Hypoxia and Its Influence on Radiotherapy Response of HPV-Positive and HPV-Negative Head and Neck Cancer

Head and neck squamous cancers are a heterogeneous group of cancers that arise from the upper aerodigestive tract. Etiologically, these tumors are linked to alcohol/tobacco abuse and infections with high-risk human papillomavirus (HPV). HPV-positive HNSCCs are characterized by a different biology and also demonstrate better therapy response and survival compared to alcohol/tobacco-related HNSCCs. Despite this advantageous therapy response and the clear biological differences, all locally advanced HNSCCs are treated with the same chemo-radiotherapy schedules. Although we have a better understanding of the biology of both groups of HNSCC, the biological factors associated with the increased radiotherapy response are still unclear. Hypoxia, i.e., low oxygen levels because of an imbalance between oxygen demand and supply, is an important biological factor associated with radiotherapy response and has been linked with HPV infections. In this review, we discuss the effects of hypoxia on radiotherapy response, on the tumor biology, and the tumor microenvironment of HPV-positive and HPV-negative HNSCCs by pointing out the differences between these two tumor types. In addition, we provide an overview of the current strategies to detect and target hypoxia.

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LINC00460 Is a Dual Biomarker That Acts as a Predictor for Increased Prognosis in Basal-Like Breast Cancer and Potentially Regulates Immunogenic and Differentiation-Related Genes

Frontiers in Oncology ◽

10.3389/fonc.2021.628027 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mireya Cisneros-Villanueva ◽

Lizbett Hidalgo-Pérez ◽

Alberto Cedro-Tanda ◽

Mónica Peña-Luna ◽

Marco Antonio Mancera-Rodríguez ◽

...

Keyword(s):

Breast Cancer ◽

Locally Advanced ◽

Stage Iv ◽

Therapy Response ◽

Public Health Problem ◽

Advanced Lung Cancer ◽

Potential Marker ◽

Basal Like Breast Cancer ◽

Locally Advanced Lung Cancer ◽

Tumor Types

Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogeneous disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non−coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified two novel tumor types from TCGA with LINC00460 deregulation. We used survival analysis to demonstrate that LINC00460 expression is a marker for poor overall (OS), relapse-free (RFS) and distant metastasis-free survival (DMFS) in basal-like BRCA patients. LINC00460 expression is a potential marker for aggressive phenotypes in distinct tumors, including HPV-negative HNSC, stage IV KIRC, locally advanced lung cancer and basal-like BRCA. We show that the LINC00460 prognostic expression effect is tissue-specific, since its upregulation can predict poor OS in some tumors, but also predicts an improved clinical course in BRCA patients. We found that the LINC00460 expression is significantly enriched in the Basal-like 2 (BL2) TNBC subtype and potentially regulates the WNT differentiation pathway. LINC00460 can also modulate a plethora of immunogenic related genes in BRCA, such as SFRP5, FOSL1, IFNK, CSF2, DUSP7 and IL1A and interacts with miR-103-a-1, in-silico, which, in turn, can no longer target WNT7A. Finally, LINC00460:WNT7A ratio constitutes a composite marker for decreased OS and DMFS in Basal-like BRCA, and can predict anthracycline therapy response in ER-BRCA patients. This evidence confirms that LINC00460 is a master regulator in BRCA molecular circuits and influences clinical outcome.

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TO COMPARE THE EFFICACY OF CONCOMITANT BOOST RADIOTHERAPY AGAINST CONCURRENT CHEMORADIATION IN LOCALLY ADVANCED HEAD AND NECK CANCER (OROPHARYNX/LARYNX/ HYPOPHARYNX)

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v4i2.946 ◽

2020 ◽

Vol 4 (2) ◽

Author(s):

Kapil Mohan Pal ◽

Amit Rana ◽

Priyanka Rana ◽

Shalini . ◽

Manoj Gupta ◽

...

Keyword(s):

Radiation Therapy ◽

Head And Neck ◽

Squamous Cell ◽

Randomized Study ◽

Locally Advanced ◽

Complete Response ◽

Upper Aerodigestive Tract ◽

Conventional Fractionation ◽

Concomitant Boost ◽

Concomitant Chemoradiation

Background: Most head and neck cancers, indeed 95% or more, are squamous cell carcinomas (SCC) and variants thereof, originating from the epithelium of the mucosal lining of the upper aerodigestive tract (UADT), and adenocarcinomas from associated secretory glands. Methods: This prospective randomized study was conducted in the Department of Radiation Therapy & Oncology, Regional Cancer Centre, IGMC, Shimla and patients were enrolled for a period of one year, from July 2012 to July 2013.It included all the eligible, previously untreated patients of squamous cell carcinoma of Head and Neck with histologically confirmed diagnosis and no evidence of distant metastasis. The sites included were oro-pharynx, hypo-pharynx and larynx with stages III, IV A and IV B. Results: On first follow up, overall there was complete response at nodal site in 50 patients(69.4%) 26 in CRT arm (70.3%) and 24 in ART arm(68.6%), however the difference was not statistically significant (p=0.875). Conclusion: There was comparable locoregional disease control with the use of accelerated six fractions a week radiation therapy compared to concomitant chemoradiation with conventional fractionation. Keywords: Six fraction, Concomitant chemoradiation, Conventional fractionation.

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Personalizing Postoperative Treatment of Head and Neck Cancers

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_201087 ◽

2018 ◽

pp. 515-522 ◽

Cited By ~ 3

Author(s):

Ellie Maghami ◽

Shlomo A. Koyfman ◽

Jared Weiss

Keyword(s):

Adjuvant Therapy ◽

Head And Neck ◽

Locally Advanced ◽

Tumor Biology ◽

Postoperative Treatment ◽

Trimodality Therapy ◽

Pathologic Features ◽

Quality Life ◽

Hpv Status ◽

The Impact

Head and neck cancer (HNC) treatment is a complex multidisciplinary undertaking. Although overtreatment can result in functional and cosmetic defects, undertreatment can result in cancer recurrence. Surgery and chemoradiotherapy are both accepted standards for the curative intent treatment of locally advanced mucosal squamous cell carcinoma of the head and neck, but are often prioritized differently depending on the site of tumor origin (e.g., oral cavity/sinonasal vs. oropharynx/larynx), tumor burden, tumor biology, quality-life considerations, and patient preference. Regardless of modalities chosen, failure to cure remains a considerable problem in locally advanced disease. For patients treated with primary surgery, high-risk pathologic features portend higher recurrence rates, and adjuvant therapy can reduce these rates and improve outcomes. This report details which tumor- and nodal-related factors are indications for adjuvant therapy, examines the impact of tumor HPV status on adjuvant treatment paradigms, and considers which systemic therapies should be used for which patients when trimodality therapy is indicated.

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Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22094981 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4981

Author(s):

Teresa Magnes ◽

Sandro Wagner ◽

Dominik Kiem ◽

Lukas Weiss ◽

Gabriel Rinnerthaler ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Locally Advanced ◽

Neck Squamous Cell Carcinoma ◽

Upper Aerodigestive Tract ◽

Hpv Status

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials.

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Targeted Treatment of Head and Neck (Pre)Cancer: Preclinical Target Identification and Development of Novel Therapeutic Applications

Cancers ◽

10.3390/cancers13112774 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2774

Author(s):

Anne M. van Harten ◽

Ruud H. Brakenhoff

Keyword(s):

Targeted Therapy ◽

Head And Neck ◽

De Novo ◽

Synthetic Lethality ◽

Therapy Response ◽

Genetic Alterations ◽

Future Perspective ◽

Upper Aerodigestive Tract ◽

Treatment Protocols ◽

Druggable Targets

Head and neck squamous cell carcinomas (HNSCC) develop in the mucosal lining of the upper-aerodigestive tract. In carcinogen-induced HNSCC, tumors emerge from premalignant mucosal changes characterized by tumor-associated genetic alterations, also coined as ‘fields’ that are occasionally visible as leukoplakia or erythroplakia lesions but are mostly invisible. Consequently, HNSCC is generally diagnosed de novo at more advanced stages in about 70% of new diagnosis. Despite intense multimodality treatment protocols, the overall 5-years survival rate is 50–60% for patients with advanced stage of disease and seems to have reached a plateau. Of notable concern is the lack of further improvement in prognosis despite advances in treatment. This can be attributed to the late clinical presentation, failure of advanced HNSCC to respond to treatment, the deficit of effective targeted therapies to eradicate tumors and precancerous changes, and the lack of suitable markers for screening and personalized therapy. The molecular landscape of head and neck cancer has been elucidated in great detail, but the absence of oncogenic mutations hampers the identification of druggable targets for therapy to improve outcome of HNSCC. Currently, functional genomic approaches are being explored to identify potential therapeutic targets. Identification and validation of essential genes for both HNSCC and oral premalignancies, accompanied with biomarkers for therapy response, are being investigated. Attentive diagnosis and targeted therapy of the preceding oral premalignant (preHNSCC) changes may prevent the development of tumors. As classic oncogene addiction through activating mutations is not a realistic concept for treatment of HNSCC, synthetic lethality and collateral lethality need to be exploited, next to immune therapies. In recent studies it was shown that cell cycle regulation and DNA damage response pathways become significantly altered in HNSCC causing replication stress, which is an avenue that deserves further exploitation as an HNSCC vulnerability for treatment. The focus of this review is to summarize the current literature on the preclinical identification of potential druggable targets for therapy of (pre)HNSCC, emerging from the variety of gene knockdown and knockout strategies, and the testing of targeted inhibitors. We will conclude with a future perspective on targeted therapy of HNSCC and premalignant changes.

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Human Papillomavirus Associated Oropharyngeal Carcinoma-Diagnosis and Management

10.5772/intechopen.96234 ◽

2021 ◽

Author(s):

Mullangath Prakasan Aparna ◽

Ravi Rejnish Kumar ◽

Malu Rafi ◽

Geethu Babu ◽

Pradeep Naveen Kumar ◽

...

Keyword(s):

Human Papillomavirus ◽

Head And Neck ◽

Locally Advanced ◽

Response To Treatment ◽

Treatment Modalities ◽

Oropharyngeal Carcinoma ◽

Upper Aerodigestive Tract ◽

Separate Clinical Entity ◽

Advanced Stages ◽

Management Of Hpv

Head and neck squamous cell carcinomas arise from the mucosa of the upper aerodigestive tract and is often driven by risk factors like tobacco and alcohol consumption. Most of the time patients present with locally advanced stages and the outcome is poor, despite recent advances in multi-modality treatment. The epidemiology of the disease has changed over the last decade with the introduction of a separate clinical entity; Human Papillomavirus (HPV) associated head and neck cancer. The tumorigenesis is different from that of tobacco and alcohol-driven malignancies. These tumors have a better response to treatment owing to their inherent genetic makeup and carry an excellent prognosis. The current school of thought is to reduce the long-term morbidities associated with various treatment modalities, as these patients tend to survive longer. The best management of HPV-associated oropharyngeal cancer is under active investigation.

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