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16 pages, 2261 KiB

Open AccessArticle

Repositioning Fenofibrate to Reactivate p53 and Reprogram the Tumor-Immune Microenvironment in HPV+ Head and Neck Squamous Cell Carcinoma

by W. Quinn O’Neill, Xiujie Xie, Shanying Gui, Heping Yu, Jacqueline Davenport, Thomas Cartwright, Marta Storl-Desmond, Esther Ryu, Ernest R. Chan, Shufen Cao, Pingfu Fu, Theodoros N. Teknos and Quintin Pan

Cancers 2022, 14(2), 282; https://doi.org/10.3390/cancers14020282 - 07 Jan 2022

Cited by 7 | Viewed by 2213

Abstract

Human papillomavirus-associated head and neck squamous cell carcinoma (HPV+ HNSCC) is recognized as a distinct disease with unique etiology and clinical features. Current standard of care therapeutic modalities are identical for HPV+ and HPV− HNSCC and thus, there remains an opportunity to develop [...] Read more.

Human papillomavirus-associated head and neck squamous cell carcinoma (HPV+ HNSCC) is recognized as a distinct disease with unique etiology and clinical features. Current standard of care therapeutic modalities are identical for HPV+ and HPV− HNSCC and thus, there remains an opportunity to develop innovative pharmacologic approaches to exploit the inherent vulnerabilities of HPV+ HNSCC. In this study, using an inducible HPVE6E7 knockdown system, we found that HPV+ HNSCC cells are addicted to HPVE6E7, such that loss of these viral oncogenes impaired tumorigenicity in vitro and in vivo. A number of druggable pathways, including PPAR and Wnt, were modulated in response to HPVE6E7 loss. Fenofibrate showed significant anti-proliferative effects in a panel of HPV+ cancer cell lines. Additionally, fenofibrate impaired tumor growth as monotherapy and potentiated the activity of cisplatin in a pre-clinical HPV+ animal model. Systemic fenofibrate treatment induced p53 protein accumulation, and surprisingly, re-programmed the tumor-immune microenvironment to drive immune cell infiltration. Since fenofibrate is FDA-approved with a favorable long-term safety record, repositioning of this drug, as a single agent or in combination with cisplatin or checkpoint blockade, for the HPV+ HNSCC setting should be prioritized. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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13 pages, 2950 KiB

Open AccessArticle

Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes

by Hira Shaikh, Julie E. McGrath, Brittany Hughes, Joanne Xiu, Pavel Brodskiy, Ammar Sukari, Sourat Darabi, Chukwuemeka Ikpeazu, Chadi Nabhan, Wolfgang Michael Korn and Trisha M. Wise-Draper

Cancers 2021, 13(24), 6309; https://doi.org/10.3390/cancers13246309 - 16 Dec 2021

Cited by 9 | Viewed by 2520

Abstract

Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients overall have a poor prognosis. However, human papillomavirus (HPV)-associated R/M oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better prognosis compared to HPV−negative disease. Immune checkpoint blockade (ICB) is the standard of [...] Read more.

Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients overall have a poor prognosis. However, human papillomavirus (HPV)-associated R/M oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better prognosis compared to HPV−negative disease. Immune checkpoint blockade (ICB) is the standard of care for R/M HNSCC. However, whether HPV and its surrogate marker, p16, portend an improved response to ICB remains controversial. We queried the Caris Life Sciences CODEai database for p16+ and p16− HNSCC patients using p16 as a surrogate for HPV. A total of 2905 HNSCC (OPSCC, n = 948) cases were identified. Of those tested for both HPV directly and p16, 32% (251/791) were p16+ and 28% (91/326) were HPV+. The most common mutation in the OPSCC cohort was TP53 (33%), followed by PIK3CA (17%) and KMT2D (10.6%). TP53 mutations were more common in p16− (49%) versus the p16+ group (10%, p < 0.0005). Real-world overall survival (rwOS) was longer in p16+ compared to p16− OPSCC patients, 33.3 vs. 19.1 months (HR = 0.597, p = 0.001), as well as non-oropharyngeal (non-OP) HNSCC patients (34 vs. 17 months, HR 0.551, p = 0.0001). There was no difference in the time on treatment (TOT) (4.2 vs. 2.8 months, HR 0.796, p = 0.221) in ICB-treated p16+ vs. p16− OPSCC groups. However, p16+ non-OP HNSCC patients treated with ICB had higher TOT compared to the p16− group (4.3 vs. 3.3 months, HR 0.632, p = 0.016), suggesting that p16 may be used as a prognostic biomarker in non-OP HNSCC, and further investigation through prospective clinical trials is warranted. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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18 pages, 2882 KiB

Open AccessArticle

Radiomics Predicts for Distant Metastasis in Locally Advanced Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

by Benjamin Rich, Jianfeng Huang, Yidong Yang, William Jin, Perry Johnson, Lora Wang and Fei Yang

Cancers 2021, 13(22), 5689; https://doi.org/10.3390/cancers13225689 - 14 Nov 2021

Cited by 16 | Viewed by 8690

Abstract

(1) Background and purpose: clinical trials have unsuccessfully tried to de-escalate treatment in locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) with the goal of reducing treatment toxicity. The aim of this study was to explore the role of radiomics [...] Read more.

(1) Background and purpose: clinical trials have unsuccessfully tried to de-escalate treatment in locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) with the goal of reducing treatment toxicity. The aim of this study was to explore the role of radiomics for risk stratification in this patient population to guide treatment. (2) Methods: the study population consisted of 225 patients with locally advanced HPV+ OPSCC treated with curative-intent radiation or chemoradiation therapy. Appearance of distant metastasis was used as the endpoint event. Radiomics data were extracted from the gross tumor volumes (GTVs) identified on the planning CT, with gray level being discretized using three different bin widths (8, 16, and 32). The data extracted for the groups with and without distant metastasis were subsequently balanced using three different algorithms including synthetic minority over-sampling technique (SMOTE), adaptive synthetic sampling (ADASYN), and borderline SMOTE. From these different combinations, a total of nine radiomics datasets were derived. Top features that minimized redundancy while maximizing relevance to the endpoint were selected individually and collectively for the nine radiomics datasets to build support vector machine (SVM) based predictive classifiers. Performance of the developed classifiers was evaluated by receiver operating characteristic (ROC) curve analysis. (3) Results: of the 225 locally advanced HPV+ OPSCC patients being studied, 9.3% had developed distant metastases at last follow-up. SVM classifiers built for the nine radiomics dataset using either their own respective top features or the top consensus ones were all able to differentiate the two cohorts at a level of excellence or beyond, with ROC area under curve (AUC) ranging from 0.84 to 0.95 (median = 0.90). ROC comparisons further revealed that the majority of the built classifiers did not distinguish the two cohorts significantly better than each other. (4) Conclusions: radiomics demonstrated discriminative ability in distinguishing patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone and may serve to risk stratify this patient population with the purpose of guiding the appropriate therapy. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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9 pages, 233 KiB

Open AccessArticle

Head and Neck Cancer among American Indian and Alaska Native Populations in California, 2009–2018

by Brooke R. Warren, Jennifer R. Grandis, Daniel E. Johnson and Alessandro Villa

Cancers 2021, 13(20), 5195; https://doi.org/10.3390/cancers13205195 - 16 Oct 2021

Cited by 3 | Viewed by 1406

Abstract

The purpose of this study was to determine the incidence of HPV-positive (HPV+) and HPV-negative (HPV-) head and neck cancer (HNC) in the American Indian/Alaska Native (AI/AN) population in California to assess whether incidence is higher among AI/ANs compared to other ethnicities. We [...] Read more.

The purpose of this study was to determine the incidence of HPV-positive (HPV+) and HPV-negative (HPV-) head and neck cancer (HNC) in the American Indian/Alaska Native (AI/AN) population in California to assess whether incidence is higher among AI/ANs compared to other ethnicities. We analyzed data from the California Cancer Registry, which contains data reported to the Cancer Surveillance Section of the Department of Public Health. A total of 51,289 HNC patients were identified for the years 2009–2018. Outcomes of interest included sex, stage at presentation, 5-year survival rate, tobacco use, and HPV status. AI/AN and White patients had the highest burden of late stage HNC (AI/AN 6.3:100,000; 95% CI 5.3–7.4, White 5.8:100,000; 95% CI 5.7–5.9) compared to all ethnicities or races (Black: 5.2; 95% CI 4.9–5.5; Asian/Pacific Islander: 3.2; 95% CI 3–3.3; and Hispanic: 3.1; 95% CI 3–3.2 per 100,000). Additionally, AI/AN and White patients had the highest burden of HPV+ lip, oral cavity, and pharynx HNC (AI/AN 0.9:100,000; 95% CI 0.6–1.4, White 1.1:100,000; 95% CI 1–1.1) compared to all ethnicities or races (Black: 0.8:100,000; 95% CI 0.7–0.9; Asian/Pacific Islander: 0.4; 95% CI 0.4–0.5; and Hispanic: 0.6; 95% CI 0.5–0.6). AI/ANs had a decreased 5-year survival rate compared to White patients (AI/AN 59.9%; 95% CI 51.9–67.0% and White 67.7%; 95% CI 67.00–68.50%) and a higher incidence of HNC in former and current tobacco users. These findings underscore the disparities that exist in HNC for California AI/AN populations. Future studies should aim to elucidate why the unequal burden of HNC outcomes exists, how to address increased tobacco usage, and HPV vaccination patterns to create culturally and community-based interventions. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

9 pages, 1063 KiB

Open AccessArticle

Impact of p16 Status and Anatomical Site in Anti-PD-1 Immunotherapy-Treated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients

by Kate Clancy, Chelsea S. Hamill, W. Quinn O’Neill, Brandon Vu, Jason Thuener, Shanying Gui, Shawn Li, Nicole Fowler, Rod Rezaee, Pierre Lavertu, Jay Wasman, Monaliben Patel, Hira Shaikh, Eric Vick, Anant Madabhushi, Trisha M. Wise-Draper, Kyunghee Burkitt, Theodoros N. Teknos and Quintin Pan

Cancers 2021, 13(19), 4861; https://doi.org/10.3390/cancers13194861 - 28 Sep 2021

Cited by 6 | Viewed by 2287

Abstract

In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed [...] Read more.

In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS; oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23–47.8); p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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19 pages, 986 KiB

Open AccessArticle

Role of IQGAP1 in Papillomavirus-Associated Head and Neck Tumorigenesis

by Tao Wei, Suyong Choi, Darya Buehler, Denis Lee, Ella Ward-Shaw, Richard A. Anderson and Paul F. Lambert

Cancers 2021, 13(9), 2276; https://doi.org/10.3390/cancers13092276 - 10 May 2021

Cited by 8 | Viewed by 2196

Abstract

Approximately 25% of head and neck squamous cell carcinomas (HNSCC) are associated with human papillomavirus (HPV) infection. In these cancers as well as in HPV-associated anogenital cancers, PI3K signaling is highly activated. We previously showed that IQ motif-containing GTPase activating protein 1 (IQGAP1), [...] Read more.

Approximately 25% of head and neck squamous cell carcinomas (HNSCC) are associated with human papillomavirus (HPV) infection. In these cancers as well as in HPV-associated anogenital cancers, PI3K signaling is highly activated. We previously showed that IQ motif-containing GTPase activating protein 1 (IQGAP1), a PI3K pathway scaffolding protein, is overexpressed in and contributes to HNSCC and that blocking IQGAP1-mediated PI3K signaling reduces HPV-positive HNSCC cell survival and migration. In this study, we tested whether IQGAP1 promotes papillomavirus (PV)-associated HNSCCs. IQGAP1 was necessary for optimal PI3K signaling induced by HPV16 oncoproteins in transgenic mice and MmuPV1 infection, a mouse papillomavirus that causes HNSCC in mice. Furthermore, we found that, at 6 months post-infection, MmuPV1-infected Iqgap1^−/− mice developed significantly less severe tumor phenotypes than MmuPV1-infected Iqgap1^+/+ mice, indicating a role of IQGAP1 in MmuPV1-associated HNSCC. The tumors resulting from MmuPV1 infection showed features consistent with HPV infection and HPV-associated cancer. However, such IQGAP1-dependent effects on disease severity were not observed in an HPV16 transgenic mouse model for HNC. This may reflect that IQGAP1 plays a role in earlier stages of viral pathogenesis, or other activities of HPV16 oncogenes are more dominant in driving carcinogenesis than their influence on PI3K signaling. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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Review

Jump to: Research

24 pages, 1349 KiB

Open AccessReview

Head and Neck Cancer Susceptibility and Metabolism in Fanconi Anemia

by Tafadzwa Chihanga, Sara Vicente-Muñoz, Sonya Ruiz-Torres, Bidisha Pal, Mathieu Sertorio, Paul R. Andreassen, Ruby Khoury, Parinda Mehta, Stella M. Davies, Andrew N. Lane, Lindsey E. Romick-Rosendale and Susanne I. Wells

Cancers 2022, 14(8), 2040; https://doi.org/10.3390/cancers14082040 - 18 Apr 2022

Cited by 1 | Viewed by 3004

Abstract

Fanconi anemia (FA) is a rare inherited, generally autosomal recessive syndrome, but it displays X-linked or dominant negative inheritance for certain genes. FA is characterized by a deficiency in DNA damage repair that results in bone marrow failure, and in an increased risk [...] Read more.

Fanconi anemia (FA) is a rare inherited, generally autosomal recessive syndrome, but it displays X-linked or dominant negative inheritance for certain genes. FA is characterized by a deficiency in DNA damage repair that results in bone marrow failure, and in an increased risk for various epithelial tumors, most commonly squamous cell carcinomas of the head and neck (HNSCC) and of the esophagus, anogenital tract and skin. Individuals with FA exhibit increased human papilloma virus (HPV) prevalence. Furthermore, a subset of anogenital squamous cell carcinomas (SCCs) in FA harbor HPV sequences and FA-deficient laboratory models reveal molecular crosstalk between HPV and FA proteins. However, a definitive role for HPV in HNSCC development in the FA patient population is unproven. Cellular metabolism plays an integral role in tissue homeostasis, and metabolic deregulation is a known hallmark of cancer progression that supports uncontrolled proliferation, tumor development and metastatic dissemination. The metabolic consequences of FA deficiency in keratinocytes and associated impact on the development of SCC in the FA population is poorly understood. Herein, we review the current literature on the metabolic consequences of FA deficiency and potential effects of resulting metabolic reprogramming on FA cancer phenotypes. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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12 pages, 258 KiB

Open AccessReview

Vaccine Strategies for Human Papillomavirus-Associated Head and Neck Cancers

by Jade Z. Zhou, Jessica Jou and Ezra Cohen

Cancers 2022, 14(1), 33; https://doi.org/10.3390/cancers14010033 - 22 Dec 2021

Cited by 19 | Viewed by 3559

Abstract

The rising incidence of oropharyngeal squamous cell cancers (OPSCC) in the United States is largely attributed to HPV. Prophylactic HPV vaccines have demonstrated effectiveness against oral infection of HPV 16 and HPV 18. We review the global epidemiology and biology of HPV-related cancers [...] Read more.

The rising incidence of oropharyngeal squamous cell cancers (OPSCC) in the United States is largely attributed to HPV. Prophylactic HPV vaccines have demonstrated effectiveness against oral infection of HPV 16 and HPV 18. We review the global epidemiology and biology of HPV-related cancers as well as the development of HPV vaccines and their use worldwide. We also review the various strategies and challenges in development of therapeutic HPV vaccines. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

17 pages, 679 KiB

Open AccessReview

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

by Marilyn Wegge, Rüveyda Dok and Sandra Nuyts

Cancers 2021, 13(23), 5959; https://doi.org/10.3390/cancers13235959 - 26 Nov 2021

Cited by 11 | Viewed by 2439

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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16 pages, 643 KiB

Open AccessReview

Immunotherapy Approaches in HPV-Associated Head and Neck Cancer

by Ricklie Julian, Malvi Savani and Julie E. Bauman

Cancers 2021, 13(23), 5889; https://doi.org/10.3390/cancers13235889 - 23 Nov 2021

Cited by 21 | Viewed by 3209

Abstract

Immunotherapy approaches for head and neck squamous cell carcinoma (HNSCC) are rapidly advancing. Human papillomavirus (HPV) has been identified as a causative agent in a subset of oropharyngeal cancers (OPC). HPV-positive OPC comprises a distinct clinical and pathologic disease entity and has a [...] Read more.

Immunotherapy approaches for head and neck squamous cell carcinoma (HNSCC) are rapidly advancing. Human papillomavirus (HPV) has been identified as a causative agent in a subset of oropharyngeal cancers (OPC). HPV-positive OPC comprises a distinct clinical and pathologic disease entity and has a unique immunophenotype. Immunotherapy with anti-PD1 checkpoint inhibitors has exhibited improved outcomes for patients with advanced HNSCC, irrespective of HPV status. To date, the clinical management of HPV-positive HNSCC and HPV-negative HNSCC has been identical, despite differences in the tumor antigens, immune microenvironment, and immune signatures of these two biologically distinct tumor types. Numerous clinical trials are underway to further refine the application of immunotherapy and develop new immunotherapy approaches. The aim of this review is to highlight the developing role of immunotherapy in HPV-positive HNSCC along with the clinical evidence and preclinical scientific rationale behind emerging therapeutic approaches, with emphasis on promising HPV-specific immune activators that exploit the universal presence of foreign, non-self tumor antigens. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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20 pages, 416 KiB

Open AccessReview

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

by Sharon Changshan Wu and Karl Münger

Cancers 2021, 13(22), 5690; https://doi.org/10.3390/cancers13225690 - 14 Nov 2021

Cited by 5 | Viewed by 2169

Abstract

Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Due to their expression pattern, they have historically been attractive targets for immunotherapies. A growing number of studies implicate CT antigens in almost [...] Read more.

Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Due to their expression pattern, they have historically been attractive targets for immunotherapies. A growing number of studies implicate CT antigens in almost all hallmarks of cancer, suggesting that they may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas. However, their role in the pathogenesis of these cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

30 pages, 1483 KiB

Open AccessReview

The Key Differences between Human Papillomavirus-Positive and -Negative Head and Neck Cancers: Biological and Clinical Implications

by Steven F. Powell, Lexi Vu, William C. Spanos and Dohun Pyeon

Cancers 2021, 13(20), 5206; https://doi.org/10.3390/cancers13205206 - 17 Oct 2021

Cited by 33 | Viewed by 4363

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a unique malignancy associated with two distinct risk factors: exposure to typical carcinogens and infection of human papillomavirus (HPV). HPV encodes the potent oncoproteins E6 and E7, which bypass many important oncogenic processes and result [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is a unique malignancy associated with two distinct risk factors: exposure to typical carcinogens and infection of human papillomavirus (HPV). HPV encodes the potent oncoproteins E6 and E7, which bypass many important oncogenic processes and result in cancer development. In contrast, HPV-negative HNSCC is developed through multiple mutations in diverse oncogenic driver genes. While the risk factors associated with HPV-positive and HPV-negative HNSCCs are discrete, HNSCC patients still show highly complex molecular signatures, immune infiltrations, and treatment responses even within the same anatomical subtypes. Here, we summarize the current understanding of biological mechanisms, treatment approaches, and clinical outcomes in comparison between HPV-positive and -negative HNSCCs. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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20 pages, 1411 KiB

Open AccessReview

Role of IQGAP1 in Carcinogenesis

by Tao Wei and Paul F. Lambert

Cancers 2021, 13(16), 3940; https://doi.org/10.3390/cancers13163940 - 04 Aug 2021

Cited by 21 | Viewed by 2843

Abstract

Scaffolding proteins can play important roles in cell signaling transduction. IQ motif-containing GTPase-activating protein 1 (IQGAP1) influences many cellular activities by scaffolding multiple key signaling pathways, including ones involved in carcinogenesis. Two decades of studies provide evidence that IQGAP1 plays an essential role [...] Read more.

Scaffolding proteins can play important roles in cell signaling transduction. IQ motif-containing GTPase-activating protein 1 (IQGAP1) influences many cellular activities by scaffolding multiple key signaling pathways, including ones involved in carcinogenesis. Two decades of studies provide evidence that IQGAP1 plays an essential role in promoting cancer development. IQGAP1 is overexpressed in many types of cancer, and its overexpression in cancer is associated with lower survival of the cancer patient. Here, we provide a comprehensive review of the literature regarding the oncogenic roles of IQGAP1. We start by describing the major cancer-related signaling pathways scaffolded by IQGAP1 and their associated cellular activities. We then describe clinical and molecular evidence for the contribution of IQGAP1 in different types of cancers. In the end, we review recent evidence implicating IQGAP1 in tumor-related immune responses. Given the critical role of IQGAP1 in carcinoma development, anti-tumor therapies targeting IQGAP1 or its associated signaling pathways could be beneficial for patients with many types of cancer. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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10 pages, 697 KiB

Open AccessReview

Value and Unmet Needs in Non-Invasive Human Papillomavirus (HPV) Testing for Oropharyngeal Cancer

by Alec J. Kacew and Glenn J. Hanna

Cancers 2021, 13(3), 562; https://doi.org/10.3390/cancers13030562 - 02 Feb 2021

Cited by 4 | Viewed by 2756

Abstract

The burden of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has risen, now representing the most common HPV-related malignancy. For years, researchers have explored the utility of measuring HPV-related markers from mouth, throat, and blood samples, often with the aim of gathering more information [...] Read more.

The burden of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has risen, now representing the most common HPV-related malignancy. For years, researchers have explored the utility of measuring HPV-related markers from mouth, throat, and blood samples, often with the aim of gathering more information about an existing HPV-related tumor in a given patient. We review the widely varying methods for collecting and testing saliva and blood samples and offer guidance for standardizing these practices. We then review an array of clinical contexts in which non-invasive testing holds the most promise for potentially addressing unmet needs. In particular, such testing could help clinicians and researchers monitor the effects of vaccination and treatment. Meanwhile, due to the currently incomplete understanding of how carrying HPV relates to infection and subsequent oncogenesis, non-invasive testing methods may not be suitable for the screening setting at this time. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) Associated Head and Neck Cancers: From Basic Biology to Clinical Challenges)

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