HPV-related squamous cell carcinoma of oropharynx: a review

2020 ◽  
Vol 73 (10) ◽  
pp. 624-629
Author(s):  
Siavash Rahimi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Control ◽  
Standard Technique ◽  
Hpv Infection ◽  
Head And Neck Cancers ◽  
Direct Demonstration ◽  
Staging Systems

In early 1930, R. E. Shope paved the way for the recognition of human papillomavirus (HPV) as a causative agent of some types of cancers. In early 2000, the relationship between HPV and a subset of head and neck cancers, mostly located in the oropharynx, was discovered. In the last 20 years, we have made great progress in the recognition and treatment of HPV-positive head and neck cancers. However, there are still grey areas that leave room to subjective interpretation and need to be addressed. The majority of high risk (HR) HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) shows a ‘basaloid’ morphology, and despite the variegated morphological spectrum of this malignancy, highlighted by some very recent publications, there is a lack of consensus on a universal morphological classification of HPV-OPSCC. The advent of immunohistochemistry with p16 ink4a (p16) protein made the diagnosis of HPV-related OPSCC more straightforward; currently patients with OPSCC are stratified in p16-positive and p16-negative. Although p16 is an excellent surrogate of HR HPV infection, it is not the direct demonstration of the presence of virus. At present, there is no univocal ‘gold-standard’ technique for the detection of oncogenic HPV infection. It is well known that HR HPV-related (OPSCC) bear significantly better survival outcome than HPV-negative cases. Consequently, the eighth edition of the American Joint Committee on Cancer and the Union for International Cancer Control now have separate staging systems for these two distinct malignancies. The present review discusses the salient features of HR HPV-driven OPSCC.

scholarly journals A Current Update on Human Papillomavirus-Associated Head and Neck Cancers

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 922 ◽  
Author(s):  
Ebenezer Tumban
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Region ◽  
Hpv Infection ◽  
Head And Neck Cancers ◽  
Oral Transmission ◽  
Future Challenges

Human papillomavirus (HPV) infection is the cause of a growing percentage of head and neck cancers (HNC); primarily, a subset of oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, and laryngeal squamous cell carcinoma. The majority of HPV-associated head and neck cancers (HPV + HNC) are caused by HPV16; additionally, co-factors such as smoking and immunosuppression contribute to the progression of HPV + HNC by interfering with tumor suppressor miRNA and impairing mediators of the immune system. This review summarizes current studies on HPV + HNC, ranging from potential modes of oral transmission of HPV (sexual, self-inoculation, vertical and horizontal transmissions), discrepancy in the distribution of HPV + HNC between anatomical sites in the head and neck region, and to studies showing that HPV vaccines have the potential to protect against oral HPV infection (especially against the HPV types included in the vaccines). The review concludes with a discussion of major challenges in the field and prospects for the future: challenges in diagnosing HPV + HNC at early stages of the disease, measures to reduce discrepancy in the prevalence of HPV + HNC cases between anatomical sites, and suggestions to assess whether fomites/breast milk can transmit HPV to the oral cavity.

scholarly journals HPV infections in head and neck cancers (HNSCC) – clinical course and efficiency of therapy

2019 ◽  
Vol 65 (3) ◽  
Author(s):  
Mateusz Sikora ◽  
Magda Przesławska ◽  
Rafał Becht
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Clinical Course ◽  
Host Immune Response ◽  
Hpv Infection ◽  
Head And Neck Cancers ◽  
Immunosuppressive Effect

Head and neck cancers represent a heterogenous group of neoplasms. Among them, the most frequently occurring is squamous cell carcinoma. Risk factors that can contribute to the development of head and neck cancers are smoking, high proof alcohol abuse and human papilloma virus (HPV) infection. Head and neck cancers may be divided into HPV positive and HPV negative. This division shows the different landscape of carcinogenesis, median age of onset, etiopathogenesis, clinical course and treatment efficiency. Head and neck squamous cell carcinoma (HNSCC), especially HPV positive, belongs to highly immunogenic cancers. Its development relates to HPV infection and host immune response, especially with T regulatory lymphocytes response. Programmed cell death protein-1 (PD-1), which shows immunosuppressive effect on host’s immune system, takes part  in cancerogenesis. That favours carcinogenesis. The development of immuno-oncology and better understanding of HNSCC pathogenesis has contributed to developments in immunotherapy, a method of care which is used preferably in the treatment of advanced, refractory or relapsed cancers that did not respond to standard-of care cancer treatments – in the case of HNSCC it is surgical resection with possible radiochemotherapy or chemotherapy. The idea of immunotherapy is to remove tumor immunosuppressive effect and to boost host immune response to eliminate neoplasm.This article shows a review of current knowledge and new methods of therapy concerned with HNSCC treatment, especially HPV positive HNSCC.

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

scholarly journals Effectiveness of planned surveillance for detecting second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma

2020 ◽  
Vol 50 (10) ◽  
pp. 1162-1167 ◽  
Author(s):  
Takeshi Shinozaki ◽  
Chikatoshi Katada ◽  
Kiyoto Shiga ◽  
Takahiro Asakage ◽  
Tetsuji Yokoyama ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Endoscopic Resection ◽  
Squamous Cell ◽  
Head And Neck Cancers ◽  
Transoral Surgery ◽  
Second Primary ◽  
Laryngeal Function

Abstract Background Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients’ outcomes and the quality of life; however, an adequate surveillance schedule remains unclear. Methods We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3–6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter. Results During the median follow-up period of 49.4 months (1.3–81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function. Conclusions Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.

Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma

2015 ◽  
pp. 123-128 ◽  
Author(s):  
Pedro Henrique Isaacsson Velho ◽  
Gilberto Castro ◽  
Christine H. Chung
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Anticancer Agents ◽  
Neck Region ◽  
Hpv Infection ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma ◽  
Preclinical Data

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosal epithelia in the head and neck region. The most common risk factors are tobacco use, alcohol consumption, and HPV infection, particularly in the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct from the HPV-negative HNSCC; however, deregulations within the phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway with a gain-of-function in HNSCC. This article reviews the basic biology and clinical data from the trials involving anticancer agents targeting the PI3K pathway in HNSCC. It also discusses the difficulties of translating the preclinical data to tangible clinical efficacy of these agents in patients with HNSCC even when there is significant preclinical data suggesting the PI3K pathway is a promising therapeutic target in HNSCC. We conclude that additional studies to determine appropriate patient selection for the activation of PI3K pathway and to develop targeted agents either as a monotherapy or combination therapy with favorable toxicity profiles are required before a broader clinical application.

HPV infection in head and neck squamous cell carcinoma

Toukeibu Gan ◽  
2009 ◽  
Vol 35 (4) ◽  
pp. 360-364 ◽  
Author(s):  
Yutaka Tokumaru ◽  
Masato Fujii ◽  
Noboru Habu ◽  
Yoko Yajima ◽  
Tatsuo Matsunaga ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma

Comparison of HPV E6,E7 mRNA/PD-L1 assay using flow cytometry and p16 IHC expression in oral cancer samples.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 114-114 ◽  
Author(s):  
Yvette Carrasco ◽  
Amanda Chargin ◽  
Haitham Mirghani ◽  
Bruce Kendrick Patterson
Keyword(s):  
Flow Cytometry ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Single Cells ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv E6

114 Background: Research into causality of head and neck squamous cell carcinoma (HNSCC) has found a link to HPV infections affiliated with better survival than tobacco associated HNSCC. Currently, p16 immunohistochemistry is used as a predictive biomarker for HPV infection in HNSCC. We were interested in looking at an additional biomarker, HPV E6,E7 mRNA overexpression by flow cytometry, to see if it correlated with p16 status. Each test looks at a different marker of HPV infection, p16 as a surrogate of E7 activity, and E6,E7 mRNA overexpression as a marker of transcriptionally active and integrated virus. Currently p16 positive samples are confirmed with an ISH assay. Additionally, we looked at the PD-L1 expression in these tumors to see if it correlated with HPV mRNA overexpression. Advances in immuno-oncology have brought immunotherapy to the forefront of cancer treatment including HNSCC. Methods: Swabs were collected from Institut Gustave Roussy patients with lesions of the oral pharynx. Swabs were placed into a vial with a proprietary fixation solution and shipped overnight for processing. Upon receipt, samples were passed through a 35 uM filter to remove aggregates. Cells underwent in situ hybridization with E6, E7 mRNA probes (HPV OncoTect), were labeled with PD-L1 Ab, and then stained with a cell cycle dye identify single nucleated cells prior to analysis on the flow cytometer. FFPE biopsy tissue of the lesion was tested with p16 IHC. Positive samples were confirmed by ISH. Results: We analyzed samples from 27 patients with oral cancer with the combined E6, E7 mRNA/PD-L1 assay by flow cytometry and p16/ISH. Concordance between HPV E6,E7 mRNA positive results and p16 positive confirmed by ISH was 74%. Interestingly, PD-L1 expression was seen only in samples without HPV infection (according to HPV E6,E7 mRNA flow result). Samples are still being accrued and updated data will be presented at the meeting. Conclusions: Here we report a novel assay to quantify both HPV E6, E7 mRNA and PD-L1 simultaneously in single cells from head and neck squamous cell carcinoma. In addition, the ability to characterize both E6,E7 mRNA expression and PD-L1 in one test can provide clinicians with insight into treatment options.

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