Ferlay, J. et al. In the United States, HNSCC accounts for approximately 5% of … Bonner, J. Genetics Home Reference has merged with MedlinePlus. Trends in incidence of cancers of the oral cavity and pharynx – United States 2007–2016. However, to date, only a subset of patients with HNSCC are expected to respond to immune checkpoint inhibitors, and reliable predictive biomarkers are needed. and JavaScript. Hu, Z. et al. Res. Mager, D. L. et al. Ann. Clin. 139, 617–622 (2013). Consensus recommendations from the College of American Pathologists include testing all newly diagnosed oropharyngeal cancers for HPV by immunohistochemistry for p16INK4A, with a diagnostic threshold of diffuse nuclear and cytoplasmic staining in >70% of tumour cells149 (Fig. The transition from dysplasia to carcinoma in situ involves loss of 11q13, 13q21 and 14q32, whereas loss of 6p, 8, 4q27 and 10q23 is observed in the progression to invasive carcinoma. Chaturvedi, A. K. et al. Oncol. COVID-19 pandemic: effects and evidence-based recommendations for otolaryngology and head and neck surgery practice. Throughout treatment, attention to symptom management, functional rehabilitation and appropriate incorporation of palliative care services are key to maintaining performance status and QOL, and supporting patients at the end of life. Historically treatment of head and neck cancers involved surgical resection followed by radiation therapy for advanced tumors. In addition to E6 and E7, E5 also has a role in oncogenic transformation by helping to drive cell cycle progression66,67. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. ), U54CA209891 (J.R.G. Neoplasia 16, 789–800 (2014). ), R01DE023685 (J.R.G. The second chemo session hammered me, and the radiotherapy sessions started taking their toll. Aberrant expression of MMPs and HIF1α and their effect on HNSCC progression are discussed later. 375, 1856–1867 (2016). Furthermore, unlike cervical cancer, HPV-positive HNSCC lacks a cytological or gross precursor lesion. However, the average latency period of 10–30 years from initial oral infection to ultimate diagnosis of p16INK4A-positive oropharyngeal cancer means that risk factors might be remote143. B. Use of larynx-preservation strategies in the treatment of laryngeal cancer: American Society of Clinical Oncology clinical practice guideline update. The immune cell abundance and composition of HPV-positive tumours and HPV-negative tumours are notably different103,104. Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review. ), and NIH/NCI P30CA023074 (J.E.B.). 110, 422–428 (2014). 5, 18 (2016). Bonomo, P. et al. Prognosis of Stage III/IV resectable locally advanced head and neck squamous cell carcinoma is poor, and post-operative RT after radical resection has remained the standard treatment for this type of cancer since 1970, when Fletcher et al. Quality assessment in supportive care in head and neck cancer. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults. In addition to genetic alterations, epigenetic changes also have a role in driving HNSCC oncogenesis. HNSCC is caused by a variety of factors that can alter the DNA in cells. J. Clin. Clinical update on head and neck cancer: molecular biology and ongoing challenges. You are using a browser version with limited support for CSS. 16, 645–655 (2015). By the time of the third chemo session I absolutely knew and felt that I was in a war of attrition. & Leemans, C. R. The value of quality-of-life questionnaires in head and neck cancer. 8, 3475–3488 (2015). ΔNp63 promotes HNSCC tumour growth by multiple mechanisms, including suppression of apoptosis and p16INK4A expression and induction of mitogenic signalling73,74,75,76. Numerous studies have shown that the TME of most HNSCC tumours is highly immunosuppressive104,110. Global Cancer Observatory (GLOBOCAN): 323, 795–801 (1990). 88, 300–306 (2009). Cancer 113, 3036–3046 (2008). The awareness that HPV contributes to oropharyngeal HNSCC in the majority of patients has markedly affected clinical practice. 37, 1704–1712 (2019). Int. (eds). Cell Biol. et al. Cancer Res. Squamous cell carcinoma of the head and neck - Conditions - GTR - NCBI N. Engl. Chan, K. C. A. et al. Hecht, S. S. Tobacco smoke carcinogens and lung cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 127. Smoking Cessation: a Report of the Surgeon General. FDA approval of these agents for HNSCC treatment confirmed the power of harnessing the immune system for HNSCC therapy. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells. CAFs secrete a broad range of growth factors (such as EGF, VEGF and HGF), cytokines (such as IL-6) and chemokines that promote tumour cell growth, angiogenesis and recruitment of immunosuppressive immune cells99,100. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Proc. ), the Health and Medical Research Fund by the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region no. J. Biol. c | A p16INK4A-positive oropharyngeal squamous cell carcinoma characterized by diffuse nuclear and cytoplasmic staining for the cell cycle protein p16INK4A by immunohistochemistry, indicative of human papillomavirus (HPV)-positive disease (×10). Canc Netw. J. Infect. World Health Organization. Partlova, S. et al. Cancer Cell 9, 45–56 (2006). Whatever happens, it’s clear that the fear of falling badly sick again and spending days in hospital is something that consciously or unconsciously besets me and probably all surviving patients with cancer.”. Cancer Discov. Definitive treatment with CRT is recommended as non-surgical treatment for patients with advanced T stage (≥T3), more than one involved node or a single bulky node, and for function preservation. Med. The epidermal growth factor receptor (EGFR; also known as HER1) monoclonal antibody cetuximab is approved by the FDA as a radiation sensitizer, alone or in combination with chemotherapy, for the treatment of patients with recurrent or metastatic disease4. Tackling NCDs: ‘best buys’ and other recommended interventions for the prevention and control of noncommunicable diseases. Last, the RAS–MAPK pathway, which contributes to the growth and survival of HNSCC tumour cells, was found by one group to be infrequently mutated in HNSCC tumours, whereas this pathway was found by another group to be mutated in 18% of HNSCC tumours59. An analysis conducted in the USA employing the National Cancer Database showed that patients undergoing curative radiotherapy at facilities with high case numbers and academic centres showed higher survival than patients treated at centres with low case numbers234. These squamous cell cancers are often referred to as squamous cell carcinomas of the head and neck. In cancer, secondary prevention typically involves screening, such as mammography to find and treat early stage breast cancers or Papanicolaou smears to identify and ablate pre-cancerous HPV lesions of the cervix. JAMA Otolaryngol. High-risk HPV types and head and neck cancer. Hashibe, M. et al. Amit, M. et al. J. BMC Med. Differentiation of basal epithelial cells leads to their detachment from the basement membrane and upward migration, with progressively increasing differentiation leading to the sloughing off of terminally differentiated, non-proliferating cells. Two additional members of the TP53 gene family, TP63 and TP73, are frequently altered in HNSCC. Microbial signatures associated with oropharyngeal and oral squamous cell carcinomas. Fortunately, numerous clinical trials are ongoing and precision medicine approaches are emerging. HPV vaccination has been shown to prevent infection with HNSCC-causing HPV types, including HPV-16 and HPV-18, which are responsible for the majority of HPV-positive HNSCC. Burtness, B. et al. Immunohistochemical analyses of HNSCC tumours indicate that ~80% of ALDH1+ cells are in close proximity (≤100 μm) to a blood vessel, suggesting that the CSCs reside primarily in perivascular niches43. Biopsy can help determine if the squamous cell cancer is a low-risk tumor or a high-risk tumor that requires more aggressive treatment. Wang, Z. et al. Background Despite the use of resection and postoperative radiotherapy, high-risk squamous-cell carcinoma of the head and neck frequently recurs in the original tumor bed. Isayeva, T., Li, Y., Maswahu, D. & Brandwein-Gensler, M. Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. IARC https://monographs.iarc.fr/agents-classified-by-the-iarc/ (2020). 13-cis-retinoic acid in the treatment of oral leukoplakia. This paper underscores the high risk of developing second primary tumors in carcinogen-associated HNSCC. 75, 2468–2477 (2015). Acta Gene Regul. Oncol. ); Epidemiology (V.W.Y.L. Polo-like kinase 2 acting as a promoter in human tumor cells with an abundance of TAp73. A number of molecular biomarkers of HNSCC CSCs have been proposed, with CD44, CD133 and ALDH1 being the most extensively validated and associated with prognostic significance. 10, 295–305 (2008). Head Neck 42, 456–466 (2020). Phase IB/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumors. Hypofractionated radiotherapy for patients with early-stage glottic cancer: patterns of care and survival. Immune checkpoint inhibitor toxicity in head and neck cancer: from identification to management. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. Loss of TP53 seems to have a role in reprogramming sensory neurons in the HNSCC TME to an adrenergic, tumour-promoting phenotype102. With the increase in incidence and improved survival, more people have to cope with living beyond a diagnosis of HNSCC and its treatment (see Box 1). I had anticipated this would take longer and I think it’s a benefit of having been irradiated on one side of the throat only. Prevention of carcinogen-induced oral cancer by sulforaphane. J. Clin. New DNA methylation markers and global DNA hypomethylation are associated with oral cancer development. Cancer Res. [No authors listed] Tipifarnib targets HRAS-mutant cancers. In the specific case of HPV-positive HNSCC, the viral E5, E6 and E7 proteins promote immune evasion by effects on cellular gene and protein expression in tumour cells115,116. & Group, H. P. V. S. Prevalence of oral human papillomavirus by vaccination status among young adults (18-30 years old). 100, 261–269 (2008). J. Radiat. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov Sci. Marur, S. et al. & Grandis, J. R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Augsten, M. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Head Neck Surg. Stromal features are predictive of disease mortality in oral cancer patients. B. J. Blanchard, P. et al. Mutations in RAS genes are infrequent, with HRAS mutations being the most common (~4% of tumours). Samanna, V., Ma, T., Mak, T. W., Rogers, M. & Chellaiah, M. A. Actin polymerization modulates CD44 surface expression, MMP-9 activation, and osteoclast function. Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses. In a model of ordered histological progression of HNSCC68, mucosal epithelial cell hyperplasia is followed by dysplasia, and carcinoma in situ precedes the development of invasive carcinoma. Linge, A. et al. Parke, S. C. et al. Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. J. Radiat. Leon, X. et al. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, 36, 3091–3100 (2018). Ann Oncol. cell carcinomas and correlation with patient outcome. Amplification of CCND1, resulting in overexpression of cyclin D1, is associated with the progression of dysplastic lesions to carcinoma in situ and with a poor clinical prognosis57,90 (Fig. Oncogene 35, 5781–5794 (2016). Google Scholar. Although hazard discrimination has probably improved for HPV-positive HNSCC, prospective outcomes data are needed to validate the eighth edition. Califano, J. et al. Ferris, R. L. et al. Hyperprogression is most likely in those with HPV-negative disease, or with bulky local or regional recurrence, and when immunotherapy is used without chemotherapy. Lancet Oncol. Cancer 33, 476–480 (2014). (2) published a report on prognosis after post-operative radiotherapy. A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Metabolic activation of carcinogens results in the formation of reactive metabolites, which, if not detoxified and excreted, can damage DNA, typically by generating bulky DNA adducts. Clin. Nat. Even though patient-derived xenografts are a more accurate model of the patient tumour than cell lines, the xenograft stroma largely consists of mouse cells and these models are generally grown in immunocompromised mice. Given the limitations of preclinical models to study immune perturbations, the development of novel clinical trial platforms in conjunction with immune profiling approaches offer opportunities to test the effect of novel immunotherapies in the clinical setting with minimal risk249. IARC https://gco.iarc.fr/today (2018). Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. 68, 394–424 (2018). Fung, S. Y., Lam, J. W. & Chan, K. C. Clinical utility of circulating Epstein-Barr virus DNA analysis for the management of nasopharyngeal carcinoma. See our, URL of this page: https://medlineplus.gov/genetics/condition/head-and-neck-squamous-cell-carcinoma/. 349, 2091–2098 (2003). Induction chemotherapy may also be used to control disease when curative surgery cannot immediately be accessed, as has been the case in areas with surging incidence of COVID-19 (ref.200). Cancer Epidemiol. Wang, H. et al. Effect of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the United States. These feelings stayed with me for months, even after I returned to work 6 months later. J. Pathol. 71, 3688–3700 (2011). 49, 322–325 (2013). E6 may possess other transforming activities beyond p53 degradation but these functions are less well characterized61,62,63. The recognition that patients with HPV-associated oropharyngeal cancer, small tumours or a light smoking history enjoy exceptionally high survival150,201, but are treated with aggressive multimodality regimens that were evaluated predominantly in the more treatment-resistant HPV-negative population, raises the question as to whether the toxicities and risks of such full-dose therapy are always warranted. Dis. These families have inherited disorders that increase the risk of multiple types of cancer. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. 111, 490–497 (2019). Cancer Discov. However, these alterations are largely restricted to HPV-negative tumours, owing to the action of HPV E6 and E7 proteins in eliminating p53 and RB1 (p16INK4A inhibits phosphorylation of RB1). Elevated αSMA levels in HNSCC tumours correlate with poor prognosis101. Entering my last week of radiotherapy, I was dehydrated, underfed, and weak to the point of having to lie down while waiting for the radiotherapy sessions. More recently, the EPOC trial investigated erlotinib, a small-molecule inhibitor of EGFR, in patients with OPLs who had loss of heterozygosity (LOH) at 9p and 3p. STAT3 signalling drives the expression of genes that promote cellular proliferation and survival as well as genes encoding growth factors and cytokines that promote immunosuppression (such as VEGF, IL-6, IL-10 and TGFβ)94. Saada-Bouzid, E. et al. The estimated age-standardized rates (ASRs) of head and neck squamous cell carcinoma (HNSCC) incidence worldwide are shown for men and women combined10,11,12. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. This study led to the FDA approval of cetuximab for HNSCC. 1. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Wkly Rep. 65, 661–666 (2016). Sci. and J.R.G. Furthermore, the role of tumour mutational burden as a predictive biomarker for immunotherapy remains incompletely understood and efforts are underway to establish guidelines that are designed to harmonize tumour mutational burden evaluation and reporting241. Treatment planning should aim for the most highly curative approach, while optimizing preservation of function. 3). Prognostic impact of AJCC/UICC 8th edition new staging rules in oropharyngeal squamous cell carcinoma. Educ. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Yang, X. et al. J. Clin. In the USA, HPV vaccination is generally administered at the discretion of the paediatrician and the parents, with only Virginia, Rhode Island and the District of Columbia requiring the HPV vaccine for public school attendance. The use of tri-modality therapy (that is, the addition of CRT following surgery) is known to increase the late toxicities of radiation, including chronic dysphagia and aspiration, and might increase the risk of non-cancer-related mortality in survivors186. Oncol. The DAHANCA 6 randomized trial: effect of 6 vs 5 weekly fractions of radiotherapy in patients with glottic squamous cell carcinoma. No screening strategy has proved to be effective, and careful physical examination remains the primary approach for early detection. 48, 1–9 (2012). In addition, alcohol is metabolized to acetaldehyde, which is known to form DNA adducts58. Phys. Clin. Infiltrating immune cells also make contact with the viral particles. Histopathology images of hyperplasia, dysplasia, carcinoma in situ and invasive carcinoma are reprinted from ref.250, Springer Nature Limited. Institutional clinical trial accrual volume and survival of patients with head and neck cancer. Swartz, J. E. et al. J. Toxicol. & Markowitz, L. E. Use of a 2-dose schedule for human papillomavirus vaccination – updated recommendations of the Advisory Committee on Immunization Practices. A. et al. 141, 1214–1235 (2017). Thus, in contrast to many other solid tumour malignancies that are frequently driven by mutations in RAS or other oncogenes, HNSCC might be more frequently driven by loss of tumour suppressors. Australia’s experience. d | A p16INK4A-negative oropharyngeal squamous cell carcinoma demonstrates minimal staining by the same anti-p16INK4A antibody, a staining intensity that is indicative of HPV-negative disease (×40). These signatures might prove useful for predicting response to different therapies, particularly checkpoint inhibition. Google Scholar. Although a proportion of oral pre-malignant lesions (OPLs), which present as leukoplakia (white patches) or erythroplakia (red patches), progress to invasive cancer, the majority of patients present with advanced-stage HNSCC without a clinical history of a pre-malignancy. An international multi-center study. Incidence and mortality trends in oral and oropharyngeal cancers in China, 2005–2013. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Zhang, L. W. et al. Among patients with recurrent or metastatic HNSCC, some may be cured by salvage resection, re-irradiation (particularly for nasopharyngeal cancer)204 or metastasectomy (particularly for HPV-positive cancer)205 (Fig. 33, 3235–3242 (2015). Oncol. 157, S1–S30 (2017). Cisplatin every 3 weeks versus weekly with definitive concurrent radiotherapy for squamous cell carcinoma of the head and neck. Res. Verdonck-de Leeuw, I. M., van Nieuwenhuizen, A. As HNSCC is derived from the stratified epithelium of the upper aerodigestive mucosa, the histopathological spectrum is characterized by the extent of cellular atypia and squamous differentiation (Fig. Detailed molecular characterization as well as immune profiling of HNSCC suggests that incorporation of prognostic and predictive biomarkers into clinical management may overcome obstacles to targeted therapies and enable prolonged survival. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J. Radiol. Wang, Z., Valera, J. C., Zhao, X., Chen, Q. A unique, reticulated squamous epithelium lines the crypt structure and gaps or fissures in the basement membrane and basal layer also occur. Phys. Mehrtash, H. et al. 10, 1254 (2019). Cell Physiol. J. Med. HNSCC is generally not inherited; it typically arises from mutations in the body's cells that occur during an individual's lifetime. Oncol. Slaughter, D. P., Southwick, H. W. & Smejkal, W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Impact of treatment expertise on the outcome of patients with head and neck cancer treated within 6 randomized trials. Patel, B. P., Shah, S. V., Shukla, S. N., Shah, P. M. & Patel, P. S. Clinical significance of MMP-2 and MMP-9 in patients with oral cancer. N. Engl. Development and validation of a combined hypoxia and immune prognostic classifier for head and neck cancer. J. Clin. PubMed Central  Author information: (1)UPMC Hillman Cancer Center, 5150 Centre Avenue, 5th floor, Room 552, Pittsburgh, PA, 15232, USA. Mol. A minority of patients with HNSCC who are treated with immune checkpoint inhibition may experience accelerated disease progression, often termed hyperprogression206. Among patients with expression of the biomarker PDL1, defined as a combined positive score (CPS) of ≥20 or ≥1 (when CPS reflects all PDL1-expressing tumour cells, macrophages and immune cells as a proportion of the total number of tumour cells counted), survival was superior for pembrolizumab monotherapy than for chemotherapy plus cetuximab (14.9 versus 12.3 months, respectively). A. DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. WHO global report on trends in prevalence of tobacco smoking 2015. WHO https://apps.who.int/iris/handle/10665/156262 (2015).

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