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

Powell, Steven; Vu, Lexi; Spanos, William C.; Pyeon, Dohun

doi:10.3390/cancers13205206

Cited by 52 publications

(50 citation statements)

References 204 publications

(251 reference statements)

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“…Patients with HNSCC present higher frequency of effector memory T cells and reduced frequency of naive T cells in the peripheral blood compared to healthy individuals ( 56 ). Higher frequency of central memory T cells is also observed in HNSCC patients compared to healthy individuals ( 57 ).The evaluation of memory T cell populations in blood samples with HPV infection shows higher frequency of effector memory T cells and lower frequency of naïve T cells in HPV+ HNSCC patients compared to HPV- HNSCC patients. There is no difference in the frequency of central memory T cells considering HPV status in HNSCC ( 57 ).…”

Section: T Cell Exhaustion and Memory Formation On Hnsccmentioning

confidence: 99%

“…Higher frequency of central memory T cells is also observed in HNSCC patients compared to healthy individuals ( 57 ).The evaluation of memory T cell populations in blood samples with HPV infection shows higher frequency of effector memory T cells and lower frequency of naïve T cells in HPV+ HNSCC patients compared to HPV- HNSCC patients. There is no difference in the frequency of central memory T cells considering HPV status in HNSCC ( 57 ). Effector memory T cells are also found in high frequency in the TME, but no difference is observed in the frequency of this population comparing HPV+ HNSCC and HPV- HNSCC ( 44 ).…”

Section: T Cell Exhaustion and Memory Formation On Hnsccmentioning

confidence: 99%

“…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 ( 57 ). The cellular responses observed on HNSCC are mediated by biochemical signal transduction and they may reflect genetic mutations.…”

Section: Gene Mutations and Cell Signaling In Hnsccmentioning

confidence: 99%

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The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy

et al. 2022

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Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities of tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco and alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy are the standard treatments, though the 5-year overall survival is less than 50%. The advances in genomics, molecular medicine, immunology, and nanotechnology have shed a light on tumour biology which helps clinical researchers to obtain more efficacious and less toxic therapies. Head and neck tumours possess different immune escape mechanisms including diminishing the immune response through modulating immune checkpoints, in addition to the recruitment and differentiation of suppressive immune cells. The insights into the HNSCC biology and its strong interaction with the tumour microenvironment highlights the role of immunomodulating agents. Recently, the knowledge of the immunological features of these tumours has paved the way for the discovery of effective biomarkers that allow a better selection of patients with odds of improving overall survival through immunotherapy. Specially biomarkers regarding immune checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 and anti-CTLA-4 in combination with standard therapy or as monotherapy. New immunotherapies to treat head and neck cancer carcinomas, such as CAR T cells and nanoparticles have been the center of attention and in this review, we discuss the necessity of finding targets for the T cell in the cancer cells to generate CAR T cells, but also the relevance of evaluating specificity and safety of those therapies.

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Section: T Cell Exhaustion and Memory Formation On Hnsccmentioning

confidence: 99%

Section: T Cell Exhaustion and Memory Formation On Hnsccmentioning

confidence: 99%

Section: Gene Mutations and Cell Signaling In Hnsccmentioning

confidence: 99%

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The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy

et al. 2022

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“…Moreover, molecularly, HPV+ and HPV− HNSCC are significantly different. Comprehensive genomic and transcriptomic analyses revealed deep differences occurring in their mutational and transcriptional profiles ( Table 1 ) [ 1 , 15 , 16 , 17 , 18 ]. The higher mutational burden in HPV− compared to HPV+ HNSCC could be explained by carcinogens derived from tobacco and alcohol consumption.…”

Section: Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

“…They induce DNA adducts formation, leading to hypermutations and chromosomal instability, and, finally, to tumorigenesis. On the other hand, within HPV+ HNSCC, genetic and transcriptional alterations are predominantly induced by viral infection through two main approaches: (i) a crucial role is exerted by the oncoviral proteins E6 and E7 that dramatically impair the host cell homeostasis by interacting and destabilizing a large number of host proteins, and (ii) linearization and integration of viral DNA in the host genome lead to genomic instability with genomic rearrangements such as amplifications, deletions, inversions and chromosomal translocations [ 1 , 15 ]. Beyond the differences in their genomic and transcriptomic profiles, HPV+ and HPV− HNSCC are also characterized by different epigenetic landscapes.…”

Section: Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies

Ghiani

Chiocca

2022

IJMS

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Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence of 650,000 new cases and 350,000 deaths per year worldwide and a male to female ratio of 3:1. The main risk factors are alcohol and tobacco consumption and Human Papillomavirus (HPV) infections. HNSCC cases are divided into two subgroups, the HPV-negative (HPV−) and the HPV-positive (HPV+) which have different clinicopathological and molecular profiles. However, patients are still treated with the same therapeutic regimens. It is thus of utmost importance to characterize the molecular mechanisms underlying these differences to find new biomarkers and novel therapeutic targets towards personalized therapies. Epigenetic alterations are a hallmark of cancer and can be exploited as both promising biomarkers and potential new targets. E6 and E7 HPV oncoviral proteins besides targeting p53 and pRb, impair the expression and the activity of several epigenetic regulators. While alterations in DNA methylation patterns have been well described in HPV+ and HPV− HNSCC, accurate histone post-translational modifications (hPTMs) characterization is still missing. Herein, we aim to provide an updated overview on the impact of HPV on the hPTMs landscape in HNSCC. Moreover, we will also discuss the sex and gender bias in HNSCC and how the epigenetic machinery could be involved in this process, and the importance of taking into account sex and/or gender also in this field.

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Association of Human Papillomavirus Status With Suicide Risk Among Patients With Head and Neck Cancer

Chakoma

Moon

Osazuwa‐Peters

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceHuman papillomavirus (HPV) is strongly associated with head and neck cancer, and HPV status is considered a prognostic factor. Being a sexually transmitted infection, HPV-related cancers may have greater risk of stigma and psychological distress; however, the potential association of HPV-positive status with psychosocial outcomes, such as suicide, is understudied in head and neck cancer.ObjectiveTo investigate the association between HPV tumor status and suicide risk among patients with head and neck cancer.Design, Setting, and ParticipantsThis population-based retrospective cohort study included adult patients with clinically confirmed cases of head and neck cancer based on HPV tumor status from the Surveillance, Epidemiology, and End Results database from January 1, 2000, to December 31, 2018. Data analysis was conducted from February 1 to July 22, 2022.Main Outcomes and MeasuresThe outcome of interest was death by suicide. Primary measure was HPV status of tumor site, dichotomized as positive or negative. Covariates included age, race, ethnicity, marital status, cancer stage at presentation, treatment modality, and type of residence. Cumulative risk of suicide among patients with HPV-positive and HPV-negative head and neck cancer was assessed using Fine and Gray competing risk models.ResultsOf 60 361 participants, the mean (SD) age was 61.2 (13.65) years, and 17 036 (28.2%) were women; there were 347 (0.6%) American Indian, 4369 (7.2%) Asian, 5226 (8.7%) Black, 414 (0.7%) Native Hawaiian or Other Pacific Islander, and 49 187 (81.5%) White individuals. A competing risk analysis showed a significant difference in the cumulative incidence of suicide between HPV-positive cancers (5-year suicide-specific mortality, 0.43%; 95% CI, 0.33%-0.55%) and HPV-negative cancers (5-year suicide-specific mortality, 0.24%; 95% CI, 0.19%-0.29%). Tumor status that was HPV positive was associated with increased suicide risk in the unadjusted model (hazard ratio [HR], 1.76; 95% CI, 1.28-2.40), but not the fully adjusted model (adjusted HR, 1.18; 95% CI, 0.79-1.79). Among people with oropharyngeal cancer only, HPV status was associated with increased suicide risk, but the width of the confidence interval prevented definitive conclusion (adjusted HR, 1.61; 95% CI 0.88-2.94).Conclusions and RelevanceThe results of this cohort study suggest that patients with HPV-positive head and neck cancer have similar risk of suicide as patients with HPV-negative cancer, despite differences in overall prognosis. Early mental health interventions may be associated with reduced suicide risk in all patients with head and neck cancer and should be assessed in future work.

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

Cited by 52 publications

References 204 publications

The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy

The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies

Association of Human Papillomavirus Status With Suicide Risk Among Patients With Head and Neck Cancer

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