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1.
Cells ; 13(13)2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38994960

RÉSUMÉ

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.


Sujet(s)
Marqueurs biologiques tumoraux , Carcinome épidermoïde de la tête et du cou , Humains , Marqueurs biologiques tumoraux/métabolisme , Marqueurs biologiques tumoraux/génétique , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/génétique , Pronostic , Infections à papillomavirus/virologie , Infections à papillomavirus/complications , Infections à papillomavirus/génétique , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/génétique , Papillomaviridae/génétique , Régulation de l'expression des gènes tumoraux
2.
Viruses ; 16(6)2024 Jun 03.
Article de Anglais | MEDLINE | ID: mdl-38932197

RÉSUMÉ

HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A-D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV-related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV-driven anogenital and head and neck cancers.


Sujet(s)
Tumeurs de la tête et du cou , Papillomavirus humain de type 16 , Infections à papillomavirus , Phylogenèse , Humains , Infections à papillomavirus/virologie , Infections à papillomavirus/épidémiologie , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/épidémiologie , Papillomavirus humain de type 16/génétique , Papillomavirus humain de type 16/classification , Femelle , Variation génétique , Tumeurs du col de l'utérus/virologie , Tumeurs du col de l'utérus/épidémiologie , Génome viral , Tumeurs de l'anus/virologie , Tumeurs de l'anus/épidémiologie , Mâle , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/génétique
3.
Front Immunol ; 15: 1414298, 2024.
Article de Anglais | MEDLINE | ID: mdl-38938577

RÉSUMÉ

Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer development. Conventional therapies achieve only limited efficiency, especially in recurrent or metastatic HNSCC. As the immune landscape decisively impacts the survival of patients and treatment efficacy, this study comprehensively investigated the immunological tumor microenvironment (TME) and its association with patient outcome, with special focus on several dendritic cell (DC) and T lymphocyte subpopulations. Therefore, formalin-fixed paraffin-embedded tumor samples of 56 HNSCC patients, who have undergone resection and adjuvant radiotherapy, were analyzed by multiplex immunohistochemistry focusing on the detailed phenotypic characterization and spatial distribution of DCs, CD8+ T cells, and T-helper cell subsets in different tumor compartments. Immune cell densities and proportions were correlated with clinical characteristics of the whole HNSCC cohort and different HPV- or hypoxia-associated subcohorts. Tumor stroma was highly infiltrated by plasmacytoid DCs and T lymphocytes. Among the T-helper cells and CD8+ T cells, stromal regulatory T cells and intraepithelial exhausted CD8+ T cells expressing programmed cell death protein-1 (PD-1+) and/or lymphocyte-activation gene-3 (LAG-3+) were the predominant phenotypes, indicating an immunosuppressive TME. HPV-associated tumors showed significantly higher infiltration of type I and type II conventional DCs (cDC1, cDC2) as well as several CD8+ T cell phenotypes including exhausted, activated, and proliferating T cells. On the contrary, tumors with hypoxia-associated gene signatures exhibited reduced infiltration for these immune cells. By multivariate Cox regression, immune-related prognostic factors were identified. Patient clusters defined by high infiltration of DCs and T lymphocytes combined with HPV positivity or low hypoxia showed significantly prolonged survival. Thereby, cDC1 and CD8+ T cells emerged as independent prognostic factors for local and distant recurrence. These results might contribute to the implementation of an immune cell infiltration score predicting HNSCC patients' survival and such patient stratification might improve the design of future individualized radiochemo-(immuno)therapies.


Sujet(s)
Lymphocytes T CD8+ , Cellules dendritiques , Tumeurs de la tête et du cou , Carcinome épidermoïde de la tête et du cou , Microenvironnement tumoral , Humains , Cellules dendritiques/immunologie , Carcinome épidermoïde de la tête et du cou/immunologie , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/mortalité , Mâle , Femelle , Lymphocytes T CD8+/immunologie , Adulte d'âge moyen , Microenvironnement tumoral/immunologie , Tumeurs de la tête et du cou/immunologie , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/mortalité , Sujet âgé , Lymphocytes TIL/immunologie , Lymphocytes TIL/métabolisme , Pronostic , Adulte , Infections à papillomavirus/immunologie , Infections à papillomavirus/complications , Infections à papillomavirus/virologie
4.
Cells ; 13(12)2024 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-38920662

RÉSUMÉ

Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-ß signaling were hallmarks of SChigh tumors, whereas SClow tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of PTEN mutation and PIK3CA copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the TP53 mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SClow tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models.


Sujet(s)
Phosphatidylinositol 3-kinases , Transduction du signal , Carcinome épidermoïde de la tête et du cou , Microenvironnement tumoral , Humains , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/métabolisme , Phosphatidylinositol 3-kinases/métabolisme , Nerfs périphériques/anatomopathologie , Nerfs périphériques/métabolisme , Nerfs périphériques/virologie , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/métabolisme , Mutation/génétique , Sérine-thréonine kinases TOR/métabolisme , Phosphatidylinositol 3-kinases de classe I/métabolisme , Phosphatidylinositol 3-kinases de classe I/génétique , Cellules de Schwann/métabolisme , Cellules de Schwann/anatomopathologie , Cellules de Schwann/virologie , Phosphohydrolase PTEN/métabolisme , Phosphohydrolase PTEN/génétique , Régulation de l'expression des gènes tumoraux , Protéine p53 suppresseur de tumeur/métabolisme , Protéine p53 suppresseur de tumeur/génétique
5.
Anticancer Res ; 44(7): 2921-2931, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38925841

RÉSUMÉ

BACKGROUND/AIM: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we investigated the presence of tumor antigens HPV E6/E7 and wild-type p53-specific T-cell responses, and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC were stimulated with HPV E6/E7 or wild-type p53-derived peptide mixture and evaluated using the interferon-γ enzyme-linked immunosorbent spot assay. Flow cytometry was performed to analyze the proportion of T-cell subsets and T cells expressing immune checkpoint molecules. RESULTS: HPV E6/E7-specific T cells were detected in 22 (95.7%) of 23 patients, whereas wild-type p53-specific T cells were detected in 3 (15.0%) of 20 patients. Seven (43.8%) of 16 patients exhibited wild-type p53-specific T-cell responses, as determined using whole proteins instead of peptides. Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 (45.0%) of 20 patients. Flow cytometric analysis of PBMCs revealed that responders exhibiting enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had a significantly higher proportion of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells than non-responders. CONCLUSION: Our findings indicate that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Blockade of checkpoint pathways can enhance T-cell responses in certain patients, probably via activated T cells, Tregs, and/or exhausted CD4+ T cells.


Sujet(s)
Tumeurs de la tête et du cou , Inhibiteurs de points de contrôle immunitaires , Infections à papillomavirus , Carcinome épidermoïde de la tête et du cou , Humains , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Carcinome épidermoïde de la tête et du cou/immunologie , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/traitement médicamenteux , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Tumeurs de la tête et du cou/immunologie , Tumeurs de la tête et du cou/virologie , Infections à papillomavirus/immunologie , Infections à papillomavirus/virologie , Antigènes néoplasiques/immunologie , Protéines des oncogènes viraux/immunologie , Protéine p53 suppresseur de tumeur/immunologie , Adulte , Agranulocytes/immunologie , Agranulocytes/métabolisme , Papillomaviridae/immunologie , Lymphocytes T/immunologie , Virus des Papillomavirus humains
6.
J Med Virol ; 96(6): e29746, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38884391

RÉSUMÉ

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high-risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV-driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription-quantitative PCR (RT-qPCR), offer sensitive HPV detection. Liquid-based RT-qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost-effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.


Sujet(s)
Tumeurs de la tête et du cou , Infections à papillomavirus , Humains , Infections à papillomavirus/diagnostic , Infections à papillomavirus/virologie , Infections à papillomavirus/complications , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/diagnostic , Carcinome épidermoïde de la tête et du cou/virologie , Papillomavirus humain de type 16/génétique , Papillomavirus humain de type 16/isolement et purification , Papillomavirus humain de type 16/pathogénicité , Papillomaviridae/génétique , Papillomaviridae/isolement et purification , Papillomavirus humain de type 18/génétique , Papillomavirus humain de type 18/isolement et purification , Virus des Papillomavirus humains
7.
Cells ; 13(12)2024 Jun 08.
Article de Anglais | MEDLINE | ID: mdl-38920638

RÉSUMÉ

Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.


Sujet(s)
Protéines membranaires , Protéines suppresseurs de tumeurs , Humains , Mâle , Femelle , Pronostic , Protéines suppresseurs de tumeurs/métabolisme , Protéines suppresseurs de tumeurs/génétique , Adulte d'âge moyen , Protéines membranaires/métabolisme , Protéines membranaires/génétique , Infections à papillomavirus/virologie , Infections à papillomavirus/complications , Papillomaviridae/génétique , Sujet âgé , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/métabolisme , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Estimation de Kaplan-Meier , Adulte
8.
Sci Rep ; 14(1): 14148, 2024 06 19.
Article de Anglais | MEDLINE | ID: mdl-38898137

RÉSUMÉ

The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.


Sujet(s)
Tumeurs de l'oropharynx , Infections à papillomavirus , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Marqueurs biologiques tumoraux/métabolisme , Carcinome épidermoïde/virologie , Carcinome épidermoïde/métabolisme , Carcinome épidermoïde/anatomopathologie , Lignée cellulaire tumorale , Glycoprotéines/métabolisme , Tumeurs de l'oropharynx/virologie , Tumeurs de l'oropharynx/métabolisme , Tumeurs de l'oropharynx/anatomopathologie , Papillomaviridae/génétique , Infections à papillomavirus/virologie , Infections à papillomavirus/métabolisme , Infections à papillomavirus/complications , Infections à papillomavirus/anatomopathologie , Pronostic , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/métabolisme , Carcinome épidermoïde de la tête et du cou/anatomopathologie
9.
Front Biosci (Landmark Ed) ; 29(6): 220, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38940026

RÉSUMÉ

BACKGROUND: The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments. METHODS: This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted p-value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO. RESULTS: The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include ECT2, LAMC2, and DSG2, which predominantly influence differentiating between sample groups. They were followed in importance by FAT1, PLOD2, COL1A1, and PLAU. The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas". CONCLUSIONS: Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.


Sujet(s)
Marqueurs biologiques tumoraux , Tumeurs de l'oropharynx , Humains , Tumeurs de l'oropharynx/génétique , Tumeurs de l'oropharynx/virologie , Marqueurs biologiques tumoraux/génétique , Infections à papillomavirus/génétique , Infections à papillomavirus/virologie , Intelligence artificielle , Régulation de l'expression des gènes tumoraux , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/virologie , Algorithmes , Analyse de séquence d'ARN/méthodes , Apprentissage machine , Papillomaviridae/génétique , Carcinome épidermoïde/génétique , Carcinome épidermoïde/virologie
10.
Sci Rep ; 14(1): 14276, 2024 06 20.
Article de Anglais | MEDLINE | ID: mdl-38902523

RÉSUMÉ

Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV-) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV-), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.


Sujet(s)
, Tumeurs de l'oropharynx , Infections à papillomavirus , Tomodensitométrie , Humains , Tumeurs de l'oropharynx/virologie , Tumeurs de l'oropharynx/imagerie diagnostique , Tumeurs de l'oropharynx/anatomopathologie , Tomodensitométrie/méthodes , Infections à papillomavirus/imagerie diagnostique , Infections à papillomavirus/virologie , Infections à papillomavirus/anatomopathologie , Mâle , Femelle , Papillomaviridae , Adulte d'âge moyen , Sujet âgé , Carcinome épidermoïde/imagerie diagnostique , Carcinome épidermoïde/virologie , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/imagerie diagnostique , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Charge tumorale , Virus des Papillomavirus humains
11.
Cancer Biol Ther ; 25(1): 2350249, 2024 Dec 31.
Article de Anglais | MEDLINE | ID: mdl-38722731

RÉSUMÉ

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.


Sujet(s)
Tumeurs de la tête et du cou , Microbiote , Infections à papillomavirus , Carcinome épidermoïde de la tête et du cou , Microenvironnement tumoral , Humains , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/mortalité , Tumeurs de la tête et du cou/immunologie , Tumeurs de la tête et du cou/microbiologie , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/génétique , Femelle , Infections à papillomavirus/virologie , Infections à papillomavirus/immunologie , Infections à papillomavirus/complications , Mâle , Microbiote/génétique , Microenvironnement tumoral/immunologie , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/microbiologie , Carcinome épidermoïde de la tête et du cou/immunologie , Carcinome épidermoïde de la tête et du cou/mortalité , Pronostic , Adulte d'âge moyen , Papillomaviridae/génétique , Sujet âgé
12.
Braz J Med Biol Res ; 57: e13368, 2024.
Article de Anglais | MEDLINE | ID: mdl-38775547

RÉSUMÉ

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.


Sujet(s)
Marqueurs biologiques tumoraux , Tumeurs de la tête et du cou , Carcinome épidermoïde de la tête et du cou , Humains , Pronostic , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/virologie , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/analyse , Tumeurs de la tête et du cou/génétique , Mâle , Femelle , Régulation de l'expression des gènes tumoraux , Microenvironnement tumoral , Adulte d'âge moyen
13.
Head Neck Pathol ; 18(1): 36, 2024 May 06.
Article de Anglais | MEDLINE | ID: mdl-38709462

RÉSUMÉ

BACKGROUND: To determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC. METHODS: Fifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV. RESULTS: p16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%. CONCLUSION: Findings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.


Sujet(s)
Carcinome épidermoïde , Tumeurs de la lèvre , Infections à papillomavirus , Humains , Femelle , Infections à papillomavirus/complications , République d'Afrique du Sud , Tumeurs de la lèvre/virologie , Tumeurs de la lèvre/anatomopathologie , Sujet âgé , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Mâle , Carcinome épidermoïde/virologie , Carcinome épidermoïde/anatomopathologie , Adulte , Études de cohortes , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Papillomavirus humain de type 16/génétique
14.
PeerJ ; 12: e17391, 2024.
Article de Anglais | MEDLINE | ID: mdl-38784388

RÉSUMÉ

Objective: To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design: Meta-analysis and systematic evaluation. Data sources: The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies: Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results: A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], P = 0.0004; HR = 1.79, 95% CI [1.40-2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], P < 0.0001; HR = 1.66, 95% CI [1.07-2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], P = 0.28). Conclusions: Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number: CRD42023445619.


Sujet(s)
Cétuximab , Chimioradiothérapie , Cisplatine , Tumeurs de l'oropharynx , Infections à papillomavirus , Humains , Cétuximab/usage thérapeutique , Cétuximab/effets indésirables , Cétuximab/administration et posologie , Tumeurs de l'oropharynx/virologie , Tumeurs de l'oropharynx/anatomopathologie , Tumeurs de l'oropharynx/mortalité , Tumeurs de l'oropharynx/radiothérapie , Tumeurs de l'oropharynx/thérapie , Tumeurs de l'oropharynx/traitement médicamenteux , Cisplatine/usage thérapeutique , Cisplatine/administration et posologie , Infections à papillomavirus/virologie , Infections à papillomavirus/mortalité , Pronostic , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/radiothérapie , Carcinome épidermoïde de la tête et du cou/traitement médicamenteux , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Carcinome épidermoïde de la tête et du cou/mortalité , Carcinome épidermoïde de la tête et du cou/thérapie , Stadification tumorale , Papillomaviridae , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/effets indésirables , Survie sans progression , Virus des Papillomavirus humains
15.
J Robot Surg ; 18(1): 226, 2024 May 28.
Article de Anglais | MEDLINE | ID: mdl-38806847

RÉSUMÉ

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.


Sujet(s)
Tumeurs de l'oropharynx , Interventions chirurgicales robotisées , Humains , Interventions chirurgicales robotisées/méthodes , Études rétrospectives , Tumeurs de l'oropharynx/chirurgie , Tumeurs de l'oropharynx/virologie , Tumeurs de l'oropharynx/anatomopathologie , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Résultat thérapeutique , Récidive tumorale locale , Australie/épidémiologie , Adulte , Infections à papillomavirus/complications , Infections à papillomavirus/chirurgie , Carcinome épidermoïde/chirurgie , Carcinome épidermoïde/virologie , Carcinome épidermoïde/anatomopathologie , Marges d'exérèse , Carcinome épidermoïde de la tête et du cou/chirurgie , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Évidement ganglionnaire cervical/méthodes , Sujet âgé de 80 ans ou plus
16.
Br J Cancer ; 130(12): 1936-1942, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38714747

RÉSUMÉ

BACKGROUND: Gut microbiome modulation to boost antitumor immune responses is under investigation. METHODS: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis. RESULTS: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics. CONCLUSIONS: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.


Sujet(s)
Chimioradiothérapie , Microbiome gastro-intestinal , Tumeurs de l'oropharynx , Infections à papillomavirus , Humains , Tumeurs de l'oropharynx/thérapie , Tumeurs de l'oropharynx/microbiologie , Tumeurs de l'oropharynx/virologie , Mâle , Femelle , Adulte d'âge moyen , Chimioradiothérapie/méthodes , Sujet âgé , Infections à papillomavirus/complications , Études prospectives , Carcinome épidermoïde de la tête et du cou/thérapie , Carcinome épidermoïde de la tête et du cou/microbiologie , Carcinome épidermoïde de la tête et du cou/virologie , Adulte , Fèces/microbiologie
17.
mSphere ; 9(6): e0013124, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38747609

RÉSUMÉ

Ethan L. Morgan works on human papillomaviruses (HPVs), with a specific interest in identifying how HPV induces tumor formation. In this mSphere of Influence article, he reflects on how three papers influenced him. "Comprehensive genomic characterization of head and neck squamous cell carcinomas" (The Cancer Genome Atlas Network, Nature 517:576-582, 2015, https://doi.org/10.1038/nature14129) and "Integrated genomic and molecular characterization of cervical cancer" (The Cancer Genome Atlas Network, Nature 543: 378-384, 2017, https://doi.org/10.1038/nature21386) showed him the power behind comprehensive multi-omic analyses to understand disease biology, while "Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response" (J. Sitz et al., Proc Natl Acad Sci U S A 116:19552-19562, 2019, https://doi.org/10.1073/pnas.1906102116) reinforced how this can be used to undercover potential new drug targets in HPV-associated disease.


Sujet(s)
Génomique , Humains , Infections à papillomavirus/virologie , Papillomaviridae/génétique , Papillomaviridae/pathogénicité , Tumeurs du col de l'utérus/virologie , Tumeurs du col de l'utérus/génétique , Femelle , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/génétique , Multi-omique
18.
Arch Oral Biol ; 163: 105975, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38626700

RÉSUMÉ

OBJECTIVES: To compare amino acid metabolism patterns between HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) patients and identify key genes for a prognostic model. DESIGN: Utilizing the Cancer Genome Atlas dataset, we analyzed amino acid metabolism genes, differentiated genes between HPV statuses, and selected key genes via LASSO regression for the prognostic model. The model's gene expression was verified through immunohistochemistry in clinical samples. Functional enrichment and CIBERSORTx analyses explored biological functions, molecular mechanisms, and immune cell correlations. The model's prognostic capability was assessed using nomograms, calibration, and decision curve analysis. RESULTS: We identified 1157 key genes associated with amino acid metabolism in HNSCC and HPV status. The prognostic model, featuring genes like IQCN, SLC22A1, SYT12, and TLX3, highlighted functions in development, metabolism, and pathways related to receptors and enzymes. It significantly correlated with immune cell infiltration and outperformed traditional staging in prognosis prediction, despite immunohistochemistry results showing limited clinical identification of HPV-related HNSCC. CONCLUSIONS: Distinct amino acid metabolism patterns differentiate HPV-positive from negative HNSCC patients, underscoring the prognostic model's utility in predicting outcomes and guiding therapeutic strategies.


Sujet(s)
Acides aminés , Tumeurs de la tête et du cou , Infections à papillomavirus , Carcinome épidermoïde de la tête et du cou , Humains , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/métabolisme , Pronostic , Acides aminés/métabolisme , Infections à papillomavirus/métabolisme , Infections à papillomavirus/virologie , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/métabolisme , Femelle , Immunohistochimie , Mâle , Nomogrammes , Marqueurs biologiques tumoraux/métabolisme , Adulte d'âge moyen , Papillomaviridae
19.
JAMA Otolaryngol Head Neck Surg ; 150(5): 444-450, 2024 May 01.
Article de Anglais | MEDLINE | ID: mdl-38573644

RÉSUMÉ

Importance: The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown. Objective: To determine if preoperative circulating tumor HPV DNA (ctHPVDNA) is associated with disease burden in patients with HPV+ OPSCC who have undergone transoral robotic surgery (TORS). Design, Setting, and Participants: This cross-sectional study comprised patients with HPV+ OPSCC who underwent primary TORS between September 2021 and April 2023 at one tertiary academic institution. Patients with treatment-naive HPV+ OPSCC (p16-positive) and preoperative ctHPVDNA levels were included, and those who underwent neck mass excision before ctHPVDNA collection were excluded. Main Outcomes and Measures: The main outcome was the association of increasing preoperative ctHPVDNA levels with tumor size and lymph node involvement in surgical pathology. The secondary outcome was the association between preoperative ctHPVDNA levels and adverse pathology, which included lymphovascular invasion, perineural invasion, or extranodal extension. Results: A total of 70 patients were included in the study (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ctHPVDNA levels ranged from 0 fragments/milliliter of plasma (frag/mL) to 49 452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 patients (83%) had positive results for ctHPVDNA, 1 (1.4%) had indeterminate results, and 11 (15.6%) had negative results. The sensitivity of detectable ctHPVDNA for identifying patients with pathology-confirmed HPV+ OPSCC was 84%. Twenty-seven patients (39%) had pathologic tumor (pT) staging of pT0 or pT1, 34 (49%) had pT2 staging, and 9 patients (13%) had pT3 or pT4 staging. No clinically meaningful difference between detectable and undetectable preoperative ctHPVDNA cohorts was found for tumor size or adverse pathology. Although the median preoperative ctHPVDNA appeared to be higher in pT2 through pT4 stages and pN1 or pN2 stages, effect sizes were small (pT stage: η2, 0.002 [95% CI, -1.188 to 0.827]; pN stage: η2, 0.043 [95% CI, -0.188 to 2.600]). Median preoperative log(TTMV-HPV DNA) was higher in active smokers (8.79 [95% CI, 3.55-5.76]), compared with never smokers (5.92 [95% CI, -0.97 to 1.81]) and former smokers (4.99 [95% CI, 0.92-6.23]). Regression analysis did not show an association between tumor dimension or metastatic lymph node deposit size and preoperative log(TTMV-HPV DNA). After univariate analysis, no association was found between higher log(TTMV-HPV DNA) levels and adverse pathology. Conclusions and Relevance: In this cross-sectional study, preoperative ctHPVDNA levels were not associated with disease burden in patients with HPV+ OPSCC who underwent TORS.


Sujet(s)
ADN viral , Tumeurs de l'oropharynx , Infections à papillomavirus , Humains , Mâle , Femelle , Études transversales , Tumeurs de l'oropharynx/virologie , Tumeurs de l'oropharynx/chirurgie , Tumeurs de l'oropharynx/anatomopathologie , Tumeurs de l'oropharynx/sang , Adulte d'âge moyen , ADN viral/analyse , ADN viral/sang , Infections à papillomavirus/virologie , Infections à papillomavirus/sang , Infections à papillomavirus/complications , Sujet âgé , Interventions chirurgicales robotisées , ADN tumoral circulant/sang , Période préopératoire , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/sang , Carcinome épidermoïde de la tête et du cou/chirurgie , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Charge tumorale , Papillomaviridae/génétique
20.
Clin Otolaryngol ; 49(4): 384-403, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38658385

RÉSUMÉ

OBJECTIVES: About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers. DESIGN: A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria. RESULTS AND CONCLUSIONS: The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.


Sujet(s)
Tumeurs de la tête et du cou , Récidive tumorale locale , Infections à papillomavirus , Carcinome épidermoïde de la tête et du cou , Humains , Récidive tumorale locale/virologie , Récidive tumorale locale/génétique , Carcinome épidermoïde de la tête et du cou/virologie , Carcinome épidermoïde de la tête et du cou/thérapie , Carcinome épidermoïde de la tête et du cou/génétique , Infections à papillomavirus/virologie , Infections à papillomavirus/complications , Tumeurs de la tête et du cou/virologie , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/thérapie , Tumeurs de la tête et du cou/génétique , Marqueurs biologiques tumoraux/génétique , Papillomaviridae/génétique
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