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Frontiers in Bioscience (Landmark... Jun 2024The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the...
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 -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 , , and , which predominantly influence differentiating between sample groups. They were followed in importance by , , , and . 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.
Topics: Humans; Oropharyngeal Neoplasms; Biomarkers, Tumor; Papillomavirus Infections; Artificial Intelligence; Gene Expression Regulation, Neoplastic; Squamous Cell Carcinoma of Head and Neck; Algorithms; Sequence Analysis, RNA; Machine Learning; Papillomaviridae; Carcinoma, Squamous Cell
PubMed: 38940026
DOI: 10.31083/j.fbl2906220 -
Cancer Radiotherapie : Journal de La... Jun 2024The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could...
PURPOSE
The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers.
MATERIAL AND METHODS
We performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method.
RESULTS
Median age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was -2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was -4.6Gy (P<0.001).
CONCLUSION
Multicriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.
PubMed: 38937203
DOI: 10.1016/j.canrad.2024.01.003 -
Tumour Virus Research Jun 2024HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related cancer in the developed world. HPV16...
HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related cancer in the developed world. HPV16 is in ∼90 % of HPV + OPCs, with episomal genomes in the majority of cases. Most existing HPV16+ cancer cell lines derive from outside the oropharynx and harbor integrated HPV genomes. Thus, there is need for OPC preclinical models to evaluate standard and experimental therapeutics in the presence of episomal HPV16 oncogenic drivers. Here we characterize HPV genome structures in eight HPV16+ OPC patient-derived xenografts (PDXs), and evaluate their responses to standard chemotherapy. HPV genome state was investigated by combining Southern blot, T5 exonuclease assay, whole genome sequencing, and RNAseq data. This analysis revealed complexity and variation in integrated vs. episomal HPV forms across PDXs and demonstrated that four PDXs predominantly contain episomal HPV16. Episomal status did not ensure favorable in vivo responses to cisplatin therapy, despite the more favorable prognosis previously attributed to episomal HPV + tumors; this could be due to the small number present in the dataset. Our analysis establishes PDX models as test platforms for novel therapies designed to target maintenance of the episomal forms of HPV16 that commonly appear in OPC.
PubMed: 38936774
DOI: 10.1016/j.tvr.2024.200285 -
The Laryngoscope Jun 2024To document the 10-year results of transoral mandibular preservation surgery for patients with T1-2 squamous cell carcinoma (SCC) arising from the lateral oropharynx.
OBJECTIVES
To document the 10-year results of transoral mandibular preservation surgery for patients with T1-2 squamous cell carcinoma (SCC) arising from the lateral oropharynx.
METHODS
This was a retrospective 30-year review using STROBE guidelines at an academic, tertiary referral center. A total of 294 patients with T1-2 SCC of the lateral oropharynx were reviewed. Only 19% of patients were never-smokers, suggesting a predominantly HPV-negative population. All patients had transoral mandibular preservation surgery. Follow-up therapy included neck dissection (76.5%), induction chemotherapy (57.8%), and postoperative radiation therapy (31.6%) Local control, survival, and functional endpoints, as well as the consequences of local recurrence, were analyzed.
RESULTS
The 10-year local disease control was 88.3%. Local recurrence was salvaged in 50% of cases, resulting in an overall 94.5% local control rate. The overall 10-year survival was 50%. Mortality was related to metachronous second primary cancer (MSPC) (29.2%), medical comorbidities (25.7%), uncontrolled local recurrence (10%), and complications following transoral resection (4.2%). In multivariate analysis, the development of an MSPC significantly increased (p < 0.005) the risk of death. Overall, 95.2% of patients achieved mandibular preservation. However, gastrostomy and tracheostomy dependence occurred in 1% and 0.3% of cases, respectively.
CONCLUSIONS
For a patient population with a significant percentage of tobacco-associated oropharyngeal cancer (OPC), transoral surgery was associated with long-term minimal postoperative complications and a high rate of local control. MSPC was the main cause of death during the first 10 postoperative years. Such long-term figures support transoral surgery as an effective first-line treatment for early-stage predominantly tobacco-related OPC.
LEVEL OF EVIDENCE
4 Laryngoscope, 2024.
PubMed: 38932658
DOI: 10.1002/lary.31574 -
Viruses Jun 2024HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified... (Review)
Review
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.
Topics: Humans; Papillomavirus Infections; Phylogeny; Head and Neck Neoplasms; Human papillomavirus 16; Female; Genetic Variation; Uterine Cervical Neoplasms; Genome, Viral; Anus Neoplasms; Male; Squamous Cell Carcinoma of Head and Neck
PubMed: 38932197
DOI: 10.3390/v16060904 -
Journal of Medical Virology Jun 2024
Topics: Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Chemoradiotherapy; Prognosis; Aged; Radiotherapy; Aged, 80 and over; Papillomaviridae
PubMed: 38922943
DOI: 10.1002/jmv.29535 -
Cells Jun 2024Head 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...
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.
Topics: Humans; Male; Female; Prognosis; Tumor Suppressor Proteins; Middle Aged; Membrane Proteins; Papillomavirus Infections; Papillomaviridae; Aged; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Biomarkers, Tumor; Kaplan-Meier Estimate; Adult
PubMed: 38920638
DOI: 10.3390/cells13121002 -
BMC Oral Health Jun 2024Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and...
BACKGROUND
Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.
METHODS
A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.
RESULTS
Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043).
CONCLUSIONS
We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
Topics: Humans; Oropharyngeal Neoplasms; Male; Female; Middle Aged; Prognosis; LIM Domain Proteins; Biomarkers, Tumor; Carcinoma, Squamous Cell; Aged; Transcription Factors; Membrane Glycoproteins; Adult; Ki-67 Antigen; Hyaluronan Receptors; Tumor Suppressor Protein p53; Papillomavirus Infections; Immunohistochemistry; Aged, 80 and over; Survival Rate
PubMed: 38918827
DOI: 10.1186/s12903-024-04510-4 -
BMC Cancer Jun 2024Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We...
BACKGROUND
Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer.
PATIENTS AND METHODS
We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period.
RESULTS
We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers.
CONCLUSIONS
Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.
Topics: Humans; Male; Female; Laryngeal Neoplasms; Middle Aged; Oropharyngeal Neoplasms; Aged; Surveys and Questionnaires; Prospective Studies; Depression; Mouth Neoplasms; Adult; Quality of Life; Finland; Social Class; Neoplasm Staging; Socioeconomic Factors; Time-to-Treatment
PubMed: 38914952
DOI: 10.1186/s12885-024-12517-x -
AJNR. American Journal of Neuroradiology Jun 2024Long-term post-treatment surveillance imaging algorithms for head and neck squamous cell carcinoma are not standardized due to debates over optimal surveillance strategy... (Review)
Review
BACKGROUND
Long-term post-treatment surveillance imaging algorithms for head and neck squamous cell carcinoma are not standardized due to debates over optimal surveillance strategy and efficacy. Consequently, current guidelines do not provide long-term surveillance imaging recommendations beyond 6 months.
PURPOSE
We performed a systematic review to evaluate the impact of long-term imaging surveillance (i.e., imaging beyond 6 months following treatment completion) on survival in patients treated definitively for head and neck squamous cell carcinoma.
DATA SOURCES
A search was conducted on PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and Web of Science for English literature published between 2003 and 2024 evaluating the impact of long-term surveillance imaging on survival in patients with head and neck squamous cell carcinoma.
STUDY SELECTION
718 abstracts were screened and 9 underwent full-text review, with 2 articles meeting inclusion criteria. The Risk of Bias in Non-randomized Studies of Interventions assessment tool was used.
DATA ANALYSIS
A qualitative assessment without a pooled analysis was performed for the two studies meeting inclusion criteria.
DATA SYNTHESIS
No randomized prospective controlled trials were identified. Two retrospective two-arm studies were included comparing long-term surveillance imaging with clinical surveillance and were each rated as having moderate risk of bias. Each study included heterogeneous populations with variable risk profiles and imaging surveillance protocols. Both studies investigated the impact of long-term surveillance imaging on overall survival and came to a different conclusion with one study reporting a survival benefit for long-term surveillance imaging with FDG PET/CT in patients with stage III or IV disease or an oropharyngeal primary tumor and the other study demonstrating no survival benefit.
LIMITATIONS
Limited heterogeneous retrospective data available precludes definitive conclusions on the impact of long-term surveillance imaging in head and neck squamous cell carcinoma.
CONCLUSIONS
There is insufficient quality evidence regarding the impact of long-term surveillance imaging on survival in patients treated definitively for head and neck squamous cell carcinoma. There is a lack of standardized definition of long-term surveillance, variable surveillance protocols, and inconsistencies in results reporting, underscoring the need for a prospective multi-center registry assessing outcomes.
ABBREVIATIONS
HNSCC = Head and Neck Squamous Cell Carcinoma; RT= radiotherapy; NCCN = National Comprehensive Cancer Network; MPC = metachronous primary cancer; CR = complete response; OS = overall survival; CRT = chemoradiotherapy; HPV = human papillomavirus; PFS = progression-free survival; CFU = clinical follow up; NI-RADS = Neck Imaging Reporting and Data System.
PubMed: 38914430
DOI: 10.3174/ajnr.A8392