it is still a complex tumor type for pathologists because there are numerous histologic variants with unusual morphologic features, several non-squamous carcinomas in the differential diagnosis that can have similar morphology and even squamous differentiation, and because of the increasing recognition of human papillomavirus (HPV) in a subset of the tumors. In addition, the unique and complex anatomy of the sinonasal tract can make proper staging and management of patients' tumors quite challenging. This article reviews sinonasal tract squamous cell carcinoma in depth and provides the latest data on Schneiderian papillomas and HPV in their pathogenesis.
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Affiliation(s)
- James S. Lewis
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41
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Banet N, Rooper LM, Maleki Z. Metastatic HPV-related head and neck squamous cell carcinoma to the lung and mediastinal lymph nodes in aspirated cytology material: A diagnostic pitfall. Diagn Cytopathol 2016; 44:206-14. [PMID: 26764038 DOI: 10.1002/dc.23425] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 12/10/2015] [Accepted: 12/16/2015] [Indexed: 01/10/2023]
Abstract
BACKGROUND Although HPV-related head and neck squamous cell carcinoma (HNSCC) has good prognosis, a small proportion of patients develop distant metastases and have worse outcomes. Such metastases can be particularly difficult to diagnose in the lung and mediastinum, where they show extensive morphologic overlap with primary pulmonary neoplasms. This case series discusses metastatic HPV-related HNSCC in lung and mediastinal fine needle aspiration (FNA) cytology. METHODS The cytopathology archives were searched for lung and mediastinal FNA specimens of patients with HNSCC. Specimens were included if either the index FNA or the patient's original HNSCC was positive for HPV by DNA in-situ hybridization (ISH). Ten such cases were identified. Patient demographics and primary tumor details were tabulated from the electronic medical record. All FNA slides and stains were reviewed. RESULTS The ten patients (mean age of 58.2 years) included 4 smokers. Smears from all cases were hypercellular and hyperchromatic, with focal keratinization in 6/10 (60%). Core biopsies and cell blocks showed basaloid morphology with variable amounts of necrosis. All ten FNAs were diffusely positive for p16 (100%) and 7/9 cases stained (77.8%) were positive for HPV DNA ISH. CONCLUSIONS Metastatic HPV-related HNSCC to the lung and mediastinal lymph nodes share the characteristic basaloid, minimally keratinizing morphology seen in Primary HNSCC cytology. Poorly differentiated pulmonary squamous cell carcinoma and neuroendocrine carcinomas are the primary differentials. Although primary lung neoplasms are not HPV-related, p16 positivity can be seen in both squamous cell and small cell lung carcinomas. HPV ISH allows definitive diagnosis of metastatic HPV-related HNSCC.
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Affiliation(s)
- Natalie Banet
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Lisa M Rooper
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Zahra Maleki
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, Maryland
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42
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Abstract
The nasal cavity and paranasal sinuses occupy the top of the upper respiratory tract and form pneumatic spaces connected with the atmosphere. They are located immediately beneath the base of the cranium, where crucial vital structures are harbored. From this region, very much exposed to airborne agents, arise some of the more complex and rare benign and malignant lesions seen in humans, whose difficulties in interpretation make this remarkable territory one of the most challenging in the practice of surgical pathology. Contents of this chapter cover inflammations and infections, polyps and pseudotumors, fungal and midfacial destructive granulomatous lesions, as well as benign, borderline, and malignant neoplasms. Among the neoplasms, emphasis is made on those entities characteristic or even unique for the sinonasal region, such as Schneiderian papillomas, glomangiopericytoma, intestinal- and non-intestinal-type adenocarcinomas, olfactory neuroblastoma, nasal-type NK-/T-cell lymphoma, and teratocarcinosarcoma. Moreover, recently recognized entities involving this territory, i.e., HPV-related non-keratinizing carcinoma, NUT carcinoma, and SMARCB1-deficient basaloid carcinoma, are also discussed in the light of their specific molecular findings. Furthermore, the text is accompanied by numerous classical and recent references, several tables, and 100 illustrations.
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Affiliation(s)
- Antonio Cardesa
- University of Barcelona, Anatomic Pathology Hospital Clínic University of Barcelona, Barcelona, Spain
| | - Pieter J. Slootweg
- Radboud Univ Nijmegen Medical Center, Pathology Radboud Univ Nijmegen Medical Center, Nijmegen, The Netherlands
| | - Nina Gale
- University of Ljubljana,, Institute of Pathology, Faculty of Medic University of Ljubljana,, Ljublijana, Slovenia
| | - Alessandro Franchi
- University of Florence, Dept of Surg & Translational Medicine University of Florence, Florence, Italy
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43
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Laco J, Sieglová K, Vošmiková H, Dundr P, Němejcová K, Michálek J, Čelakovský P, Chrobok V, Mottl R, Mottlová A, Tuček L, Slezák R, Chmelařová M, Sirák I, Vošmik M, Ryška A. The presence of high-risk human papillomavirus (HPV) E6/E7 mRNA transcripts in a subset of sinonasal carcinomas is evidence of involvement of HPV in its etiopathogenesis. Virchows Arch 2015; 467:405-415. [PMID: 26229021 DOI: 10.1007/s00428-015-1812-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Revised: 06/08/2015] [Accepted: 07/13/2015] [Indexed: 02/03/2023]
Abstract
The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.
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Affiliation(s)
- Jan Laco
- The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
| | - Kateřina Sieglová
- The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic
| | - Hana Vošmiková
- The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic
| | - Pavel Dundr
- Department of Pathology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic
| | - Kristýna Němejcová
- Department of Pathology, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic
| | - Jaroslav Michálek
- Department of Clinical and Molecular Pathology, Palacky University Olomouc, Faculty of Medicine and Dentistry and University Hospital Olomouc, Olomouc, Czech Republic
| | - Petr Čelakovský
- Department of Otorhinolaryngology and Head and Neck Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Viktor Chrobok
- Department of Otorhinolaryngology and Head and Neck Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Radovan Mottl
- Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Alena Mottlová
- Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Luboš Tuček
- Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Radovan Slezák
- Department of Dentistry, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Marcela Chmelařová
- Institute for Clinical Biochemistry and Diagnostics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Igor Sirák
- Department of Oncology and Radiotherapy, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Milan Vošmik
- Department of Oncology and Radiotherapy, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Aleš Ryška
- The Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic
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Pitiyage G, Lei M, Guererro Urbano T, Odell E, Thavaraj S. Biphenotypic human papillomavirus-associated head and neck squamous cell carcinoma: a report of two cases. Diagn Pathol 2015; 10:97. [PMID: 26169909 PMCID: PMC4501075 DOI: 10.1186/s13000-015-0334-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 06/25/2015] [Indexed: 11/11/2022] Open
Abstract
Human papillomavirus-associated oropharyngeal squamous cell carcinoma is now recognised as a subtype of head and neck cancer with distinct clinical, molecular and histological characteristics. The majority of these carcinomas are of non-keratinising squamous type but there is a growing number of histomorphologic variants of this disease. Here we describe the clinical, histomorphologic and immunophenotypic features of two cases of human papillomavirus-associated oropharyngeal squamous cell carcinoma demonstrating a clearly delineated biphasic differentiated and undifferentiated phenotype.
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Affiliation(s)
- Gayani Pitiyage
- Head and Neck Pathology, 4th Floor Tower Wing, Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, UK.
| | - Mary Lei
- Department of Clinical Oncology, Lower Ground Floor, Lambeth Wing, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, Westminster Bridge Rd, London, SE1 7EH, UK.
| | - Teresa Guererro Urbano
- Department of Clinical Oncology, Lower Ground Floor, Lambeth Wing, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, Westminster Bridge Rd, London, SE1 7EH, UK.
| | - Edward Odell
- Head and Neck Pathology, 4th Floor Tower Wing, Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, UK. .,Mucosal and Salivary Biology, King's College London Dental Institute, 4th Floor Tower Wing, Great Maze Pond, London, SE1 9RT, UK.
| | - Selvam Thavaraj
- Head and Neck Pathology, 4th Floor Tower Wing, Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, UK. .,Mucosal and Salivary Biology, King's College London Dental Institute, 4th Floor Tower Wing, Great Maze Pond, London, SE1 9RT, UK.
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Baldassarri R, Aronberg R, Levi AW, Yarbrough WG, Kowalski D, Chhieng D. Detection and genotype of high-risk human papillomavirus in fine-needle aspirates of patients with metastatic squamous cell carcinoma is helpful in determining tumor origin. Am J Clin Pathol 2015; 143:694-700. [PMID: 25873503 DOI: 10.1309/ajcpcza4pszcfhq4] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
OBJECTIVES Recent studies have shown that human papillomavirus (HPV) is associated with a certain subset of head and neck squamous cell carcinoma (HNSCC)-namely, those arising in the oropharynx. The objective of this study is to determine the efficacy, detection, and genotype of high-risk (HR) HPV using the Roche cobas 4800 system (Roche Molecular System, Pleasanton, CA). METHODS Forty-two fine-needle aspirate (FNA) specimens from 37 patients with cervical (n = 36) or mediastinal (n = 5) lymphadenopathy or a left parapharyngeal mass (n =1) were included in this prospective study. HR-HPV testing was performed on residual FNA material after direct smear preparation and, if positive, was further delineated into HPV 16/18 genotypes using the Roche cobas 4800 system. Follow-up included review of histologic material and/or electronic health records. RESULTS Among those HNSCCs that were positive for HR-HPV, 18 (100%) of 18 originated from the oropharynx, whereas only two (13%) of 15 HR-HPV-negative HNSCCs originated from the oropharynx (χ(2) test, P < .05). p16 immunohistochemical assay and HPV 16 in situ hybridization on corresponding histologic specimens were concordant with cytologic HR-HPV results. CONCLUSIONS HR-HPV detection and genotyping can be performed on lymph node FNAs with metastatic squamous cell carcinoma using the Roche cobas 4800 system. The presence of HR-HPV and/or HPV 16 is a reliable indicator of the metastatic squamous cell carcinoma originating from the oropharynx.
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Affiliation(s)
| | - Ryan Aronberg
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | - Angelique W. Levi
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | | | - Diane Kowalski
- Department of Pathology, Yale University School of Medicine, New Haven, CT
| | - David Chhieng
- Department of Pathology, Yale University School of Medicine, New Haven, CT
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Dutta R, Husain Q, Kam D, Dubal PM, Baredes S, Eloy JA. Laryngeal Papillary Squamous Cell Carcinoma. Otolaryngol Head Neck Surg 2015; 153:54-9. [DOI: 10.1177/0194599815581613] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 03/23/2015] [Indexed: 11/16/2022]
Abstract
Objective Papillary squamous cell carcinoma has emerged as a distinct entity from the more common keratinizing squamous cell carcinoma. The basis behind this distinction relates not only to its histologic variation but also to its overall prognosis and survival. The objective of this study was to demonstrate the incidence, demographics, and long-term survival of laryngeal papillary squamous cell carcinoma (LPSCC) and how it relates to other laryngeal malignancies using a population-based database. Study Design Analysis of a population-based tumor registry. Methods The United States National Cancer Institute’s Surveillance, Epidemiology, and End Results registry was used to perform a retrospective analysis. Patients diagnosed with LPSCC from 1973 to 2011 were identified. Data endpoints extracted included patient demographics, incidence, and survival. Results Three-hundred seventy cases of LPSCC were identified, corresponding to 0.5% of all laryngeal tumors. There was a 3:1 male predilection, without a significant racial preference. Most tumors identified were localized (T1) and at stage 1. The 1-year, 5-year, and 10-year disease-specific survival (DSS) for LPSCC was 97.1%, 83.1%, and 73.9%, respectively, compared with 87.9%, 64.5%, and 50.5% for other laryngeal malignancies ( P values <.0001). Surgery was associated with a higher overall DSS in both LPSCC (87.4% vs 78.8%) and other laryngeal malignancies (70% vs 59.4%) when compared with other treatment modalities. Conclusion This analysis of the largest sample of LPSCC demonstrates a better prognosis for this pathology compared with other laryngeal malignancies.
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Affiliation(s)
- Rahul Dutta
- Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Qasim Husain
- Department of Otolaryngology–Head and Neck Surgery, Columbia University Medical Center, New York, New York, USA
- Department of Otolaryngology–Head and Neck Surgery, Weill Cornell Medical College, New York, New York, USA
| | - David Kam
- Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Pariket M. Dubal
- Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Soly Baredes
- Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA
- Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Jean Anderson Eloy
- Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA
- Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Rutgers New Jersey Medical School, Newark, New Jersey, USA
- Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, USA
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Westra WH. The pathology of HPV-related head and neck cancer: implications for the diagnostic pathologist. Semin Diagn Pathol 2015; 32:42-53. [PMID: 25804343 DOI: 10.1053/j.semdp.2015.02.023] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
A subset of head and neck squamous cell carcinomas are caused by the human papillomavirus (HPV). This HPV-related form of head and neck squamous cell carcinoma (HPV-HNSCC) has captured the attention of the oncology community for its rising incidence, its link to non-traditional risk factors, and its divergent clinical behavior. To diagnose this special form of head and neck squamous cell carcinoma is to provide important prognostic information and, in some instances, redirect clinical therapy. The diagnosis of HPV-HNSCC is aided by a strong appreciation for its characteristic microscopic findings and by an awareness of aberrant features that set apart a growing list of HPV-HNSCC morphologic variants. This review will delineate the microscopic appearance of HPV-HNSCC, spotlight ways in which the misinterpretation of these microscopic features can lead to diagnostic confusion, offer recommendations for appropriate terminology when diagnosing HPV-HNSCC, and provide examples of specific diagnostic scenarios where HPV testing can inform the diagnostic process.
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Affiliation(s)
- William H Westra
- Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Otolaryngology/Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
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El-Mofty SK. Human papillomavirus-related head and neck squamous cell carcinoma variants. Semin Diagn Pathol 2015; 32:23-31. [PMID: 25804342 DOI: 10.1053/j.semdp.2015.02.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
During the last few decades, a phenotypically distinct type of head and neck squamous cell carcinoma (SCC), which is etiologically related to human papillomavirus (HPV), has emerged, and its prevalence continues to increase. The tumors are site-specific with special predilection for the oropharynx. They are morphologically and molecularly distinct and are responsive to different types of treatment modalities, with excellent clinical outcome, in spite of early lymph node metastasis. Microscopically, the carcinomas are nonkeratinizing SCCs. More recently, other variants that are believed to be etiologically related to HPV are reported. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in these HPV-related variants. This review is an attempt to answer some of these questions based on information derived from available yet limited number of publications. The variants to be discussed include nonkeratinizing SCC (NKSCC), NKSCC with maturation (hybrid type), keratinizing SCC (KSSC), basaloid squamous carcinoma (BSCC), undifferentiated carcinoma (UC), papillary SCC (PSCC), small cell carcinoma, adenosquamous carcinoma (AdSCC), and spindle cell (sarcomatoid) carcinoma.
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Affiliation(s)
- Samir K El-Mofty
- Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8118, St Louis, Missouri 63110.
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Leon ME, Shamekh R, Coppola D. Human papillomavirus-related squamous cell carcinoma of the anal canal with papillary features. World J Gastroenterol 2015; 21:2210-2213. [PMID: 25717259 PMCID: PMC4326161 DOI: 10.3748/wjg.v21.i7.2210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 09/05/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
Human papillomavirus (HPV) related squamous cell carcinoma (SCC) involving the anal canal is a well-known carcinoma associated with high-risk types of HPV. HPV-related SCC with papillary morphology (papillary SCC) has been described in the oropharynx. We describe, for the first time, a case of anal HPV-related squamous carcinoma with papillary morphology. The tumor arose from the anal mucosa. The biopsies revealed a superficially invasive SCC with prominent papillary features and associated in situ carcinoma. The tumor cells were positive for p16 and were also positive for high-risk types of HPV using chromogenic in situ hybridization. The findings are consistent with a HPV-related SCC of the anal canal with papillary features. This tumor shows histologic features similar to a papillary HPV-related SCC of the oropharynx. Additional studies are needed to characterize these lesions.
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MESH Headings
- Aged, 80 and over
- Anus Neoplasms/chemistry
- Anus Neoplasms/pathology
- Anus Neoplasms/therapy
- Anus Neoplasms/virology
- Biomarkers, Tumor/analysis
- Biopsy
- Carcinoma, Papillary/chemistry
- Carcinoma, Papillary/pathology
- Carcinoma, Papillary/therapy
- Carcinoma, Papillary/virology
- Carcinoma, Squamous Cell/chemistry
- Carcinoma, Squamous Cell/pathology
- Carcinoma, Squamous Cell/therapy
- Carcinoma, Squamous Cell/virology
- Chemoradiotherapy
- DNA, Viral/genetics
- Female
- Human Papillomavirus DNA Tests
- Humans
- Immunohistochemistry
- In Situ Hybridization
- Neoplasm Invasiveness
- Papillomaviridae/genetics
- Papillomaviridae/isolation & purification
- Papillomavirus Infections/complications
- Papillomavirus Infections/virology
- Treatment Outcome
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Histopathology of human papillomavirus-related oropharyngeal carcinoma: a review of classic and variant forms. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.mpdhp.2015.02.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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